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The Pituitary Foundation Information Booklets

Working to support pituitary patients, their carers & families 2 Pituitary Disease Factfile Contents and Introduction

Introduction 3 cross-referenced. Resources are provided on A Guide to 5 each Factsheet and an additional separate list, Non-functioning pituitary tumours 6 including organisations, is also included. 9 Abbreviations Cushing’s disease 13 ACTH Adrenocorticotrophic 16 AVP (ADH) 20 ADH Antidiuretic hormone CSF 24 CT Computed tomography insipidus 27 DDAVP Traumatic brain 29 DI Pituitary 30 FSH Follicle-stimulating hormone Radiotherapy 33 GH LH Luteinising hormone Hormone replacement therapy 37 GnRH Gonadotrophin-releasing hormone 40 PRL Psychological Issues 44 MRI Magnetic resonance imaging Referrals – Who and When to refer 46 TSH -stimulating hormone Resource list 49

Introduction - about this factfile Helpline: These Factsheets were written in response to for general patient support enquiries requests by General Practitioners and their 0117 370 1320 pituitary patients for more information on Monday to Friday 10:00am to 4:00pm pituitary disease. The Pituitary Foundation has already produced an excellent set of patient Endocrine Nurse Helpline: booklets explaining how pituitary disease can 0117 370 1317 Mondays 6:00pm to affect patients’ lives, the kind of treatments 9:00pm and Thursdays 9:00am to 1:00pm available and general advice on how to cope with particular problems. This Factfile includes [email protected] more detailed information, specifically written www.pituitary.org.uk for the GP. Each Factsheet gives background information on the condition, how it is investigated and possible treatments. Since many of the investigations and treatments may be used for several different syndromes, the information on the sheets is extensively

Pituitary Disease Factfile 3 Acknowledgements Disclaimer: We would like to thank the many specialists in Every care has been taken in the compilation the world of who have written of this Factfile to ensure it reflects current these sheets including Stephanie Baldeweg, practice (as at publishing date). Knowledge and Peter Bayliss, Claire Blessing, Peter Clayton, clinical practice continually evolve. The reader Jurgen Honneger, Trevor Howlett, Stafford is therefore advised to check with a specialist Lightman, John Monson, John Newell-Price, endocrinologist or with a product manufacturer Peter Trainer and John Wass. They, alongside if they have any concerns. The publishers and patients and GPs, read and made valued authors are not responsible for any errors or contributions to achieve this updated Factfile. omissions or for any consequences from the © 1999, 2006, 2011 and 2014 to be reviewed application of the information presented in this June 2016. Factfile.

4 Pituitary Disease Factfile Pituitary Foundation fact sheet 1 apoplexy Pituitary A guide to A guide to

A Guide to Pituitary Apoplexy

Bleeding or reduced blood flow in the The or pituitary may not can result in pituitary show on a Computerised Tomography (CT) damage. This is called pituitary apoplexy. scan. Blood tests are also important to check if If there is only reduced blood flow with the produced by the pituitary gland no bleeding, this condition is also called are adequate. pituitary infarction. It usually happens in In the event of pituitary apoplexy urgent people with pre-existing pituitary tumours. treatment is required. This consists of intravenous The Greek word ‘apoplexy’ literally means fluids, corticosteroids and close monitoring. sudden brain dysfunction. Surgery may be required to relieve the pressure The pituitary gland is situated in a bony and swelling around the pituitary gland. This hollow and is surrounded by important usually can be done by making a small incision structures, such as the nerves responsible for inside the nostril (). With vision. In apoplexy the gland swells suddenly treatment, the majority of patients recover and if and this can cause pressure in the surrounding the vision was affected it often gradually improves. brain structures. The swelling can also cause the If the vision was severely affected at the beginning, pituitary gland to stop producing one or more it may not fully recover. If the pituitary gland does of the pituitary hormones. not function properly after recovery patients may Up to 5% of patients with pituitary tumours need hormone replacement therapy. Patients will may develop apoplexy at some point. In need regular check ups at a specialist endocrine fact, studies have shown that bigger tumours clinic to monitor the condition. (macroadenomas) carry a higher risk of apoplexy In 2010, a national working group developed compared with smaller ones (microadenomas). guidelines for the management of pituitary High or low blood pressure, head injury, certain apoplexy, to increase awareness amongst doctors such as warfarin, cardiac surgery and and to standardise and improve the treatment of very rarely certain endocrine dynamic tests may this rare, but potentially life-threatening condition. increase the risk of apoplexy. It is important that pituitary apoplexy is Indicative References diagnosed and treated. If it remains untreated, 1. Murad-Kejbou S, Eggenberger E. Pituitary apoplexy may cause seriously ill health and apoplexy: evaluation, management, and even death. The most common symptoms are prognosis. Current Opinion in Ophthalmology , nausea or , changes in 2009; 20:456-61. eye-sight, such as double vision, restriction in eye 2. Nawar R, AbdelMannan D et al. Pituitary movement and drowsiness. These symptoms are Tumor Apoplexy: A Review. Journal of not unique in apoplexy but may occur in other Intensive Care Medicine 2008; 23(2): 75-90. conditions such as , subarachnoid 3. Randeva HS, Schoebel J et al. Classical haemorrhage or (rarely) migraine, from which pituitary apoplexy: clinical features, pituitary apoplexy has to be distinguished. The management best way to diagnose pituitary apoplexy is a and outcome. Clin Endocrinology (Oxf) 1999; Magnetic Resonance Imaging (MRI) scan. 51:181-188.

Pituitary Disease Factfile 5 Pituitary Foundation fact sheet 2

Non-functioning pituitary tumours

The most common type of pituitary tumour In the presence of pressure signs/ pituitary tumours pituitary

Non-functioning is non-functioning (i.e. it does not cause symptoms excessive hormone production). Tumours of Patients will usually need transsphenoidal this type most commonly become apparent surgery (factsheet 10), which may be followed when the patient has visual symptoms or by radiotherapy to prevent recurrence (factsheet

due to pressure on the 11). If pituitary hormones are deficient, and it is often the optician who refers the pituitary hormone replacement therapy will be patient with abnormal visual fields to the GP given (factsheet 12). (in which case the GP would want to refer to an ophthalmologist who, in turn, is likely to Patient management refer to an endocrinologist). The tumour may Post-operative also damage the adjacent, normal pituitary Most patients will have improved, or at least gland (causing hypopituitarism - factsheet 6) stabilised, visual fields. Removal of the nasal or occasionally compress the , packing, if this method used, is often the causing hyperprolactinaemia (factsheet 5). only part of the procedure that patients find uncomfortable. Some patients may find that Please see ‘Who and When to Refer’ (factsheet 15). their frequency of headaches changes. Other complications, such as Cerebral Spinal Fluid Presenting symptoms (CSF) leaks can occur, although rarely, and • visual disturbance need to be treated by a further small operative • oligomenorrhoea or amenorrhoea in women procedure (factsheet 10). • tiredness and lack of energy • reduced and potency in men Long-term • headache Regular assessments may be needed. MRI scans are usually repeated within the Investigations first post-operative months and follow-up scans An MRI scan will be carried out to determine are initially carried out at increasing intervals the size and site of the tumour. Visual field tests from 6 months to 5 years. are used to determine the degree of functional impairment of the visual pathway. Blood tests Radiotherapy will be needed to assess pituitary function. Pituitary radiotherapy (factsheet 11) may be used after surgery to reduce the risk of regrowth Treatment possibilities of the tumour. Since radiotherapy can cause In the absence of pressure signs/ hypopituitarism at variable times after symptoms treatment, patients should be tested for Patients may not need treatment, but will be pituitary function on a regular basis, probably monitored closely using MRI scans and visual field at 6 months, 1 year, 2 years and then bi- or checks at intervals of 6 or 12 months. Alternatively triennially. surgery or, rarely, radiotherapy may be advised.

6 Pituitary Disease Factfile Non-functioning pituitary tumours 7

OUP (2009)

www.pituitary.org.uk (www.endotext.org/ (www.endotext.org/ Pituitary Disease Factfile Pituitary Disease www.pituitary.org.uk. The Pituitary Gland: its conditions & PituitaryThe explained Hormones Pituitary Surgery & Radiotherapy Have I inherited this, will my children this, will my children I inherited Have get it? circumstances all but very exceptional In is no hereditary link. there good if the tumour is treated promptly. promptly. tumour is treated good if the stopping any in is effective Treatment further cases. visual loss in almost all stopped? my periods Why have the pituitaryThe tumour may prevent the hormones being able to secrete from menstruationthat control and fertility. Oxford Handbook of Endocrinology Handbook Oxford (Eds). Wass and JAH Turner H • • links available information and resource Other at GPs For Source’ Endocrine ‘Your Endotext.org www.endotext.org neuroendo/index.htm) website Foundation PituitaryThe www.pituitary.org.uk Resources for patients Resources Foundation Pituitary The from available our website or Helpline Helpline Nurse or our Endocrine booklets information Patient

Will my sight return after treatment? my sight return Will are recovery The chances of at least partial firstly in the upper outer quadrant, then the whole temporal field (the field of vision on both left and right sides of the head as opposed to central vision). symptom. Visual acuity (vision that can be Visual symptom. spectacles) may not wearing by corrected reduced, be changed, but visual fields are apparatus. When the pituitaryapparatus. enlarges, compression caused by visual problems often the first of the visual pathway are Why do I bump into objects? The pituitary normally sits under the optic patient needs hormone replacement therapy patient needs hormone replacement patients may ask Questions is growth hormone deficient e.g., if energy hormone is growth lacking, otherwise therapy for replacement that replacement therapy is increased when increased therapy is that replacement physical or seriously ill or under major (factsheet 6) psychological (CSF leak - factsheet 10) throat or through the nose soon after surgery the nose soon or through throat General - consider whether the patient wellbeing

• Menstrual loss – consider whether the cycle • • Ask function about erectile headaches and migraine • Treat • If ensure , the patient is on Non-urgent (but still very important) (but still very Non-urgent • Clearof the the back fluid dripping down Urgent - refer to hospital - refer Urgent • Deterioration of vision Watchpoints More specialist resources pituitary tumours pituitary Non-functioning Management of Pituitary Tumors: The Clinician’s Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R.

Laws. Humana Press, Totowa, New Jersey

Pituitary Tumours. Recommendations for service provision and guidelines for management of patients. Consensus statement of a working party (1997) RN Clayton & JAH Wass (Eds) London: Royal College of Physicians

The Diagnosis and Treatment of Pituitary Insufficiency (1997) Lamberts SWJ (Ed) Bristol, UK: BioScientifica

Endocrinology (1997) Levy A & Lightman SL New York: Oxford University Press

The Epidemiology, Pathogenesis and Management of Pituitary Tumours (1998) Webb SM (Ed) Bristol, UK: BioScientifica

8 Pituitary Disease Factfile Acromegaly 9 especially in men, leading toespecially in men, leading daytime sleepiness. are: The main features • coarsening of facial features • enlarged hands and feet • and oily skin sweating • excessive • headaches • vision disturbance • sleep apnoea • general tiredness sleep apnoea may be present,sleep apnoea Pituitary Disease Factfile Pituitary Disease Treatment possibilities Treatment evidence suggests that with Epidemiological straightforward. We strongly recommend that recommend strongly We straightforward. be to an endocrinologist rather than all referrals see ‘Who or others. Please neurosurgeon and (factsheet 15). When to Refer’ Investigations will include a GH series and an Investigations to a load analysis of the GH response as as well Test), Tolerance (Glucose and other pituitary of prolactin measurement function tests. An MRI scan will be carried out and visual field tests may be performed to and position of the adenoma. determine the size There should be a low threshold for referral for for threshold should be a low There any patient with any suspicion of acromegaly challenge in the diagnosis as the greatest is thinking of the disease. of acromegaly suspected, biochemical confirmation Once of the disease is usually or exclusion symptoms may occur, particularly tunnel carpal occur, symptoms may the weight- of Premature syndrome. Obstructive is also characteristic. bearing joints - fact sheet 3 sheet fact 60 per million 4-6 new cases per million per year 4-6 newyear cases per million per

Acromegaly most often occurs in adults aged Acromegaly Pituitary Foundation PituitaryFoundation Incidence: Prevalence: enlargement of the hands and feet and may compression Nerve of the jaw. experience growth have often been present for a decade before often been present have the diagnosis is made. The patient may notice its effects on cartilage and soft tissues. Symptomsits effects on cartilage and soft tissues. change in appearance (not usually noticed by with the patient) due tothose living or working Presenting symptoms Presenting a gradual produces GH secretion Excessive a two-fold increase in mortality, particularly in mortality, a two-fold increase disease. cardiovascular from number of body systems and is associated with number of body systems and is associated with with changes in appearance, headaches, affects a Acromegaly and tiredness. sweating years of age) is rare and is the cause of pituitary of age) is rare years associated are GH levels . Elevated ends of bones have fused (usually around 18 fused (usually around ends of bones have 30-50 years. Presentation before the growing the growing before Presentation 30-50 years. tumours co-secrete prolactin. tumours co-secrete the day and can be used, along with GH, as the day and can be used, along with GH, as of to a third Up of disease activity. a measure day. Plasma IGF-1 levels, in IGF-1 levels, Plasma day. contrast, fluctuate little during GH levels fluctuate over the over fluctuate GH levels from the and other organs the liver from of GH. under the regulation (IGF-1), which is secreted (IGF-1), which is secreted actions of GH are mediated by mediated by actions of GH are factor-1 -like growth secretion by a pituitary by macro- secretion of the Many or microadenoma. growth hormone (GH) hyper hormone growth Acromegaly is the result of is the result Acromegaly Acromegaly normalisation of GH and IGF-1 levels, life and there is some risk of developing . expectancy can be restored to normal. The is a GH receptor antagonist that treatment recommended by the consultant blocks GH action by preventing GH from will depend on the size and activity of the binding to its receptor. Unlike other forms of adenoma and also on the age of the patient. treatment, it does not attempt to inhibit GH Transsphenoidal surgery is the treatment of release from the pituitary and as GH levels choice in most cases and can be dramatically do not fall with treatment, disease activity is effective, especially for microadenomas. However, judged by measuring IGF-1. some patients may need medical treatment or Patients may develop hypopituitarism Acromegaly radiotherapy after surgery to reduce GH levels. (factsheet 6) after surgery, or several years after Some GH-secreting adenomas are treatable radiotherapy. Hormone replacement therapy by long-term medical therapy with or without will then be needed (factsheet 12). radiotherapy. The consultant may offer the patient a choice between long-term medical Watchpoints treatment, involving injections, or surgery. Urgent - refer to hospital • Deterioration of vision Medical therapy • Clear fluid dripping down the back of the Some patients may need long-term medical throat or through the nose soon after surgery treatment to maintain acceptable GH and (CSF leak - factsheet 10 Surgery) IGF-1 levels. High levels of GH, even when the Non-urgent (but still very important) patient has no symptoms, are associated with a • If the patient is on hydrocortisone, ensure 2-3-fold increase in mortality. that replacement therapy is increased when Stabilisation of GH may be achieved with a seriously ill or under major physical or agonist, particularly if the tumour psychological stress also secretes prolactin. , is effective, • Treat headaches potent and causes few side effects. However, • Treat depression the analogues and • Treat carpal tunnel syndrome , which act by inhibiting GH release • Treat osteoarthritis: refer for hip/knee from the pituitary, are much more effective in replacement if required reducing GH and IGF-1 to acceptable levels. • Ask about erectile function, 70% have Octreotide/Lanreotide are available as long- problems. Treat this, reassure that it is part of acting preparations that require to be injected the disease and that it can be treated monthly, (Sandostatin LAR and Lanreotide • The patient is likely to have obstructive Autogel). Normalisation of GH and IGF-1 apnoea and to snore very loudly. It can be can be achieved in between half and two-thirds helped by treatment to lower GH, and by of patients. Somatostatin analogues also cause continuous positive airways pressure (CPAP) tumour shrinkage in most cases, when they may • Ask about change in bowel habit as some improve surgical results. Some patients suffer increased risk of colonic polyps and colonic gastrointestinal side effects with these drugs carcinoma

10 Pituitary Disease Factfile Questions patients may ask Why do I have such bad arthritis? Growth and degenerative changes are Why do my hands hurt? common. One of the main aims of Growth can occur in the connective tissue treatment is to prevent this. of the carpal tunnel compressing the median nerve. Why do I sweat so much? Not known but when GH levels are Why do I wake up tired? normal the problem disappears.

Growth hormone causes hypertrophy of Acromegaly the nasopharyngeal tissue and sleep apnoea Have I inherited this, will my children (usually noticed by the partner). This can get it? be treated In all but very exceptional circumstances there is no hereditary link. Why am I getting headaches? A large tumour may compress surrounding tissues. Resources for patients available from The Pituitary Foundation Why can’t I get my wedding ring on? Helpline or our website www.pituitary.org.uk Hypertrophy of the soft tissues of the joints or our Endocrine Nurse Helpline causes enlargement of hands and feet. Patient Information Booklet Why has my shoe size increased? • Acromegaly See above. Other information and resource links available at www.pituitary.org.uk Why does my jaw ache when I eat an apple? For GPs Growth of the disturbs dental Endotext.org ‘Your Endocrine Source’ www. occlusion and puts increased strain on the endotext.org (www.endotext.org/neuroendo/ temporomandibular joints. index.htm) The Pituitary Foundation Website Why do I keep biting my tongue? www.pituitary.org.uk GH promotes growth of the tongue. Oxford Handbook of Endocrinology OUP (2009) Why do I have backache? JAH Wass & H Turner (Eds). Growth of cartilaginous tissues causes musculoskeletal abnormalities and degenerative changes.

Pituitary Disease Factfile 11 More specialist resources Management of Pituitary Tumors: The Clinician’s Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey

Pituitary Tumours. Recommendations for service provision and guidelines for management of Acromegaly patients. Consensus statement of a working party (1997) RN Clayton & JAH Wass (Eds) London: Royal College of Physicians

The Diagnosis and Treatment of Pituitary Insufficiency (1997) Lamberts SWJ (Ed) Bristol, UK: BioScientifica

Endocrinology (1997) Levy A & Lightman SL New York: Oxford University Press

Acromegaly. (2009) Wass JAH (Ed) BioScientifica, UK

12 Pituitary Disease Factfile Pituitary Foundation fact sheet 4

Cushing’s disease

Incidence: 5-6 new cases per million per year • thin skin - tendency to bruise • (caused by androgen excess) • violaceous striae Cushing’s • disease (i.e. an • diabetes ACTH-secreting • and fractures pituitary • psychiatric disturbance (often characterised adenoma) by amplification of previous mood swings). is the most common cause Investigations of spontaneous Overnight dexamethasone suppression test and/ Cushing’s or 24-hour urinary measurements. If syndrome; this indicates Cushing’s syndrome further tests other causes to confirm the diagnosis and to determine the are an adrenal source of excessive cortisol will be required.

tumour or an ectopic tumour secreting Normal screening tests do not always exclude Cushing’s disease ACTH. Spontaneous Cushing’s syndrome the diagnosis - if clinical suspicion is high then is caused by excessive circulating cortisol; specialist referral may still be necessary. During it is rare but is associated with a significant diagnosis and further increase in morbidity and mortality, even if dynamic endocrine tests, chest X-ray and treated. Cushing’s syndrome may also be the pituitary, adrenal and /abdomen MRI or unavoidable result of steroid treatment for CT scans may be required. allergy, asthma, arthritis or other life-threatening condition. Diagnosis and Treatment possibilities differential diagnosis of Cushing’s syndrome Transsphenoidal surgery is usually the is complex and referral to a specialist centre recommended treatment if the condition is is recommended in all cases in whom the due to a pituitary tumour. In cases where condition is suspected. The recommended surgery is contra-indicated or fails to reduce route of referral is through an endocrinologist cortisol levels, adrenalectomy and/or pituitary rather than neurosurgeon or others. Please see radiotherapy may be necessary. Some patients ‘Who and When to Refer’ (factsheet 15). may need bilateral adrenalectomy to control disease when pituitary surgery is not effective. Presenting symptoms • moon face - particularly filling in of the Patient management post-operative temporal fossa Patients in remission normally undergo • - central obesity substantial changes immediately after surgery • muscle wasting and proximal myopathy which, apart from welcome changes in physical (patients have difficulty standing from a appearance and resolution of other symptoms seated position without use of arms) and signs, may initially involve depression.

Pituitary Disease Factfile 13 This is the result of the profound change in • Patients may have major mood swings after steroid status. No further treatment may be successful treatment to lower circulating required except monitoring for recurrence of corticosteroids. This can last for many Cushing’s and regrowth of the tumour. However, months, so reassurance and treatment for most patients will require hydrocortisone therapy, depression may be necessary some on a long-term basis and patients need • Obesity is often the aspect of Cushing’s strong reassurance that feeling worse after surgery disease that female patients find most is usual, but that in the long run things improve. distressing. Weight reduction following If the patient needs hydrocortisone for more than successful treatment is often slow one year postoperatively, the outlook for long- • Patients will need exercises to restore muscle term remission is excellent. If surgery results in strength and possibly further treatment for hypopituitarism, long-term hormone replacement osteoporosis therapy will be required (factsheet 12).

Long-term Questions patients may ask

Cushing’s disease Patients require close follow up on a long-term basis. Pituitary hormone replacement therapy Why am I putting on weight? will be required after surgery in some cases, and Increased cortisol causes accumulation of requires careful specialist monitoring. Advice fat deposits and a redistribution of fats to should be given regarding the dose of steroid to the face, neck and abdomen. be taken during intercurrent illness (factsheet 12). Why am I getting hairy? Long-term effects of radiotherapy may also ACTH stimulates increased secretion of include the development of partial or complete androgens from the adrenal cortex causing hypopituitarism. Patients may need help to hirsutism. follow a suitable diet and encouragement to take regular exercise to control weight gain. Why do I feel so weak? Hypersecretion of cortisol causes the Watchpoints increased breakdown of tissue proteins. Urgent - refer to hospital One effect of this is muscle wasting, which • Deterioration of vision mainly affects the muscles of the upper • Clear fluid dripping down the back of the arms and thighs. This can make it difficult throat or through the nose soon after surgery to climb stairs, or stand after sitting. (CSF leak - factsheet 10) Non-urgent (but still very important) Why am I so moody? • If the patient is on hydrocortisone, ensure The excess steroid produced by the tumour that replacement therapy is increased when has a direct effect on the brain. It tends to seriously ill or under major physical or produce dramatic mood swings. psychological stress

14 Pituitary Disease Factfile Oxford Handbook of Endocrinology OUP (2002) Why do I bruise so easily? JAH Wass & H Turner (Eds). Increased breakdown of tissue proteins causing weakening of capillaries. More specialist resources Management of Pituitary Tumors: The Clinician’s Why have I developed stretch marks? Practical Guide (2003) (Second Edition), Increased breakdown of skin proteins Editors and authors Michael P. Powell, Stafford makes the skin more fragile L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey Why do I have backache? As above - the back muscles are weakened Pituitary Tumours. Recommendations for service by the steroids and the extra weight which provision and guidelines for management of you gain also puts a strain on them. The patients. Consensus statement of a working steroids also affect the bones of the back. party (1997) RN Clayton & JAH Wass (Eds) London: Royal College of Physicians

Have I inherited this, will my children Cushing’s disease get it? The Epidemiology, Pathogenesis and Management In all but very exceptional circumstances of Pituitary Tumours (1998) Webb SM (Ed) there is no hereditary link. Bristol, UK: BioScientifica

Oxford Textbook of Endocrinology OUP (2002) Resources for patients JAH Wass & S Shalet (Eds) available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk or our Endocrine Nurse Helpline

Patient Information Booklet • Cushing’s Other information and resource links available at www.pituitary.org.uk

For GPs Endotext.org ‘Your Endocrine Source’ www.endotext.org (www.endotext.org/ neuroendo/index.htm) The Pituitary Foundation Website www.pituitary.org.uk

Pituitary Disease Factfile 15 Pituitary Foundation fact sheet 5

Hyperprolactinaemia

Incidence: Most common secreting adenoma. slowly. In women, absent periods and/or They are more common in women and inappropriate production of breast often macroprolactinomas are more common in men. allow the diagnosis to be made early. There should be a low threshold for referral for any patient with any hyperprolactinaemia, Prolactin levels as the greatest challenge in the diagnosis of are normally hyperprolactinaemia is thinking of the disease. high during Once suspected, biochemical confirmation or exclusion of the disease is usually and . straightforward. See ‘Who and When to Refer’ Abnormally (factsheet 15). high levels of prolactin at Presenting symptoms other times • galactorrhoea may be caused • oligomenorrhoea or amenorrhoea by a prolactin- • reduced libido secreting • pituitary tumour or by a non-secreting • pressure effects (e.g., headache and visual pituitary tumour that prevents dopamine disturbance) with macroadenomas (prolactin release-inhibiting hormone) from the reaching normal Investigations prolactin-producing cells (lactotrophs) of Useful GP screening tests include basal prolactin, Hyperprolactinaemia the pituitary. Raised prolactin levels are also thyroid function tests, a careful drug history sometimes found in Cushing’s syndrome, and exclusion of pregnancy. If prolactin (normal and polycystic ovarian range <400 mU/l) is mildly elevated (400 – 1000 disease. A number of drugs increase prolactin mU/l) it should be repeated before referral. levels by blocking the action of dopamine, Dynamic prolactin stimulation tests such as e.g., , , some the TRH test have no part in the investigation anti-depressants and the . of hyperprolactinaemia. Measurement of serum Stress raises prolactin levels so the very act of prolactin on three separate occasions (at least venepuncture can result in high levels. 2 hours after rising and when patient rested) The behaviour of prolactin-secreting provides all the information necessary. tumours is defined by their size at presentation. A prolactin level >5000 mU/l usually Microprolactinomas (less than 10mm indicates a true rather than a in diameter) rarely expand to become functionless tumour causing a raised prolactin. macroprolactinomas. In men, Specialist tests include pituitary imaging tend to present late, because reduced potency (preferably MRI) and visual field testing if and loss of libido - the hormonal effects of indicated (macroadenomas) and assessment of raised prolactin levels - are subtle and develop pituitary function.

16 Pituitary Disease Factfile Macroprolactin is a biologically inactive form of Medical treatment with cabergoline, prolactin that causes no clinical problem, other , or controls than being detected in prolactin assays resulting prolactin and symptoms in the majority of in spurious elevation of serum prolactin levels. patients, but needs to be continued long term. Macroprolactin should be suspected in any In patients with microprolactinomas an attempt patient with an elevated prolactin but no to withdraw the can be made after 3 associated signs or symptoms. Most laboratories years. These drugs can be associated with some can test for macroprolactin. dizziness and nausea. This can be limited by Please see ‘Who and When to Refer’ (factsheet taking the medicine in the middle of meals or 15). last thing at night and by starting at low dose. Cabergoline is the most widely prescribed Treatment objectives and possibilities treatment for prolactinoma as it is more potent Osteoporosis is a concern in any patient and associated with fewer side-effects. However, with hypogonadism – manifest clinically as recent guidance suggests that patients taking amenorrhoea or erectile dysfunction. In any cabergoline should have regular examination of patient with one year of hypogonadism a bone the heart (echocardiography) and watch out for density scan should be performed and a major shortness of breath as cabergoline can cause (at goal in the treatment of hyperprolactinaemia is higher dosage) fibrosis of the and heart the prevention of osteoporosis. valves. There had been concern about fibrosis In addition, treatment should stop etc, but that recent large UK data suggest no galactorrhoea and restore oestrogen levels in excessive risk. Any monitoring will be advised women, and hence , fertility, by an endocrinologist. libido and to normal. Hyperprolactinaemia In men, treatment of high prolactin should Pregnancy and prolactinomas normalise levels, and hence erectile Patients should be followed during pregnancy function and libido. by an endocrinologist. Ideally it is advisable for For macroprolactinomas, an additional patients to have discussed pregnancy with their objective is to shrink the tumour in order to endocrinologist prior to conception. reduce any pressure effects, such as visual failure. Most women are advised to cease taking dopamine agonists for the duration of Patient management pregnancy and during lactation. However, many Most patients are treated medically with thousands of babies have been born to mothers the dopamine agonists cabergoline, or taking bromocriptine and there is no evidence bromocriptine, both of which reduce prolactin of an increased incidence of malformation or levels, allow oestrogen or testosterone levels miscarriage. Cabergoline treatment appears to to rise and greatly reduce the size of the be safe during pregnancy. During pregnancy, tumour. Surgery to reduce tumour size, and there is a slight risk of tumour enlargement, radiotherapy to reduce the chance of recurrence, particularly in patients with macroadenomas. are rarely required. Any patient who experiences severe headaches

Pituitary Disease Factfile 17 or visual disturbances should be seen urgently by their specialist. problems with lack of interest in sex (low libido) or impotence, excessive milk Watchpoints production or a large tumour causing Urgent - refer to hospital pressure symptoms, then there is a clear • Deterioration of vision case for treatment. If not, then the need Non-urgent (but still very important) may not seem so clear. However, prolonged • Remember that successful treatment usually sex-hormone deficiency (particularly results in restoration of fertility (particularly oestrogen in women) causes thinning of in microprolactinomas) the bones, or osteoporosis. Therefore, • Patients may be predisposed to problems most doctors believe that women without related to osteoporosis regular periods should receive treatment. • Ask about erectile function. Reassure that it is The same applies to men with low part of the disease and that it can be treated testosterone levels.

How long will I have to take tablets Questions patients may ask for prolactinoma? You will probably need to take these tablets Why do I have a discharge from my for a relatively long time, with interruption breasts? during pregnancy as described earlier. Prolactin is normally required to initiate If you have a microprolactinoma, many and maintain lactation. The secretion of specialists withdraw treatment for a trial Hyperprolactinaemia prolactin from a pituitary tumour may period every three years or so; in some have the same effect. patients the problem seems to disappear during prolonged tablet treatment. If Will a microprolactinoma grow into a you have a large tumour, your treatment macroprolactinoma? courses may last several years; tumour In the vast majority of cases, no. This very control is maintained and side-effects rarely happens. during long-term treatment are not usually a problem. Have I inherited this, will my children get it? What are my fertility prospects as a In all but very exceptional circumstances man with prolactinoma? there is no hereditary link. Tablet treatment alone may improve your sperm count and lead to the return of Do all patients with prolactinomas normal fertility, although this may take need treatment? several months. Additional treatment with Most do. If you have infertility problems, hormone injections (FSH and LH)

18 Pituitary Disease Factfile More specialist resources may also be necessary. Fertility is usually Management of Pituitary Tumors: The Clinician’s attainable. Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford Is tablet treatment better than surgery L. Lightman and Edward R. Laws. Humana for prolactinomas? Press, Totowa, New Jersey Tablet treatment is the accepted form of treatment. Occasionally (5-10%) patients Pituitary Tumours. Recommendations for service have either severe side effects or do not provision and guidelines for management of respond to cabergoline. In these patients patients. Consensus statement of a working surgery may be advised although it is party (1997) RN Clayton & JAH Wass (Eds) not always curative (70- 80%) and the London: Royal College of Physicians operation may cause hypopituitarism. The Diagnosis and Treatment of Pituitary Insufficiency (1997) Lamberts SWJ (Ed) Bristol, Resources for patients UK: BioScientifica available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk Endocrinology (1997) Levy A & Lightman SL or our Endocrine Nurse Helpline New York: Oxford University Press

Patient Information Booklet The Epidemiology, Pathogenesis and Management • Prolactinoma of Pituitary Tumours (1998) Webb SM (Ed) Other information and resource links available Bristol, UK: BioScientifica Hyperprolactinaemia at www.pituitary.org.uk

For GPs Endotext.org ‘Your Endocrine Source’ www.endotext.org (www.endotext.org/ neuroendo/index.htm)

The Pituitary Foundation Website www.pituitary.org.uk

Oxford Handbook of Endocrinology OUP (2009) H Turner & JAH Wass (Eds).

Pituitary Disease Factfile 19 Pituitary Foundation fact sheet 6

Hypopituitarism

Hormone If hypopituitarism is caused by tumour deficiency compression, function may be partially or fully caused by the recovered after surgery or medical therapy to inadequate reduce the size of the tumour. Pituitary surgery secretion of may cause hypopituitarism in a minority of one or more of cases and improve pituitary function in others, the hormones and deficiencies can be transient (particularly normally diabetes insipidus). Detailed post-operative secreted by endocrine assessment is therefore essential. the pituitary, Hypopituitarism after treatment of a is known as pituitary tumour by radiotherapy typically hypopituitarism. It may commonly be caused develops slowly and progressively over a period by compression of the normal pituitary of several years. tissue by an enlarging pituitary tumour, by pituitary surgery, or radiotherapy.

Presenting symptoms

Deficient hormone Symptoms GH (growth hormone) Growth retardation in children Adults: excessive tiredness, muscle weakness, lack of drive, impaired quality of life scores FSH/LH (>secondary hypogonadism) Hypogonadism – In men: reduced facial and body hair, low libido, impotence; in women: amenorrhoea, reduced libido, dyspareunia and hot flushes TSH (>secondary thyroid deficiency) Weight gain, decreased energy, sensitivity to cold, , dry skin ACTH (>secondary adrenal Pale appearance, , low blood pressure, deficiency) dizziness, tiredness, ‘collapse’ during intercurrent illness Hypopituitarism AVP/ADH (argine vasopressin or Thirst, and nocturia – diabetes insipidus Anti-Diuretic Hormone)

Acute hypopituitarism (e.g., pituitary steroid replacement is required for ACTH apoplexy) - sudden headache, collapse, deficiency presenting acutely and during hypothermia, hypoglycaemia and intercurrent illness in established ACTH - may be a life-threatening emergency. Prompt deficiency.

20 Pituitary Disease Factfile Investigations osmolalities but sometimes a water deprivation Tests for hypopituitarism should be performed test is required. under the guidance of an endocrinologist. Please see ‘Who and When to Refer’ (factsheet 15). Treatment possibilities Growth hormone GH deficiency in children (for full details see factsheet 12) will require referral to a paediatric endocrine GH - Synthetic GH replacement is given centre. Adult GH deficiency requires to children. The treatment of adults with GH specialist assessment. replacement is clinically effective for many Gonadal function FSH, LH, prolactin, (though not all) patients with GH deficiency. oestradiol and testosterone are assessed by NICE has issued guidelines to identify patients serum levels. Testosterone in men should be in whom treatment is indicated. measured at 9am to avoid falsely low results ACTH - Treatment is usually with due to the . In women with hydrocortisone (= cortisol), typically 3 times periods, bloods are normally performed in the daily. Prednisolone or dexamethasone is follicular phase – but measurement of a Day 21 occasionally used. Increased doses are required progesterone may be used to confirm . during acute stress including intercurrent illness If fertility is desired, then a different or surgery. Fludrocortisone is not normally approach to hormone replacement will be required in pituitary deficiency. needed and a full assessment of both partners TSH - Treatment with . Free will be carried out. T4 levels must be used for monitoring since Thyroid function In pituitary-dependent TSH levels are not informative. hypothyroidism circulating thyroid hormone FSH/LH - Treatment with oestrogen in levels are low or low-normal but TSH can women (and in women with a be low, normal or even slightly elevated. ). Testosterone replacement in men Laboratories must be asked for free thyroxine given intramuscularly (i.m. every 2-4 weeks (free T4) as well as TSH, and thyroid hormone or 3-monthly depot), transdermally (usually replacement adjusted on the basis of free via gel), orally or by implant. For fertility, thyroxine level (many laboratories will now only treatment with is required which provide TSH measurements routinely unless should only be performed at a specialist centre free T4 is specifically requested and discussed) which provides effective monitoring. Hypopituitarism Adrenal function ACTH stimulated AVP/ADH - Treatment with desmopressin secretion of cortisol is assessed using the short (DDAVP) by intranasal spray, tablets or Melts. synacthen or the insulin stress test. A basal 9am cortisol gives limited information but low Patient management levels (<200nmol/L) should prompt early (and Management of patients with hypopituitarism <100nmol/L urgent) referral. on multiple hormone-replacement therapy Diabetes insipidus The diagnosis and cause (which The Foundation believes) is best is usually obvious and if so may be confirmed achieved by life-long supervision by a specialist by measurement of basal serum and endocrine outpatient clinic. The time interval

Pituitary Disease Factfile 21 for specialist monitoring will vary with the patient and the treatment received, but controlled and, if they regrow at all, will probably be at intervals of 2-6 months grow very slowly. Outpatient appointments immediately post treatment, to annual or are usually made 12 months to 2 years biennial in the longer term. Patients may need apart. help with managing hydrocortisone therapy (factsheet 12). Will I need regular scans? Perhaps, but again, these too are carried Watchpoints out several years apart. Urgent - refer to hospital • Deterioration of vision Will I still be able to have a family? • Clear fluid dripping down the back of the Yes, if the reason for infertility is pituitary throat or through the nose soon after surgery disease. The effects of pituitary tumours (CSF leak - factsheet 10) on fertility can be treated, although some • As emergency if unable to take increased oral treatments are not currently paid for by the steroid replacement during acute intercurrent NHS (factsheet 12). illness (e.g., vomiting) Non-urgent (but still very important) If I take replacement therapy, will I • If the patient is on hydrocortisone, ensure feel exactly the same as I did before that replacement therapy is increased when my pituitary tumour developed? seriously ill or under major physical or Replacement therapy is unable to fully psychological stress match the body’s natural, intricate • Watch for gradual deterioration in hormone balance. Every patient is different endogenous pituitary function and provide and, whilst many return to fairly normal replacement therapy as required life, the main object of replacement therapy is to achieve as good a quality of life as possible for patients. Questions patients may ask Have I inherited this, will my children Will I have to take tablets in the long get it? Hypopituitarism term? In all but very exceptional circumstances If the pituitary tumour or treatment for it has there is no hereditary link. affected the function of the normal pituitary, its function does not usually recover and will need to be replaced in the long term.

Will I need regular check-ups? Yes, but pituitary tumours are usually well

22 Pituitary Disease Factfile Resources for patients available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk or our Endocrine Nurse Helpline

Patient Information Booklet • The Pituitary Gland; Its conditions and hormones explained Other information and resource links available at www.pituitary.org.uk

For GPs Endotext.org ‘Your Endocrine Source’ www.endotext.org (www.endotext.org/ neuroendo/index.htm)

The Pituitary Foundation Website www.pituitary.org.uk

Oxford Handbook of Endocrinology and Diabetes 2nd Edition OUP (2009)H Turner & JAH Wass (Eds).

Oxford Textbook of Endocrinology and Diabetes 2nd Edition OUP (2010) JAH Wass & PM Stewart (Eds)

NICE guidance of growth hormone in adults http://www.nice.org.uk Adults: http://guidance.nice.org.uk/TA64 Hypopituitarism Children: http://guidance.nice.org.uk/TA42 NICE service guidance on Brain and other CNS Tumours http://guidance.nice.org.uk/ CSGBraincns

Pituitary Disease Factfile 23 Pituitary Foundation fact sheet 7

Craniopharyngioma

Incidence: 9% approx of all childhood • Tired, difficulty recovering from minor illness intracranial tumours (ACTH, cortisol deficiency). • Tired, cold intolerance, constipation, slow pulse, dry skin (TSH/T4 deficiency). are benign tumours • Changes in behaviour. accounting for approximately 9% of all Please see ‘Who and When to Refer’ (factsheet 15). intracranial tumours in childhood, and are the most common peripituitary tumour in Investigations this age group. In adults, craniopharyngio- An MRI or CT scan determines the precise mas account for 1% of brain tumours. Their size and position. Additional tests that form behaviour is unpredictable and their origin part of the evaluation include assessments is not fully understood. They are usually of biochemical, endocrine (especially an situated close to the pituitary gland and assessment of hypothalamic-pituitary axis), hypothalamus. The tumour consists of solid psychological and visual function. parts, sometimes calcified, and cysts, which may be filled with a dense oily fluid. Treatment possibilities Because of the position of the tumour, Presenting symptoms transcranial, subfrontal surgery is almost Craniopharyngiomas can cause symptoms at always required. However some small any age, but those presenting in childhood are craniopharyngiomas may be approached by the relatively fast growing, have a more aggressive transsphenoidal route. Complete excision is rare. course and can be more difficult to treat. In most patients, partial removal is followed by Symptoms have usually been present for radiotherapy. Prior to the operation, or if the some time before diagnosis. They are usually tumour re-grows, insertion of a CSF shunt may be associated with raised intracranial pressure and required if hydrocephalus (excessive accumulation possibly anterior and posterior pituitary failure. of CSF in the ventricular system) is present.

Symptoms and signs at presentation may include: Patient management • Headaches (typically in the morning), nausea All patients require long-term follow up, to allow and vomiting (commoner in children). early detection of any tumour re-growth and to • Visual field defect (typically bilateral treat the effects of the lesion on hypothalamic temporal hemianopia - poor vision to both and pituitary function. Recurrence after surgery sides - but complete loss of vision in one or alone is common, but is less likely when both eyes can occur). radiotherapy is also given. Following surgery, at • Slow growth during childhood. approximately 2-3 months, a further assessment • Delayed or arrested puberty, and very of hypothalamic-pituitary axis is required. Many

Craniopharyngioma occasionally precocious puberty. patients will be panhypopituitary (factsheet 6), • Thirst and passing large volumes of dilute and it is relatively common for diabetes insipidus urine (diabetes insipidus). (factsheet 8) to develop.

24 Pituitary Disease Factfile Children with panhypopituitarism may need in size. This risk is considerably reduced by long-term GH (factsheet 12), cortisol, thyroid postoperative radiotherapy. and replacement. Annual MRI or CT scans to check for re-growth are especially How will I know if the important in the first 3 years after treatment. craniopharyngioma is re-growing? Other common problems post-op are There may be no symptoms. Regular MRI increased or decreased appetite (resulting scans are essential. in weight problems) and reduced powers of concentration and short-term memory loss. Will my child be able to continue at school? Watchpoints Most children remain in mainstream schooling Urgent - refer to hospital without experiencing any difficulties. • Deterioration in vision and/or recurrent Difficulties may include sight problems, headache. These may indicate regrowth and/ psychological and educational difficulties. or cyst recurrence. • Intercurrent illness, in particular vomiting and Are my other children likely to diarrhoea in patients on cortisol replacement. develop this? Hydrocortisone replacement will need to No, it is not hereditary or familial. be increased, and may need to be given by injection. Families should have hydrocortisone Will it be possible for my child to injections available for emergency use. have children? • CSF leak (very rare in children) Clear fluid With appropriate treatment at the time dripping down the back of the throat or through fertility is required, the young person should the nose soon after surgery (factsheet 10) have a good chance of achieving fertility. Non-urgent (but still very important) • Depression, psychological difficulties and Why is my child so sleepy? problems in school are relatively common in As these tumours tend to occur above children treated for craniopharyngioma. the pituitary, the part of the brain that deals with the organization of sleep and wakefulness is sometimes disturbed as the Questions patients may ask tumour grows, or by the surgical treatment. Damage to this part of the brain is often How likely is it that the associated with increased somnolence. craniopharyngioma will re-grow? If this is going to occur then the majority Why has my child’s appetite increased? of cases are within 3 years, but it may recur The part of the brain that deals with

many years later. Partial removal results in feeling full after eating is sometimes Craniopharyngioma a higher chance of the tumour increasing disturbed for the same reasons.

Pituitary Disease Factfile 25 Resources for patients The Diagnosis and Treatment of Pituitary available from The Pituitary Foundation Insufficiency (1997) Lamberts SWJ (Ed) Bristol, Helpline or our website www.pituitary.org.uk UK: BioScientifica or our Endocrine Nurse Helpline Endocrinology (1997) Levy A & Lightman SL Patient Information Booklet New York: Oxford University Press • Craniopharyngioma - Available from The Child Growth Foundation, for contact details The Epidemiology, Pathogenesis and Management go to factsheet 16. of Pituitary Tumours (1998) Webb SM (Ed) Bristol, UK: BioScientifica Other information and resource links available at www.pituitary.org.uk

For GPs Endotext.org ‘Your Endocrine Source’ www.endotext.org (www.endotext.org/ neuroendo/index.htm)

The Pituitary Foundation Website www.pituitary.org.uk

Oxford Handbook of Endocrinology OUP (2002) JAH Wass & H Turner (Eds).

More specialist resources Management of Pituitary Tumors: The Clinician’s Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey

Pituitary Tumours. Recommendations for service provision and guidelines for management of patients. Consensus statement of a working party (1997) RN Clayton & JAH Wass (Eds) London: Royal College of Physicians Craniopharyngioma

26 Pituitary Disease Factfile Pituitary Foundation fact sheet 8 Diabetes insipidus

Diabetes insipidus

The condition Investigations diabetes The diagnosis is suggested by copious volumes insipidus (DI) of dilute urine with normal or slightly raised is characterised serum sodium. A water-deprivation test for up by the passage to 8 hours with measurements of serum sodium, of large volumes blood and urine osmolalities and urine volume of urine (>3 at 2-hour intervals followed by observation of litres/24hrs), urinary responses to desmopressin (DDAVP - and persistent an artificial vasopressin), can differentiate DI thirst. It is from other causes of polyuria (i.e., persistent distinguished excessive drinking or nephrogenic DI). An from diabetes MRI scan of the pituitary region to include mellitus (sugar diabetes) by ‘insipid’ the hypothalamus and posterior pituitary is urine, i.e., lacking taste, in contrast to the necessary. ‘sweet tasting’ urine of diabetes mellitus. A common cause of DI is inadequate secretion Treatment of vasopressin, the antidiuretic hormone, Mild cases of DI (urine output 3-4 litres/24 from the posterior pituitary. However, some hrs) can be managed by ingestion of water to patients suffer from renal conditions in quench thirst. Others require desmopressin which the kidneys fail to respond correctly to (DDAVP) which can be given orally, vasopressin; this is nephrogenic DI. intranasally or parenterally. It is essential to Trauma, , granulomatous avoid chronic overdosage which will cause disease (e.g., ) or tumours in the hyponatraemia (low serum concentration region of the hypothalamus or pituitary of sodium). Very occasionally, patients with may reduce vasopressin secretion. Pituitary extensive lesions affecting the hypothalamus surgery not infrequently causes DI which may have lack of thirst as well, and this presents is usually transitory lasting a few hours or a particular challenge to management with the days; occasionally it may be permanent and need for daily weights and fixed fluid intakes. be accompanied by loss of other pituitary hormones. Pituitary surgery also causes other Long-term management forms of hypopituitarism which are covered Because of the risk of hyponatraemia, occasional elsewhere (factsheet 6). (1-3 monthly) measurements of serum sodium are advised until patients are on stable Presenting symptoms therapy, when most will only need biochemical • Polyuria, in excess of 3 litres/24hrs in adults monitoring every 6-12 months. • Thirst and (excessive drinking) • Tiredness, lethargy and reduced concentration (often the result of lack of sleep due to night-time visits to the toilet)

Pituitary Disease Factfile 27 Diabetes insipidus

Patient Information Booklet Questions patients may ask • Diabetes Insipidus Other information and resource links available at www.pituitary.org.uk Why am I so thirsty? Lack of the normal vasopressin secretion, For GPs means that the kidneys are unable to Endotext.org ‘Your Endocrine Source’ concentrate the urine. This results in a high www.endotext.org (www.endotext.org/ sodium level in the blood which stimulates neuroendo/index.htm) thirst. The Pituitary Foundation Website www.pituitary.org.uk Why do I have to visit the toilet so often? Lack of vasopressin reduces the kidneys Oxford Handbook of Endocrinology OUP ability to concentrate the urine resulting in (2002) JAH Wass & H Turner (Eds). the production of large volumes of urine. More specialist resources Why do I have headaches? Management of Pituitary Tumors: The Clinician’s This can happen after your DI is treated Practical Guide (2003) (Second Edition), and it is important to balance the dose of Editors and authors Michael P. Powell, Stafford desmopressin and the amount of fluid you L. Lightman and Edward R. Laws. Humana drink so as not to retain too much water Press, Totowa, New Jersey and develop hyponatraemia (low sodium). Pituitary Tumours. Recommendations for service Will I recover from DI? provision and guidelines for management of DI can be caused by surgical trauma patients. Consensus statement of a working or accident and may in some cases be party (1997) RN Clayton & JAH Wass (Eds) transitory, but patients may require London: Royal College of Physicians treatment for life. The Diagnosis and Treatment of Pituitary Insufficiency Is it harmful to miss a dose of DDAVP? (1997) Lamberts SWJ (Ed) Bristol, UK: Generally speaking it is safer to miss a dose of BioScientifica Endocrinology (1997) Levy A & DDAVP than to take an extra dose. You will Lightman SL New York: Oxford University Press simply notice that your thirst will be greater than normal, and you should drink more. The Epidemiology, Pathogenesis and Management of Pituitary Tumours (1998) Webb SM (Ed) Bristol, UK: BioScientifica Resources for patients available from The Pituitary Foundation Disorders of the Posterior Pituitary. Newell-Price Helpline or our website www.pituitary.org.uk and Besser. In The Oxford Textbook of Medicine or our Endocrine Nurse Helpline (Warrell, D.A., Cox, T.M., Firth, J.D. eds), 2002

28 Pituitary Disease Factfile Pituitary Foundation fact sheet 9

Traumatic brain injury and hypopituitarism

Brain injury may cause damage to the Hypopituitarism hypothalamus and/or pituitary gland. Hormone deficiency caused by the inadequate and hypopituitarism Although the true incidence of brain injury secretion of one or more of the hormones and hypopituitarism remains unclear, normally secreted by the pituitary, is known as the poor outcome for patients who go hypopituitarism. It may commonly be caused unrecognised could be devastating, with by compression of the normal pituitary tissue morbidity and the potential for mortality. by an enlarging pituitary tumour, by pituitary Therefore, it is important to raise awareness of surgery, or radiotherapy. It should, however, this issue amongst primary health care professionals. be emphasised that documented combined Most patients recover quickly from their head hypopituitarism after head injury is uncommon, injury and experience no long-term problems. and if it does occur it may have been associated However, some patients can develop problems after with very significant head injury. a few weeks, months or sometimes, years. Presenting symptoms Deficient hormone Symptoms GH (Growth Hormone) Children: Growth retardation Adults: Excessive tiredness, muscle weakness, lack of drive, impaired quality of life scores FSH/LH Hypogonadism – In men: reduced facial and body hair, ( >secondary hypogonadism) low libido, impotence. In women: amenorrhoea, reduced libido, dyspareunia and hot flushes TSH (> secondary thyroid deficiency) Weight gain, decreased energy, sensitivity to cold, constipation, dry skin ACTH (> secondary adrenal Pale appearance, weight loss, low blood pressure, deficiency) dizziness, tiredness; ‘collapse’ during intercurrent illness AVP/ADH (arginine vasopressin or Thirst, polyuria and nocturia – diabetes insipidus Anti-Diuretic Hormone)

Investigations our website www.pituitary.org.uk or our Endocrine Tests for hypopituitarism should be performed Nurse Helpline Other information and resource under the guidance of an endocrinologist. Please links available at www.pituitary.org.uk see ‘Who and When to Refer’ (factsheet no: 15) For GPs Endotext.org ‘Your Endocrine Source’ Please also see ‘Hypopituitarism’ Factsheet no: 6 for www.endotext.org (www.endotext.org/neuroendo/ explanation of hormone investigations, treatment index.htm) The Pituitary Foundation Websitewww. possibilities, management and watchpoints. pituitary.org.uk Oxford Handbook of Endocrinology and Diabetes 2nd Edition OUP (2010) JAH Wass & Resources for patients PM Stewart (Eds) NICE guidance of growth hormone available from The Pituitary Foundation Helpline or in adults http://www.nice.org.uk

Pituitary Disease Factfile 29 Pituitary Foundation fact sheet 10

Pituitary Surgery

Tumours vary in size and activity. If surgery is recommended it may be for one of three reasons: • to remove hormone-producing tissue (typically in acromegaly or Cushing’s disease) • to reduce the volume of a tumour that is compressing the or other structures

Pituitary surgery Pituitary • to reduce the volume of, or excise, non hormone-producing tissue that is likely to threaten surrounding structures in the future; for example, in a relatively young patient, in whom continued growth of the tumour is Follow-up suspected or has been proven by sequential The patient will be referred to an scans. endocrinologist for post-operative pituitary Transsphenoidal surgery is the most usual function assessment at about 5-8 weeks and method but transcranial surgery is required back to the surgeon at about 12 weeks (for in some tumours with major intracranial MRI and visual field assessment). In some cases extension. The transsphenoidal approach allows additional replacement pituitary hormones will the surgeon a clear, direct view of the tumour be needed. These appointments should, ideally, (through an operating microscope) and avoids be combined to cause minimal inconvenience a (making a hole in the skull) with to the patient. its associated slight risks of damage to the brain and epilepsy. Diabetes insipidus (factsheet 8) Endoscopic surgery is becoming the main If the patient suffers from new onset polyuria approach in many centres. Fine tubes (endoscopes) and nocturia after surgery, it is likely that they are pushed through the back of the nose. have developed a degree of diabetes insipidus MRI and/or CT scans will give the surgeon (DI). This is unusual after transsphenoidal information on the size and position of the surgery, but in all cases is highly amenable tumour. to treatment. In most cases DI is temporary Successful outcome of this surgery is very and disappears within a few months, but in dependent on the experience of the surgeon. 1-2% of patients, especially after removal of prolactinoma and Cushing’s tumours, it may be Patient management prior to surgery permanent but remain treatable. The Pituitary Foundation recommends that the initial point of referral is an endocrinologist Cerebrospinal fluid leak who will arrange for essential preliminary tests It is possible to develop a CSF leak from the (including blood tests, MRI and visual fields) to nose in the post-operative period (this is rare). be performed before surgery. This is associated with a risk of meningitis, and

30 Pituitary Disease Factfile is an inconvenience for the patient. Any flulike It is essential that all pituitary hormones are symptoms or discharge of water-like fluid from at satisfactory levels, as even small deficiencies the nose should be treated with a view to this in testosterone, thyroid hormone and possibility. Patients need to be referred back to growth hormone can make it more difficult the surgeon for treatment urgently. to lose weight. Regular monitoring with an endocrinologist is important to establish that Sinusitis hormone levels are satisfactory, but also an This is not uncommon after this operation, opportunity to discuss any weight gained.

particularly for patients with acromegaly. surgery Pituitary Symptoms usually clear given time, but Emotional impact occasionally need further treatment or an Surgical treatment which involves the head has ENT referral. a strong emotional impact for some patients. Please see ‘Psychological Issues’ (factsheet 14). Stitches Depending on the surgical technique, stitches are inserted in the upper gum or in the nostril. Questions patients may ask They are usually soluble. The wound itself will be completely healed in 3 weeks. Complete Why do I need an operation? absorption of stitches can take 3 months and A benign tumour of the pituitary gland loose ends may need to be removed/snipped may be compressing the optic nerve away. There may be some numbness around the (which lies just above it) and affecting your front teeth; this may occasionally be permanent. sight or you may have a tumour that is producing excessive amounts of hormone Weight gain which could cause you problems. A major problem for many patients is weight gain. These patients are likely to need Is it ? some encouragement to follow a suitable No, the vast majority of tumours are benign. diet and take regular exercise. This may be particularly difficult after a period of illness Will my eyesight improve after the and hospitalisation. However, including more operation? exercise into their lifestyle should also improve Once the optic nerve is no longer the patient’s general feeling of well-being. compressed most patients will notice an The adrenal glands and cortisol are improvement, this will carry on improving responsible for fat cell development. If cortisol for 6 months after the operation. However, levels are high due to having Cushing’s then if your eyesight was very poor before the weight is usually gained around the trunk operation, it may not recover so much. and in the face. If taking hydrocortisone as a replacement and the dose is too much, then weight can be gained.

Pituitary Disease Factfile 31 Oxford Handbook of Endocrinology OUP (2009) How long will I be in hospital? JAH Wass & H Turner (Eds). This varies between treatment centres, but may be 3-9 days. More specialist resources Management of Pituitary Tumors: The Clinician’s When will I be able to go back to Practical Guide (2003) (Second Edition), work? Editors and authors Michael P. Powell, Stafford Depending on the job and circumstances, L. Lightman and Edward R. Laws. Humana

Pituitary surgery Pituitary it is usually wise to plan for about 4-6 Press, Totowa, New Jersey weeks off and reassess after that time. Some patients may take longer to recover. Pituitary Tumours. Recommendations for service provision and guidelines for management of Have I inherited this, will my children patients. Consensus statement of a working get it? party (1997) RN Clayton & JAH Wass (Eds) In all but very exceptional circumstances London: Royal College of Physicians there is no hereditary link. The Diagnosis and Treatment of Pituitary Insufficiency(1997) Lamberts SWJ (Ed) Resources for patients Bristol,nUK: BioScientifica available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk Endocrinology (1997) Levy A & Lightman SL or our Endocrine Nurse Helpline New York: Oxford University Press

Patient Information Booklet The Epidemiology, Pathogenesis and Management • The Pituitary Gland; Its conditions and of Pituitary Tumours (1998) Webb SM (Ed) hormones explained Bristol, UK: BioScientifica • Pituitary Surgery & Radiotherapy

Other information and resource links available at www.pituitary.org.uk

For GPs Endotext.org ‘Your Endocrine Source’ www.endotext.org (www.endotext.org/neuroendo/index.htm)

The Pituitary Foundation Website www.pituitary.org.uk

32 Pituitary Disease Factfile Pituitary Foundation fact sheet 11

Radiotherapy

Indications for radiotherapy (Rt) use in hypopituitarismwithin 20 years of : radiotherapy, necessitating regular endocrine Following surgical resection follow up. • If tumour persists outside pituitary fossa on post-op scan. • For functioning adenoma: if hormone levels do not fall to normal post-op and/or medical therapy is not subsequently controlling hormone secretion. • Consider for patients with recurrent disease (+/- following second operation - especially if chiasm is compressed). • Patients with small volume functioning adenoma away from the optic chiasm or recurrence following conventional radiotherapy can be considered for single fraction radiotherapy (also called radio Radiotherapy surgery). For inoperable disease • If patient is fit enough to receive RT (e.g., when tumour is pressing on chiasm). Radiotherapy was once regarded as a routine treatment for pituitary adenomas, especially those A clear plastic mask made specially for each at higher risk of relapse (tumour >1cm in size). patient’s head, holds the patient’s head still Many factors have led to a reduction in the during the brief treatment. The targeting routine use of radiotherapy following surgery marks are lined up against the cross-beams of over the past 20 years: a laser set into the walls of the radiotherapy • Patients with functioning adenomas can room. The radiotherapy treatment is delivered frequently be treated with medical therapy to the target area from three directions. if hormone levels remain elevated post op, and some centres now reserve RT for those failing medical therapy e.g., in Acromegaly Benefits of radiotherapy somatostatin analogue therapy may be used first • Controls disease in 94% of cases at 10 years line and RT reserved for cases where growth and 88% at 20 years. hormone fails to reach safe levels on treatment. • Reduces local recurrence from 60% with • Changes in tumour size can now be surgery alone to 5% (surgery + RT). monitored with sequential MR imaging. • Reduces hormone secretion in 90% • Half of patients with normal pituitary cases of acromegaly, median 4 ½ years to function pre RT will develop normalisation of hormone levels.

Pituitary Disease Factfile 33 • 55% of patients with impaired visual fields or patient specific customised plan in order to treat acuity notice improvement following surgery this volume. Usually three or four treatment and RT. fields are used on a daily basis. Patient specific Note: because of the possibility of loss of normal shielding blocks or blocking leaflets in the pituitary function several years after RT, it is machine treatment head are used to reduce the essential that all patients have regular follow- volume of normal tissue irradiated. The planning ups with an endocrinologist. process can take 1 – 3 weeks.

Radiotherapy delivery Treatment Planning Radiotherapy is usually given in small doses, In order to reduce the amount of normal brain every working day, for 5-6 weeks giving a irradiated, the patient’s head should be firmly typical total dose of 45Gy in 25 fractions immobilised on to the radiotherapy treatment dose of 45 – 50 Gy. Each treatment, which is couch, thus reducing movement. This allows painless, lasts for 10 – 15 minutes – the actual the radiotherapist to minimise the margins radiotherapy about 2 minutes. Treatments are for movement added to the tumour target delivered using a Linear Accelerator (LINAC) Radiotherapy volume. Three techniques can be employed to machine. Lining up markers on the mask immobilise the patient: with laser beams embedded in the walls of • A mask can be made in one session using a the treatment room confirms the absolute thermoplastic mesh drawn down over the position of the patient relative to the treatment patient’s face, which is then attached to a firm machine, and thus safe delivery of treatment. baseboard. Using the stereotactic immobilisation ring • Or a perspex mask is moulded from a plaster ensures slightly higher precision than the mask of Paris cast of the patient’s face. This requires systems. But is more time consuming to deliver two hospital visits. A hole in the Perspex and requires specific equipment and expertise, mask is made for mouth and nostrils. Patients which is not available in all departments and its with a beard will be asked to shave to give a benefit is still being evaluated. firm fit of the mask. Accuracy for both mask Single fraction radiotherapy (radiosurgery) systems is 5-10mm. is increasingly used for pituitary adenomas • A stereotactic ring frame can be fitted using in the specific indications outlined above. skull vault screws (for a single fraction This is delivered using either a LINAC or treatment-radiosurgery) or using patient Gamma Knife® (an array of cobalt sources specific dental and occipital impressions to around the patient’s head). A dose of 100 Gy allow repeat usage for multiple treatments. to the tumour centre is delivered in a single This ring is then fixed to the treatment couch treatment. A steep dose gradient beyond with 1-3mm accuracy. the tumour edge aims to reduce the dose to A CT scan is performed with the patient in the surrounding critical structures. immobilisation device and the radiotherapist Stereotactic radiosurgery appears safe and and physicist define a treatment volume and effective with numerous studies confirming

34 Pituitary Disease Factfile this over the last few years. Patient selection is critical to success and depends in great part Questions patients may ask on the anatomy of the tumour to be treated and previous treatment given. The main How long will it take? determinant is the proximity to the optic The treatment itself only takes about 10-15 apparatus as this tolerates radiation less well. minutes, but radiotherapy has to be given in small doses over a long period (usually Adverse effects of radiotherapy 5 weeks), so you will need to attend the Transient side effects: radiotherapy clinic each working day • Skin erythema, irritation and transient hair during the treatment period. loss occurs at the sites of beam entry and exit. The hair almost always re-grows within a few Will I lose my hair? months. Generally, no. A small amount of hair is • Headache – treat symptomatically, avoid lost at the sites of radiation entry and exit steroids if possible. (i.e., the temples, above the forehead and • Tiredness, which can last for a few months. the nape of the neck typically in front of Long term, permanent side effects: each ear), but this almost always re-grows Radiotherapy • Hypopituitarism. In those patients with within a few months. normal function before RT, 30% of patients by 10 years, 50% by 19 years develop Will it hurt? hypopituitarism. They will need endocrine Treatment is much the same as having an follow up with annual pituitary function X-ray - it is quite painless. tests. • Optic nerve damage. <1% of cases show What are the possible side effects? some visual deterioration. Tiredness starts during or after the end • 2nd tumour. 1.9%at 20 years. However, of the treatment schedule and can last for techniques for RT have improved in the last several weeks. Some patients occasionally 20yrs. experience nausea, mild headache or • CVA. Relative risk of 4 compared with some reddening of the skin, but this is normal population. unusual. Rarer longer-term side effects will be discussed in more detail by the radiotherapist, however impaired pituitary function is seen in half of patients with functioning pituitaries before RT. This can occur after years. It is important the patient attends regular endocrine follow up for many years.

Pituitary Disease Factfile 35 Resources for patients Endocrinology (1997) Levy A & Lightman SL available from The Pituitary Foundation New York: Oxford University Press Helpline or our website www.pituitary.org.uk or our Endocrine Nurse Helpline The Epidemiology, Pathogenesis and Management of PituitaryTumours (1998) Webb SM (Ed) Patient Information Booklet Bristol, UK: BioScientifica • Pituitary Surgery &Radiotherapy Other information and resource links available at www.pituitary.org.uk

For GPs Endotext.org ‘Your Endocrine Source’ www.endotext.org (www.endotext.org/ neuroendo/index.htm)

The Pituitary Foundation Website Radiotherapy www.pituitary.org.uk

Oxford Handbook of Endocrinology OUP (2002) JAH Wass & H Turner (Eds).

More specialist resources Management of Pituitary Tumors: The Clinician’s Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey

Pituitary Tumours. Recommendations for service provision and guidelines for management of patients. Consensus statement of a working party (1997) RN Clayton & JAH Wass (Eds) London: Royal College of Physicians

The Diagnosis and Treatment of Pituitary Insufficiency (1997) Lamberts SWJ (Ed) Bristol, UK: BioScientifica

36 Pituitary Disease Factfile Pituitary Foundation fact sheet 12

Hormone Replacement Therapy

Patients may need hormone replacement deficiency, and who exhibit excessive tiredness, therapy for a number of reasons. Pituitary muscle weakness, weight gain, and tumours are the most common cause of depression, may benefit from GH therapy. GH hypopituitarism. The tumour may have is administered by daily subcutaneous injection. compressed or damaged the pituitary tissue The dose for adults is considerably lower than and patients found to have hypopituitarism that required for children (women require should be referred to a specialist more GH than men). The reported side effect endocrinologist. of GH therapy is fluid retention but this is Surgery to remove the tumour may rarely a problem with carefully titrated therapy cause temporary or permanent damage and in current practice. The evidence suggests that radiotherapy may (over a period of several GH therapy is clinically effective; it may also years) also irreversibly affect pituitary function. improve bone mineral density in adults with After treatment, long-term monitoring of GH deficiency. Replacement therapy with GH pituitary function is required, which should be has been approved by NICE in patients selected carried out by a specialist endocrinologist. The on the basis of a quality of life deficit. time interval between endocrine assessments will vary with the patient and the treatment FSH & LH received, but will probably be at intervals of FSH and LH secreted by the pituitary gland 6-12 months immediately post-treatment, stimulate the production of oestrogen, increasing to annual or biennial in the longer progesterone and testosterone. If FSH and LH term. are no longer produced, because of pituitary The correct route of referral is through an damage, sex hormone replacement with endocrinologist rather than neurosurgeon or oestrogen and progesterone or testosterone is Hormone Replacement others. Please see ‘Who and When to Refer’ usual, unless fertility is required. In the longer Therapy (factsheet 15). term, sex hormone replacement reduces the risk of osteoporosis and GH in both men and women. Testosterone can

GH replacement is required in children with be given as a gel, intramuscularly, by implant, low GH levels and slow growth rate. GH also buccal SR and patches. Oestrogen/progesterone has important effects in adult tissues such as can be given as skin patches or as pills. bone, fat and muscle, and lack of GH may For fertility, treatment with gonadotrophins increase mortality rates from heart disease. Until is required at a specialist centre which provides recently, the lack of widely available supplies effective monitoring. The human recombinant of GH has restricted this therapy to children. gonadotrophins available are free from possible However human recombinant growth hormone risk of new variant CJD. The objective is a is now available, which is free from risk of singleton pregnancy and a multiple pregnancy Creutzfeldt-Jacob disease (CJD), and has been should be considered as a failure of treatment. shown to be clinically effective. Adults who The specialist centre should have high- suffer from biochemically documented GH resolution ultrasonography available.

Pituitary Disease Factfile 37 HRT is safe for women of pre-menopausal age, life (several days), so that if a tablet is forgotten in whom the benefits of maintaining bone no action is required. strength outweigh the deficits, and breast cancer has not been shown to be a problem. AVP (ADH) Diabetes insipidus may be a transient effect ACTH of surgery or a long-term result of damage to ACTH deficiency is treated by prescribing the hypothalamus or posterior pituitary. AVP hydrocortisone or alternatively prednisolone (ADH) is replaced by giving desmopressin (not recommended for children). The average (referred to as DDAVP) provided as tablets, dose requirement of hydrocortisone is 20 mg nasal spray or melts. Patients should be split over the day (e.g. 10/5/5mg a day) and warned not to drink too much and a sensible most patients feel better if they have 3 doses precaution may be to leave out one treatment – on waking, midday and early evening (5 – each week to prevent water overload. DI may 6pm). In normal health, the lowest levels of disappear spontaneously. The only way to check cortisol are between 6pm and 6am. Patients will this is to stop the treatment. need to learn the situations in which a higher dose of steroid should be taken. Examples are: Prolactin (PRL) • No replacement formulation is available or • Dental treatment necessary under normal circumstances. The • Hospital treatment e.g., operations absence of prolactin may lead to an inability to Supplies of tablets and a steroid card should breast-feed. always be carried and wearing a Medic Alert Hormone Replacement or similar bracelet is important in case of accident. Learning the skill of self-injection Questions patients may ask Therapy of hydrocortisone (or encouraging another member of the family to do so) can be Will I have to take tablets in the long potentially life saving, particularly if patients term?

wish to travel to areas where medical care If, as often happens, the pituitary is not readily available. Full instruction on tumour or its treatment have caused intramuscular injection technique should be hypopituitarism, this does not usually provided by hospital clinic or general practice. recover and the patient will need long term Urgent injection of hydrocortisone is indicated replacement therapy. in emergency situations especially when intake of tablets is compromised e.g., by vomiting. Will I need regular check-ups? Yes, but as pituitary tumours are usually TSH well controlled and grow very slowly, if at In the absence of the normal production of all, outpatient appointments are usually TSH by the pituitary gland, patients require made 12 months to 2 years apart. Thyroxine. Thyroxine has a relatively long half

38 Pituitary Disease Factfile More specialist resources Will I need regular scans? Management of Pituitary Tumors: The Clinician’s Perhaps, but again, these too are carried Practical Guide (2003) (Second Edition), out years apart. Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Have I inherited this, will my children Press, Totowa, New Jersey get it? There is ongoing research into familial Pituitary Tumours. Recommendations for service incidence e.g. in Gigantism, but the provision and guidelines for management of majority of cases are sporadic. patients. Consensus statement of a working party (1997) RN Clayton & JAH Wass (Eds) London: Royal College of Physicians Resources for patients available from The Pituitary Foundation The Diagnosis and Treatment of Pituitary Helpline or our website www.pituitary.org.uk Insufficiency (1997) Lamberts SWJ (Ed) Bristol, or our Endocrine Nurse Helpline UK: BioScientifica

Patient Information Booklet Endocrinology (1997) Levy A & Lightman SL • The Pituitary Gland; Its conditions and New York: Oxford University Press hormones explained Other information and resource links available Treating Acromegaly. (1994) Wass JAH (Ed) at www.pituitary.org.uk Bristol, UK: Society for Endocrinology Hormone Replacement

For GPs The Epidemiology, Pathogenesis and Management Therapy Endotext.org ‘Your Endocrine Source’ of Pituitary Tumours (1998) Webb SM (Ed) www.endotext.org (www.endotext.org/ Bristol, UK: BioScientifica neuroendo/index.htm)

The Pituitary Foundation Website www.pituitary.org.uk

Oxford Handbook of Endocrinology OUP (2002) JAH Wass & H Turner (Eds).

Pituitary Disease Factfile 39 Pituitary Foundation fact sheet 13

Male Hypogonadism

Male hypogonadism is a state of testosterone Causes of primary hypogonadism deficiency which may result from either • Klinefelter’s syndrome (47 XXY) testicular or pituitary/ hypothalamic diseases. • Bilateral (un-descended testes) Males can be affected at any age and present • Bilateral anorchia (no testicular tissue present) with clinical features which differ according • Testicular torsion and orchitis to the timing of disease onset in relation to • Testicular tumour puberty. • Orchidectomy • or radiotherapy (affects Presenting symptoms fertility more than testosterone production) In pre-pubertal onset of testosterone deficiency, sexual development will be absent or Secondary hypogonadism: When androgen incomplete e.g., lack of genital enlargement, deficiency is the result of diseases of the lack of pubic/ axillary hair and beard growth, pituitary/ hypothalamus, the condition is lack of muscle development, lack of sexual described as secondary hypogonadism or interest and failure of the voice to break. hypogonadotrophic hypogonadism due to Spermatogenesis will not be initiated and the low levels of LH and FSH. When there infertility is the general rule. is no other concurrent pituitary hormone In post-pubertal onset of testosterone deficiency, deficit, the condition is usually called isolated the established secondary sexual characteristics are hypogonadotrophic hypogonadism. This may be poorly maintained. Symptoms include tiredness, due to a congenital deficiency in hypothalamic reduced libido and sexual functioning, reduced gonadotrophin releasing hormone (GnRH) body and facial hair and muscle mass, infertility and a lack of general well-being including Causes of secondary hypogonadism: depression. Flushing and sweating, similar to • Pituitary tumour (factsheet 3) female menopausal symptoms, may occur. • Suprasellar tumour i.e., craniopharyngioma Common to both presentations, testosterone (factsheet 8) deficiency is associated with reduced bone mass, • Isolated hypogonadotrophic hypogonadism increased risks for osteoporotic fractures and • Kallmann’s syndrome (isolated mild anaemia. hypogonadotrophic hypogonadism associated

Male Hypogonadism with an absent or impaired sense of smell) Classification of hypogonadism • (haemochromatosis or frequent Primary hypogonadism: When androgen blood transfusions) deficiency is the result of testicular diseases, the • Systemic diseases – acute and chronic condition is described as primary hypogonadism • treatment or hypergonadotrophic hypogonadism. The latter • AIDS is so-called because of high LH and FSH levels • Gross obesity from the pituitary which makes a vain attempt to Overall, pituitary tumours are the commonest stimulate the failing or absent to secrete causes of hypogonadism, followed by more testosterone. Klinefelter’s syndrome.

40 Pituitary Disease Factfile Clinical examination hypogonadism is confirmed Physical examination is important to confirm • karyotyping (Klinefelter’s syndrome - the clinical diagnosis of hypogonadism and 47XXY (80% of cases), mosaics, 48XXXY to elucidate the underlying cause. Important etc.) points include: • haemoglobin • assess pubertal progress and stature in late • bone mineral density adolescent patients • ultrasound of the testes • body, facial and pubic hair growth • body habitus (i.e., eunuchoidal limb Treatment proportions, muscle bulk, feminine fat Any potentially reversible underlying cause distribution, gynaecomastia) should be treated prior to commencing • testicular examination (assess size, position, replacement therapy. consistency i.e., very small and firm in Referral to a specialist Endocrinology centre Klinefelter’s) for investigation and subsequent management • visual field assessment which may highlight is recommended. Please see ‘Who and When to a pituitary lesion (classically a bitemporal Refer’ (factsheet 15). hemianopia resulting from chiasmal Androgen replacement can be administered in compression) the following modalities • sense of smell (absent in Kallmann’s syndrome) • Oral testosterone undecanoate (Restandol) can be given. Disadvantages include unreliable Investigations absorption requiring a twice or three times To confirm testosterone concentration is daily dosage and therefore inconsistent subnormal a single 9am measurement of testosterone replacement. This is not a reliable total testosterone usually suffices. In men over form of replacement for adult men. 50, particularly overweight patients, SHBG- • Testosterone esters (Sustanon 100 and 250) corrected free testosterone is important. are administered as a deep intramuscular injection usually every 2-3 weeks. They To differentiate primary from secondary provide reliable replacement with a good hypogonadism a single measurement of LH safety record for over 50 years. The main side and FSH will support the biochemical diagnosis effect is limited to relatively short duration, Male Hypogonadism of either primary or secondary hypogonadism. localised pain at the injection site. Nebido is the main injectable form of testosterone used; To identify the underlying cause and assess this formulation requires only 3-monthly severity of testosterone deficiency injections in to the muscles of buttocks, and • prolactin, 9am serum cortisol and thyroid provides constant testosterone levels for up function as a baseline assessment of pituitary to 14 weeks. Testosterone levels begin to rise function within 24 hours of the injection. • MRI scanning of the pituitary should • Testosterone gel is frequently used for be arranged if hypogonadotrophic replacement therapy. Average doses are

Pituitary Disease Factfile 41 50mg per day, but this needs titration by an linear growth potential. Older men should endocrinologist initially. Single sachet and ideally be treated with shorter acting preparations multiple dose preparations are available. It is in case of aggravating undetected androgen- applied once daily to to the skin surface over responsive diseases e.g., prostate cancer. Adult the shoulders, upper arms and abdomen will men may have a preference for longer acting deliver stable physiological blood levels of preparations such as testosterone implants. testosterone. The aim should be to maintain plasma • A buccal testosterone preparation called testosterone within the physiological range. It Striant SR. This is a twice daily mucoadhesive is good practice to ascertain that this has been tablet which adheres to the gum and is placed achieved in the first 3-6 months of initiating above the incisors. Psysiological levels of treatment by dose titration. Thereafter, an testosterone are achieved in most patients. annual pre-dosing check of testosterone should Side effects are infrequent and are usually be more than sufficient. local, including gum irritation, gingivitis and The clinical response should be apparent a bitter taste. within the first few weeks and best judged by Infertility resulting from secondary the patient’s own observations. Physical changes hypogonadism is usually amenable to such as genital, hair and muscle growth are treatment. In this situation there is dormant generally observed within 3-6 months. Bone testicular tissue which should respond to mineral density changes may be used as a gonadotrophin treatment with human chorionic more long-term parameter of responses and gonadotrophin (hCG) and FSH self-administered compliance to testosterone. subcutaneously twice to thrice weekly over 6-12 In older patients, monitoring the months. Primary hypogonadism including haematocrit, prostate size (digital rectal Klinefelter’s syndrome are synonymous with examination) and function (PSA) constitute irreversible and permanent infertility. sensible clinical practice. The psychological impact of infertility can Counselling in accepting the invariably be great and counselling may be required. See life-long testosterone treatment, subfertility or ‘Psychological Issues’ (factsheet 14) for basic infertility is important. information. Side effects may include gynaecomastia,

Male Hypogonadism exacerbation of prostatic disease, fluid retention Initiation and monitoring treatment: in those with pre-existing cardiac or renal disease, assessing response exacerbation of pre-existing liver dysfunction, Initial treatment will depend upon the age of obstructive sleep apnoea, polycythaemia and the patient and the underlying cause of the exacerbation of premorbid behavioural problems. hypogonadism. Younger patients are often androgen-naïve and will benefit from lower Watchpoints starting doses and gradual increase over 2-3 years Urgent - refer to hospital to the full adult replacement dose of testosterone. • back pain or urinary obstruction – may This is particularly desirable for maximising indicate prostate cancer and metastatic disease

42 Pituitary Disease Factfile • testicular mass Klinefelter’s Syndrome Association • deterioration of vision (suggesting secondary 13 York Rise, Orpington, Kent, BR6 8PR hypogonadism) Other information and resource links available at www.pituitary.org.uk Questions patients may ask For GPs Will my sex life improve? Endotext.org ‘Your Endocrine Source’ Testosterone treatment will increase www.endotext.org (www.endotext.org/ your sex drive. Sexual functioning is neuroendo/index.htm) more complicated and is dependent on several factors in addition to testosterone. The Pituitary Foundation Website Testosterone will not help erectile www.pituitary.org.uk impotence with normal sex drive Oxford Handbook of Endocrinology OUP (2002) Will I be able to have children? JAH Wass & H Turner (Eds). If the underlying cause is due to a testicular problem then invariably the patient will be More specialist resources infertile. With secondary causes hCG/FSH Management of Pituitary Tumors: The Clinician’s treatment is successful in up to 70% of cases. Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford Will it make me more aggressive? L. Lightman and Edward R. Laws. Humana Not in an antisocial sense but it will make Press, Totowa, New Jersey you have more self-confidence and be Pituitary Tumours. Recommendations for service more assertive. provision and guidelines for management of patients. Consensus statement of a working party (1997) Have I inherited this, will my children RN Clayton & JAH Wass (Eds) London: get it? Royal College of Physicians The Diagnosis and In all but very exceptional circumstances Treatment of Pituitary Insufficiency (1997) there is no hereditary link. Male Hypogonadism Lamberts SWJ (Ed) Bristol, UK: BioScientifica Endocrinology (1997) Levy A & Lightman SL Resources for patients New York: Oxford University Press available from The Pituitary Foundation Treating Acromegaly. (1994) Wass JAH (Ed) Helpline or our website www.pituitary.org.uk Bristol, UK: Society for Endocrinology or our Endocrine Nurse Helpline The Epidemiology, Pathogenesis and Management Patient Information Booklet of Pituitary Tumours (1998) Webb SM (Ed) • Male Hormones & Infertility Bristol, UK: BioScientifica

Pituitary Disease Factfile 43 Pituitary Foundation fact sheet 14

Psychological Issues

Pituitary disorders require life-long these problems, contact Changing Faces treatment. As with other chronic conditions, (factsheet 16 - Resources). many problems may arise which often Cushing’s patients usually suffer from truncal require the difficult task of disentangling obesity. Increased in Cushing’s the physiological, social and psychological affect weight and body fat distribution. They are aspects. also associated with muscle weakness, reduced In considering the psychological impact capacity for physical activity and decreased of pituitary disease, there are a number of glucose tolerance. GH therapy may help some common problems and patients will need patients (factsheet 12). sympathetic help in dealing with them. Altered body image is particularly stressful • The emotional impact of for women, and can be a major cause of • The need to adapt to altered body image depression when it affects relationships. • The feeling of ‘cure’ • Social interactions and the effects of chronic Feeling ‘cured’ illness on family Treatment, even if effective in regulating hormonal levels to what is regarded as normal, Emotional impact of neurosurgery may not be followed by a ‘feeling of cure’. Surgical treatment for pituitary disease may be Some patients who have pituitary insufficiency perceived as threatening and often produces may still feel that they have diminished overall a slower than hoped for improvement in the capacity even when they are receiving what is condition. Some patients may experience regarded as adequate hormone replacement severe symptoms similar to post traumatic therapy. stress disorder after treatment. Patients will be concerned that some of the tumour remains Social interactions and the effects of in situ and may regrow. A full recovery chronic illness on Family undoubtedly takes a considerable time and Hormonal imbalance has many consequences. building up unrealistic expectations before The effects of depression, tiredness, snoring and treatment impedes rather than helps recovery. reduced or absent sexual function are some of the aspects of pituitary disease which may lead The need to adapt to altered body image to social or family problems. Acromegaly can have a profound effect on Restoring hormonal balance should remove physical appearance causing Body Dysmorphic or improve many of these symptoms. Disorder (BDD). In acromegalics there are facial changes and enlargement of hands and feet, which, although slow to develop, are not always reversible. Some patients regard

Psychological Issues themselves as ‘freaks’, and learning to cope with this may take years rather than months. Intervention programmes exist to help with

44 Pituitary Disease Factfile Resources for patients available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk or our Endocrine Nurse Helpline

Patient Information Booklet The Pituitary Foundation well being series of booklets including Psychological Impact of Diagnosis & Treatment and Relationships & Communication with Yourself and with Others

Other information and resource links available at www.pituitary.org.uk

For GPs Endotext.org ‘Your Endocrine Source’ www.endotext.org (www.endotext.org/ neuroendo/index.htm)

The Pituitary Foundation Website www.pituitary.org.uk

More specialist resources Emotional Aspects of Pituitary Disease. (Eds) Weitzner MA, Sonino N & Knutzen R 1998 Psychotherapy and Psychosomatics 67

Management of Pituitary Tumors: The Clinician’s Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey (This contains a “patient’s eye view” chapter written by a patient.) Psychological Issues

Pituitary Disease Factfile 45 should you refer Pituitary Foundation fact sheet 15 Referrals: When

Referrals: When should you refer and to whom

Diagnosis of pituitary disease is not Who should you refer to? straightforward. Ideally to a specialist endocrinologist or a local There is a wide range of symptoms, reflecting physician with a special interest in endocrinology. the various conditions caused by a pituitary It is better to see an endocrinologist first rather tumour. Some are specific and obvious but than a surgeon as the surgeon will need to refer many are vague and may not point to the the patient to an endocrinologist in any case. In pituitary. some cases surgery is not recommended. Most GPs see only one or two cases in their The endocrinologist can arrange all the whole careers, which compounds the problem. specialist diagnostic tests to be completed prior The following tables list symptoms associated to surgery enabling accurate monitoring of with various tumour types: more details are treatment to take place. included in the specific sheets. Whilst you would not want to send every Life-long relationship patient with a headache to an endocrinologist, Life-long specialist monitoring will be required those with high circulating thyroxine and high after initial treatment to ensure the appropriate TSH should be referred. To this end a list of and optimum balance of hormones is achieved. basic tests is also included. Many patients will be on life-long hormone For acromegaly & prolactinoma especially, there replacement. In most cases a shared care should be a low threshold for referral for any protocol is established between the specialist patient with any suspicion of these conditions and the patient’s GP. as the greatest challenge in their diagnosis is thinking of the disease. Once suspected, Presenting symptoms biochemical confirmation or exclusion of the These are the main symptoms; see individual disease is usually straightforward. sheets for additional information.

Main symptoms common to various tumour types Associated with: Visual disturbance Non-functioning (NF), acromegaly, hyperprolactinaemia, craniopharyngioma Oligomenorrhoea or amenorrhoea NF, hyperprolactinaemia, hypogonadism Reduced libido in men & women, NF, hyperprolactinaemia hypogonadism and reduced potency in men Headache NF, acromegaly, hyperprolactinaemia, craniopharyngioma Tiredness and lack of energy NF, acromegaly, hypopituitarism (especially loss of GH and/or ACTH).

46 Pituitary Disease Factfile should you refer Referrals: When

Main symptoms specific to one or two types of tumour Associated with: Coarsening of facial features Acromegaly Enlarged hands and feet, growth of the jaw Acromegaly Carpal tunnel syndrome Acromegaly Excessive sweating and oily skin Acromegaly Sleep apnoea Acromegaly Moon face - particularly filling in of the Cushing’s temporal fossa Weight gain - central obesity Cushing’s Muscle wasting and proximal myopathy Cushing’s (patients have difficulty standing from a seated position without use of arms) Thin skin - tendency to bruise Cushing’s Hirsutism (caused by androgen excess) Cushing’s Violaceous striae Cushing’s Hypertension Acromegaly, Cushing’s Diabetes Acromegaly, Cushing’s Osteoporosis and fractures Cushing’s Psychiatric disturbance (often characterised by Cushing’s amplification of previous personality traits) Galactorrhoea Hyperprolactinaemia Growth retardation in children. Any pituitary tumour causing hypopituitarism and Growth Hormone Deficiency (GHD), craniopharyngioma In adults: excessive tiredness, muscle weakness, Hypopituitarism - GH deficiency lack of drive, impaired quality of life Tired, difficulty recovering from minor illness Hypopituitarism - (ACTH, cortisol deficiency), craniopharyngioma Weight gain, decreased energy, sensitivity to Hypopituitarism - TSH deficiency. cold, constipation, dry skin Pale appearance, weight loss, low blood Hypopituitarism – ACTH deficiency pressure, dizziness, tiredness, ‘collapse’ during intercurrent illness

Pituitary Disease Factfile 47 should you refer Referrals: When

Main symptoms specific to one or two types of tumour Associated with: Thirst, polydipsia, polyuria and nocturia Hypopituitarism - AVP deficiency - diabetes insipidus, craniopharyngioma Delayed or arrested puberty, and very Craniopharyngioma occasionally precocious puberty. Dyspareunia and hot flushes in women Hypogonadism Absence of or incomplete sexual development: Pre-pubertal onset of testosterone deficiency - - lack of genital enlargement male hypogonadism - lack of pubic/ axillary hair and beard growth - lack of muscle development - lack of sexual interest - failure of the voice to break. - spermatogenesis will not be initiated and infertility is the general rule. Poorly maintained established secondary sexual Post-pubertal onset of testosterone deficiency characteristics: - tiredness - reduced libido and – male hypogonadism sexual functioning - reduced body and facial hair and muscle mass, infertility

48 Pituitary Disease Factfile Pituitary Foundation fact sheet 16

Resources: Information and Support

For patients For GPS Resources: information Publications produced by The Pituitary Endotext.org ‘Your Endocrine Source’ Foundation, available both as printed matter www.endotext.org and support and via our website www.pituitary.org.uk (www.endotext.org/neuroendo/index.htm)

Patient information booklets The Pituitary Foundation Website

• The Pituitary Gland; Its conditions and www.pituitary.org.uk hormones explained • Acromegaly Endocrinology (1997) Levy A & Lightman SL • Cushing’s New York: Oxford University Press Treating • Diabetes Insipidus Acromegaly. (1994) Wass JAH (Ed) Bristol, • Prolactinoma UK: Society for Endocrinology • Male Hormones & Infertility Issues • Pituitary Surgery & Radiotherapy The Epidemiology, Pathogenesis and Management • Psychological Issues in Pituitary Disease (Series) of Pituitary Tumours (1998) Webb SM (Ed) • Employment Bristol, UK: BioScientifica • Weight Control & Nutrition • Hydrocortisone Advice for Adults Emotional aspects of pituitary disease (1998) • Hydrocortisone Advice for Parents Weitzner MA, Sonono N & Knutzen R (Eds). • Pituitary Patients Handbook Psychotherapy and Psychosomatics 67

Proceedings of several Pituitary Endocrinology (1997) Levy A & Lightman SL. Foundation conferences New York: Oxford University Press Clinical These proceedings include many aspects of Endocrinology (1998) Grossman AB Oxford: pituitary disease such as articles on growth Blackwell Science hormone, new aspects of surgery, visual problems and reports of workshops on acromegaly, Treating Acromegaly (1994) Wass JAH (Ed) Cushing’s, diabetes insipidus, hypopituitarism, Bristol, UK: Society for Endocrinology prolactinoma, psychological problems, self image and patient-consultant communication.

Pituitary Life: The Pituitary Foundation’s magazine These contain useful articles on all aspects of pituitary disease written by both medical specialists and patients. Examples include information on taking steroids, experiences of testosterone therapy, etc.

Pituitary Disease Factfile 49 Resources: Information and Support

Resources: information This information is correct at time of publication and support Name of organisation Website Phone number Addison’s Disease Self Help Group addisons.org.uk British Society for Paediatric

Endocrinology and Diabetes bsped.org.uk British Thyroid Foundation btf-thyroid.org 0870 770 7933 Diabetes UK diabetes.org.uk 0345 123 2399 Congenital Adrenal Hyperplasia cahisus.co.uk Carers UK carersuk.org 0808 808 7777 Changing Faces changingfaces.org.uk 0300 012 0275 Child Growth Foundation childgrowthfoundation.org 0208 995 0257 Contact a Family cafamily.org.uk 0808 808 3555 Headway headway.org.uk 0808 800 2244 Sexual Advice Association sda.uk.net Kallmann’s Syndrome hypohh.net Medic Alert medicalert.org.uk 01908 951045 Multiple Endocrine Neoplasia amend.org.uk National Osteoporosis Society nos.org.uk 01761 471 771 Premature daisynetwork.org.uk Pre-menstrual Syndrome pms.org.uk 0844 815 7311 Polycystic disease verity-pcos.org.uk RNIB rnib.org.uk 0303 123 9999 Tall Persons Club tallclub.net 07000 825 512 Turners Syndrome Support Society tss.org.uk 0300 111 7520 Other useful contacts site self-help.org.uk

50 Pituitary Disease Factfile Pituitary Disease Factfile 51 The Pituitary Foundation © 2014 version 3: The Pituitary Foundation 86-88 Colston Street, This material may not be stored or reproduced Bristol, BS1 5BB in any form nor by any means without the www.pituitary.org.uk permission of The Pituitary Foundation. Helpline: 0117 370 1320 Version 4 to be reviewed June 2016 Administration Line: 0117 370 1333

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