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The Pituitary Foundation Information Booklets

Working to support pituitary patients, their carers & families

GP fact file A5 update Nov 2020.indd 1 05/11/2020 15:07 Introduction 3 A Guide to 5 Non-functioning pituitary tumours 6 9 Cushing’s disease 13 16 20 Craniopharyngioma 24 27 Traumatic brain injury 29 Pituitary surgery 30 Radiotherapy 33 Hormone replacement therapy 37 40 Psychological Issues 44 Referrals – Who and When to refer 46 Resource list 49

2 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 2 05/11/2020 15:07 Introduction - about this factfile Abbreviations These Factsheets were written in response to ACTH Adrenocorticotrophic hormone requests by General Practitioners and their AVP (ADH) pituitary patients for more information on ADH Antidiuretic hormone pituitary disease. The Pituitary Foundation has CSF Cerebrospinal fluid already produced an excellent set of patient CT Computed tomography booklets explaining how pituitary disease can DDAVP Desmopressin affect patients’ lives, the kind of treatments DI Diabetes insipidus available and general advice on how to cope FSH Follicle-stimulating hormone with particular problems. This Factfile includes GH Growth hormone more detailed information, specifically written LH Luteinising hormone for the GP. Each Factsheet gives background GnRH Gonadotrophin-releasing hormone information on the condition, how it is PRL investigated and possible treatments. Since many MRI Magnetic resonance imaging of the investigations and treatments may be used TSH Thyroid-stimulating hormone for several different syndromes, the information on the sheets is extensively cross-referenced. Resources are provided on each Factsheet and an Helpline: additional separate list, including organisations, for general patient support enquiries is also included. 0117 370 1320 [email protected] Acknowledgements Monday to Friday 10:00am to 4:00pm We would like to thank the many specialists in the world of who have written Endocrine Nurse Helpline: these sheets including Stephanie Baldeweg, 0117 370 1317 (scheduled hours) Peter Bayliss, Claire Blessing, Peter Clayton, www.pituitary.org.uk Jurgen Honneger, Trevor Howlett, Stafford Lightman, John Monson, John Newell-Price, Peter Trainer and John Wass. They, alongside Disclaimer: patients and GPs, read and made valued Every care has been taken in the compilation contributions to achieve this Factfile. of this Factfile to ensure it reflects current practice (as at publishing date). Knowledge and clinical practice continually evolve. The reader is therefore advised to check with a specialist endocrinologist or with a product manufacturer if they have any concerns. The publishers and authors are not responsible for any errors or omissions or for any consequences from the application of the information presented in this Factfile.

Pituitary Disease Factfile 3

GP fact file A5 update Nov 2020.indd 3 05/11/2020 15:07 Pituitary apoplexy Pituitary Foundation fact sheet 1 A guide to A guide to

A Guide to Pituitary Apoplexy

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

4 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 4 05/11/2020 15:07 Pituitary Foundation fact sheet 2

Non-functioning pituitary tumours

The most common type of pituitary tumour In the presence of pressure signs/ pituitary tumours is non-functioning (i.e. it does not cause ex- symptoms Non-functioning cessive hormone production). Tumours of this Patients will usually need transsphenoidal type most commonly become apparent when surgery (factsheet 10), which may be followed the patient has visual symptoms or headaches by radiotherapy to prevent recurrence (factsheet

due to pressure on the optic nerve and it is of- 11). If pituitary hormones are deficient, pituitary ten the optician who refers the patient with hormone replacement therapy will be given abnormal visual fields to the GP (in which (factsheet 12). case the GP would want to refer to an oph- thalmologist who, in turn, is likely to refer Patient management to an endocrinologist). The tumour may also Post-operative damage the adjacent, normal pituitary gland Most patients will have improved, or at least (causing hypopituitarism - factsheet 6) or oc- stabilised, visual fields. Removal of the nasal casionally compress the pituitary stalk, caus- packing, if this method used, is often the ing 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 visual field assessments may be needed. MRI scans are usually repeated within the first Investigations post-operative months and follow-up scans are An MRI scan will be carried out to determine initially carried out at increasing intervals from 6 the size and site of the tumour. Visual field tests 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 treatment, symptoms patients should be tested for pituitary function Patients may not need treatment, but will be on a regular basis, probably at 6 months, 1 year, monitored closely using MRI scans and visual field 2 years and then bi- or triennially. checks at intervals of 6 or 12 months. Alternatively surgery or, rarely, radiotherapy may be advised.

Pituitary Disease Factfile 5

GP fact file A5 update Nov 2020.indd 5 05/11/2020 15:07 Pituitary Foundation fact sheet 2

Watchpoints pituitary tumours Non-functioning Urgent - refer to hospital good if the tumour is treated promptly. • Deterioration of vision Treatment is effective in stopping any • Clear fluid dripping down the back of the further visual loss in almost all cases. throat or through the nose soon after surgery

(CSF leak - factsheet 10) Why have my periods stopped? The tumour may prevent the pituitary from Non-urgent (but still very important) being able to secrete the hormones that • If the patient is on hydrocortisone, ensure control and fertility. that replacement therapy is increased when seriously ill or under major physical or Have I inherited this, will my children psychological stress (factsheet 6) get it? • Treat headaches and migraine In all but very exceptional circumstances • Ask about erectile function there is no hereditary link. • General wellbeing - consider whether the patient is growth hormone deficient e.g., if energy lacking, otherwise for replacement therapy • Menstrual cycle loss – consider whether the Resources for patients patient needs hormone replacement therapy available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk or our Endocrine Nurse Helpline Questions patients may ask Patient information booklets Why do I bump into objects? • The Pituitary Gland: its conditions & Hormones The pituitary normally sits under the optic explained apparatus. When the pituitary enlarges, • Pituitary Surgery & Radiotherapy visual problems caused by compression Other information and resource links available of the visual pathway are often the first at www.pituitary.org.uk. symptom. Visual acuity (vision that can be corrected by wearing spectacles) may not For GPs be changed, but visual fields are reduced, Endotext.org ‘Your Endocrine Source’ firstly in the upper outer quadrant, then www.endotext.org (www.endotext.org/ the whole temporal field (the field of vision neuroendo/index.htm) on both left and right sides of the head as The Pituitary Foundation website opposed to central vision). www.pituitary.org.uk

Will my sight return after treatment? Oxford Desk Reference Endocrinology (2018) H The chances of at least partial recovery are Turner, R Eastell, A Grossman (editors)

6 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 6 05/11/2020 15:07 Pituitary Foundation fact sheet 3

Acromegaly

Incidence: 4-6 new cases per million per year The main features are: Prevalence: 60 per million • coarsening of facial features • enlarged hands and feet • carpal tunnel syndrome Acromegaly is the result of growth hormone • excessive sweating and oily skin (GH) hypersecretion by a pituitary macro- or • headaches microadenoma. Many of the actions of GH • vision disturbance are mediated by insulin-like growth factor-1 • sleep apnoea (IGF-1), which is secreted from the liver and • general tiredness other organs under the regulation of GH. GH Acromegaly levels fluctuate over the day. Plasma IGF-1 There should be a low threshold for referral for levels, in contrast, fluctuate little during the any patient with any suspicion of acromegaly day and can be used, along with GH, as a as the greatest challenge in the diagnosis of measure of disease activity. Up to a third of acromegaly is thinking of the disease. Once tumours co-secrete prolactin. suspected, biochemical confirmation or exclusion Acromegaly most often occurs in adults aged of the disease is usually straightforward. We 30-50 years. Presentation before the growing ends strongly recommend that all referrals be to an of have fused (usually around 18 years of endocrinologist rather than neurosurgeon or age) is rare and is the cause of pituitary gigantism. others. Please see ‘Who and When to Refer’ Elevated GH levels are associated with changes in (factsheet 15). appearance, headaches, sweating and tiredness. Acromegaly affects a number of body systems and Investigations if untreated is associated with a two-fold increase in Investigations will include a GH series and an mortality, particularly from cardiovascular disease. analysis of the GH response to a glucose load (Glucose Tolerance Test), as well as measurement Presenting symptoms of prolactin and other pituitary function tests. Excessive GH secretion produces a gradual change An MRI scan will be carried out and visual field in appearance (not usually noticed by those living tests may be performed to determine the size and or working with the patient) due to its effects on position of the adenoma. cartilage and soft tissues. Symptoms have often been present for a decade before the diagnosis is Treatment possibilities made. The patient may notice enlargement of the Epidemiological evidence suggests that with hands and feet and may experience growth of the normalisation of GH and IGF-1 levels, life jaw. Nerve compression symptoms may occur, expectancy can be restored to normal. The particularly carpal tunnel syndrome. Premature treatment recommended by the consultant will osteoarthritis of the weight-bearing joints is also depend on the size and activity of the adenoma characteristic. Obstructive sleep apnoea may be and also on the age of the patient. Transsphenoidal present, especially in men, leading to daytime surgery is the treatment of choice in most cases sleepiness. and can be dramatically effective, especially for

Pituitary Disease Factfile 7

GP fact file A5 update Nov 2020.indd 7 05/11/2020 15:07 microadenomas. However, some patients may need inhibit GH release from the pituitary and as GH medical treatment or radiotherapy after surgery to levels do not fall with treatment, disease activity reduce GH levels. Some GH-secreting adenomas is judged by measuring IGF-1. are treatable by long-term medical therapy with or Patients may develop hypopituitarism without radiotherapy. The consultant may offer (factsheet 6) after surgery, or several years after the patient a choice between long-term medical radiotherapy. Hormone replacement therapy treatment, involving injections, or surgery. will then be needed (factsheet 12).

Medical therapy Watchpoints Acromegaly Some patients may need long-term medical Urgent - refer to hospital treatment to maintain acceptable GH and • Deterioration of vision IGF-1 levels. High levels of GH, even when the • Clear fluid dripping down the back of the patient has no symptoms, are associated with a throat or through the nose soon after surgery 2-3-fold increase in mortality. (CSF leak - factsheet 10 Surgery) Stabilisation of GH may be achieved with a Non-urgent (but still very important) dopamine agonist, particularly if the tumour • If the patient is on hydrocortisone, ensure also secretes prolactin. Cabergoline, is effective, that replacement therapy is increased when potent and causes few side effects but there seriously ill or under major physical or can be a rare side effect of impulsive control psychological stress disorder (a strong desire to gamble or an • Treat headaches increased sex drive). This usually settles when • Treat depression treatment is stopped. However, the somatostatin • Treat carpal tunnel syndrome analogues octreotide and lanreotide, which act • Treat osteoarthritis: refer for hip/knee by inhibiting GH release from the pituitary, are replacement if required much more effective in reducing GH and IGF- • Ask about erectile function, 70% have 1 to acceptable levels. Octreotide/Lanreotide are problems. Treat this, reassure that it is part of available as long-acting preparations that require the disease and that it can be treated to be injected monthly, (Sandostatin LAR and • The patient is likely to have obstructive apnoea Lanreotide Autogel). Normalisation of GH and to snore very loudly. It can be helped by and IGF-1 can be achieved in between half and treatment to lower GH, and by continuous two-thirds of patients. Somatostatin analogues positive airways pressure (CPAP) also cause tumour shrinkage in most cases, • Ask about change in bowel habit as some when they may improve surgical results. Some increased risk of colonic polyps and colonic patients suffer gastrointestinal side effects with carcinoma these drugs and there is some risk of developing • Patient may need colonoscopy. gallstones. Pegvisomant is a GH receptor antagonist that blocks GH action by preventing GH from binding to its receptor. Unlike other forms of treatment, it does not attempt to

8 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 8 05/11/2020 15:07 Acromegaly 9 05/11/2020 15:07 Pituitary Disease Factfile Disease Pituitary Why do I have such bad arthritis? bad such do I have Why changes are and degenerative Growth main aims of of the common. One this. is to prevent treatment so much? do I sweat Why normal are but when GH levels known Not disappears. the problem children my will this, I inherited Have it? get all but very circumstances In exceptional is no hereditary link. there Resources for patients for Resources Foundation Pituitary The from available www.pituitary.org.uk or our website Helpline Helpline Nurse or our Endocrine Booklet Information Patient • Acromegaly links available information and resource Other at www.pituitary.org.uk GPs For www. Source’ Endocrine ‘Your Endotext.org endotext.org (www.endotext.org/neuroendo/ index.htm) Website Foundation PituitaryThe www.pituitary.org.uk Why do I have backache? do I have Why of cartilaginous tissues causes Growth and abnormalities musculoskeletal changes. degenerative Why do I keep biting my tongue? my biting do I keep Why of the tongue. growth GH promotes Why does my jaw ache when I eat an when I eat ache jaw my does Why apple? dental disturbs of the mandible Growth on the strain increased puts and occlusion joints. temporomandibular Why has my shoe size increased? size shoe my has Why above. See Why can’t I get my wedding ring on? ring wedding my I get can’t Why the soft tissues of the joints of Hypertrophy causes enlargement of hands and feet. Why am I getting headaches? am I getting Why surrounding A large tumour may compress tissues. Why do I wake up tired? do I wake Why hormone causes hypertrophy of Growth the nasopharyngeal tissue and sleep apnoea the partner).(usually noticed by This can be treated Why do my hands hurt? hands do my Why tissue can occur in the connective Growth the compressing of the carpal tunnel median nerve. Questions patients may ask may patients Questions GP fact file A5 update Nov 2020.indd 9 Pituitary Foundation fact sheet 4

Cushing’s disease

Incidence: 5-6 new cases per million per year • hypertension • diabetes • and fractures Strictly speaking, if the source of the problem • psychiatric disturbance (often characterised by is the pituitary gland, then the correct amplification of previous mood swings). name is Cushing’s Disease. Whereas, if it originates anywhere else, then the correct Investigations name is Cushing’s Syndrome. Cushing’s Overnight dexamethasone suppression test and/ disease (i.e. an ACTH-secreting pituitary or 24-hour urinary cortisol measurements. If adenoma) is the most common cause of this indicates Cushing’s syndrome further tests spontaneous Cushing’s syndrome; other to confirm the diagnosis and to determine the causes are an adrenal tumour or an ectopic source of excessive cortisol will be required. tumour secreting ACTH. Spontaneous Normal screening tests do not always exclude Cushing’s syndrome is caused by excessive the diagnosis - if clinical suspicion is high then circulating cortisol; it is rare but is associated specialist referral may still be necessary. During

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

10 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 10 05/11/2020 15:07 This is the result of the profound change in • Patients may have major mood swings after cortisol status. No further treatment may be successful treatment to lower circulating required except monitoring for recurrence of corticosteroids. This can last for many months, Cushing’s and regrowth of the tumour. However, so reassurance and treatment for depression most patients will require hydrocortisone therapy, may be necessary some on a long-term basis and patients need • Obesity is often the aspect of Cushing’s disease strong reassurance that feeling worse after surgery that female patients find most distressing. is usual, but that in the long run things improve. Weight reduction following successful If the patient needs hydrocortisone for more than 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

Patients require close follow up on a long-term Cushing’s disease 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 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

Pituitary Disease Factfile 11

GP fact file A5 update Nov 2020.indd 11 05/11/2020 15:08 Why do I bruise so easily? Increased breakdown of tissue proteins causing weakening of capillaries.

Why have I developed stretch marks? Increased breakdown of skin proteins makes the skin more fragile

Why do I have backache? As above - the back muscles are weakened by the steroids and the extra weight which you gain also puts a strain on them. The steroids also affect the bones of the back.

Cushing’s disease Have I inherited this, will my children get it? In all but very exceptional circumstances there is no hereditary link.

Resources for patients 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

12 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 12 05/11/2020 15:08 Pituitary Foundation fact sheet 5

Hyperprolactinaemia

Incidence: Most common secreting adenoma. Once suspected, biochemical confirmation or They are more common in women and exclusion of the disease is usually straightforward. macroprolactinomas are more common in men. See ‘Who and When to Refer’ (factsheet 15).

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

Pituitary Disease Factfile 13

GP fact file A5 update Nov 2020.indd 13 05/11/2020 15:08 Please see ‘Who and When to Refer’ (factsheet night and by starting at low dose. 15). 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. A rare with hypogonadism – manifest clinically as side effect can be impulse-control disorder - a amenorrhoea or erectile dysfunction. In any strong desire to gamble or increased sex drive; patient with one year of hypogonadism a this usually settles when treatment is stopped. density scan should be performed and a major However, recent guidance suggests that goal in the treatment of hyperprolactinaemia is patients taking cabergoline should have regular the prevention of osteoporosis. examination of the heart (echocardiography) and In addition, treatment should stop watch out for shortness of breath as cabergoline galactorrhoea and restore oestrogen levels in can cause (at higher dosage) fibrosis of the women, and hence menstruation, fertility, libido lungs and heart valves. There had been concern and vaginal lubrication to normal. In men, about fibrosis etc, but that recent large UK data treatment of high prolactin should normalise suggest no excessive risk. Any monitoring will levels, and hence erectile function be advised by an endocrinologist. and libido. For macroprolactinomas, an additional Pregnancy and prolactinomas objective is to shrink the tumour in order to Patients should be followed during pregnancy reduce any pressure effects, such as visual failure. by an endocrinologist. Ideally it is advisable for patients to have discussed pregnancy with their Patient management endocrinologist prior to conception. Hyperprolactinaemia Most patients are treated medically with Most women are advised to cease taking the dopamine agonists cabergoline, or dopamine agonists for the duration of pregnancy bromocriptine, both of which reduce prolactin and during lactation. However, many thousands levels, allow oestrogen or testosterone levels to of babies have been born to mothers taking rise and greatly reduce the size of the tumour. bromocriptine and there is no evidence of Surgery to reduce tumour size, and radiotherapy an increased incidence of malformation or to reduce the chance of recurrence, are rarely miscarriage. Cabergoline treatment appears to required. be safe during pregnancy. During pregnancy, Medical treatment with cabergoline, there is a slight risk of tumour enlargement, quinagolide, or bromocriptine controls prolactin particularly in patients with macroadenomas. and symptoms in the majority of patients, but Any patient who experiences severe headaches or needs to be continued long term. In patients with visual disturbances should be seen urgently by microprolactinomas an attempt to withdraw the their specialist. medication can be made after 3 years. These drugs can be associated with some dizziness Watchpoints and nausea. This can be limited by taking the Urgent - refer to hospital medicine in the middle of meals or last thing at • Deterioration of vision

14 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 14 05/11/2020 15:08 Non-urgent (but still very important) sex-hormone deficiency (particularly • Remember that successful treatment usually oestrogen in women) causes thinning of results in restoration of fertility (particularly the bones, or osteoporosis. Therefore, most in microprolactinomas) doctors believe that women without regular • Patients may be predisposed to problems periods should receive treatment. The same related to osteoporosis applies to men with low testosterone levels. • Ask about erectile function. Reassure that it is part of the disease and that it can be treated How long will I have to take tablets for prolactinoma? You will probably need to take these tablets Questions patients may ask for a relatively long time, with interruption during pregnancy as described earlier. Why do I have a discharge from my If you have a microprolactinoma, many breasts? specialists withdraw treatment for a trial Prolactin is normally required to initiate period every three years or so; in some and maintain lactation. The secretion of patients the problem seems to disappear prolactin from a pituitary tumour may have during prolonged tablet treatment. If you the same effect. have a large tumour, your treatment courses may last several years; tumour control is Will a microprolactinoma grow into a maintained and side-effects during long- macroprolactinoma? term treatment are not usually a problem. In the vast majority of cases, no. This very rarely happens. What are my fertility prospects as a Hyperprolactinaemia man with prolactinoma? Have I inherited this, will my children Tablet treatment alone may improve your get it? count and lead to the return of In all but very exceptional circumstances normal fertility, although this may take there is no hereditary link. several months. Additional treatment with hormone injections (FSH and LH) Do all patients with prolactinomas may also be necessary. Fertility is usually need treatment? attainable. Most do. If you have infertility problems, problems with lack of interest in sex (low Is tablet treatment better than surgery libido) or impotence, excessive milk for prolactinomas? production or a large tumour causing Tablet treatment is the accepted form of pressure symptoms, then there is a clear case treatment. Occasionally (5-10%) patients for treatment. If not, then the need may not have either severe side effects or do not seem so clear. However, prolonged respond to cabergoline. In these patients

Pituitary Disease Factfile 15

GP fact file A5 update Nov 2020.indd 15 05/11/2020 15:08 surgery may be advised although it is not always curative (70- 80%) and the operation may cause hypopituitarism.

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

Patient Information Booklet • Prolactinoma 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 Hyperprolactinaemia

16 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 16 05/11/2020 15:08 Pituitary Foundation fact sheet 6

Hypopituitarism

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

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, vaginal dryness 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 (argine vasopressin or Thirst, polyuria and nocturia – diabetes insipidus Anti-Diuretic Hormone) Hypopituitarism

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

Pituitary Disease Factfile 17

GP fact file A5 update Nov 2020.indd 17 05/11/2020 15:08 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 specialist to children. The treatment of adults with GH 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 circadian rhythm. In women with hydrocortisone (= cortisol), typically 2 or 3 times periods, bloods are normally performed in the daily. Prednisolone is occasionally used. Increased follicular phase – but measurement of a Day 21 doses are required during acute stress including may be used to confirm ovulation. intercurrent illness or surgery. Fludrocortisone If fertility is desired, then a different approach is not normally required in pituitary deficiency. to hormone replacement will be needed and a TSH - Treatment with levothyroxine. Free T4 full assessment of both partners will be carried levels must be used for monitoring since TSH out. levels are not informative. Thyroid function In pituitary-dependent FSH/LH - Treatment with oestrogen in hypothyroidism circulating thyroid hormone women (and progestogen in women with a levels are low or low-normal but TSH can be low, ). Testosterone replacement in men normal or even slightly elevated. Laboratories given intramuscularly (i.m. every 2-4 weeks or must be asked for free thyroxine (free T4) as 3-monthly depot), transdermally (usually via well as TSH, and thyroid hormone replacement gel), or by implant. For fertility, treatment with adjusted on the basis of free thyroxine level is required which should only be (many laboratories will now only provide performed at a specialist centre which provides TSH measurements routinely unless free T4 is effective monitoring. specifically requested and discussed) AVP/ADH - Treatment with desmopressin Hypopituitarism Adrenal function ACTH stimulated (DDAVP) by intranasal spray, tablets or Melts. secretion of cortisol is assessed using the short synacthen or the insulin stress test. A basal Patient management 9am cortisol gives limited information but low Management of patients with hypopituitarism levels (<200nmol/L) should prompt early (and on multiple hormone-replacement therapy <100nmol/L urgent) referral. (which The Foundation believes) is best achieved Diabetes insipidus The diagnosis and cause by life-long supervision by a specialist endocrine is usually obvious and if so may be confirmed outpatient clinic. The time interval for specialist by measurement of basal serum and urine monitoring will vary with the patient and

18 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 18 05/11/2020 15:08 the treatment received, but will probably be usually made 12 months to 2 years apart. at intervals of 2-6 months immediately post treatment, to annual or biennial in the longer Will I need regular scans? term. Patients may need help with managing Perhaps, but again, these too are carried out hydrocortisone therapy (factsheet 12). several years apart.

Watchpoints Will I still be able to have a family? Urgent - refer to hospital Yes, if the reason for infertility is pituitary • Deterioration of vision disease. The effects of pituitary tumours • Clear fluid dripping down the back of the on fertility can be treated, although some throat or through the nose soon after surgery treatments are not currently paid for by the (CSF leak - factsheet 10) NHS (factsheet 12). • As emergency if unable to take increased oral steroid replacement during acute intercurrent If I take replacement therapy, will I illness (e.g., vomiting) feel exactly the same as I did before Non-urgent (but still very important) my pituitary tumour developed? • If the patient is on hydrocortisone, ensure Replacement therapy is unable to fully that replacement therapy is increased when match the body’s natural, intricate hormone seriously ill or under major physical or balance. Every patient is different and, psychological stress whilst many return to fairly normal life, the • Watch for gradual deterioration in endogenous main object of replacement therapy is to pituitary function and provide replacement achieve as good a quality of life as possible therapy as required for patients.

Have I inherited this, will my children Questions patients may ask get it? In all but very exceptional circumstances Will I have to take tablets in the long there is no hereditary link. term? If the pituitary tumour or treatment for it has Hypopituitarism 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 controlled and, if they regrow at all, grow very slowly. Outpatient appointments are

Pituitary Disease Factfile 19

GP fact file A5 update Nov 2020.indd 19 05/11/2020 15:08 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

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

20 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 20 05/11/2020 15:08 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). Craniopharyngiomas are benign tumours • Changes in behaviour. accounting for approximately 9% of all in- Please see ‘Who and When to Refer’ (factsheet 15). tracranial tumours in childhood, and are the most common peripituitary tumour in this Investigations age group. In adults, craniopharyngiomas An MRI or CT scan determines the precise account for 1% of brain tumours. Their be- size and position. Additional tests that form haviour is unpredictable and their origin is part of the evaluation include assessments of not fully understood. They are usually situ- biochemical, endocrine (especially an assessment ated close to the pituitary gland and hypo- of hypothalamic-pituitary axis), psychological thalamus. The tumour consists of solid parts, and visual function. sometimes calcified, and cysts, which may be filled with a dense oily fluid. Treatment possibilities Because of the position of the tumour, transcranial, Presenting symptoms subfrontal surgery is almost always required. Craniopharyngiomas can cause symptoms at However some small craniopharyngiomas may any age, but those presenting in childhood are be approached by the transsphenoidal route. relatively fast growing, have a more aggressive Complete excision is rare. In most patients, partial course and can be more difficult to treat. removal is followed by radiotherapy. Prior to the Symptoms have usually been present for operation, or if the tumour re-grows, insertion of some time before diagnosis. They are usually a CSF shunt may be required if hydrocephalus associated with raised intracranial pressure and (excessive accumulation of CSF in the ventricular possibly anterior and posterior pituitary failure. 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 temporal treat the effects of the lesion on hypothalamic and hemianopia - poor vision to both sides - but pituitary function. Recurrence after surgery alone complete loss of vision in one or both eyes can is common, but is less likely when radiotherapy occur). is also given. Following surgery, at approximately • Slow growth during childhood. 2-3 months, a further assessment of hypothalamic- • Delayed or arrested , and very pituitary axis is required. Many patients will be

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

Pituitary Disease Factfile 21

GP fact file A5 update Nov 2020.indd 21 05/11/2020 15:08 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 have injections available for emergency use. 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 the children treated for craniopharyngioma. pituitary, the part of the brain that deals with the organization of sleep and wakefulness is sometimes disturbed as the tumour grows, Questions patients may ask or by the surgical treatment. Damage to this part of the brain is often associated with How likely is it that the 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 feeling

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

22 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 22 05/11/2020 15:08 Resources for patients available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk or our Endocrine Nurse Helpline

Patient Information Booklet • Craniopharyngioma - Available from The Child Growth Foundation, for contact details go to factsheet 16.

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 Craniopharyngioma

Pituitary Disease Factfile 23

GP fact file A5 update Nov 2020.indd 23 05/11/2020 15:08 Diabetes insipidus Pituitary Foundation fact sheet 8

Diabetes insipidus

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

24 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 24 05/11/2020 15:08 Diabetes insipidus

Resources for patients Why do I have to visit the toilet so often? available from The Pituitary Foundation Lack of vasopressin reduces the kidneys Helpline or our website www.pituitary.org.uk ability to concentrate the urine resulting in or our Endocrine Nurse Helpline the production of large volumes of urine. Patient Information Booklet Why do I have headaches? • Diabetes Insipidus & DI for teenagers booklet. This can happen after your DI is treated Other information and resource links available at and it is important to balance the dose of www.pituitary.org.uk desmopressin and the amount of fluid you drink so as not to retain too much water For GPs and develop hyponatraemia (low sodium). Endotext.org ‘Your Endocrine Source’ www. endotext.org (www.endotext.org/neuroendo/ Will I recover from DI? index.htm) DI can be caused by surgical trauma or The Pituitary Foundation accident and may in some cases be transitory, Website www.pituitary.org.uk but patients may require treatment for life.

Is it harmful to miss a dose of DDAVP? Generally speaking it is safer to miss a dose of DDAVP than to take an extra dose. You will simply notice that your thirst will be greater than normal, and you should drink more.

Pituitary Disease Factfile 25

GP fact file A5 update Nov 2020.indd 25 05/11/2020 15:08 Pituitary Foundation fact sheet 9

Traumatic brain injury and hypopituitarism

Brain injury may cause damage to the Hypopituitarism Traumatic brain injury and hypopituitarism hypothalamus and/or pituitary gland. Hormone deficiency caused by the inadequate Although the true incidence of brain injury secretion of one or more of the hormones and hypopituitarism remains unclear, the normally secreted by the pituitary, is known as poor outcome for patients who go unrecognised hypopituitarism. It may commonly be caused by could be devastating, with morbidity and the compression of the normal pituitary tissue by an

potential for mortality. enlarging pituitary tumour, by pituitary surgery, Therefore, it is important to raise awareness of or radiotherapy. It should, however, be emphasised this issue amongst primary health care professionals. that documented combined hypopituitarism after Most patients recover quickly from their head injury head injury is uncommon, and if it does occur and experience no long-term problems. However, it may have been associated with very significant some patients can develop problems after a few head injury. 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 Resources for patients Tests for hypopituitarism should be performed available from The Pituitary Foundation Helpline under the guidance of an endocrinologist. Please or our website www.pituitary.org.uk or our see ‘Who and When to Refer’ (factsheet no: 15) Endocrine Nurse Helpline Other information and Please also see ‘Hypopituitarism’ Factsheet no: 6 for resource links available at www.pituitary.org.uk explanation of hormone investigations, treatment For GPs Endotext.org ‘Your Endocrine Source’ possibilities, management and watchpoints. www.endotext.org (www.endotext.org/neuroendo/ index.htm) The Pituitary Foundation Website www. pituitary.org.uk

26 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 26 05/11/2020 15:08 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 optic chiasm or other structures

• to reduce the volume of, or excise, non Pituitary surgery 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 endocrinologist scans. for post-operative pituitary function assessment Transsphenoidal surgery is the most usual at about 5-8 weeks and back to the surgeon method but transcranial surgery is required in at about 12 weeks (for MRI and visual some tumours with major intracranial extension. field assessment). In some cases additional The transsphenoidal approach allows the surgeon replacement pituitary hormones will be needed. a clear, direct view of the tumour (through an These appointments should, ideally, be combined operating microscope) and avoids a craniotomy to cause minimal inconvenience to the patient. (making a hole in the skull) with 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 and approach in many centres. Fine tubes (endoscopes) nocturia after surgery, it is likely that they have are pushed through the back of the nose. developed a degree of diabetes insipidus (DI). MRI and/or CT scans will give the surgeon This is unusual after transsphenoidal surgery, information on the size and position of the but in all cases is highly amenable to treatment. tumour. In most cases DI is temporary and disappears Successful outcome of this surgery is very within a few months, but in 1-2% of patients, dependent on the experience of the surgeon. especially after removal of prolactinoma and Cushing’s tumours, it may be permanent but Patient management prior to surgery 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 is an inconvenience for the patient. Any flulike

Pituitary Disease Factfile 27

GP fact file A5 update Nov 2020.indd 27 05/11/2020 15:08 symptoms or discharge of water-like fluid from in testosterone, thyroid hormone and growth the nose should be treated with a view to this hormone can make it more difficult to lose weight. possibility. Patients need to be referred back to Regular monitoring with an endocrinologist is the surgeon for treatment urgently. important to establish that hormone levels are satisfactory, but also an opportunity to discuss Sinusitis any weight gained. This is not uncommon after this operation, particularly for patients with acromegaly. Emotional impact

Pituitary surgery Symptoms usually clear given time, but Surgical treatment which involves the head has a occasionally need further treatment or an strong emotional impact for some patients. ENT referral. Please see ‘Psychological Issues’ (factsheet 14).

Stitches Depending on the surgical technique, stitches Questions patients may ask are inserted in the upper gum or in the nostril. They are usually soluble. The wound itself will Why do I need an operation? be completely healed in 3 weeks. Complete A benign tumour of the pituitary gland absorption of stitches can take 3 months and may be compressing the optic nerve loose ends may need to be removed/snipped (which lies just above it) and affecting your away. There may be some numbness around the sight or you may have a tumour that is front teeth; this may occasionally be permanent. producing excessive amounts of hormone which could cause you problems. Weight gain A major problem for many patients is weight Is it cancer? gain. These patients are likely to need some No, the vast majority of tumours are benign. encouragement to follow a suitable diet and take regular exercise. This may be particularly difficult Will my eyesight improve after the after a period of illness and hospitalisation. operation? However, including more exercise into their Once the optic nerve is no longer lifestyle should also improve the patient’s general compressed most patients will notice an feeling of well-being. improvement, this will carry on improving The adrenal glands and cortisol are responsible for 6 months after the operation. However, for fat cell development. If cortisol levels are if your eyesight was very poor before the high due to having Cushing’s then weight is operation, it may not recover so much. usually gained around the trunk and in the face. If taking hydrocortisone as a replacement and How long will I be in hospital? the dose is too much, then weight can be gained. This varies between treatment centres, but It is essential that all pituitary hormones are may be 3-9 days. at satisfactory levels, as even small deficiencies

28 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 28 05/11/2020 15:08 When will I be able to go back to work? Depending on the job and circumstances, it is usually wise to plan for about 4-6 weeks off and reassess after that time. Some patients may take longer to recover.

Have I inherited this, will my children

get it? Pituitary surgery In all but very exceptional circumstances there is no hereditary link.

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 • 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

Pituitary Disease Factfile 29

GP fact file A5 update Nov 2020.indd 29 05/11/2020 15:08 Pituitary Foundation fact sheet 11

Radiotherapy

Indications for radiotherapy (Rt) use within 20 years of radiotherapy, necessitating in : regular endocrine follow up. Following surgical resection • 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 Radiotherapy fraction radiotherapy (also called radio 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 if to the target area from three directions. hormone levels remain elevated post op, and some centres now reserve RT for those failing medical therapy e.g., in Acromegaly somatostatin Benefits of radiotherapy analogue therapy may be used first line and RT • Controls disease in 94% of cases at 10 years reserved for cases where growth hormone fails to and 88% at 20 years. reach safe levels on treatment. • Reduces local recurrence from 60% with • Changes in tumour size can now be monitored surgery alone to 5% (surgery + RT). with sequential MR imaging. • Reduces hormone secretion in 90% • Half of patients with normal pituitary cases of acromegaly, average 4 ½ years to function pre RT will develop hypopituitarism normalisation of hormone levels.

30 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 30 05/11/2020 15:08 • 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 fields and RT. are used on a daily basis. Patient specific shielding Note: because of the possibility of loss of normal blocks or blocking leaflets in the machine pituitary function several years after RT, it is treatment head are used to reduce the volume of essential that all patients have regular follow-ups normal tissue irradiated. The planning process can with an endocrinologist. 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 typical irradiated, the patient’s head should be firmly total dose of 45Gy in 25 fractions dose of 45 – immobilised on to the radiotherapy treatment 50 Gy. Each treatment, which is painless, lasts couch, thus reducing movement. This allows for 10 – 15 minutes – the actual radiotherapy the radiotherapist to minimise the margins for about 2 minutes. Treatments are delivered movement added to the tumour target volume. using a Linear Accelerator (LINAC) machine. Three techniques can be employed to immobilise Lining up markers on the mask with laser beams Radiotherapy the patient: embedded in the walls of the treatment room • A mask can be made in one session using a confirms the absolute position of the patient thermoplastic mesh drawn down over the relative to the treatment machine, and thus safe patient’s face, which is then attached to a firm delivery of treatment. Using the stereotactic baseboard. immobilisation ring ensures slightly higher • Or a perspex mask is moulded from a plaster precision than the mask systems. But is more of Paris cast of the patient’s face. This requires time consuming to deliver and requires specific two hospital visits. A hole in the Perspex mask equipment and expertise, which is not available is made for mouth and nostrils. Patients with in all departments and its benefit is still being a beard will be asked to shave to give a firm fit evaluated. of the mask. Accuracy for both mask systems Single fraction radiotherapy (radiosurgery) is 5-10mm. is increasingly used for pituitary adenomas in • A stereotactic ring frame can be fitted using the specific indications outlined above. This skull vault screws (for a single fraction is delivered using either a LINAC or Gamma treatment-radiosurgery) or using patient Knife® (an array of cobalt sources around the specific dental and occipital impressions to patient’s head). A dose of 100 Gy to the tumour allow repeat usage for multiple treatments. centre is delivered in a single treatment. A This ring is then fixed to the treatment couch steep dose gradient beyond the tumour edge with 1-3mm accuracy. aims to reduce the dose to surrounding critical A CT scan is performed with the patient in the structures. immobilisation device and the radiotherapist Stereotactic radiosurgery appears safe and and physicist define a treatment volume and effective with numerous studies confirming

Pituitary Disease Factfile 31

GP fact file A5 update Nov 2020.indd 31 05/11/2020 15:08 this over the last few years. Patient selection is critical to success and depends in great part on Questions patients may ask the anatomy of the tumour to be treated and previous treatment given. The main determinant How long will it take? is the proximity to the optic apparatus as this The treatment itself only takes about 10-15 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 lost • Headache – treat symptomatically, avoid at the sites of radiation entry and exit (i.e., steroids if possible. the temples, above the forehead and the • Tiredness, which can last for a few months. nape of the neck typically in front of each Radiotherapy Long term, permanent side effects: ear), but this almost always re-grows within • Hypopituitarism. In those patients with 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 some What are the possible side effects? 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 • Stoke. 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 a functioning pituitary before RT. This can occur after years. It is important the patient attends regular endocrine follow up for many years.

32 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 32 05/11/2020 15:08 Resources for patients available from The Pituitary Foundation Helpline or our website www.pituitary.org.uk or our Endocrine Nurse Helpline

Patient Information Booklet • 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 Radiotherapy

Pituitary Disease Factfile 33

GP fact file A5 update Nov 2020.indd 33 05/11/2020 15:08 Pituitary Foundation fact sheet 12

Hormone Replacement Therapy

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

GH levels and slow growth rate. GH also has is required at a specialist centre which provides important effects in adult tissues such as bone, effective monitoring. The objective is a singleton fat and muscle, and lack of GH may increase pregnancy and a multiple pregnancy should mortality rates from heart disease. However be considered as a failure of treatment. The human recombinant growth hormone is now specialist centre should have high-resolution available, and has been shown to be clinically ultrasonography available. HRT is safe for effective. Adults who suffer from biochemically women of pre-menopausal age, in whom the documented GH deficiency, and who exhibit benefits of maintaining bone excessive tiredness, muscle weakness, weight strength outweigh the deficits, and breast cancer gain, anxiety and depression, may benefit from has not been shown to be a problem. GH therapy. GH is administered by daily subcutaneous injection. The dose for adults

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GP fact file A5 update Nov 2020.indd 34 05/11/2020 15:08 ACTH AVP (ADH) ACTH deficiency is treated by prescribing Diabetes insipidus may be a transient effect hydrocortisone or alternatively prednisolone of surgery or a long-term result of damage to (not recommended for children). The average the hypothalamus or posterior pituitary. AVP dose requirement of hydrocortisone is 20 mg (ADH) is replaced by giving desmopressin split 2-3 times a day day (e.g. 10/5/5mg a day) (referred to as DDAVP) provided as tablets, and most patients feel better if they have 3 nasal spray or melts. Patients should be warned doses – on waking, midday and early evening (5 not to drink too much and a sensible precaution – 6pm). In normal health, the lowest levels of may be to leave out one treatment each week cortisol are between 6pm and 6am. Patients will to prevent water overload. DI may disappear need to learn the situations in which a higher spontaneously. The only way to check this is to dose of steroid should be taken. Examples are: stop the treatment. • Infections • Dental treatment Prolactin (PRL) • Hospital treatment e.g., operations No replacement formulation is available or Supplies of tablets and a steroid card should necessary under normal circumstances. The always be carried and wearing a Medic Alert absence of prolactin may lead to an inability to or similar bracelet is important in case of breast-feed. accident. Learning the skill of self-injection of hydrocortisone (or encouraging another member of the family to do so) can be potentially life Questions patients may ask saving, particularly if patients wish to travel to Hormone Replacement areas where medical care is not readily available. Will I have to take tablets in the long Full instruction on intramuscular injection term? Therapy technique should be provided by hospital If, as often happens, the pituitary tumour or clinic or general practice. Urgent injection its treatment have caused hypopituitarism, of hydrocortisone is indicated in emergency this does not usually recover and the patient

situations especially when intake of tablets is will need long term replacement therapy. compromised e.g., by vomiting. Will I need regular check-ups? TSH Yes, but as pituitary tumours are usually In the absence of the normal production of well controlled and grow very slowly, if at TSH by the pituitary gland, patients require all, outpatient appointments are usually Thyroxine. Thyroxine has a relatively long half made 12 months to 2 years apart. life (several days), so that if a tablet is forgotten no action is required. Pituitary related TSH Will I need regular scans? levels are different to more common hypothyroid Perhaps, but again, these too are carried out levels; any dose adjustment of thyroxine refer to years apart. endocrinologist.

Pituitary Disease Factfile 35

GP fact file A5 update Nov 2020.indd 35 05/11/2020 15:08 Have I inherited this, will my children get it? There is ongoing research into familial incidence e.g. in Gigantism, but the majority of cases are sporadic.

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/ Hormone Replacement neuroendo/index.htm) Therapy The Pituitary Foundation Website www.pituitary.org.uk

36 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 36 05/11/2020 15:08 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 • Chemotherapy or radiotherapy (affects Presenting symptoms fertility more than testosterone production) In pre-pubertal onset of testosterone deficiency, sexual development will be absent or incomplete Secondary hypogonadism: When androgen e.g., lack of genital enlargement, lack of pubic/ deficiency is the result of diseases of the pituitary/ axillary hair and beard growth, lack of muscle hypothalamus, the condition is described as development, lack of sexual interest and failure secondary hypogonadism or hypogonadotrophic of the voice to break. Spermatogenesis will not hypogonadism due to the low levels of LH and be initiated and infertility is the general rule. FSH. When there is no other concurrent pituitary In post-pubertal onset of testosterone deficiency, hormone deficit, the condition is usually called the established secondary sexual characteristics are isolated hypogonadotrophic hypogonadism. poorly maintained. Symptoms include tiredness, This may be due to a congenital deficiency in reduced libido and sexual functioning, reduced hypothalamic gonadotrophin releasing hormone body and facial hair and muscle mass, infertility (GnRH) and a lack of general well-being including depression. Flushing and sweating, similar to female Causes of secondary hypogonadism: menopausal symptoms, may occur. • Pituitary tumour (factsheet 3) Common to both presentations, testosterone • Suprasellar tumour i.e., craniopharyngioma deficiency is associated with reduced bone mass, (factsheet 8) increased risks for osteoporotic fractures and • Isolated hypogonadotrophic hypogonadism mild anaemia. • Kallmann’s syndrome (isolated hypogonado- trophic hypogonadism associated with an ab-

Classification of hypogonadism sent or impaired sense of smell) Male Hypogonadism Primary hypogonadism: When androgen • Iron overload (haemochromatosis or frequent deficiency is the result of testicular diseases, the blood transfusions) condition is described as primary hypogonadism • Systemic diseases – acute and chronic or hypergonadotrophic hypogonadism. The latter • Glucocorticoid treatment 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 gonads to secrete causes of hypogonadism, followed by Klinefelter’s more testosterone. syndrome.

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GP fact file A5 update Nov 2020.indd 37 05/11/2020 15:08 Clinical examination is confirmed Physical examination is important to confirm • karyotyping (Klinefelter’s syndrome - 47XXY the clinical diagnosis of hypogonadism and to (80% of cases), mosaics, 48XXXY etc.) elucidate the underlying cause. Important points • haemoglobin include: • bone mineral density • assess pubertal progress and stature in late • ultrasound of the testes adolescent patients • body, facial and pubic hair growth Treatment • body habitus (i.e., eunuchoidal limb Any potentially reversible underlying cause proportions, muscle bulk, feminine fat should be treated prior to commencing distribution, gynaecomastia) replacement therapy. • testicular examination (assess size, position, Referral to a specialist Endocrinology centre consistency i.e., very small and firm in for investigation and subsequent management Klinefelter’s) is recommended. Please see ‘Who and When to • visual field assessment which may highlight Refer’ (factsheet 15). a pituitary lesion (classically a bitemporal Androgen replacement can be administered in hemianopia resulting from chiasmal the following modalities compression) • Testosterone esters (Sustanon 100 and 250) • sense of smell (absent in Kallmann’s syndrome) are administered as a deep intramuscular injection usually every 2-3 weeks. They Investigations provide reliable replacement with a good To confirm testosterone concentration is safety record for over 50 years. The main side subnormal a single 9am measurement of effect is limited to relatively short duration, total testosterone usually suffices. In men over localised pain at the injection site. Nebido is 50, particularly overweight patients, SHBG- the main injectable form of testosterone used; corrected free testosterone is important. this formulation requires only 3-monthly injections in to the muscles of buttocks, and To differentiate primary from secondary provides constant testosterone levels for up hypogonadism a single measurement of LH to 14 weeks. Testosterone levels begin to rise

Male Hypogonadism and FSH will support the biochemical diagnosis within 24 hours of the injection. of either primary or secondary hypogonadism. • Testosterone gel is frequently used for replacement therapy. Average doses are To identify the underlying cause and assess 50mg per day, but this needs titration by an severity of testosterone deficiency endocrinologist initially. Single sachet and • prolactin, 9am serum cortisol and thyroid multiple dose preparations are available. It is function as a baseline assessment of pituitary applied once daily to to the skin surface over function the shoulders, upper arms and abdomen will • MRI scanning of the pituitary should be deliver stable physiological blood levels of arranged if hypogonadotrophic hypogonadism testosterone.

38 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 38 05/11/2020 15:08 Infertility resulting from secondary hypogonadism within the first few weeks and best judged by the is usually amenable to treatment. In this situation patient’s own observations. Physical changes such there is dormant testicular tissue which should as genital, hair and muscle growth are generally respond to gonadotrophin treatment with human observed within 3-6 months. Bone mineral chorionic gonadotrophin (hCG) and FSH self- density changes may be used as a more long- administered subcutaneously twice to thrice term parameter of responses and compliance to weekly over 6-12 months. Primary hypogonadism testosterone. including Klinefelter’s syndrome are synonymous In older patients, monitoring the haematocrit, with irreversible and permanent infertility. prostate size (digital rectal examination) and The psychological impact of infertility can function (PSA) constitute sensible clinical be great and counselling may be required. See practice. ‘Psychological Issues’ (factsheet 14) for basic Counselling in accepting the invariably life- information. long testosterone treatment, subfertility or infertility is important. Initiation and monitoring treatment: Side effects may include gynaecomastia, assessing response exacerbation of prostatic disease, fluid retention Initial treatment will depend upon the age of in those with pre-existing cardiac or renal disease, the patient and the underlying cause of the exacerbation of pre-existing liver dysfunction, hypogonadism. Younger patients are often obstructive sleep apnoea, polycythaemia and androgen-naïve and will benefit from lower exacerbation of premorbid behavioural problems. starting doses and gradual increase over 2-3 years to the full adult replacement dose of testosterone. Watchpoints This is particularly desirable for maximising linear Urgent - refer to hospital growth potential. Older men should ideally be • back pain or urinary obstruction – may indicate treated with shorter acting preparations in case prostate cancer and metastatic disease of aggravating undetected androgen-responsive • testicular mass diseases e.g., prostate cancer. Adult men may have • deterioration of vision (suggesting secondary a preference for longer acting preparations such as hypogonadism) testosterone implants.

The aim should be to maintain plasma Male Hypogonadism testosterone within the physiological range. It Questions patients may ask is good practice to ascertain that this has been achieved in the first 3-6 months of initiating Will my sex life improve? treatment by dose titration. Thereafter, an Testosterone treatment will increase annual pre-dosing check of testosterone should your sex drive. Sexual functioning is be more than sufficient. more complicated and is dependent on The clinical response should be apparent several factors in addition to testosterone.

Pituitary Disease Factfile 39

GP fact file A5 update Nov 2020.indd 39 05/11/2020 15:08 Testosterone will not help erectile impotence with normal sex drive

Will I be able to have children? If the underlying cause is due to a testicular problem then invariably the patient will be infertile. With secondary causes hCG/FSH treatment is successful in up to 70% of cases.

Will it make me more aggressive? Not in an antisocial sense but it will make you have more self-confidence and be more assertive.

Have I inherited this, will my children get it? In all but very exceptional circumstances there is no hereditary link.

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

Patient Information Booklet • Male Hormones & Infertility Klinefelter’s Syndrome www.ksa-uk.net/

Male Hypogonadism 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

40 Pituitary Disease Factfile

GP fact file A5 update Nov 2020.indd 40 05/11/2020 15:08 Pituitary Foundation fact sheet 14

Psychological Issues

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

to help with these problems, contact Changing Psychological Issues Faces (factsheet 16 - Resources). Cushing’s patients usually suffer from truncal

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GP fact file A5 update Nov 2020.indd 41 05/11/2020 15:08 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 Psychological Issues

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GP fact file A5 update Nov 2020.indd 42 05/11/2020 15:08 should you refer

Pituitary Foundation fact sheet 15 Referrals: When

Referrals: When should you refer and to whom

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

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).

Pituitary Disease Factfile 43

GP fact file A5 update Nov 2020.indd 43 05/11/2020 15:08 should yourefer 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

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GP fact file A5 update Nov 2020.indd 44 05/11/2020 15:08 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

Pituitary Disease Factfile 45

GP fact file A5 update Nov 2020.indd 45 05/11/2020 15:08 Pituitary Foundation fact sheet 16

Resources: Information and Support

Resources: information For patients Pituitary Life: The Pituitary Publications produced by The Pituitary Foundation’s magazine and support Foundation, available both as printed matter These contain useful articles on all aspects and via our website www.pituitary.org.uk of pituitary disease written by both medical specialists and patients. Examples include Patient information booklets information on taking steroids, experiences of

• The Pituitary Gland; Its conditions and testosterone therapy, etc. hormones explained • Acromegaly For GPS • Cushing’s Endotext.org ‘Your Endocrine Source’ • Diabetes Insipidus www.endotext.org • Prolactinoma (www.endotext.org/neuroendo/index.htm) • Male Hormones & Infertility Issues • Pituitary Surgery & Radiotherapy The Pituitary Foundation Website • Psychological Issues in Pituitary Disease (Series) www.pituitary.org.uk • Employment • Weight Issues & Nutrition Oxford Desk Reference Endocrinology (2018) • Hydrocortisone Advice for Adults H Turner, R Eastell, A Grossman (editors) and • Hydrocortisone Advice for Parents Your hormones https://www.yourhormones. • Pituitary Patients Handbook info/

Proceedings of several Pituitary Foundation conferences These proceedings include many aspects of pituitary disease such as articles on growth hormone, new aspects of surgery, visual problems and reports of workshops on acromegaly, Cushing’s, diabetes insipidus, hypopituitarism, prolactinoma, psychological problems, self image and patient-consultant communication.

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GP fact file A5 update Nov 2020.indd 46 05/11/2020 15:08 Resources: Information and Support

This information is correct at time of publication Resources: information

Name of organisation Website Phone number and support 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 01243 810093 Congenital Adrenal Hyperplasia cahisus.co.uk Changing Faces changingfaces.org.uk 0300 012 0275 Child Growth Foundation childgrowthfoundation.org 01243 810093 Kallmann’s Syndrome hypohh.net Multiple Endocrine Neoplasia amend.org.uk RNIB rnib.org.uk 0303 123 9999 Tall Persons Club tallclub.co.uk Turners Syndrome Support Society tss.org.uk 0300 111 7520

Pituitary Disease Factfile 47

GP fact file A5 update Nov 2020.indd 47 05/11/2020 15:08 The Pituitary Foundation © 2020 Version 4. To be reviewed February 86 Colston Street, 2022 Th is material may not be stored or Bristol, BS1 5BB reproduced in any form nor by any means www.pituitary.org.uk without the permission of Th e Pituitary Helpline: 0117 370 1320 Foundation.

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GP fact file A5 update Nov 2020.indd 48 05/11/2020 15:08