Endocrinology Lecture 9 Dr Azeem Alam, MBBS BSc (Hons) Surgical AFP Guy’s and St. Thomas’ Hospital [email protected] (1) www.bitemedicine.com www.facebook.com/biteemedicine Content reviewed on the 23/04/2020. @bitemedicine 1 Learning objectives • 2 endocrinology topics: Acromegaly and Prolactinoma • Case-based discussion(s) to identify the top differentials and why • Theory to cover pathophysiology, diagnostic criteria, investigations and management • Quiz (Mentimeter and multi-step SBAs) www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 2 Case 1 History A 41-year-old male presents to his GP with profuse sweating and visual disturbance. He has also noticed numbness in his right hand. He has been feeling very tired due to difficulty sleeping. On examination, thick skin is noted and he has course facial features. Observations HR 96, BP 148/102, RR 18, SpO2 98%, Temp 37.0°C. www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 3 Acromegaly: Pathophysiology Definition: a multi-systemic and progressive condition caused by excessive secretion of growth hormone (GH) Aetiology • Most common cause is pituitary somatotroph adenoma (95-99% of cases) • Rarely because of ectopic secretion from neuroendocrine tumours Risk factors • MEN 1: pituitary adenomas, primary hyperparathyroidism, and pancreatic neuroendocrine tumours • McCune-Albright syndrome www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 4 (2) 5 Pathophysiology www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 6 Clinical features Symptoms Signs Visual disturbance Bitemporal hemianopia Headaches Facial features: • Prominent jaw and supra-orbital ridge • Prognathism • Splaying of teeth • Macroglossia Rings and shoes are tight Spade-like hands Tingling in hands (carpal tunnel) Deep, husky voice Polyuria/polydipsia (T2DM) Sweaty palms Hypertension www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 7 Clinical features (3) (4) (5) www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 8 Differentials Acromegaly Gigantism Definition Oversecretion of Oversecretion of growth hormone growth hormone before the fusion of growth plates Age Onset in adulthood Onset in childhood Facial features Large lips, tongue Prominent forehead and protruding jaw and jaw Height Unaffected Increased for age of child Onset of puberty Unaffected Delayed Gonadal Unaffected Reduced development (hypogonadal) www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 9 Investigations Bedside • ECG: acromegaly can cause cardiomyopathy and heart failure Bloods • Insulin-like growth factor 1: first line investigation and raised in disease • Oral glucose tolerance test: a glucose load should cause suppression of GH normally. In acromegaly, there is failure of GH suppression Imaging • Pituitary MRI: visualisation of pituitary adenoma • CT chest, abdomen and pelvis: very rarely can be due to an ectopic source Special tests • Visual field testing www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 11 Management First line • Surgery: trans-sphenoidal resection of the pituitary Second line • Medical: dopamine agonists (e.g. cabergoline) in mild disease and somatostatin analogues (e.g. octreotide) in severe disease • Pegvisomant is a GH antagonist which is sometimes used, although very expensive Third line • Radiotherapy: reserved for patients who are refractory to medical and surgical treatment www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 13 Complications Acromegaly Gigantism Cardiac • Cardiomyopathy • Heart failure • Hypertension Respiratory • Obstructive sleep apnoea Neurological • Carpal tunnel syndrome • Proximal myopathy Endocrine • T2DM • Panhypopituitarism Gastrointestinal • Colorectal cancer www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 15 Recap • Acromegaly is most commonly caused by a pituitary somatotroph adenoma leading to a state of GH excess • First line investigations include IGF-1 and OGTT • First line management is with trans-sphenoidal surgery • Medical therapy includes somatostatin analogues, dopamine agonists, and growth hormone antagonists • Radiotherapy is reserved for refractory cases www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 16 Top decile question www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 17 Case 2 History A 21-year-old female presents to the GP with visual disturbance and irregular menstrual periods. She has been taking a combined oral contraceptive pill for the last 2 years. She has no known past medical history. Observations (6) HR 85, BP 125/85, RR 17, SpO2 97%, Temp 37.5°C www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 19 Pathophysiology Definition: a benign lactotroph adenoma that secretes prolactin Aetiology • Prolactin-secreting pituitary adenomas • Most occur sporadically • Genetic causes (5% of cases) • MEN-1 • Carney complex • Familial isolated pituitary adenoma syndrome Risk factors • Female gender • 20-50 years of age • Genetic predisposition Pathophysiology Pituitary size • Microadenomas: ≤ 10 mm • Macroadenomas: > 10 mm • With suprasellar extension may result in bitemporal hemianopia Functional pituitary adenoma (60%) • Secretory pituitary adenomas • Associated with hormone secretion and therefore hyperpituitarism • Commonly one hormone secretion • Prolactinoma is associated with excessive prolactin secretion Non-functional pituitary adenoma (40%) • Typically gonadotroph adenomas account for 80-90% • Chromophobic (7) Pathophysiology (8) Clinical features Symptoms Signs Visual changes Bitemporal hemianopia Galactorrhoea Gynecomastia: males Amenorrhoea or oligomenorrhoea Infertility Loss of libido Erectile dysfunction: males www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 24 Differentials Drug-induced hyperprolactinaemia Aetiology • Antipsychotics • Antidepressants • Opiates • Anti-emetics • Oestrogens • H2 blockers • Verapamil Features • Prolactin levels drop after stopping the drugs www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 25 Investigations Bloods • Serum prolactin: > 400 mU/L • Macroprolactin: assess in asymptomatic patients Imaging • Pituitary MRI Special tests • Visual field testing Consider alternative causes • Pregnancy • Antipsychotics • Primary hypothyroidism www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 26 Management Medical • Dopamine agonist: cabergoline is preferred; dose increased for larger tumours • COCP: consider for patients with amenorrhoea and a microadenoma Surgical • Transphenoidal surgery: if unresponsive or unable to tolerate medical therapy Pregnancy: addendum to webinar presentation • Discontinue dopamine agonist as soon as possible (most patients) • Selected patients with macroadenomas may continue therapy • Bromocriptine is not technically teratogenic but does cross the placenta during the first 4 weeks of development, which is a critical period for early organogenesis • For more information visit: JCEM. Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline. https://academic.oup.com/jcem/article/96/2/273/2709487 www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 29 Recap • A prolactinoma is a benign pituitary adenoma secreting prolactin • Commonly associated with young women • Bitemporal hemianopia is usually secondary to a macroadenoma. Other features include amenorrhoea, galactorrhoea, loss of libido and erectile dysfunction • Prolactin levels and an MRI are useful investigations • Dopamine agonists are your first line management www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 30 Top decile question www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 31 Further information • We need your feedback! • Lecture series / schedule • New, interactive website coming very soon • Stay up-to-date! • Website: www.bitemedicine.com • Facebook: https://www.facebook.com/biteemedicine • Instagram: @bitemedicine • Email: [email protected] • Want to get involved? Contact us at [email protected] to get your information pack Buy our textbook at www.bitemedicine.com 33 References 1. Shutterstock. https://www.shutterstock.com/image-vector/structure-hypothalamicpituitary-thyroid-axis-hpt- 1147605182 2. Shutterstock. https://www.shutterstock.com/image-vector/growth-hormone-somatotropin-secreted-by- pituitary-314873366 3. Philippe Chanson and Sylvie Salenave / CC BY (https://creativecommons.org/licenses/by/2.0) 4. Philippe Chanson and Sylvie Salenave / CC BY (https://creativecommons.org/licenses/by/2.0). https://upload.wikimedia.org/wikipedia/commons/1/1a/Acromegaly_prognathism.JPEG 5. Offices of Kenneth Yamanaka, DDS / Public domain. https://upload.wikimedia.org/wikipedia/commons/1/1f/Acromegalyteethgapping.jpg 6. Ceridwen commonswiki. https://commons.wikimedia.org/wiki/File:Pilule_contraceptive.jpg#globalusage 7. National Endocrine and Metabolic Diseases Information Service, NIH. / Public domain. https://upload.wikimedia.org/wikipedia/commons/7/7f/Prolactinoma-art.jpg 8. US Government / Public domain. https://upload.wikimedia.org/wikipedia/commons/9/9d/Illu_endocrine_system_New.png Buy our textbook at www.bitemedicine.com 34.