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 topics: and

• 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 (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

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5 Pathophysiology

www.bitemedicine.com Instagram: @bitemedicine Facebook: /biteemedicine 6 Clinical features

Symptoms Signs Visual disturbance Bitemporal hemianopia 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

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(3) (4)

(5)

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Acromegaly 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)

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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 • CT chest, abdomen and pelvis: very rarely can be due to an ectopic source

Special tests • Visual field testing

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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

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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

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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

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

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Drug-induced Aetiology • Antipsychotics • Antidepressants • Opiates • Anti-emetics • Oestrogens • H2 blockers • Verapamil Features • Prolactin levels drop after stopping the drugs

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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

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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

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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

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