Endocrinology

Question 1

What are the three types of corticosteroids produced by the adrenal cortex and what do they do?

Answer 1

(1) Glucocorticoids - e.g. cortisol. These affect carbohydrate, lipid and protein metabolism.
(2) Mineralocorticoids - e.g. aldosterone. These control sodium and potassium balance.
(3) Androgens - sex hormone which have only a weak effect until peripheral conversion to testosterone and dihydrotestosterone.

Corticotrophin releasing factor (CRF) from the hypothalamus stimulates ACTH secretion from the pituitary gland which in turn stimulates cortisol and androgen production by the adrenal cortex. Cortisol is excreted as urinary free cortisol and various oxogenic steroids.

Question 2

What is Cushing’s Syndrome?

Answer 2

The clinical state produced by chronic glucocorticoid excess and the loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and loss of circadian rhythm of cortisol secretion (normally highest on waking). The chief cause is oral steroids. Endogenous causes are rare. 80% are due to raised ACTH; of these, a pituitary adenoma (Cushing’s disease) is the commonest cause.

Question 3

Discuss the two ACTH-dependent causes of Cushing’s syndrome.

(1) Cushing’s disease
(2) Ectopic ACTH production

Answer 3

(1) Cushing’s disease - bilateral adrenal hyperplasia from an ACTH-secreting pituitary adenoma. Equally affects men and women peaking between the ages of 30-50. A low dose dexamthasone test leads to no change in plasma cortisol but 8mg may be enough to more than halve morning cortisol (as occurs in normals).
(2) Ectopic ACTH production - Especially in small cell lung cancer and carcinoid tumours. Specific features include increased pigmentation (due to highly raised ACTH), hypokalaemic metabolic alkalosis (high cortisol leads to mineralocorticoid activity), weight loss, hyperglycaemia. Classical features of Cushing’s are often absent. Dexamethasone even in high doses (8mg) fails to suppress cortisol production.

(Also RARELY - ectopic CRF (corticotrophin releasing factor) production can be caused - some medullary thyroid and prostate cancers).

Question 4

What SYMPTOMS might you expect to see in Cushing’s syndrome?

Answer 4

Weight gain
Mood change (depression, lethargy, irritability, psychosis)
Proximal weakness
Gonadal dysfunction (irregular menstrual cycle, hirsutism, erectile dysfunction).
Acne
Recurrent Achilles’ tendon rupture
Occasionally virilization if female (clitoral enlargement, increased muscle strength, acne, hirsutism, frontal hair thinning, deepening of the voice, menstrual disruption due to anovulation).

Question 5

What SIGNS might you expect to see in Cushing’s syndrome?

Answer 5

Central obesity
Plethoric (red faced/ruddy)
Moon face
Buffalo neck hump
Supraclavicular fat distribution
Skin and muscle atrophy
Bruises
Purple abdominal striae
Osteoporosis
Hyperglycaemia 
Infection prone
Poor healing

Question 6

Discuss treatment of Cushing’s syndrome - dependent on cause

(1) Iatrogenic
(2) Cushing’s disease
(3) Adrenal adenoma or carcinoma
(4) Ectopic ACTH

Answer 6

(1) Iatrogenic - stop medications if possible
(2) Cushing’s disease - selective removal of pituitary adenoma (trans-sphenoidally). Bilateral adrenalectomy if source unlocatable or recurrence post-op.
(3) Adrenal adenoma or carcinoma - Adrenalectomy ‘cures’ adenomas but rarely cures cancer. Radiotherapy and adrenolytic drugs (Mitotane) follows if carcinoma.
(4) Ectopic ACTH - Surgery it tumour located and hasn’t spread. Metyrapone, ketoconazole and fluconazole to lower cortisol secretion pre-op or if awaiting effects of radiation. Intubation and mifepristone (competes with cortisol at receptors) + etomidate (blocks cortisol synthesis) May be needed e.g. in severe ACTH-associated psychosis.