MRCOG Part 1 · Endocrinology · Adrenal and Thyroid Glands and the Pancreas

Adrenal Gland: MRCOG Part 1 questions and key facts

The adrenal gland is divided into a three-layered cortex and a central medulla, each producing distinct hormones critical to metabolic, electrolyte, and vascular homeostasis. The outer cortex comprises the zona glomerulosa synthesising mineralocorticoids, the zona fasciculata producing glucocorticoids, and the zona reticularis secreting androgens. Cortisol governs hepatic gluconeogenesis and immune modulation, following a circadian peak in the early morning. The adrenal medulla, composed of neuroendocrine chromaffin cells stimulated by preganglionic acetylcholine, secretes catecholamines. Part 1 questions test the zonal source of each hormone, the biochemical pattern of adrenal insufficiency and Cushing's syndrome, and medullary physiology. Key conditions include congenital adrenal hyperplasia presenting with ambiguous genitalia, endocrine hypertension from phaeochromocytoma, iatrogenic or pituitary-driven Cushing's syndrome, and primary adrenal insufficiency causing life-threatening Addisonian crises with hypotension, hypoglycaemia, hyponatraemia and hyperkalaemia.

The Uterio bank has 40 questions on this topic. 3 arebelow in full; the syllabus detail is in the Endocrinology study guide.

How the exam tests Adrenal Gland

  • Zonal organisation of the adrenal cortex, matching each distinct histological layer to its specific steroid hormone product and regulatory mechanism.
  • Clinical and biochemical profiles of adrenal insufficiency, contrasting low cortisol with compensatory elevated ACTH and classic electrolyte disturbances.
  • Diagnostic differentiation of hypercortisolism, separating Cushing's syndrome from pituitary Cushing's disease, and recognising exogenous steroid use as the commonest cause.
  • Pathophysiology and presentation of phaeochromocytoma, focusing on chromaffin cell origin, preganglionic acetylcholine stimulation, and the episodic symptom triad.

High-yield facts

  1. The zona glomerulosa secretes aldosterone, the zona fasciculata synthesises cortisol, and the zona reticularis produces androgens including dehydroepiandrosterone and androstenedione.
  2. Aldosterone acts on the distal nephron (late distal tubule and collecting duct) to increase sodium reabsorption and enhance potassium excretion.
  3. Cortisol directly stimulates hepatic gluconeogenesis, enhances muscle protein catabolism, promotes lipolysis, and decreases peripheral glucose uptake in skeletal muscle.
  4. Serum cortisol concentrations follow a circadian rhythm, reaching peak levels in the early morning and declining to a nadir late in the evening.
  5. Primary adrenal insufficiency features low serum cortisol alongside elevated adrenocorticotropic hormone, accompanied by hyponatraemia, hyperkalaemia, and relative eosinophilia and lymphocytosis.
  6. In primary adrenal insufficiency, Addisonian crisis is characterised by profound hypotension, hypoglycaemia, hyponatraemia, hyperkalaemia, abdominal pain, nausea, and vomiting.
  7. Defective 21-hydroxylase accounts for 90 to 95 percent of congenital adrenal hyperplasia, causing female virilisation and severe neonatal salt-wasting crises through aldosterone deficiency.
  8. Exogenous glucocorticoids cause most Cushing's syndrome overall, whereas pituitary ACTH-secreting adenomas account for approximately 70 percent of endogenous cases (textbooks quote 70 to 80 percent).
  9. The rate-limiting step in catecholamine biosynthesis is the conversion of tyrosine to DOPA, catalysed by the enzyme tyrosine hydroxylase.
  10. Chromaffin cells in the adrenal medulla release adrenaline and noradrenaline when directly stimulated by acetylcholine released from preganglionic sympathetic neurons.
  11. Phaeochromocytoma arises from medullary chromaffin cells, presenting with paroxysmal hypertension alongside the classic triad of severe headache, palpitations, and profuse diaphoresis.
  12. Juxtaglomerular cells in renal afferent arterioles release renin during hypotension, initiating the renin-angiotensin-aldosterone axis that drives zona glomerulosa aldosterone secretion.

Common pitfalls

  • Mistaking macula densa cells for the site of renin secretion; macula densa cells sense sodium chloride, but juxtaglomerular cells secrete renin.
  • Expecting hypertension in an Addisonian crisis; cortisol and aldosterone deficiency produce severe hypotension, hypovolaemia, and vascular collapse.
  • Confusing the commonest overall cause of Cushing's syndrome, which is exogenous steroids, with the commonest endogenous cause, a pituitary ACTH-secreting microadenoma.

Practice questions: Adrenal Gland

Single best answer, exactly as the exam asks. Commit to an option before opening the explanation.

Question 1

Endocrinology

In a patient with suspected primary adrenal insufficiency (Addison's disease), which of the following laboratory findings would support the diagnosis?

  1. AElevated serum cortisol, low ACTH
  2. BElevated serum cortisol, elevated ACTH
  3. CLow serum cortisol, low ACTH
  4. DLow serum cortisol, elevated ACTH
  5. ENormal serum cortisol, elevated ACTH
Show answer and explanation

Correct answer: D. Low serum cortisol, elevated ACTH

Key takeaway

In primary adrenal insufficiency (Addison's disease), you'll find low serum cortisol, elevated ACTH because the adrenal glands aren't functioning, leading to low cortisol and a compensatory rise in pituitary ACTH secretion.

In primary adrenal insufficiency (Addison's disease), the adrenal glands themselves are damaged or dysfunctional. This leads to reduced production of cortisol and, usually, aldosterone. Because the adrenal glands are not producing enough cortisol, serum cortisol levels will be low. The pituitary gland, sensing low cortisol, will attempt to stimulate the adrenal glands by releasing more adrenocorticotropic hormone (ACTH). Therefore, ACTH levels will be elevated in a compensatory manner.

The other options are incorrect:

Elevated serum cortisol, low ACTH: This combination would point towards an ACTH-independent cause of Cushing's syndrome (excess cortisol), such as an adrenal tumour.

Elevated serum cortisol, elevated ACTH: This points to an ACTH-dependent cause of Cushing's, such as a pituitary tumour producing excessive ACTH (Cushing's disease), or an ectopic source of ACTH.

Low serum cortisol, low ACTH: This indicates secondary adrenal insufficiency. The problem is not in the adrenal gland itself, but rather the pituitary gland not producing enough ACTH to stimulate the adrenals. This could be due to pituitary damage or suppression of the hypothalamic-pituitary-adrenal axis (e.g., from long-term steroid use).

Normal serum cortisol, elevated ACTH: This pattern is atypical and doesn't fit neatly into primary or secondary adrenal insufficiency. This might be seen in very early stages of disease or with a partial adrenal dysfunction, but further investigation would be needed.

Question 2

Endocrinology

A patient presents with episodic hypertension. Which constellation of findings is MOST suggestive of a phaeochromocytoma?

  1. AExcessive thirst, headache, and forceful heartbeats
  2. BSevere headache, lightheadedness, and difficulty sleeping
  3. CExcessive thirst, lightheadedness, and forceful heartbeats
  4. DSevere headache, rapid heart rate, and excessive sweating
  5. EExcessive sweating, blurry vision, forceful heartbeats
Show answer and explanation

Correct answer: D. Severe headache, rapid heart rate, and excessive sweating

Key takeaway

Phaeochromocytoma, a catecholamine-secreting tumour, classically presents with severe headache, rapid heart rate, and excessive sweating due to episodic surges in adrenaline and noradrenaline.

Episodic (paroxysmal) hypertension suggests a secondary cause rather than essential hypertension. Phaeochromocytomas are catecholamine-secreting tumours arising from chromaffin cells, usually within the adrenal medulla. These tumours release adrenaline and noradrenaline, leading to characteristic symptoms.

Severe headache, rapid heart rate, and excessive sweating represent the classic triad for a phaeochromocytoma. The episodic release of catecholamines causes surges in blood pressure (leading to headache), increased heart rate (palpitations, or a rapid heartbeat), and excessive sweating (diaphoresis) due to sympathetic overactivity.

None of the other combinations contains all three features of the triad, and each includes at least one feature that does not belong. Excessive thirst, headache, and forceful heartbeats includes thirst, which is not a typical symptom of catecholamine excess. Severe headache, lightheadedness, and difficulty sleeping lacks both the tachycardia and the sweating, and offers lightheadedness, which can occur with postural hypotension in phaeochromocytoma but is not a main clinical feature, and insomnia, which is non-specific. Excessive thirst, lightheadedness, and forceful heartbeats combines two non-specific features with palpitations alone and omits both headache and sweating. Excessive sweating, blurry vision, forceful heartbeats omits headache and adds blurred vision, which is not part of the classic presentation.

Question 3

Endocrinology

A newborn female presents with ambiguous genitalia. Which enzyme deficiency is most likely responsible?

  1. A17α-hydroxylase
  2. B21-hydroxylase
  3. CAromatase
  4. D5α-reductase
  5. E11β-hydroxylase
Show answer and explanation

Correct answer: B. 21-hydroxylase

Key takeaway

Ambiguous genitalia in a newborn female is most commonly caused by 21-hydroxylase deficiency: the block in cortisol synthesis diverts precursors towards adrenal androgens, which virilise the external genitalia in utero.

Congenital adrenal hyperplasia (CAH) encompasses several autosomal recessive disorders, each stemming from an enzyme deficiency in the cortisol synthesis pathway. These deficiencies lead to an accumulation of precursor steroids and a diversion of the pathway toward androgen production. This is particularly noticeable in a newborn female.

21-hydroxylase deficiency is the most common cause (90-95% of cases) of CAH and often presents with ambiguous genitalia in newborn females due to prenatal exposure to excessive androgens. It can also lead to potentially life threatening salt-wasting crises in the neonatal period due to aldosterone deficiency. The deficiency results in cortisol deficiency, diverting intermediates towards androgen production, causing virilisation of female infants.

11β-hydroxylase deficiency also causes CAH with virilisation, but it's less frequent than 21-hydroxylase deficiency. It differs in that it usually also causes hypertension due to the build-up of mineralocorticoid precursors.

17α-hydroxylase deficiency is a rarer form of CAH that presents with hypertension and hypokalaemia. It does not cause ambiguous genitalia in females; instead, affected females present with absent or delayed puberty. Males may have ambiguous genitalia or female external genitalia.

Aromatase deficiency affects the conversion of androgens to oestrogens, leading to virilisation of female fetuses. Affected mothers may also experience virilisation during pregnancy. However this is a much rarer enzyme deficiency.

5α-reductase deficiency affects the conversion of testosterone to dihydrotestosterone (DHT). This only affects the development of male external genitalia; therefore, 46,XY individuals have ambiguous genitalia at birth. It would not explain ambiguous genitalia in a newborn female.

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What the syllabus covers under adrenal gland

  • Adrenal Cortex
  • Adrenal Medulla
  • Adrenal Disorders

Read the full section in the Endocrinology guide, or check the next exam dates.