AIM • STEP 10
Student Memory Support
Adrenal Cortical Hyperfunction: Cushing Syndrome, Hyperaldosteronism and Adrenogenital Syndrome
4th Year MBBS • ENDOCRINE + REPRODUCTION • High-yield memory reinforcement and last-minute revision
1. High-Yield Flashcards
Tap each question to reveal the answer.
Q: Which adrenal cortical zones produce aldosterone, cortisol and adrenal androgens?
A: Zona glomerulosa → aldosterone; zona fasciculata → cortisol; zona reticularis → adrenal androgens.
Q: What mainly regulates cortisol secretion?
A: Hypothalamic CRH → pituitary ACTH → adrenal cortisol, with cortisol providing negative feedback.
Q: What is the key distinction between Cushing syndrome and Cushing disease?
A: Cushing syndrome is glucocorticoid excess from any cause; Cushing disease is caused specifically by a pituitary ACTH-secreting adenoma.
Q: Why do patients with Cushing syndrome develop proximal muscle weakness?
A: Excess cortisol promotes protein catabolism and muscle wasting.
Q: What is the basic diagnostic sequence after endogenous hypercortisolism is confirmed?
A: Measure ACTH → classify as ACTH-dependent or ACTH-independent → perform targeted localization.
Q: What is the principle of the dexamethasone suppression test?
A: Dexamethasone provides glucocorticoid negative feedback → lowers ACTH → normally suppresses cortisol secretion.
Q: What biochemical pattern suggests primary hyperaldosteronism?
A: Inappropriately high aldosterone activity with suppressed renin.
Q: Why can primary hyperaldosteronism cause metabolic alkalosis?
A: Aldosterone increases distal hydrogen-ion secretion along with potassium loss.
Q: What is the central mechanism of congenital adrenal hyperplasia causing androgen excess?
A: Cortisol synthesis falls → negative feedback falls → ACTH rises → adrenal hyperplasia and precursor diversion toward androgen synthesis.
Q: Which biochemical marker is important in 21-hydroxylase deficiency?
A: 17-hydroxyprogesterone.
Q: How does 11β-hydroxylase deficiency differ clinically from salt-wasting 21-hydroxylase deficiency?
A: 11β-hydroxylase deficiency may cause hypertension because mineralocorticoid-active steroid precursors accumulate.
Q: How do glucocorticoids produce their principal genomic effects?
A: They bind intracellular glucocorticoid receptors → alter gene transcription → modify inflammatory and metabolic responses.
Q: Which glucocorticoid is long-acting with minimal mineralocorticoid activity?
A: Dexamethasone.
Q: Which drug blocks glucocorticoid action without directly reducing cortisol synthesis?
A: Mifepristone, a glucocorticoid receptor antagonist.
Q: Which cortisol synthesis inhibitor blocks 11β-hydroxylase?
A: Metyrapone.
Q: What is the major electrolyte danger of spironolactone?
A: Hyperkalaemia due to reduced aldosterone-mediated potassium excretion.
2. Mnemonics
Mnemonic Title:
Adrenal Cortex Layers
Mnemonic Word:
GFR = Salt • Sugar • Sex
Meaning:
Glomerulosa → aldosterone (“salt”); Fasciculata → cortisol (“sugar”); Reticularis → adrenal androgens (“sex”).
Mnemonic Title:
Cortisol Synthesis Inhibitors
Mnemonic Word:
KAM
Meaning:
Ketoconazole, Aminoglutethimide and Metyrapone reduce adrenal steroid/cortisol synthesis at different enzymatic steps.
Mnemonic Title:
CAH Blood-Pressure Distinction
Mnemonic Word:
21 = SALT • 11 = PRESSURE
Meaning:
Severe 21-hydroxylase deficiency may cause salt wasting; 11β-hydroxylase deficiency may cause hypertension from mineralocorticoid-active precursors.
3. Memory Tables
Table 1 — Major Adrenal Cortical Hyperfunction Patterns
| Feature | Cushing Syndrome | Primary Hyperaldosteronism | Adrenogenital Syndrome / CAH |
|---|---|---|---|
| Main abnormality | Excess glucocorticoid effect | Excess aldosterone | Enzyme defect with androgen excess in major forms |
| Key clue | Central obesity, weakness, purple striae | Hypertension + suppressed renin | Virilization / androgen excess |
| Diagnostic direction | Confirm cortisol excess → ACTH | Aldosterone relative to renin | Steroid precursor profile |
| Treatment principle | Treat source ± block cortisol synthesis/action | Surgery or mineralocorticoid blockade | Glucocorticoid ± mineralocorticoid replacement |
Table 2 — Drugs Used in Adrenal Hormone Excess
| Drug | Target | Main Effect | Memory Adverse Effect |
|---|---|---|---|
| Mifepristone | Glucocorticoid receptor | Blocks cortisol action | Hypokalaemia / uterine effects |
| Ketoconazole | Steroidogenic CYP enzymes | Reduces cortisol synthesis | Hepatotoxicity |
| Metyrapone | 11β-hydroxylase | Reduces cortisol synthesis | Androgenic/mineralocorticoid precursor effects |
| Aminoglutethimide | Cholesterol → pregnenolone step | Broad steroid suppression | Sedation / dizziness |
| Spironolactone | Mineralocorticoid receptor | Blocks aldosterone effects | Hyperkalaemia / endocrine effects |
4. Rapid Revision Points — Last-Minute Revision
Must Remember:
- All adrenal cortical steroid hormones are derived from cholesterol.
- ACTH mainly regulates cortisol and adrenal androgen secretion; RAAS and potassium mainly regulate aldosterone.
- Purple striae and easy bruising in Cushing syndrome reflect loss of collagen and connective-tissue strength.
- Cushing evaluation: establish hypercortisolism first, then use ACTH to direct localization.
- Normal serum potassium does not exclude primary hyperaldosteronism.
- Primary hyperaldosteronism can produce hypertension, hypokalaemia and metabolic alkalosis.
- 21-hydroxylase deficiency may cause androgen excess with salt wasting.
- 11β-hydroxylase deficiency may cause androgen excess with hypertension.
- Long-term glucocorticoids can cause osteoporosis, infection risk, hyperglycaemia and HPA-axis suppression.
- Mifepristone blocks cortisol action; ketoconazole, metyrapone and aminoglutethimide reduce steroid synthesis.
Common KMU Trap: Cushing disease is only the pituitary ACTH-secreting form of Cushing syndrome.
5. Clinical Memory Hooks
Central obesity + thin limbs + purple striae
→
think cortisol excess causing fat redistribution and protein catabolism.
→
think cortisol excess causing fat redistribution and protein catabolism.
Hypertension + suppressed renin ± low potassium
→
think autonomous aldosterone excess.
→
think autonomous aldosterone excess.
Virilization + salt wasting in a child
→
think severe 21-hydroxylase deficiency.
→
think severe 21-hydroxylase deficiency.
Long-term glucocorticoid therapy stopped abruptly
→
risk of adrenal insufficiency because CRH–ACTH drive has been suppressed.
→
risk of adrenal insufficiency because CRH–ACTH drive has been suppressed.
6. Starred High-Yield Exam Points
- ⭐ Cushing syndrome = cortisol excess from any cause; Cushing disease = pituitary ACTH-secreting adenoma.
- ⭐ Suppressed ACTH after confirmed endogenous hypercortisolism points toward an ACTH-independent adrenal source.
- ⭐ Dexamethasone suppresses ACTH through glucocorticoid negative feedback; abnormal suppression is used in Cushing evaluation.
- ⭐ Primary hyperaldosteronism is characterized by aldosterone activity inappropriate for suppressed renin.
- ⭐ 21-hydroxylase deficiency: low cortisol → high ACTH → adrenal hyperplasia + androgen excess; severe disease may salt-waste.
- ⭐ Metyrapone inhibits 11β-hydroxylase; ketoconazole inhibits steroidogenic CYP enzymes; aminoglutethimide blocks an early steroid-synthesis step.
- ⭐ Spironolactone blocks mineralocorticoid receptors; hyperkalaemia is the key electrolyte adverse effect.