A patient undergoes an insulin tolerance test (ITT). Despite adequate hypoglycemia (glucose < 2.2 mmol/L), his cortisol rises to only 380 nmol/L (normal > 500 nmol/L). Which level of the hypothalamo-pituitary-adrenal axis is most likely impaired?
- A Adrenal cortex — primary adrenal insufficiency
- B Cannot be determined by ITT alone ✓
- C Anterior pituitary — secondary adrenal insufficiency
- D Hypothalamus — tertiary adrenal insufficiency
Explanation
The ITT tests the integrity of the entire hypothalamo-pituitary-adrenal axis by inducing neuroglycopenic stress, which normally stimulates hypothalamic CRH → pituitary ACTH → cortisol. A blunted response confirms HPA axis insufficiency but cannot localize the defect to hypothalamus vs pituitary without concurrent ACTH measurement; a low ACTH points to pituitary (secondary), while a normal or elevated ACTH with low cortisol points to adrenal (primary). Tertiary (hypothalamic) and secondary (pituitary) causes produce similar ACTH patterns and often require a CRH stimulation test to distinguish.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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