A 32-year-old man with coarse facial features, enlarged hands, and bitemporal visual field loss has a pituitary macroadenoma. During a 75 g oral glucose tolerance test, his growth hormone level fails to fall below 5 ng/mL and shows a paradoxical rise at 60 minutes. What explains the failure of glucose to suppress GH in this patient?

• A IGF-1 resistance causing compensatory GH overproduction only postprandially
• B Excess somatostatin tone from the intact hypothalamus overriding glucose signals
• C Elevated free fatty acids mimicking the fasting state at the pituitary level
• D Autonomous GH secretion by the adenoma with loss of hypothalamic feedback control ✓

Explanation

In healthy subjects, hyperglycemia raises free fatty acids and insulin, suppresses GHRH, and increases somatostatin, driving GH below 1 ng/mL. Somatotroph adenomas secrete GH autonomously and retain only partial responsiveness to hypothalamic input, so suppression fails and paradoxical rises occur in some tumors. Elevated FFA normally suppresses GH rather than stimulating it, which eliminates option C as the explanation.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.