A 45-year-old man undergoes testing for suspected acromegaly. Paradoxical GH secretion in response to oral glucose load (GH rises rather than falls) is found. The mechanism of this paradoxical response is:

• A Somatotroph adenoma cells aberrantly express GHRH receptors or GH secretagogue receptors that respond to glucose metabolites, bypassing normal somatostatin suppression ✓
• B GH-secreting tumor cells express aberrant glucose receptors causing stimulated secretion
• C Oral glucose stimulates GIP, which directly stimulates GH release
• D Glucose-induced hyperinsulinemia increases IGF-1, which stimulates GH by short-loop feedback

Explanation

Normally, oral glucose suppresses GH by augmenting somatostatin release and reducing GHRH sensitivity in somatotrophs. In GH-secreting adenomas, tumor cells may express ectopic receptors (e.g., for TRH, GHRH, dopamine, GIP, or GH secretagogues) and often have constitutively active Gs-alpha mutations (gsp oncogene in ~40%), rendering them insensitive to normal somatostatin inhibition. The paradoxical GH rise to glucose is a recognized feature of acromegaly used diagnostically. IGF-1 exerts negative short-loop feedback on GH; hyperinsulinemia does not increase GH. GIP may paradoxically stimulate GH in acromegaly through ectopic GIP receptors, but the core mechanism is resistance to normal suppressive regulation.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.