A patient with major depressive disorder shows a blunted TSH response to TRH stimulation testing, despite normal basal TSH and free T4 levels. Which hypothalamic factor is most likely responsible for this altered TRH responsiveness in depression?

• A Excessive somatostatin tone
• B Chronic hypercortisolemia ✓
• C Dopamine excess
• D Reduced GHRH secretion

Explanation

Chronic hypercortisolemia in depression suppresses TRH gene expression in the paraventricular nucleus and reduces TRH secretion, leading to a blunted TSH response to exogenous TRH. This is part of HPA axis dysregulation in depression. While somatostatin can inhibit TSH, hypercortisolemia is the most well-documented mechanism for blunted TRH test response in major depressive disorder.

Reference: Ganong's Review of Medical Physiology, 26th ed.

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