Loss of Dopamine Inhibition (Stalk Effect)
The most likely explanation is D: Loss of dopamine inhibition from pituitary stalk compression by the large mass, a phenomenon known as the "stalk-section effect" or "pseudoprolactinoma." 1, 2
Key Diagnostic Reasoning
The clinical scenario presents three critical features that point away from a true prolactinoma:
Mildly elevated prolactin with a large mass - The degree of prolactin elevation typically correlates with tumor size in true prolactinomas, with levels usually exceeding 4,000 mU/L (approximately 200 ng/mL) in macroprolactinomas 2
Low levels of other pituitary hormones - This indicates a non-functioning pituitary adenoma causing mass effect and compression of normal pituitary tissue 1
Serial dilution performed - This crucial step rules out the "hook effect" (assay interference), which occurs in approximately 5% of macroprolactinomas when extremely high prolactin concentrations saturate the immunoassay, producing falsely low measurements 1, 2
Why Not the Other Options?
A. Prolactinoma is unlikely because true prolactinomas of this size would typically produce prolactin levels well above 200 ng/mL, often exceeding 500-1000 ng/mL 2. The mild elevation (typically <100 μg/L or <2000 mU/L) with a large mass suggests stalk compression rather than autonomous prolactin secretion 2.
B. Ectopic prolactin production is exceedingly rare and would not explain the low levels of other pituitary hormones or the presence of a pituitary mass 3.
C. Increased TRH from primary hypothyroidism can cause hyperprolactinemia, but this should have been excluded as part of the initial workup, and would not explain the large pituitary mass or panhypopituitarism 2.
E. Assay interference (hook effect) has been specifically ruled out by performing serial dilutions, which is the definitive test to exclude this phenomenon 1, 2.
Pathophysiology of Stalk Compression
When a non-functioning pituitary mass compresses or deviates the pituitary stalk, it interrupts the normal dopaminergic inhibition from the hypothalamus to the lactotroph cells 2. This loss of tonic dopamine inhibition results in mild-to-moderate prolactin elevation, typically in the range of 25-100 ng/mL 2. Importantly, research has shown that the degree of prolactin elevation does not correlate well with the extent of stalk compression or deviation visible on MRI 4.
Clinical Pitfall to Avoid
The Endocrine Society specifically warns against missing this diagnosis: do not assume a large pituitary mass with elevated prolactin is automatically a prolactinoma 1. The distinction is critical because non-functioning adenomas causing stalk compression require different management (often surgical) compared to prolactinomas (which respond to dopamine agonist therapy) 1, 2.