What explains the mildly elevated prolactin levels in a patient with a large pituitary mass and low levels of other pituitary hormones?

Loss of Dopamine Inhibition (Stalk Effect)

The mildly elevated prolactin in this patient with a large pituitary mass and hypopituitarism is best explained by loss of dopamine inhibition due to stalk compression (Answer D), not a prolactinoma.

Pathophysiology of Stalk Effect

The key to this diagnosis lies in understanding normal prolactin regulation:

• Prolactin is unique among pituitary hormones in being under tonic inhibition by hypothalamic dopamine 1
• When a large pituitary mass compresses the pituitary stalk, it interrupts the inhibitory dopaminergic tone on lactotroph cells, resulting in elevated prolactin levels 2
• This "stalk effect" or "pseudoprolactinoma" produces mild to moderate prolactin elevation, typically less than 100-200 μg/L 2, 3

Why This is NOT a Prolactinoma

The clinical presentation argues strongly against a true prolactinoma:

• True prolactinomas produce prolactin levels that directly correlate with tumor size 4
• Prolactin levels exceeding 200 μg/L (or 4,000 mU/L in children/adolescents) indicate a prolactinoma 2, 3
• Macroprolactinomas typically produce prolactin levels >250 μg/L, often in the thousands 5
• The presence of hypopituitarism (low levels of other pituitary hormones) with only mildly elevated prolactin is the hallmark of stalk compression rather than a functioning prolactinoma 2

Critical Diagnostic Pitfall: The Hook Effect

Before finalizing this diagnosis, you must exclude assay interference:

• Approximately 5% of patients with macroprolactinomas show paradoxically normal or mildly elevated prolactin due to the "high-dose hook effect" 4, 5, 2
• This occurs when extremely high prolactin concentrations saturate the immunoassay's signaling antibody, producing falsely low measurements 4, 6
• Serial dilutions of serum (1:1 and 1:10) must be performed whenever a large pituitary mass shows disproportionately low prolactin levels 4, 5, 2
• If dilution reveals markedly elevated prolactin (often >2,000 μg/L), the diagnosis changes to macroprolactinoma 6

Ruling Out Other Options

Option A (Prolactinoma): Unlikely given the mild elevation relative to tumor size 2, 3

Option B (Ectopic prolactin production): Extremely rare and not associated with pituitary masses or hypopituitarism 1

Option C (Increased TRH): While primary hypothyroidism can cause hyperprolactinemia through compensatory TRH hypersecretion, this would not explain the large pituitary mass or the pan-hypopituitarism 2

Option E (Assay interference): Must be excluded first through serial dilutions, but if prolactin remains mildly elevated after dilution, stalk compression is the diagnosis 4, 5

Clinical Algorithm

1. Order serial dilutions (1:1 and 1:10) of the prolactin sample immediately 4, 5
2. If prolactin remains mildly elevated after dilution: Diagnosis is stalk compression by non-functioning adenoma or other mass lesion 2
3. If prolactin rises dramatically with dilution (>2,000 μg/L): Diagnosis is macroprolactinoma with hook effect 6
4. Exclude hypothyroidism, medications (dopamine antagonists), and renal/hepatic disease as contributing factors 2, 1