How Hyperprolactinemia Affects Thyroid Function
Primary Mechanism: Hypothyroidism Causes Hyperprolactinemia (Not the Reverse)
The relationship between prolactin and thyroid function is unidirectional—primary hypothyroidism causes hyperprolactinemia, not the other way around. 1, 2
Hypothyroidism Leading to Elevated Prolactin
Primary hypothyroidism causes hyperprolactinemia in 43% of women and 40% of men with frank hypothyroidism, and in 36% of women and 32% of men with subclinical hypothyroidism. 2
The mechanism involves compensatory hypersecretion of thyrotropin-releasing hormone (TRH), which directly stimulates prolactin release from pituitary lactotrophs in addition to stimulating TSH. 2
This TRH-mediated hyperprolactinemia can produce pituitary hyperplasia that must be distinguished from a true prolactinoma on imaging. 2
Prolactin levels in hypothyroidism are typically modest, rarely exceeding 100 ng/mL (4.34 nmol/L), though exceptional cases up to 323 ng/mL have been reported when combined with macroprolactinemia. 3
Hyperprolactinemia Does NOT Cause Hypothyroidism
Despite increased dopaminergic inhibition of TSH release that occurs in hyperprolactinemic patients, this does not lead to clinical hypothyroidism. 4
Hyperprolactinemic patients maintain biochemical euthyroidism through compensatory mechanisms—slightly elevated basal TSH levels and TSH responses to TRH (within normal range) counteract the increased dopaminergic inhibition. 4
The hypothalamic dopamine system in hyperprolactinemia may suppress TSH release, but thyroid function remains normal through this compensatory TSH elevation. 4
Critical Diagnostic Pitfall to Avoid
Always exclude hypothyroidism before diagnosing a prolactinoma, as untreated hypothyroidism with pituitary hyperplasia can mimic a prolactin-secreting adenoma. 1, 2, 5
Measure TSH and free T4 in every patient with hyperprolactinemia before proceeding to pituitary MRI or dopamine agonist therapy. 1, 5
Treatment of the underlying hypothyroidism with levothyroxine will normalize prolactin levels and resolve pituitary hyperplasia, avoiding unnecessary dopamine agonist therapy or surgery. 1, 3
In cases where prolactin remains elevated after thyroid replacement, consider macroprolactinemia (10-40% of hyperprolactinemia cases) as a concurrent cause. 3
Paradoxical Effect During Thyroid Replacement
During initial thyroid hormone replacement in hypothyroid patients with hyperprolactinemia, prolactin levels may transiently and paradoxically increase before normalizing. 6
This occurs because small doses of thyroid hormone initially activate lactotrophs more than they enhance hypothalamic dopaminergic inhibition. 6
As euthyroidism is achieved, both basal prolactin and prolactin response to dopamine antagonists normalize. 6