Functional hyperprolactinemia and primary hypothyroidism: myth or reality in clinical practice?

Background: Hyperprolactinemia is a frequent clinical condition with different etiologies. Although primary hypothyroidism is often considered a leading cause of mild hyperprolactinemia, the supporting evidence is limited and often based on small studies with single prolactin (PRL) measurements, especially in cases of subclinical hypothyroidism. This study aims to evaluate the prevalence of thyroid dysfunction in patients assessed for hyperprolactinemia.
Patients and methods: This retrospective study included patients undergoing cannulated PRL sampling (three serial measurements) and TSH assessment on the first sample, between January 2013 and May 2024, at Padova University Hospital. Patients were stratified by the degree of PRL elevation and TSH levels. PRL-secreting pituitary adenoma, functional hyperprolactinemia and normal pituitary function were assessed through review of medical history.
Results: Of 292 patients with available data, 233 fulfilled the inclusion criteria. Hyperprolactinemia was confirmed in 91/233 patients (39%). Among these, 27% had increased TSH compared to 18% in the normoprolactinemic group (p=0.073). No significant differences in TSH levels were observed when comparing subgroups of patients with varying degrees of PRL excess (p=0.474). PRL levels from cannulated samples and their mean values were not significantly higher in patients with hypothyroidism. Bivariate correlation analysis revealed no significant association between TSH and PRL levels.
Conclusion: Our findings suggest a low probability of hypothyroidism as a primary cause of hyperprolactinemia: TSH increase should not delay the diagnostic evaluation for hyperprolactinemia, due to the low probability of thyroid dysfunction. Further studies are necessary to confirm these findings and improve clinical practice.