Verapamil acute administration: a new dynamic test in hyperprolactinemic states

Area of Science:

• Endocrinology
• Pharmacology
• Neuroendocrinology

Background:

• Hyperprolactinemia (elevated prolactin levels) can stem from pituitary tumors (tumoral hyperprolactinemia, THPRL) or other causes (idiopathic hyperprolactinemia, IHPRL).
• Distinguishing between THPRL and IHPRL is crucial for appropriate patient management and treatment strategies.

Purpose of the Study:

• To evaluate the efficacy of the calcium-channel blocker verapamil (VER) in differentiating THPRL from IHPRL.
• To investigate the effect of VER on prolactin (PRL) secretion in patients with hyperprolactinemia and healthy controls.

Main Methods:

• Acute administration of verapamil (VER) and placebo on separate days to patients with THPRL, IHPRL, and healthy controls.
• Serum PRL levels were measured to assess the response to VER.
• Intravenous (IV) VER administration and comparison of oral formulations were conducted in healthy subjects.

Main Results:

• VER administration significantly increased serum PRL in IHPRL and healthy controls, but not in THPRL patients, showing no overlap.
• VER stimulated PRL secretion in patients with minimal incidental MRI lesions, with a blunted response in those with PRL near the upper normal limit.
• VER administered intravenously did not stimulate PRL release in normal subjects, suggesting oral formulations may involve hepatic metabolism.

Conclusions:

• The VER test is a valuable tool for distinguishing between THPRL and IHPRL.
• The test cannot differentiate pseudoprolactinomas (THPRL due to reduced dopaminergic tone) from other forms of THPRL.
• Calcium influx appears less critical in the pathophysiology of chronic PRL secretion disorders.