Prolactinomas: resistance assessment via metabolomic characteristics

A. Shutova*^a (Dr), L. Dzeranova^a (Dr), E. Pigarova^a (Dr), L. Usoltseva^a (Mrs), V. Ioutsi^a (Mr), J. Panov^a (Mr), N. Fedorova^a (Dr), E. Przhiyalkovskaya^a (Dr), S. Vorotnikova^a (Dr)

^a Federal state budgetary institution "National Medical Research Centre of Endocrinology" Ministry of Health of the Russian Federation, Moscow, RUSSIAN FEDERATION

* shutova.aleksandra@gmail.com

Introduction: Prolactinomas are the most common type of pituitary adenomas, accounting up to 40 % of them and represent a significant cause of infertility and hypogonadism. About 20% of patients with prolactinomas do not respond satisfactory (resistant) even to high dose dopamine agonist treatment. The etiology of treatment’s resistance is a subject of lively discussion and worth noticing that there are no clear prognostic signs.

Aim: The aim of our study was to assess absorption and metabolism of cabergoline in patients with dopamine agonist-resistant prolactinomas.

Materials and methods: In patients (n=4) with resistant prolactinomas (no normalization of PRL, no menses with max tolerated dose of cabergoline more than 3 mg a week) and one with normal effect of the drug we conducted a specific pharmacokinetic test: 1) cabergoline was preliminary withdrawn 4 days before the test; 2) at 9:00 the blood was taken before and 30-, 60-, 90-, 120-minutes and 4 hours after taking the cabergoline in a fixed doze of 0.5 mg. The concentration of cabergoline substance in the serum was measured using high-performance liquid chromatography-mass spectrometry method (LC-MS/MS).

Results: It is shown that the serum cabergoline concentration curve in 3 patients with resistance to treatment doesn’t represent expected pharmacokinetic peaks (the growth rate less than + 1-50%). The pharmacokinetic curve of 1 resistant patient represented a cabergoline concentration peak at 30 min point (the growth rate +175%) with subsequent decline to baseline levels. The serum cabergoline concentration curve of drug-sensitive patient is characterized by an already significant baseline concentration that becomes progressively higher reaching an outstanding peak (the growth rate +112%) at the end of the test period.

Conclusion: Our pilot results show that the patients with dopamine-resistant prolactinomas may have a defect in forming (absorption or metabolic abnormalities) an adequate blood concentrations of the drug as well as genetic or receptors alterations. Clinical map of prolactinoma’s resistance to therapy is full of black spots. Understanding the underlying mechanisms will allow us to develop personalized treatment strategy.

The author has declared no conflict of interest.