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Recurrence of Hyperprolactinemia after Withdrawal of Long-Term Cabergoline Therapy

Division of Endocrinology and Metabolism (J.K., R.S., G.S.W.), Johns Hopkins University School of Medicine; and Johns Hopkins University School of Public Health (G.Y.), Baltimore, Maryland 21201

Address all correspondence to: J. Kharlip, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 333, Baltimore, Maryland 21201. E-mail: jkharlip{at}gmail.com.

Context: Recurrence of hyperprolactinemia after cabergoline withdrawal ranges widely from 36 to 80%. The Pituitary Society recommends withdrawal of cabergoline in selected patients.

Objective: Our aim was to evaluate recurrence of hyperprolactinemia in patients meeting The Pituitary Society guidelines.

Design: Patients were followed from the date of discontinuation to either relapse of hyperprolactinemia or the day of last prolactin test.

Setting: We conducted the study at an academic medical center.

Patients: Forty-six patients meeting Pituitary Society criteria (normoprolactinemic and with tumor volume reduction after 2 or more years of treatment) participated in the study.

Interventions: After withdrawal, if prolactin returned above reference range, another measurement was obtained within 1 month, symptoms were assessed by questionnaire, and magnetic resonance imaging was performed.

Main Outcome Measures: We measured risk of and time to recurrence estimates as well as clinical predictors of recurrence.

Results: Mean age of patients was 50 ± 13 yr, and 70% were women. Thirty-one patients had microprolactinomas, 11 had macroprolactinomas, and four had nontumoral hyperprolactinemia. The overall recurrence was 54%, and the estimated risk of recurrence by 18 months was 63%. The median time to recurrence was 3 months (range, 1–18 months), with 91% of recurrences occurring within 1 yr after discontinuation. Size of tumor remnant prior to withdrawal predicted recurrence [18% increase in risk for each millimeter (95% confidence interval, 3–35; P = 0.017)]. None of the tumors enlarged in the patients experiencing recurrence, and 28% had symptoms of hypogonadism.

Conclusions: Cabergoline withdrawal is practical and safe in a subset of patients as defined by The Pituitary Society guidelines; however, the average risk of long-term recurrence in our study was over 60%. Close follow-up remains important, especially within the first year.

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				A. Klibanski Dopamine Agonist Therapy in Prolactinomas: When Can Treatment Be Discontinued? J. Clin. Endocrinol. Metab., July 1, 2009; 94(7): 2247 - 2249. [Full Text] [PDF]