High biochemical recurrence rate after withdrawal of cabergoline in prolactinomas: is it necessary to restart treatment?
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ORIGINAL ARTICLE
High biochemical recurrence rate after withdrawal of cabergoline in prolactinomas: is it necessary to restart treatment? Etual Espinosa-Cárdenas1 Miriam Sánchez-García1 Claudia Ramírez-Rentería2 Victoria Mendoza-Zubieta1 Ernesto Sosa-Eroza 1 Moises Mercado2 ●
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Received: 27 April 2020 / Accepted: 8 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Treatment with dopamine agonists (DA) is highly effective in patients with prolactinomas. In selected patients, discontinuation of DA after several years of successful treatment is possible, however, hyperprolactinemia recurs in 60–80% of them. It is unclear what is the clinical significance of these recurrences and hence, whether or not reinitiation of therapy is necessary. Objectives To evaluate the recurrence rate in prolactinoma patients after DA withdrawal and the necessity to restart treatment. Methods Patients with >2 years of treatment with cabergoline (CBG) who achieved normoprolactinemia and a > 50% reduction in tumor size were included. DA dose was down titrated until withdrawal. Basal tumor size, as well as PRL and gonadal steroid levels were recorded at diagnosis, at withdrawal of DA and every 3–6 months for 1–3 years. Results Fifty patients were included (38 women, 34 macroprolactinomas). After withdrawal, 34 (68%) presented recurrence of hyperprolactinemia. PRL levels 50% reduction in tumor size in over 90% of patients with microprolactinomas, 70–80% with macroprolactinomas < 40 mm and in 55% of patients with tumors > 40 mm [4, 8–10]. The major drawback of DA treatment of prolactinomas is the need for life-long therapy [3, 11].
Endocrine
Discontinuation of DA after several years of successful treatment has been attempted since the late 1980s with recurrence rates between 65 and 80% [11–13]. According to a recent meta-analysis, factors associated with a successful withdrawal of DA include a normal PRL concentration, the absence of tumor remnant on MRI and the requirement of a relatively low DA dose [10, 12, 14, 15]. In most cases, recurrences after DA discontinuation are biochemical rather than clinical, and information regarding the long-term outcome of these patients is scarce [5, 11, 13, 16–23]. This study was designed to evaluate the long-term outcome of patients with prolactinomas in whom recurrence of hyperprolactinemia occurred after DA discontinuation, trying to identify factors associated with clinically significant relapses, and thus establishing real-life criteria that would justify the reinitiation of pharmacological treatment.
previously described [24]. When suspected, the hook effect was ruled out by performing the assay in 1:100 diluted serum samples. Hormones were determined by the next commercially available immunoassays: total testosterone (ECLIA, Elecsys, Roche Diagnostics, Switzerland, REF 122,11776061), TSH (Atellica TSH3-UL, Siemens, Germany), Free T4 (FT4) (Atellica FT4, Siemens, Germany) cortisol (Liaison assay, REF 313261,
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