Second Attempt of Cabergoline Withdrawal in Patients with Prolactinomas after a Failed First Attempt: Is it Worthwhile?

Abstract

Successful discontinuation of cabergoline (CAB) treatment has been reported in 31–75% of prolactinomas patients treated for at least 2 years. In contrast, it is not well established whether CAB therapy can be successfully withdrawn after a failed first attempt. This prospective open trial was designed to address this topic and to try to identify possible predictor factors. Among 180 patients with prolactinomas on CAB therapy, the authors selected those who fulfilled very strict criteria, particularly additional CAB therapy for at least 2 years, normalization of serum prolactin (PRL) levels following CAB restart, no tumor remnant >10 mm, no previous pituitary radiotherapy or surgery; and current CAB dose ≤1.0 mg/week. Recurrence was defined as an increase of PRL levels above the upper limit of normal. A total of 34 patients (70.6% female) treated with CAB for 24–30 months were recruited. Ten patients (29.4%) remained without evidence of recurrence after 24–26 months of follow-up. Twenty-four patients (70.6%) recurred within 15 months (75% within 12 months) after drug withdrawal and ~80% were restarted CAB. Median time to recurrence was 10.5 months (range, 3–15). Despite overlapping values, non-recurring patients had significantly lower mean PRL levels before withdrawal. Moreover, the recurrence rate was lower in subjects without visible tumor on pituitary magnetic resonance imaging (MRI) than in those with small remnant tumor (60 vs. 79%), though the difference was not statistically significant (P = 0.20). No other characteristic could be identified as a predictor of successful CAB discontinuation. In conclusion, a second attempt of CAB withdrawal after two additional years of therapy may be successful, particularly in patients with lower PRL levels and no visible tumor on pituitary MRI. Close monitoring of PRL level is mandatory, especially within the first year after withdrawal, where most recurrences are detected.

The Role of Isotretinoin Therapy for Cushing’s Disease: Results of a Prospective Study

“…After cessation of retinoic acid administration, UFC appeared to slowly rebound to pretreatment levels. However, very interestingly, long-lasting normalization of UFC was observed in one patient after drug discontinuation, suggesting a durable inhibitory effect of retinoic acid on the tumoral corticotroph [ 31 ], similarly to what happens in some prolactinomas patients after cabergoline withdrawal [ 56 , 57 ] and a few acromegalic subjects following octreotide LAR interruption [ 58 , 59 ].…”

Terapia dei prolattinomi: quando sospendere?

“…Nei pazienti in cui la sospensione del trattamento con DA sia seguita da una recidiva di malattia, è suggerito di riprendere la terapia con i DA [1,2]. Tuttavia, la reintroduzione del trattamento non è da considerarsi definitiva, in quanto nei pazienti in cui siano rispettati i criteri suggeriti dalle linee guida della Pituitary Society del 2006 dopo due ulteriori anni di trattamento è possibile effettuare un secondo tentativo di sospensione, che è stato dimostrato essere efficace nel determinare persistente normoprolattinemia in circa un terzo dei casi [28,29].…”

Controversial issues in the management of hyperprolactinemia and prolactinomas – An overview by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism

“…Two independent studies (173,174) have investigated the outcome of a second attempt at CAB withdrawal in patients with recurrence of hyperprolactinemia after the first withdrawal, receiving additional CAB therapy for at least 2 years. The results of these studies have demonstrated that a second attempt at CAB withdrawal after 2 additional years of therapy may be successful in approximately 30% of patients (173,174).…”

“…Most patients relapse within the first year, during which the patient should be subjected to a stricter monitoring of PRL levels (e.g., every 3 months) (164)(165)(166)(167)(168)(169). In virtually all studies, all recurrences were observed within 24 months of DA discontinuation (162)(163)(164)(165)(166)(167)(168)(169)(170)(171)(172)(173). In cases of hyperprolactinemia recurrence, the risk of tumor growth is very low (< 10%) (88,160,162,169).…”