Objective: The aim was to formulate practice guidelines for the diagnosis and treatment of hyperprolactinemia. Participants: The Task Force consisted of Endocrine Society-appointed experts, a methodologist, and a medical writer. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society, The European Society of Endocrinology, and The Pituitary Society reviewed and commented on preliminary drafts of these guidelines. Conclusions: Practice guidelines are presented for diagnosis and treatment of patients with elevated prolactin levels. These include evidence-based approaches to assessing the cause of hyperprolactinemia, treating drug-induced hyperprolactinemia, and managing prolactinomas in nonpregnant and pregnant subjects. Indications and side effects of therapeutic agents for treating prolactinomas are also presented. (J Clin Endocrinol Metab 96: 273–288, 2011)

Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.

/pdf/advances-in-the-treatment-of-prolactinomas-5a8n14833q.pdf

Advances in the treatment of prolactinomas.

Hyperprolactinemia and prolactinomas.

Context: Dopamine agonists are the treatment of choice for prolactinomas and symptomatic idiopathic hyperprolactinemia However, the optimal treatment strategy and treatment duration is not clear in all details Objective: The aim of the study was to assess the effect of dopamine agonist withdrawal in patients with idiopathic hyperprolactinemia and prolactinomas Data Sources: PubMed, the Cochrane Library, the Web of Science, and EMBASE were searched electronically No restriction was made with respect to language Study Selection: Studies reporting the proportion of normoprolactinemic patients after withdrawal of dopamine agonist or studies in which this proportion could be calculated were eligible Both observational studies and clinical trials were eligible Nineteen studies were included in the meta-analysis, with a total of 743 patients Data Extraction: Data extraction was performed by two reviewers independently Data Synthesis: The pooled proportion of patients with persisting normoprolactinemia a

https://repository.ubn.ru.nl/bitstream/handle/2066/89490/89490.pdf

Recurrence of hyperprolactinemia after withdrawal of dopamine agonists: systematic review and meta-analysis.

Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. The most important clinical problems associated with prolactinomas are hypogonadism, infertility and hyposexuality. In patients with macroprolactinomas, mass effects, including visual field defects, headaches and neurological disturbances, can also occur. The objectives of therapy are normalization of prolactin levels, to restore eugonadism, and reduction of tumor mass, both of which can be achieved in the majority of patients by treatment with dopamine agonists. Given their association with minimal morbidity, these drugs currently represent the mainstay of treatment for prolactinomas. Novel data indicate that these agents can be successfully withdrawn in a subset of patients after normalization of prolactin levels and tumor disappearance, which suggests the possibility that medical therapy may not be required throughout life. Nevertheless, multimodal therapy that involves surgery, radiotherapy or both may be necessary in some cases, such as patients who are resistant to the effects of dopamine agonists or for those with atypical prolactinomas. This Review reports on efficacy and safety of pharmacotherapy in patients with prolactinomas.

Medical treatment of prolactinomas

Although two thirds or more of patients with microprolactinoma achieve normal serum prolactin levels over the long term after withdrawal of dopamine agonist therapy, there is no agreement on the appropriate duration of treatment, and treatment is not always interrupted. In this retrospective analysis of 89 patients, 84 women and 5 men with a mean age of 33 years, remissions were analyzed in 67 patients treated with 0.5 to 3 mg cabergoline weekly and 22 others given 2.5 to 10 mg bromocriptine daily. The mean duration of therapy was 3.1 years, and patients were followed for at least 1 year after treatment ended. None of the patients received medication other than a dopamine agonist. Seven women discontinued treatment when they became pregnant. All patients were symptomatic and hyperprolactinemic when first seen. Among 57 patients (64%) who had a recurrence after treatment stopped were 46 (81%) who had recurrent symptomatic hyperprolactinemia within 12 months after stopping treatment. The average interval was 9.6 months. Thirty-two patients, 36% of the total, achieved remission after at least 1 year of follow up; the mean duration of remission was 3.6 years. Nearly 85% of these patients remained in remission for longer than 2 years. Four of them were asymptomatic despite being hyperprolactinemic. The 2 dopamine agonists were equally effective. The overall median duration before relapse after discontinuance of treatment was 12 months. Logistic regression analysis failed to demonstrate an association between the risk of recurrence and age at presentation, imaging of an adenoma, or the duration of treatment. When dopamine agonist therapy is abruptly withdrawn after 2 years or longer in patients with microprolactinoma, 30% to 40% achieve long-term remission without side effects. Because symptomatic hyperprolactinemia may develop more than 1 year after treatment stops, long-term follow up is essential.

Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas

Summary
Objective Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long-term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment-naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal.

Design  Retrospective analysis of clinic records of 89 patients (mean age 32·7 ± 8·4 years, 84 women and 5 men) who had received either cabergoline (n = 67) (0·5–3 mg weekly) or bromocriptine (n = 22) (2·5–10 mg daily) for a mean duration of 3·1 years.

Results  Following withdrawal of therapy, 57 subjects developed recurrence (64%) and the mean time to recurrence was 9·6 months (range 1–44 months), while 32 subjects (36%) remained in remission beyond 1 year (mean 3·6 years, range 1–7 years). There was no difference in remission rates between subjects treated with cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship between pretreatment prolactin concentration and risk of recurrent symptomatic hyperprolactinaemia was observed. No subjects developed clinical features to suggest tumour expansion following therapeutic discontinuation.

Conclusions  This study confirms that abrupt withdrawal of chronic dopamine agonist therapy, following 2 to 3 years of treatment is safe and associated with long-term remission in 30–40% of subjects with microprolactinomas. This therapeutic strategy is convenient and applicable in clinical practice.

Long‐term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas

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Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas

Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas

Long‐term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas