Overview

This will be a multicenter, prospective, randomized, open-label trial with women harboring microprolactinomas and treatment naïve. The sample will be added consecutively and randomized into 2 unblinded groups: the high dosage group will receive a high cabergoline (CAB) dose for a period of \~6 months vs the standard dosage group, which will use the lowest needed dose of CAB to achieve normoprolactinemia for 2 years. The primary outcome will be remission rate.

Eligibility

Inclusion Criteria:

• 1\. Willing and able to provide written informed consent prior to any study-related procedures
• 2\. Adults \>18 years old
• 3\. Pre-menopausal women
• 4\. Presence of signs and symptoms matching prolactinoma
• 5\. Hyperprolactinemia, defined as a prolactin (PRL) level ≥2 times the local laboratory maximum level of normality, present at the time of enrolment
• 6\. Presence of an identifiable pituitary mass on MRI with a maximum diameter of less than 1cm, independently of Knosp/invasiveness of the cavernous sinus
• 7\. Treatment naïve
• 8\. Females who engage in heterosexual intercourse must agree to use either a highly effective or a clinically acceptable method of contraception from the beginning of screening to the last study visit, which will include:
• Hysterectomy or bilateral salpingectomy
• Bilateral tubal occlusion or ligation
• Vasectomized partner
• Intrauterine device (copper or hormonal)
• Progestogen-only contraception (oral, injectable or implantable)
• Male or female condom with or without spermicide
• Sexual abstinence (only when it is the usual and preferred lifestyle of the subject)

Exclusion Criteria:

• 1\. History of primary hyperparathyroidism
• 2\. Use of combined hormonal contraceptive within the past 4 weeks
• 3\. Pregnancy or current pregnancy desire
• 4\. Prolactinoma associated with a known genetic syndrome
• 5\. Familial history of pituitary adenoma
• 6\. Renal failure (estimated glomerular filtration rate \<30 mL/min /1.73m2)
• 7\. IGF-1 level above the age-adjusted normal range of the local laboratory (IGF 1 \>1x ULNR)
• 8\. Idiopathic hyperprolactinemia (normal MRI) or presence of macroprolactinemia
• 9\. Concomitant mental condition rendering her unable to understand the nature, scope, and possible consequences of the study, and/or decompensated psychiatric disease (i.e. gambling or severe obsessive-compulsive disorder), as judged by the Investigator
• 10\. Chronic use of drugs related to hyperprolactinemia (such as metoclopramide, methyldopa, ranitidine, and opioid-related analgesics)
• 11\. Resistant prolactinoma, defined as non-normalization of PRL levels with 2mg/w of CAB
• 12\. Patients in the high dosage group who did not use 3.5mg/w of CAB for an entire 6 months (due to intolerance or non-compliance) or failed to achieve the target dose for any other reason
• 13\. Active malignant disease within the last 5 years, except basal and squamous cell carcinoma of the skin with complete local excision
• 14\. Any decompensated chronic condition (i.e. heart failure NYHA 3-4, diabetes with HbA1c \>8.5%, hypothyroidism with TSH \>10 mIU/L) that, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes
• 15\. Male sex
• 16\. Cushing stigmas (moon face, muscle weakness, red striation) or suspicious
• 17\. Prior radiotherapy of the pituitary gland area for any reason
• 18\. Additional pituitary tumor-directed therapy, including temozolomide, everolimus, lapatinib, or cytotoxic chemotherapy
• 19\. Hepatopathy with AST/TGO or ALT/TGP \>3x the upper limit of normality