Prolactinomas are the most common pituitary adenomas (approximately 40% of cases), and they represent an important cause of hypogonadism and infertility in both sexes. The magnitude of prolactin (PRL) elevation can be useful in determining the etiology of hyperprolactinemia. Indeed, PRL levels > 250 ng/mL are highly suggestive of the presence of a prolactinoma. In contrast, most patients with stalk dysfunction, drug-induced hyperprolactinemia or systemic diseases present with PRL levels < 100 ng/mL. However, exceptions to these rules are not rare. On the other hand, among patients with macroprolactinomas (MACs), artificially low PRL levels may result from the so-called "hook effect". Patients harboring cystic MACs may also present with a mild PRL elevation. The screening for macroprolactin is mostly indicated for asymptomatic patients and those with apparent idiopathic hyperprolactinemia. Dopamine agonists (DAs) are the treatment of choice for prolactinomas, particularly cabergoline, which is more effective and better tolerated than bromocriptine. After 2 years of successful treatment, DA withdrawal should be considered in all cases of microprolactinomas and in selected cases of MACs. In this publication, the goal of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) is to provide a review of the diagnosis and treatment of hyperprolactinemia and prolactinomas, emphasizing controversial issues regarding these topics. This review is based on data published in the literature and the authors' experience.

Context and objective: The interaction between pregnancy and acromegaly has been studied only retrospectively. We used prospective data to assess those interactions. Design: Prospective, interventional, multicentric study. Patients: Ten pregnancies in eight acromegalic patients were included according to the following criteria: previous diagnosis of acromegaly; and active acromegaly before pregnancy. Sellar magnetic resonance image (MRI), GH, and IGF1 measurements were carried out before pregnancy. The exclusion criterion was radiotherapy. Intervention: Withdrawal of pharmacological treatment (octreotide and/or cabergoline and/or pegvisomant) following pregnancy diagnosis. Main outcome measures: Clinical/biochemical evaluations throughout pregnancy/puerperium and sellar MRI after delivery; and GH and IGF1 measurements before pregnancy. GH was measured by an interference-free IFMA assay during pregnancy and IGF1 by measured by Immulite 2000 assay in patients and 64 control pregnancies. Results: No tumor growth was observed. Nine deliveries were at term and one at 35 weeks (preeclampsia). All newborns were healthy. Mean IGF1 levels before and during pregnancy were similar, but increased significantly during puerperium. As IGF1 in controls increased after midgestation, the prevalence of controlled IGF1 rose significantly from 2/10 (!20 weeks) to 9/10 (O30 weeks). Diabetes mellitus and hypertension/preeclampsia developed in one patient in each group; both complications were nonsignificantly (PZ0.06) associated with IGF1 O1.3 ULN before pregnancy. Conclusions: Acromegaly control usually improved and tumor growth was not stimulated during pregnancy in spite of withdrawal of drug treatment. Drug treatment can be discontinued in most patients. Uncontrolled disease before pregnancy may pose a higher risk for diabetes and hypertension.

Bromocriptine (BRC) and other dopamine agonist drugs are the first-choice treatment for prolactinomas. However, the major disadvantage is the need for prolonged therapy. We retrospectively studied 131 patients [62 microprolactinoma (MIC), 69 macroprolactinoma (MAC)], who achieved serum prolactin (PRL) normalization during BRC use. Twenty-seven percent of them (31% MIC and 69% MAC) underwent previous surgery. Twenty-seven patients (20.6%: 25.8% MIC and 15.9% MAC) persisted with normoprolactinemia after a median time of 44 months of BRC withdrawal. The median time of BRC use was 47 months. There were no statistically significant differences regarding age, gender, BRC initial dose, length of BRC use, tumor size, pregnancy during treatment, previous surgery, or radiotherapy among patients who persisted with normoprolactinemia and those who did not, using both univariate and multivariate analysis. BRC-induced prolactinoma cell alterations are highly controversial; and so, whether the mechanism of PRL normalization after BRC withdrawal is related to BRC use or whether it is attributable to natural history is a matter for debate. A periodic assessment of PRL levels during BRC (and other dopamine-agonist drugs) withdrawal is recommended to avoid the unnecessary maintenance of therapy in a subset of patients with prolactinomas.

Persistence of cortisol response (DeltaF > 193 nmol/l) to desmopressin in the early postoperative period can help to identify Cushing's disease patients with initial remission who present risk for later recurrence.

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Although it is a rare condition, the accurate diagnosis and treatment of Cushing's disease is important due to its higher morbidity and mortality compared to the general population, which is attributed to cardiovascular diseases, diabetes mellitus and infections. Screening for hypercortisolism is recommended for patients who present multiple and progressive clinical signs and symptoms, especially those who are considered to be more specific to Cushing's syndrome, abnormal findings relative to age (e.g., spinal osteoporosis and high blood pressure in young patients), weight gain associated with reduced growth rate in the pediatric population and for those with adrenal incidentalomas. Routine screening is not recommended for other groups of patients, such as those with obesity or diabetes mellitus. Magnetic resonance imaging (MRI) of the pituitary, the corticotropin-releasing hormone (CRH) test and the high-dose dexamethasone suppression test are the main tests for the differential diagnosis of ACTH-dependent Cushing's syndrome. Bilateral and simultaneous petrosal sinus sampling is the gold standard method and is performed when the triad of initial tests is inconclusive, doubtful or conflicting. The aim of this article is to provide information on the early detection and establishment of a proper diagnosis of Cushing's disease, recommending follow-up of these patients at experienced referral centers. Arch Endocrinol Metab. 2016;60(3):267-86

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