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.

BackgroundWomen with previous gestational diabetes mellitus (pGDM) face a higher risk of developing type 2 diabetes and, consequently, a higher cardiovascular risk. This study aimed to compare the carotid intima-media thickness (cIMT) from young women with pGDM to those with metabolic syndrome (MS) and to healthy controls (CG) to verify whether a past history of pGDM could be independently associated with increased cIMT.MethodsThis is a cross-sectional study performed in two academic referral centers. Seventy-nine women with pGDM, 30 women with MS, and 60 CG aged between 18 and 47 years were enrolled. They all underwent physical examination and had blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDLc), and triglycerides determined. The cIMT was measured by ultrasound in several carotid segments. The primary endpoint was cIMT and clinically relevant parameters included as predictors were: age, systolic blood pressure, waist, BMI, total cholesterol, LDLc, triglycerides, fasting glucose, previous history of GDM as a whole group, previous history of GDM without MS, presence of DM, presence of MS, and parity.ResultscIMT was significantly higher in pGDM when compared to CG in all sites of measurements (P < 0.05) except for the right common carotid. The pGDM women showed similar cIMT measurements to MS in all sites of measurements, except for the left carotid bifurcation, where it was significantly higher than MS (P < 0.001). In a multivariate analysis which included classical cardiovascular risk factors and was adjusted for confounders, pGDM was shown to be independently associated with increased composite cIMT (P < 0.01). The pGDM without risk factors further showed similar cIMT to MS (P > 0.05) and an increased cIMT when compared to controls (P < 0.05).ConclusionsPrevious GDM was independently associated with increased composite cIMT in this young population, similarly to those with MS and regardless the presence of established cardiovascular risk factors.

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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OBJECTIVE:Aneurysmal subarachnoid hemorrhage puts patients at high risk for the development of pituitary insufficiency. We evaluated the incidence of pituitary dysfunction in these patients and its correlation with clinical outcome.METHODS:Pituitary function was tested in 66 consecutive patients in the first 15 days after aneurysmal subarachnoid hemorrhage. The following were measured in all patients: thyroid-stimulating hormone, free thyroxine, triiodothyronine, luteinizing hormone, follicle-stimulating hormone, total testosterone (in males), estradiol (in females), prolactin, serum cortisol, plasma adrenocorticotropic hormone, growth hormone and insulin growth factor.RESULTS:The endocrine assessment was made at a mean of 7.4 days (standard deviation ±6.6) after subarachnoid hemorrhage. Forty-four (66.7%) female and 22 (33.3%) male patients were evaluated. Thirty-nine patients (59.1%) had some type of pituitary dysfunction. Follicle-stimulating hormone/luteinizing hormone deficiency was the most frequent disorder (34.8%), followed by growth hormone/insulin growth factor (28.7%), adrenocorticotropic hormone (18.1%) and thyroid-stimulating hormone (9%). Seventeen (25.7%) patients showed deficiencies in more than one axis. A greater incidence of hormone deficiency was observed in patients with a Glasgow Coma Scale score ≤13 (t test, p = 0.008), Hunt-Hess grade ≥4 (t test, p<0.001), or Fisher grade 4 (t test, p = 0.039). Hormone deficiency was not significantly associated (p>0.05) with increased hospitalization or clinical outcome.CONCLUSION:Pituitary dysfunction was identified in a substantial portion of patients with previous aneurysmal subarachnoid hemorrhage, but no association was found between this dysfunction and poor clinical outcome.

The endocrine profiles associated with long and short lactational amenorrhea were assessed in a longitudinal study in which morning blood samples were drawn in 48 women from the first postpartum month until the recovery of ovulation and in a cross-sectional study in which the samples were drawn throughout 24 h at the end of the third postpartum month in 10 fully nursing and amenorrheic women. PRL, LH, FSH, estradiol (E2), progesterone, cortisol, and dehydroepiandrosterone sulfate were measured. In both studies we detected a smaller PRL increase in response to suckling (P less than 0.001) and higher E2 levels (P less than 0.001) in nursing women who ovulated within 6 months postpartum compared to those in women who did not. Such differences were observed early after delivery when all women were fully nursing and amenorrheic. These results suggest some probable sources of variability in the duration of lactational amenorrhea in our population. The greater PRL response to suckling associated with longer amenorrhea may be due to higher sensitivity of the breast-hypothalamus-pituitary system or a stronger suckling stimulus in this group. Differences in plasma E2 levels between longer and shorter periods of amenorrhea may reflect dissimilar endogenous production, intake, or clearance of estrogens.

Objective: To study glucose profiles of gestational diabetes (GDM) patients with 72 h of continuous glucose monitoring (CGM) either before (GDM1) or after (GDM2) dietary counseling, comparing them with nondiabetic (NDM) controls. Design and methods: We performed CGM on 22 GDM patients; 11 before and 11 after dietary counseling and compared them to 11 healthy controls. Several physiological and clinical characteristics of the glucose profiles were compared across the groups, including comparisons for pooled 24-h measures and hourly median values, summary measures representing glucose exposure (area under the median curves) and variability (amplitude, standard deviation, interquartile range), and time points related to meals. Results: Most women (81.8%) in the GDM groups had fasting glucose <95 mg/dL, suggesting mild GDM. Variability, glucose levels 1 and 2 h after breakfast and dinner, peak values after dinner and glucose levels between breakfast and lunch, were all significantly higher in GDM1 than NDM (P < 0.05 for all comparisons). The GDM2 results were similar to NDM in all aforementioned comparisons (P > 0.05). Both GDM groups spent more time with glucose levels above 140 mg/dL when compared with the NDM group. No differences among the groups were found for: pooled measurements and hourly comparisons, exposure, nocturnal, fasting, between lunch and dinner and before meals, as well as after lunch (P > 0.05 for all). Conclusion: The main differences between the mild GDM1 group and healthy controls were related to glucose variability and excursions above 140 mg/dL, while glucose exposure was similar. Glucose levels after breakfast and dinner also discerned the GDM1 group. Dietary counseling was able to keep glucose levels to those of healthy patients.

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.