Diagnosis of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.

Treatment of hyperprolactinemia in women: A Position Statement from the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and the Brazilian Society of Endocrinology and Metabolism (SBEM).

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.

Special features on insulin resistance, metabolic syndrome and vascular complications in hypopituitary patients.

Pituitary hormone deficiency, hypopituitarism, is a dysfunction resulting from numerous etiologies, which can be complete or partial, and is therefore heterogeneous. This heterogeneity makes it difficult to interpret the results of scientific studies with these patients.Adequate treatment of etiologies and up-to-date hormone replacement have improved morbidity and mortality rates in patients with hypopituitarism. As GH replacement is not performed in a reasonable proportion of patients, especially in some countries, it is essential to understand the known consequences of GH replacement in each subgroup of patients with this heterogeneous dysfunction.In this review on hypopituitarism, we will address some particularities regarding insulin resistance, which is no longer common in these patients with hormone replacement therapy based on current guidelines, metabolic syndrome and its relationship with changes in BMI and body composition, and to vascular complications that need to be prevented taking into account the individual characteristics of each case to reduce mortality rates in these patients.

Intrasellar xanthogranuloma mimicking macroadenoma.

Intracranial xanthogranulomas (XGs) have been found at various sites, but xanthogranuloma of the sellar region is extremely rare. We report about a case of sellar XG in a 34-year-old female. Magnetic resonance imaging showed a solid-cystic mass located at the sella turcica. The cystic component was hyperintense on the T1-weighted image (WI) and T2WI. The solid component was hyperintense on T1WI and hypointense on T2WI. There was peripheral enhancement after gadolinium administration. The diagnosis of cystic macroadenoma was considered before surgery. Final diagnosis of XG was confirmed by histopathological examination after surgical resection. Gross total resection of the lesion was achieved using the microscope through endoscopic endonasal transsphenoidal approach. The patient had a good outcome and no symptom of diabetes insipidus, hormonal evaluation did not show any alterations compatible with hypopituitarism and prolactin levels were normal XG should receive diagnostic consideration for the sellar mass lesions with cystic components hyperintense on T1WI and T2WI, solid components hyperintense on T1WI and hypointense on T2WI, and CT without evidence of calcifications. It is important to consider the possibility of XG when pertinent, as it facilitates a proper surgical approach strategy.

Reconsidering the olfactory and brain structures in Kallmann's syndrome: New findings in the analysis of volumetry.

OBJECTIVE: Kallmann's syndrome (KS) is characterized by hypogonadotropic hypogonadism and olfactory disorders. The complementary exams for evaluating of patients with hypogonadotrophic hypogonadism are important for the diagnosis and management of these patients. PATIENTS: We performed a well-established olfactory Sniffin' Stick test (SST) on 17 adult patients with KS and brain magnetic resonance imaging (MRI) to evaluate olfactory structures and further analysis by Freesurfer, a software for segmentation and volumetric evaluation of brain structures. We compared the Freesurfer results with 34 healthy patients matched for age and sex and performed correlations between the data studied. RESULTS: More than half of the patients with KS reported preserved smell but had olfactory disorders in the SST. In the MRI, 16 patients showed changes in the olfactory groove, the olfactory bulb-tract complex was altered in all of them and 52% had symmetrical structural changes. Interestingly, the pituitary gland was normal in only 29%. Regarding correlations, symmetrical changes in the olfactory structures were related to anosmia in 100%, while asymmetric changes induced anosmia in only 50% (p = .0294). In Freesurfer's assessment, patients with KS, compared to controls, had lower brainstem volume. In those with aplastic anterior olfactory sulcus, the brainstem volume was lower than in hypoplasia (p = .0333). CONCLUSIONS: Olfactory assessment and MRI proved to be important auxiliary tools for the diagnosis and management of patients with KS. New studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS. Further studies are needed to confirm the decrease in brainstem volume found by the Freesurfer software in patients with KS.

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity.

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism.

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.

Genetics, clinical features and outcomes of non-syndromic pituitary gigantism: experience of a single center from Sao Paulo, Brazil.

PURPOSE: Non-syndromic pituitary gigantism (PG) is a very rare disease. Aryl hydrocarbon receptor-interacting protein (AIP) and G protein-coupled receptor 101 (GPR101) genetic abnormalities represent important etiologic causes of PG and may account for up to 40% of these cases. Here, we aimed to characterize the clinical and molecular findings and long-term outcomes in 18 patients (15 males, three females) with PG followed at a single tertiary center in Sao Paulo, Brazil. METHODS: Genetic testing for AIP and GPR101 were performed by DNA sequencing, droplet digital PCR and array comparative genomic hybridization (aCGH). RESULTS: Pathogenic variants in the AIP gene were detected in 25% of patients, including a novel variant in splicing regulatory sequences which was present in a sporadic male case. X-LAG due to GPR101 microduplication was diagnosed in two female patients (12.5%). Of interest, these patients had symptoms onset by age 5 and 9 years old and diagnosis at 5 and 15 years, respectively. X-LAG, but not AIP, patients had a significantly lower age of symptoms onset and diagnosis and a higher height Z-score when compared to non-X-LAG. No other differences in clinical features and/or treatment outcomes were observed among PG based on their genetic background. CONCLUSION: We characterize the clinical and molecular findings and long-term outcome of the largest single-center PG cohort described so far.

Insulin signaling in the whole spectrum of GH deficiency

ABSTRACT GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91

Insulin Sensitivity Is Not Decreased in Adult Patients With Hypopituitarism Without Growth Hormone Replacement.

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, (p = 0.0913) and by the area under the glucose infusion rate curve, (p = 0.0628). These patients showed lower levels of fasting glycemia (p = 0.0128), insulin (p = 0.0007), HOMA-IR (p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass (p = 0.0381) and lower values of percentage of free fat mass (p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fat mass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR.

Insulin signaling in the whole spectrum of GH deficiency.

GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91.

Panhypopituitarism Without GH Replacement: About Insulin Sensitivity, CRP Levels, and Metabolic Syndrome.

A complete deficiency of anterior pituitary hormones from several etiologies characterizes Panhypopituitarism (PH). Despite advances in treatment, patients with PH maintain high rates of morbidity and mortality, a reason to investigate some insulin sensitivity, metabolic and inflammatory parameters that could be related to the increase of these indicators. This was a cross-sectional study comprising 41 PH patients under hormonal replacement, except for growth hormone, and 37 individuals in a control group (CG) with similar age, gender and body mass index (BMI). We assessed clinical data as age, sex, BMI, waist circumference, waist/hip ratio (WHR), history of hypertension, diabetes mellitus and dyslipidemia as well as fasting glycaemia, insulin, HOMA-IR, HbA1c, high-sensitivity CRP (hs-CRP), and lipid profile. PH patients presents lower values of glycaemia, insulin, HOMA-IR (0.88 vs 2.1) and WHR, but higher levels of hs-CRP (0.38 vs 0.16mg/dl) when compared with the CG. Although the occurrence of dyslipidemia was higher in patients with PH, the frequency of metabolic syndrome was similar between the groups. In multivariate linear regression analysis, the PH group independently predicted lower HOMA-IR and WHR values. In conclusion, this study demonstrated that patients with PH without GH replacement have lower HOMA-IR and WHR values and higher levels of hs-CRP than a CG paired by age, gender and BMI. The diagnosis of dyslipidemia was more frequent in patients with PH, but the occurrence of MS was similar to CG. Further studies are needed to confirm our findings and to better understand the metabolic characteristics of patients with PH.

Three new Brazilian cases of 17α-hydroxylase deficiency: clinical, molecular, hormonal, and treatment features.

BACKGROUND: Deficiency of 17α-hydroxylase (17OHD) is a rare form of adrenal hyperplasia. Diagnosis is generally delayed, impairing appropriate treatment. CASE PRESENTATION: Here, we report the clinical, molecular, hormonal, and treatment data of three unrelated 17OHD patients, aged 14-16 years with hypergonadotrophic hypogonadism; uncontrolled hypertension; primary adrenal insufficiency; and high progesterone, low to normal potassium, and low dehydroepiandrosterone, androstenedione, and testosterone levels. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) at baseline and after an adrenocorticotropic hormone test showed low cortisol and cortisone and high deoxycorticosterone (DOC) and corticosterone levels; both DOC/21-deoxycortisol and costicosterone/cortisol ratios were very high. Patient 2 had 46,XX karyotype and patients 1 and 3, had 46,XY. A molecular analysis showed that two of the patients were homozygous for p.W406R mutation and the other patient was compound heterozygous for p.W406R and p.P428L. Hypertension was controlled only after the administration of both prednisone and mineralocorticoid antagonist. CONCLUSIONS: Hypertension in young women must lead to diagnostic suspicion, even in the pre-pubertal period. The basal level of progesterone is an indicator of 17OHD. Mineral and glucocorticoid ratios obtained from LC-MS/MS can reinforce the diagnosis. Hypertension can be controlled using glucocorticoid replacement therapy and mineralocorticoid antagonist.

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

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.

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

ABSTRACT 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.

Pituitary carcinoma: A case report and discussion of potential value of combined use of Ga-68 DOTATATE and F-18 FDG PET/CT scan to better choose therapy.

BACKGROUND: Pituitary carcinoma is extremely rare and carries a very poor prognosis. In most cases, apparently indolent tumors become malignant; however, there are no satisfactory biomarkers for predicting tumor behavior. Thus, scientific advances in the search for new biological markers, diagnostic methods, and therapies are needed to improve the prognosis of these patients. CASE DESCRIPTION: We report the case of a woman with initial diagnosis of nonfunctioning pituitary adenoma which evolved to carcinoma after 4 years. Diagnosis was confirmed after biopsy of metastatic pulmonary nodules, in which neoplastic cells were immunohistochemically positive for chromogranin, synaptotophysin, prolactin, and growth hormone. Investigation with conventional somatostatin receptor scintigraphy, positron emission tomography-computed tomography (PET-CT) with Ga-68 DOTATATE and F-18 fluorodeoxyglucose (FDG) are showed. During temozolomide therapy, our patient had severe pancytopenia resulting in death from generalized infection despite 10 days of intensive care. CONCLUSION: The present case of an aggressive pituitary carcinoma rising from a typical adenoma illustrates the importance of developing new prognostic biomarkers in these cases. In addition to demonstrating a serious side effect with the use of temozolomide, our case report suggests that the combined use of Ga-68 DOTATATE and F-18 FDG PET-CT scan may scale somatostatin receptors vs. tumor aggressiveness, therefore, helping to better choose the therapy for aggressive pituitary tumors.

Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism / Hormônio tireoestimulante e resistência insulínica: sua associação com a síndrome do ovário policístico sem hipotireoidismo clínico

Abstract Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR)≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 - 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.

Resumo Objetivo Este estudo analisou a efetividade do hormônio tireoestimulante (TSH) como preditor da resistência insulínica (IR), bem como a associação do TSH com os parâmetros clínicos e metabólicos de mulheres com síndrome do ovário policístico (PCOS) sem hipotireoidismo clínico. Desenho do Estudo Estudo de corte transversal com inclusão de mulheres com PCOS e sem hipotireoidismo clínico (n =168). Métodos Utilizou-se análise através de curva ROC (Receiver operating characteristic) para determinar o valor de corte para o nível sérico de TSH que poderia maximizar a sensibilidade e especificidade para o diagnóstico de IR considerada com avaliação da homeostase de resistência insulínica (HOMA-IR) ≥ 2.71. Parâmetros clínicos e metabólicos foram comparados de acordo com o ponto de corte de TSH determinado e com a presença de IR. Resultados Níveis séricos de TSH ≥2.77 mIU/L estiveram associados com o diagnóstico de IR, com sensibilidade de 47.9% e especificidade de 65.3%. Não foram evidenciadas diferenças nos parâmetros clínicos, hormonais e metabólicos quando TSH < 2.77 ou TSH de 2.77 - 10 mIU/L. Conclusão Em mulheres com PCOS sem hipotireoidismo, TSH ≥2.77 mIU/L está associado a IR, porém com baixa sensibilidade, mostrando que a dosagem de TSH não é um bom preditor de IR nesta população. Também não se evidenciou alteração clínica ou metabólica que justificasse alteração na investigação desta população. Assim, a resistência insulínica deve ser investigada em todas as mulheres com PCOS, independente dos níveis séricos de TSH.

Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism.

Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 - 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥ 2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.

Objetivo Este estudo analisou a efetividade do hormônio tireoestimulante (TSH) como preditor da resistência insulínica (IR), bem como a associação do TSH com os parâmetros clínicos e metabólicos de mulheres com síndrome do ovário policístico (PCOS) sem hipotireoidismo clínico. Desenho do Estudo Estudo de corte transversal com inclusão de mulheres com PCOS e sem hipotireoidismo clínico (n =168). Métodos Utilizou-se análise através de curva ROC (Receiver operating characteristic) para determinar o valor de corte para o nível sérico de TSH que poderia maximizar a sensibilidade e especificidade para o diagnóstico de IR considerada com avaliação da homeostase de resistência insulínica (HOMA-IR) ≥ 2.71. Parâmetros clínicos e metabólicos foram comparados de acordo com o ponto de corte de TSH determinado e com a presença de IR. Resultados Níveis séricos de TSH ≥ 2.77 mIU/L estiveram associados com o diagnóstico de IR, com sensibilidade de 47.9% e especificidade de 65.3%. Não foram evidenciadas diferenças nos parâmetros clínicos, hormonais e metabólicos quando TSH < 2.77 ou TSH de 2.77 ­ 10 mIU/L. Conclusão Em mulheres com PCOS sem hipotireoidismo, TSH ≥ 2.77 mIU/L está associado a IR, porém com baixa sensibilidade, mostrando que a dosagem de TSH não é um bom preditor de IR nesta população. Também não se evidenciou alteração clínica ou metabólica que justificasse alteração na investigação desta população. Assim, a resistência insulínica deve ser investigada em todas as mulheres com PCOS, independente dos níveis séricos de TSH.

Standard hormone therapy is inadequate for bone density in premature ovarian insufficiency.

To assess standard dose hormone therapy (HT) and bone mass in premature ovarian insufficiency (POI), 239 women with POI, 132 using standard estrogen dose HT and 107 women without HT, were evaluated. All underwent bone mineral density (BMD) evaluation in the lumbar spine (LS) and total femur (TF). Mean age, age at last period and body mass index (BMI) for the untreated and for the HT groups were 38.1 ± 6.1 and 36.8 ± 7.3 years; 31.4 ± 7.3 and 30.7 ± 7.2 years; 26.6 ± 7.1 and 25.8 ± 4.6 kg/m2, respectively, (p=NS). The women taking standard dose HT started treatment at the age of 33.8 ± 6.3 years and had been on hormone treatment for 3 years at the time of the bone densitometry examination. The BMD in LS was 1.06 ± 0.15 and 1.00 ± 0.17 g/cm2 (p = 0.003); the BMD in TF was 0.92 ± 0.19 and 0.91 ± 0.13 g/cm2 (p = 0.039), respectively, for the untreated and HT groups. A 45% altered BMD (osteopenia/osteoporosis) in LS was verified in women without treatment and 60.1% in those using the standard dose TH (p = 0.01). The BMD in TF was altered in 32.3% in those without HT and 36.4% in the HT users (p = 0.34). In conclusion, standard dose HT was not adequate to reduce impaired bone mass in the spine and femur of women with POI.