Evidence of brain metabolism redistribution from neocortex to primitive brain structures in early acute COVID-19 respiratory syndrome.

BACKGROUND: Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms. RESULTS: Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4-20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (< 2 SD) was observed in up to a third of patients. Associations were found between hypoxia, inflammation, coagulation markers, and [18F]FDG uptake in various brain structures. CONCLUSIONS: Brain metabolism is clearly affected during the acute phase of COVID-19 respiratory syndrome in neurologically asymptomatic or oligosymptomatic patients. The most frequent finding is marked hypermetabolism in evolutionary ancient structures such as lenticular nucleus and thalami. Neocortical metabolism was reduced in up to one third of patients, suggesting a redistribution of brain metabolism from the neocortex to evolutionary ancient brain structures in these patients.

Changes in calcium metabolism and bone mineral density in new users of medroxyprogesterone acetate during the first year of use.

OBJECTIVE: To evaluate calcium metabolism and bone mineral density (BMD) in new users of depot medroxyprogesterone acetate (DMPA) in the first year of use. METHODS: This prospective, non-randomized study, conducted at the University of Campinas, São Paulo, Brazil, was carried out between February 2011 and February 2013. Women aged from 18 to 40 with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) <30 and with no known history of disease or medication use who chose to use DMPA were paired by age (±1 year) and BMI (±1) with women commencing the use of a copper intrauterine device (IUD). The primary outcomes were BMD measured by dual-energy X-ray absorptiometry and calcium metabolism markers; other variables were body composition and lifestyle habits. Repeated measures analysis of variance (ANOVA) and multiple regression analyses were used to evaluate associations. RESULTS: Twenty-seven women using DMPA and 24 using IUD were evaluated, with a mean age of 29.7 years and 28.6 years, respectively. The DMPA group presented with a 3.6% (P<0.001) loss of lumbar spine BMD, a 2.1% (P=0.100) loss of femoral neck BMD and higher phosphorus (P=0.014) concentrations at 12 months compared to the IUD group. The decreases in BMD were associated with the use of DMPA, while total mass and coffee intake were found to be protective factors. CONCLUSION: Changes in calcium metabolism and a decrease in BMD were found in the DMPA group at 12 months.

Effect of thyroid-stimulating hormone in 68Ga-DOTATATE PET/CT of radioiodine-refractory thyroid carcinoma: a pilot study.

BACKGROUND: Radioiodine-refractory thyroid carcinomas (RAIRs) are characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin levels, and negative whole-body radioiodine scans. Interestingly, RAIRs continue to express somatostatin receptors and can be identified with Ga-DOTATATE PET/CT imaging. OBJECTIVE: The objective of this study was to compare lesion detectability in Ga-DOTATATE PET/CT performed with elevated thyroid-stimulating hormone (eTSH) levels with suppressed thyroid-stimulating hormone (sTSH) levels. PATIENTS AND METHODS: Fifteen patients with RAIR were prospectively enrolled in this pilot study. All patients underwent two Ga-DOTATATE PET/CT studies: with sTSH and with eTSH (after 30 days of levothyroxine withdrawal). All studies were blindly evaluated for differences pertaining to maximum standardized uptake values, detection of local recurrence, cervical lymph node (LN) metastases, cervical levels involved, distant LN metastases, lung metastases, and bone metastases. Reference standard consisted of fluorine-18-fluorodeoxyglucose PET/CT imaging, neck ultrasound, biopsy, and follow-up. RESULTS: Ga-DOTATATE PET/CT performed with both sTSH or eTSH was highly sensitive (91-100%) for detecting RAIR metastases. Ga-DOTATATE PET/CT with eTSH detected a higher total number of lesions (P=0.002), higher rate of cervical and distant LN metastases (P=0.002 and 0.0313, respectively), and significantly higher maximum standardized uptake values for cervical and distant LN metastases (P=0.0010 and 0.0078, respectively) when compared with sTSH. CONCLUSION: Ga-DOTATATE PET/CT presents a high sensitivity in detecting metastatic lesions in patients with RAIR. Detectability increases with iodine-resistance, both with and without higher thyroid-stimulating hormone levels. These findings might improve staging and subsequent treatment planning, especially with radiolabeled somatostatin analogs.

The Role of SPECT/CT Lymphoscintigraphy and Radioguided Sentinel Lymph Node Biopsy in Managing Papillary Thyroid Cancer.

IMPORTANCE: Single-photon emission computed tomography/computed tomography (SPECT/CT) and radioguided sentinel lymph node biopsy (rSLNB) are techniques that could potentially benefit surgeons and pathologists in the identification of sentinel lymph node (SLN) metastases in patients with papillary thyroid carcinoma (PTC). Evidence suggests that these novel techniques lead to substantial changes in PTC management by reducing understaging and of occult lymph node (LN) metastases and optimizing neck surgery by increasing the necessity of lateral lymphadenectomy and decreasing central lymphadenectomy. OBJECTIVES: To correlate the presence of LN metastases in PTC with clinical and pathological features using SPECT/CT and rSLNB. DESIGN, SETTING, AND PARTICIPANTS: For this prospective cohort study from June 2010 to November 2013, 42 patients with thyroid nodules suspicious for papillary carcinoma or classified as malignant on cytology examination without suspicion of lymph node metastases by clinical and ultrasound examinations were recruited from a single public medical institution. INTERVENTIONS: All 42 patients underwent preoperative lymphoscintigraphy after an ultrasound-guided peritumoral injection of Technetium Tc 99m nanocolloid. Cervical images were acquired with a SPECT/CT scanner 15 minutes after radiotracer injection. Approximately 2 hours after lymphoscintigraphy, the patients were submitted to intraoperative rSLNB using a handheld gamma probe. All SLNs identified were removed alongside with non-SLNs from the same compartment. Papillary thyroid carcinoma, SLNs and non-SLNs were submitted for histopathology and immunohistochemical analyses. RESULTS: Of the 42 patients initially enrolled, 37 were included in analysis, including 6 men and 31 women with a mean (range) age of 47 (22-83) years. Overall, T stage was as follows: T1, 23 patients (62.2%); T2, 8 patients (21.6%); and T3, 6 patients (16.2%). Sentinel lymph nodes were identified in 92% of the patients, and among these metastases were present in 17 patients (46%). The SLNs were false-negative in 3 patients. Metastases in the lateral compartment ocurred in 7 patients (18%). There was a significant association between LN metastases and tumor size (odds ratio, 1.06; 95% CI, 1.00-1.13; P = .02), with a Cohen d effect of 0.683 (medium to large effect). Overall, 17 patients (46%) with LN metastases had management changed because they were submitted to higher radioiodine ablation doses and closer clinical surveillance. CONCLUSIONS AND RELEVANCE: Radioguided SLNB is able to detect occult cervical lymph node metastases in patients with papillary thyroid carcinoma, and in 7 patients (18%) rSLNB detected lymph node metastases in the lateral compartments. The rSLNB technique lead to management change in 14 patients (37.8%).

Thyroid imaging reporting and data system score combined with Bethesda system for malignancy risk stratification in thyroid nodules with indeterminate results on cytology.

CONTEXT: The thyroid imaging reporting and data system (TI-RADS) was designed to better select patients who had undergone fine-needle aspiration biopsies (FNABs) with high sensitivity and accuracy. However, the combination of TI-RADS scores and Bethesda system categories in indeterminate thyroid nodules has not been examined extensively. OBJECTIVE: This study aimed to stratify indeterminate thyroid nodules (Bethesda categories III, IV and V) according to risk of malignancy as determined by combining TI-RADS score with Bethesda system classification. DESIGN: Retrospective study. Histopathological, cytological and ultrasound (US) data were available for 242 cases after surgery, including 136 indeterminate nodules. METHODS: All thyroid cytopathological slides and US reports were reviewed and classified according to Bethesda system and TI-RADS categories. The malignancy rate was determined for each Bethesda category, TI-RADS score and both methods combined of indeterminate nodules. RESULTS: The malignancy rates were 8·7%, 51·3% and 67·5% for Bethesda categories III, IV and V, respectively. Based on histopathological comparison, the accuracy was 66·7% for TI-RADS greyscale. TI-RADS 3 and 4A scores were observed in 80% of Bethesda III cases, which led to 80% sensitivity and 90% of negative predictive value (NPV). In contrast, for nodules scored as TI-RADS 4B and 5, the combined cytological results of Bethesda IV and V resulted in a higher risk of malignancy (75% and 76·9%, respectively, P < 0·001). CONCLUSIONS: In view of the high NPV of TI-RADS 3/4A only in Bethesda III category, a surgical approach could be considered for lesions defined as Bethesda III, IV and V when TI-RADS 4B and 5 were concomitant.

High Prevalence of Infertility among Women with Graves' Disease and Hashimoto's Thyroiditis.

Objectives. To evaluate the prevalence of infertility in women with Graves' disease (GD) or Hashimoto's thyroiditis (HT) and associated factors. Material and Methods. This cross-sectional study was conducted at the Endocrinology Clinic for Thyroid Autoimmune Diseases, with 193 women aged 18-50 years with GD and 66 women aged 18-60 years with HT. The women were interviewed to obtain data on their gynecological and obstetric history and family history of autoimmune diseases. Their medical records were reviewed to determine the characteristics of the disease and to confirm association with other autoimmune diseases. Infertility was defined as 12 months of unprotected sexual intercourse without conception. Results. The prevalence of infertility was 52.3% in GD and 47.0% in HT. Mean age at diagnosis was 36.5 years and 39.2 years, in GD and HT, respectively. The mean number of pregnancies was lower in women who were 35 years old or younger at diagnosis and was always lower following diagnosis of the disease, irrespective of age. The only variable associated with infertility was a shorter time of the disease in HT. Conclusions. The prevalence of infertility was high in women with GD and HT and affected the number of pregnancies in young women.

Value of ultrasound and cytological classification system to predict the malignancy of thyroid nodules with indeterminate cytology.

Although fine-needle aspiration cytology is considered the gold standard for evaluating thyroid nodules, in about 10-30% of the cases, cytology is indeterminate. This study aimed to determine the value of cytological classification system and ultrasound (US) to predict malignancy in indeterminate thyroid nodule. This retrospective analysis enrolled 80 patients surgically treated at a single center, 75% (60) with benign vs. 25% (20) with malignant lesions at final histology. The clinical, scintigraphic, sonographic, and cytological classification (Bethesda) variables were analyzed in these selected cases of indeterminate cytology, and a prediction model was designed after the multivariate analysis. There was a 25% prevalence of malignancy (20/80). There were no differences in gender, serum thyroid-stimulating hormone and FT4 levels, thyroid auto-antibodies, thyroid dysfunction, and scintigraphic results between benign and malignant nodule groups. The border irregularity in sonographic study was at increased risk for malignancy. The cytological analysis based on Bethesda System (category IV) was an independent predictor for malignancy in indeterminate thyroid nodules. After the multivariate analysis, the model obtained showed border irregularity and Bethesda System category IV as predictive factors of malignancy in indeterminate thyroid nodules, featuring 76.9% of accuracy. This study confirmed a significant increase of risk for malignancy in thyroid nodules with indeterminate cytology showing Bethesda System category IV and suspicious features at US. These findings enhance our current limited predictive armamentarium and can be used to guide surgical decision making.

Value of repeat ultrasound-guided fine-needle aspiration in thyroid nodule with a first benign cytologic result: impact of ultrasound to predict malignancy.

This study aimed to investigate the value of repeat ultrasound-guided fine-needle aspiration (FNAC-US) in benign thyroid nodules and determine the ultrasound (US) predictors of malignancy in this group of nodules. The authors studied 35 of 143 nodules with initially benign cytological result who underwent serial re-biopsy (FNAC-US). By means of surgery, malignancy histology results were confirmed in 10 (28.5%) cases (G1) versus 25 (71.5%) benign nodules (G2). The clinical, lab, scintigraphyc, and US features were compared between the two groups to predict malignancy in thyroid nodules with initially benign cytological result. The cytological finding of 28/35 nodules were change to indeterminate cytology (Bethesda system category III or IV) at second and/or ≥third cytological study. In this group of 28 cases, 23 (82.1%) was identified until the third procedure. The interval between first and third re-biopsy was 13 months (median). There were no differences in age, gender, thyrotropin (TSH) levels, thyroid auto-antibodies, or thyroid dysfunctions. The scintigraphy showed cold nodule in 80% of G1 versus 78.9% of G2 (NS). Sonographic studies showed malignant suspected US features in G1: microcalcifications, central flow, hypoechogenicity, and border irregularity. This study suggests repeating FNAC-US in nodules with first benign cytologic result and suspicious US features of malignancy for at least two times (until the third FNAC) in about 13 months horizon.

Role of ultrasound, clinical and scintigraphyc parameters to predict malignancy in thyroid nodule.

BACKGROUND: This study aimed to evaluate clinical, laboratory, ultrasound (US) and scintigraphyc parameters in thyroid nodule and to develop an auxiliary model for clinical application in the diagnosis of malignancy. METHODS: We assessed 143 patients who were surgically treated at a single center, 65% (93) benign vs. 35% (50) malignant lesions at final histology (1998-2008). The clinical, laboratory, scintigraphyc and US features were compared and a prediction model was designed after the multivariate analysis. RESULTS: There were no differences in gender, serum TSH and FT4 levels, thyroid auto-antibodies (TAb), thyroid dysfunction and scintigraphyc results (P=0.33) between benign and malignant nodule groups. The sonographic study showed differences when the presence of suspected characteristics was found in the nodules of the malignant lesions group, such as: microcalcifications, central flow, border irregularity and hypoechogenicity. After the multivariate analysis the model obtained showed age (>39 years), border irregularity, microcalcifications and nodule size over 2 cm as predictive factors of malignancy, featuring 81.7% of accuracy. CONCLUSIONS: This study confirmed a significant increase of risk for malignancy in patients of over 39 years and with suspicious features at US.

Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C.

OBJECTIVE: The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. PATIENTS AND METHODS: We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. RESULTS: At baseline, TD prevalence was 6.82% (n = 20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95% CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. CONCLUSION: Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34% of TD was transient.

Comparison of three systems of classification in predicting the outcome of diabetic foot ulcers in a Brazilian population.

OBJECTIVE: The aim was to compare three ulcer classification systems as predictors of the outcome of diabetic foot ulcers: the Wagner, the University of Texas (UT) and the size (area, depth), sepsis, arteriopathy, denervation system (S(AD)SAD) systems in a specialist clinic in Brazil. METHODS: Ulcer area, depth, appearance, infection and associated ischaemia and neuropathy were recorded in a consecutive series of 94 subjects. A novel score, the S(AD)SAD score, was derived from the sum of individual items of the S(AD)SAD system, and was evaluated. Follow-up was for at least 6 months. The primary outcome measure was the incidence of healing. RESULTS: Mean age was 57.6 years; 57 (60.6%) were male. Forty-eight ulcers (51.1%) healed without surgery; 11 (12.2%) subjects underwent minor amputation. Significant differences in terms of healing were observed for depth (P=0.002), infection (P=0.006) and denervation (P=0.002) using the S(AD)SAD system, for UT grade (P=0.002) and stage (P=0.032) and for Wagner grades (P=0.002). Ulcers with an S(AD)SAD score of or=10 (P<0.001). CONCLUSIONS: All three systems predicted ulcer outcome. The S(AD)SAD score of ulcer severity could represent a useful addition to routine clinical practice. The association between outcome and ulcer depth confirms earlier reports. The association with infection was stronger than that reported from the centres in Europe or North America. The very strong association with neuropathy has only previously been observed in Tanzania. Studies designed to compare the outcome in different countries should adopt systems of classification, which are valid for the populations studied.

Severe rhabdomyolysis due to adipsic hypernatremia after craniopharyngioma surgery.

UNLABELLED: The association of diabetes insipidus and adipsia after craniopharyngioma surgery has high morbidity. Hypernatremia can be caused by adipsia and be aggravated by diabetes insipidus. Rhabdomyolysis rarely occurs. CASE REPORT: This is the first report of a diabetic patient with craniopharyngioma who developed diabetes insipidus and adipsia after surgery, evolving with severe hypernatremia that caused considerable rhabdomyolysis. CONCLUSION: The importance of the evaluation of muscle integrity when under hypernatremic states is pointed out. Although adipsia may have a simple solution through volunteer water ingestion, serious consequences such as repeated severe hypernatremia episodes and intense rhabdomyolysis with high morbidity could occur, if adipsia is not diagnosed.

Severe rhabdomyolysis due to adipsic hypernatremia after craniopharyngioma surgery

The association of diabetes insipidus and adipsia after craniopharyngioma surgery has high morbidity. Hypernatremia can be caused by adipsia and be aggravated by diabetes insipidus. Rhabdomyolysis rarely occurs. DASE REPORT: This is the first report of a diabetic patient with craniopharyngioma who developed diabetes insipidus and adipsia after surgery, evolving with severe hypernatremia that caused considerable rhabdomyolysis. CONCLUSION: The importance of the evaluation of muscle integrity when under hypernatremic states is pointed out. Although adipsia may have a simple solution through volunteer water ingestion, serious consequences such as repeated severe hypernatremia episodes and intense rhabdomyolysis with high morbidity could occur, if adipsia is not diagnosed.

A associação de diabetes insipidus e adipsia após cirurgia de craniofaringioma implica em alta morbidade. Hipernatremia pode desenvolver-se devido a adipsia e ser agravada por diabetes insipidus. Rabdomiólise raramente ocorre. DESCRIÇÃO DO CASO: Esta é a primeira descrição de paciente diabético com craniofaringioma que desenvolveu diabetes insipidus e adipsia após a cirurgia, evoluindo com hipernatremia grave e conseqüente rabdomiólise maciça. CONCLUSÃO: Ressalta-se a necessidade de avaliar a integridade muscular na vigência de estados hipernatrêmicos. Apesar de apresentar solução simples, como ingestão voluntária de água, pode haver sérias conseqüências se o diagnóstico de adipsia não é realizado, como episódios repetidos de hipernatremia grave com rabdomiólise intensa e elevada morbidade.

Pancytopenia in untreated patients with Graves' disease.

Severe pancytopenia is a rare but severe complication of thyrotoxicosis. In this report, we describe four patients with Graves' disease who presented with pancytopenia at diagnosis. Methimazole (30-40 mg/d) or propylthiouracil (400 mg/d) restored normal hematopoiesis in three of the patients. The remaining patient evolved to aplastic anemia under therapy with methimazole (60 mg/d), but had an increased peripheral blood count that almost reached normal values after radioiodinetherapy and standard immunosuppressive treatment with antithymocyte globulin (700 mg/d, intravenous infusion for 5 days), oral cyclosporin (400 mg/d), prednisone (30-60 mg/d), and granulocyte colony-stimulating factor (150 microg subcutaneous injection, 3 times per week). We conclude that: (1) a hematologic evaluation of all patients with Graves' disease should be performed before administering antithyroid drugs, (2) antithyroid drugs may be administered to patients with pancytopenia and bone marrow hypercellularity but a reevaluation of the bone marrow must be done if there is no recovery of the peripheral blood cell count when euthyroidism state is achieved, (3) standard immunosuppressive treatment of aplastic anemia caused by antithyroid drugs restores normal hematopoiesis, and (4) a thyroid evaluation of patients with pancytopenia should be done, even though no related symptoms are found.

High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs: predictive factors of failure in [131I]iodide therapy in Graves' disease.

BACKGROUND AND OBJECTIVE: Several factors may interfere with the success rate of radioiodine therapy (RIT) in Graves' disease. Our aim was to evaluate, retrospectively, some of these factors in the outcome of RIT. METHODS: Patient gender, age at diagnosis, ophthalmopathy, disease duration, thyroid size, drug used as clinical treatment, thionamide withdrawal period during RIT preparation, FT4, TSH and [99mTc]pertechnetate thyroid uptake prior to RIT were studied as potential interference factors for RIT success. Eighty-two Graves' disease patients were submitted to RIT after thionamide treatment failure. Prior to RIT, 67 patients were receiving methimazole and 15 propylthiouracil. Thirty-three patients received thionamides during RIT; in 49 patients the medication was withdrawn for 2-30 days. [99mTc]pertechnetate thyroid uptake was determined before RIT. Fixed doses of 370 MBq of [131I]iodide were administered to all patients. RESULTS: Eleven patients became euthyroid; 40 became hypothyroid and 31 remained hyperthyroid. There was no association between outcome and age at diagnosis, gender, ophthalmopathy, pre-RIT FT4, TSH, antithyroid antibodies or thyrostatic drug. Multiple logistic regression showed higher probability of treatment success in patients with thyroid mass <53 g (odds ratio (OR)=8.9), with pre-RIT thyroid uptake <12.5% (OR=4.1) and in patients who withdrew thionamide before RIT (OR=4.9). CONCLUSIONS: Fixed doses of 370 MBq of radioiodine seem to be practical and effective for treating Graves' disease patients with [99mTc]pertechnetate uptake <12.5% and thyroid mass <53 g. This treatment is clearly not recommended for patients with large goitre. In contrast to what could be expected, patients with a high pre-RIT thyroid uptake presented a higher rate of RIT failure.

Endocrine-metabolic effects of the treatment with pioglitazone in obese patients with polycystic ovary syndrome.

The hyperandrogenism found in polycystic ovary syndrome (PCOS) can be a consequence of hyperinsulinemia as a result of peripheral insulin resistance. Metformin and insulin sensitizers have become a potential therapeutic tool for treating these patients; however, there are few studies with pioglitazone in PCOS. Elevated luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratios and LH hyper-responsivity to stimulation with gonadotropin-releasing hormone (GnRH) are common findings in PCOS. The reason why hyperinsulinemia produces hyperandrogenism and whether insulin action on the pituitary alters gonadotropin liberation remain unknown. In the present study, we evaluated the effect of pioglitazone (30 mg/day for 2 months) on insulin response to an oral glucose tolerance test (OGTT), serum levels of androgens and sex hormone-binding globulin (SHBG), and pituitary gonadotropin response to GnRH stimulation in 15 obese PCOS women. We found a significant decrease in insulin response to the OGTT and also in total and free testosterone levels, an increase in SHBG and a reduction in the LH response to GnRH stimulation after pioglitazone treatment. In conclusion, this short-term treatment with pioglitazone decreased hyperinsulinemia and hyperandrogenemia in obese PCOS patients, and there was a significant reduction in LH response to GnRH stimulation. Further research should be carried out to establish the risks and benefits of pioglitazone, which would assist in the physiopathologic comprehension of PCOS.