Plasma signatures of Congenital Generalized Lipodystrophy patients identified by untargeted lipidomic profiling are not changed after a fat-containing breakfast meal.

BACKGROUND: The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. CGL patients experience shortened life expectancy. The plasma lipidomic profile has not been characterized fully in CGL, nor has the extent of dietary intake in its modulation. The present work investigated the plasma lipidomic profile of CGL patients in comparison to eutrophic individuals at the fasted state and after a breakfast meal. METHOD: Blood samples from 11 CGL patients and 10 eutrophic controls were collected after 12 h fasting (T0) and 90 min after an ad libitum fat-containing breakfast (T90). The lipidomic profile of extracted plasma lipids was characterized by non-target liquid chromatography mass spectrometry. RESULTS: Important differences between groups were observed at T0 and at T90. Several molecular species of fatty acyls, glycerolipids, sphingolipids and glycerophospholipids were altered in CGL. All the detected fatty acyl molecular species, several diacylglycerols and one triacylglycerol species were upregulated in CGL. Among sphingolipids, one sphingomyelin and one glycosphingolipid species showed downregulation in CGL. Alterations in the glycerophospholipids glycerophosphoethanolamines, glycerophosphoserines and cardiolipins were more complex. Interestingly, when comparing T90 versus T0, the lipidomic profile in CGL did not change as intensely as it did for control participants. CONCLUSIONS: The present study found profound alterations in the plasma lipidomic profile of complex lipids in CGL patients as compared to control subjects. A fat-containing breakfast meal did not appear to significantly influence the CGL profile observed in the fasted state. Our study may have implications for clinical practice, also aiding to a deeper comprehension of the role of complex lipids in CGL in view of novel therapeutic strategies.

Cardiovascular Risk, Obesity, and Sociodemographic Indicators in a Brazilian Population.

Background and Aims: Cardiovascular diseases (CVDs) are the leading cause of death globally and in Brazil. Evidence suggests that the risk of CVDs differs by race/ethnicity. Scarce information exists about the association between CVD risk, obesity indicators and sociodemographic characteristics in the Brazilian population. Objectives: We aimed to assess the CVD risk following the Framingham risk score in relation to the population's sociodemographic profile. Further, we examined the association between anthropometric markers and risk of CVDs. Methods: A total of 701 subjects aged ≥20 years from North-eastern Brazil were recruited randomly to participate in a population-based, cross-sectional survey. Age-adjusted data for CVD risk, sociodemographic characteristics, and anthropometric indices were assessed, and their relationships examined. Results: High CVD risk (Framingham risk score ≥10%) was observed in 18.9% of the population. Males (31.9 vs. 12.5%) and older subjects (age ≥45 years: 68.9% vs. age <45 years: 4.2%) had significantly higher risk of CVDs, whereas those employed in manual labor showed lower risk (7.6 vs. 21.7%). Central obesity measures like waist-to-hip ratio and waist-to-height ratio were more strongly associated with predicted CVD risk than body mass index. Conclusions: Our population had a high risk of CVDs using the Framingham risk score. Cost-effective strategies for screening, prevention and treatment of CVDs may likely reduce disease burden and health expenditure in Brazil. Central obesity measures were strongly associated with predicted CVD risk and might be useful in the clinical assessment of patients. Follow-up studies are warranted to validate our findings.

Race/ethnicity and challenges for optimal insulin therapy.

AIMS: We aimed to review insulin dosing recommendations, insulin regulation and its determinants, glycaemic response to carbohydrates, and the efficacy and safety of insulin therapy in different races/ethnicities. METHODS: We searched for articles in PubMed and Google Scholar databases up to 31 March 2021, with the following keywords: "ethnicity", "diabetes", "insulin", "history of insulin", "insulin therapy", "food/rice", "carbohydrate intake", "insulin resistance", "BMI", "insulin dosing", "insulin sensitivity", "insulin response", "glycaemic index", "glycaemic response", "efficacy and safety", with interposition of the Boolean operator "AND".In addition, we reviewed the reference lists of the articles found. RESULTS: The differential effect of race/ethnicity has not yet been considered in current insulin therapy guidelines. Nevertheless, body size and composition, body mass index, fat distribution, diet, storage, and energy expenditure vary significantly across populations. Further, insulin sensitivity, insulin response, and glycaemicresponse to carbohydrates differ by ethnicity. These disparities may lead to different insulin requirements, adversely impacting the efficacy and safety of insulin therapy among ethnic groups. CONCLUSIONS: Race/ethnicity affects glucose metabolism and insulin regulation.Until now, international guidelines addressing racial/ethnic-specific clinical recommendations are limited. Comprehensive updated insulin therapy guidelines by ethnicity are urgently needed.

Altered acylated ghrelin response to food intake in congenital generalized lipodystrophy.

BACKGROUND: Patients with congenital generalized lipodystrophy (CGL) have very low levels of leptin and are described as having a voracious appetite. However, a direct comparison between CGL and eutrophic individuals is lacking, regarding both appetite parameters and acylated ghrelin, the hormone form that is active in acute food intake stimulation. The objective of the present study was to address whether and in what extent the subjective appetite parameters and acylated ghrelin response to a meal are affected in CGL individuals, in comparison to eutrophic individuals. Additionally, an obese group was included in the study, to allow the comparison between a leptin-resistant and a leptin-deficient condition on these aspects. METHODS: Eutrophic controls (EUT, n = 10), obese subjects (OB, n = 10) and CGL (n = 11) were fasted overnight and then received an ad libitum meal. Blood was collected and the visual analogue scale was applied before and 90 minutes after the meal. An additional blood sample was collected at 60 minutes for ghrelin determination. RESULTS: The CGL patients showed low fasting levels of leptin and adiponectin, dyslipidemia, and insulin resistance. The caloric intake was similar among the 3 groups. However, both CGL (p = 0.02) and OB (p = 0.04) had shorter satiation times than EUT. The CGL patients also had lower satiety time (p = 0.01) and their sensation of hunger was less attenuated by the meal (p = 0.03). Fasting acylated ghrelin levels were lower in CGL than in EUT (p = 0.003). After the meal, the levels tended to decrease in EUT but not in CGL and OB individuals. CONCLUSION: The data indicate that, although not hyperphagic, the CGL patients present appetite disturbances in relation to eutrophic individuals. Their low fasting levels of acylated ghrelin and the absence of the physiological drop after meal intake suggest a role of these disturbances in hunger attenuation and satiety but not in acute satiation.

Glycated Hemoglobin in the Diagnosis of Diabetes Mellitus in a Semi-Urban Brazilian Population.

The study evaluated glycated hemoglobin (HbA1c) as a diagnostic tool for diabetes and pre-diabetes in the Brazilian population. Further, the homeostasis model assessment of insulin resistance (HOMA-IR) was also examined against HbA1c values to identify the most suitable cut-off points for HOMA-IR to predict the risk of diabetes. A cross-sectional study was conducted among 714 randomly selected subjects. HbA1c, fasting, and 2 h plasma glucose values were measured. Insulin resistance estimates were calculated with HOMA-IR. The receiver operating characteristic curve assessed HbA1c performance. The adjusted prevalence rate of diabetes mellitus was 14.7%, and pre-diabetes 14.2%. The optimal HbA1c cut-off value was ≥6.8% for the diagnosis of diabetes, and ≥6.0% for pre-diabetes. The area under the curve using HbA1c was 0.85 (95% CI: 0.80-0.90) for detecting diabetes and 0.61 (95% CI: 0.55-0.67) for pre-diabetes. The optimal HOMA-IR cut-off value was 2.06 for HbA1c at 6.8%. The HbA1c cut-off value of ≥6.8% may be suitable for diagnosing diabetes in the Brazilian population. Our results do not support the use of HbA1c to diagnose pre-diabetes. A HOMA-IR cut-off point of 2.06 was a sensitive marker to assess the risk of diabetes.

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.

Microvascular Complications in Type 1 Diabetes: A Comparative Analysis of Patients Treated with Autologous Nonmyeloablative Hematopoietic Stem-Cell Transplantation and Conventional Medical Therapy.

OBJECTIVE: To explore the impact on microvascular complications, long-term preservation of residual B-cell function and glycemic control of patients with type 1 diabetes treated with autologous nonmyeloablative hematopoietic stem-cell transplantation (AHST) compared with conventional medical therapy (CT). RESEARCH DESIGN AND METHODS: Cross-sectional data of patients treated with AHST were compared with patients who received conventional therapy from the Brazilian Type 1 Diabetes Study Group, the largest multicenter observational study in type 1 diabetes mellitus in Brazil. Both groups of patients had diabetes for 8 years on average. An assessment comparison was made on the presence of microvascular complications, residual function of B cell, A1c, and insulin dose of the patients. RESULTS: After a median of 8 years of diagnosis, none of the AHST-treated patients (n = 24) developed microvascular complications, while 21.5% (31/144) had at least one (p < 0.005) complication in the CT group (n = 144). Furthermore, no case of nephropathy was reported in the AHST group, while 13.8% of CT group (p < 0.005) developed nephropathy during the same period. With regard of residual B-cell function, the percentage of individuals with predicted higher C-peptide levels (IDAA1C ≤ 9) was about 10-fold higher in the AHST group compared with CT (75 vs. 8.3%) (p < 0.001) group. Among AHST patients, 54.1% (13/24) had the HbA1c < 7.0 compared with 13.1% in the CT (p < 0.001) group. CONCLUSION: Patients with newly diagnosed type 1 diabetes treated with AHST presented lower prevalence of microvascular complications, higher residual B-cell function, and better glycemic control compared with the CT group.

Evaluation of clinical and laboratory parameters used in the identification of index cases for genetic screening of familial hypercholesterolemia in Brazil.

BACKGROUND AND AIMS: There is controversy on the accuracy of different diagnostic criteria for familial hypercholesterolemia (FH). The aim of this study is to assess the performance of different clinical criteria used to identify individuals for FH genetic cascade screening in Brazil. METHODS: All index cases (IC) registered in the Hipercol Brasil program between 2011 and 2016 were analyzed. Inclusion criteria were age ≥18 years and elevated LDL-cholesterol (LDL-C) levels, with a conclusive result in the genetic test, whether positive or negative. Initially, we tested the multivariable association between clinical and laboratory markers and the presence of an FH causing mutation. Then, we analyzed sensitivity, specificity, positive and negative predictive values for the LDL-C quartile distribution, LDL-C as a continuous variable, as well as the performance measures for the Dutch Lipid Clinic Network (DLCN) score to identify a mutation. RESULTS: Overall, 753 ICs were included and an FH causing mutation was found in 34% (n = 257) of the subjects. After multivariable analysis, LDL-C as a continuous variable, tendon xanthomas and corneal arcus were independently associated with the presence of FH mutations. LDL-C values ≥ 230 mg/dL (5.9 mmol/L) had the best tradeoff between sensitivity and specificity to diagnose a mutation. The DLCN score presented a better performance than LDL-C to identify a mutation, area under the ROC curve were 0.744 (95% CI: 0.704-0.784) and 0.730 (95% CI: 0.687-0.774), respectively, p=0.014. CONCLUSIONS: In our population, LDL ≥230 mg/dL is a feasible criterion to indicate ICs to genetic testing.

Body fat distribution in women with familial partial lipodystrophy caused by mutation in the lamin A/C gene.

Familial partial lipodystrophy (FPLD), Dunnigan variety, is an autosomal dominant disorder caused due to missense mutations in the lamin A/C (LMNA) gene encoding nuclear lamina proteins. Patients with FPLD are predisposed to metabolic complications of insulin resistance such as diabetes. We sought to evaluate and compare body fat distribution with dual-emission X-ray absorptiometry in women with and without FPLD and identify densitometric, clinical and metabolic features.

Urinary calcium excretion and insulin resistance in patients with acromegaly.

BACKGROUND: Renal complications in acromegaly include glomerular hyperfiltration, insulin resistance, hypercalciuria and urolithiasis. The aim of this study was to investigate whether urinary calcium (U(Ca)) excretion is a direct consequence of growth hormone secretion or secondary to hyperfiltration and/or insulin resistance. METHODS: We performed a cross-sectional study of 58 patients diagnosed with acromegaly. Demographic data were obtained, serum analysis was performed, including insulin-like growth factor (IGF)-1, and 24-h urine collection, to measure urinary protein excretion, U(Ca) and phosphate excretion, as well as fractional excretion of sodium and potassium. We also calculated the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Patients were predominantly male (60.3%), and their mean age was 45.9 ± 14 years. Hypercalciuria was present in 24% of patients. Patients with higher HOMA-IR had higher IGF-1 levels, a trend toward higher body mass index and higher U(Ca) excretion. In univariate analysis, U(Ca) excretion was associated with HOMA-IR (r = 0.472, P = 0.001), phosphaturia (r = 0.457, P = 0.001), IGF-1 (r = 0.398, P = 0.002) and creatinine clearance (r = 0.394, P = 0.001). HOMA-IR and phosphaturia were independently associated with U(Ca) excretion. No independent associations were found between phosphaturia and HOMA-IR or IGF-1. CONCLUSIONS: The present study revealed an association between hypercalciuria and insulin resistance in patients with acromegaly. Further studies are required to fully understand the pathogenesis of these abnormalities in patients with acromegaly.

Role of the addition of cabergoline to the management of acromegalic patients resistant to longterm treatment with octreotide LAR.

The aim of this prospective open trial was to evaluate the efficacy in normalizing IGF-I levels of the addition of cabergoline to the treatment of acromegalic patients partially responsive to Octreotide-LAR (OCT-LAR), a long acting somatotastin analog (SSA). Fifty-two patients who did not achieve hormonal control after longterm therapy (at least, 12 months) with OCT-LAR (30 mg every 28 days intramuscularly) were given cabergoline in addition to the SSA treatment. Normalization of IGF-I levels was achieved in 40.4% of patients by 6 months after the addition of cabergoline (1.0-3.0 mg/week; mean, 2.19 ± 0.64), and these patients were considered responsive. Compared to non-responsive subjects, responsive patients had significantly lower mean %ULNR-IGF-I and GH levels. However, the rate of hyperprolactinemia and positive immunohistochemical staining for PRL was similar in both groups, before the addition of cabergoline. Responsive patients were followed for at least 12 months on combination treatment and persisted with normal IGF-I levels. Patients with baseline %ULNR IGF-I up to 220% and/or GH up to 5 ng/ml were those who benefited the most from combination treatment. No patients with %ULNR-IGF-I>250% reached normalization of IGF-I levels. Our findings demonstrated that the addition of cabergoline, even at relatively low doses, is effective in both short- and long-term control of IGF-I levels in acromegalic patients partially responsive to octreotide LAR, particularly in those with mild/moderately elevated GH/IGF-levels, irrespective of prolactin status.

Dysglycemias in pregnancy: from diagnosis to treatment. Brazilian consensus statement.

There is an urgent need to find consensus on screening, diagnosing and treating all degrees of dysglycemia that may occur during pregnancies in Brazil, considering that many cases of dysglycemia in pregnant women are currently not diagnosed, leading to maternal and fetal complications. For this reason the Brazilian Diabetes Society (SBD) and the Brazilian Federation of Gynecology and Obstetrics Societies (FEBRASGO), got together to introduce this proposal. We present here a joint consensus regarding the standardization of clinical management for pregnant women with any degree of dysglycemia, on the basis of current information, to improve medical assistance and to avoid related complications of dysglycemia in pregnancy to the mother and the fetus. This consensus aims to standardize the diagnosis among general practitioners, endocrinologists and obstetricians allowing the dissemination of information in basic health units, public and private services, that are responsible for screening, diagnosing and treating disglycemic pregnant patients.

Influência dos níveis séricos de IGF-I e de testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos / Influence of serum IGF-I and testosterone on lipid and glycemic profile in acromegalic men

OBJETIVOS: Investigar a influência do IGF-I e testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos. MÉTODOS: Foram avaliados 15 homens acromegálicos. RESULTADOS: Os pacientes hipogonádicos apresentaram HDL-c mais baixo e triglicérides, LDL-c, glicemia, GH e IGF-I mais elevados. Os valores de IGF-I correlacionaram-se inversamente com HDL-c (r = - 0,57, p = 0,04) e diretamente com triglicerídeos (r = 0,62, p = 0,01) e glicemia (r = 0,66, p = 0,008), enquanto a testosterona correlacionou-se diretamente com HDL-c (r = 0,52, p = 0,05) e inversamente com triglicerídeos (r = - 0,57, p = 0,02); LDL (r = - 0,53, p = 0,04) e glicemia (r = - 0,54, p = 0,03). O IGF-I e a testosterona correlacionaram-se inversamente (r = - 0,585, p = 0,028). CONCLUSÃO: Estes resultados sugerem que a intervenção mais importante na redução do risco cardiovascular nesses pacientes é o controle da atividade da doença.

OBJECTIVES: To evaluate the influence of IGF-I and testosterone on the lipid profile and glycemia in acromegalic men. METHODS: Fifteen acromegalic men were studied. RESULTS: The hypogonadic patients presented lower HDL-c and higher tryglicerides, LDL-c, glycemia, GH and IGF-I. Serum IGF-I was inversely correlated with HDL-c (r = - 0.57, p = 0.04) and directly with TG (r = 0.62, p = 0.01) and glycemia (r = 0.66, p = 0.008), whereas serum testosterone correlated directly with HDL-c (r = 0.52, p = 0.05) and inversely with TG (r = - 0.57, p = 0.02), LDL-c (r = - 0.53, p = 0.04) and fasting blood glucose (r = - 0.54, p = 0.03). IGF-I and testosterone were inversely correlated (r = - 0.585, p = 0.028). CONCLUSION: These results suggest that the most important intervention in reducing cardiovascular risk in these patients is to control the activity of the disease.

[Influence of serum IGF-I and testosterone on lipid and glycemic profile in acromegalic men]. / Influência dos níveis séricos de IGF-I e de testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos.

OBJECTIVES: To evaluate the influence of IGF-I and testosterone on the lipid profile and glycemia in acromegalic men. METHODS: Fifteen acromegalic men were studied. RESULTS: The hypogonadic patients presented lower HDL-c and higher tryglicerides, LDL-c, glycemia, GH and IGF-I. Serum IGF-I was inversely correlated with HDL-c (r = - 0.57, p = 0.04) and directly with TG (r = 0.62, p = 0.01) and glycemia (r = 0.66, p = 0.008), whereas serum testosterone correlated directly with HDL-c (r = 0.52, p = 0.05) and inversely with TG (r = - 0.57, p = 0.02), LDL-c (r = - 0.53, p = 0.04) and fasting blood glucose (r = - 0.54, p = 0.03). IGF-I and testosterone were inversely correlated (r = - 0.585, p = 0.028). CONCLUSION: These results suggest that the most important intervention in reducing cardiovascular risk in these patients is to control the activity of the disease.

Restless legs syndrome and quality of sleep in type 2 diabetes.

OBJECTIVE: To investigate the presence of restless legs syndrome (RLS) and the quality of sleep in a population of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The study population was composed of 100 consecutive patients regularly attending a diabetes clinic at the University Hospital of the Federal University of Ceará. The subjects' quality of sleep was assessed by the Pittsburgh Sleep Quality Index, and excessive daytime sleepiness (EDS) was measured by the Epworth Sleepiness Scale. The RLS was diagnosed using the four minimum criteria defined by the International Restless Legs Syndrome Study Group. Other relevant clinical and laboratory parameters were obtained by interview and chart review. RESULTS: RLS was found in 27% of patients. Poor sleep quality was present in 45% of cases and was associated with age (P = 0.04), peripheral neuropathy (P = 0.001), and RLS (P = 0.000). EDS was found in 26% of patients. Logistic regression analysis revealed an association between RLS and peripheral neuropathy (odds ratio 12.85 [95% CI 2.83-58.40], P = 0.001). CONCLUSIONS: RLS is common in type 2 diabetic patients and can be a major cause of sleep disruption in these patients.

Effect of maternal use of antiretroviral agents on serum insulin levels of the newborn infant.

OBJECTIVE: The aim of this study was to investigate the effect of antiretroviral drugs on neonatal serum insulin levels. RESEARCH DESIGN AND METHODS: A prospective study was conducted on 57 pregnant women divided into three groups: the zidovudine (ZDV) group, HIV-infected women taking ZDV (n = 20); the triple treatment group, HIV-infected women taking triple antiretroviral agents ZDV + lamivudine + nelfinavir (n = 25); and the control group, pregnant women considered normal from a clinical and laboratory standpoint (n = 12). Blood was collected from the umbilical cord of newborn infants upon delivery for measurement of insulin level. The insulin measurements were performed in duplicate by radioimmunoassay. RESULTS: Demographic and anthropometric data were homogeneous, and pregnant women with a personal and family history of diabetes were excluded. There was no difference between groups regarding glycemia in the newborn. Median newborn insulin doses were 2.9, 4.8, and 6.5 muU/ml for the triple treatment, ZDV, and control groups, respectively (P < 0.05). CONCLUSIONS: Use of triple therapy during pregnancy induced a significant decrease in serum levels of neonatal insulin compared with the control group. Active surveillance of short- and long-term adverse events is imperative to issue a definitive statement regarding the impact that use of protease inhibitors during pregnancy will have on infant metabolism.

Picnodisostose: relato de dois casos / Pycnodysostosis: report of two cases

Picnodisostose (PYCD) é uma rara displasia esquelética autossômica recessiva, decorrente de defeito no gene codificador da enzima catepsina K, caracterizada por baixa estatura (BE), osteoesclerose, acroosteólise, deformidades crânio-faciais e fragilidade óssea. Embora a BE seja característica, deficiência de GH tem sido relatada apenas em parte dos casos de PYCD. Apresentamos dois casos isolados, com quadros clínico-radiológicos característicos. Caso 1: 9 anos, masculino, pais consangüíneos, apresentando BE, osteoesclerose, fragilidade óssea, exoftalmia bilateral, fronte ampla, braquicefalia, alargamento das suturas cranianas, fontanelas abertas, micrognatia, implantação anormal dos dentes, braquidactilia, unhas distróficas e acrosteólise das falanges distais. Caso 2: 17 anos, masculino, com BE, nariz proeminente, braquicefalia, plastibasia, falha de fechamento de suturas e fontanelas, hipoplasia mandibular, dentição anormal, osteoesclerose difusa, braquidactilia, acrosteólise das falanges distais e aumento das pregas cutâneas nas mãos. Ambos apresentaram níveis basais normais de TSH, T4 livre, gonadotrofinas e testosterona, e da resposta do GH e do cortisol, durante teste farmacológico. Em conclusão, a PYCD parece ser uma condição heterogénea com apresentação clínica variável. Assim, embora não tenha sido observado nestes casos, mas tendo em vista as descrições prévias, consideramos importante que pacientes com PYCD sejam rotineiramente submetidos à avaliação hormonal.

Carcinoma papilifero oculto da tireoide com metastases ganglionares a distancia relato de um caso / Occult papillary thyroid carcinoma with distant ganglionary metastasis; a case report

Os autores relatam um caso de carcinoma papilifero oculto da tireoide com comprometimento linfatico extenso e a distancia, ressaltando a raridade desta apresentaçao. Tecem comentarios sobre a incidencia e prognostico do carcinoma papolifero oculto da tireoide. Finalizam fazendo uma breve revisao dos casos existentes na literatura medica