Differences in Puberty of Girls before and during the COVID-19 Pandemic.

In the COVID-19 pandemic, there was an increase in consultations for precocious puberty. We aim to analyze differences in female puberty before and during the COVID-19 pandemic. A cross-sectional analytical study was designed at the Pediatric Endocrinology Clinic of the University Hospital of the Federal University of Maranhão in São Luis, Brazil. We included 55 girls with precocious puberty, 22 who started puberty during the pandemic and 33 who started puberty before the pandemic. Clinical, anthropometric, laboratory and imaging variables were compared between groups. Statistics were performed to determine if there was a statistical difference between the groups. Girls with puberty during the pandemic had higher Z-scores for weight (1.08 ± 1.29 versus 0.69 ± 0.83; p = 0.04), lower ovarian volume (1.88 ± 0.95 versus 3.15 ± 2.31; p = 0.01), and smaller differences between thelarche noticed by the parents and the diagnosis (6.63 ± 5.21 versus 12.15 ± 9.96; p = 0.02). The association between precocious puberty during the pandemic with higher Z-scores for weight, lower ovarian volume, and a reduction in the time between the perception of pubertal findings by parents and the diagnosis suggests the influence of the pandemic on the normal time of puberty.

Early Markers of Cardiovascular Disease Associated with Clinical Data and Autosomal Ancestry in Patients with Type 1 Diabetes: A Cross-Sectional Study in an Admixed Brazilian Population.

Patients with type 1 diabetes (T1D) have a higher risk of developing cardiovascular disease (CVD), which is a major cause of death in this population. This study investigates early markers of CVD associated with clinical data and autosomal ancestry in T1D patients from an admixed Brazilian population. A cross-sectional study was conducted with 99 T1D patients. The mean age of the study sample was 27.6 years and the mean duration of T1D was 14.4 years. The frequencies of abnormalities of the early markers of CVD were 19.6% in the ankle-brachial index (ABI), 4.1% in the coronary artery calcium score (CACS), and 5% in the carotid Doppler. A significant percentage of agreement was observed for the comparison of the frequency of abnormalities between CACS and carotid Doppler (92.2%, p = 0.041). There was no significant association between the level of autosomal ancestry proportions and early markers of CVD. The ABI was useful in the early identification of CVD in asymptomatic young patients with T1D and with a short duration of disease. Although CACS and carotid Doppler are non-invasive tests, carotid Doppler is more cost-effective, and both have limitations in screening for CVD in young patients with a short duration of T1D. We did not find a statistically significant relationship between autosomal ancestry proportions and early CVD markers in an admixed Brazilian population.

Genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in Type 1 Diabetes from an admixed Brazilian population.

This study aimed to investigate the relationship between genetic ancestry inferred from autosomal and Y chromosome markers and HLA genotypes in patients with Type 1 Diabetes from an admixed Brazilian population. Inference of autosomal ancestry; HLA-DRB1, -DQA1 and -DQB1 typifications; and Y chromosome analysis were performed. European autosomal ancestry was about 50%, followed by approximately 25% of African and Native American. The European Y chromosome was predominant. The HLA-DRB1*03 and DRB1*04 alleles presented risk association with T1D. When the Y chromosome was European, DRB1*03 and DRB1*04 homozygote and DRB1*03/DRB1*04 heterozygote genotypes were the most frequent. The results suggest that individuals from Maranhão have a European origin as their major component; and are patrilineal with greater frequency from the R1b haplogroup. The predominance of the HLA-DRB1*03 and DRB1*04 alleles conferring greater risk in our population and being more frequently related to the ancestry of the European Y chromosome suggests that in our population, the risk of T1D can be transmitted by European ancestors of our process miscegenation. However, the Y sample sizes of Africans and Native Americans were small, and further research should be conducted with large mixed sample sizes to clarify this possible association.

Novel Mutation in the Hemojuvelin Gene (HJV) in a Patient with Juvenile Hemochromatosis Presenting with Insulin-dependent Diabetes Mellitus, Secondary Hypothyroidism and Hypogonadism.

BACKGROUND Juvenile hemochromatosis is a rare genetic disease that leads to intense iron accumulation. The disease onset usually occurs before the third decade of life and causes severe dysfunction in various organs. The most classical clinical findings are hypogonadotropic hypogonadism, cardiomyopathy, liver fibrosis, glycemic changes, arthropathy and skin pigmentation. However, secondary hypothyroidism is not reported in these patients. Juvenile hemochromatosis has an autosomal recessive inheritance and might be type 2A or type 2B, due to mutation in either the hemojuvelin gene (HJV) or hepcidin antimicrobial peptide (HAMP) gene. CASE REPORT A 26-year-old female patient was admitted with a recent history of diabetic ketoacidosis. Three months after that admission, she presented with arthralgia, diffuse abdominal pain, adynamia, hair loss, darkening of the skin and amenorrhea. Severe iron overload was found and findings in the hepatic biopsy were compatible with hemochromatosis. An upper abdominal magnetic resonance imaging (MRI) showed iron deposition in the liver and pancreas and pituitary MRI exhibited accumulation on the anterior pituitary. After 16 months the patient presented with dyspnea and lower limb edema, and cardiac MRI indicated iron deposition in the myocardium. The patient was diagnosed with juvenile hemochromatosis presenting with hypogonadotropic hypogonadism, cardiomyopathy, insulin-dependent diabetes mellitus, and secondary hypothyroidism. A novel homozygous mutation, c.697delC, in the HJV gene was detected. CONCLUSIONS We describe for the first time a severe and atypical case of juvenile hemochromatosis type 2A presenting classical clinical features, as well as secondary hypothyroidism resulting from a novel mutation in the HJV gene.

Differential Expression of HMGA1 and HMGA2 in pituitary neuroendocrine tumors.

Defining biomarkers for invasive pituitary neuroendocrine tumors (PitNETs) is highly desirable. The high mobility group A (HMGA) proteins are among the most widely expressed cancer-associated proteins. Indeed, their overexpression is a frequent feature of human malignancies, including PitNETs. We show that nonfunctioning PitNETs (NF-PitNETs) express significantly higher levels of HMGA1 than somatotropinomas (GHs) and corticotropinomas (ACTHs). Furthermore, HMGA2 expression was detected only in NF-PitNETs and was significantly higher in larger tumors than in smaller tumors. HMGA expression analysis generally focuses on nuclear staining. Here, cytoplasmic HMGA staining was also found. PitNETs displayed strong nuclear HMGA1 and strong cytoplasmic HMGA2 immunoreactivity. Interestingly, the HMGA1 and HMGA2 nuclear expression levels were significantly higher in invasive adenomas than in noninvasive adenomas. The highest levels of nuclear HMGA2 were found in GHs. In conclusion, we show that overexpression of nuclear HMGA proteins could be a potential biomarker of invasive PitNETs, particularly HMGA2 for GHs. HMGA2 might be a reliable biomarker for NF-PitNETs.

Higher Income and Integration into the Workforce Are the Main Factors Associated with Quality of Life in Acromegalic Patients in Northeastern Brazil.

OBJECTIVE: To identify the factors associated with quality of life in patients with acromegaly with follow-up at the referral service in neuroendocrinology of the state of Maranhão, northeast Brazil. METHODS: The Acromegaly Quality of Life Questionnaire (Acro-QoL) was used. Factors independently associated with quality of life were identified using multivariate linear regression, with p values < 0.05 considered significant. RESULTS: The multivariate linear regression analysis indicated a positive association between being integrated into the job market and quality of life scores in the overall domain (ß = 0.288, p = 0.003), psychological domain (ß = 0.291, p = 0.032), and personal relationship domain (ß = 0.314, p = 0.019). We also observed a positive association with income and the quality of life scores in all domains as follows: overall domain (ß = 0.037, p = 0.003), physical domain (ß = 0.988, p = 0.001), psychological domain (ß = 0.342, p = 0.008), physical appearance domain (ß = 0.270, p = 0.049), and personal relationship domain (ß = 0.315, p = 0.012). CONCLUSION: For patients with acromegaly living in one of the least developed regions of Brazil, integration into the job market and a higher income were associated with a better quality of life.

Fatores de Risco Cardiovascular e sua Relação com o Nível de Escolaridade numa População Universitária / Cardiovascular Risk Factors and their Relationship with Educational Level in a University Population

Fundamentos: O menor grau de escolaridade na população parece estar associado com a maior prevalência dos fatoresde risco cardiovascular (FRCV). Contudo, poucos estudos avaliaram esse fato através de análise clínica e laboratorial em centros universitários. Objetivo: Avaliar a prevalência dos FRCV em servidores de universidade pública. Métodos: Estudo transversal, analítico, randomizado, com 319 participantes de uma coorte de servidores universitários. Analisou-se a prevalência dos FRCV através da medição dos níveis glicêmicos e pressóricos, perfil lipídico, índices antropométricos e foram realizadas análises comparativas de subgrupos de diferentes níveis de escolaridade. Realizou-se análise de regressão logística multivariada para avaliar a associação independente entre nível de escolaridade e presença dos FRCV. Resultados: Média de idade 46,0±10,0 anos, 52,5% mulheres, 56,0% com nível superior de escolaridade, 85,6% pertencentes às classes socioeconômicas B e C. Prevalência dos FRCV: diabetes mellitus (DM) 9,4%; hipertensão arterial sistêmica(HAS) 36,7%; dislipidemia 50,5%; tabagismo 21,9%; sobrepeso 59,6%; obesidade 13,2%; sedentarismo 27,9%. O grupo de menor nível de escolaridade se associou de forma independente com maior prevalência de DM e sedentarismo, quando comparado ao grupo dos servidores com nível superior (docentes e não docentes). DM=odds ratio 2,4(IC95% 1,05-5,5) e p=0,036; sedentarismo=odds ratio 2,2 (IC95% 1,3-3,7) e p=0,003. Os subgrupos não apresentaramdiferenças quanto às demais variáveis.

Background: The lower level of education in the population appears to be associated with a higher prevalence of cardiovascular risk factors(CVRF). However, few studies have assessed this fact by means of clinical and laboratory analysis in universities. Objective: To evaluate the prevalence of cardiovascular risk factors in public servants at a public university.Methods: Cross-sectional, analytical and randomized study, with 319 participants of a cohort composed of university public servants.CVRF prevalence was assessed by measuring blood glucose and blood pressure levels, lipid profile and anthropometric indices, and comparative analyses were made of subgroups with different education levels. A multivariate logistic regression analysis was used to assess the independentassociation between education level and presence of CVRF.Results: Mean age 46.0±10.0 years old, 52.5% women, 56.0% with higher education level, 85.6% belonging to B and C socioeconomic classes. Prevalence of CVRF: diabetes mellitus (DM) - 9.4%; systemic hypertension (SH) - 36.7%; dyslipidemia - 50.5%; smoking - 21.9%;overweight - 59.6%; obesity - 13.2%; sedentary lifestyle - 27.9%. The group with the lowest level of education had an independent association,with higher prevalence of DM and sedentary lifestyle, as compared to the group of public servants with higher level of education (teachersand non-teachers). DM=odds ratio 2.4 (95% CI 1.05 to 5.5) and p=0.036; sedentary lifestyle=odds ratio 2.2 (95% CI 1.3 to 3.7) andp=0.003. The subgroups showed no differences regarding the other variables. Conclusion: In this study, individuals with higher levels of education showed lower prevalence of diabetes and sedentary lifestyle.

Can we predict long-term remission after somatostatin analog withdrawal in patients with acromegaly? Results from a multicenter prospective trial.

Somatostatin analogs (SSAs) represent the mainstay of therapy in acromegaly. One of the potential disadvantages is the expected need to maintain therapy indefinitely in previously non-irradiated patients. The aim of this multicenter prospective open trial was to evaluate the likelihood of successful discontinuation of SSA therapy in well-controlled acromegalic patients who fulfilled very strict criteria: two or more years of treatment with the long-acting SSA octreotide LAR (OCT-LAR), a stable dose and injections interval every 4 weeks or longer for the previous year, GH levels <2.5 ng/ml and normal IGF-1 levels for age, a tumor remnant <10 mm, no history of radiotherapy, and no use of cabergoline or pegvisomant over the previous 6 months. Disease recurrence was defined as an increase of IGF-1 to levels above 1.2-fold the upper limit of normal (ULN). Out of 220 patients, 20 patients (12 women and 8 men; mean age, 48.1 ± 10.3 years; age range, 27-64) treated for 2.74 ± 0.64 years (range, 2.0-4.4) were included in this prospective study and OCT-LAR therapy was stopped. Four patients (20 %) remained without clinical and biochemical/neuroradiological evidence of disease recurrence after 12-18 months of follow-up. Sixteen patients (80 %) relapsed biochemically within 9 months after drug withdrawal and restarted OCT-LAR at the same previous dose. Compared to recurring subjects, non-recurring patients had significantly lower mean IGF-1 (× ULN) levels but there were some overlapping values in both groups. No other characteristic could be identified as a predictor of successful OCT-LAR discontinuation. Our findings demonstrated that OCT-LAR withdrawal, though rare, is possible in well-selected acromegalic patients treated for at least 2 years and considered optimally controlled in hormonal and neuroradiological terms.

Thyroid cancer in patients with acromegaly: a case-control study.

Several studies have associated acromegaly with an increased risk of benign and malignant tumors. While simple and multinodular goiters are common findings in acromegaly, the prevalence of thyroid cancer is uncertain. The objective of this study was to estimate the prevalence of thyroid cancer in a series of acromegalic patients from three hospitals in northeast of Brazil. The methodology used included morphological, cytological and histological thyroid analysis of acromegalic patients and volunteers over 18 years, matched for age and sex and with nodule (s) ≥1 cm. The subjects of this study were 124 acromegalic patients, including 76 females (61.3%) and 48 men (38.7%), with a mean age 45.1 years. Results of the study showed that thyroid ultrasonography was normal in 31 cases (25%), 25 had diffuse goiter (20.1%), 67 had nodules (54%) and one agenesis of the right lobe (0.8%). Thirty-six patients underwent fine needle aspiration biopsy (FNAB) of their nodules and 9 cases of papillary cancer were found (7.2%). The control group consisted of 263 subjects, 156 females (59.3%) and 107 males (40.7%), mean age 44.7 years. In ultrasound assessment, 96 had nodules (36.5%). Of these, 13 were punctured and 2 cases of papillary carcinoma were found (0.7%). These results gave an odds ratio of 10.21 (p = 0.0011, 95% CI 2.17 to 48.01). These findings demonstrate an increased prevalence of thyroid cancer, statistically significant when compared to our control group. Thus, it is suggested that acromegalic patients should be routinely submitted to thyroid ultrasound evaluation, followed by FNAB of nodules when indicated.

Acromegalic cardiomyopathy in an extensively admixed population: is there a role for GH/IGF-I axis?

BACKGROUND: A specific acromegaly-related cardiomyopathy has been described in the literature, largely in Caucasians, which is independent of other risk factors, mainly hypertension. OBJECTIVE: This study assessed the cardiac changes in acromegalics of significant ethnic diversity and also the relevance of the aetiopathogenic factors involved, such as disease activity and hypertension. DESIGN: It is a cross-sectional study with a comparative control group. PATIENTS AND METHODS: In this study, 37 acromegalic patients (20 Intermediate-skinned (IS), 14 Dark-skinned (DS) and three Light-skinned (LS) individuals) and 74 controls matched by age, gender and hypertension were evaluated. Cardiac morphology and function were addressed using echocardiography parameters. RESULTS: The mean age of patients was 46.9 ± 12.8 years, with 67.6% being women and 43.2% hypertensive. The prevalence of left ventricular hypertrophy (LVH) between acromegalics was 56.8% vs 10.8% in the controls (P < 0.001). About 86% of patients with LVH had active disease (P = 0.023). Logistic regression revealed that disease activity presented a stronger association (OR = 5.925; CI = 1.085-32.351; P = 0.040) with LVH than hypertension (OR = 3.237; CI = 0.702-14.924; P = 0.132). When DS acromegalics were compared with IS ones, no statistically significant differences were observed. CONCLUSION: Chronically hyperactive somatotropic axis remains as an independent and determining factor in the development of left ventricular hypertrophy, as it is more associated with this condition than hypertension in a largely admixed population with a high degree of African ancestry.