Leandra Steinmetz

Inhibin A production after gonadotropin stimulus: a new method to detect ovarian tissue in ovotesticular disorder of sex development.

Background/Aims: While laboratory methods for the detection of testicular tissue are well standardized, currently there is no available test to demonstrate the presence of ovarian tissue. We evaluated the effectiveness of gonadal stimulation with luteinizing hormone (LH)/follicle-stimulating hormone (FSH) for the detection of ovarian tissue in patients with disorders of sex development (DSD). Methods: Ten patients with congenital adrenal hyperplasia (CAH) as ovarian-positive controls, 10 with cryptorchidism (ovarian-negative controls), 13 patients with DSD of no defined etiology and 7 patients with ovotesticular DSD (true hermaphroditism, TH) were included in the study. They underwent a daily injection of both LH and FSH on 3 consecutive days. LH, FSH, estradiol, testosterone and inhibin A were measured before treatment, 24 h after the 1st dose and 24 h after the 3rd dose. Results: Estradiol increased in all CAH and TH patients, with a median value of 155.1 and 92.6 pg/ml, respectively, after the 3rd injection. Inhibin A also increased in all CAH and TH patients, with a median value of 70.4 and 32.2 pg/ml, respectively, after the 3rd injection. There was no change in these hormones in the other groups. Conclusion: The LH/FSH stimulation test might be a useful method to detect the presence of ovarian tissue.

Menstrual Cycle Recovery in Patients with Anorexia Nervosa: The Importance of Insulin-Like Growth Factor 1

Background: Follow-up visits of patients recovering from anorexia nervosa (AN) have shown that some patients do not resume menstrual cycles despite returning to the normal weight for their age and height. Aim: To verify whether leptin, insulin-like growth factor 1 (IGF-1) or another hormonal marker could be a good predictor of the return of menses. Patients and Methods: This prospective study included female adolescents diagnosed with AN or eating disorders not otherwise specified (EDNOS) and who were being treated in an ambulatory care unit during nutritional recovery. Body mass index and leptin, luteinizing hormone, estradiol and IGF-1 levels of these patients were evaluated. Blood samples were collected in the 1st (T1), 5th (T2), 10th (T3), 15th (T4) and 20th (T5) weeks of treatment. The hormone levels during nutritional recovery and at the time of the resumption of menses were analyzed. Results: The hormonal profiles improved after nutritional recovery, with IGF-1 correlating the most with the resumption of menses and nutritional recovery (p = 0.0001). At the resumption of menstruation, the patients showed IGF-1 levels >342.8 ng/ml. Conclusion: IGF-1 was the best predictor of the return of menses in female adolescents with AN or EDNOS.

A novel DAX1/NR0B1 mutation in a patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism

We report a case of adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HH) due to a novel DAX1 mutation. A 19-month-old boy with hyperpigmentation and failure to thrive came to our service for investigation. Three brothers of the patient had died due to adrenal failure, and a maternal cousin had adrenal insufficiency. Adrenoleukodystrophy was excluded. MRI showed normal pituitary and hypothalamus. Plasma hormone evaluation revealed high ACTH (up to 2,790 pg/mL), and low levels of androstenedione, DHEA-S, 11-deoxycortisol, and cortisol. At 14 years of age the patient was still prepubescent, his weight was 43.6 kg (SDS: -0.87) and his height was 161 cm (SDS: -0.36), with normal body proportions. In the GnRH test, basal and maximum values of LH and FSH were respectively 0.6/2.1 and < 1.0/< 1.0 U/L. Molecular investigation identified a novel mutation that consists of a deletion of codon 372 (AAC; asparagine) in exon 1 of DAX1. This mutation was not found in a study of 200 alleles from normal individuals. Prediction site analysis indicated that this alteration, located in the DAX1 ligand-binding domain, may damage DAX1 protein. We hypothesize that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient.

Pesquisa de tecido prostático em pacientes 46, XX portadoras da forma clássica de hiperplasia congênita das suprarrenais

ABSTRACT Objectives: To describe the presence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia (CAH); to evaluate the sensitivity and specificity of prostatic specific antigen (PSA) measured in congenital adrenal hyperplasia patients with regard to the detection of prostatic tissue in pelvic MRI. Methods: We studied 52 children and adolescents, 32 with the classical form of congenital adrenal hyperplasia, 10 boys and 10 girls without CAH. Pelvic MRI was performed in all patients to detect prostatic tissue. Prosta-te specific antigen, testosterone and dihydrotestosterone were measured in all patients. We used Receiver Operating Characteristic Curve for PSA discrimination capacity. Results: Five girls with congenital adrenal hyperplasia showed image of prostatic tissue on pelvic MRI. Prostate specific antigen showed sensitivity and specificity of 100% and 88.9%, respectively, taking 0.1 ng/mL as the cutoff level. Conclusions: The incidence of prostatic tissue in 46,XX patients with the classical form of congenital adrenal hyperplasia was 15.6%. PSA demons-trated to be a good marker of prostatic tissue in these patients and should be used to screen patients to be submitted to image studies.

Deficiência de 5alfa-redutase tipo 2: experiências de Campinas (SP) e Salvador (BA)

OBJECTIVE: To report the experience regarding patients with steroid 5a-reductase type 2 deficiency from three different clinical services in Brazil. CASUISTIC AND METHODS: Twenty five patients with clinical and hormonal features of 5a-reductase deficiency from 23 families (15 from Bahia, 7 from Sao Paulo and 1 from Minas Gerais) were included in this study. Clinical, hormonal and molecular data were evaluated. The molecular analysis of the five exons of the SRD5A2 gene was done by automatic or manual sequencing of PCR products. RESULTS: In ten families, SRD5A2 mutations were found in homozygosis (5 with G183S, 2 with R246W, 1 with G196S, 1 with del642T, 1 with 217_218insC), in three in compound heterozygosis (1 with Q126R/IVS3+1G>A, 1 with Q126R/del418T, 1 with Q126R/G158R) while other three were heterozygous, with only one deleterious mutation (1 with G196S, 1 with A207D, and 1 with R246W). In seven cases, no sequencing abnormalities were detected. The G183S substitution was the most frequently found among miscigenated patients (Afro-Euro-Brazilians) from Bahia. Hormonal and clinical findings did not differ between patients with or without mutations, exception made to a higher frequency of consanguinity and greater severity of genital ambiguity in the first group. CONCLUSION: Our results reinforce the importance of molecular investigation for the diagnosis of this disease and point out to the finding of a very frequent mutation (G183S) in our series, especially in patients with mixed ethnic background from Bahia, and the description of mutations that have only been reported in Brazilian patients so far.

Identification and functional analysis of a novel inactivating mutation (A804D) of the calcium-sensing receptor gene.

Relatively little is known about patients’ understanding of thyrotoxicosis and its treatment. Lincoln et al . (2000) found that patient knowledge of the disorder was limited, in an endocrine clinic with no routine provision of printed material or formal education programme. Thyrotoxic patients need to be aware of the symptomatology associated with the condition as well as potential side-effects of antithyroid drugs. Agranulocytosis, although rare (Cooper, 2003), is potentially fatal, and patients with suggestive symptoms should stop their medication immediately, and seek urgent medical advice. In this endocrine clinic, patients with thyrotoxicosis receive written information sheets detailing the major symptoms, treatment options and potential side-effects, and also have personal and telephone access to an endocrine specialist nurse. The aim of this study was to determine the level of knowledge of thyrotoxicosis and its treatment among patients attending the clinic who had been treated with antithyroid drugs. Consecutive patients were asked to respond to a postal questionnaire relating to information contained within the information sheets. Ethical approval was obtained. Responders were asked to identify thyrotoxic symptoms from a list. The correct course of action to be taken in the event of a sore throat developing on antithyroid medication was also selected from a list in a two-part question. A ‘total knowledge score’ was calculated for each patient, the maximum achievable score being 16. A subscore was also calculated for questions relating to antithyroid treatment (the ‘treatment score’), with a maximum achievable value of 8. Patients were asked to rate their perception of the adequacy of information received. Questionnaires were posted to 162 patients [median age 42 years (range 21–86), 84% female] and 57 completed questionnaires were returned. The majority of individuals (98%) had had at least three attendances at the endocrine clinic prior to completing the questionnaire. Only 30% of responders were aware of all six thyrotoxic symptoms listed. The most commonly recognized symptoms were weight loss (84% of responders), heat intolerance (83%) and palpitations (83%). The median knowledge score was 12·1 (range 2–16). There was a negative correlation between total score and age ( ρ = − 0·47, P < 0·001). Sixty-nine per cent of individuals perceived themselves to have received adequate information about thyroid disease. However, median knowledge scores were identical regardless of whether patients felt they had received adequate information or not. Only 42% of individuals identified a ‘drop in blood count’ as a potential side-effect of antithyroid medication. Overall, 51% of responders knew the correct course of action to take should a sore throat develop while on antithyroid drugs. Of the 40 patients (74% of responders) who perceived that they had received adequate information about antithyroid medications, 40% were unaware of the correct action required. The median treatment score was 6 (range 0–8), and worsened with age ( ρ = − 0·42, P = 0·001). Patients who felt they had received adequate information about treatment had better treatment scores [6·0 (0– 8) vs. 3·5 (0–6); P = 0·006]. We have demonstrated that understanding of key issues pertaining to thyrotoxicosis is disappointing. Less than half of the responders were aware of agranulocytosis as a potential sideeffect of antithyroid drugs. Only half knew the correct course of action to take in the face of suspected agranulocytosis, despite the fact that a much greater proportion of individuals felt they had received adequate information about treatment. This level of knowledge is particularly poor in view of the provision of information sheets and contact with an endocrine specialist nurse throughout this study. The influence of patient age on consultations was demonstrated by Callahan et al . (2000), who reported that although older patients reported greater satisfaction during consultations, they were given less health education and asked fewer questions. Lincoln et al . (2000) found that knowledge of thyrotoxicosis among patients was limited. Patients’ knowledge and satisfaction improved whether they received information leaflets alone or together with group education. In our study, patients were already receiving information sheets, but still demonstrated inadequate knowledge. The present study demonstrates that we need to be more active in providing education about key aspects of thyrotoxicosis and its treatment during every consultation. Furthermore, we need to check patients’ understanding of the information we have imparted, as there is a discrepancy between patient perception of adequacy of education and actual knowledge gained.

Decrease of Serum Alkaline Phosphatase after Three Cycles of Pamidronate Disodium in Children with Severe Osteogenesis Imperfecta

We evaluated 13 patients (6 girls) with severe OI treated with intravenous PD given as cycles of 3 days. The interval among the cycles is 2, 3 or 4 months, and the dose of PD (mg/kg/day) is 0.5, 0.75 or 1.0 for patients aged less than 2 years, 2–3 years and more than 3 years, respectively. The serum level of AP was evaluated before the first, second, third and fourth cycle of PD. The value of the mean before the first cycle was compared to values of the mean before the other cycles through paired t test (p ! 0.05 was significant).

Diabetes mellitus in childhood: an emerging condition in the 21st century

The International Diabetes Federation (IDF-2015) estimates the existence of 30,900 children under 15 years old with type 1 diabetes mellitus (DM1) in Brazil, and an increase of 3.0% per year is expected. This review focused on meta-analysis and pediatric diabetes update articles in order to draw attention to the need of planning coping strategies to support this serious public health problem in coming years. DM1 is considered an immuno-mediated disease with a complex transmission influenced by genetic and environmental factors responsible for a gradual destruction of the insulin producing pancreatic beta cells. Seroconversion to DM1-associated autoantibodies and abnormalities in metabolic tests that assess insulin secretion and glucose tolerance can be used as predictive criteria of beta cells functional reserve and the onset of the clinical disease. Symptomatic DM1 treatment is complex and the maintenance of good metabolic control is still the only effective strategy for preserving beta cell function. Disease duration and hyperglycemia are both risk factors for the onset of chronic vascular complications that negatively affect the quality of life and survival of these patients. In this regard, health teams must be trained to provide the best possible information on pediatric diabetes, through continuing education programs focused on enabling these young people and their families to diabetes self-management.