Adrenal Insufficiency and Glucocorticoid Use During the COVID-19 Pandemic

The coronavirus disease 2019 (COVID-19) is an emerging pandemic challenge. Acute respiratory distress syndrome (ARDS) in COVID-19 is characterized by a severe cytokine storm. Patients undergoing glucocorticoid (GC) replacement therapy for adrenal insufficiency (AI) represent a highly vulnerable group that could develop severe complications due to the SARS-CoV-2 infection. In this review, we highlight the strategies to avoid an adrenal crisis in patients with AI and COVID-19. Adrenal crisis is a medical emergency and an important cause of death. Once patients with AI present symptoms of COVID-19, the dose of GC replacement therapy should be immediately doubled. In the presence of any emergency warning signs or inability to administer oral GC doses, we recommend that patients should immediately seek Emergency services to evaluate COVID-19 symptoms and receive 100 mg hydrocortisone by intravenous injection, followed by 50 mg hydrocortisone intravenously every 6 h or 200 mg/day by continuous intravenous infusion

Effect of Acute and Chronic Oral Zinc Administration in Hyperprolactinemic Patients

The inverse relationship between zinc (Zn++) and prolactin (PRL) was detected in in vitro studies, whereas in vivo results are contradictory. In order to evaluate this controversial subject we studied patients with hyperprolactinemia. Basal serum Zn++ levels and serum PRL response to acute and chronic oral Zn++ administration were evaluated in seven patients with prolactinomas and one with idiopathic hyperprolactinemia. Serum PRL levels did not change after acute oral Zn++ administration (37.5 mg), although Zn++ levels increased from 1.11±0.15 to 2.44±0.39 μg/mL (P<0.05). ZnZn++ administration (47.7 mg daily) during 60 days increased serum Zn++ levels from 1.11 ± 0.15 to 1.59 ± 0.58 μg/mL (p < 0.05) but caused no change in serum PRL levels. The TRH tolerance test (200 μg) was performed before and after 60 days of Zn++ administration, and PRL response to TRH was unchangeable and similar in both tests. We concluded that acute or chronic Zn++ administration does not inhibit PRL secretion in basal condition or by TRH effect in hyperprolactinemic patients

Effects of Interactive Musical Activities on the Well-being of Children with Urogenital Anomalies during Hospitalization for Surgery

Background: Hospitalizations and surgeries are stressful situations mainly for children. It is extremely important to search for strategies that can help to reduce suffering and stress in children during medical treatments, contributing then to the process of humanization in health care. Due to the therapeutic potential of music, we believe that it could be an alternative to help children to cope better with the situation of anxiety and stress arising from a hospitalization. This research intended to evaluate the effect of interactive musical activities in reducing stress in children hospitalized for urological surgery. Methods: Fifty-four children were invited for the study of which 40 participated. Twenty-two of those were part of the experimental group and 18 of the control group. The experimental group participated in 15 to 30 minutes daily sessions of playful interactive musical activities during hospitalization (~5 days), except on the day of surgery. The Child Stress Scale - ESI, the drawing-and-story procedure for analysis of the feelings towards surgery and salivary cortisol at 8:00 AM and 4:00 PM were used to evaluate the degree of stress in these children. Results: The stress score obtained before and after surgery significantly decreased in both groups, mainly in the experimental group. There was no significant difference in positive and negative feelings towards the surgery in both groups. Salivary cortisol levels between the 2 groups were also similar. Conclusion: A positive effect of musical activities in children’s stress reduction during the hospitalization period was observed, indicating that these procedures can contribute to the well-being of these patients. Keywords: Hospitalized child, Music, Stress, Music therapy, Urogenital abnormalities/surger

Frequency of genetic polymorphisms of PXR gene in the Brazilian population

INTRODUCTION: PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. METHODS: DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. RESULTS: Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913 C&gt;T and -6994T&gt;C occurred at a higher frequency comparedtothe Africanalleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C&gt;T allele was found at a similar frequency to those described in Caucasians and Africans (p &gt; 0.05). CONCLUSION: We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians

Frequency of genetic polymorphisms of PXR gene in the Brazilian population

INTRODUCTION: PXR polymorphisms have been implicated in modulating CYP3A4 and PXR expression, potentially accounting for interindividual differences in drug metabolism. The prevalence of PXR polymorphisms varies among ethnic groups and data on the allelic distribution in the highly mixed Brazilian population is lacking. The aim of this study was to analyze genetic variations in the PXR gene in Brazilians and to compare the results to other ethnic groups. METHODS: DNA samples from 117 healthy Brazilians underwent PCR amplification and sequencing. RESULTS: Eleven polymorphisms were identified, 3 of which are highly associated with differences in CYP3A4 expression. We also identified 1 new synonymous variant in 1.3% of the alleles. Among the functional polymorphisms, -25913 C>T and -6994T>C occurred at a higher frequency comparedtothe Africanalleles (p < 0.05) but at a lower frequency compared to Caucasian alleles. The 8055 C>T allele was found at a similar frequency to those described in Caucasians and Africans (p > 0.05). CONCLUSION: We observed that functional variants of the PXR were frequent in our sample of the Brazilian population. Our results suggest that PXR gene variants may be of interest in pharmacogenetic studies involving Brazilians

Low estrogen doses normalize testosterone and estradiol levels to the female range in transgender women

OBJECTIVE: The ideal dosage of cross-sex hormones remains unknown. The aim of this study was to evaluate the luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin levels after low-dose estrogen therapy with or without cyproterone acetate in transgender women. METHODS: The serum hormone and biochemical profiles of 51 transgender women were evaluated before gonadectomy. Hormone therapy consisted of conjugated equine estrogen alone or combined with cyproterone acetate. The daily dose of conjugated equine estrogen was 0.625 mg in 41 subjects and 1.25 mg in 10 subjects, and the daily dose of cyproterone acetate was 50 mg in 42 subjects and 100 mg in one subject. RESULTS: Estrogen-only therapy reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 731.5 to 18 ng/dL, 6.3 to 1.1 U/L and 9.6 to 1.5 U/L, respectively. Estrogen plus cyproterone acetate reduced the testosterone, luteinizing hormone and follicle-stimulating hormone levels from 750 to 21 ng/dL, 6.8 to 0.6 U/L and 10 to 1.0 U/L, respectively. The serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, estradiol and prolactin in the patients treated with estrogen alone and estrogen plus cyproterone acetate were not significantly different. The group receiving estrogen plus cyproterone acetate had significantly higher levels of gamma-glutamyltransferase than the group receiving estrogen alone. No significant differences in the other biochemical parameters were evident between the patients receiving estrogen alone and estrogen plus cyproterone acetate. CONCLUSION: In our sample of transgender women, lower estrogen doses than those usually prescribed for these subjects were able to adjust the testosterone and estradiol levels to the physiological female range, thus avoiding high estrogen doses and their multiple associated side effects

Mutação nova no GNAS em um menino com pseudo-hipoparatireoidismo tipo Ia e dosagens séricas normais de cálcio e fósforo

The objective of this study was to describe a new mutation in GNAS in a family with pseudohypoparathyroidism type Ia (PHP Ia), a rare osteometabolic disease. An 8-month-old boy was seen by an Endocrinologist due to obesity and low growth velocity. Noteworthy, his mother exhibited typical Albright hereditary osteodystrophy (AHO) phenotype. The clinical diagnosis of PHP Ia was suspected. The GNAS coding region from mother and son was amplified and directly sequenced. A novel heterozygous missense mutation (c.673T>C) was identified in exon 5 in both patients. In this family, the mother's clinical picture was the clue for the son's diagnosis. Molecular analysis of GNAS confirmed the diagnosis of PHP Ia in both patients and the child's early diagnosis was possible. Moreover, this novel missense substitution expands the spectrum of GNAS mutations associated with this disorder and allows for genetic counseling of this family.O objetivo deste estudo foi descrever uma nova mutação no GNAS em uma família com pseudo-hipoparatireoidismo tipo Ia (PHP Ia), doença osteometabólica rara. Um garoto de oito meses foi visto por um endocrinologista por obesidade e baixa velocidade de crescimento. Chamava a atenção o fato de sua mãe apresentar fenótipo típico da osteodistrofia hereditária de Albright (OHA). O diagnóstico clínico de PHP Ia foi suspeitado. A região codificadora do GNAS da mãe e do filho foi amplificada e submetida ao sequenciamento direto. Uma nova mutação missense em heterozigose (c.673T>C) foi identificada no éxon 5 em ambos. O quadro clínico materno foi a pista para o diagnóstico do filho. A análise molecular do GNAS confirmou o diagnóstico de PHP Ia nos dois pacientes possibilitando o diagnóstico precoce da criança. Além disso, essa nova substituição missense expande o espectro de mutações no GNAS associadas a essa doen­ça e permite o aconselhamento genético nesta família

Mutation analysis of NANOS3 in Brazilian women with primary ovarian failure

OBJECTIVES: Primary ovarian failure is a rare disorder, and approximately 90% of cases are of unknown etiology. The aim of this study was to search for mutations in NANOS3, a gene that was recently related to the etiology of primary ovarian failure, in a group of Brazilian women. METHODS: We screened for NANOS3 DNA variants in 30 consecutive women who were previously diagnosed with primary ovarian failure, of unknown etiology and compared the results with those from 185 women with normal fertility. The NANOS3 gene was amplified by polymerase chain reaction using pairs of specific primers and then sequenced. The resulting sequences were compared with control sequences available in the National Center for Biotechnology and Information database. RESULTS: No mutations in NANOS3 were found in primary ovarian failure patients, but four previously described polymorphisms were identified at a similar frequency in the control and primary ovarian failure groups. CONCLUSIONS: Mutations in NANOS3 were not associated with primary ovarian failure in the present cohort

An activating mutation in the CRHR1 gene is rarely associated with pituitary-dependent hyperadrenocorticism in poodles

OBJECTIVES: Pituitary-dependent hyperadrenocorticism is the most common cause of naturally occurring hypercortisolism in dogs. CRHR1 expression in human and dog corticotrophinomas suggested that this gene affects pituitary tumorigenesis. The present study aimed to investigate mutations in the CRHR1 coding region in poodles with pituitary-dependent hyperadrenocorticism. METHODS: Fifty poodles with pituitary-dependent hyperadrenocorticism and 50 healthy poodles were studied. Genomic DNA was amplified by PCR and analyzed by Sanger sequencing. RESULTS: The novel CRHR1 p.V97M mutation was identified in one dog. This valine residue, located in the amino-terminal extracellular domain, exhibits high affinity for its corticotropin-releasing hormone (CRH) ligand. Bioinformatic analysis revealed structural rearrangements in the mutant protein, with a 17% increase in the surface binding affinity between CRHR1 and CRH. In vitro functional studies showed that mutant CRHR1 induced higher ACTH secretion than the wild type after stimulation with human CRH. CONCLUSION: These results suggest that germline activating mutations in CRHR1 may be a rare cause of pituitary hyperadrenocorticism in poodles

Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease

OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype