RESUMO
Adrenal hypoplasia congenita, attributed to NR0B1 pathogenic variants, accounts for more than 50% of the incidence of primary adrenal insufficiency in children. Although more than 250 different deleterious variations have been described, no genotype-phenotype correlation has been defined to date. We report a case of an adopted boy who reported the onset of an adrenal crisis at 2 weeks of age, requiring replacement therapy with mineralocorticoids and glucocorticoids for 4 months. For 3 years, he did well without treatment. At almost 4 years of age, the disorder was restarted. A long follow-up showed the evolution of hypogonadotropic hypogonadism. Molecular studies on NR0B1 revealed a novel and deleterious deletion-insertion-inversion-deletion complex rearrangement sorted in the 5'-3' direction, which is described as follows: (1) deletion of the intergenic region (between TASL and NR0B1 genes) and 5' region, (2) insertion of a sequence containing 37 bp at the junction of the intergenic region of the TASL gene and a part of exon 1 of the NR0B1 gene, (3) inversion of a part of exon 1, (4) deletion of the final portion of exon 1 and exon 2 and beginning of the 3'UTR region, (5) maintenance of part of the intergenic sequence (between genes MAGEB1 and NR0B1, telomeric sense), (6) large posterior deletion, in the same sense. The path to molecular diagnosis was challenging and involved several molecular biology techniques. Evaluating the breakpoints in our patient, we assumed that it was a nonrecurrent rearrangement that had not yet been described. It may involve a repair mechanism known as nonhomologous end-joining (NHEJ), which joins two ends of DNA in an imprecise manner, generating an "information scar," represented herein by the 37 bp insertion. In addition, the local Xp21 chromosome architecture with sequences capable of modifying the DNA structure could impact the formation of complex rearrangements.
Assuntos
Insuficiência Adrenal , Receptor Nuclear Órfão DAX-1 , Pré-Escolar , Humanos , Masculino , Insuficiência Adrenal/genética , Insuficiência Adrenal/patologia , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/congênito , Receptor Nuclear Órfão DAX-1/genética , Seguimentos , Estudos de Associação Genética/métodos , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Hipoadrenocorticismo Familiar/genética , Mutação/genética , Fenótipo , Recém-Nascido , AdolescenteRESUMO
PURPOSE: To investigate the accuracy of cutoff values of the morning serum cortisol (MSC) using the cortisol stimulus test (CST) insulin tolerance test (ITT) and 250 mcg short Synacthen test (SST) as the reference standard tests, to better define its clinical role as a tool in the diagnostic investigation of adrenal insufficiency (AI) AI. METHODS: An observational study was conducted with a retrospective analysis of MSC in adult patients who had been submitted to a CST to investigate AI between January 2014 and December 2020. The normal cortisol response (NR) to stimulation was defined based on the cortisol assay. RESULTS: 371 patients underwent CST for suspected AI, 121/371 patients (32.6%) were diagnosed with AI. ROC curve analysis showed an area under the curve (AUC) for MSC of 0.75 (95% CI 0.69 - 0.80). The best MSC cutoff values to confirm AI were < 3.65, < 2.35 and < 1.5 mcg/dL with specificity of 98%, 99%, and 100%, respectively. MSC > 12.35, > 14.2 and > 14.5 mcg/dL had sensitivity of 98%, 99%, and 100%, respectively, being the best cutoff values to exclude AI. Almost 25% of patients undergoing CST for possible AI had MSC values between < 3.65 mcg/dL (6.7% of patients) and > 12.35 mcg/dL (17.5% of patients), making the formal CST testing unnecessary if we consider these cutoff values. CONCLUSION: With the most modern cortisol assays, MSC could be used as a diagnostic tool, with high accuracy to confirm or exclude AI, avoiding unnecessary CST; thus, reducing expenses and safety risks during AI investigation.
Assuntos
Insuficiência Adrenal , Hidrocortisona , Adulto , Humanos , Estudos Retrospectivos , Insuficiência Adrenal/diagnóstico , Curva ROC , Fatores de TempoRESUMO
Paracoccidioidomycosis is caused by a fungus (Paracoccidioides brasiliensis), which is endemic to Brazil. It is most frequently found in the lungs, with haematogenous and lymphatic spread. The condition is more prevalent in men, between 30 and 60 years old, commonly rural workers. It is the third leading cause of death among chronic infectious diseases today. The systemic disease has an insidious and nonspecific course, with adrenal involvement being observed in 5% of cases and requiring the destruction of 80% of the glands for symptoms of adrenal insufficiency to appear. Isolated involvement of this gland is quite rare. In this case report, however, our patient presented wasting and adrenal insufficiency with isolated adrenal involvement by the fungus.
Assuntos
Insuficiência Adrenal , Paracoccidioidomicose , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Paracoccidioidomicose/diagnóstico , Paracoccidioidomicose/tratamento farmacológico , Paracoccidioidomicose/epidemiologia , Pulmão , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/tratamento farmacológico , Síndrome , BrasilRESUMO
X-linked adrenal hypoplasia congenita is a rare cause of primary adrenal insufficiency. Mutations in the NR0B1 gene cause a loss of function in the DAX1 receptor, which activates genes involved in the development and function of the hypothalamic-pituitary-gonadal axis. Objective: To describe a case of adrenal hypoplasia congenita secondary to a mutation in the NR0B1 gene and identified the differential diagnoses of the pediatric patient with adrenal insufficiency and hypogonadotropic hypogonadism. Clinical Case: A 4-year-old male patient with no relevant history and from a rural area was admitted to the emergency room due to a 15-days of emesis, asthenia, adynamia, myalgia, and ataxic gait. On the physical examination, hypotension, hyponatremia, and hyperkalemia, as well as mucosal hyperpigmentation and bilateral cryptorchidism were observed, therefore, adrenal crisis was diagnosed, starting fluid resuscitation with saline solution, hydrocortisone, and fludrocortisone, which stabilized the patient. Adrenal hyperplasia congenita, innate metabolic error, and infectious or autoimmune etiology were ruled out as etiology. A clinical exome test was performed which iden tified the variant c.1275A > T; p.Arg425Ser (Transcript ENST00000378970.5) in the NR0B1 gene consistent with X-linked adrenal hypoplasia congenita. Management of the patient continued with glucocorticoids and mineralocorticoids with favorable clinical course at 7 years of follow-up. Con clusion: A novel pathogenic variant associated with X-linked adrenal hypoplasia is described. Variants in the NR0B1 gene should be a differential diagnosis in a male patient with the association of primary adrenal insufficiency and hypogonadism.
Assuntos
Doença de Addison , Insuficiência Adrenal , Doenças Genéticas Ligadas ao Cromossomo X , Pré-Escolar , Humanos , Masculino , Doença de Addison/diagnóstico , Doença de Addison/genética , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/genética , Insuficiência Adrenal/congênito , Receptor Nuclear Órfão DAX-1/genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Hipoadrenocorticismo Familiar/genética , MutaçãoRESUMO
Allgrove syndrome is an autosomal recessive disease mostly caused by mutations in the AAAS gene. It has variable clinical features but its cardinal features comprise the triad of achalasia, alacrimia and adrenal insufficiency. It typically develops during the first decade of life, but some cases have second and third decades onset. We describe a 25-year-old woman with Allgrove syndrome who had progressive amyotrophy, achalasia, dry eyes and adrenal insufficiency since childhood. Awareness of its neurological manifestations and multisystem features helps to shorten the time for diagnosis and allow appropriate symptomatic treatment.