Deficiência combinada de 17α-hidroxilase/17,20 liase devido à mutação p.R96W no gene CYP17 em um paciente brasileiro

Congenital adrenal hyperplasia (CAH) resulting from 17α-hydroxylase/17,20-lyase deficiency is a rare autosomal recessive disease and the second most common form of CAH in Brazil. We describe the case of a Brazilian patient with CYP17 deficiency (17α-hydroxylase/17,20-lyase deficiency) caused by a homozygous p.R96W mutation on exon 1 of the CYP17 gene, an unusual genotype in Brazilian patients with this form of CAH. The patient, raised as a normal female, sought medical care for lack of pubertal signs and primary amenorrhea at the age of 16 years. At evaluation, the presence of a 46,XY karyotype, hypertension and hypokalemia were observed. We emphasize the recognition of CYP17 deficiency in the differential diagnosis of cases of hypergonadotrophic hypogonadism and hypertension in young patients who need specific treatment for both situations.A hiperplasia adrenal congênita (HAC), em razão da deficiência de 17α-hidroxilase/17,20-liase, é uma doença autossômica recessiva rara e a segunda causa mais comum de HAC no Brasil. Descrevemos o caso de um paciente brasileiro portador da deficiência 17α-hidroxilase/17,20- liase (CYP17) em homozigose para a mutação p.R96W no éxon 1 do gene da CYP17A1, uma mutação incomum entre os casos brasileiros descritos com essa forma de HAC. Esse paciente, criado como um indivíduo normal do sexo feminino, procurou atendimento por ausência de sinais puberais e amenorreia primária aos 16 anos de idade. Durante a avaliação, constataram-se um cariótipo 46,XY e a presença de hipertensão e hipocalemia. Enfatizamos o reconhecimento da deficiência da CYP17 dentre os possíveis diagnósticos em um paciente jovem com hipogonadismo hipergonadotrófico e hipertensão, os quais necessitam de tratamento particularizado para ambas as situações.Universidade Federal do Rio Grande do Sul Hospital de Clínicas de Porto AlegreUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of MedicineUniversity of Texas Southwestern Medical Center Department of Internal MedicineUNIFESP, EPM, Department of MedicineSciEL

Enhancing Cushing’s disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS

IntroductionThe differential diagnosis between Cushing’s disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available.ObjectiveThis retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS), applying different cutoff values.MethodsA total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy.ResultsUsing the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance.DiscussionACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing’s syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS