17α-HYDROXYLASE DEFICIENCY IS AN UNDERDIAGNOSED DISEASE: HIGH FREQUENCY OF MISDIAGNOSES IN A LARGE COHORT OF BRAZILIAN PATIENTS.

OBJECTIVE: 17α-Hydroxylase deficiency (P450c17D) is characterized by hypogonadism and mineralocorticoid hypertension. We aimed to estimate the relative incidence and spectrum of preliminary misdiagnoses in Brazilian P450c17D patients.

METHODS: In this cross-sectional study, we reviewed, updated, and analyzed data of 40 P450c17D patients (21 XY, 19 XX).

RESULTS: Complete data were unavailable for 2 patients. Seven patients were relatives of an index case. Of the 31 index cases, 29 (94%) received a total of 16 misdiagnoses (1-4 per patient) before confirmation of P450c17D. Essential hypertension (55%), pure gonadal dysgenesis (35%), and androgen resistance syndrome (21%) were the most frequent misdiagnoses. Median ages at initial and final diagnosis were 13.2 and 16.5 years, respectively, with an average interval to diagnosis of 3.2 years. Initially, 38 (95%) patients had hypertension, and 75% had hypokalemia. Primary amenorrhea and sexual infantilism were present in 95% patients, and 73% were at Tanner stage I. All had low-to-undetectable estrogens and androgens with elevated gonadotropins and progesterone (580 ± 53 ng/dL). Several had recurrent infections in childhood and neurological issues prior to final diagnosis and/or had siblings who died of infectious diseases or unknown causes before puberty.

CONCLUSION: The high percentage of prior misdiagnoses in P450c17D patients may be attributable to the rarity of and relative unfamiliarity with the disease, its varied clinical presentation, and the limited access to critical steroid dosages and genotyping. Reduced sex steroids, and elevated gonadotropins and progesterone levels, in addition to mineralocorticoid hypertension, are pathognomonic of P450c17D. CYP17A1 gene mutations provide a definitive diagnosis.

ABBREVIATIONS: ACTH = adrenocorticotropic hormone CAH = congenital adrenal hyperplasia CYP17A1 = 17α-hydroxylase enzyme DOC = deoxycorticosterone HH = hypergonadotropic hypogonadism P450c17D = 17α-hydroxylase deficiency TS = Tanner stage.