Elabd Souha, Almohareb Ohoud, AlJaroudi Dania, Al Zahrani Ali, Brema Imad
Obesity, Endocrine, and Metabolism Center, King Fahad Medical City, Riyadh, SAU.
Department of Reproductive Endocrine and Infertility Medicine, King Fahad Medical City, Riyadh, SAU.
Cureus. 2024 Jan 12;16(1):e52191. doi: 10.7759/cureus.52191. eCollection 2024 Jan.
Congenital adrenal hyperplasia (CAH) consists of variable disorders of sex determination and differentiation. 17α-hydroxylase deficiency (17OHD) is an uncommon form of those disorders, which is typically characterized by hypertension, hypokalemia, failure of puberty, and ambiguous genitalia. The 17α-hydroxylase enzyme is encoded by the CYP17A1 gene and it is required for the synthesis of cortisol and sex steroids. The affected females with 17OHD usually present with primary amenorrhea and delayed puberty, which are associated with hypertension and hypokalemia while male patients might show female external genitalia, pseudohermaphroditism, or variable degrees of ambiguous genitalia with intra-abdominal testes in addition to hypertension and hypokalemia as well. We present two Saudi siblings (19 and 16 years old) who were diagnosed with the rare CAH subtype of 17OHD after presenting with long-standing hypertension, refractory hypokalemia, and failure of puberty. It is interesting that both siblings had biochemical primary adrenal insufficiency; however, both patients did not clinically present with an acute adrenal crisis, which is likely due to the effect of increased levels of deoxycorticosterone. Additionally, although both patients have similar phenotypes and clinical presentations, they have different karyotypes. This again highlights the variability of the manifestations that can result from 17OHD even with an identical mutation in the same family. Both patients were treated successfully with dexamethasone, which has led to the normalization of hypertension, resolution of hypokalemia, and discontinuation of anti-hypertensive medications and potassium supplements after several years of treatment. However, the entire management is quite challenging and requires a multidisciplinary approach regarding difficult issues such as gender identity and assignment and fertility issues in addition to a life-long follow-up.
先天性肾上腺增生（CAH）包括多种性发育和分化障碍疾病。17α-羟化酶缺乏症（17OHD）是这些疾病中一种不常见的类型，其典型特征为高血压、低钾血症、青春期发育迟缓以及生殖器模糊不清。17α-羟化酶由CYP17A1基因编码，是合成皮质醇和性类固醇所必需的。患有17OHD的女性通常表现为原发性闭经和青春期发育延迟，同时伴有高血压和低钾血症，而男性患者除高血压和低钾血症外，可能表现为女性外生殖器、假两性畸形或不同程度的生殖器模糊不清以及腹腔内睾丸。我们报告了两名沙特兄弟姐妹（分别为19岁和16岁），他们在出现长期高血压、难治性低钾血症和青春期发育迟缓后，被诊断为罕见的17OHD型CAH亚型。有趣的是，这两名兄弟姐妹均有生化性原发性肾上腺功能不全；然而，两名患者临床上均未出现急性肾上腺危象，这可能是由于脱氧皮质酮水平升高的影响。此外，尽管两名患者具有相似的表型和临床表现，但他们的核型不同。这再次凸显了即使在同一家族中存在相同突变，17OHD仍可导致表现形式的变异性。两名患者均用地塞米松成功治疗，经过数年治疗后，高血压恢复正常，低钾血症得到缓解，抗高血压药物和钾补充剂停用。然而，整个管理颇具挑战性，除了终身随访外，还需要针对性别认同和分配以及生育问题等难题采取多学科方法。
