Discussion
Congenital adrenal hyperplasia (CAH) encompasses different genetic anomalies. 17 OHD represents approximately 1% of all causes of CAH, which is inherited in an autosomal recessive pattern. The lack of this enzyme results in an excess of potent mineralocorticoids such as DOC, which leads to hypertension and hypokalemia. Additionally, 17 OHD causes a deficit in the cortisol production and thus an adrenal insufficiency.Regarding the gonadal sex steroids, 17 OHD precipitates their decrease, and therefore generates a hypergonadotropic hypogonadism[2]. Depending on the severity of the molecular abnormality, various forms of this disease are reported. While the complete enzymatic deficiency results in a severe phenotype with an absence of virilization in 46, XY patients and impuberism in 46, XX, which corresponds to the phenotypic presentation of our patient, the partial form is characterized by a milder clinical manifestation:more frequently encountered normotension, secondary amenorrhea and possible virilization in 46, XYmales [3]. Biochemically 17 OHD ischaracterizedby high levels of DOC, and low levels of DHEAS, androstenedione, 17 OHP and cortisol [2].
The management of 17 OHD is based mainly on the treatment of hypertension, hypokalemia and hypogonadism. The cornerstone treatment is hydrocortisone which enables the reinstitution of the negative feedback on the corticotropic axis and thus diminishes ACTH levels and consequently the production of the excess mineralocorticoids. This helps to control hypertension and hypokalemia. Besides, spironolactone acts both as an antihypertensive agent and a potassium sparing diuretic, is considered a drug of choice in these cases. As for the management of hypogonadism, 46, XY patients with female phenotype can be prescribed with hormonal therapy aiming to prevent osteoporosis, cardiovascular complications of sex steroids deficiency but also to induce secondary sexual characteristics[4]. Furthermore, the presence of the Y material and specifically the TSPY: testis specific protein y linked 1 gene, is incriminating in the development of gonadal malignancies. While gonadectomy is not recommended in 17 OHD patients due to lack of data concerning this subject, a radiological surveillance of the testis seems crucial in order to detect neoplasm[5].
Our case has many peculiarities. First, the late age of diagnosis of 17 OHD. Indeed, most of the 17 OHD cases are diagnosed at puberty, and the primary clinical manifestation of this disorder is usually the abnormal sexual development. Interestingly, patients with 17 OHD never exhibit signs of adrenal crisis. This can be explained mainly by the excess of corticosterone, an agonist hormone of the glucocorticoid receptor. Consequently, this phenomenon helps to clarify the late age of the diagnosis.
Second, the moderate elevation of ACTH level seen in our patient could result from the increasing level of corticosterone which can impact the ACTH secretion and explain the absence of higher levels of this latter hormone in some cases[6].
Another intriguing finding is the skeletal deformations found in our patient which makes our case unique. In fact, no other cases of 17 OHD showed similar features. This leads us to the differential diagnosis: P450 oxidoreductase deficiency. However, the atypical skeletal malformations, the normality of the 17 OHP pleads against this latter diagnosis[7]. Nevertheless, a predominant deficit in 17-alpha hydroxylase over the 21 hydroxylase, seen in some patients of PORD can be consisting with our case.
Regarding the limitations of this study, we recognize that the genetics are a crucial substance for the diagnosis of this disorder as well as the hormonal evaluation of 17 OHP, progesterone, and pregnenolone before and after ACTH stimulation test. Unfortunately, these exams are not available in our hospital.