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.