ISSN: 1301-2193 E-ISSN: 1308-9846
  • Turkish Journal of
    Endocrinology and Metabolism


17-alpha hydroxylase (17OHD) deficiency is an uncommon cause of congenital adrenal hyperplasia (CAH) resulting from mutation in the CYP17 gene (1). The gene is expressed in the adrenal gland and gonads. 17OHD catalyzes two successive reactions: 17α hydroxylation of pregnenolone and progesterone, and 17,20-lyase reaction of the 17α-hydroxylated products (2). 17OHD is an autosomal recessive disease leading to the deficiency of enzyme activity which results in impaired synthesis of cortisol, androgen and sex steroids. Additionally, it results in an elevation of ACTH secretion and consequent overproduction of mineralocorticoids. The disease is characterized by hypertension, hypokalemic alkalosis and deficient secondary sexual characteristics; with primary amenorrhea in females and 46 XY disorder of sex development (DSD) in males as distinctive clinical features (3). Features of DSD in males may be small phallus, cryptorchidism, pseudovaginal pouch, and perineal hypospadias. It was first described in 1966 (4), and to date, nearly 150 cases of 17OHD have been reported (5). Herein, we present a female patient with both clinical and hormonal characteristics of 17OHD who has been treated inadequately before the current diagnosis. Our aim is sharing our experiences about this very rare disease.

Case Report

A 35-year-old woman was referred to Erciyes University Medical School, Department of Endocrinology because of persisting hypokalemia, weakness, and fatigue. She reported neither spontaneous menarche nor pubarche in her medical history. Her puberty was induced by using oral contraceptive agents. She had used oral contraceptive agents regularly until her demand of pregnancy. She was admitted to an infertility clinic in another hospital when she was 25 years old. Her medical history showed that in vitro fertilization (IVF) was tried twice but no pregnancy was achieved. At that time, she had hypertension with hypokalemia. However, no further examination was performed for the etiology of hypokalemia and hypertension in this young woman. Briefly, she had primary amenorrhea, mild polyuria, hypokalemia, infertility, and hypertension. Physical examination revealed blood pressure of 150/100 mmHg, body mass index of 24 kg/m2, breast development tanner II, and atrophic cervix.

On laboratory evaluation, she had hypokalemia, diabetes mellitus, primary adrenal insufficiency, hypergonadotropic hypogonadism, and increased levels of 11-deoxycorticosterone, progesterone, and sodium (Table 1). Serum progesterone being the immediate proximal hormone, prior to 17-hydroxy progesterone was elevated confirming the diagnosis of 17OHD. The computed tomography of the adrenal glands revealed bilateral adrenal thickening (Figure 1). Her karyotype was 46XX. The clinical and laboratory findings in addition to adrenal enlargement raised the possibility of 17OHD. Hormonal investigations were compatible with 17OHD and genotyping showed homozygous p.P409L (c.1226 C>T) mutation located in exon 7 which abolishes both 17OHD and 17,20 lyase activities of CYP17A1 protein (6).

After starting dexamethasone 0.5 mg/day, her potassium level normalized, and blood pressure became normal. In addition, metformin (2000 mg/day) was given for the treatment of diabetes mellitus.


17OHD is a rare autosomal recessive form of CAH. It accounts for approximately 1% of all cases with CAH (7). It results in decreased androgens, cortisol, estrogen whilst increased ACTH, FSH, LH levels (3,8). The cortisol levels in patients without treatment are low, but they do not have severe symptoms of cortisol deficiency, because corticosterone has glucocorticoid activity. Thus, our patient did not present with symptoms of cortisol deficiency. Patients with 17OHD usually present with hypertension, hypokalemia and delayed puberty and, our patient had all of them. She had severe hypokalemia, hypertension and infertility. 17OHD activity is normally present in either adrenals or gonads (9), and therefore, most patients are hypertensive and hypogonadal (10).

Both primary renal disorders and endocrine disorders (apparent mineralocorticoid excess syndrome and other uncommon forms of congenital adrenal hyperplasia) may cause hypokalemia, hypertension and infertility (11). Therefore, differential diagnosis for such a patient has to be made carefully by laboratory and imaging studies.

Glucocorticoid therapy is essential for the amelioration of hypertension, hypokalemia and mild adrenal insufficiency (8). However, in women, fertility is generally difficult, because egg maturation and ovulation are not sufficiently supported by the steroid production of ovaries.
Due to the low incidence of adrenal crisis and other severe symptoms in untreated 17OHD, the diagnosis often delays. Recognition of 17OHD is difficult even after puberty, therefore, inappropriate managements are frequently encountered. For instance, IVF in the presented case is not a logical treatment option for pregnancy. Deficiency of 17-OH enzyme is caused by mutation of the CYP17 gene. More than 50 mutations have been reported so far (12,13). Recent studies showed that cytosine to guanin transition in exon 7 can cause a substitution of the amino acids, proline and arginine (12). We also found a mutation in exon 7 in our case which may let us think that amino acid 409 is prone to be mutated.

In conclusion, this case report emphasizes that CAH due to 17OHD should be considered in adult hypertensive female patients with sexual infantilism, primary amenorrhea, hypokalemia as well as male patients with ambiguous or feminine external genitalia. Importantly, before using expensive assisted reproduction techniques, such as IVF in an amenorrheic woman, a clinical, hormonal and eventually molecular evaluation should be performed to establish the correct diagnosis.

Conflicts of Interest

There are no conflicts of interest.


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