Congenital adrenal hyperplasia due to 17-alpha-hydoxylase/17, 20-lyase deficiency presenting with hypertension and pseudohermaphroditism: first case report from Oman

This is the first report of congenital adrenal hyperplasia [CAH] due to combined 17 alpha-hydroxylase/17, 20 lyase deficiency in an Omani patient who was initially treated for many years as a case of hypertension. CAH is an uncommon disorder that results from a defect in steroid hormones biosynthesis in the adrenal cortex. The clinical presentation depends on the site of enzymatic mutations and the types of accumulated steroid precursors. A 22-year-old woman who was diagnosed to have hypertension since the age of 10 years who was treated with anti-hypertensive therapy was referred to the National Diabetes and Endocrine Centre, Royal Hospital, Oman. The patient also had primary amenorrhea and features of sexual infantilism. Full laboratory and radio-imaging investigations were done. Adrenal steroids, pituitary function and karyotyping study were performed and the diagnosis was confirmed by molecular mutation study. Laboratory investigations revealed adrenal steroids and pituitary hormones profile in addition to 46XY karyotype that are consistent with the diagnosis of CAH due to 17 alpha-hydroxylase deficiency. Extensive laboratory workup revealed low levels of serum cortisol [and its precursors 17 alpha-hydroxyprogesterone and ll'deoxycortisol], adrenal androgens [dehydroepiandrosterone sulfate and androstenedione], and estrogen [estradiol]; and high levels of mineralocorticoids precursors [11-deoxycorticosterone and corticosterone] with high levels of ACTH, FSH and LH. Mutation analysis revealed CYP17Al-homozygous mutation [c.287G>A p.Arg96Gln] resulting in the complete absence of 17 alpha-hydroxylase/17, 20-lyase activity. The patient was treated with dexamethasone and ethinyl estradiol with cessation of anti-hypertensive therapy. A review of the literature was conducted to identify previous studies related to this subtype of CAH. This is the first biochemically and genetically proven case of CAH due to 17 alpha-hydroxylase/17, 20-lyase deficiency in Oman and in the Arab World described in the literature

Validity of serum testosterone, free androgen index, and calculated free testosterone in women with suspected hyperandrogenism

There are technical limitations for the currently available methods of measuring serum total and free testosterone in females. The study objectives were to evaluate the usefulness of serum total testosterone, sex hormone-binding globulin [SHBG], free androgen index [FAI], and calculated free testosterone [CFT] in the assessment of androgen status in women investigated for suspected hyperandrogenism. This is a case control study that was conducted during the period from 1[st] May 2011 to 31[st] October 2011 on 122 patients aged [18-45 years] whom were referred to the Clinical Biochemistry Laboratory from the Endocrinology and Gynecology Clinics, Royal Hospital, Oman. Women with no clinical feature or laboratory data indicative of hormonal dysfunction and with midluteal progesterone >30 nmol/L were selected as controls [group 1; n=18]. The patients were divided into subgroups based on the clinical/laboratory diagnosis of polycystic ovary syndrome [PCOS [group 2; n=19], hirsutism [group 3; n=18], menstrual disturbances [irregularities] or infertility [group 4; n=49], as well as combination of PCOS or hirsutism and menstrual disturbances or infertility [group 5;n=18]. Serum total testosterone and SHBG were measured, FAI was calculated as percentage ratio of total testosterone to SHBG values, and CFT was calculated according to Vermeulen equation. There was a statistically significant difference in the mean levels of testosterone, FAI and CFT in each patient group compared with the control group. For diagnosing hyperandrogenism, each indicator was selected at the recommended cut-off: testosterone >3.0 nmol/L, SHBG <30 nmol/L, FAI >5%, and CFT >32 pmol/L. In group 2, 89.5% and 94.7% of the patients had increased FAI and CFT, respectively; compared with 36.4% for increased testosterone. In group 3, 88.9% and 88.9% of the patients had similarly increased FAI and CFT, respectively; compared with 66.7% for testosterone. In group 4, patients had 63.3% and 73.5% elevated FAI and CFT, respectively; compared with 53.1% for testosterone, while in group 5, patients had 83.3% and 88.9% elevated FAI and CFT, respectively, compared with 61.1% for testosterone. The diagnosis of hyperandrogenism was most obvious when using CFT or FAI than testosterone alone. It is thus recommended to include these calculated parameters [CFT and/or FAI] in the routine investigation and assessment of women with disorders related to clinical or biochemical hyperandrogenism

Vitamin D status in healthy Omani women of childbearing age. Study of female staff at the Royal Hospital, Muscat, Oman

Sunlight exposure has a vital role in vitamin D synthesis. Although vitamin D deficiency has been well documented in temperate zones, studies have been scarce in tropical countries where the population is well covered and for various reasons avoids sun exposure. The objective of this study was to investigate serum 25-hydroxyvitamin D [25[OH]D] levels and its relationship to biochemical bone profile, exposure to sunlight and vitamin D intake amongst Omani women of childbearing age. 41 apparently healthy women working at the Royal Hospital, Muscat, Oman and aged 18-45 years, with mean +/- SD of 29 +/- 6 years, were included in this study conducted in December 2006. They completed a questionnaire regarding the duration of sun exposure, food intake and type of clothing worn. Blood samples were collected from them and analyzed for serum 25[OH]D, calcium, phosphate, alkaline phosphatise and parathyroid hormone levels. All the women had a 25[OH]D level <50 nmol/L as the cut-off for deficiency. 25[OH]D levels were strongly correlated with the lack of sun exposure [r = 0.672, P < 0.001] and a significant correlation was also found between 25[OH] D level and food intake [r = 0.482, P < 0.01]. Subclinical 25[OH]D deficiency may be prevalent amongst Omani women. Risk factors such as poor sunlight exposure should be addressed in women of childbearing age and, if increased sunlight exposure is not possible, oral supplementation should be considered to avoid all the consequence and complications of vitamin D deficiency