Vitamin D Status in Healthy Omani Women of Childbearing Age : Study of female staff at the Royal Hospital, Muscat, Oman

Objectives: 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. Methods: 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 analysed for serum 25(OH)D, calcium, phosphate, alkaline phosphatise and parathyroid hormone levels. Results: 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). Conclusion: 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

Are Tubes Containing Sodium Fluoride Still Needed for the Measurement of Blood Glucose in Hospital Laboratory Practice?

Objectives: To compare glucose values obtained using sodium flouride (NaF) tubes and serum separation tubes (SST) in a tertiary care hospital laboratory setting.  Methods: This study was conducted at the Clinical Biochemistry Laboratory, Royal Hospital, Oman. During the study period (1 September–30 November 2013), 50 pairs (one NaF tube and one SST) of patient’s blood specimens were randomly collected. Following separation of plasma (NaF tubes) and serum (SST), glucose concentrations were measured by hexokinase assay using the Architect c8000. Fifteen pairs of these tubes were kept in the refrigerator at 4°C and plasma/serum glucose concentrations were measured daily up to seven days after collection.  Results: Comparing plasma (NaF) and serum (SST) results of glucose values (n=50) showed an average difference of 0.00mmol/L (range -0.60 to +0.60mmol/L). Bland Altman analysis gave a non-significant constant bias of 0.10 ±0.195mmol/L (bias ±SD). Pearson correlation between plasma (NaF) and serum (SST) glucose concentrations revealed a significant correlation approaching unity with r2= 0.9991. No significant differences in glucose values were noted for both plasma and serum in 15 pairs of NaF and SST tubes when analyzed seven days following refrigeration. Hemolysis was observed in five (10%) NaF tubes compared with two (4%) SST.  Conclusion: There is no difference in glucose values collected from plasma NaF tubes or serum SST, and so SST can be used in hospital laboratory settings as there are practical advantages, including cost-effectiveness and reduction in blood volume drawn when utilizing these tubes for glucose and other tests from a single blood collection tube

Validity of Serum Testosterone, Free Androgen Index, and Calculated Free Testosterone in Women with Suspected Hyperandrogenism

Objectives: There are technical limitations for the currently available methods of measuring serum total and free testosteronein 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.Methods: This is a case control study that was conducted during the period from 1st May 2011 to 31st 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.Results: 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 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.Conclusion: 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

Validity of Cancer Antigen-125 (CA-125) and Risk of Malignancy Index (RMI) in the Diagnosis of Ovarian Cancer

Objective: We sought to determine the validity of cancer antigen 125 (CA-125) and the risk of malignancy index (RMI) in the diagnosis of ovarian cancer in women presenting with adnexal lesions of various histopathology types. Methods: This retrospective cross- sectional study included all women with adnexal lesions who were evaluated at the Royal Hospital, Oman, between January 2012 and December 2014. The inclusion criteria included women who underwent surgical intervention and who had preoperative CA-125 testing and pelvic ultrasound in the work-up plan of their management. The surgical intervention was usually followed by a histopathological diagnosis of the nature of the lesion, which was used as the gold standard for the evaluation of both CA-125 and RMI. Results: The cohort included 361 women who had serum CA-125 and pelvic ultrasound prior to the surgical intervention of the adnexal lesion. Of these women, 61 (17%) had malignant ovarian lesions. Using the proposed cut-off 35 U/ml for CA-125 and 200 for RMI, the CA-125 test was more sensitive for detecting the majority of malignant ovarian tumors compared to the RMI (69% vs. 57%). Both tests were more sensitive in detecting epithelial ovarian cancer compared to other ovarian cancers. However, RMI was more specific in excluding benign ovarian lesions compared to CA-125 (81% vs. 68%). Additionally, RMI had a better area under the curve compared to CA-125 (0.771 vs. 0.745; p<0.005). Lowering the RMI cut-off to 150 resulted in a better sensitivity (62% vs. 57%) and had an acceptable specificity (78% vs. 81%) compared to a cut-off of 200. Conclusion: Both CA-125 and RMI have good validity in the diagnosis of ovarian tumors. CA-125 has higher sensitivity; however, RMI has higher specificity. In combination, CA-125 might be more valid for the diagnosis of malignant ovarian cancer while RMI is more valid for excluding the diagnosis of these tumors. Differential use of these two tools will improve the triage of women with suspected ovarian tumors since both are measured in their work-up. We recommended the use of both tools in primary care to reduce referral to gynecology or oncology units

A Novel Mutation Causing 17-β-Hydroxysteroid Dehydrogenase Type 3 Deficiency in an Omani Child: First Case Report and Review of Literature

This is the first case report in Oman and the Gulf region of a 17-β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-β-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections (25mg once monthly) were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia (stage 4). Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections (50mg once monthly for six months) were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene (NM_000197.1:c.576G>A.Trp192*). This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this disorder

Evaluation of HE4, CA-125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) in the Preoperative Assessment of Patients with Adnexal Mass

Objectives: To evaluate the validity and compare the performance of cancer antigen-125 (CA-125), human epididymis protein 4 (HE4), the risk of malignancy index (RMI), and the risk of ovarian malignancy algorithm (ROMA) in the diagnosis of ovarian cancer in patients with ovarian lesions discovered during their preoperative work-up investigations. Methods: This prospective, cross-sectional study looked at patients who attended the gynecology department at the Royal Hospital, Muscat, from 1 March 2014 to 30 April 2015, for the evaluation of an ovarian lesion. The inclusion criteria included women who underwent surgical intervention and who had a preoperative pelvic ultrasound with laboratory investigation for CA-125 and HE4. The study validated the diagnostic performance of CA-125, RMI, HE4, and ROMA using histopathological diagnosis as the gold standard. Results: The study population had a total of 213 cases of various types of benign (77%) and malignant (23%) ovarian tumors. CA-125 showed the highest sensitivity (79%) when looking at the total patient population. When divided by age, the sensitivity was 67% in premenopausal women. In postmenopausal women, CA-125 had lower sensitivity (89%) compared to RMI, HE4, and ROMA (93% each). A high specificity of 90% was found for HE4 in the total patient population, 93% in premenopausal women and 75% in postmenopausal women. CA-125 had the highest specificity (79%) in postmenopausal women. Both CA-125 and RMI were frequently elevated in benign gynecological conditions particularly in endometriosis when compared to HE4 and ROMA. We also studied modifications of the optimal cut-offs for the four parameters. Both CA-125 and RMI showed a significant increase in their specificity if the cut-off was increased to ≥ 60 U/mL for CA-125 and to ≥ 250 for RMI. For HE4, we noted an improvement in its specificity in postmenopausal women when its cut-off was increased to140 pmol/L. Conclusions: HE4 and ROMA showed a very high specificity, but were less sensitive than CA-125 and RMI in premenopausal women. However, they were of comparable sensitivity in postmenopausal women and were valuable in distinguishing benign ovarian tumors or endometriosis from ovarian cancer. Modifying the cut-off values of the different markers resulted in a higher accuracy compared to the standard cut-offs, but at the expense of reduced sensitivity

Congenital Adrenal Hyperplasia due to 17-alpha-hydoxylase/17,20-lyase Deficiency Presenting with Hypertension and Pseudohermaphroditism: First Case Report from Oman

Abstract This is the first report of congenital adrenal hyperplasia (CAH) due to combined 17α-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 17α-hydroxylase deficiency. Extensive laboratory workup revealed low levels of serum cortisol (and its precursors 17α-hydroxyprogesterone and 11-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 CYP17A1-homozygous mutation (c.287G&gt;A p.Arg96Gln) resulting in the complete absence of 17α-hydroxylase/17,20-lyase activity. The patient was treated with dexamethasone and ethinyl estradiol with cessation of antihypertensive 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 17α-hydroxylase/17,20-lyase deficiency in Oman and in the Arab World described in the literature

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 17α-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 17α-hydroxylase deficiency. Extensive laboratory workup revealed low levels of serum cortisol (and its precursors 17α-hydroxyprogesterone and 11-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 CYP17A1-homozygous mutation (c.287G>A p.Arg96Gln) resulting in the complete absence of 17α-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 17α-hydroxylase/17,20-lyase deficiency in Oman and in the Arab World described in the literature

A Rare Case of Adrenal Pheochromocytoma with Unusual Clinical and Biochemical Presentation: A Case Report and Literature Review

A 50-year-old Omani woman presented to the Outpatient Clinic, Royal Hospital, Oman with right upper abdominal pain and backache that had lasted 10 days. She had no palpitation, sweating, or hypertension (blood pressure 122/78mmHg). The patient’s history revealed that she had a similar incidence of abdominal pain two months prior, which was a "dull ache" in nature and somewhat associated with headache. The pain was relieved using a mild analgesic drug. Abdominal ultrasonography showed a right adrenal mass, and both computed tomography and magnetic resonance imaging of the adrenal glands confirmed a right adrenal mass consistent with adrenal pheochromocytoma. However, clinical biochemistry tests revealed normal levels of plasma catecholamines (dopamine, norepinephrine, and epinephrine) and metanephrine, which are unusual findings in adrenal pheochromocytoma. Meanwhile, the patient had markedly raised plasma normetanephrine (10-fold) which, together with the normal metanephrine, constitutes a metabolic profile that is compatible with extra-adrenal pheochromocytoma. The patient also had markedly raised chromogranin A (16-fold), consistent with the presence of a neuroendocrine tumor. Laparoscopic right adrenalectomy was done and the adrenal tumor was excised and retrieved in total. Histopathology and immunohistochemistry confirmed the diagnosis of adrenal pheochromocytoma; the tumor cells being positive for chromogranin, synaptophysin, and S-100 protein. Following surgery, the patient did well and showed full recovery at follow-up after three months. Molecular genetic testing showed no pathogenic mutation in pheochromocytoma genes: MAX, SDHA, SDHAF2, SDHB, SDHC, SDHD, VHL, and PRKAR1A. A review of the literature was conducted to identify the pathophysiology and any previous reports of such case. To our knowledge, this is the first report in Oman of the extremely rare entity of pheochromocytoma with an unusual clinical and biochemical scenario