Effect of dietary status on plasma-fractionated metanephrines in healthy individuals measured by Elisa.

Pheochromocytoma is a rare tumor that typically originates in the adrenal glands, often causing the over-production of catecholamines. The aim of this study was to determine whether dietary status could affect the concentration of plasma-fractionated metanephrines. This study was conducted at the Chemical Pathology Laboratory, Royal Hospital, Oman. Three plasma samples were collected from each participant (16 male and 16 female) over three consecutive days (day one: dietary restriction,day two: excess intake of restricted foods, day three: random sample following the typical diet for each participant). Samples were collected and centrifuged to obtain the plasma, which was then stored at -20°C prior to analysis. Metanephrine and normetanephrine concentrations were measured by comparative ELISA. Plasma metanephrine and normetanephrine measured under the three different dietary conditions for each individual were not significantly different and within normal range. Pearson correlation coefficient analysis of plasma concentration of metanephrines within individual patients under the three dietary conditions revealed positive correlation. We found no significant effect of dietary status on plasma metanephrine or normetanephrine concentration. Therefore, samples taken under any dietary condition may be used to determine plasma MN and NMN concentration. However, dietary restrictions in the diagnosis of Pheochromocytoma need further investigations.

Reference Ranges of Serum Anti-Müllerian Hormone in Healthy Reproductive-aged Omani Women.

Objectives: Anti-Müllerian hormone (AMH), a glycoprotein that belongs to the transforming growth factor-beta superfamily, is important for women's health. We aimed to determine the age-specific reference range of serum AMH in healthy Omani women from reproductive ages to menopause. Methods: This cross-sectional cohort study was conducted among a group of healthy 20-50 years old Omani women. The participants were required to have body mass index < 32 kg/m2, regular periods, no history of chronic illness, polycystic ovary syndrome, or gynecological operation. They were also required to not be using any hormonal contraceptive. Serum concentrations of AMH, follicle-stimulating hormone, luteinizing hormone, progesterone, and hemoglobin A1c were measured. AMH-age nomogram and AMH levels were compared between the six selected age groups. Results: The subjects were 319 Omani women aged 20-50 years. Serum AMH concentrations were found to decrease progressively with increasing age. An exponential model defined as √AMH = 479.02 × 0.91age was selected to explain the reduction in AMH with age (R2 = 0.298). The median AMH levels were 26.61 pmol/L for those aged 20-25 years, 20.89 pmol/L for 26-30 years, 19.92 pmol/L for 31-35 years, 13.71 pmol/L for 36-40 years, 9.24 pmol/L for 41-45 years, and 0.68 pmol/L for 46-50 years. The recommended 2.5th to 97.5th percentiles of AMH level, as reference ranges for various age groups, were found to be: 10.63-55.64 pmol/L (20-25 years), 3.74-61.88 pmol/L (26-30 years), 5.49-47.56 pmol/L (31-35 years), 2.15-48.91 pmol/L (36-40 years), 0.92-41.26 pmol/L (41-45 years), and 0.14-5.10 pmol/L (46-50 years). Conclusions: This study (the first in Oman) determined the age-specific reference ranges of serum AMH in healthy Omani women in the age range of 20-50 years.

Rare NF1 microdeletion syndrome in an Omani patient.

Neurofibromatosis-1 phenotype combined with webbed neck and short stature in a young Omani patient was revealed to be due to a de novo germ-line heterozygous 1.7 Mb microdeletion at 17q11.2. This lead to the diagnosis of NF1 microdeletion syndrome.

Genetic mutations associated with neonatal diabetes mellitus in Omani patients.

BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare disorder worldwide where diabetes is diagnosed in the first 6 months of life. However, Oman has a relatively high incidence of NDM. METHODS: In this study, we investigated the genetic etiologies underlying NDM and their prevalence in Oman. We collected a cohort of 24 NDM patients, with and without genetic diagnosis, referred to our center from 2007 to 2015. All patients without a genetic diagnosis were tested for mutations in 23 NDM-associated genes using a custom-targeted next-generation sequencing (NGS) panel and methylation analysis of the 6q24 locus. RESULTS: A genetic abnormality was detected in 15/24 (62.5%) of our Omani NDM patients. We report the detection of 6q24 methylation abnormalities and KCNJ11 mutations for the first time in Omani NDM patients. Unlike Western populations where NDM is predominantly due to mutations in the KCNJ11, ABCC8 and INS genes, NDM due to homozygous GCK gene mutations were most prevalent in Oman, having been observed in seven out of 15 NDM patients in whom we established the genetic etiology. This reflects the high degree of consanguinity which makes recessive conditions more likely. CONCLUSIONS: The results of this study are likely to impact any future strategy to introduce genetic testing for NDM disorders within the national healthcare system in Oman.

Prevalence of dyslipidemia in the Iraqi adult population.

OBJECTIVE: To establish the prevalence of dyslipidemia in the Iraqi adult population in Mosul, Iraq, according to the different recommended criteria. METHODS: The study was carried out from October 2003 to April 2004, with 871 apparently healthy volunteers (413 males, 458 females) aged 20-70 year ([mean +/- SD] 41.2 +/- 13.8 year). Fasting blood specimens were collected from all subjects for measurement of serum lipid profile including triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), and ratios of cholesterol such as TC:HDL-C, LDL-C:HDL-C, and TG:HDL-C. Classification was carried out according to the different cut-off levels as recommended by the 2001 American National Cholesterol Education Program (NCEP) III using thresholds of TG > or = 150 mg/dl (2.0 mmol/L), LDL-C > or = 100 mg/dl (2.6 mmol/L), HDL-C<40 mg/dl (1.04 mmol/L), and non-HDL-C> or 130 mg/dl (3.37 mmol/L). The criteria of the 1998 British Hyperlipidemia Association (BHA) were also followed using thresholds of TG > or =180 mg/dl (2.4 mmol/L), TC > or 194 mg/dl (5.0 mmol/L), LDL-C > or = 116 mg/dl (3.0 mmol/L), HDL-C< or =45 mg/dl (1.15 mmol/L), TC:HDL-C> or =5.0, HDL-C:DL-C> or =2.5, and TG:HDL-C> or =3.0. RESULTS: Based on the American NCEP III criteria, the dyslipidemic states were noted with high TG (41.6%), high LDL-C (57.8%), low HDL-C (49.9%), and high non-HDL-C (56.8%) from the subjects. Based on the BHA criteria, high TG (24.5%), high TC (32.7%), high LDL-C (37.8%), high TC:HDL-C (30.9%), high LDL-C HDL-C (55.7%), and high TG:HDL-C (58.3%) were noted. CONCLUSION: Dyslipidemia is common in the Iraqi population, and this was identified at different recommendation criteria.

Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center Experience at Royal Hospital, Oman.

OBJECTIVES: To evaluate the significance of serum chromogranin A (CgA) status in patients with and without different neuroendocrine tumors (NETs) by conducting a retrospective assessment of the diagnostic utility and limitations of CgA as a biomarker for NETs in a tertiary care hospital in Oman. METHODS: We conducted a retrospective analysis of CgA requests referred to the Clinical Biochemistry Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March 2014). During this time, 302 CgA tests for 270 patients (119 males and 151 females; age range 11-86 years and mean±standard deviation (SD) 44.0±18.0 years), were requested. Of these CgA tests, 245 tests were performed for 245 patients investigated for the diagnosis of NETs, and 57 CgA tests were performed for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA levels were analyzed using the enzyme-linked immunosorbent assay based on a cut-off value of 22 IU/L. RESULTS: Of the 302 CgA tests reviewed, 197 (65.2%) were within the quoted normal range; however, 105 (34.8%) had CgA > 22 IU/L. Of the 245 patients with first-line CgA, 38 patients (15.5%) had NET that included carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma, lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The mean±SD of CgA in these patients with NETs was 205.0±172.0 IU/L. Meanwhile, there were 45 (18.3%) patients with CgA > 22 IU/L (83.0±116.0 IU/L) who did not have NETs. The conditions/diseases included: essential hypertension, chronic kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes mellitus). Of the 25 patients with known NET who were followed-up, there were 57 CgA results (29 with CgA ≤ 22 IU/L and 28 with CgA > 22 IU/L). The overall clinical sensitivity of CgA in the diagnosis of NETs was 84.2%, overall specificity was 78.2%, positive predictive value was 41.5%, negative predictive value was 96.4%, and overall efficiency was 79.2%. In patients with individual NET, a good reflection in CgA was noticed in the follow-up period following surgery or therapy. CONCLUSIONS: Serum CgA is a sensitive and effective noninvasive laboratory test for the clinical detection and management of NETs. Awareness of the pitfalls of the tests in patients with non-NET conditions, particularly chronic diseases and use of certain drugs, is important to be considered during the interpretation of the CgA levels.

Validity of Prostate Health Index and Percentage of [-2] Pro-Prostate-Specific Antigen as Novel Biomarkers in the Diagnosis of Prostate Cancer: Omani Tertiary Hospitals Experience.

OBJECTIVES: Prostate cancer is the leading cancer in older men. The Ministry of Health Oman Cancer Incidence Registry 2013 lists cancer of the prostate as the first most common cancer in males. Therefore, early detection is important and prostate-specific antigen (PSA) is widely used as an established laboratory test. However, despite its wide use, its value in screening, particularly in asymptomatic males, is controversial when considering the risks and benefits of early detection. METHODS: This prospective, observational study included 136 males (67.0±8.9 years; range 45-90) who were scheduled for a prostate biopsy in two different tertiary care teaching hospitals in Oman: the Royal Hospital and Sultan Qaboos University Hospital. Blood specimens from these patients were collected at the same setting before obtaining a prostatic biopsy. Three PSA markers (total PSA (tPSA), free PSA (fPSA), and [-2]proPSA (p2PSA)) were measured and the Prostate Health Index (phi) calculated. The histopathological report of the prostatic biopsy for each patient was obtained from the histopathology laboratory of the concerned hospital along with clinical and laboratory data through the hospital information system. RESULTS: Phi has the highest validity markers compared with other prostate markers, with a sensitivity of 82.1%, specificity of 80.6%, and area under the curve (AUC) value of 0.81 at a cutoff of 41.9. The other prostatic markers showed sensitivities and specificities of 78.6% and 25.9% for tPSA; 35.7% and 92.6% for %fPSA; and 64.3% and 82.4% for %p2PSA, respectively. The AUCs at the best cutoff values were 0.67 at 10.1 µg/L for tPSA; 0.70 at 11.6% for %fPSA; and 0.55 at 1.4% for %p2PSA. An association between phi values and aggressiveness of prostate malignancy was noted. Of the 28 patients with prostate cancer, 22 patients had tPSA > 4 µg/L. However, no patient had phi in the low-risk category, and five, six, and 17 patients had phi in the moderate-, high-, and very high-risk categories, respectively. CONCLUSIONS: Phi outperforms tPSA and fPSA when used alone or in combination, and appears to be more accurate than both markers in excluding prostate cancer before biopsy. Use of this biomarker helps clinicians to avoid unnecessary biopsies, particularly in patients with gray-zone tPSA level. Phi is the strongest marker that correlates proportionally with Gleason Score; therefore, it is also useful in predicting the aggressiveness of the disease. This is the first reported experience for the use of p2PSA and phi in Oman, the Middle East, and North Africa.

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.

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 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.

A Novel Mutation Causing 17-ß-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-ß-hydroxysteroid dehydrogenase type 3 (17-ß-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-ß-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.

Performance indicators and validity of serum fructosamine assay as a diagnostic test in a screening program for diabetes mellitus.

OBJECTIVE: To evaluate the performance indicators and validity of fructosamine assay as a diagnostic tool in screening for Diabetes mellitus (DM). METHODS: Fasting plasma glucose (FPG) and serum fructosamine (FA) were compared in 1015 subjects aged >or= 25 years from different urban and rural areas in Mosul city, Northern Iraq. The subjects were classified into 5 groups: Group 1: Subjects with FPG < 6.1 mmol/L (n=883), Group 2: Subjects with impaired FPG 6.1-6.9 mmol/L (n=29), Group 3: New diabetics diagnosed solely by new 1997 American Diabetes Association (ADA) criteria with FPG 7.0-7.7 mmol/L (n=20), Group 4: New diabetics diagnosed according to old 1980-1985 World Health Organization (WHO) criteria with FPG >or= 7.8 mmol/L (n=23), and Group 5: Known diabetics (n=60). Subjects in groups 2 and 3 underwent a standard 75 gm oral glucose tolerance test (OGTT) as recommended by the WHO. Reclassification of subjects into 3 groups according to FPG or 2hPG, or both was carried out for all subjects. Group A (non-diabetics): Subjects with FPG < 6.1 mmol/L or 2hPG < 7.8 mmol/L, or both (n=910). Group B (Diabetics): Subjects with FPG >or= 7.8 mmol/L or 2hPG >or= 11.1 mmol/L, or both (n=92) including 60 known diabetics in group 5 and 23 new diabetics in group 4 in addition to 2 subjects in group 2 and 7 subjects in group 3. Group C (impaired glucose tolerance, IGT): Subjects with 2hPG between 7.8-11.1 mmol/L (n=13). RESULTS: Having all subjects had their serum FA being measured; the Receiver Operator Characteristic (ROC) curve was constructed on the data to determine the trade off between sensitivity and specificity of the FA test in the diagnosis of DM. This construction decided that serum FA value of 2.65 mmol/L would be the cutoff point, or the positivity criterion in the calculation of the validity parameters of FA test. Of 910 non-diabetics, 886 subjects had measured FA values within the 95th percentile, while 24 had FA higher than the cutoff point. Consequently, FA in non-diabetics yielded 886 (true negatives) and 24 (false positives). Of the 92 diabetics, 30 subjects had normal FA values, while 62 diabetics showed FA higher than the cutoff point. Consequently, FA in diabetics yielded 30 (false negatives) and 62 (true positives). Accordingly, the sensitivity, specificity, positive predictive value, negative predictive value, accuracy rate, positive likelihood ratio and negative likelihood ratio were 67.3%, 97.3%, 72.3%, 96.7%, 94.6%, 26 and 2.99. A highly significant correlation was observed between FPG and measured FA in non-diabetics (r=0.85, p<0.0001) and diabetics (r=0.92, p<0.0001). No significant correlation was observed between serum FA and albumin in non-diabetics (r= 0.14, p>0.05) and diabetics (r=0.08, p>0.05). CONCLUSION: Fructosamine test shows a moderate sensitivity with a high specificity as a diagnostic test for diabetes mellitus. The considerable overlap between diabetics and non-diabetics limit its usefulness. It is recommended that fructosamine test is not a suitable screening test for the disease. Measurement of plasma glucose (fasting or post-OGTT) remains the corner stone as a diagnostic test.

Comparison between Three Different Equations for the Estimation of Glomerular Filtration Rate in Omani Patients with Type 2 Diabetes Mellitus.

OBJECTIVES: Estimated glomerular filtration rate (eGFR) is an important component of a patient's renal function profile. The Modification of Diet in Renal Disease (MDRD) equation and the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation are both commonly used. The aim of this study was to compare the performance of the original MDRD186, revised MDRD175 and CKD-EPI equations in calculating eGFR in type 2 diabetes mellitus (T2DM) patients in Oman. METHODS: The study included 607 T2DM patients (275 males and 332 females, mean age ± standard deviation 56 ± 12 years) who visited primary health centres in Muscat, Oman, during 2011 and whose renal function was assessed based on serum creatinine measurements. The eGFR was calculated using the three equations and the patients were classified based on chronic kidney disease (CKD) stages according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines. A performance comparison was undertaken using the weighted kappa test. RESULTS: The median eGFR (mL/min/1.73 m(2)) was 92.9 for MDRD186, 87.4 for MDRD175 and 93.7 for CKD-EPI. The prevalence of CKD stage 1 was 55.4%, 44.7% and 57% while for stages 2 and 3 it was 43.2%, 54% and 41.8%, based on MDRD186, MDRD175 and CKD-EPI, respectively. The agreement between MDRD186 and CKD-EPI (к 0.868) was stronger than MDRD186 and MDRD175 (к 0.753) and MDRD175 and CKD-EPI (к 0.730). CONCLUSION: The performances of MDRD186 and CKD-EPI were comparable. Considering that CKD-EPI-based eGFR is known to be close to isotopically measured GFR, the use of MDRD186 rather than MDRD175 may be recommended.

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 r(2)= 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.

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.

Diagnostic utility of coeliac disease: a descriptive study in a tertiary care hospital, oman.

OBJECTIVES: The prevalence of coeliac disease in Oman is unknown. We aim to estimate the prevalence of coeliac disease in at-risk subjects, describe the clinical characteristics and laboratory findings associated with coeliac disease and the validity of serological testing for coeliac disease at the Royal Hospital, Oman over a period of three years. METHODS: This is a retrospective case finding study. The medical and laboratory records were reviewed for patients for whom serum antiendomysium IgA antibodies were requested at the Royal Hospital during a 3-year period (1(st) Jan 2006-31(st) Dec 2008). The data were extracted in order to assess the following: a) Prevalence rate of coeliac disease among at-risk subjects; b) Clinical characteristics in patients with coeliac disease and clinical manifestations for which the requesting clinicians considered coeliac disease as a possible diagnosis, including their specialties; c) Laboratory tests results in patients with coeliac disease; and d) Validity of antiendomysium antibodies testing in comparison with histopathology of jejunal biopsies for diagnosing coeliac disease. RESULTS: The study included 431 patients (250 females, 181 males) who were suspected of having (or screened for) coeliac disease. The median of age was 15 years (range: 9 months-74 years) with mean ± SD 18.95 ± 14.1 years. Of these, 15 (3.5%) patients (10 females, 5 males) with a median age of 19 years and mean 21.4 ± 13.0 years (range: 2.5-38 years), had positive antiendomysium antibodies results with median (range) of 160 (40-320) IU/L and mean± SD 204.5 ± 160 IU/L. Of these 15 patients, 13 had positive jejunal histopathological changes indicative of coeliac disease; the remaining 2 patients had no biopsy examination. Of the 44 patients with negative antiendomysium antibodies <10 IU/L who had jejunal biopsy, 41 were negative and 3 had histopathological changes suggestive of mild coeliac disease. All the 3 patients had serum total IgA levels within the reference range. The calculated validity indicators for antiendomysium antibodies were: sensitivity 81.3%, specificity 100%, positive predictive value 100%, negative predictive value 93.2% and efficiency 94.7%. The most common mode of presentation in patients with coeliac disease was gastrointestinal features, type 1 diabetes mellitus, anemia, short stature and hypothyroidism. The seropositivity in tye 1 diabetics was 4.9%. Investigations for coeliac disease were most frequently made by endocrinologists (pediatric and adult) who accounted for 53.8% followed by gastroenterologists (pediatric and adult) with 40.6% with less consideration by the other clinicians (5.6%). CONCLUSION: The availability of highly specific and sensitive serological test and increased awareness for coeliac disease among some medical specialties has increased the number of diagnosed cases of coeliac disease. The requesting for serological test is being made mainly by endocrinologists and gastroenterologists.

Estimated Glomerular Filtration Rate (eGFR): A Serum Creatinine-Based Test for the Detection of Chronic Kidney Disease and its Impact on Clinical Practice.

Chronic kidney disease (CKD) is an important epidemic and public health problem that is associated with a significant risk for vascular disease and early cardiovascular mortality as well as progression of kidney disease. Currently it is classified into five stages based on the glomerular filtration rate (GFR) as recommended by many professional guidelines. Radiolabelled methods for measuring GFR are accurate but not practical and can be used only on a very limited scale while the traditional methods require timed urine collection with its drawback of inaccuracy, cumbersomeness and inconvenience for the patients. However, the development of formula- based calculation of estimated GFR (eGFR) has offered a very practical and easy approach for converting serum creatinine value into GFR result taking into consideration patient's age, sex, ethnicity and weight (depending on equation type). The commonly used equations include Cockraft and Gault (1976), Modification of Diet in Renal Disease (MDRD) (1999) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2009). It is the implementation of these equations particularly the MDRD that has raised the medical awareness in the diagnosis and management of CKD and its adoption by many guidelines in North America and Europe. The impact and pitfalls of each of these equations in the screening, diagnosis and management of patients with CKD are presented and discussed in this review.

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 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. METHODS: 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. 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 <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. 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.

Indicators of Renal Glomerular and Tubular Functions in Patients with Beta-Thalassaemia Major: A cross sectional study at the Royal Hospital, Oman.

OBJECTIVES: There are limited data concerning the assessment of renal function in beta-thalassaemia major, with no study of such involvement in Omani patients. The objective of this study was to establish the pattern of renal glomerular and tubular function using traditional and specific laboratory tests in patients with beta-thalassaemia major. METHODS: This cross-sectional study, from January-July 2008, included 30 patients of the Thalassaemia Clinic at the Royal Hospital, Oman, with transfusion-dependent homozygous beta-thalassaemia major. They included 15 males and 15 females, aged 16-32 years with mean ± standard deviation of 21.23 ± 3.42 years. The medical records were reviewed and renal function states assessed as follows: serum creatinine, estimated glomerular filtration rate (eGFR); urea; phosphate, fractional excretion of filtered sodium (FENa); urine albumin: creatinine index; urine ß2-microglobulin:creatinine index; tubular reabsorption of phosphate (TRP), and tubular maximum phosphate reabsorption (TmP)/GFR. RESULTS: All patients had eGFR >90 ml/min/1.73m(2); serum creatinine <90 µmol/L; serum urea <6.0 mmol/L, and urine albumin:creatinine <2.5 mg/mmol. Only 2 (6.7%) patients had FENa >1% and 3 (10.0%) patients had urine ß2-microglobulin: creatinine >22 µg/mmol. All patients had TRP >0.85, of whom seven (23.3%) patients had values within the range of 0.85-0.95 and 23 (76.7%) had values >0.95. Also, all patients had TmP/GFR >1.0 mmol/L, of whom only one (3.3%) patient had TmP/GFR of 1.0-1.5, and 29 (96.7%) patients had TmP/GFR >1.5 mmol/L. Finally, 24 (80%) patients had serum phosphate >1.4 mmol/L. Linear regression revealed a highly significant correlation between serum phosphate and TmP/GFR (r = 0.904, P < 0.001). CONCLUSION: Renal function, glomerular and tubular, appears to be well preserved in beta-thalassaemia major. Almost all renal function indicators were within the recommended ranges. Raised TmP/GFR and TRP were noted in the majority of patients, reflecting an up-trend in serum phosphate and therefore increasing renal phosphate reabsorption.