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

novel mutation causing 17-beta-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-beta-hydroxysteroid dehydrogenase type 3 [17-beta-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-beta-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 [25 mg 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 [50 mg 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

Are tubes containing sodium fluoride still needed for the measurement of blood glucose in hospital laboratory practice?

To compare glucose values obtained using sodium flouride [NaF] tubes and serum separation tubes [SST] in a tertiary care hospital laboratory setting. 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. 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. 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

Comparison between serum holotranscobalamin and total vitamin B12 as indicators of Vitamin B12 status

This study aims to assess the usefulness of serum holotranscobalamin [holo TC], the fraction of vitamin B12 that is available for tissue uptake, compared with total vitamin B12 in patients investigated for vitamin B12 disorders. Serum samples were randomly selected from 76 patients [48females, 28 males; age range 12-69 years] referred to the Clinical Biochemistry Laboratory, Royal Hospital for the assessment of vitamin B12 status. For each patient, serum total vitamin B12 was determined by chemiluminescent microparticle immunoassay on Architect 2000 analyzer and holo TC[active vitamin B12] level was determined by microparticle enzyme immunoassay on Axsym analyzer [both from Abbott, USA]. Comparison of the data was conducted to reflect the mean, standard deviation [SD] and correlation coefficient between the two groups. The mean [SD] for serum holo TC and total vitamin B12 were 46.5[32.2] pmol/L and 316.3[165.6] pmol/L respectively. There was a significant correlation between holo TC and total vitamin B12 [r=0.765, P<0.001] and the regression equation was expressed as; y= a+bx [i.e: holot TC = 1.5+0.14 total vitamin B12]. Also, the results were assessed for any misclassification when comparing holo TC and the total vitamin B12 in terms of whether each or both values agree or disagree for classifying the patients as having normal or abnormal [low or high] results, based on the cut-off thresholds of the kit's quoted reference range for holo TC of 9-123 pmol/L and for total vitamin B12 of 140-600 pmol/L. Accordingly, in69 [90.8%] samples, there was a parallel agreement/ classification of results, both being normal or abnormal. In 61 [80.4%] patients, both results were normal, whereas in 4 [5.2%] patients, both results were high, and in 4 [5.2%] patients both results were low. However, in 7[9.8%] cases, there was disagreement/ misclassification of results; 6 [7.8%] patients, holo TC was normal while total vitamin B12 was low, and in 1 [1.4%] patient, holo TC was normal while total vitamin B12 was low, and in 1 [1.4%] patient, holo TC was normal while total vitamin B 12 was high. It can be recommended that holo TC and total vitamin B 12, alone and in combination, have almost equal diagnostic efficiency reflector of vitamin B 12 status. Further comparison studies based on a gold standard method for classifying vitamin B 12 status are worth considering

Prevalence of endocrinopathies in patients with beta-thalassaemia major: a cross-sectional study in Oman

Beta-thalassaemia major is a common medical problem worldwide. There is little data dealing with the nature prevalence of different endocrine disorders in this disease in Sultanate of Oman. To establish the prevalence and times of occurrence of endocrine disorders in patients with beta-thalassaemia major. This cross-sectional study was conducted during Jan-Jul 2008 and dealt with 30 Omani patients with transfusion-dependent homozygous beta-thalassaemia major who were consulting Thalassaemia Clinic, Royal Hospital. They included 15 males and 15 females, aged 16 to 32 years with median of 21 years and mean +/- SD of 21.23 +/- 3.42 years. The medical records of these patients were reviewed and their endocrine functions were assessed. This assessment included pituitary and gonadal function, thyroid function, bone profile [including Parathyroid Hormone], morning cortisol and fasting glucose. These profiles were reviewed to exclude hypogonadism, hypothyroidism, hypoparathyroidism, hypoadrenalism or diabetes mellitus. Hypogonadism was reported in 22 [73.3%] patients [13 Female, 9 male]. Low levels of Follicle-Stimulating Hormone [FSH] and low Luteinizing Hormone [LH] with low estradiol [in females] or testosterone [in males] was noted in 15 [50.0%] patients [7 female, 8 male]. Normal [but inappropriately low] levels of FSH and LH with low estradiol [in females] or testosterone [in males] was noted in 7 [23.3%] patients [6 female, 1 male]. Primary hypothyroidism was present in only 1 [3.3%] patient [female] who Hypoparathyroidism was found in 3 [10.0%] patients [2 female, 1 male]. Diabetes mellitus with high fasting glucose was noted in 8 [26.7%] patients [2 female, 6 male]. Morning cortisol levels for all patients were within the reference range with no suspicion of hypoadrenal cortical function. Eight [26.7%] patients had no endocrine disorder, 12 [40.0%] patients had one disorder, 8 [26.7%] patients had 2 disorders, and 2[6.7%] patients had 3 endocrine disorders. There was no significant difference [p>0.050] in mean serum ferritin in thalassaemics with or without endocrinopathy, regardless of the number of endocrinopathy. There is high prevalence of endocrine disorders among Omani beta-thalassaemic adult patients. This signifies the importance of awareness for their development and monitoring for early detection and replacement therapy. No relationship between serum ferritin and development of endocrinopathy was noted