R990G Polymorphism of calcium sensing receptor gene Is associated with high Parathyroid Hormone levels in subjects with Vitamin D deficiency: a cross-sectional study

Single nucleotide polymorphisms (SNPs), R990G and A986S of the calcium sensing receptor (CaSR) gene, are shown to influence response of parathyroid hormone (PTH) in subjects with optimal vitamin D levels. This cross-sectional study was conducted in subjects with vitaminDdeficiency (VDD) to observe association’s betweenCaSR polymorphisms, plasma iPTH, and serumcalcium levels. Adult females ( = 140) with known VDD, intact parathyroid hormone (iPTH), and calcium levels were recruited for genotype analysis.The frequencies of the 986 alleles GG, GT, and TT were 68%, 25%, and 7%, respectively, whereas the frequencies of the 990 alleles AA, AG, and GG were 80%, 8.9%, and 11.1%, respectively.Thesubjects with GG genotype of R990G polymorphism had higher iPTH levels (148.65 versus 91.47 and 86.1 pg/mL for GG versus AA, AG, resp., = 0.008) and lower calcium levels (8.4 versus 9.04 and 9.07mg/dL for GG versus AA, AG, resp., = 0.002). No such association of A986S polymorphism with plasma iPTH or serum calcium levels was observed in the present study. Patients with VDD bearing the GG genotype of R990G SNPs are prone to have higher iPTH levels and lower calcium

Fibroblast growth factor 23 (FGF23) levels, phosphate Intake and its association with Indices of renal handling of phosphate in healthy volunteers

FGF23 is a novel phosphaturic hormone; we aimed to assess the FGF23 levels and its association with dietary phosphate intake and indices of renal handling of phosphate in this study. Prospective study was conducted in which dietary phosphate intake was assessed by food frequency questionnaire (FFQ) along with blood and spot urine samples were collected after overnight fast for determining serum phosphate, FGF23, fractional excretion of phosphate (FePO4 ) and tubular maximum for phosphate (TmP/GFR). FGF23 (C-Term) was measured by a sandwich ELISA. The mean dietary phosphate intake of eighty healthy adults (mean age of 29 ± 5 years) was 1220 ± 426 mg; median FGF23 was 49.9 RU/ml (IQR=33, 76) and mean FePO4 was 7 ± 4.7. Subjects were stratified into two groups according to serum phosphate levels. Significant difference was not found in dietary phosphate intake and FGF23 levels in the two groups. However, TmP/GFR and creatinine were significantly different in the two groups. FePO4 was high in both the groups. Overall a rising pattern of FGF23 levels was seen with increasing serum phosphate levels. Significant positive correlation was found between FGF23 and dietary phosphate (r=0.22, p\u3c0.05) and negative correlation was seen between FGF23 and FePO4 (r=-0.260, p\u3c0.05)

Role of serum angiotensin converting enzyme in sarcoidosis

This study was conducted to determine the role of Serum Angiotensin Converting Enzyme (SACE) as a marker in the differential diagnosis of pulmonary diseases and prognosis of sarcoidosis, A retrospective analysis of 113 medical records of patients at The Aga Khan University Hospital, with laboratory investigation for SACE was performed. Among 113 patients, 51 cases were found to have sarcoidosis, 44 of them had SACE levels greater than 52 lU/L (mean ACE 104.44). SACE levels were also found elevated in other clinical conditions like tuberculosis (mean 58.64 lUlL), but the enzyme level were less (p0.04) than those found in sarcoidosis (mean (92-97 lUlL). SACE activity was found to be considerably lower in other chronic lung diseases such as, fibrosing alveolitis (mean 43.98 lUlL), interstitial lung disease (mean 42.11 lU/L) and chronic obstructive lung disease (mean 40.85 lUlL). Twenty patients of sarcoidosis, who received steroid tretalment subsequently showed a decline in the SACE levels. SACE is a useful marker in differential diagnosis as 37.2% cases of sarcoidosis compared to only 9.09% of tuberculosis had SACE levels greater than 100 lUlL. In addition, our data also suggest that serum ACE is useful for the diagnosis as well as monitoring prognosis in sarcoidosis (JPMA 48:131,1998)

Illuminating the dark side-vitamin D status in different localities of Karachi

Abstract This study was conducted to determine the association between place of residence (grouped into neighbourhoods), and 25-hydroxy D (25[OH]D) levels of individuals of Karachi. Addresses of 4788 individuals tested for 25[OH]D at the clinical laboratory of the Aga Khan University (AKU), Karachi, from January 2007 to June 2008 were reviewed. The neighbourhoods were categorized into ten, based on locality attributes. A high overall prevalence (74%) of vitamin D deficiency (VDD) was observed. There was a significant difference (p-value \u3c 0.01) between mean log 25[OH]D levels amongst neighbourhoods grouped according to distinct housing structure attributes and localities. A high frequency of VDD in all the studied localities of an urban city warrant dietary vitamin D supplementation and food fortification

X-linked hypophosphatemic osteomalacia with PHEX mutation presenting late in Pakistan

Abstract.introduction.and.importance: Autosomal dominant hypophosphatemic rickets is the most common form of rare rickets, commonly manifests in children but sometimes the condition remains undiagnosed due to lack of knowledge &/or awareness of treating physicians or surgeons.Case presentation: We describe a case of 43 years old female with multiple fragility fractures since childhood, corrected surgically but never investigated. She had stunted growth, bowing deformities and loss of teeth.Clinical discussion: A detailed history and examination along with metabolic and genetic work up mounted the diagnosis of X linked hypophosphatemic osteomalacia. The pathophysiology involves the mutation or the loss of the phosphate regulating gene on PHEX, that causes reduced mineralization of bones and teeth.Conclusion: Diagnostic delay in this patient resulted in increased disabilities affecting her mobility and lif estyle

Frequency of macroprolactin in hyperprolactinemia

Objective: To determine the frequency of Macroprolactin (MaPRL) in patients with increased total prolactin and its clinical and financial impact. Study Design: Cross-sectional study. Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from March to May 2015. Methodology: Patients with high total prolactin were screened by polyethylene glycol (PEG) precipitation for determination of MaPRL. Clinical history, imaging work-ups, and cost incurred in further investigations were collected by telephonic interview after verbal consent. Patients were stratified into true hyperprolactinemia and macroprolactinemia after PEG treatment, based on monomeric prolactin levels. Medical records of cases registered with AKUH were reviewed to confirm the diagnosis. Results: Two hundred and thirty-nine patients were identified with high prolactin levels. Macroprolactinemia was identified in 145 (60.7%) and true hyperprolactinemia in 94 (39.3%) patients. Galactorrhea was significantly more in true hyperprolactinemic females (p=0.022), followed by visual disturbances (p=0.01) and headache (p=0.006). Moreover, as majority of population were females, the clinical features in the macroprolactinemia group as compared to true hyperprolactinemic group were mostly related to non-pituitary causes like drug intake [42.5% (54) vs. 37% (30)], heat intolerance due to thyroidal illness [41.7% (53) vs. 38.3% (31)] and surgery [26.8% (34) vs 22.2% (18)] in females. Further radiological workup (MRI, CT) were conducted in 35 (37.2%) patients with true hyperprolactinemia. Twenty-one (60%) of the patients were confirmed to have pituitary adenomas. In eight (5.5%) patients with MaPRL, only one had pituitary microadenoma on radiological workup. Total cost impact on the basis of investigations, was significantly higher in the group undergone imaging, despite 7 out of 8 individuals found to have normal imaging results. The median total cost in true hyperprolactinemic group undergone imaging was Rs. 4370 (IQR=2412.5, 22850) as compared to macroprolactinemic groups; Rs. 3,250 (IQR=2150, 4278). There was significant difference in the cost burden of both the groups (p \u3c0.001).Conclusion: High frequency of MaPRL was identified in patients with hyperprolactinemia. Screening with PEG precipitation in hyperprolactinemic sera is simple and cost-effective