Standardisation of a two-site PTH immunoradiometric assay using various solid phase formats.

Background & objectives: Estimation of parathyroid hormone (PTH) levels is important in the management of metabolic bone disorders. Here we describe a simple, sensitive and specific second generation immunoradiometric assay (IRMA) to detect intact PTH levels using different solid phase matrices. Different methods for immobilization of antibodies have also been evaluated. Methods: Experiments were carried out with physical adsorption of antibodies, covalent coupling using 2 per cent glutaraldehyde and N,N`carbonyldiimidazole. In all cases, antibodies raised against C-terminal were used as solid phase agent. Detector antibodies were N terminal antibodies that were radio-iodinated with 125I followed by gel purification. Several of the antibodies coupled to various solid phase matrices were incubated with PTH standards and the detector antibody as well as the commercially available tracer from DiaSorin kit to identify a suitable match pair. Results: The best pair was polyclonal C-terminal PTH antibody along with the kit tracer from DiaSorin with regards to antibody coated to magnetic cellulose particles. Among the various antibodies and the solid phases evaluated, the best assay was obtained with the matched pair of antibodies (70×G67 and 70×G68) from Fitzgerald immobilized on polystyrene tubes. The polyclonal antibody against C-terminal PTH was chosen as the capture antibody and 125I labelled polyclonal antibody against N-terminal PTH as the tracer. The sample values obtained in the antibody coated tubes were comparable to those obtained using a commercial kit. Interpretation & conclusions: The results indicated the feasibility of adopting this system for further development into a PTH IRMA for regular production as there is no indigenous kit available for intact PTH.

Bone disease in thyrotoxicosis.

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis.

Vitamin D status in India – Its implications and remedial measures.

Vitamin D deficiency is epidemic in India despite of plenty of sunshine. The interpretation of vitamin D levels should be done with the solar zenith angle, minimal erythemal dose, skintype, UV Index and geographical location. All Indian studies uniformly point to low 25(OH)D levels in the populations studies despite abundant sunshine. All studies have uniformly documented low dietary calcium intake compared to Recommended Daily/Dietary Allowances (RDA) by Indian Council of Medical Research (ICMR). The vitamin D status of children is very low in both urban and rural population studied. Pregnant women and their new born had low vitamin D status. The effect of short course of loading doses of vitamin D doesn’t have a lasting effect and a maintenance dose is needed. Low 25(OH)D levels has its implications of lower peak bone mass and lower BMD compared to west. There may be a public health need to fortify Indian foods with vitamin D. ©

Vitamin D status in Andhra Pradesh : a population based study.

BACKGROUND & OBJECTIVE: Data on the vitamin D status of the population in a tropical country like India have seldom been documented. Vitamin D deficiency is presumed to be rare. We carried out this study to document the dietary habits, serum calcium, 25(OH)vitamin D [25(OH)D], and parathyroid hormone levels of urban and rural population in a State in south India. METHODS: A total of 943 healthy urban and 205 rural adult subjects and 76 urban and 70 rural healthy children were studied for their dietary pattern, serum calcium, phosphorus, alkaline phosphatase, 25(OH)D, and N-tact parathyroid hormone levels (N-tact PTH). RESULTS: The daily dietary calcium intake of both the urban and rural population was low compared to that of recommended daily/dietary allowances (RDA) issued by Indian Council of Medical Research (ICMR). Dietary calcium and phosphorus were significantly lower(P<0.0001) in both the rural adult and children compared to that of the urban adult and children. The dietary phytate to calcium ratio was significantly (P<0.0001) higher in rural adult and children compared to that of urban adult and children. N-tact PTH levels negatively correlated with 25(OH)D in rural (r=-0.24; P<0.002), in urban adult subjects (r=-0.12; P<0.0001) and in rural and urban children (r=-0.2; P<0.05). The 25(OH)D levels of rural adult subjects were significantly higher (P<0.001) than that of urban adult subjects in both males and female groups. The 25(OH)D levels of both the urban and rural children were low. INTERPRETATION & CONCLUSION: Low dietary calcium intake and 25(OH)D levels were associated with deleterious effect on bone mineral homeostasis. Prospective longitudinal studies are required to assess the effect on bone mineral density, a surrogate marker for fracture risk and fracture rates.

Primary octreotide LAR therapy in GH-secreting pituitary adenoma.

A case of a 54-year-old male with active acromegaly and severe aortic stenosis treated primarily with octreotide LAR 20 mg/ IM/month for six months is reported here. His serum growth hormone level declined and was sustained throughout the period of six months (basal GH level 21.8 ng/ml; 1.2 ng/ml six months after therapy; mean+/-SD during six months of therapy 1.36+/-0.34 ng/ml; range 0.9 - 1.9 ng/ml). The post-treatment, postgadolinium, T1 weighted sagittal magnetic resonance images showed disappearance of the growth hormone secreting adenoma. The use of octreotide LAR as primary therapy in active acromegaly is discussed along with a brief review of literature.

Metastasising pituitary neuroendocrinal tumour with peptide secretion.

A 26-year-old male presented with prolactin-secreting invasive pituitary macroadenoma, which was partially excised with right pterional craniotomy. Post-operative computerized tomography revealed persistence of the tumour and hence he was started on oral bromocriptine therapy. His therapeutic compliance was poor. Seven years later he presented with further increase in size of the pituitary macroadenoma with hepatic and gastric metastasis. Upper gastrointestinal endoscopic biopsy of the metastatic lesions and immunohistochemical staining diagnosed it as a neuroendocrinal tumour with peptide secretion. He was initially treated with oral bromocriptine alone and later along with octreotide.

Clinical utility of ketoconazole in cases of adrenocortical carcinoma.

Ketoconazole, an imidazole derivative is known to decrease adrenal steroid biosynthesis by inhibiting cytochrome P450 dependent adrenal enzymes. Three patients of adrenal carcinoma treated with ketoconazole, 600-1200 mg daily showed significant fall in plasma and urinary cortisol levels, but no reduction in tumor size, one patient developed liver dysfunction which reverted back to normal on discontinuing the drug.