Background:Vitamin D supplementation precipitating hypercalcemic crisis is often the first manifestation in patients with granulomatous disorders.Methods:We report our experience on patients presenting with hypercalcemic crisis due to granulomatous disorder and the role of Vitamin D supplementation in the precipitation of hypercalcemic crisis in them.Results:The study included five patients with granulomatous disorders who presented with hypercalcemic crisis. All patients initially presented with nonspecific constitutional symptoms to other health-care centers to receive high-dose Vitamin D supplementation (60,000 U/week or 600,000 U intramuscular single dose). All of these patients presented with hypercalcemic crisis (serum calcium: 16.04 ± 0.3 mg/dl) to our centers after a period of 32.8 ± 9.62 days. Three patients were diagnosed to have sarcoidosis, and two were diagnosed to have tuberculosis. All five patients had parathyroid hormone-independent hypercalcemia with elevated serum 1,25-dihydroxy Vitamin D. Serum angiotensin-converting enzyme level was elevated in all the three patients with sarcoidosis. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography was performed in two patients with sarcoidosis which demonstrated diffusely increased tracer uptake in liver. In these two patients, liver biopsy confirmed the diagnosis.Conclusions:High-dose Vitamin D supplementation is most often the underlying cause of hypercalcemic crisis in patients with granulomatous disorders. Hence, high-dose Vitamin D supplementation should be used judiciously.

IntrOductIOnPrimary hypothyroidism is a common disorder especially in women. A recent multi-centric Indian study reported a prevalence of hypothyroidism to be 10.95% with higher prevalence in women (15.86%) [1]. With increasing availability of thyroid testing facilities, hypothyroidism is often detected at early stages, initially requiring replacement with smaller doses of L-thyroxine (25-50µg/day). In these patients, replacement dose of L-thyroxine increases with progressive damage of thyroid gland and consequent decrease in function of the thyroid. So, increase in need for replacement doses of L-thyroxine over time may be part of the natural history of autoimmune thyroiditis. However, many factors increase the need for replacement dose of L-thyroxine in patients with primary hypothyroidism who are on full replacement doses (≥1.6µg/ day). These factors include conditions that increase Thyroxine Binding Globulin (TBG) levels such as use of oral contraceptive pills and chronic active hepatitis, weight gain, development of malabsorption syndromes and initiation of drugs which interfere with absorption of thyroxine etc., [2]. However, it is often forgotten that development of nephrotic syndrome increases the need for L-thyroxine replacement [3][4][5].It is well-known that nephrotic syndrome leads to urinary loss of thyroxine and triiodothyronine along with TBG leading to elevation of Thyroid Stimulating Hormone (TSH) [6][7][8][9]. The effect of loss of TBG and thyroxine in patients with hypothyroidism who newly develop nephrotic syndrome is not well studied. Here, we have studied the effect of newly diagnosed nephrotic syndrome on the dose of L-thyroxine replacement in previously diagnosed patients with primary hypothyroidism who were on full, stable dose of L-thyroxine replacement for at least one year. MAterIAls And MethOdsThe study was conducted between January 2012 and December 2015 at Department of Nephrology in a tertiary health care center at Bengaluru, Karnataka, India. The study was approved by institutional ethics committee and a written informed consent was obtained from all participants. All adult patients with previously diagnosed primary hypothyroidism and newly diagnosed nephrotic syndrome were screened for the study. Patients who were not on full replacement doses of L-thyroxine (<1.6µg/day) and whose L-thyroxine doses were modified during the previous year were excluded from the study. Patients with hypothyroidism who are not on full dose of LT4 replacement often need increment in replacement doses due to progression of the disease. To avoid the confounding effect of progression of the disease on change in L-thyroxine dose, patients who were not on full stable dose of L-thyroxine were excluded from the study.Primary hypothyroidism was defined as increase in serum TSH (>10µIU/L) at initial diagnosis. Autoimmune hypothyroidism was defined as primary hypothyroidism with elevated antithyroperoxidase antibody (≥9U/ml) or evidence of lymphocytic thyroiditis on fine needle aspiration cytology. Nephrotic s...

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