Thyroid Autoimmunity and Subclinical Hypothyroidism in Prolactinoma: A Case Control Study.

Background: This study was aimed at determining the frequency of thyroid autoimmunity and subclinical hypothyroidism in patients with hyperprolactinemia due to prolactinoma compared to well-matched healthy controls. Methods: This was a cross-sectional study wherein 78 treatment naïve prolactinoma patients and ninety-two healthy control subjects were recruited. Serum prolactin (PRL), thyroid-stimulating hormone (TSH), total thyroxine (T4), circulating anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-Tg) antibody levels were measured in all study subjects. Progression of the antibody-positive population to subclinical hypothyroidism was determined. Results: The median PRL level among patients was 166 ng/ml (IQR 85-467) compared to 11.4 ng/ml (IQR 8.5-15.9) in controls (P < 0.001). There was no significant difference in levels of T4 (P = 0.83) and TSH (P = 0.82) between the cases and controls. Overall, 25% of patients had the presence of anti-thyroid antibodies as compared to 20% of controls (P = 0.56). SCH was more common in antibody-positive hyperprolactinemia subjects compared with antibody-positive controls. Conclusion: We did not find an increased prevalence of thyroid autoimmunity among untreated prolactinoma patients compared to healthy controls. At the same time, subclinical hypothyroidism was more common in thyroid antibody-positive patients with hyperprolactinemia than positive controls.

Vitamin D Toxicity: A Prospective Study from a Tertiary Care Centre in Kashmir Valley.

BACKGROUND: Vitamin D toxicity (VDT), a "not uncommon" cause of hypercalcemia, can be life-threatening and cause substantial morbidity, if not treated promptly. AIMS: To describe presentation, management, and outcome in 32 patients with VDT diagnosed over 3 years. MATERIALS AND METHODS: Patients presenting with VDT at a tertiary care centre in Srinagar Kashmir India were included. Evaluation included detailed history and biochemical tests including serum calcium, phosphate, creatinine, intact parathyroid hormone (iPTH), 25-hydroxy Vitamin D (25-OHD), and 24-hour urinary calcium. RESULTS: The clinical manifestations of the 32 patients (median age 65; range 3-77 years) included gastrointestinal symptoms (constipation and vomiting), polyuria/polydipsia, altered sensorium, pancreatitis, acute kidney injury, and nephrocalcinosis. The median total serum calcium level was 13.95 (range 11.10-17.20) mg/dl and median 25-OHD level was 306 (range 105-2800) ng/ml. All patients had suppressed or low normal iPTH and hypercalciuria and 78% had azotemia. All patients had received multiple intramuscular injections of vitamin D3. The median cumulative dose was 4,200,000 (range, 1,800,000-30,000,000) IU. The median time to resolution of hypercalcemia was 7 months (range 4-18 months). CONCLUSION: We conclude that VDT is an increasingly common cause of symptomatic hypercalcemia. VDT needs prolonged follow up as it takes months to abate its toxicity. Enhancing awareness among general practitioners regarding the toxicity resulting from high doses of vitamin D is the key to prevent VDT. We suggest that VDT be considered in patients, especially the elderly, presenting with polyuria, polydispsia, vomiting, azotemia, or encephalopathy.

Association of FoxP3 promoter polymorphisms with the risk of Graves' disease in ethnic Kashmiri population.

Graves' disease is a multifactorial autoimmune disorder of the thyroid gland, with some extra-thyroidal complications like eye and skin abnormalities in some patients. GD is more prevalent in women than men and is the leading cause of hyperthyroidism worldwide. A complex interaction between genetic and environmental factors is the proposed cause which triggers immune system to produce autoantibodies stimulating the TSH receptor, leading to clinical manifestations such as hyperthyroidism, diffuse thyroid enlargement (goiter) and often ophthalmopathy in affected individuals. Various Single nucleotide gene polymorphisms (SNPs) have been associated with the risk of GD development including promoter SNPs in Forkhead Box P3 (FOXP3). FOXP3 is an important regulatory factor for T cell development and differentiation and therefore has a prominent role in suppression of autoimmune reactions which may lead to predisposition of GD. There have been some studies on the association of FOXP3 SNPs with GD, but no such investigation has been carried out in ethnic Kashmiri population. So, we aimed to study a possible association of FOXP3 promoter SNPs (-3279C/A, -2383C/T & -3499 A/G) with GD. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to genotype 285 individuals (135 GD cases and 150 healthy controls) and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for -3279C/A SNP [OR, 3.48; 95% CI (2.05-5.92); P < 0.001] and -2383C/T SNP [OR, 5.62; 95% CI (2.43-13.00); P < 0.001], while no significant association was seen in case of -3499 A/G SNP. We conclude that -3279C/A and -2383C/T SNPs have a highly significant association with the risk of GD development in Kashmiri population.

Association of polymorphic variants of IL-1ß and IL-1RN genes in the development of Graves' disease in Kashmiri population (North India).

PURPOSE: Graves' disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1ß has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1ß gene promoter region (-511 T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population. METHODS: A total of 135 Graves' disease patients and 150 healthy individuals were included in the study. PCR and PCR-based restriction analysis methods were done for IL-1RNVNTR and IL-1ß gene polymorphisms respectively. RESULTS: We found statistically significant increased frequencies of the C/C + CT genotype (P = 0.001; odds ratio (OR) = 5.04, 95% confidence interval (CI) = 3.02-8.42) and the C allele (P = 0.001; OR = 3.10, 95% CI = 2.14-4.50) in IL-1ß gene promoter polymorphism (rs16944) with GD patients compared to normal controls. Also in the exon 5 (rs1143634), a significant increase in frequency of the C/C homozygous genotype (P = 0.001; OR = 0.18, 95% CI = 0.11-0.30) and C allele (P = 0.001; OR = 0.31, 95% CI = 0.20-0.48) was observed in GD cases as against controls. For IL-1RNVNTR (rs2234663), we didn't observe any significant difference in the allelic and genotypic frequencies between cases and controls. CONCLUSION: Our findings suggest that both promoter and exon polymorphisms of IL-1ß gene have a significant role in the risk of developing GD, whereas IL-1RNVNTR has no association with GD.

Metabolic abnormalities in patients with prolactinoma: response to treatment with cabergoline.

BACKGROUND: Hyperprolactinemia has been associated with changes in body composition and metabolic abnormalities. Normalization of prolactin (PRL) with dopamine agonists has been found to reverse these abnormalities. This study was designed to assess the anthropometric and metabolic alterations associated with prolactinoma and response of these abnormalities to cabergoline treatment. METHODS: In a non-randomised matched prospective design, 19 consecutive patients with prolactinoma (median PRL 118.6 (105.3) µg/L) and 20 controls were studied. The controls were age, gender and body mass index (BMI) matched. Anthropometric data and metabolic variables were studied at baseline, 3 and 6 months after cabergoline treatment. RESULTS: Patients with prolactinoma had increased level of fasting plasma glucose (P < .001), LDL-cholesterol (P = .001) and triglycerides (TG) (P = .009) as compared to age, gender and BMI matched healthy controls. There was a significant decrease of body weight at 3 months (P = .029), with a further decline at 6 months (P < .001) of cabergoline therapy. In addition, there was a significant decrement of BMI (P < .001), waist circumference (P = .003), waist-hip ratio (P = .03) and total body fat (P = .003) at 6 months of cabergoline treatment. A significant decline in plasma glucose (P < .001), total cholesterol (P = .009), LDL-cholesterol (P < .001) and TG (P < .001) was seen after 6 months of cabergoline treatment. CONCLUSIONS: Patients with prolactinoma have adverse metabolic profile compared with matched controls. Normalization of PRL with cabergoline corrects all the metabolic abnormalities.

Primary hyperparathyroidism presenting as recurrent acute pancreatitis: A case report and review of literature.

The association between pancreatitis and primary hyperparathyroidism (PHPT) is controversial. We report a 32-year-old man who presented with recurrent episodes of acute pancreatitis. Primary hyperparathyroidism was diagnosed after the fourth episode of pancreatitis. He had no additional risk factors for pancreatitis. Eighteen months after successful parathyroid surgery, there has been no recurrence of abdominal pain and his serum calcium is within the normal range.