Changes in clinical & biochemical presentations of primary hyperparathyroidism in India over a period of 20 years.

Background & objectives: With the advent of serum chemistry autoanalyzer and routine estimation of serum calcium as a part of annual physical examination, there has been a dramatic change in the presentation of primary hyperparathyroidism (PHPT) from symptomatic to asymptomatic disease in the United States. However, such trend has not been documented from India. We carried out this retrospective study to analyse the changes in clinical presentations of PHPT patients over a period of two decades in a tertiary care centre in north India. Methods: This retrospective study included patients with PHPT treated at a single centre of north India between March1990 and October 2010. Two decades were divided into four different time periods, i.e. 1990 to 1994, 1995 to 1999, 2000 to 2004 and 2005 to 2010. Clinical presentations, biochemical parameters and surgical outcomes were compared between different time periods using appropriate statistical methods. Results: Data of 202 patients with PHPT with male: female ratio of 3:7 were analyzed. There was a rise in the number of cases of PHPT diagnosed in the last decade compared to the previous decade (28 cases vs 174 cases, P<0.001). Change in the mean age, male: female ratio, lag time for the diagnosis of PHPT and clinical presentations of PHPT (predominance of bone and stone symptoms) did not differ across different time periods. Non-significant decrease in serum calcium levels at the time of diagnosis of PHPT and a significant, decline in the serum alkaline phosphatase levels (P<0.01) were found in the last decade, however, iPTH levels were higher in the last decade (pP<0.05). There was no change in the site and size of parathyroid adenoma in the two decades, however, postoperative symptomatic hypocalcemia was less frequent in the last decade. Interpretation & conclusions: The findings of this retrospective analysis show that the PHPT still remains symptomatic disease with increasing awareness over the last two decades in our center. There was not much change in the clinical presentation, in the past two decades.

Effect of gender, biochemical parameters & parathyroid surgery on gastrointestinal manifestations of symptomatic primary hyperparathyroidism.

Background & objectives: Information on gastrointestinal manifestations and then response after curative parathyroid surgery is scarce in symptomatic primary hyperparathyroidism (PHPT). This study was carried out to analyse gastrointestinal manifestations in patients with PHPT and their associations with biochemical parameters. Methods: This retrospective study included 153 patients with symptomatic primary hyperparathyroidism (PHPT). The signs and symptoms pertaining to gastrointestinal system were analyzed. The difference of symptoms between men and women and difference in biochemical parameters in presence of different symptoms were evaluated. The relationship between serum calcium, phosphate and parathyroid hormone (PTH) levels with presence of gallstone and pancreatitis was also studied. Result: Of the 153 patients, 46 (30%) were men. The mean age was 39.2 ± 13.9 yr. Nearly 80 per cent of PHPT patients had at least one symptom/ sign related to gastrointestinal system. The most common gastrointestinal manifestations were abdominal pain 66 (43%), constipation 55 (36%), and nausea/or vomiting 46 (30%). Nearly one-fourth 34 (22%) of patients had a history of either gallstone disease or cholecystectomy or both. The prevalence of gallstone disease was higher in women (P<0.05). Imaging and biochemical evidence of pancreatitis was found in 27 (18%) patients. Pancreatitis was more common in men compared to women (P<0.05) despite the higher prevalence of gallstones in women. Serum calcium, phosphate or PTH levels were not associated with high risk for gallstone disease, however, serum calcium (P<0.05) was associated with 1.3 times higher risk of developing pancreatitis. In majority of patients, gastrointestinal manifestations resolved within three months of curative parathyroidectomy. Except two patients, none had recurrence of pancreatitis. Interpretation & conclusions: The study revealed that the gastrointestinal symptoms were common in patients with symptomatic PHPT. There was not much gender difference in gastrointestinal symptoms except higher occurrence of gallstones in women and pancreatitis in men. There was no difference in biochemical profile between those who had and did not have gastrointestinal symptoms.

Effect of zoledronic acid on bone mineral density in patients of celiac disease: A prospective, randomized, pilot study.

Background & objectives: The symptoms of celiac disease (CD) are varied and metabolic bone disease (MBD) is less recognized amongst all manifestations in CD patients. Bone disease in CD is attributed to secondary hyperparathyroidism, which in turn is associated with increased bone remodelling. Improvement in bone mineral density (BMD) with gluten free diet (GFD) is known, but the data on efficacy of bisphosphonates in CD patients are limited. Bisphosphonates being a potent inhibitor of bone resorption may be useful in patients with CD having low BMD. The aim of the present investigation was to study the effect of zoledronic acid on BMD in CD patients. Methods: A total of 28 CD patients were randomized to receive GFD, calcium and cholecalciferol (group A), and zoledronic acid (group B). Baseline biochemical tests and T-score by dual energy x-ray absorptiometer were done and repeated after 12 months. Results: The T-score showed improvement in the control arm (group A) from -3.31 ± 1.46 to -2.12 ± 1.44, a gain of 35.9 per cent (P<0.05) and in drug arm (group B) -2.82 ± 1.27 to -1.06 ± 1.84, registering a gain of 62.4 per cent (P<0.001). However, there was no difference in improvement of T-score in zoledronic acid group as compared to the control group. Interpretation & conclusions: Administration of zoledronic acid was not found to be better than GFD alone in increasing BMD in CD patients with low BMD in this pilot study.

Recurrent diabetic myonecrosis: A rare complication of a common disease.

Spontaneous aseptic diabetic muscle infarction (DMI) is one of the rare complications of diabetes. We report a case of type 2 diabetes mellitus with advanced microvascular complications presenting with severe muscular pain. She was diagnosed as DMI on the basis of clinical presentation, radiological and histopathological investigations. She was managed conservatively. During 18 months of follow up, she had good improvement but subsequently other muscle groups were involved suggesting recurrent DMI.

Fibrous dysplasia & McCune-Albright syndrome: An experience from a tertiary care centre in north India.

Background & objectives Fibrous dysplasia (FD) is a rare metabolic bone disease and information available from India is limited to only anecdotal case reports. We describe the clinical profile and therapeutic outcome of 25 patients with FD observed over a period of 14 yr in a tertiary care centre from north India. Methods In this retrospective study patients (n = 25) with diagnosis of fibrous dysplasia based on either classical radiological features and/or histological evidence on bone biopsy, were analyzed. Associated endocrinopathies if any, were evaluated. The diagnosis of McCune Albright syndrome (MAS) was considered when fibrous dysplasia was accompanied by either café-au-lait macules and/or endocrinopathies. The clinical presentation, biochemical parameters and imaging were analysed. Seven patients received bisphosphonate therapy. The final outcome and side effects were noted. Results Age of the patients ranged from 7 to 48 yr (mean ± SD, 24.2 ± 11.4 yr) with a lag time between onset of symptoms and presentation ranging from 1 to 20 yr (mean ± SD, 6.6 ± 6.2 yr). The mean duration of follow up was 3.5 ± 2.1 yr. Eighteen (72%) patients had polyostotic disease while the remaining had monostotic FD. Eight patients had endocrinopathies: five had acromegaly, one each had gonadotropin independent precocious puberty (GIPP), hyperthyroidism and hypophosphatemic rickets. One child with GIPP later developed hyperthyroidism. McCune Albright syndrome was observed in 10 (40%) patients. A majority of the patients underwent various minor or major surgical procedures and seven patients received bisphosphonates for recurrent pathological fractures. Bone pain was reduced in all bisphosphonate treated patients with a decrease in subsequent fractures. Interpretation & conclusions This series of FD patients from north India shows the varying presentations of this rare disease. Medical treatment with bisphosphonates appears to be potentially rewarding.

A pilot study on hypothalamo-pituitary-adrenocortical axis in primary hyperparathyroidism.

Background & objectives: Parathormone (PTH) and calcium, both have been shown to stimulate adrenal steroidogenesis in animal models and in vitro experiments. This is attributed to structural similarity between 15-25 amino acid region of the parathyroid hormone (PTH) and 1-11 amino acid region of adrenocorticotropin (ACTH). However, there are no in vivo human data regarding the effect of PTHcalcium axis on adrenocortical function. Materials: Ten patients with primary hyperparathyroidism underwent evaluation for cortisol dynamics including 0800 h and 2000 h plasma cortisol on day 1, cortisol response to insulin induced hypoglycaemia (IIH) on day 2, and 1 mg overnight dexamethasone suppression test (ONDST) on day 4. Serum aldosterone was also measured at 0800 h in fasting state on salt ad libitum for three days. These parameters were repeated 3 months after curative parathyroidectomy. Results: Basal plasma cortisol level at 0800 h and 2000 h were within upper normal range and loss of circadian rhythm in cortisol secretion was observed in half and forty per cent of patients had nonsuppressibility with ONDST. The defined peak cortisol response to insulin induced hypoglycaemia (>550 nmol/l) was achieved in all and nearly one third of patients had exaggerated response (>2000 nmol/l). After curative parathyroidectomy, the abnormalities in circadian rhythm and non-suppressibility with ONDST continued to prevail in 40 per cent of patients. The peak cortisol response to IIH showed a decrement but remained higher than normal. No correlation was observed between circulating parathyroid hormone and calcium with cortisol levels. Serum aldosterone was in upper normal range pre - and postoperatively, though it decreased postoperatively, but it could not attain a statistical significance (p = 0.5). Interpretation & conclusion: Abnormalities in hypothalamo-pituitary-adrenocortical axis in primary hyperparathyroidism do occur, however these are inconsistent and do not recover in majority of patients even after 3 months of curative parathyroidectomy.