Frequency & predictors of pancreatitis in symptomatic primary hyperparathyroidism

Background & objectives: The frequency and predictors of pancreatitis in primary hyperparathyroidism (PHPT) are not well understood. The objective of the present study was to evaluate the frequency of pancreatitis in patients with PHPT and its association with clinical and biochemical parameters of the disease. Methods: In this retrospective study all consecutive patients with PHPT registered in the PHPT registry (www.indianphptregistry.com) from the year 2004 to 2013 were included. The clinical, biochemical and radiological parameters related to pancreatitis were evaluated in histologically proven PHPT patients. Results: A total of 218 patients (63 men; mean age: 40.6±14.4 yr) underwent surgery for PHPT during the study. Pancreatitis occurred in 35 [16%, 18 acute and 17 chronic pancreatitis (CP)] patients and male:female ratio was 1:0.94. Skeletal manifestations were seen less frequently in PHPT with pancreatitis as compared to that of PHPT without pancreatitis. PHPT with pancreatitis had significantly higher serum calcium (12.4±2.0 vs. 11.7±1.5 mg/dl, P <0.05) in comparison to PHPT without pancreatitis. PHPT with acute pancreatitis (AP) had higher serum calcium (P <0.05) and parathyroid hormone (PTH) (P <0.05) levels than PHPT with CP. Curative parathyroidectomy improved the symptoms associated with pancreatitis as there was no recurrence in AP group, whereas recurrence was observed only in about 10 per cent patients of the CP group. Interpretation & conclusions: Pancreatitis was observed in 16 per cent of PHPT patients with male predominance in the study population. No recurrence of AP was observed after curative surgery. It may be proposed that serum amylase with calcium and PTH should be measured in all patients of PHPT with pain abdomen to rule out pancreatitis.

Evaluation of hypothalamic-pituitary-adrenal axis in patients with atopic dermatitis.

Background: Most of the research on atopic dermatitis (AD) has focused on the pathophysiological role of the immune system in AD, and the role of endocrine signals in the pathology of AD has not been explored. Current research has shown a link between the neuroendocrine and immune functions. Aim: The aim was to measure the serum basal cortisol levels and cortisol levels following a low-dose ACTH stimulation test in patients with AD before and after treatment with corticosteroids. Methods: Three groups of patients with AD were evaluated: mild, moderate, and severe. Basal cortisol levels following an ACTH stimulation test were measured before and after treatment with topical steroids when an improvement in the disease activity by 75% as determined by the SCORAD index was observed. Results: Eighteen patients of the severe group at baseline showed an impaired hypothalamic-pituitary-adrenal (HPA) axis with cortisol levels <250 nmol/l during their first visit. A total of 13 of 18 patients regained their HPA axis activity when the baseline cortisol was measured after using topical corticosteroids which resulted in 75% improvement in the disease activity. Conclusions: The disease activity rather than the use of topical costicosteroids is responsible for the low basal levels in patients with severe AD.

Efficacy of cabergoline on rapid escalation of dose in men with macroprolactinomas.

Background & objectives: Since cabergoline has a long half-life and sustained occupancy of dopamine (D2) receptors in lactotrophs, its doses are slowly built up either monthly or two monthly. This possibly results in delayed normalization of serum prolactin and slow reduction in tumour size. This study was planned to assess the efficacy and safety of rapid escalation of cabergoline doses in men with macroprolactinomas. Materials: Fifteen consecutive men with macroprolactinomas underwent evaluation for anterior pituitary functions, visual fields, quality of life (QOL) score and magnetic resonance imaging (MRI), at baseline and after 6 months of cabergoline therapy. Serum prolactin and testosterone levels were assessed at monthly intervals. Cabergoline was started at a dosage of 0.5 mg twice per week and increased to 1.5 mg twice per week (3 mg ) by the third week, as 3 mg is usually considered as effective dose. Subsequent increase in doses was done as per protocol. Results: The mean age of patients at presentation was 31.7 ± 3.3 yr and duration of symptoms was 25.0 ± 3.6 months. Serum prolactin at baseline was 6249.3 ± 3259.2 μg/l with a tumour volume of 28.9 ± 8.3 cm3. Eighty six per cent of the patients had visual field defects while 53 per cent had decreased visual acuity. The mean dose of cabergoline required was 3.2 mg/wk. Symptoms improved in majority (93%) of patients after four weeks of cabergoline therapy with a dramatic fall in serum prolactin by 99 per cent from 6249.3 ± 3259.2 to 46.9 ± 14.9 μg/l and it was normalized in 93 per cent of the patients by 8.2 wk. Improvement in visual field defects was noted in all but one, after one month and there was further improvement at 6 months. All patients had >25 per cent reduction in tumour size, and 73 per cent had > 50 per cent reduction after six months of cabergoline therapy. Basal circulating testosterone levels were low in 11 (73%) patients and started improving from first month of cabergoline therapy and became normal in around half of the patients after 6 months. No major side effects were observed requiring discontinuation of cabergoline therapy. Interpretation & conclusions: Our preliminary findings show that rapid build-up of cabergoline doses increases its efficacy as well as rapidity of response in terms clinical improvement, normalization of serum prolactin and gonadal functions and reduction in tumour size, without compromising its safety in men with macroprolactinomas. Further studies with a larger sample size and control group for comparison need to be done to confirm these findings.

Hypophosphataemic rickets/osteomalacia: A descriptive analysis.

Background & objectives: Hypophosphataemic rickets/osteomalacia (HRO) is an uncommon metabolic bone disorder which affects all ages and either sex. It is characterized by low concentration of serum phosphate levels leading to impairment of mineralization of bone matrix with variable aetiology. We present clinical profile and treatment outcome of 17 patients of HRO. Methods: Seventeen consecutive patients (8 were < 18 yr of age, with median age of presentation being 27.5 yr) of HRO who came to the department of Endocrinology in a tertiary care hospital in north India from January 2000 to December 2006 were included in the present study. Their aetiology, clinical features, biochemical parameters, radiographic features, treatment and outcome were analyzed. Results: HRO was commoner in females (70.5%) with positive family history observed in 6 (35.3%) patients. Common presenting features were short stature (58.8%), backache (58.8%), bony deformities (58.8%), joint pain (52.9%), fractures (29.4%) and dental abnormalities (23.5%). Radiological abnormalities noted were generalized bony deformities (58.8%), fractures (29.4%), and pseudo fractures (17.6%). Mesenchymal tumours were localized in the pelvis in one patient and in the right jaw in another. The patients were treated with calcium (elemental calcium 1 g/d) and oral phosphate supplements (dose 30 – 50mg/kg/day in divided doses) along with active vitamin D supplements (dose 1- 3 μg/day) and followed up for a mean of 2 yr. Two patients also received growth hormone (GH) therapy in the dose of 2U/day for 6 and 18 months respectively. Symptomatic well being was reported by all the patients and improvement was noted in the levels of phosphate (P<0.005) and alkaline phosphatase (P<0.05) after treatment. Interpretation & Conclusions: A diagnosis of HRO should be considered in all patients presenting with short stature, deformities or musculoskeletal pains along with low serum phosphate with normal iPTH and 25 – hydroxy vitamin D.

Osteogenesis imperfecta.

Background: Osteogenesis imperfecta (OI) is a rare metabolic bone disorder characterized by increased bone fragility, low bone mass, recurrent fractures and numerous extra-osseus features. Many patients remain undiagnosed and unattended particularly in developed countries. Presently, medical management with bisphosphonates has changed the scenario. Materials and Methods: Twenty consecutive patients of OI were enrolled over a period of four years. Their clinical features, radiology, and biochemical parameters and treatment outcome were analysed. Results: Of the 20 patients, 16 (80%) were male and 4 (20%) were female. Mean age (SD) of the patients was 20.8 (13.8) years. All the patients had presented with fractures, the number of fractures per person varying from 1 to 20. Long bones were predominantly involved and thirteen (65%) had deformities of long bones. Ten (50%) had a positive family history of fractures after trivial traum. Eleven (55%) patients had dentiginous imperfecta (DI) and ten (50%) had blue sclerae at presentation. Impaired hearing was present in 1 patient only. Calcium profile was normal. Nine patients received pamidronate. Fracture frequency and pain decreased remarkably in these patients. Conclusion: Patients with OI presented late, predominantly with fracture of long bones, deformities and blue sclerae. Pamidronate therapy remarkably decreased fractures and pain in these patients. ©

Ectopic Cushing's syndrome: experience from a tertiary care centre.

BACKGROUND & OBJECTIVE: Ectopic secretion of adrenocorticotropic hormone (ACTH) is rare, contributing to 10 per cent cases of endogenous Cushing's syndrome. We describe our experience of about two decades of patients with ectopic Cushing's syndrome (ECS) seen at a tertiary care centre from north India. METHODS: Records of patients with ECS from 1985 to 2006 were retrospectively reviewed that included the presenting manifestations, clinical symptoms and signs, biochemical investigations including plasma cortisol, ACTH and high dose dexamethasone suppression test (HDDST), imaging modalities to localize the non pituitary source of ACTH production, management and follow up of these patients. RESULTS: The study group included 12 patients (7 men) with mean (+/-SD) age at presentation 27.6 +/- 9.5 yr (range 13 to 48 yr) and the mean lag period between onset of symptoms and the diagnosis was 18.3 +/- 12.9 months with a range of 3 to 48 months. The weight loss (41.7%) followed by hyperpigmentation (25%) and infections (16.7%) were the common presenting manifestations. Cuticular atrophy (100%), hypertension (100%), bruise (92%) and proximal myopathy (83%) were the commonest signs. Plasma cortisol at 0800 h was 1267.3 +/- 483.3 nmol/l and at 2200 h was 1214.9 +/- 442.6 nmol/l indicating loss of circadian rhythm. The mean plasma ACTH was 221.1 +/- 55.9 (range 21.7 to 950 pg/ml). All but 2 patients had non-suppressibility of 0800 h plasma cortisol with HDDST. Five patients had thymic carcinoid, 3 had bronchial and one each had islet, hepatic and gut carcinoid and one had medullary thyroid carcinoma as a cause of ectopic ACTH secretion. The mean duration of follow up of these patients was 42.6 months and only two could sustain cure while remaining had either residual or recurrence. INTERPRETATION & CONCLUSION: Ectopic Cushing's syndrome is a rare disease with varied manifestations and associated with increased morbidity and mortality. It presents with clinical features quite similar to classical Cushing's. Surgery with removal of primary tumour was found to be treatment of choice.

Does Paget's disease exist in India?: A series of 21 patients.

OBJECTIVE: Paget's disease of bone has been described as a few case reports from India. The aim of the present study is to document the existence of Paget's disease (PD) in India. MATERIAL AND METHODS: We describe demography, clinical manifestations, biochemical and radiological profile and the treatment outcome of 21 patients of PD. RESULTS: Mean (+/-SD) age of these patients at presentation was 49.2 +/- 17.6 years and the male to female ratio was 2.5:1. Common clinical manifestations included backache, headache and bone pains. Others were fracture, joint pain, deafness, gait ataxia, visual impairment and difficulty in biting. Two patients presented with hydrocephalus and one had recurrent paraparesis. Fifteen (71.4%) patients had polyostotic and six (28.6%) had monoostotic Paget's disease. More commonly involved bones were skull and spine (61.9%) followed by pelvis (38.1%), femur (33.3%), tibia (9%) and ulna (9%). Mean (+/-SD) serum alkaline phosphatase at diagnosis was 1514 +/- 1168 IU/L and nine months after treatment with bisphosphonates decreased to 454 +/- 406 IU/ L(P<0.03). CONCLUSION: This illustrates that Paget's disease does exist in India and a high index of suspicion is required to clinch the diagnosis.

Hypomagnesaemia masquerading as hypoparathyroidism.

Magnesium deficiency is a common clinical problem. Dietary malabsorption and renal wasting are the commonest causes. Hypomagnesemia induces a state of functional hypoparathyroidism due to decreased secretion of parathormone (PTH) as well as resistance to its action. Contrary to typical autoimmune hypoparathyroidism, it is associated with decreased levels of serum phosphate. We report a patient who presented with hypocalcemic tetany associated with hypomagnesaemia due to renal wasting. Subsequently, he improved with magnesium supplementation of therapy.

Juvenile hyperthyroidism: an experience.

OBJECTIVE: To analyze the clinical profile of juvenile hyperthyroidism at presentation, their treatment outcome; predictors of remission and relapse. METHODS: Retrospective analysis of medical records of 56 patients with juvenile hyperthyroidism seen over a period of 16 years. A cohort of 38 females and 18 males with mean (+/-SD) age of 14.9 +/- 3.4 years (range 3 to 18 years) was analyzed. RESULTS: Majority of patients was in the age group of 12-16 years. Common symptoms observed at presentation were weight loss (82.1%), excessive sweating (78.6%), heat intolerance (76.8%), increased appetite (73.2%) and diarrhea in 48.2%. In addition, accelerated linear growth was observed in 7.1% of patients. Goiter was present in 98.2% of children; 94.5% of which was diffuse and 4.8% was multinodular. The mean ((+/-SD) T3 was 4.8 +/- 3.4 ng/mL (N, 0.6-1.6), T4 was 218 +/- 98 ng/mL (N, 60-155) and TSH was 0.44 +/- 0.36 (N, 0.5-5.5 microIU/mL). TMA positivity seen in 36.9% of patients. All patients were treated with carbimazole; subsequently 4 patients required thyroidectomy and one required radioactive iodine ablation. Mean (+/-SD) duration of follow-up in our patients was 4.9 +/- 3 years, ranging between 1.6 to 16 years and mean (+/-SD) duration of treatment was 34.4 +/- 22.6 months (range 12 to 120 months). Mean (+/-SD) duration to achieve euthyroidism was 5.2 +/- 4.7 months, ranging between 1-33 months. On intention to treat analysis, remission with carbimazole was achieved in 47.6%, remaining patients failed to achieve remission with drug treatment. CONCLUSION: Graves disease is the commonest cause of juvenile hyperthyroidism. Carbimazole is safe, effective, cheap, and easily available form of therapy. It is occasionally associated with serious side effects but requires prolonged follow up.

Pathophysiology of prediabetes.

Type 2 diabetic patients pass through a phase of impaired glucose tolerence and/or impaired fasting glucose known as 'prediabetic state'. Prediabetic state form a part of syndrome X, other components being obesity, hypertension, dyslipidaemia, hyperinsulinaemia and insulin resistance. The pathophysiology of prediabetes is similar to type 2 diabetes mellitus, two basic defects are insulin resistance and early beta cell failure. In prediabetes, the rapid oscillations of insulin secretion are lost and amplitude of large pulses are decreased. When insulin is delivered in a pulsatile fashion that mimics the normal rapid oscillation, its hypoglycaemic effects are greater. In prediabetes, the glycaemic excursions after each meal are high and early insulin responses to meals tend to be lower than normal but the second phase of insulin secretion is delayed and prolonged.

Co-occurrence of emphysematous cystitis and emphysematous myositis in type 2 diabetes.

Emphysematous cystitis (EC) and emphysematous myositis (EM) are rare disorders and concurrent occurrence of both in a patient with type 2 diabetes has not been reported previously. We report a patient who presented with pneumaturia and later with pain in thigh and diagnosed of both concurrently.

Unconjugated hyperbilirubinemia in nonalcoholic steatohepatitis--is it Gilbert's syndrome?

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have normal liver function tests except for raised transaminases until they have progressed to cirrhosis of liver. The objective of this study was to evaluate patients of NASH for the presence of hyperbilirubinemia at presentation. METHOD: Sixty-seven patients of NASH were studied for the presence of hyperbilirubinemia at presentation. All patients were worked up for the presence of cirrhosis and hemolytic work up and fasting test were done in those found with unconjugated hyperbilirubinemia. RESULTS: Five out of 67 patients (7.5%) of NASH were found to have unconjugated hyperbilirubinemia. Though the fasting test was not positive, they all had a negative hemolytic workup and none of them had underlying cirrhosis. Clinical characteristics of patients with unconjugated hyperbilirubinemia were similar to those with normal serum bilirubin levels. CONCLUSION: Unconjugated hyperbilirubinemia in patients with NASH may suggest an associated Gilbert's syndrome.

Efficacy of once- or twice-daily extended release metformin compared with thrice-daily immediate release metformin in type 2 diabetes mellitus.

BACKGROUND: The extended-release formulation of metformin (MXR) prolongs drug absorption in the upper gastrointestinal tract and permits once-daily dosing in patients with type 2 diabetes mellitus (T2DM). This newer formulation may enhance patient compliance with oral therapy compared to conventional immediate-release metformin (MIR) in T2DM. OBJECTIVES: To analyse whether a switch from thrice daily MIR to once or twice daily MXR wouldachieve comparable degrees of glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: We conducted an open study of the efficacy and tolerability of MXR in 40 patients with T2DM who had achieved moderate or good glycemic control with MIR alone or in combination with other antihyperglycemic agents. After a lead in period of 3 months patients were switched over to a specific brand of MIR at baseline (Visit 0). Patients were subsequently followed for 4 more visits. These visits were done monthly, after taking MIR in a dose of 1-2 g/day (Visit 1); MXR as a single dose at dinner but 0.5 g less than baseline dose of MIR (Visit 2); MXR, 1-2 g/day as a single dose at bedtime, with strength same as that of baseline dose of MIR (Visit 3); and MXR, 1-2 g/day in two divided doses keeping dose same as baseline MIR (Visit 4). Glycemic control was assessed by a four-point glucose profile (fasting and three postprandial levels) at each visit. RESULTS: At visit 2, when patients had been on 500 mg lesser dose of MXR for 1 month, glucose profile worsened. However, glycemic control, at visit 3, returned to earlier levels when dose of MXR was increased back to original dose. Overall the MXR formulation was well tolerated with minor gastrointestinal adverse effects, reported by only 3 patients. CONCLUSION: Patients with T2DM who had been receiving thrice-daily MIR achieved comparable glycemic control when therapy was switched to once- or twice-daily MXR at the same total daily dose.

Young boy with multiple periarticular swellings and discharging sinuses: tumoral calcinosis.

A young boy with periarticular nodules and discharging sinuses diagnosed as tumoral calcinosis is described. The case is reported to highlight its rarity and low index of suspicion for this disease. Mechanisms of these solid tumours deposits and their management are discussed.