Persistent Elevation of Parathormone Levels after Surgery for Primary Hyperparathyroidism.

BACKGROUND: Persistent elevation of serum parathyroid hormone (PTH) despite normocalcemia have been documented in 8- 40% of patients after parathyroidectomy. We hereby report our experience from different centers across India to determine clinical significance of postoperatively elevated PTH levels and review relevant literature. METHODS: We conducted a retrospective case series study and reviewed all the patients who underwent surgery for primary hyperparathyroidism (PHPT) from April 2010 to January 2020. RESULTS: Total of 201 patients was diagnosed as PHPT. Out of available follow-up data of 180 patients, a total of 54 patients (30%) had persistently elevated PTH (PePTH) at 1 month. Patients with PePTH were older with higher preoperative serum calcium, iPTH, alkaline phosphatase and lower serum phosphate and 25-hydroxy vitamin D3 levels. Creatinine clearance was found to be significantly lower in patients with PePTH. Multiple linear regression analysis revealed that preoperative 25-OH D3 concentration, creatinine clearance and iPTH are the factors influencing persistent elevation of PTH levels. Significantly lower serum calcium and higher alkaline phosphatase levels were observed in PePTH patients with preoperative 25-OH D3 levels <20 ng/mL. Thirty patients at 6 months, 24 patients at 1 year, 18 patients at 2 years and 9 patients at 3 years had eucalcemic PTH elevation. Nine out of 126 (7%) patients with normal initial postoperative calcium and iPTH levels developed PePTH, with none culminating into recurrent hyperparathyroidism. CONCLUSION: Though the pathogenesis of such a phenomenon still remains to be elucidated, a multifactorial mechanism appears to play a role.

Prediction of remission after metabolic surgery using a novel scoring system in type 2 diabetes - a retrospective cohort study.

BACKGROUND: Remission of diabetes is seen in more than 60% of patients after bariatric surgery. There is extensive variability in the remission rates between different surgical procedures. We analyzed our database and aimed to develop an easy scoring system to predict the probability of diabetes remission after two surgical procedures i.e. Ileal Interposition coupled with Sleeve Gastrectomy (IISG) or Diverted Sleeve Gastrectomy (IIDSG). METHODS: In this retrospective study, we analyzed records pertaining to patients who underwent IISG (n = 46) and IIDSG (n = 29). The primary outcome measure was diabetes remission (A1c <6.5% and not requiring hypoglycemic drugs). We identified seven preoperative clinical variables (age, duration of diabetes, body mass index, micro and macrovascular complications, use of insulin and stimulated C-peptide) based on our previous reports to be included in the diabetes remission score (DRS). The DRS score (7 - 14) was compared between the patients with and without remission in both the surgery groups. RESULTS: Mean DRS in patients who underwent IISG was 9.2 ± 1.4. Twenty one (46%) had a remission in diabetes. DRS was significantly lower in patients with remission than patients without remission (8.1 ± 0.8 versus 10.2 ± 0.9, p < 0.0001). Mean DRS in patients who underwent IIDSG was 10.4 ± 1.3. Twenty one (72%) had a remission in diabetes. DRS was significantly lower in patients with remission than patients without remission (9.7 ± 0.8 versus 12.0 ± 0.5, p < 0.0001). Patients with a DRS ≥ 10 in IISG group and more than 12 in IIDSG group did not get into remission. CONCLUSION: Preoperative DRS can be a useful tool to select the type of surgical procedure and to predict the postoperative diabetes remission. TRIAL REGISTRATION: NCT00834626.

Glycemic variability: Clinical implications.

Glycemic control and its benefits in preventing microvascular diabetic complications are convincingly proved by various prospective trials. Diabetes control and complications trial (DCCT) had reported variable glycated hemoglobin (HbA1C) as a cause of increased microvascular complications in conventional glycemic control group versus intensive one. However, in spite of several indirect evidences, its link with cardiovascular events or macrovascular complications is still not proved. Glycemic variability (GV) is one more tool to explain relation between hyperglycemia and increased cardiovascular risk in diabetic patients. In fact GV along with fasting blood sugar, postprandial blood sugar, HbA1C, and quality of life has been proposed to form glycemic pentad, which needs to be considered in diabetes management. Postprandial spikes in blood glucose as well as hypoglycemic events, both are blamed for increased cardiovascular events in Type 2 diabetics. GV includes both these events and hence minimizing GV can prevent future cardiovascular events. Modern diabetes management modalities including improved sulfonylureas, glucagon like peptide-1 (GLP-1)-based therapy, newer basal insulins, and modern insulin pumps address the issue of GV effectively. This article highlights mechanism, clinical implications, and measures to control GV in clinical practice.

Carbimazole-induced cholestatic hepatitis in Graves' disease.

Antithyroid medications are one of the treatment options for Graves' disease. Carbimazole is widely used as the drug of choice, except in pregnancy, where propythiouracil is preferred by many. It is generally well-tolerated. Its side-effects include allergy, upper gastrointestinal upset, a rare occurrence of granulocytosis, and others. Hepatitis is another rare, but serious side-effect. We report a healthy 30-year-old male patient with Graves' disease, who developed cholestatic jaundice after Carbimazole therapy for four months. He made a full recovery after the drug was discontinued. An idiosyncratic mechanism seemed likely.

Clinical analysis of hypertension in children: an urban Indian study.

Hypertension in children, although an uncommon entity, is associated with end-organ damage. We tried to study the clinical profile of hypertension in children presented to our hospital. The medical records from January 1990 to December 2010 of all children aged 18 years and younger with hypertension were studied. The patients were divided into four age groups (infants, pre-school age, school age and adolescents) Presenting symptoms and other clinical parameters were thoroughly evaluated. The results were compared with previous studies on hypertension in children. A total of 135 patients were selected (male:female 103:32), with mean age of 0.4 ± 2.1 years (range: six months to 17 years). The most common age group affected was the adolescents group (42.9%). The most common clinical feature at presentation was dizziness (30.3%), followed by headache and chest discomfort (22.9%). Transient hypertension was detected in 34 patients (25.2%), and was most common in the adolescent age group, whereas sustained hypertension was noticed in 101 patients (74.8%) and was the most common in the school age group (36/45, 80%). Forty-two patients (31.1%) presented with hypertensive crisis. Nine patients were considered to have essential hypertension. The chief causes included chronic glomerulonephritis in 56 (41.5%), endocrine disorders in 21 (15.5%), obstructive uropathy in 16 (11.8%), reflux nephropathy in 12 (8.8%) and renovascular disease in 5 (3.7%). Takayasu's disease was the most common cause of renovascular hypertension. Coarctation of aorta was the most common cause of hypertension in infancy, being present in 40% of the cases. Hypertension in children may be easily underestimated but is a potentially life-threatening problem. Most of them are asymptomatic and a large chunk has an underlying etiology. Primary care clinicians should promptly identify patients with hypertension and treat them immediately and appropriately to prevent damage to the cardiovascular organs.

Endocrinology of parturition.

The myometrium must remain relatively quiescent during pregnancy to accommodate growth and development of the feto-placental unit, and then must transform into a highly coordinated, strongly contracting organ at the time of labour for successful expulsion of the new born. The control of timing of labour is complex involving interactions between mother, fetus and the placenta. The timely onset of labour and delivery is an important determinant of perinatal outcome. Both preterm birth (delivery before 37 week of gestation) and post term pregnancy (pregnancy continuing beyond 42 weeks) are both associated with a significant increase in perinatal morbidity and mortality. There are multiple paracrine/autocrine events, fetal hormonal changes and overlapping maternal/fetal control mechanisms for the triggering of parturition in women. Our current article reviews the mechanisms for uterine distension and reduced contractions during pregnancy and the parturition cascade responsible for the timely and spontaneous onset of labour at term. It also discusses the mechanisms of preterm labour and post term pregnancy and the clinical implications thereof.

Implications of serum paraoxonase activity in obesity, diabetes mellitus, and dyslipidemia.

Human serum paraoxonase 1 (PON1) is an enzyme with esterase activity, and is physically bound to high-density lipoproteins (HDL). It plays a key role in the action of HDL toward protection of lipoprotein and biological membrane against oxidative damage. It may have a protective role against atherosclerosis by virtue of its action on hydrolyzing lipid peroxides and preventing accumulation of phospholipids in oxidized low-density lipoprotein (LDL). PON1 is hypothesized to be an indicator of the risk of atherosclerosis and coronary artery disease development. Numerous studies have implicated PON1 activity in relation to various endocrine disorders. The current article reviews the clinical perspectives of PON1 activity with regards to obesity, diabetes mellitus with its complications, and dyslipidemia.

Clinical profile of coexisting conditions in type 1 diabetes mellitus patients.

AIMS: Type 1 diabetes mellitus (T1DM) is associated with various genetic and autoimmune diseases implicated in its etiopathogenesis. We hereby profile the clinical association of such diseases among patients from our center. METHODS: Consecutive patients of T1DM presenting to department of Endocrinology from May 1997 to December 2011 were retrospectively analyzed in context of associated clinical profile. RESULTS: Among 260 patients diagnosed as T1DM, 21 (8%) had hypothyroidism, 4 (1.5%) had hyperthyroidism and 2 (0.7%) had primary adrenal insufficiency. Eighteen patients (7%) had celiac disease, 9 (3.5%) had Turner's syndrome, 5 patients (1.9%) had Klinefelter's syndrome, whereas Down's syndrome and Noonan's syndrome was present in 2 and 1 patients (0.7%) respectively. One patient had Wolframs' syndrome and 1 patients had myasthenia gravis. Systemic lupus erythematosus and rheumatoid arthritis were present in 3 and 1 patients respectively. Total of 5 patients with cerebral palsy, 4 cases with deaf mutism, 4 cases with acute psychosis and 16 patients with depression were noted. Mean age of study patients was 20.8±9.8 years (range, 3-23 years). CONCLUSION: Various conditions including genetic (Down, Turner, Noonan, and Klinefelter's), autoimmune (thyroid and adrenal disorders, myasthenia gravis, SLE, rheumatoid arthritis) and central nervous system diseases were the associated diseases encountered in our patients. Routine screening is required for early diagnosis and treatment of associated co morbidities.

ACE inhibitors or ARBs for diabetic nephropathy: the unrelenting debate.

Adequate control of blood pressure is of paramount importance in delaying the progression of renal disease in diabetic patients. Drugs acting on renin angiotensin aldosterone axis are of proven value in diabetes. Particularly angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have benefits beyond blood pressure control. The current article focuses on various studies supporting the use of ACEIs and ARBs in diabetic subjects.

Genetics of type 2 diabetes mellitus and other specific types of diabetes; its role in treatment modalities.

Type 2 diabetes mellitus (T2DM) is among the most challenging health issues of the 21st century and is associated with an alarming rise in the incidence. The pathophysiological processes that lead to development of T2DM are still unclear, however impairment in insulin secretion and/or action is clearly indicated. Type 2 diabetes is a polygenic disorder with multiple genes located on different chromosomes contributing to its susceptibility. Analysis of the genetic factors is further complicated by the fact that numerous environmental factors interact with genes to produce the disorder. Only a minority of cases of type 2 diabetes are caused by single gene defects and one example is maturity onset diabetes of the young (MODY). Previous studies indicated that variants in genes encoding the pancreatic ß-cell K+ATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) are associated with neonatal diabetes. Six different types of maturity onset diabetes of young (MODY) have been identified based on characteristic gene defect. The common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ (PPAR-γ) gene was confirmed in several studies to be associated with type 2 diabetes as well. More recently, studies reported variants within a novel gene, TCF7L2, as a putative susceptibility gene for type 2 diabetes across many ethnic backgrounds around the world. MODY patients respond better to sulphonylureas and metformin, while neonatal diabetes patients with genetic mutations can be changed from insulin to oral drugs. We hereby provide a comprehensive review on the role of genetics in type 2 diabetes mellitus.

Pheochromocytoma with inferior vena cava thrombosis: An unusual association.

Pheochromocytomas have been described in association with vascular abnormalities like renal artery stenosis. A 48-year-old man was admitted to our hospital with the complaints of headache, sweating, anxiety, dizziness, nausea, vomiting and hypertension. For last several days, he was having a dull aching abdominal pain. Abdominal computed tomography (CT) revealed the presence of a left adrenal pheochromocytoma. An inferior vena cava (IVC) venogram via the right jugular vein demonstrated occlusion of the IVC inferior to the right atrium. Surgical removal of pheochromocytoma was done, followed by anticoagulant treatment for IVC thrombosis, initially with subcutaneous low molecular weight heparin, and then with oral warfarin, resulting in restoration of patency. To the best of our knowledge, the occurrence of pheochromocytoma in IVC thrombosis has not been reported so far from India. Possible mechanisms of such an involvement are discussed.

Reversible mitral and aortic regurgitation due to pioglitazone.

OBJECTIVE: To report the occurrence of pioglitazone-induced reversible valvular regurgitant lesions. METHODS: Clinical, laboratory, and imaging data are reported on a patient with known type 2 diabetes mellitus, who was prescribed pioglitazone to achieve better glycemic control. RESULTS: We present a case report of a 50-year-old woman, in whom diabetes had been diagnosed 5 years previously, who developed severe mitral and aortic regurgitation during 5 months of treatment with pioglitazone along with clinical and laboratory indications of fluid retention. Echocardiography 5 months after discontinued use of pioglitazone showed regression of regurgitant lesions and normalization of pertinent laboratory variables. CONCLUSION: Five months of treatment with pioglitazone could potentially induce major cardiac valvular dysfunction, which was reversible in our patient. This report emphasizes the importance of carefully monitoring patients during treatment with thiazolidinediones.

Hypertriglyceridemia-induced recurrent acute pancreatitis: A case-based review.

Hypertriglyceridemia is a rare, but well-known cause of acute pancreatitis. A serum triglyceride level of more than 1000 to 2000 mg / dl is the identifiable risk factor. It typically presents as an episode of acute pancreatitis or recurrent acute pancreatitis. The clinical course and routine management of Hypertriglyceridemia-induced pancreatitis is similar to other causes. A thorough family history is important, as is the identification of secondary causes of hypertriglyceridemia. The mainstay of therapy includes dietary restriction of fatty meal and fibric acid derivatives. We hereby report the case of a 37-year-old lady with a family history of dyslipidemia presenting with recurrent episodes of acute pancreatitis. We also review the literature for pathogenesis and management of hyperlipidemia.

Aberrant angiogenesis: The gateway to diabetic complications.

Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes.

Neuropsychiatric screening in type 2 diabetes mellitus.

Diabetes mellitus is considered to be one of the most psychologically demanding of the chronic medical illnesses and is often associated with several psychiatric disorders. Psychiatric disorders can be a risk factor for, as well as a complication of, diabetes leading to bidirectional association between the two morbidities. Physicians caring for people with diabetes must be trained to recognize and manage comorbid psychiatric conditions that commonly occur. Our current article reviews the various screening procedures for effective evaluation of the neuropsychiatric illnesses coexisting with diabetes and other pertinent issues.

Pheochromocytoma with renal artery stenosis: A case-based review of literature.

Pheochromocytomas have been described to be associated with rare vascular abnormalities, most common of them being renal artery stenosis. A 45-year-old woman was admitted to our hospital with complaints of headache, sweating, anxiety, dizziness, nausea, vomiting and severe hypertension. Hypertension was confirmed to result from both excess catecholamine production and hyperreninemia of left kidney. The technical images (abdominal CT and renal arteriography) revealed the presence of a left adrenal pheochromocytoma and stenosis of the renal artery. Surgical removal of pheochromocytoma and correction of renal artery stenosis restored the postoperative plasma catecholamine, renin and blood pressure to normal. To our belief, this is the first such case report from India citing this rare association. We conclude that when the two diseases occur simultaneously, both must be diagnosed accurately and treated in a different manner. We also hereby review the existing literature.

Effect of diabetes on alteration of metabolism in cardiac myocytes: therapeutic implications.

Diabetic cardiomyopathy is a distinct entity in humans. It leads to ventricular dysfunction independent of and additive to coronary artery disease and hypertension. Clinical and experimental studies have pointed to the role of metabolic derangements in the development of diabetic cardiomyopathy. Altered insulin signaling in diabetes leads to decreased myocyte glucose uptake and utilization, associated with an increased concentration of free fatty acids. This results in decreased glucose oxidation and increased fatty acid oxidation. Fatty acids increase mitochondrial oxygen consumption for ATP production and stimulate the uncoupling proteins in mitochondria. These proteins decrease the mitochondrial protein gradient, leading to fall in ATP production. The resultant defect in myocardial energy production impairs myocyte contraction and diastolic function. This is the hallmark of diabetic cardiomyopathy at earlier stages. In later stages diabetes impairs the myocyte ischemic defense mechanism, leading to increased cardiovascular morbidity and mortality. Other factors contributing toward causation of diabetic cardiomyopathy are collagen accumulation leading to reduced myocardial compliance, accumulation of advanced glycation end product-modified extracellular matrix proteins with subsequent inelasticity of vessel walls and myocytes, abnormal myocardial calcium handling leading to altered mechanics, endothelial dysfunction, cardiac autonomic neuropathy, and impairment of ischemic preconditioning. Trimetazidine acts a metabolic switch, favoring glucose over free fatty acids as the substrate for metabolism in cardiac myocytes.