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.

A case of Liddle's syndrome; unusual presentation with hypertensive encephalopathy.

Liddle's syndrome is a rare cause of secondary hypertension. Identification of this disorder is important because treatment differs from other forms of hypertension. We report an interesting case of a 35-year-old lady, a known diabetic and hypertensive patient, who presented with features of hypertensive encephalopathy. The family history was unremarkable. Past treatment with various combinations of antihypertensive medications including spironolactone, all at high doses, failed to control her blood pressure. Upon evaluation, the patient had hypokalemic alkalosis, low 24-h urine potassium and suppressed plasma renin activity. Although these findings were similar to hyperaldosteronism, plasma aldosterone was lower than the normal range. Blood pressure decreased markedly after administration of amiloride. Along with hyporeninemic hypo-aldosteronism, the non-responsiveness to spironolactone and good response to amiloride established the diagnosis of Liddle's syndrome.

Genetic analysis of a family with complete androgen insensitivity syndrome.

Androgen insensitivity causes impaired embryonic sex differentiation leading to developmental failure of normal male external genitalia in 46 XY genetic men. It results from diminished or absent biological actions of androgens, which is mediated by the androgen receptor (AR) in both the embryo and secondary sexual development. Mutations in the AR located on the X chromosome are responsible for the disease. Almost 70% of affected individuals inherit the mutation from their carrier mother. We hereby report a 10-year-old girl with all the characteristics of complete androgen insensitivity syndrome (CAIS). Similar scenario was observed in 3 maternal aunts, Sequencing of the AR gene in all the family members revealed C 2754 to T transition in exon 6. It was concluded that the C 2754 to T transition rendered the AR incapable of both ligand-binding and activating the transcription and was the cause of CAIS in the patient.

Type 2 diabetes mellitus: An unusual association with Down's syndrome.

Down's syndrome (DS) is known to be associated with autoimmune disease including type 1 diabetes. To the best of our knowledge, there are no reports of DS with type 2 diabetes mellitus in the literature. We hereby report two cases of DS with type 2 diabetes.

Surgical revascularization techniques for diabetic foot.

Diabetes is an important risk factor for atherosclerosis. The diabetic foot is characterized by the presence of arteriopathy and neuropathy. The vascular damage includes non-occlusive microangiopathy and macroangiopathy. Diabetic foot wounds are responsible for 5-10% of the cases of major or minor amputations. In fact, the risk of amputation of the lower limbs is 15-20% higher in diabetic populations than in the general population. The University of Texas classification is the reference classification for diabetic wounds. It distinguishes non-ischemic wounds from ischemic wounds which are associated with a higher rate of amputation. The first principles of treatment are the control of pain of an eventual infection. When ischemia is diagnosed, restoration of pulsatile blood flow by revascularization may be considered for salvaging the limb. The treatment options are angioplasty with or without stenting and surgical bypass or hybrid procedures combining the two. Distal reconstructions with anastomosis to the leg or pedal arteries have satisfactory limb-salvage rates. Subintimal angioplasty is a more recent endovascular technique. It could be suggested for elderly patients who are believed to be unsuitable candidates for a conventional bypass or angioplasty. The current article would focus on the various revascularization procedures.

Correlation of vitamin D, bone mineral density and parathyroid hormone levels in adults with low bone density.

BACKGROUND: Bone mineral densiy (BMD) is known to be affected by serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels. Indian data pertinent to above observation is scant. Our study aimed to investigate the relationships between serum 25-hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels and bone mineral density (BMD) in a cohort of Indian patients. MATERIALS AND METHODS: Adults with or without fragility fractures with low BMD at the hip or lumbar spine were evaluated clinically along with laboratory investigations. T-scores of the hip and spine were derived from BMD-DEXA (dual-energy X-ray absorptiometry). Multivariate regression models were used to investigate the relationships between serum 25(OH) D, iPTH and BMD. RESULTS: Total of 102 patients (male:female = 38:64) with a mean age of 62.5 ± 6.4 years were included in the study. Forty-four patients had osteopenia. Osteoporosis was present in 58 patients. The mean values for serum 25(OH) D and iPTH levels were 21.3 ± 0.5 ng/ml and 53.1 ± 22.3 pg/ml, respectively. In 84.3% of patients, serum 25(OH) D levels were below 30 ng/ml (Normal = 30-74 ng/ml), confirming vitamin D deficiency. There was no association between 25(OH) D levels and BMD at the hip or lumbar spine (P = 0.473 and 0.353, respectively). Both at the hip and lumbar spine; iPTH levels, male gender, body mass index (BMI) and age were found to be significant predictors of BMD. Patients with higher BMI had significantly lower BMD and T-score. At levels <30 ng/ml, 25(OH) D was negatively associated with iPTH (P = 0.041). CONCLUSION: Among our cohort of patients with low BMD, no direct relationship between serum 25(OH) D levels and BMD was observed. However, a negative correlation between iPTH and 25(OH) D at serum 25(OH) D concentrations <30 ng/ml. Serum iPTH levels showed a significant negative association with BMD at the hip and lumbar spine. Our findings underscore the critical role of parathyroid hormone in bone metabolism and health.

Fetal endocrinology.

Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition.

Carotid intima media thickness in type 2 diabetes mellitus with ischemic stroke.

BACKGROUND: Diabetes mellitus is associated with high cardiovascular risk. Carotid intima media thickness (CIMT) is used commonly as a noninvasive test for the assessment of degree of atherosclerosis. The objective of this study was to find out the cut-off point for CIMT for ischemic stroke in patients with type 2 diabetes mellitus (T2DM) and to correlate CIMT with various parameters like smoking, hypertension, lipid profile and duration of T2DM. MATERIALS AND METHODS: A total of 80 subjects in the age group of 30-75 years (M:F = 57:23) were selected and divided into three groups, i.e. diabetes with ischemic stroke, diabetes and healthy subjects. All the participants were subjected to B-mode ultrasonography of both common carotid arteries to determine CIMT, along with history taking, physical examination and routine laboratory investigations including included fasting and 2-hour postprandial blood sugar, blood urea, serum creatinine, lipid profile, glycated hemoglobin, and microalbuminuria. RESULTS: Patients with T2DM with or without ischemic stroke were found to have significantly higher prevalence of increased CIMT and a value greater than 0.8 mm was found to be associated with the occurrence of stroke. The mean carotid IMT of the group as a whole was 0.840 ± 0.2 mm. The mean carotid IMT was not significantly different between T2DM patients with or without ischemic stroke (1.06 ± 0.2 vs. 0.97 ± 0.26 mm, P = 0.08). However, the mean CIMT was significantly higher in diabetic subjects compared to healthy subjects (1.01 ± 0.28 mm vs. 0.73 ± 0.08, P = 0.006). Other parameters like higher age, smoking, hypertension, hyperlipidemia, low HDL cholesterol, the glycemic parameters and the duration of diabetes were independently and significantly related to CIMT. CONCLUSION: A high CIMT is a surrogate and reliable marker of higher risk of ischemic stroke amongst type 2 diabetic patients. Our study demonstrates the utility of carotid IMT as a simple non-invasive screening test for the assessment of atherosclerosis risk/prognosis in type 2 diabetics.

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.

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.

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.

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.

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.

Coexistence of pheochromocytoma with uncommon vascular lesions.

BACKGROUND: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. MATERIALS AND METHODS: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. RESULTS: Of the 50 patients with pheochromocytoma, 7 (14%) had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. CONCLUSION: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis.

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.

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.

Sturge-Weber syndrome: presentation with partial hypopituitarism.

Sturge-Weber syndrome (SWS) is a rare disorder involving central nervous system abnormalities. It manifests with a facial port-wine birthmark and a vascular malformation of the brain. Infants and children present with seizures and stroke-like episodes with focal neurologic deficits. Patients with Sturge-Weber syndrome carry the additional risk of developing hypothalamic-pituitary dysfunction, secondary to their central nervous system dysfunction. Although one would suspect the hypothalamic-pituitary axis would be at risk for impairment given the abnormalities that often occur in Sturge-Weber syndrome, they are not commonly recognized by clinicians. Increased awareness of this potential complication in patients with this rare disease of Sturge-Weber syndrome is needed. We hereby report a case of SWS with partial hypopituitarism and consider it to be important that these patients should undergo routine evaluation of pituitary function in the face of any relevant clinical manifestations.

Ovarian granulosa cell tumor: An uncommon presentation with primary amenorrhea and virilization in a pubertal girl.

A 16-year-old girl presented with primary amenorrhea and excess hair growth on her body and face for the last three years, along with pain and a mass in her lower abdomen for last one year. Examination revealed hirsutism and other virilizing features, with an irregular mass in the lower abdomen corresponding to 16 weeks'gestation. Serum testosterone was 320 ng / dl and ultrasonogram of the pelvis revealed a solid mass of 5 × 4 cm in the left adnexa. Suspecting it to be a virilizing tumor of the left ovary, the patient was subjected to staging laparotomy, which revealed stage 1a ovarian involvement amenable to surgical resection alone. Histopathological examination confirmed the diagnosis of granulosa cell tumor of the ovary. Postoperatively the serum testosterone returned to 40 ng / dl and her menstrual cycle started after two months of surgery.

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.