Diagnostic approach in 46, XY DSD: an endocrine society of bengal (ESB) consensus statement.

OBJECTIVES: 46, XY difference/disorder of sex development (DSD) is a relatively uncommon group of heterogeneous disorders with varying degree of underandrogenization of male genitalia. Such patients should be approached systematically to reach an aetiological diagnosis. However, we lack, at present, a clinical practice guideline on diagnostic approach in 46, XY DSD from this part of the globe. Moreover, debate persists regarding the timing and cut-offs of different hormonal tests, performed in these cases. The consensus committee consisting of 34 highly experienced endocrinologists with interest and experience in managing DSD discussed and drafted a consensus statement on the diagnostic approach to 46, XY DSD focussing on relevant history, clinical examination, biochemical evaluation, imaging and genetic analysis. CONTENT: The consensus was guided by systematic reviews of existing literature followed by discussion. An initial draft was prepared and distributed among the members. The members provided their scientific inputs, and all the relevant suggestions were incorporated. The final draft was approved by the committee members. SUMMARY: The diagnostic approach in 46, XY DSD should be multidisciplinary although coordinated by an experienced endocrinologist. We recommend formal Karyotyping, even if Y chromosome material has been detected by other methods. Meticulous history taking and thorough head-to-toe examination should initially be performed with focus on external genitalia, including location of gonads. Decision regarding hormonal and other biochemical investigations should be made according to the age and interpreted according to age-appropriate norms Although LC-MS/MS is the preferred mode of steroid hormone measurements, immunoassays, which are widely available and less expensive, are acceptable alternatives. All patients with 46, XY DSD should undergo abdominopelvic ultrasonography by a trained radiologist. MRI of the abdomen and/or laparoscopy may be used to demonstrate the Mullerian structure and/or to localize the gonads. Genetic studies, which include copy number variation (CNV) or molecular testing of a candidate gene or next generation sequencing then should be ordered in a stepwise manner depending on the clinical, biochemical, hormonal, and radiological findings. OUTLOOK: The members of the committee believe that patients with 46, XY DSD need to be approached systematically. The proposed diagnostic algorithm, provided in the consensus statement, is cost effective and when supplemented with appropriate genetic studies, may help to reach an aetiological diagnosis in majority of such cases.

Juvenile Hypothyroidism: A Clinical Perspective from Eastern India.

INTRODUCTION: Juvenile hypothyroidism (JH) can have deleterious effects on growth, pubertal development, and scholastic performance of children. In India, there is a paucity of data on acquired hypothyroidism in children, in contrast to congenital hypothyroidism. Our objective was to assess the profile of JH in a referral clinic from eastern India. MATERIALS AND METHODS: For this study, 100 patients with documented acquired hypothyroidism (subclinical and overt) (aged <18 years), from eastern India, were evaluated retrospectively. Evaluation included history as well as clinical, biochemical, and ultrasonography parameters. RESULTS: Out of the 100 participants, 74% had overt hypothyroidism (OH), while 26% had subclinical hypothyroidism (SCH). The majority of the participants were females (66%). The mean age at detection was 8.95 ± 3.96 years in the SCH group and 8.38 ± 3.29 years in the OH group. A family history of thyroid disorder and/or goiter was present in 35% of the patients. Goiter was the most common presentation in both SCH and OH, with overall prevalence of 58%. Height below 3rd percentile was significantly higher (28%) in OH group compared to 4% in SCH group. Five percent of OH subjects were obese. Worsening school performance was reported in only 9% of subjects. Only 4% (all males) presented with delayed puberty, while one female (1%) presented with precocious puberty. Sixty-four percent of OH group were TPOAb positive compared to only 15% in SCH group. Five percent of our study population had type-1 diabetes mellitus (T1DM) and 7% had Down syndrome (DS). CONCLUSION: In our study, JH showed significantly higher female preponderance and TPOAb positivity in OH group, in comparison to SCH group. Family history of thyroid disorder and/or goiter was present in a significant proportion of patients. Goiter was the most common presentation of JH. Height deceleration, weight gain, and fatigue were the other common presentations. Prevalence of short stature was significantly higher in OH group. Interestingly, in contrast to prevalent notion, only 5% of OH were obese and worsening school performance was observed to be rare. Puberty disorders (both delayed and precocious) may occur in JH as seen here. Because of strong association, those with T1DM or DS should be screened for JH and vice versa in TIDM.

Kidney Disease in Type 2 Diabetes Mellitus and Benefits of Sodium-Glucose Cotransporter 2 Inhibitors: A Consensus Statement.

Diabetic kidney disease (DKD) occurs in approximately 20-40% of patients with type 2 diabetes mellitus. Patients with DKD have a higher risk of cardiovascular and all-cause mortality. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and antihyperglycemic drugs form the mainstay of DKD management and aim to restrict progression to more severe stages of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) control hyperglycemia by blocking renal glucose reabsorption in addition to preventing inflammation, thereby improving endothelial function and reducing oxidative stress; consequently, this class of prescription medicines is emerging as an important addition to the therapeutic armamentarium. The EMPA-REG OUTCOME, DECLARE TIMI 58, and CANVAS trials demonstrated the renoprotective effects of SGLT2i, such as restricting decline in glomerular filtration rate, in the progression of albuminuria, and in death due to renal causes. The renoprotection provided by SGLT2i was further confirmed in the CREDENCE study, which showed a 30% reduction in progression of chronic kidney disease, and in the DELIGHT study, which demonstrated a reduction in albuminuria with dapagliflozin compared with placebo (- 21.0%, confidence interval [CI] - 34.1 to - 5.2, p = 0.011). Furthermore, a meta-analysis demonstrated a reduced risk of dialysis, transplantation, or death due to kidney disease (relative risk 0.67; 95% CI 0.52-0.86; p = 0.0019) and a 45% risk reduction in worsening of renal function, end-stage renal disease, or renal death (hazard ratio 0.55, CI 0.48-0.64, p < 0.0001) with SGLT2i, irrespective of baseline estimated glomerular filtration rate. Thus, there is emerging evidence that SGLT2i may be used to curb the mortality and improve the quality of life in patients with DKD. However, clinicians need to effectively select candidates for SGLT2i therapy. In this consensus statement, we have qualitatively synthesized evidence demonstrating the renal effects of SGLT2i and proposed recommendations for optimal use of SGLT2i to effectively manage and delay progression of DKD.

Prevalence of diabetes and impaired fasting glucose in a selected population with special reference to influence of family history and anthropometric measurements--the Kolkata policeman study.

AIMS AND OBJECTIVES: The aim of this study was to estimate the prevalence of diabetes as well as IFG in a population of policemen and to evaluate the possible influence of some risk factors. MATERIAL AND METHODS: It was an epidemiological study on a group of policemen in Kolkata. Diagnosis of diabetes was based on history and fasting plasma glucose. The study population was divided in three categories: normoglycaemic, IFG and diabetes. BMI, waist circumference, WHR and waist-to-height ratio were estimated. RESULTS: Out of 2160 subjects with a mean age of 36.4 yrs (between 20 and 60 yrs), diabetes was found in 11.5% (10.4% known and 1.1% newly diagnosed) and 6.2% had IFG. Prevalence of diabetes was found to be increasing with age (p < 0.001). There was no statistically significant difference in BMI when compared between groups (normoglycaemic, IFG and diabetes). Waist circumference, waist-to-height ratio and WHR of normoglycaemic group were significantly less than those with IFG and diabetes; however there was no statistically significant difference between the diabetes and IFG groups. Parental history had significant influence on the prevalence of diabetes; a 37.5% prevalence was found in persons with history of biparental diabetes and 20.8% with uniparental diabetes, whereas it was only 9.9% without any family history (p < 0.01 and p < 0.05, respectively.). CONCLUSION: The prevalence of diabetes in the study population was high and was strongly influenced by family history, age and abdominal adiposity, without having any appreciable impact of BMI.

Hypothyroidism and obesity: An intriguing link.

According to common perception, hypothyroidism is held responsible for obesity. However, linking them causally is controversial. Overt hypothyroidism is associated with modest weight gain, but there is a lack of clarity regarding subclinical hypothyroidism. Novel view indicates that changes in thyroid-stimulating hormone (TSH) could well be secondary to obesity. The increasing prevalence of obesity further confounds definition of normal TSH range in population studies. Thyroid autoantibody status may help in establishing the diagnosis of subclinical hypothyroidism in obesity. High leptin levels may play a role in the hyperthyrotropinemia of obesity and also increase susceptibility to thyroid autoimmunity and subsequent hypothyroidism. There is at most a modest effect of L-T4 treatment in overt hypothyroidism in inducing weight loss; benefit in subclinical hypothyroidism is not established with no data supporting thyroid hormone use in euthyroid obese patients.

Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes.

CONTEXT: The perception of non-alcoholic fatty liver disease (NAFLD) as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM) patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis. AIMS: To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT), new onset treatment naive T2DM and normal glucose tolerance (NGT) with and without NAFLD. SETTINGS AND DESIGN: Cross-sectional clinic-based study. SUBJECTS AND METHODS: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients. STATISTICAL ANALYSIS USED: Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables), Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively. RESULTS: NAFLD was significantly associated with higher alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT <25 U/L and GGT <15 U/L had highest negative predictivity whereas ALT >40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample. CONCLUSIONS: Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary diagnostic work-ups and early detection of NAFLD to reduce the risk of cirrhosis, hepatocellular carcinoma and classical cardiovascular disease in T2DM and IGT patients.

Infants with dilated cardiomyopathy and hypocalcemia.

Hypocalcemia is a rare reversible cause of dilated cardiomyopathy (DCM) and congestive heart failure; however, there are few reported cases, especially in infants. We describe 12 infants presenting with DCM and congestive cardiac failure who were found to have hypocalcemia. Vitamin D deficiency was the cause of hypocalcemia in all cases. The infants improved on supplementation with vitamin D and calcium.

Primary adrenal insufficiency in case of antiphospholipid syndrome.

Addison's disease or primary adrenal insufficiency (PAI) is a rare manifestation of antiphospholipid syndrome (APS). PAI is the most common among the endocrinologic manifestations and can also rarely be the presenting symptom of APS. Venous thrombosis and/or adrenal hemorrhage are the leading cause of PAI in APS. Autoimmune adrenal failure is postulated to be another possible mechanism. We report a case of PAI in a 44-year-old lady preceding primary APS, probably autoimmune, without any evidence of adrenal hemorrhage or infarction. High index of clinical suspicion for PAI in APS is needed; conversely APS should be considered as a possible pathogenetic process in patients presenting with Addison's disease where the etiology is not obvious.

Three cases of thyrotoxic periodic paralysis due to painless thyroiditis.

We present three cases of thyrotoxic periodic paralysis (TPP) due to painless thyroiditis presenting as acute quadriparesis. All responded to potassium supplementation and propranolol. TPP may be due to thyrotoxicosis of any etiology, commonly Grave's disease. The absence of clinical signs of thyrotoxicosis can delay diagnosis and treatment. Thyroid function tests should be a routine evaluation in all cases of hypokalemic periodic paralysis.

Juvenile hypothyroidism presenting with hypertrichosis, multicystic ovaries, and pituitary adenoma.

Primary hypothyroidism may present with atypical features in children. Here we report a 6-year-old female child with primary hypothyroidism presenting with a combination of several atypical features in the form of hypertrichosis, bilateral cystic ovaries, and feedback pituitary adenoma.

Childhood obesity: Determinants, evaluation, and prevention.

Childhood obesity is a grave issue, which needs to be addressed urgently because it leads to several medical and psychosocial problems in children. High prevalence is being increasingly reported in children from developing countries as well. The combination of our genetic propensity to store fat, the ready availability of calorie dense foods, and sedentary lifestyle promotes overweight. The child's food environment at home and parental obesity are strong determinants. Urban poor in developed countries and urban rich in developing countries are both at risk. In developing countries, a number of beliefs passed down over generations are other important determinants. Evaluation includes assessing the child's lifestyle, excluding weight-promoting medication history; poor linear growth needs endocrine evaluation; genetic syndromes should be considered if there are clinical pointers. Overweight children should be evaluated for hypertension, dyslipidemia, T2DM, and NAFLD. Therapeutic lifestyle changes targeting food habits and physical activity through parental participation and social support are the cornerstones of preventing childhood obesity. Active travel and play by making the built environment more accessible, ban on 'junk' food advertising, and effective health education through active participation of clinicians, school systems, and the media will go a long way in reversing anticipated trends in childhood obesity.

Outcome in acromegaly: A retrospective analysis.

INTRODUCTION: Many of the treatment modalities recommended for acromegaly are either too expensive or not available in large parts of India. There is a dearth of treatment and outcome data in Indian patients. AIMS AND OBJECTIVES: The purpose of this study was to analyze the treatment modalities used and the respective outcomes which include remission, recurrence, hypopituitarism, other complications, and mortality. MATERIALS AND METHODS: This is a retrospective data analysis of 15 acromegaly patients treated at a tertiary care hospital in eastern India. A remission criteria of nadir growth hormone level <1 µg/dl after Oral Glucose tolerance test (OGTT) and normal age related IGF-1 levels was used. RESULTS: All patients (100%) had macroadenomas. Surgery could not be done in five (33%); three (19.8%) refused, two (13.2%) had comorbidities. Transsphenoidal surgery (TSS) achieved remission in four out of ten (40%). Conventional radiotherapy (CRT) failed in all five patients and caused hypopituitarisn in three (60%). Cabergoline (CAB) either alone or following surgery achieved remission in one out of four (25%) though symptomatic relief and tolerability were remarkable. One patient (7%) had pituitary apoplexy with remission, two patients (14.3%) died due to CVA. CONCLUSIONS: TSS remains the treatment of choice in acromegaly, though in macroadenomas the success is limited. A sizeable proportion of patients refuse or are unfit for surgery. As most of the recommended options are very costly or unavailable, alternative treatment options generally used are CRT or CAB which have limited efficacy. Incidence of hypopituitarism, following CRT is very high.

Varied presentations of Sheehan's syndrome at diagnosis: A review of 18 patients.

INTRODUCTION: Sheehan's syndrome (SS) occurs due to ischemic pituitary necrosis as a result of severe postpartum hemorrhage (PPH). AIMS AND OBJECTIVES: The aim of the present study was to review the presenting features of SS at diagnosis. MATERIALS AND METHODS: We retrospectively reviewed 18 cases of SS at diagnosis. Presenting clinical features, laboratory data, pituitary hormone deficiencies, and magnetic resonance imaging (MRI) of the sella were analyzed. RESULTS: Age ranged from 28-71 years with a mean age of 47 ± 14.44 years. Time to diagnosis of SS was 6-33 years with a mean of 15.35 ± 6.74 years. Four (22.2%) patients were referred from emergency for hyponatremia, one each (5.6%) for hypotension, hypoglycemia, and vomiting. Three (16.7%) patients presented with asthenia and weight loss, two (11.1%) with slightly raised thyroid stimulating hormone (TSH). Only six (33.3%) presented with classic features of amenorrhea. None presented with isolated lactational failure or apoplexy after PPH. Seventeen (94.4%) patients had lactational failure; thirteen (72.2%) did not menstruate following last delivery. Lactotroph and gonadotroph failure were present in all at diagnosis but corticotrophs preservation was documented in three (16.7%) and thyrotroph in two (11.1%) patients. Twelve (66.7%) patients had empty sella while six (33.3%) had partial empty sella on MRI. CONCLUSION: SS has variable features at diagnosis and may present to different specialties. The clinical features of hypopituitarism are often subtle, leading to delay in diagnosis. History of PPH, lactational failure and cessation of menses are important clues. Thyrotroph, corticotroph axis may be preserved in some SS patients.

Early treatment with low fixed dose (5 mCi) radioiodine therapy is effective in Indian subjects with Graves' disease.

There is little consensus regarding the most appropriate dosage regimen for radioiodine treatment in Graves' disease. The authors evaluated the efficacy of low fixed dose (5mCi) of radioiodine therapy, in terms of its cure rate and promptness of control, as well possible factors influencing the outcome. One hundred and twenty five consecutive patients with Graves' disease with persistent disease activity despite receiving carbimazole were treated with 5 mCi fixed dose of I131. Patients, who remained hyperthyroid at 1 year, received a second dose of 7.5 mCi of I113. After first dose 73.6% were cured (36.8% hypothyroid and 36.8% euthyroid), while 26.4% patients did not respond. Those who achieved cure had significantly lesser goiter size (84.6% with grade I goiter and 70.7% with grade II) and had received significantly shorter duration of prior carbimazole therapy (22 +/- 10 months versus 63 +/- 27 months) (p < 0.01). Age, sex, baseline T3, T4, 24 hour I131 uptake did not affect the cure rate. Mean time to response was 7 +/- 4 months. One hundred and three (82.4%) patients were cured after 2 doses while only 22 (17.6%) were nonresponsive. Hence, low fixed dose (5mCi) radio active iodine (RAI) therapy seems to be effective in Graves' disease particularly in patients with small sized goiter and short duration of pretherapy with thionamides.