Variation in Clinical Presentation, Metabolic Profile, Hormonal Parameters and Inflammatory Markers in Polycystic Ovary Syndrome Women with and without Polycystic Ovary Morphology Appearance.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with a spectrum of presentation. Studies have reported considerably different rates in terms of the incidence of polycystic ovary morphology (PCOM) in patients with PCOS with inconsistent results regarding the effects of PCOM in them. Aims: The aim of this study was to determine the differences in clinical presentation, metabolic profile, hormonal parameters and inflammatory markers in PCOS women with and without PCOM on ultrasonography (USG). Settings and Design: A total of 70 PCOS women were recruited. To analyse the differences between various parameters, the patients were divided into two groups based on the presence or absence of PCOM on USG of the pelvis as per the Rotterdam criteria. Materials and Methods: A total of 37 patients had PCOM as per the diagnostic criteria for PCOS (Group 1), while 33 patients did not have PCOM on USG and were designated as Group 2. All participants underwent a detailed clinical evaluation and biochemical investigations, including high-sensitivity C-reactive protein, serum adiponectin, luteinising hormone, follicle-stimulating hormone, total testosterone and serum anti-Mullerian hormone. The homeostasis model assessment of IR (HOMA-IR) was calculated using standard equations. Statistical Analysis Used: The mean and Standard deviation were computed for all continuous variables. Frequencies and proportions were calculated for categorical variables. Comparisons of the mean scores between the study groups were assessed using the Unpaired Student's t-test. The mean score of the subgroups was also compared using the unpaired Student's t-test. P < 0.05 was considered significant for all statistical inferences. Results: The mean LDL and mean triglyceride were higher in Group 2, which was statistically significant (P = 0.004 and P ≤ 0.001, respectively). The mean hs-CRP was found to be higher in Group 2, which was statistically significant (P = 0.005). The mean AMH was higher in Group 1, which was statistically significant (P = 0.002). Group 1 had higher adiponectin levels, which was statistically significant (P = 0.04). Conclusion: The above findings suggest that patients without diagnostic PCO morphology have a worse metabolic profile compared to those with PCO morphology on USG. Obese patients without PCO morphology probably have a higher cardiovascular risk compared to obese patients with PCO morphology.

Correlation of Markers of Inflammation with Hormonal, Metabolic Parameters, Insulin Resistance and Adiposity Indices in First-Degree Relatives of Patient with Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is a state of chronic low-grade inflammation. Low-grade inflammation has been linked to the development of cardiovascular disease (CVD). There is evidence of clustering for metabolic syndrome, hypertension, dyslipidaemia in type 2 diabetes mellitus and insulin resistance (IR) in mothers, fathers, sisters and brothers of women with PCOS. Aims: The aim is to study the levels of inflammatory markers and IR in first-degree relatives of patients with PCOS and find any correlation with hormonal parameters, metabolic parameters and adiposity indices in them. Settings and Design: A total of 66 first-degree relatives of a patient with PCOS were included in this cross-sectional study. Materials and Methods: All participants underwent detailed clinical evaluation and biochemical investigations, including high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), luteinising hormone (LH), follicle-stimulating hormone (FSH) and total testosterone (only in females). Homeostasis model assessment of IR (HOMA-IR), lipid accumulation product and visceral adiposity index were calculated using standard equations. Visceral adipose tissue thickness and subcutaneous adipose tissue thickness were assessed using ultrasonography. Statistical Analysis Used: Spearman's and Pearson's correlation coefficients were used to analyse the correlation between different non-parametric and parametric data, respectively. Multiple linear regression was used to correlate multiple dependent factors. Results: The mean hs-CRP level was 2.4 ± 1.1 mg/L, which is greater than the cut-off of 2 mg/L and hs-CRP >2 mg/L was found in 62% (n = 41) participants. The mean IL-6 (3.5 ± 1.1 pg/ml) and total white blood cell count (7244 ± 2190/mm3) were in the normal range. The mean HOMA-IR was 2.35 ± 0.76, which is elevated, considering HOMA IR >2 as a predictor of IR and metabolic syndrome. HOMA IR >2 was found in 64% (n = 42) of the participants. Inflammatory markers were significantly correlated with LH and HOMA IR, even after multiple linear regression was fitted for each marker individually. Conclusion: Apparently, healthy first-degree relatives of PCOS patients had evidence of chronic low-grade inflammation. The chronic inflammation in them correlated well with HOMA-IR and LH but was independent of body mass index. This low-grade inflammation may predispose the first-degree relatives of PCOS to CVD.

Accuracy of various tests alone and in combination to differentiate IHH from CDGP.

Context: Constitutional delay in growth and puberty (CDGP) is a normal physiological variant of delayed puberty in both sexes and is the most common cause of delayed puberty. Idiopathic hypogonadotropic hypogonadism (IHH) is due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH) with normal structure and function of the anterior pituitary after exclusion of secondary causes of hypogonadotropic hypogonadism. To differentiate CDGP from IHH is crucial because it not only helps in decision making in management but also lessen anxiety of the parents. Aim: In this study we aimed to find out the accuracy of hormonal tests used individually as well as in various combinations to distinguish cases of IHH from CDGP. Methods: A cohort of 34 boys with delayed puberty were recruited in this study. Detailed history, clinical examination, hormonal analysis including basal serum testosterone, inhibin-B, LH, FSH as well as GnRH analogue stimulated gonadotrophins and testosterone along with hCG stimulated testosterone was done. At 6 monthly follow-up, detailed clinical examination was repeated and the cohort was followed until 2 years. Results: Out of the 29 boys taken for final analysis, CDGP was diagnosed in 23 boys and IHH in 6 boys. Basal LH, basal inhibin-B, 3 hours post leuprolide LH and 72 hours post hCG testosterone were significantly higher in CDGP than IHH. However, no statistically significant difference was observed between basal FSH, basal testosterone and 3 hours post leuprolide FSH between these two groups. When basal LH (cut-off <0.565 IU/L) and basal inhibin-B (cut-off <105 pg/ml) were taken together the sensitivity and specificity were increased to 100% as was for the combination of basal LH (cutoff <0.565 IU/L) and 3 hours post leuprolide LH (cutoff <6.16 IU/L) for diagnosis of IHH. Both combinations have PPV of 100% and NPV of 100%. A combination of 3 hours post leuprolide LH with 72 hours post hCG testosterone also has good sensitivity (100%), specificity (96%), PPV (90%) and NPV (100%). Conclusion: Differentiating IHH from CDGP is a challenging task due to considerable overlap in their clinical as well as hormonal profiles. Therefore we suggest that a combination of basal LH and basal inhibin-B may be considered as a useful screening tool to differentiate IHH from CDGP rather than the cumbersome and invasive stimulation tests.

Prevalence of Insulin Resistance in Type 1 Diabetes Mellitus and Its Correlation with Metabolic Parameters: The Double Trouble.

OBJECTIVE: The phenotype of type 1 diabetes mellitus has changed over the last few decades. Little attention has been paid to the presence of insulin resistance in individuals with type 1 diabetes mellitus. The appearance of insulin resistance in type 1 diabetes mellitus patients has been labeled as "double diabetes." This phenotype of double diabetes has been seen to have higher rate of microvascular as well as macrovascular complica- tions. The aim of the current study was to estimate the burden of insulin resistance in patients with type 1 diabetes mellitus and its correlation with various metabolic parameters and microvascular complications. MATERIALS AND METHODS: It was a cross-sectional study in which a total of 95 type 1 diabetes mellitus patients (children/adolescents (<18 years) and adults ≥18 years) presenting to Endocrinology OPD were screened for the presence of insulin resistance using estimated glucose disposal rate. Estimated glucose disposal rate (mg/kg/min) was calculated as = 21.16- (0.09 ×WC) - (3.407×HTN) - (0.551×HbA1c [%]) where, WC is waist circumference (cm) and HTN is hypertension (1= yes, 0 = no). Based on previous studies, an estimated glucose disposal rate <8 was considered to have the presence of insulin resistance and double diabetes. RESULTS: Using an estimated glucose disposal rate <8 as the cut-off for the presence of insulin resistance, the overall prevalence was 16.8%. Prevalence was high in adults 12 (29.3%) compared to children/adolescents 4 (7.4%) which was statistically significant [χ2 = 7.95; P = .004]. In comparison of the anthropometric and metabolic parameters in those with an estimated glucose disposal rate <8 versus ≥8, there was a significant statistical difference. Those having an estimated glucose disposal rate <8 had higher age, longer duration of diabetes, and body mass index [P ≤ .05]. Also, they had poor glycemic control, higher blood pressure, triglycerides, low-density lipoproteins levels. Using Spearman correlation coefficient there was a statistically significant (P < .05) negative correlation between the estimated glucose disposal rate and various anthropo- metric as well as metabolic parameters. CONCLUSION: This study shows that with increasing duration of disease, insulin resistance (low estimated glucose disposal rate) could be a serious problem in type 1 diabetes mellitus patients, especially in those who are metabolically unhealthy. As insulin resistance could be a major contributing factor in the onset and progression of various vascular complications, evaluation of the presence of insulin resistance using estimated glucose disposal rate could be useful in recognizing individuals who would benefit the most from preventa- tive strategies.

Utility of Epicardial Fat Thickness in Subclinical Hypothyroid Children to Determine Existence of Subclinical Atherosclerosis in Them.

Context: Adult studies have shown the association of subclinical hypothyroid (SCH) with various cardiovascular dysfunction, which indicates SCH may be a potentially modifiable risk factor of CV disease and mortality. However, there is still controversy about the association of cardiovascular dysfunction in children with SCH. Epicardial fat thickness (EFT) is a reliable and sensitive marker of cardiovascular risk and has become an emerging modality to predict CV risks. Aims: To measure the EFT in children with subclinical hypothyroidism and compare with healthy children. To find its correlation with subclinical atherosclerosis. To compare EFT between TPO positive and TPO negative subclinical hypothyroid patients. Materials and Methods: Children of subclinical hypothyroidism (TSH >5 mIU/ml with normal FT3, FT4, and age and sex matched control were included as per inclusion and exclusion criteria. Clinical data was collected from all study subjects. Thyroid function tests including FT3, FT4 and TSH, TPO antibody, fasting insulin, hsCRP, Lp(a), USG neck for carotid intima media thickness (CIMT), USG brachial artery for flow mediated dilation (FMD) and echocardiography for epicardial fat thickness (EFT) were done in all patients. Results: A total 42 number of SCH and 50 age and sex matched controls were recruited and screened for various parameters of subclinical atherosclerosis. EFT was significantly higher in the cases than in the controls (6.27 mm vs 4.54 mm) with P value < 0.001. Brachial FMD was significantly lower in cases than the cohort (4.5% vs 8.93%, P < 0.001). Difference in CIMT was not significant amongst the cases and controls. EFT failed to correlate with the level of TSH though it had significant positive correlation with hsCRP. The patients who were TPO positive, had higher fasting insulin, HOMAIR, hsCRP, Lp(a) than those who were TPO negative. Conclusion: Results of this study show the presence of subclinical atherosclerosis in children with SCH regardless of the aetiologies. The patients of Hashimoto thyroiditis had significantly high insulin resistance and inflammation than the SCH patients of other aetiologies.

Rapid Differential Diagnosis of Thyrotoxicosis Using T3/T4 Ratio, FT3/FT4 Ratio and Color Doppler of Thyroid Gland.

CONTEXT: Establishing the etiology of thyrotoxicosis is of utmost importance to plan the appropriate line of therapy. However, certain scenarios such as absence of pathognomonic clinical features of Graves' disease in some patients, or non-availability of radionuclide scanning and newer generation TRAb assays especially in resource-poor settings, necessitates utilization of other, simple and effective measures to differentiate between the two common causes of thyrotoxicosis, Graves' disease (GD) and Destructive thyroiditis (DT). AIMS: The aim of this work was to study the role of FT3/FT4 ratio, T3/T4 ratio and color flow Doppler ultrasound in treatment-naïve patients with thyrotoxicosis, in comparison to Tc-99m pertechnetate thyroid scanning in the differentiation of thyrotoxicosis due to GD and DT. MATERIALS AND METHODS: Clinical data was collected from all study subjects. Thyroid function tests including FT3, FT4, T3, T4 and TSH, TSH Receptor Antibody (TRAb), Technetium Tc 99m pertechnetate scan and the mean peak systolic velocity in inferior thyroid artery (mean PSV-ITA) by color Doppler ultrasonography of thyroid gland was done in all patients. RESULTS: A total of 83 treatment-naïve patients with thyrotoxicosis (61 with GD and 22 with DT) were studied. Mean PSV-ITA, T3/T4 ratio and FT3/FT4 ratio showed a sensitivity of 85.2%, 73.8%, and 77.04%, and a specificity of 90.9%, 72.7%, and 59.09%, respectively. The three parameters in combination yielded a positive predictive value of 100% in the diagnosis of Graves' disease. CONCLUSION: Results of this study show that inferior thyroid artery blood flow, T3/T4 ratio and FT3/FT4 ratio are useful parameters in the differentiation between GD and DT.

Relationship of Vitamin D Status with Thyroid Autoimmunity in New Onset Autoimmune Hypothyroidism.

Background: Study of serum vitamin D level in new onset hypothyroid patients and its correlation with thyroid related parameters and antibody titers. Objectives: We aimed to compare serum vitamin D level in new onset hypothyroid patients versus controls. Furthermore we evaluated for any association of vitamin D status with hypothyroid state and its correlation with various thyroid related parameters. Methodology: In this cross sectional study , 61 new onset hypothyroid subjects (cases) and 40 age, sex and BMI matched healthy individuals (controls) were recruited. Measurements of serum vitamin D, thyroid hormones, thyroid peroxidase antibody (TPO-Ab), parathyroid hormone (PTH), calcium and phosphorus were done for all study participants. Results: The mean serum vitamin D in cases (22.95±8.59 ng/ml) was significantly lower than the controls (27.9±7.85 ng/ml) (p<0.01). The prevalence of vitamin D deficiency was significantly higher among hypothyroid subjects than controls (p=0.009). Hypothyroid subjects with vitamin D deficiency group had significantly higher TSH level, greater thyroid volume and elevated anti TPO titres than those with vitamin D sufficiency. Serum vitamin D level had significant inverse correlation with anti TPO-Abtiters even after adjustment for age, sex and BMI. Conclusion: Serum vitamin D is significantly low in new onset hypothyroid patients than healthy controls. Hypothyroid patients with vitamin D deficiency have significantly higher TSH, antibody titres and thyroid volume. A significant negative correlation was observed between serum vitamin D leveland anti TPO titres. Moreover, serum vitamin D remained an independent predictor of TPO level among hypothyroid subjects.

A RARE CASE OF ACROMEGALY AND AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: CASE REPORT AND BRIEF REVIEW OF LITERATURE.

OBJECTIVE: Acromegaly is a classic endocrine disorder caused by a growth hormone (GH)-secreting pituitary adenoma in an overwhelming majority of patients. The diagnosis may be delayed by several years due to the slow growing and insidious nature of the disease. Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by multiple renal cysts and various other systemic manifestations. The purpose of this article is to report a rare case of acromegaly with coexistent ADPKD. METHODS: We report a case of 42-year-old female with acromegaly and ADPKD along with a brief review of literature. RESULTS: The patient was referred to us for evaluation of progressive acral enlargement and coarsening of facial features. Endocrine evaluation confirmed the diagnosis of acromegaly due to an underlying GH-secreting pituitary macroadenoma. She was also found to have ADPKD. We discuss the clinical features and management of the patient. CONCLUSION: The association of pituitary adenomas and ADPKD is very rare and interesting. All affected individuals with pituitary adenomas and ADPKD in the literature are women. Furthermore, all reported pituitary adenomas in these individuals (including ours) are functional GH-secreting ones. These findings argue against a mere chance association between the two diseases.

The Bhubaneswar Declaration on Sports Endocrinology, 2018.

Sports and endocrinology are complex interrelated disciplines. Sports and exercise modulate endocrine and metabolic health, and are used to prevent and manage disease. Endocrine and metabolic function influence participation and performance in sports activity. The Bhubaneswar Declaration, released on the occasion of the Endocrine Society of India Conference, resolves to promote the science of sports endocrinology. The authors commit to optimize endocrine health in sports persons, encourage safe use of sports to promote health, and prevent misuse of endocrine interventions in sports.

Study of Visceral and Subcutaneous Abdominal Fat Thickness and Its Correlation with Cardiometabolic Risk Factors and Hormonal Parameters in Polycystic Ovary Syndrome.

AIM OF THE STUDY: This study aimed to compare the different adiposity parameters, namely visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) between patients with polycystic ovary syndrome (PCOS) and controls. In addition, it aimed to correlate these adiposity indices with hormonal parameters as well as cardiovascular (CV) risk factors in patients with PCOS. MATERIALS AND METHODS: Newly diagnosed PCOS patients of reproductive age group according to Rotterdam criteria were included. Age- and body mass index (BMI)-matched healthy females with normal menstrual cycles were taken as controls. All the study participants underwent detailed clinical, biochemical, and hormonal evaluation. Transabdominal ultrasound (US) was performed for detailed ovary imaging and assessment of adiposity (SAT and VAT) parameters. RESULTS: A total of 58 PCOS patients and 40 age- and BMI-matched controls were included. PCOS patients had significantly higher levels of androgens (P < 0.001), elevated highly sensitive C-reactive protein (P = 0.007), and higher degree of insulin resistance (P < 0.001) than controls. PCOS patients had a mean SAT of 2.37 ± 0.7 cm and mean VAT of 8.65 ± 1.78 cm. These parameters were significantly higher than controls who had a mean SAT of 2.01 ± 0.7 cm (P = 0.014) and mean VAT of 7.4 ± 1.89 cm (P = 0.003), despite both groups having similar BMI. Among PCOS cohort, VAT correlated positively with total testosterone (r = 0.295, P = 0.025) and negatively with dehydroepiandrosterone sulfate (r = -0.210, P = 0.114). However, no significant correlation was observed between SAT and androgens in PCOS group. CONCLUSION: PCOS patients, whether obese or nonobese, had elevated visceral adiposity than controls. VAT correlated positively with adverse CV risk factors and testosterone in PCOS patients. Hence, a simple and inexpensive ultrasonography screening of visceral fat may identify women who have adverse metabolic profile and enhanced CV risk.

Effect of parental history of diabetes on markers of inflammation, insulin resistance and atherosclerosis in first degree relatives of patients with type 2 diabetes mellitus.

AIM AND OBJECTIVE: To study the effect of parental history of diabetes on markers of inflammation, insulin resistance, adiposity indices and carotid intima media thickness (cIMT) in first degree relatives of patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Normal glucose tolerant (NGT) first degree relatives of T2DM patients of age group 20-40 years designated as FHpositive were enrolled in the cross sectional study. Depending on the parental history of diabetes they were divided into three groups: family history positive in father (FHfather), family history positive in mother (FHmother) and family history positive in both (FHboth). Age, sex and BMI matched controls without any history of diabetes in their parents designated as FHnegative were taken for comparison. All subjects underwent detailed clinical evaluation and biochemical investigations. cIMT and adiposity indices like visceral adipose tissue thickness (VAT) and subcutaneous adipose tissue thickness (SAT) were assessed using ultrasonography. RESULTS: No difference existed with regards to BMI, hsCRP, degree of insulin resistance, adiposity markers and cIMT between FHmother and FHfather group. Subjects in FHboth group had significantly higher degree of insulin resistance, subclinical inflammation, increased atherosclerosis and adiposity indices in contrast to those who have a single parent T2DM family history. CONCLUSIONS: hsCRP and cIMT are significantly higher in the first degree relatives of type2 diabetes mellitus patients than controls. Individuals with history of T2DM in both parents have significantly worse glycemic status, increased cIMT and adverse cardiovascular risk profile than those with T2DM history in only single parent.

Spondylocarpotarsal synostosis syndrome. A rare case of short stature and congenital scoliosis.

Spondylocarpotarsal synostosis is a very rare skeletal disorder characterized by vertebral malsegmentation defects. Apart from severe vertebral defects, the disease is associated with carpal and tarsal synostosis which is quite characteristic for the disease. We report a case of young child who presented with short stature and congenital scoliosis. The radiological and clinical findings were compatible with the above diagnosis. Apart from the classical findings, the patient had evidence of odontoid aplasia which has not earlier been described in association with this disorder. We report this case for rarity of this disorder and the associated novel finding.

Neurological manifestations of Graves' disease: A case report and review of the literature.

Graves' disease (GD) is characterized by a hyperfunctioning thyroid gland due to stimulation of the thyroid-stimulating hormone receptor by autoantibodies directed against it. Apart from thyrotoxicosis, other clinical manifestations include ophthalmopathy, dermopathy, and rarely acropachy. GD is an organ-specific autoimmune disorder, and hence is associated with various other autoimmune disorders. Myasthenia gravis (MG) is one such disease, which is seen with patients of GD and vice versa. Though the association of GD and myasthenia is known, subtle manifestations of latter can be frequently missed in routine clinical practice. The coexistence of GD and ocular MG poses a significant diagnostic dilemma to treating physicians. The ocular manifestations of myasthenia can be easily missed in case of GD and falsely attributed to thyroid associated ophthalmopathy due to closely mimicking presentations of both. Hence, a high degree of the clinical vigil is necessary in such cases to appreciate their presence. We present a similar case which exemplifies the above said that the clinical challenge in diagnosing coexistent GD and ocular myasthenia.

Endocrine alterations in HIV-infected patients.

AIMS AND OBJECTIVES: To study the frequency of thyroid, adrenal and gonadal dysfunction in newly diagnosed HIV-infected patients and to correlate them at different levels of CD4 cell counts. MATERIALS AND METHODS: Forty-three HIV-positive cases were included in the study group. Cases were divided into three groups on the basis of CD4 cell count. Serum free T3, free T4, TSH, Cortisol, FSH, LH, testosterone and estradiol were estimated by the radioimmunoassay method. Hormone levels between cases were compared and their correlation with CD4 count was analyzed. RESULTS: Prevalence of gonadal dysfunction (88.3%) was the most common endocrine dysfunction followed by thyroid (60.4%) and adrenal dysfunction (27.9%). Secondary hypogonadism (68.4%) was more common than primary (31.6%). Low T3 syndrome, that is, isolated low free T3, was the most common (25.6%) thyroid dysfunction followed by secondary hypothyroidism (16.2%) and subclinical hypothyroidism (11.6%). Adrenal excess (16.3%) was more common than adrenal insufficiency (11.6%). The difference in hormonal dysfunction between male and female was statistically insignificant (P > 0.05). 27.9% of patients had multiple hormone deficiency. There was negligible or no correlation between CD4 count and serum hormone level. CONCLUSION: In our study, endocrine dysfunction was quite common among HIV-infected patients but there was no correlation between hormone levels and CD4 count. Endocrine dysfunctions and role of hormone replacement therapy in HIV-infected patient needs to be substantiated by large longitudinal study, so that it will help to reduce morbidity, improve quality of life.

Berardinelli-Seip congenital lipodystrophy: an autosomal recessive disorder with rare association of duodenocolonic polyps.

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive disorder characterized by a nearly complete absence of adipose tissue and generalized muscular appearance. This condition is associated with various dermatological and systemic manifestations. We report a 5-year-old boy, with clinical and metabolic presentation resembling BSCL and unusual features, such as diabetes detected at an early age and multiple duodenal and colonic polyps.

Pigmentation in vitamin B12 deficiency masquerading Addison's pigmentation: A rare presentation.

A 35-year-female presented with generalized weakness, weight loss, and progressive pigmentation was worked up for suspicion of Addisons disease. On examination hyper pigmentation was noted on both palmar and dorsal aspect of hands involving knuckles, creases, feet, tongue, oral mucosa and gluteal region. There was no evidence of hypocortisolemia as initially suspected, and literature search revealed a possibility of vitamin B12 deficiency. She had megaloblastic anemia with a low serum vitamin B12, mostly due to poor dietary intake. Her hyper pigmentation resolved with vitamin B12 supplementation. Skin biopsy showed increased pigmentation at stratum spinosum and basal-layer. The mechanism of hyper pigmentation in vitamin B12 deficiency was due to an increase in melanin synthesis.