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.

Diagnostic Utility of Mean Peak Systolic Velocity of Superior Thyroid Artery in Differentiating Graves' Disease from Thyroiditis.

Background Differentiating Graves' disease from thyroiditis can be at times clinically challenging. The gold standard test (thyroid nuclear imaging scan) is expensive, not routinely available, and has radiation exposure. Color Doppler ultrasonography of thyroid represents a suitable alternate which can be used for differentiating these conditions by studying thyroid blood flow parameters. Aim We aimed to investigate the use of thyroid blood flow parameters' assessment of the superior thyroid artery (STA) and common carotid artery (CCA) with color Doppler ultrasonography for differentiating Graves' disease from thyroiditis. Materials and Methods This is a cross-sectional study on 111 patients with newly diagnosed thyrotoxicosis (82 with Graves' disease and 29 with thyroiditis) and 45 years of age and sex-matched healthy controls. All patients underwent detailed clinical and necessary investigations. Color Doppler ultrasonography of the thyroid gland and spectral flow analysis of both superior thyroid arteries was done using standard protocol. Sensitivity and specificity for mean peak systolic velocity of STA (STA-PSV) cut-offs were calculated using receiver operating characteristic curves. Results Patients with Graves' disease have significantly higher free tri-iodothyronine (FT3) levels, free thyroxine (FT4) levels, antithyroid stimulating hormone receptor antibody (TRAb) levels, and thyroid volume as compared with those with thyroiditis. The mean STA-PSV of patients with Graves' disease was significantly higher than thyroiditis and control group. Mean STA-PSV greater than 54.3 cm/s had 82.9% sensitivity and 86.2% specificity in diagnosing Graves' disease. Mean PSV-STA/PSV-CCA ratio of 0.40 was 80.5% sensitive and 86.2% specific for Graves' disease. Conclusion Mean STA-PSV has high sensitivity and specificity in differentiating Graves' disease from thyroiditis and can be used routinely in clinical practice as a cheap and invaluable diagnostic tool.

Evaluation of Vitamin D Status and its Impact on Thyroid Related Parameters in New Onset Graves' Disease- A Cross-sectional Observational Study.

AIMS AND OBJECTIVE: We aimed to compare serum vitamin D level in new onset Graves' disease versus age and sex matched controls. Furthermore, we assessed the correlation of vitamin D with hormonal parameters and antibody titers in Graves' disease. MATERIALS AND METHODS: In total, 84 patients of new onset Graves' disease and 42 age and sex matched healthy individuals were recruited. Biochemical and hormonal investigations that included serum calcium, phosphorous, free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), 25 hydroxy vitamin D (25(OH) D), and parathyroid hormone (PTH) were done for all subjects. Thyrotropin receptor antibody (TRAb) was measured only for Graves' disease patients. RESULTS: The patients with Graves' disease had significantly lower 25(OH) D levels (19.2 ± 8.9 ng/ml) as compared to control subjects (23.8 ± 12.5 ng/ml) (P = 0.019). Thyroid hormone levels, thyroid volume, and TRAb titers did not differ significantly between vitamin D deficient Graves' disease group (25(OH)D <20 ng/ml) and vitamin D non deficient Graves' disease group (25(OH)D ≥20 ng/ml). Furthermore, serum vitamin D level did not correlate significantly with thyroid hormones, thyroid volume, or TRAb titers among Graves' disease. The odds ratio (OR) for association of vitamin D deficiency (VDD) state and Graves' disease was 1.62 (95% CI 0.77-3.41). Vitamin D sufficiency state was associated significantly with lower risk of Graves' disease (OR = 0.38, 95% CI 0.15-0.95). CONCLUSION: Serum vitamin D levels are significantly lower in new onset Graves' disease. No significant correlation between vitamin D and thyroid hormones, thyroid volume, or TRAb titers was found in these patients. VDD state is not associated with Graves' disease.

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.

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.

Perrault syndrome with growth hormone deficiency: a rare autosomal recessive disorder.

Perrault syndrome is a rare genetically heterogeneous autosomal recessive group of disorders described in 1951 by Perrault as gonadal dysgenesis with deafness. Here we present a rare case of sporadic Perrault syndrome with short stature and growth hormone deficiency (GHD). Although there was a report on partial GHD in Perrault, our case is a first of its kind with documented GHD (Nishi Y, Hamamoto K, Kajiyama M, Kawamura I. The Perrault syndrome: clinical report and review. Am J Med Genet 1988;31:623-9). We report this case because of the rarity of keeping this condition as a differential diagnosis while evaluating for short stature with amenorrhea.

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.

All males do not have 46 xy karyotype: A rare case report.

The sex of an embryo is determined by genetic sex due to presence or absence of Y chromosome, but it may not be true in all. We hereby report an interesting case of a phenotypic male carrying a female karyotype (46 XX). A 26-year-old male presented with bilateral gynecomastia, poor development of secondary sexual characters and azospermia. On evaluation patient had hypergonadotrophic hypogonadism and chromosomal analysis revealed 46 XX karyotype. The ultrasound revealed no Mullerian structures. Fluorescent in situ hybridization (FISH) showed sex determining region of Y chromosome (SRY) gene locus on X chromosome.

Autoimmune thyroid disorders-An update.

BACKGROUND: Autoimmune thyroid disease (AITD), a common organ specific autoimmune disorder is seen mostly in women between 30-50 yrs of age. Thyroid autoimmunity can cause several forms of thyroiditis ranging from hypothyroidism (Hashimoto's thyroiditis) to hyperthyroidism (Graves'Disease). Prevalence rate of autoimmune mediated hypothyroidism is about 0.8 per 100 and 95% among them are women. Graves' disease is about one tenth as common as hypothyroidism and tends to occur more in younger individuals. Both these disorders share many immunologic features and the disease may progress from one state to other as the autoimmune process changes. Genetic, environmental and endogenous factors are responsible for initiation of thyroid autoimmunity. At present the only confirmed genetic factor lies in HLA complex (HLA DR-3) and the T cell regulatory gene (CTLA 4). A number of environmental factors like viral infection, smoking, stress & iodine intake are associated with the disease progression. The development of antibodies to thyroid peroxidase (TPO) thyroglobulin (TG) and Thyroid stimulating hormone receptor (TSH R) is the main hallmark of AITD. Circulating T Lymphocytes are increased in AITD and thyroid gland is infiltrated with CD4+ and CD8+ T Cells. Wide varieties of cytokines are produced by infiltrated immune cells, which mediate cytotoxicity leading to thyroid cell destruction. Circulating antibodies to TPO and TG are measured by immunofluorescense, hemagglutination, ELISA & RIA. TSHR antibodies of Graves' disease can be measured in bioassays or indirectly in assays that detect antibody binding to the receptor.