Endocrinology and Metabolism

Anaplastic cancer of the thyroid: The viper in the pit Krishna G Seshadri Indian Journal of Endocrinology and Metabolism 2019 23(1):1-2

Stretched penile length and testicular size from birth to 18 years in boys from Western Maharashtra Vijay K Jaiswal, Vaman Khadilkar, Anuradha Khadilkar, Nikhil Lohiya Indian Journal of Endocrinology and Metabolism 2019 23(1):3-8 Background: Genital stage and testicular volume examination and assessment are essential for assessment of growth puberty in boys. There is paucity of Indian data for penile and testicular parameters particularly in pubertal years. Aim: The aim of this study is to present normative data for penile length, testicular volume, and testicular length from birth to 18 years in boys from western Maharashtra and to correlate these parameters with sexual maturity staging (SMR) (Tanner staging). Materials and Methods: A cross-sectional observational study was undertaken in apparently healthy boys from 0 to 18 years of age from western Maharashtra from October 2016 to October 2017. Age, anthropometric parameters, stretched penile length (SPL), testicular volume, and testicular length were measured. Pubertal stage was categorized using Tanner staging. Data were entered in Microsoft excel 2013 and using SPSS version 16. LMS method was used to construct age-specific Z-scores for SPL, testicular volume, and testicular length. Results: A total of 843 boys were enrolled in the study. Mean SPL was 4.1 ± 0.4, 5.4 ± 0.8, and 10.2 ± 1.7 cm at 1, 10, and 18 years of age, respectively, and showed a gradual rise from birth to 18 years. Mean testicular volume was 1.8 ± 0.5, 3.3 ± 1.2, and 24.1 ± 3.5 ml, whereas testicular length was 1.3 ± 0.4, 2.1 ± 0.5, and 4.4 ± 0.7 cm respectively, at 1, 10, and 18 years, respectively. The magnitude of increase for SPL and testicular volume was greater around 9–10 years. The increase in SPL and testicular size was hand in hand with SMR for genital development as well as for axillary and pubic hair stages. Conclusion: Normative data on SPL, testicular volume, and testicular length from western Maharashtra are presented. These data may be useful in disorders of puberty and genitalia in boys.

High prevalence of genital mycotic infections with sodium-glucose co-transporter 2 inhibitors among Indian patients with type 2 diabetes Ajay Aggarwal, Roopak Wadhwa, Dheeraj Kapoor, Rajeev Khanna Indian Journal of Endocrinology and Metabolism 2019 23(1):9-13 Introduction: Genital mycotic infections are common among patients with poorly controlled diabetes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) induced pharmacological glycosuria increases the risk of these infections (2–3 fold) among patients with type 2 diabetes (T2D). The data about incidence of these infections in Indian setting is unclear. Aim: To study the prevalence of genital mycotic infections caused by SGLT2i among Indian patients with T2D. Materials and Methods: We collected data of 205 patients with T2D on SGLT2i for more than 1-month duration. Patients with symptoms and/or signs suggestive of genital mycotic infections and who had positive response to antifungal treatment were considered to have infection. Data were collected for a period of 2 months from July to August 2017. Results: Among 205 patients, mean age was 52.4 ± 8.7 years and percentage of females was 52.2%. Among SGLT2i, empagliflozin, canagliflozin and dapagliflozin were prescribed to 50.7%, 30.2% and 19.1% patients, respectively. The mean duration of treatment with SGLT2i was 7.6 ± 5.9 months. At least, one episode of genital mycotic infection occurred in 53 (25.9%) patients and 25 (12.2%) had second episode. Incidence of these infections was marginally higher in females than males with no statistically significant difference (P = ns). There was no significant correlation between age, sex, duration of disease, duration of treatment, glycaemic control, type and dose of SGLT2i used with the incidence of genital mycotic infections (P = ns). The patients who had knowledge of side effects of the drug and observed precautions had significantly lesser incidence of infections (P < 0.001). Majority of the infections were mild in nature and responded well to treatment. Conclusion: There is a very high risk of genital mycotic among Indian patients with T2D on SGLT2i. All patients should be educated about the risk of genital mycotic infections when on SGLT2i and precautions needed to minimise the risk.

Evaluation of changes in insulin sensitivity in prepubertal small for gestational age children treated with growth hormone Carmen Sydlik, Claudia Weissenbacher, Julia Roeb, Susanne Bechtold-Dalla Pozza, Heinrich Schmidt Indian Journal of Endocrinology and Metabolism 2019 23(1):14-21 Background: Although growth hormone (GH) therapy for children born small for gestational age (SGA) has been approved for many years, there are still concerns about increasing their risk for insulin resistance and diabetes mellitus type 2. Monitoring of glucose homeostasis is therefore generally recommended, but there is no consensus on either the methods or consequences. Methods and Aims: The aim of our study was to analyze the oral Glucose Tolerance Tests (oGTTs) which were performed yearly from baseline to 4 years of GH therapy in a collective of 93 SGA children, who were prepubertal during the whole follow-up. We looked for correlations with auxological and laboratory data as well as predictive baseline results for glucose homeostasis during further treatment. Results: While glucose levels remained constant, insulin secretion increased from baseline to the first year of GH therapy. Insulin sensitivity index (ISI) showed no significant change afterwards; HOMA1, HOMA2, and QUICKI stabilized after the second year. For all indices mean values never reached pathological levels and no cases of diabetes mellitus were induced. Higher gestational age, lower birth length, and older age at start of GH therapy were associated with lower insulin sensitivity. No predictive factors for later insulin resistance could be found. Conclusion: As expected, in GH-treated prepubertal SGA children insulin resistance was induced, but not to pathological levels. No special risk factors for disturbed glucose homeostasis could be identified. Based on our opinion, performing oGTTs in GH-treated SGA children at baseline and in puberty should remain mandatory, but the current study recommendations regarding further surveillance of glucose homeostasis are questionable.

Coexistence of autoimmune disorders and type 1 diabetes mellitus in children: An observation from Western Part of India Balram Sharma, Hardeva R Nehara, Sanjay Saran, Vijay K Bhavi, Anshul K Singh, Sandeep K Mathur Indian Journal of Endocrinology and Metabolism 2019 23(1):22-26 Introduction: Type 1 diabetes mellitus (T1DM) is associated with various autoimmune disorders like celiac disease, thyroid disorder, adrenal failure, etc. However, how common is this association in Indian children is not clearly known. Objective: To assess the prevalence of other coexisting autoimmune disorders in children with T1DM. Materials and Methods: In this cross-sectional study, patients requiring insulin and ketosis-prone diabetic and with history of diabetic ketoacidosis/undetectable fasting C-peptide levels were included. Beside demographic and clinical data, detailed biochemistry evaluations were performed. Celiac disease was diagnosed as per the ESPGHAN diagnostic criteria. ACTH stimulation test was done to confirm the adrenal insufficiency in patients with basal serum cortisol <5 μg/dL. Thyroid function test (TSH) and anti-TPO antibody were assessed in all patients. Screening for other autoimmune disorders was done only when clinically indicated or symptoms or family history was suggestive of presence of such disorder. Results: Among 150 patients enrolled, 64.66% were males and mean age was 13.48 ± 3.29 years (range 3–18 years). Mean age at diagnosis of T1DM was 10.0 ± 3.63 years and duration of diabetes was 3.46 ± 3.18 years. The prevalence of antibodies positive against autoimmune diseases was anti-tTG IgA (20.7%), anti-TPO (33.7%), anti-CCP ab (1.3%), and ANA (0.7%). Significantly higher proportion of females had raised anti-TPO antibodies than males (47.2% vs. 25.8%, P = 0.006). Celiac disease was most common association (24.8%) followed by hypothyroidism (14.1%) and Grave's disease (3.3%). Significantly higher proportion of females had hypothyroidism than males (25.0% vs. 8.2%, respectively, P = 0.005). Prevalence of raised anti-tTG and anti-TPO did not differ significantly by the age (P = 0.841 and P = 0.067) or duration of T1DM (P = 0.493 and P = 0.399). Conclusion: In this part of country, celiac disease, hypothyroidism, and Graves's disease are common associations in children with T1DM.

Effect of vitamin D supplementation on bone turnover markers in children and adolescents from North India Raman K Marwaha, MK Garg, A Mithal, Sushil Gupta, Manoj Shukla, Aditi Chadha Indian Journal of Endocrinology and Metabolism 2019 23(1):27-34 Objectives: Vitamin D is known to play an important role in bone mineral metabolism. Its deficiency may affect growth and status of bone markers in children. Hence, we undertook to study the status of bone markers in children with vitamin D deficiency (VDD) and impact of vitamin D3 supplementation on them. Materials and Methods: Total 468 out of 615 children and adolescents with VDD, who were given either of the three doses (600, 1000, and 2000) of vitamin D supplementation, were included in the study. These 468 children with pre- and postsupplementation preserved samples with available anthropometry, serum biochemistry, 25-hydroxy-vitamin D, and parathormone were evaluated for bone formation (procollagen type 1 amino-terminal propeptide [P1NP]) and resorption (β-cross laps [CTx]) markers. Results: The mean age and body mass index of these children were 11.3 ± 2.3 years (boys: 11.5 ± 2.4; girls: 12.2 ± 1.2 years; P = 0.03) and 18.1 ± 3.8 kg/m2 (boys: 18.2 ± 3.9; girls: 17.6 ± 3.2 kg/m2; P = 0.208), respectively. There were 8.8% subjects with severe, 42.7% with moderate, and 48.5% with mild VDD. There was a significant decline in serum P1NP (from 691 ± 233 ng/ml to 640 ± 259 ng/ml, P < 0.001) and CTx (from 1.67 ± 0.53 ng/ml to 1.39 ± 0.51 ng/ml, P < 0.001) following supplementation. Though decline in serum P1NP and CTx levels was observed in both boys and girls, among all three supplementation groups and VDD categories, the effect was more marked in serum CTx than P1NP levels. Conclusions: Vitamin D supplementation in VDD children resulted in decrease in both bone formation (P1NP) and resorption (CTx). The impact, however, was more marked on bone resorption than bone formation.

Evaluation of vitamin D status and its impact on thyroid related parameters in new onset Graves' disease- A cross-sectional observational study Swayamsidha Mangaraj, Arun K Choudhury, Basanta M Swain, Pradosh K Sarangi, Binoy K Mohanty, Anoj K Baliarsinha Indian Journal of Endocrinology and Metabolism 2019 23(1):35-39 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.

Drug prescription patterns and cost analysis of diabetes therapy in India: Audit of an endocrine practice Rajiv Singla, Jatin Bindra, Ankush Singla, Yashdeep Gupta, Sanjay Kalra Indian Journal of Endocrinology and Metabolism 2019 23(1):40-45 Drug therapy in diabetes care along the duration of diabetes has been documented scarcely in literature, especially from Indian subcontinent. An audit of an endocrine practice from New Delhi was conducted to understand the current diabetes practice and its direct cost to the patient. Aims: The aim of this study was to analyze the current trend in the use of antidiabetes as well as other drugs for comorbidities along the duration of diabetes. The study also aimed to analyze the direct drug cost to patients. Settings and Design: Retrospective cross-sectional study. Subjects and Methods: Data captured in clinic electronic medical records of an endocrine practice was analyzed. Statistical Analysis Used: Data was analyzed descriptively using machine learning codes on python platform. Results: Records of 489 people who attended the clinic during the 6-month period were retrieved. Data of 403 people with diabetes were analyzed after exclusion of incomplete data. Use of antidiabetic drug increased from 1.44 (0.78) [mean (standard deviation)] in people with a duration of diabetes <5 years to 3.18 (1.05) in people with 20+ years of diabetes. The mean number of antidiabetic drug usage seems to plateau at 15 years of diabetes. About 46% of people with 20+ years of diabetes required insulin therapy. Prescription patterns involving a combination of different drug classes in patients were also analyzed. The cost of diabetes therapy increases linearly along the duration of diabetes. Conclusion: This study provides valuable insights on temporal prescription patterns of antidiabetic drugs from an endocrine practice. Metformin remains the most preferred drug across the entire duration of diabetes. Dipeptidyl peptidase-4 inhibitors seem to be fast catching up with sulfonylureas as a second-line treatment after metformin. After 20 years or more of diabetes duration, 46% people would require insulin for glycemic control.

A comparison between silent and symptomatic renal stones in primary hyperparathyroidism Raiz Ahmad Misgar, Ashish Sehgal, Shariq Rashid Masoodi, Arshad Iqbal Wani, Mir Iftikhar Bashir, Ajaz Ahmad Malik, Munir Ahmad Wani, Muzaffar Maqsood Wani, Imtiyaz Ahmad Wani Indian Journal of Endocrinology and Metabolism 2019 23(1):46-49 Background: Nephrolithiasis is a common complication of primary hyperparathyroidism (PHPT), and in a subgroup of patients stones are clinically silent. Patients with silent and symptomatic stones may differ biochemically. There is a scarcity of data available comparing patients with silent and symptomatic renal stones in PHPT. Aims: To characterize patients with PHPT with nephrolithiais and to compare patients with silent and symptomatic stones. Materials and Methods: We reviewed clinical data of 186 patients with PHPT managed at our center from January 1996 to December 2017. Silent renal stones were defined as ultrasonography finding of renal stones without symptoms. Symptomatic renal stones were defined as those with symptoms or a history of graveluria or any procedure for nephrolithiasis. A 5-mm diameter was set as the cut-off between micro- and macrolithiasis. We compared those with (n = 95) and without (n = 91) stones, and, among stone formers, those with symptoms (n = 66) and silent (n = 29) were compared. Results: There was no significant difference between stone formers and nonstone formers with respect to biochemical parameters. Patients with silent renal stones had significantly lower serum calcium and higher phosphate, than those with symptomatic stones. Most (75%) patients with silent renal stones had microlithiais, while only a fifth (22%) with symptomatic renal stones had microlithiasis. Conclusion: Nephrolithiasis is a common complication of PHPT. Most patients with silent renal stones had microlithiasis and biochemical features of less severe disease. Patients with silent renal stones may represent early mild stage of PHPT.

Adverse effect profile and effectiveness of sodium glucose co-transporter 2 inhibitors (SGLT2i) - A prospective real-world setting study Harmandeep Kaur Gill, Parjeet Kaur, Shama Mahendru, Ambrish Mithal Indian Journal of Endocrinology and Metabolism 2019 23(1):50-55 Background: Clinical trials have shown promising results in terms of glycemic control and weight reduction with the use of sodium glucose co-transporter 2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM). However, real-world evidence from standard clinical practice especially from Asia is still limited. The aim of this study was to evaluate the safety and effectiveness of SGLT2i in patients with T2DM in real-world setting. Methods: This was a prospective observational longitudinal study involving consecutive patients with T2DM, initiated on SGLT2i from 1 April 2015 to 31 March 2016. The adverse effects and metabolic parameters were evaluated at 3 monthly intervals up to 1 year. Results: Total 486 patients were initiated on SGLT2i. At baseline, mean age, glycosylated haemoglobin (HbA1c), and weight was 51.03 ± 9.82 years, 8.76 ± 1.59%, and 89.32 ± 16.04 kg, respectively. Data of 388 patients were available at 6 months of follow-up for analysis of adverse effects profile. About 38.6% patients experienced adverse effects. Genitourinary tract infection was the most common adverse effect (20.6%) followed by generalized weakness (10.5%). Significant reduction in mean weight and HbA1c reduction seen at 6 months (n = 202): 3.2 kg and 1.26%, respectively, and at 12 months (n = 104): 3.9 kg and 1.27%, respectively. Conclusion: In this real-world study of patients with T2DM living in hot climate, use of SGLT2i was associated with adverse effects in higher proportion of patients than those reported in clinical trials, but effectiveness was comparable. Patient guidance regarding adequate hydration and hygiene can maximize the benefits of this promising class of drugs.