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   2020| September-October  | Volume 24 | Issue 5  
    Online since November 9, 2020

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Endocrine involvement in COVID-19: Mechanisms, clinical features, and implications for care

September-October 2020, 24(5):381-386
Coronavirus 2019 (COVID -19) has rapidly emerged as a global pandemic with multi-system involvement. Involvement of the endocrine system is expected in COVID-19 as the interplay between severe acute respiratory syndrome corona virus-2 (SARS CoV-2) and the endocrine system occurs at multiple levels. The widespread presence of ACE-2 receptors on various tissues suggests scope for direct viral infection. The interactions via the activation of inflammatory mediators and indirect immune-mediated damage are also postulated. Evidence so far suggests that COVID-19 can cause functional hypopituitarism by direct and indirect effects on the hypothalamo-pituitary axis resulting in inappropriate adrenal response to stress. Several reports highlight possible immune-mediated damage to thyroid glands resulting in subacute thyroiditis. COVID-19 is implicated in precipitating hyperglycemia in known diabetics and uncovering insulin resistance in those previously undiagnosed. COVID-19 has also been shown to trigger Type 1 Diabetes with ketosis. Various mechanisms including direct virus-induced beta cell apoptosis and immune-mediated beta-cell damage have been demonstrated. The presence of virus in semen has unclear clinical significance at present. In this mini-review summarize the endocrine manifestations reported so far in COVID-19 disease and explore mechanisms to decipher how SARS CoV-2 may affect various endocrine organs.
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Endocrine week - Abstracts

September-October 2020, 24(5):452-505
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Efficacy and safety of novel dipeptidyl-peptidase-4 inhibitor evogliptin in the management of type 2 diabetes mellitus: A meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Aishwarya Krishnamurthy, Lokesh Kumar Sharma, Meha Sharma
September-October 2020, 24(5):434-445
Aims: No meta-analysis is available which has summarized and holistically analyzed the efficacy and safety of evogliptin. We undertook this meta-analysis to address this gap in knowledge Methods: Electronic databases were searched for RCTs involving diabetes patients receiving evogliptin in intervention arm and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in fasting glucose, postprandial glucose, lipids, insulin resistance, patients achieving glycemic targets of HbA1c <7% and <6.5%, and adverse events. Results: From initially screened 57 articles, data from six RCTs involving 887 patients was analyzed [three having sitagliptin/linagliptin as active comparator; three having placebo in control group]. Evogliptin was noninferior to sitagliptin/linagliptin regarding HbA1c reduction at 12 weeks [mean difference (MD) -0.06%; 95%CI: -0.23–0.11%; P = 0.48] and 24 weeks (MD 0.04%; 95%CI: -0.11–0.19%; P = 0.60) follow-up. Evogliptin was superior to placebo regarding HbA1c reduction at 12-weeks (MD -0.57%; 95%CI: -0.62– -0.52%; P < 0.001) and 24 weeks (MD -0.28%; 95%CI: -0.47 – -0.09%; P = 0.004). Evogliptin was noninferior to sitagliptin/linagliptin regarding patients achieving HbA1c <7% and <6.5% at 12 weeks and 24 weeks follow-up. Total adverse events [Risk ratio (RR) 0.98; 95% CI: 0.72–1.32; P = 0.89] and severe adverse events (RR 0.65; 95% CI: 0.25–1.67; P = 0.37) were not significantly different among groups. Patients receiving evogliptin did not have increased symptomatic (RR 0.46; 95% CI: 0.10–2.16; P = 0.32) and asymptomatic (RR 1.09; 95% CI: 0.61–1.97; P = 0.77) hypoglycaemia. Conclusion: Evogliptin is well tolerated and has good glycemic efficacy over 6 months use for T2DM management
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On psychology and psychiatry in diabetes
Gumpeny R Sridhar
September-October 2020, 24(5):387-395
Managing diabetes requires dealing with diet, medications, and self-monitoring, besides other pressures of daily living. It, therefore, requires collaboration among individuals with diabetes, their families, and significant others including the social milieu in which they reside. Psychological stress plays critical role in the cause and course of diabetes, particularly in mastering various self-management skills, which are essential for adequate management of diabetes. It is possible to measure and to resolve such stressors. Besides the patient and the family, the built environment which the person occupies must be conducive for healthy living. This is a key component in providing an appropriate physical and psychosocial environment. Lacunae in any of the built environmental parameters compromise social and psychological well-being. Psychiatric conditions are also common in diabetes. Both depression and distress are bi-directionally associated with diabetes. The presence of one condition increases the risk of developing the other. In addition, medications used for the treatment of psychiatric conditions have adverse effects on body weight and insulin sensitivity. One must carefully weigh the risk and benefit of the drug class with potential adverse effects. Therefore, identification and management of psychological and psyciatric aspects in subjects with diabetes is an integral and critical component in treating subjects with diabetes.
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Neurocognitive functions and brain volume in patients with endogenous cushing's syndrome before and after curative surgery

September-October 2020, 24(5):396-401
Introduction: Cushing's syndrome (CS) leads to various neuropsychiatric manifestations due to structural and functional changes of the brain and contributes significantly in the impairment of health-related quality of life. Aim and Objective: This study is conducted with aims to evaluate neurocognitive functions and brain volume in patients with endogenous Cushing's syndrome before and after curative surgery. Methods: The diagnosis of CS was made by clinical features, abnormal cortisol dynamics, ACTH levels, and imaging studies. Neuropsychiatric tests (Beck depression Index, Spatial span test, PGI memory scale, Color trail test, Verbal fluency test), and Brain volume (Bi-caudate and third ventricular diameter) were done before and after curative surgery. Results: Fifteen patients of CS were included for the study; all patients underwent curative surgery, neuropsychiatric assessment, and brain volume measurements. Nine patients were followed successfully till remission and repeat evaluation of these patients was done. Depression was the most common neuropsychiatric illness. Severity of depression positively correlated with 0800 h plasma cortisol and ACTH. Patients with higher severity of depression had maximum improvement after curative surgery. Significant decrease in the third ventricular, as well as bicaudate diameter, was observed after curative surgery (P < 0.01). Conclusion: Neuropsychiatric functions and structural brain changes reverse after curative surgery in patients with endogenous CS, however, long term follow-up is required to know whether these changes reverse completely or not.
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The President's message, 2019-20 strengthening endocrinology: Towards a sustainable future
Sanjay Kalra
September-October 2020, 24(5):377-380
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Health-related quality of life in acromegaly patients: Results from generic and disease-specific questionnaires

September-October 2020, 24(5):402-405
Introduction: Acromegaly is associated with high morbidity, but still controversial impact on the overall quality of life (QoL). Material and Methods: We evaluated QoL using a generic (SF-36) and a disease-specific questionnaire (AcroQoL) in an acromegalic cohort. Results: Sixty-nine patients answered the questionnaires and had their records reviewed. In the SF-36 questionnaire, except for the Social Aspects domain, all others revealed a reduction in scores from 9.7 to 38.9%, when compared to the non-acromegalics. The cure was positively correlated with mental health (P = 0.023) and drug control was correlated with mental health (P = 0.023) and functional capacity (P = 0.013). In the AcroQoL questionnaire, the mean scores ranged from 54.7% to 72.8%. The use of antidepressants correlated with lower scores on the total AcroQoL (P = 0.039) and physical complaints (P = 0.003). The growth hormone value at diagnosis showed an inverse correlation with the total AcroQoL score (P = 0.014), Appearance Issues subscale (P = 0.081), and Personal Relations (P = 0.002). IGF-1 values at diagnosis and at the last visit showed no statistical correlation with any of the questionnaires. Conclusion: The finding of a reduction in QoL scores with both SF-36 and AcroQoL allows us to suggest this evaluation as part of the initial assessment and follow-up in acromegaly, to act globally on the individual's health condition.
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Clinical and severity profile of acute pancreatitis in a hospital for low socioeconomic strata

September-October 2020, 24(5):416-421
Introduction: There is an upsurge in the incidence of acute pancreatitis over the last few decades; although the case fatality rate has remained unchanged. This may either be due to increased incidence of gallstone disease or improvement in diagnostic modalities. It is a potentially life threatening disease with varying severity of presentation. Methods: This observational analytical study was conducted in the Department of General Surgery in our hospital for a period of one year. All patients of acute pancreatitis were included in the study as per inclusion & exclusion criteria. Observations and Results: Total 62 Patients were included in the study. Gall stones disease is the most common cause of acute pancreatitis. The mean age of the patients in the study was 39 years. 28 females and 34 male patients were present. 22 patients of the patients had severe disease as per Atlanta classification. Four out of these 22 severe pancreatitis patients expired. All patients in the severe pancreatitis group had mild to life threatening complications and pleural effusion was the most common followed by necrosis. There was notable difference in terms of hospital stay between mild group and severe group of AP. Conclusion: The clinician should be aware that acute pancreatitis can occur in any age group and gender due to different etiology. The severity of AP does not depend on etiology, age or gender and it is associated with significant morbidity and mortality. SAP can be diagnosed on clinicoradiological basis and appropriate management can be done in those patients.
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Etiology and clinical profile of patients with tall stature: A single-center experience

September-October 2020, 24(5):428-433
Background: There is no published literature on the profile of patients with tall stature (TS) from India. This study aimed to evaluate the etiological and clinical profile of patients with TS referred to our hospital. Materials and Methods: We performed a retrospective review of records of patients referred to us for evaluation of TS (January 2007 to March 2020). Relevant clinical, anthropometric, biochemical, and radiological data at presentation were recorded, and the final diagnosis reviewed. Results: The study included 16 subjects (6 boys, 10 girls) with a mean age at presentation of 13.2 ± 3.6 years. Most subjects were pubertal (n = 10) and belonged to the overweight or obese category (n = 10). The mean height and height standard deviation score (SDS) were 172.3 ± 20.3 cm and 3.6 ± 1.5, respectively, while mean mid-parental height (MPH) and MPH SDS were 168.8 ± 8.8 cm and 1.2 ± 0.9, respectively. The etiological diagnoses were familial TS (n = 9), acrogigantism (n = 3), obesity-related TS (n = 2), constitutional advancement of growth (n = 1), and Marfan syndrome (n = 1). The mean height SDS in subjects with acrogigantism was 6.4 ± 1.2 compared to 3.0 ± 0.6 in those with other etiologies of TS. Only one girl with familial TS and significantly increased predicted adult height (+4.56 SDS) opted for sex steroid therapy. Conclusion: Familial TS is the most common diagnosis among patients referred for evaluation to our hospital. One should consider the possibility of acrogigantism in patients with growth acceleration, extreme TS, and markedly increased gap between height SDS and MPH SDS. Most patients with familial TS require reassurance and sex steroid therapy should be reserved for highly selected cases.
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Efficacy of fluorescein green dye in assessing intra-operative parathyroid gland vascularity and predicting post-thyroidectomy hypocalcaemia- A novel prospective cohort study

September-October 2020, 24(5):446-451
Background: Postoperative hypocalcaemia (POH) after total thyroidectomy (TT) is a common complication. Parathyroid hormone (PTH), an accurate predictor of POH cannot assess intra-operative viability of parathyroid glands (PGs). Different dyes including indocyanine green or carbon nanoparticles have been used, but they are expensive and not widely available. Fluorescein green dye (FD) has been used as a low-cost alternative to study viability of various organs, but seldom tried in visualizing PGs. This novel study aims to assess utility of FD in determining parathyroid viability and predicting POH. Material and Method: Total 72 out of 88 patients undergoing TT between January and December 2019 were included. Two ml of 25% FD was given intravenously before wound closure and attempts were made to visualize PGs under blue light. A numerical score was given according to the number of PGs visualized. Intact-PTH and corrected calcium were measured on postoperative day 1 and patients observed for POH. Results: No PGs were visualized in 6 patients, 1 in 13, 2 in 30, 3 in 16 & 4 in 7 patients. Mean PTH was 6, 16.9, 31.6, 33.2 and 48.5 respectively. Corrected-calcium was 7.08, 7.7, 7.9, 8.5 and 8.5 respectively. All patients with score 0 received supplementary IV calcium, while 53.8% (score-1), 30% (score-2), 0% (scores-3, 4) received the same. Sensitivity, specificity and ROC of PG score of ≥2 on FD in predicting POH were 100%, 44% and 0.83 respectively. Conclusion: FD visualization of parathyroids post TT is feasible and can be used as low cost efficacious method to predict POH.
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High thyroid-stimulating hormone level in down's syndrome: A mere resetting of hypothalamopituitary axis in subclinical hypothyroidism?

September-October 2020, 24(5):406-409
Objective: Hyperthyrotropinemia (HT) or reduced thyroid function in Down syndrome (DS) is not uncommon, causes range from glandular dysgenesis to altered hypothalamopituitary axis. In the present study, we have compared hypothyroid Indian children with and without DS (NDS), especially focusing on family history, goiter, and biochemical features. Methods: We conducted this retrospective observational study from previous medical records of children with DS (1-17 years) having an elevated TSH (≥5 mIU/L) who were consecutively referred for with HT to Endocrinology OPD of a tertiary care hospital in India. Records from hypothyroid children (1-17 years) without Down Syndrome (NDS) were evaluated as controls. Free thyroxine (FT4), anti-thyroid peroxidase (TPO) antibody were measured and congenital hypothyroidism was excluded in all subjects. Results: Thirty-four DS cases [median age 8 years (IQR: 2-14), M: F = 13:21] and 34 controls [median age 10.5 years (IQR: 7-13.25), M: F = 13:21] were comparable in terms of age and sex, Median age of presentation was significantly earlier in case of DS vs NDS [7 years vs. 10 years]. DS children had significantly less family history of thyroid disorders compared to NDS [14.7% vs 64.7%]. Goiter was significantly less common in patients with DS [DS - 32.25% vs. NDS - 73.5%, P = 0.001]. Anti-TPO antibody positivity was significantly less common in patients with DS [DS- 41% vs. NDS- 73.5%, P = 0.014]. Conclusion: There is a significant difference in presentation in hypothyroid children with DS compared to NDS. DS children with hypothyroidism compared to NDS, had earlier presentation, lower incidence of traceable family history, goiter, and anti-TPO-antibody positivity.
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Paget's disease of bone in Tunisia: A study of 69 patients

September-October 2020, 24(5):422-427
Context: Paget's disease of bone is a common bone disease with a striking variation in its incidence and characteristics in different parts of the world. It is uncommonly reported in African patients. Aims: Given the lack of studies describing the characteristics of patients with Paget's disease of bone in North Africa, we aimed to describe demographic, clinical, biochemical, and imaging characteristics, as well as treatment outcomes of Tunisian patients with Paget's disease of bone. Subjects and Methods: This bicentric and retrospective study included patients with Paget's disease of bone. Clinical, laboratory, radiological profile, and response to treatment were analyzed. Results: Sixty-nine patients were identified. The mean age was 64.9 ± 11.6 years and 52.2% were women. One patient reported a positive family history. Seven patients were asymptomatic. Bone pain was the most common presenting symptom. Eight patients had a history of malignancy. In three patients, Paget's disease of bone was diagnosed as part of a metastatic workup. Monostotic disease was found in half of the cases. The most commonly involved sites were pelvis (43.5%), femur (21.7%), and spine (21.7%). The mean serum alkaline phosphatase level at presentation was 591 U/L (68–8380). Two patients received salmon calcitonin (2.8%) and 47 patients (68.1%) received bisphosphonates. After a mean follow-up of 55 months (2–240 months), bone pain improved in 43.1% of patients and the serum alkaline phosphate levels had normalized in 22 of them (43.1%). During follow-up, there was no malignant transformation. Conclusions: In this series of Tunisian patients, Paget's disease of bone had a female predominance and was usually monostotic. The clinical and radiological presentations were similar to the European series.
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Evaluation of gonadotropin responses and response times according to two different cut-off values in luteinizing hormone releasing hormone stimulation test in girls
Servan Ozalkak, Semra Çetinkaya, Fatma Can Budak, Şenay Savaş Erdeve, Zehra Aycan
September-October 2020, 24(5):410-415
Background: In this study, we aimed to evaluate FSH, LH responses obtained during LHRH-ST according to two different cut-off values, to determine the diagnostic response times, and to find the optimal blood collection times that could reduce the economic and time burden of LHRH-ST. Materials and Methods: Patients who underwent LHRH-ST in our clinic with the preliminary diagnosis of precocious puberty (PP) between 01/08/2016 and 31/12/2017 were retrospectively enrolled to the study. In this study 207 girls with PP were included and some of them (102 according to C1 and 139 according to C2) had central PP (CPP). Test response and response times were evaluated according to both cut-off values of stimulated peak LH pubertal responses as 5 mIU/ml (the 1st cut-off = C1) and 3.3 mIU/ml (the 2nd cut-off = C2). Results: Totally, 207 girls with a mean age of 7.5 ± 1.22 (3.4-9.5) years were included in the study. With LHRH-ST; 49.2% (n = 102), 67% (n = 139) of the cases were in pubertal period according to C1, C2, respectively. According to C1; pubertal LH was present in 94.1% (n = 96) of 102 patients who reached pubertal LH value in 45th minutes. The highest pubertal response was obtained in the 45th minute. According to C2, of 139 patients who reached pubertal LH; pubertal LH was determined in 98.5% (n = 137) in the 45th minute. Pubertal LH levels were determined according to both cut-off values in all 27 patients with baseline LH ≥0.31 mIU/ml. Conclusion: It was determined that measuring LH at 45th minutes during LHRH-ST was sufficient in 94.1% of the cases according to C1 and 97.1% of the cases according to C2. It was concluded that the 30th, 45th, and 60th minute samples were enough to assess pubertal LH response in 100%of the cases. If the basal LH is found to be ≥0.31 mIU/ml in girls with puberty findings, we recommend that the diagnosis of precocious puberty would be made without performing LHRH-ST.
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