Hypothalamic-Pituitary Adrenal Axis Status 3 Months After Recovery From COVID-19 Infection.

CONTEXT: Coronavirus disease 2019 (COVID-19) predominantly involves the lungs, albeit many other organ systems, including the hypothalamic-pituitary-adrenal (HPA) axis, can be affected due to the expression of the angiotensin-converting enzyme 2 (ACE2) binding receptor. Few studies have reported the involvement of adrenal gland and the HPA axis during the acute phase of COVID-19; however, the data on the long-term effect of COVID-19 on the HPA axis after acute infection is scarce. OBJECTIVE: To assess and compare the changes in HPA axis in mild, moderate and severe COVID-19 categories at ≥ 3 months after acute infection. METHODS: A prospective, observational study was conducted to assess the HPA axis status among COVID-19 subjects at least 3 months after recovery from acute infection. The study was conducted from June 2021 to May 2022. Subjects visited the hospital in the fasting state (8.00-9.00am), serum cortisol levels were measured at baseline, 30 and 60 minutes after a 1-µg short Synacthen test (SST). RESULTS: A total of 66 subjects ≥ 18 years of age were included in the study. The mean age (SD) was 49.13 ± 11.9 years, 45(68.18%) were male and 21 (31.81%) were female subjects. The mean BMI in the study was 25.91 ± 4.26 kg/m2. Seventeen (25.8%) subjects had mild, twelve (18.2%) had moderate and thirty-seven (56.1%) subjects had severe COVID-19 infection. Out of the sixty-six subjects with COVID-19, nine subjects (9/66, 13.63%) had peak serum cortisol < 496.62 nmol/L suggestive of adrenal insufficiency (AI). SST peak serum cortisol levels did not differ significantly across the disease severity [Mild, (628.50 ± 214.65 nmol/L) vs moderate, [603.39 ± 161.95 nmol/L) vs severe, (597.59 ± 163.05 nmol/L), P = 0.617]. Six subjects with AI came for follow-up at 12 months, and all had normal HPA axis. CONCLUSION: HPA axis is affected in 13.63% (9/66) of subjects at least 3 months after recovery from COVID-19 infection. AI in COVID-19 might be transient and would recover spontaneously. These findings have important implications for the clinical care and long-term follow-up of subjects after COVID-19 infection.

Phosphate Homeostasis and Disorders of Phosphate metabolism.

Phosphate is indispensable for human life and evolutionary changes over several millions of years have established tightly regulated mechanisms to ensure phosphate homeostasis. In this process, calcium and phosphate metabolism have come to be intricately linked together. Three hormones (PTH, FGF23 and Calcitriol) maintain the fine balance of calcium and phosphate metabolism through their actions at three sites (the gut, the kidneys and the skeleton). Disorders that disrupt this balance can have serious clinical consequences. Acute changes in serum phosphate levels can result in life threatening complications like respiratory failure and cardiac arrythmias. Chronic hypophosphataemia predominantly affects the musculoskeletal system and presents as impaired linear growth, rickets, osteomalacia and dental problems. Hyperphosphataemia is very common in the setting of chronic kidney disease and can be difficult to manage. A thorough understanding of calcium and phosphate homeostasis is essential to diagnose and treat conditions associated with hypo and hyperphosphataemia. In this review, we will discuss the calcium and phosphate metabolism, aetiologies and management of hypo and hyperphosphataemia.

Adrenal crisis in a patient with APS2 due to COVID-19: A case report.

COVID-19 (corona virus disease 2019), caused by the severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has spread throughout the globe and affected millions of people worldwide. Here, we report a patient with autoimmune polyglandular syndrome type 2 who presented with adrenal crisis, precipitated by COVID-19. We intend to highlight the importance of stress dosing in preventing adrenal crisis in patients with adrenal insufficiency (AI). A uniform structured education programme is needed to improve knowledge and practices in patients with AI in our country.

Pituitary Dysfunction Following Snakebite Envenomation: A Clinico-Radiological Assessment of 15 Cases and Review of the Literature.

Background: Snakebite envenomation (SE) is an important tropical disease in India, causing significant morbidity and mortality among patients. The hormonal deficiencies due to the involvement of the pituitary in case of SE can present in either acute or delayed setting. Hypopituitarism (HP) is often an underrecognized and relatively rarely reported complication of this neglected disease. Methods: We present here the data of 15 patients diagnosed to have HP following systemic SE and are being currently followed-up in the Endocrinology outpatient department of a tertiary care hospital of South India. The study was approved by the Institute ethics committee, and informed onsent was taken from all the study patients. The study was a record-based retrospective analysis of the patients with HP following SE. Clinical data including lag time in diagnosis and type of snake were determined. Further, hormonal data including all the anterior pituitary functions (thyroid stimulating hormone, free T4, cortisol, insulin-like growth factor (IGF-1) luteinizing hormone, follicular-stimulating hormone, testosterone; prolactin) and water deprivation test to determine diabetes insipidus (DI) in patients with polyuria on follow-up were extracted from the records and the hospital information system. An experienced neuroradiologist examined the magnetic resonance imaging (MRI) findings of the pituitary. Results: The mean age of the patients was 43 ± 9 years and 80% were male. Around 90% of patients belonged to upper-lower socioeconomic status according to the modified Kuppuswamy scale. The commonest snake species reported was Russell's viper. Thirteen patients had delayed HP. The median duration from snakebite to onset of HP symptoms was 1 year (range 0.33-10 years). However, the median time from snakebite to the diagnosis of HP was 7 years (range 1-13 years). Central hypothyroidism and hypogonadism were present in all subjects. However, central hypocortisolism was noted in 93% of patients. Low IGF-1 was noted in all the six patients where data were available. One patient had partial central DI. Thirteen out of 15 patients had reduction of pituitary volume in MRI. Conclusion: HP in patients with SE can appear slowly and the diagnosis is frequently delayed for years. Following snakebite, multiple pituitary hormone deficiencies associated with radiological abnormalities like a significant reduction in the pituitary volume are common.

Effect of Thyroxine Replacement on Leydig Cell and Sertoli Cell Function in Men with Hypothyroidism.

CONTEXT: Thyroid hormones play an important role in reproductive and sexual function in both sexes. Comprehensive information on the ill-effects of hypothyroidism on Leydig cell, Sertoli cell and germ cell function is lacking in the existing literature. AIMS: To investigate the effect of primary hypothyroidism and its treatment on testicular function - Sertoli cell, Leydig cells, seminal fluid and spermatozoa. METHODS AND MATERIAL: This study was carried out as a descriptive study with a before-after study design in the endocrine department of a tertiary care hospital in South India. Forty treatment naïve, overtly primary hypothyroid, consenting male patients were included. Hormones assessed were free T3, free T4, thyroid stimulating hormone, follicle stimulating hormone [FSH], luteinizing hormone [LH], prolactin, testosterone, inhibin B[INHB], and insulin like factor 3[INSL3]. Semen analysis was done according to WHO 2010 guidelines in 37 subjects. Sexual function questionnaires like Androgen Deficiency in Aging Male [ADAM], and Arizona Sexual Experience Scale [ASEX] were used. After ensuring euthyroid state for consecutive 6 months with adequate dose of thyroxine sodium, reassessment of all parameters was done. RESULTS: At baseline, 72.5 % had a low serum testosterone value (< 230 ng/dl), 67.56 % had low total sperm motility, 72.97% had low total progressive sperm motility, 80% had low ADAM score and 72.72% had low ASEX score. A raised prolactin level was seen in 32.5% of study subjects. Hypogonadotropic hypogonadism was more common than hypergonadotropic hypogonadism (89.66% vs. 10.34%). On restoration of euthyroidism, all these parameters improved. Serum INSL3 and LH increased significantly after thyroxine replacement, unlike FSH and INHB. CONCLUSIONS: Leydig cell function seemed more severely affected by hypothyroidism as compared to Sertoli cell function. Among sperm function parameters, motility was predominantly affected.

An unusual cause of pulmonary calcification.

Metastatic pulmonary calcification (MPC) is an uncommon entity resulting from abnormalities in calcium-phosphorus homoeostasis. Most cases reported in the literature are among patients with chronic kidney disease receiving haemodialysis. Primary hyperparathyroidism is a relatively common condition affecting calcium homoeostasis, in which MPC can rarely occur. We report the case of one such patient who presented with severe hypercalcaemia and features of interstitial lung disease. Radiographic imaging was normal and the diagnosis was clinched by diffuse pulmonary uptake in 99mTechnetium-methylene diphosphate scan.

The Effectiveness of a Brief Psychological Intervention for Patients with Diabetes-Related Distress.

BACKGROUND: Diabetes-related distress (DRD) is the negative emotional and psychological reaction to living with diabetes mellitus (DM). DRD has been reported to affect glycemic control and self-management practices adversely. Limited research is available on the effectiveness of psychological interventions for DRD. We aimed to study the effectiveness of a brief psychological intervention for patients with DRD. METHODS: The findings of a targeted brief psychological intervention conducted for patients with DRD, as a part of psycho-endocrinology liaison services in a general hospital, are reported. Details regarding the assessment and intervention given were collected from the patients' records. Forty-one patients with DRD diagnosed using Diabetes Distress Scale (DDS) were given the single session intervention consisting of brief diabetes education focusing on physical activity and medication adherence, relaxation techniques, and illness-specific problem-solving strategies. Effectiveness was assessed using change in Clinical Global Impression-Severity (CGI-S), patient-rated visual analog scale, brief physical activity questionnaire, and medication adherence at baseline and 2-month follow-up. RESULTS: Analysis using Wilcoxon signed rank test found a significant change in the follow-up scores on all the assessment scales. CONCLUSIONS: The study highlights the benefits of brief intervention for reducing DRD, thus reducing the emotional burden of living with DM.

Insulin Sensitivity and Beta-Cell Function in Graves' Disease and Their Changes with the Carbimazole-Induced Euthyroid State.

BACKGROUND AND OBJECTIVE: Thyroid hormones play an important role in intermediate metabolism, and abnormal glucose tolerance is often observed in patients with hyperthyroidism. Several pathogenic mechanisms have been proposed as contributors. However, there is no conclusive evidence in the existing literature regarding the predominant underlying pathophysiology. Our objective was to determine the changes in insulin resistance parameters and beta-cell function in patients with Graves' disease following restoration of a euthyroid state. METHODOLOGY: This was an observational study with a before-after study design. Forty-five treatment-naïve adults with Graves' diseases were included and 36 completed the study. An oral glucose tolerance test was performed at baseline and after 3 months of achieving a stable euthyroid state to assess glucose tolerance, insulin sensitivity, and beta-cell function. All patients were treated with antithyroid medication. The outcome measures studied were the Homeostasis Model Assessment-2 Insulin Resistance (HOMA2-IR), Matsuda index, and Insulin Secretion-Sensitivity Index (ISSI)-2. RESULTS: Two-thirds of the patients had abnormal glucose tolerance at baseline. Among those with abnormal glucose tolerance at baseline, 34.7% had persistent abnormality during follow-up. During follow-up, no significant change was noted in the indices of insulin resistance. Patients with abnormal glucose tolerance had a significantly lower ISSI-2 index at baseline and it improved after achieving a euthyroid state. CONCLUSIONS: Abnormal glucose tolerance is a significant metabolic consequence in patients with Graves' disease. Decreased beta-cell function was observed among those with abnormal glucose tolerance and it improved during follow-up. In a proportion of patients, abnormal glucose tolerance persisted after 3 months, emphasizing the need for continued follow-up.

Osteoporosis and malignancy: a dicey combination.

Osteoporosis is the most common metabolic bone disorder worldwide, especially in women. Postmenopausal status is the most common risk factor for osteoporosis in elderly women. The operational diagnosis of osteoporosis is usually made with the help of central dual energy X-ray absorptiometry scan. Clinically, osteoporosis is suspected in the background of one or more fractures of the hip, vertebra, proximal humerus or pelvis in the absence of local disease or high-energy trauma. Serious underlying illness can present with vertebral fractures and can be missed if other clues from clinical examination and investigations are overlooked. We report a case emphasising this aspect.

Puzzling thyroid function test.

A 13-½-year-old boy was referred to the Department of Endocrinology as a case of thyrotoxicosis for initiation of antithyroid medication. His chief complaint was a swelling in front of the neck, which was incidentally noted by his mother 2 weeks prior to presentation. He denied any history of symptoms suggestive of hyperthyroidism or ophthalmological involvement. His physical examination was unremarkable except for a grade 2 goitre. Thyroid function test revealed elevated free triiodothyronine and tetraiodothyronine in the face of an unsuppressed thyroid-stimulating hormone level. Technetium-99 uptake scan showed increased uptake indicating enhanced thyroid activity. However, he was clinically euthyroid. This raised the possibility of resistance to thyroid hormones, which was confirmed by documenting similar thyroid function test abnormalities in other members of his family and genetic testing. The family was reassured of the benign nature of the condition.