Evaluation of the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness

ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo-pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.

Evaluation of the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness.

Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo-pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.

Calculated plasma osmolality at hospital admission correlates well with eGFR and D-Dimer, a simple outcome predictor and guiding tool for management of severe COVID-19 patients.

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.

Evaluation of simple and cost-effective immuno- haematological markers to predict outcome in hospitalized severe COVID-19 patients, with a focus on diabetes mellitus - A retrospective study in Andhra Pradesh, India.

BACKGROUND AND AIMS: COVID-19 pandemic has strained the health infrastructure globally, providing an opportunity to identify cost-effective biomarkers. We aimed to identify simple hematological prognostic markers in hospitalized severe COVID-19 patients with and without diabetes. METHODS: Retrospective study of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 154 patients, including diabetic subset n = 57) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for total leucocyte count (TLC), absolute neutrophil count (ANC), neutrophil lymphocyte ratio (NLR), and derived neutrophil lymphocyte ratio (dNLR) in order to prognosticate the outcome. RESULTS: Among 154 severe COVID-19 patients, significant association with mortality was seen with respect to TLC(p < 0.001), ANC (p < 0.001), NLR(p < 0.001) and dNLR(p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for TLC 8950 cells/mm3 (area under curve (AUC)-0.764, odds ratio (OR)-7.53), ANC 7679 cells/mm3 (AUC-0.789, OR-8.14), NLR 5.13 (AUC-0.741, OR-4.77), dNLR 3.44 (AUC -0.741, OR-4.43) respectively.In diabetic subset, the cut-offs for TLC was 8950 cells/mm3 (AUC -0.762, OR-14.9), ANC 6510 cells/mm3 (AUC -0.773, OR-16.8), NLR 5.13(AUC -0.678, OR-6) and dNLR 3.25(AUC -0.685, OR-4.7) respectively. CONCLUSIONS: In severe COVID-19 patients irrespective of diabetes, a simple, applicable total leucocyte count cut-off, 8950 cells/mm3 , together with easily derived cut-offs for ANC, NLR, dNLR may serve as cost-effective prognosticators of clinical outcome. A normal TLC may be misleading in the intensive care and the above applicable cut-off for TLC serves as an early warning tool for high-risk identification and better in-hospital management. Even with similar or lower cut-offs, diabetics had a higher mortality.

Consensus on Choice of Insulin Pen Devices in Routine Clinical Practice in India.

Although insulin delivery devices are widely used by the patients, there is a paucity of published guidelines to help professionals manage their patients in insulin therapies. To provide simple and easily implementable guidelines to health care physicians on the choice of insulin delivery devices in routine clinical practice, experts in diabetes gathered together and discussed the recommendations at the National insulin Summit 2018. An ideal insulin delivery device should accurately deliver the prescribed dose of insulin and be easy to use. Recommendations are: (1) insulin should be initiated by using an insulin device if the patient seems to discontinue insulin therapy. (2) Pen devices offer accurate dosing than a syringe and vial and are associated with cost savings in the long term. (3) Switching over from syringes and vial to disposable pen devices improves adherence. (4) FlexPen® offers better accuracy, and it requires lower dose force and injection force than SoloStar® and KwikPen® (5). Durable delivery pens such as NovoPen® 4 maintain accuracy and low dose force compared with vials and syringes. (6) One pen should be used by only one patient. (7) Regular counseling on the proper use of the pen device is required regularly. This consensus-based recommendation is a useful reference tool for health care practitioners to initiate insulin therapy in patients with diabetes by using the appropriate insulin pen device.

Postpartum Follow-up in Women Diagnosed with Subclinical Hypothyroidism during Pregnancy.

BACKGROUND: Management guidelines about the thyroid disease in pregnancy are silent about the postpartum course of new onset subclinical hypothyroidism (SCH). Hence, we analyzed the 2 years outcome of SCH diagnosed during pregnancy. MATERIALS AND METHODS: We conducted this retrospective study using the medical records of patients with new onset SCH during pregnancy between 2010 and 2013 (n = 718). Patients who stopped their levothyroxine after delivery with a 2-year follow-up record were included. We excluded patients with known thyroid disorders and continuous use of drugs that affect the thyroid results. The patients were divided into two groups (Group 1 - euthyroid and Group 2 - hypothyroid) based on the final outcome after 2 years. The data were analyzed using appropriate statistical methods and a P < 0.05 was considered statically significant. RESULTS: A total of 559 (77.8%) women stopped levothyroxine after delivery, and the final follow-up data were available for 467 patients only. At the end of 2 years, 384 (82.2%) remained euthyroid, and the remaining 83 (17.8%) developed hypothyroidism. SCH and overt hypothyroidism were seen in 22 and 61 patients, respectively. Group 2 patients had higher mean age (25.5 vs. 23.6 years), goiter (51 vs. 2%), initial thyroid stimulating hormone (7.9 vs. 5.1 µIU/mL), and thyroid antibody positivity (76 vs. 13%) (P < 0.001). CONCLUSION: The majority of patients with SCH during pregnancy remain euthyroid after delivery. Advanced age, goiter, positive family history, and thyroid autoimmunity increase the future risk of hypothyroidism in patients with SCH diagnosed during pregnancy.

Improvement in subclinical cognitive dysfunction with thyroxine therapy in hypothyroidism: A study from tertiary care center.

AIM: To evaluate the effect of hypothyroidism (both overt and subclinical) on cognitive function using latencies of P300 auditory evoked potentials (AEPs). P300 latency suggests that shorter latency times are related to better cognitive performance. P300 latencies were also done after thyroxine replacement to see the effect of treatment on cognitive function. MATERIALS AND METHODS: Biochemically proven new onset cases with hypothyroidism (overt and subclinical) were enrolled into the study, AEPs of these two groups when compared with matched controls. After detailed history and physical examination, P300 potentials were recorded at two points Cz and Pz (Cz: On the midline of the head at the vertex, Pz: On the midline of the head between the vertex and occipital protuberance) using a Nicolet Viking Select neuro diagnostic system version 10.0. The study was done in electrophysiology lab in Osmania Medical College. RESULTS: A patient characteristics of both cases and controls were comparable. The cases consisted of two groups, overt hypothyroid cases 24, mean thyroid stimulating hormone (TSH) values in them was 94, subclinical cases 21 in whom mean TSH value was 12.3. Mean P300 latencies of all cases at Cz was 342.42 ± 29.5 ms, and at Pz was 345.4 ± 30 ms. Mean P300 latencies of controls at Cz was 296.4 ± 34 ms and at Pz was 297.9 ± 33 ms (difference in P < 0.001). Mean P300 values in overt cases were 362.6 ± 32.9 ms at Cz, and at Pz it was 362.5 ± 33.9 ms. Mean P300 values in subclinical cases were 319.3 ± 30.9 ms at Cz, and at Pz it was 316.4 ± 27.9 ms. P300 values in overt cases were highly significant as compared to controls, and P300 values in the subclinical cases versus controls were also significant (P < 0.001). CONCLUSION: P300 latency prolongation in both clinical and subclinical hypothyroid cases shows that cognitive function is affected adversely in hypothyroidism including the subclinical hypothyroid cases. Larger studies evaluating the effect of subclinical hypothyroidism on cognitive function are needed with objective means such as the AEPs P300.

An unusual combination of Klinefelter syndrome and growth hormone deficiency in a prepubertal child.

Klinefelter syndrome (KS) is the most common chromosomal aneuploidy in males. It is very difficult to diagnose this disorder in childhood due to absence of significant manifestations before puberty. These patients usually present with tall stature. We report a case of KS with short stature due to growth hormone deficiency. The boy's height was below the 3rd centile with significant delay in bone age. He responded well to growth hormone injections. In view of mental subnormality karyotyping was done, which revealed KS (47XXY).

Functioning adrenal myelolipoma: A rare cause of hypertension.

Co-occurrence of adrenal incidentaloma with hypertension calls for evaluation of endocrine causes including pheochromocytoma, Cushing's disease, and primary aldosteronism. We are reporting 40-years-old man who presented with hypertension and adrenal mass. He had elevated metanephrines, histology of resected adrenal mass revealed adrenal myelolipoma, and immuno-histochemistry was positive for chromogranin A. Both his blood pressure and urinary metanephrines returned to normal after surgery. The association of hypertension and adrenal myelolipoma may not be entirely coincidental, as it may be associated with secreting catecholamine. Literature on such an uncommon association is reviewed briefly as well.

Association of tumor necrosis factor alpha, interferon gamma and interleukin 10 gene polymorphisms with peripheral neuropathy in South Indian patients with type 2 diabetes.

UNLABELLED: Diabetic peripheral neuropathy (DPN) is a major global health threat and a common complication of diabetes. Peripheral nerve complications due to irregular cytokine production are eminent factors in many inflammatory diseases. The present study focused on gene polymorphisms of pro and anti-inflammatory cytokines that may be responsible for nerve damage in diabetic neuropathy. We examined three common functional SNPs primarily at the positions on genes of tumor necrosis alpha (TNFalpha) -308G/A, interferon gamma (IFNgamma) +874A/T and interleukin (IL) 10 -1082G/A in order to establish their association with peripheral neuropathy in type 2 diabetes. RESULTS: Genotypic frequencies obtained from TNFalpha -308G/A gene analysis in DPN group comprised 86.4% of G/A, 10.6% of G/G and 3% of A/A genotype, where as the control group had 94% of G/A, 2% of G/G and 4% of A/A which could not reach the statistical significance with the disease after Bonferroni correction. The IFNgamma +874 A/T polymorphism in patient group revealed 33.3% of A/A, 47.5% of A/T and 19.2% of T/T genotype. The A/A genotype had attained statistical significance of P=0.04 (P corrected); OR 2; 95% CI 1.14-3.64 when compared to controls. The IL10 -1082 G/A polymorphism in the patient group has showed 62.6% of A/A, 21.2% of G/A, 16.2% of G/G genotype, revealing significant association with G/G genotype (P<0.01, OR 2.9; 95% CI 1.47-5.84) when compared to controls. CONCLUSION: Our findings indicate that the tested markers within the IFNgamma and IL-10 genes, but not the TNFalpha gene, are significantly associated with peripheral neuropathy in South Indian type 2 diabetic patients. The study shows that the 'high-producer' IL-10 -1082 G/G genotype and the 'low-producer' IFNgamma +874 A/A genotype may be responsible for the down regulation of immune response leading to inflammation in this setting.