Clinical course and outcome of patients with ACTH-dependent Cushing's syndrome infected with novel coronavirus disease-19 (COVID-19): case presentations.

OBJECTIVE: To analyze the clinical presentations of patients with endogenous Cushing's syndrome (CS) affected by Coronavirus disease-19 (COVID-19). MATERIALS AND METHODS: Patients who were referred to our clinic with active CS from 31st March to 15th May 2020 were screened for COVID-19 using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Late-night serum cortisol (64-327 nmol/L), late-night salivary cortisol (LNSC) (0.5-9.4 nmol/L), or 24-h urinary free cortisol (24 hUFC) (100-379 nmol/24 h) were measured by electrochemiluminescence immunoassay. RESULTS: Among 22 patients with active CS we found three cases affected by COVID-19. Nonspecific inflammation markers were within the reference range or slightly elevated in these patients. A 71-year-old woman with newly diagnosed CS (late-night serum cortisol >1750 nmol/L, LNSC 908.6 nmol/L) developed dyspnea as an only symptom and died from bilateral polysegmantal hemorrhagic pneumonia 7 days later. A 38-year-old woman with a 5-year medical history of active Cushing's disease (CD) (late-night serum cortisol 581.3 nmol/L, 24 hUFC 959.7 nmol/24-h) suffered from dyspnea, cough, fever (39.3 °C) and chest pain. Oxygen therapy, antibiotics and symptomatic treatments lead to full recovery 24 days later. A 66-year-old woman with a 4-year medical history of mild CD (late-night serum cortisol 603.4 nmol/L, LNSC 10.03 nmol/L) tested positive for COVID-19 in routine screening and remained asymptomatic. CONCLUSIONS: The outcome of COVID-19 in patients with CS depends on the severity of hypercortisolism. Thus, severe hypercortisolism is a warning sign that CS affected by COVID-19 could require emergency care despite a lack of clinical presentations and low inflammation biomarkers.

Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population.

BACKGROUND: The association of type 2 diabetes mellitus (T2DM) with the KCNJ11, CDKAL1, SLC30A8, CDKN2B, and FTO genes in the Russian population has not been well studied. In this study, we analysed the population frequencies of polymorphic markers of these genes. METHODS: The study included 862 patients with T2DM and 443 control subjects of Russian origin. All subjects were genotyped for 10 single nucleotide polymorphisms (SNPs) of the genes using real-time PCR (TaqMan assays). HOMA-IR and HOMA-ß were used to measure insulin resistance and ß-cell secretory function, respectively. RESULTS: The analysis of the frequency distribution of polymorphic markers for genes KCNJ11, CDKAL1, SLC30A8 and CDKN2B showed statistically significant associations with T2DM in the Russian population. The association between the FTO gene and T2DM was not statistically significant. The polymorphic markers rs5219 of the KCNJ11 gene, rs13266634 of the SLC30A8 gene, rs10811661 of the CDKN2B gene and rs9465871, rs7756992 and rs10946398 of the CDKAL1 gene showed a significant association with impaired glucose metabolism or impaired ß-cell function. CONCLUSION: In the Russian population, genes, which affect insulin synthesis and secretion in the ß-cells of the pancreas, play a central role in the development of T2DM.

Risk of Herpes Zoster in Individuals on Biologics, Disease-Modifying Antirheumatic Drugs, and/or Corticosteroids for Autoimmune Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Studies examining the risk of herpes zoster (HZ) associated with immunosuppressants, such as biologics, nonbiological disease-modifying antirheumatic drugs (nbDMARDs), or corticosteroids, have generated conflicting results. METHODS: We conducted a systematic literature search from January 1946 to February 2016. Search terms related to HZ, rheumatoid arthritis, psoriasis, psoriatic arthritis, systemic lupus erythematous, or inflammatory bowel disease, biologics, nbDMARDS, and corticosteroids were used. We included randomized controlled trials (RCTs) and observational studies reporting associations between immunosuppressants and HZ outcomes in adults. For RCTs, we used the Mantel-Haenszel fixed-effects model to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for HZ risk. For observational studies, adjusted ORs were pooled separately using random-effects inverse variance models. RESULTS: Data were pooled from 40 eligible RCTs (20136 patients) and 19 observational studies (810939 patients). Biologics were associated with a greater risk of HZ than control (RCTs: OR = 1.71, 95% CI = 1.11-2.64; observational studies: OR = 1.58, 95% CI = 1.39-1.81). In RCTs, the OR of non-tumor necrosis factor (TNF) blockers was 2.19 (95% CI 1.20-4.02), but that of TNF blockers was not significantly different from control. Increased risks of HZ with nbDMARDs (OR = 1.21; 95% CI = 1.15-1.28) and corticosteroids (OR = 1.73; 95% CI = 1.57-1.89) were observed in observational studies, but few RCTs examined these comparisons. CONCLUSIONS: Immunocompromised patients receiving biologics were associated with an increased risk of HZ. The risk is also increased with corticosteroids and nbDMARDs. These findings raise the issue of prophylaxis with zoster vaccine in patients initiating immunosuppressive therapy for autoimmune diseases.

Levothyroxine replacement therapy in patients with subclinical hypothyroidism and coronary artery disease.

OBJECTIVE: To assess the potential benefits and risks associated with levothyroxine (LT4) therapy in patients with subclinical hypothyroidism (SH) and concomitant coronary artery disease (CAD). METHODS: We enrolled 33 patients (4 male and 29 female subjects) with SH and CAD in this study. The study cohort consisted of 2 groups: 19 patients who were randomly assigned to receive LT4 therapy, titrated to maintain a normal serum thyrotropin level (main group), and 14 patients who did not receive any LT4 replacement therapy (control group). Variables of the lipid profile and left ventricular diastolic function were measured and 24-hour electrocardiographic monitoring was performed before randomization and at 6-month follow-up. Medical therapy for the CAD remained unchanged throughout the 6-month study period. RESULTS: In the main group, no statistically significant differences were found in the lipids, variables of left ventricular diastolic function, and heart rate pattern between the hypothyroid and euthyroid states. Individual analysis revealed, however, that LT4 therapy was beneficial in terms of lipid abnormalities in those patients with lower body mass index, shorter history of CAD, and higher cholesterol levels at baseline. In the control group, we noted statistically significant prolongation of early filling deceleration time after 6 months, which indicated less flexibility of the left ventricular myocardium and diastolic myocardial dysfunction with long-term SH. In reference to adverse effects of LT4 therapy, 5 of the 19 patients had an increased rate of ventricular premature beats. These 5 patients were significantly older and initially had more supraventricular and ventricular premature beats than the rest of the main group. No ST depressions were recorded during LT4 therapy. CONCLUSION: In patients with SH and CAD, LT4 therapy can be beneficial in diminishing lipid abnormalities in those with lower body mass index, briefer duration of CAD, and higher levels of cholesterol at baseline. Patients in our study who experienced adverse effects of LT4 treatment were older and had more supraventricular premature beats at baseline in comparison with the other patients.