Improvement in Serum Magnesium Levels With Sodium-Glucose Cotransporter 2 Inhibitors.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with a modest but significant increase in serum magnesium levels. This report describes improvement in serum magnesium and associated symptoms after initiating SGLT2i therapy in a patient with refractory hypomagnesemia. A 58-year-old woman presented with persistent hypomagnesemia refractory to oral magnesium supplements. She had history of type 2 diabetes mellitus, hypothyroidism, fibromyalgia, and degenerative disk disease. The cause of hypomagnesemia was attributed to excessive renal losses. Laboratory investigations revealed serum magnesium of 1.2 mg/dL with fractional excretion of magnesium of 8.9%. She was started on empagliflozin 10 mg daily. Within 4 weeks of therapy, her serum magnesium level corrected with symptomatic improvement, which was sustained a few weeks later. Subsequently, her oral magnesium supplements dose was reduced. SGLT2i has been shown to improve magnesium levels in patients with urinary magnesium wasting. Several mechanisms have been postulated, but the exact physiology remains unknown. SGLT2i have been efficacious for glycemic control, renal protection, decreasing the risk of atherosclerotic cardiovascular disease events, and cardiac mortality in patients with diabetes. In addition, renal and cardiac benefits are also demonstrated in patients without diabetes. This observation demonstrates that SGLT2i can improve the management of patients with otherwise intractable hypomagnesemia.

Mixed Corticomedullary Tumor of the Adrenal Gland: A Case Report and Literature Review.

Adrenal mixed corticomedullary tumors (MCMTs) are composed of an admixture of cortical and medullary cells. Owing to the presence of two distinct components of different embryonic lineage, these tumors are extremely rare. Less than 30 tumors of this type have been reported to date. MCMTs have varied presentation including hypertension, Cushing syndrome or even as adrenal incidentalomas. Also noted is a slightly higher female preponderance. We report a case of a 26-year-old female who was evaluated for uncontrolled hypertension. A renal ultrasound followed by MRI abdomen revealed a 9.3 × 8.1 × 7.0 cm partially cystic, partially solid enhancing mass in the region of/replacing the left adrenal gland. Hormonal work-up was significant for elevated catecholamines concerning pheochromocytoma. She underwent laparoscopic left adrenalectomy, with adequate pre-operative adrenergic blockade. Histology and immunochemical testing were consistent with a mixed corticomedullary tumor. She was monitored annually for recurrence of the tumor. We also performed a comprehensive review of literature of the cases published so far to the best of our knowledge.

Hyperglycemia in COVID-19 infection without diabetes mellitus: Association with inflammatory markers.

BACKGROUND: New onset hyperglycemia is common in patients with severe coronavirus disease 2019 (COVID-19) infection. Cytokine storm due to COVID-19 infection is an essential etiology for new-onset hyperglycemia, but factors like direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced pancreatic ß-cell failure have also been postulated to play a role. AIM: We plan to investigate further the mechanisms underlying SARS-CoV-2 infection-induced hyperglycemia, particularly the rationale of the cytokine-induced hyperglycemia hypothesis, by evaluating the association between inflammatory markers and new onset hyperglycemia in non-diabetic patients with COVID-19 infection. METHODS: We conducted a retrospective case-control study on adults without diabetes mellitus hospitalized for COVID-19 infection. The serum levels of glucose and inflammatory markers at presentation before initiation of corticosteroid were collected. Hyperglycemia was defined as glucose levels ≥ 140 mg/dL. C-Reactive protein (CRP) ≥ 100 mg/L, ferritin ≥ 530 ng/mL, lactate dehydrogenase (LDH) ≥ 590 U/L, and D-dimer ≥ 0.5 mg/L were considered elevated. We used the χ 2 test for categorical variables and the Mann-Whitney U test for continuous variables and calculated the logistic regression for hyperglycemia. RESULTS: Of the 520 patients screened, 248 met the inclusion criteria. Baseline demographics were equally distributed between patients with hyperglycemia and those who were normoglycemic. Serum inflammatory markers in patients with or without new-onset hyperglycemia were elevated as follows: CRP (58.1% vs 65.6%, P = 0.29), ferritin (48.4% vs 34.9%, P = 0.14), D-dimer (37.1% vs 37.1%, P = 0.76) and LDH (19.4% vs 11.8%, P = 0.02). Logistic regression analysis showed LDH odds ratio (OR) = 1.623 (P = 0.256). We observed significantly higher mortality (24.2% vs 9.1%, P = 0.001; OR = 2.528, P = 0.024) and length of stay (8.89 vs 6.69, P = 0.026) in patients with hyperglycemia. CONCLUSION: Our study showed no association between CRP, ferritin, LDH, D-dimer levels, and new-onset hyperglycemia in non-diabetic patients with COVID-19 infection. It also shows an increased mortality risk and length of stay in patients with hyperglycemia. With new-onset hyperglycemia being closely associated with poor prognostic indices, it becomes pivotal to understand the underlying pathophysiological mechanisms behind the SARS-CoV-2 infection-induced hyperglycemia. We conclude that the stress hyperglycemia hypothesis is not the only mechanism of SARS-CoV-2 infection-induced hyperglycemia but rather a multicausal pathogenesis leading to hyperglycemia that requires further research and understanding. This would help us improve not only the clinical outcomes of COVID-19 disease and inpatient hyperglycemia management but also understand the long-term effects of SARS-CoV-2 infection and further management.

Hypertension and Severe Hypokalemia Associated With Oral Ingestion of Topical Hydrocortisone Cream.

Background: Topical use of corticosteroids causes systemic effects, but systemic toxicity by ingesting topical corticosteroid cream has not been reported. We describe a patient admitted with ingestion of over-the-counter (OTC) hydrocortisone cream. Case Report: A 64-year-old woman presented with 2-weeks of generalized weakness. She had a history of hypertension, anxiety, depression, and chronic fatigue syndrome, but medical records were unavailable and she was not on any medications. She reported taking prednisone 7.5 mg daily for several years, which was discontinued 5 months ago. Due to worsening symptoms, she started ingesting OTC topical hydrocortisone as replacement and admitted to consuming 2 squirts of 1% hydrocortisone cream twice daily over the previous month leading up to hospitalization. Her pulse rate was 77/min, blood pressure was 232/110 mmHg. There was no pedal edema, elevated jugular venous pressure, hirsutism, muscle wasting, or purplish skin striae. Labs revealed potassium 1.5 mg/dL (3.6-5.4), serum cortisol 61.5 µg/dL (2.3-19.4), Creatine Kinase 1864 IU/L (24-173), undetectable adrenocorticotropic hormone. She received potassium, labetalol, and intravenous fluids. Her serum cortisol level decreased to 11 µg/dL and potassium to 4.1 mg/dL within 24 hours. She left the hospital against medical advice on Day 2. Discussion: Although both prednisone and hydrocortisone have glucocorticoid properties, only hydrocortisone has mineralocorticoid properties. Hydrocortisone 20 mg provides a mineralocorticoid effect equivalent to 0.1 mg fludrocortisone. Conclusion: Hydrocortisone cream was confirmed as the source of exogenous corticosteroid by an undetectable adrenocorticotropic hormone and rapid decrease in cortisol following discontinuation. Incorrect use of OTC medications can lead to life-threatening side effects.

Assessment of Predictive Factors of Hepatic Steatosis Diagnosed by Vibration Controlled Transient Elastography (VCTE) in Chronic Hepatitis C Virus-Infected Patients.

This retrospective, cross-sectional study aimed to evaluate the predictive factors of moderate/severe hepatic steatosis diagnosed by vibration-controlled transient elastography (VCTE). It included 158 adult patients with suspected nonalcoholic fatty liver disease (NAFLD) evaluated by VCTE in an outpatient setting of a community-based teaching hospital. Patients with significant alcohol consumption, oral contraceptive use, hepatitis B disease, autoimmune hepatitis, and primary biliary cirrhosis were excluded. Steatosis was categorized as S0-S1 (mild) and S2-S3 (moderate/severe) based on the controlled attenuation parameter (CAP) score. Results demonstrated the mean values of BMI (p = 0.001), kiloPascals [kPa] (fibrosis) raw score (p = 0.009), obesity (p = 0.001), diabetes mellitus [DM] (p = 0.014), and comorbidities status [chronic hepatitis C(HCV), DM, obesity, HCV+DM] (p = 0.028) were significantly different between the two arms of the study viz. S0-S1 (mild) and S2-S3 (moderate/severe). A multinomial logistic regression analysis of the comorbidities associated with hepatic steatosis revealed a good level of prediction (R2-0.584) for hepatic steatosis. Of all the variables analyzed, obesity was the most impactful vavriable. Furthermore, the -2 log-likelihood of the regressed model in patients with HCV and hepatic steatosis did not show a significant correlation when adjusted for obesity. Obesity had a significant independent association with steatosis (chi-square value = 52, df = 12). Interestingly, DM independently predicted a weak association with steatosis (chi-square value = 0.825, df = 3). In conclusion, our study demonstrates that hepatic steatosis is independently associated with metabolic parameters like obesity and DM. Management of these risk factors in patients with HCV may be vital to reducing the risk of steatosis and progression to fibrosis.

Thyroiditis after mRNA Vaccination for COVID-19.

Background: SARS-CoV-2 has been known to cause multisystemic involvement, gaining entry through ACE-2 and TMPRSS2 receptors. COVID-19 vaccine-associated thyroiditis cases are now being reported. Case Report. Case 1. A 36-year-old woman with a history of right hemithyroidectomy for a benign thyroid nodule, on a stable dose of levothyroxine with euthyroid labs, presented with progressively worsening left neck pain, episodic palpitations, and heat intolerance after the second dose of mRNA1273 (Moderna) vaccine. Examination revealed an enlarged and tender left lobe of the thyroid with suppressed TSH but normal free T4 and ESR, signifying subacute thyroiditis. She was managed conservatively without corticosteroids or beta-blockers, and her symptoms resolved. A follow-up revealed increasing TSH, and levothyroxine was restarted. Case 2. A 33-year-old man with a history of anxiety disorder on Sertraline, presented with a two-week history of palpitations, heat intolerance, and 10-pound weight loss after the second dose of BNT162b2 (Pfizer-BioNTech) vaccine. Examination revealed a normal thyroid gland with no tenderness with elevated thyroid peroxidase and thyroglobulin antibodies. Ultrasound showed a diffusely heterogeneous thyroid with increased vascularity, suggesting silent thyroiditis. Follow-up revealed a hypothyroid phase with high TSH for which levothyroxine supplementation was started. Discussion. COVID-19 vaccine-associated subacute and silent thyroiditis have occurred following all three kinds of available vaccines, characterized by an initial thyrotoxic phase, followed by a hypothyroid phase and a recovery phase. Hypotheses include an immune response triggering thyroid inflammation or cross-reactivity with viral proteins. Conclusions: COVID-19 vaccine-associated thyroiditis is rare, but long-term monitoring of these patients is essential to ensure appropriate diagnosis and management of the potential hypothyroid phase.

Acute myeloid leukemia and myelofibrosis: Simultaneous transformation of essential thrombocythemia during treatment with hydroxyurea.

Essential thrombocytosis (ET) is usually an indolent disease but can uncommonly evolve into acute myeloid leukemia (AML) with a grim prognosis of 2-7 months. Studies report a lower incidence of leukemic transformation when compared to fibrotic transformation. The risk of transformation depends on the age, duration of disease, and tumor biology. Hydroxyurea, a cytoreductive agent, is generally associated with minimal adverse reactions; however, there are conflicting data on its effect on leukogenecity. We describe a rare case of a 79-year-old female developing disseminated intravascular coagulation due to the transformation of ET to both AML and myelofibrosis while being treated with hydroxyurea for 8 years.

Optimal Blood Glucose Monitoring Interval for Insulin Infusion in Critically Ill Non-Cardiothoracic Patients: A Pilot Study.

OBJECTIVE: The American Diabetes Association and the Society of Critical Care Medicine recommend monitoring blood glucose (BG) every 1-2 hours in patients receiving insulin infusion to guide titration of insulin infusion to maintain serum glucose in the target range; however, this is based on weak evidence. We evaluated the compliance of hourly BG monitoring and relation of less frequent BG monitoring to glycemic status. MATERIALS AND METHODS: Retrospective chart review performed on 56 consecutive adult patients who received intravenous insulin infusion for persistent hyperglycemia in the ICU at Saint Vincent Hospital, a tertiary care community hospital an urban setting in Northeast region of USA. The frequency of fingerstick blood glucose (FSBG) readings was reviewed for compliance with hourly FSBG monitoring per protocol and the impact of FSBG testing at different time intervals on the glycemic status. Depending on time interval of FSBG monitoring, the data was divided into three groups: Group A (<90 min), Group B (91-179 min) and Group C (≥180 min). RESULTS: The mean age was 69 years (48% were males), 77% patients had preexisting type 2 diabetes mellitus (T2DM). The mean MPM II score was 41. Of the 1411 readings for BG monitoring on insulin infusion, 467 (33%) were in group A, 806 (57%) in group B and 138 (10%) in group C; hourly BG monitoring compliance was 12.6%. The overall glycemic status was similar among all groups. There were 14 (0.99%) hypoglycemic episodes observed. The rate of hypoglycemic episodes was similar in all three groups (p=0.55). CONCLUSION: In patients requiring insulin infusion for sustained hyperglycemia in ICU, the risk of hypoglycemic episodes was not significantly different with less frequent BG monitoring. The compliance to hourly blood glucose monitoring and ICU was variable, and hypoglycemic episodes were similar across the groups despite the variation in monitoring.

Tale of fat and fib - cardiac lipoma managed with radiofrequency ablation: A case report.

BACKGROUND: Cardiac lipoma and lipomatous hypertrophy of interatrial septum (LHIS) are very rare disorders with distinct pathological features. While cardiac lipoma is a well-circumscribed encapsulated tumor of mature adipocytes, LHIS is due to entrapment of fat cells in the interatrial septum during embryogenesis. Although a biopsy is the definitive diagnostic test, these disorders can be differentiated by a cardiac magnetic resonance imaging (MRI). Treatment of LHIS is not warranted in asymptomatic patients. In symptomatic patients, surgical resection is the only recommended treatment, which has shown to improve good long-term prognosis. CASE SUMMARY: A 63-year-old Caucasian woman with past medical history significant for hypertension, hypothyroidism, right breast ductal cell carcinoma treated with mastectomy and breast implant, platelet granule disorder, asthma requiring chronic intermittent prednisone use, presented to the outpatient cardiology office with recent onset exertional dyspnea, palpitations, weight gain and weakness. Initial workup with electrocardiogram and holter monitor did not reveal significant findings. During the subsequent hospitalization for community acquired pneumonia, the patient developed symptomatic paroxysmal atrial fibrillation. Transthoracic echocardiogram showed a right ventricular mass. A biopsy was not pursued given the high risk of bleeding due to platelet granule disorder. Cardiac MRI showed characteristic features consistent with cardiac lipoma and LHIS. Prednisone was discontinued. Genetic testing for arrhythmogenic right ventricular dysplasia and 24-h urine cortisol test was negative. As multiple attempts at rhythm control failed with sotalol and flecainide, pulmonary vein isolation and right atrial isthmus radiofrequency ablation were done. She is in follow-up with symptomatic relief and no recurrence of atrial fibrillation for 10 mo. CONCLUSION: Benign fatty lesions in heart include solitary lipoma, lipomatous infiltration and lipomatous hypertrophy of interatrial septum. Although transvenous biopsy provides a definitive diagnosis, Cardiac MRI is superior to computed tomography and aids in differentiating benign from malignant lesions. Surgical excision of cardiac lipoma along with capsule and pedicle removal generally prevents recurrence, but with our patient's unusual tumor features and comorbidities proscribed a surgical approach. Symptom management with antiarrhythmics and ablation techniques were successfully utilized.

Hypocalcemia with Immune Checkpoint Inhibitors: The Disparity among Various Reports.

Immune-related adverse events affecting parathyroid function are rarely reported with immune checkpoint inhibitors (ICPIs). Activating calcium-sensing receptor antibodies causing autoimmune hypoparathyroidism with nivolumab was recently reported. KEYNOTE-189 and CHECKMATE-067 trials reported a 21-29% hypocalcemia event rate, but the etiology of hypocalcemia was not reported. A chart review was performed to study patients receiving ICPI from 2015 to 2018 at multiple sites affiliated with Saint Vincent Hospital. The study population was divided into two groups based on the presence or absence of calcium altering conditions or medications. True hypocalcemia incidence was calculated after correcting calcium for albumin from the initiation of ICPI to their last follow-up. Group 1 (n = 83) includes patients with no calcium altering conditions or medications. Group 2 (n = 98) includes patients on calcium supplements (n = 17), vitamin D (n = 44), bisphosphonates (n = 24), >stage IIIB chronic kidney disease (CKD) (n = 5), and bone metastasis (n = 38). Hypocalcemia events in Group 1 vs. Group 2 were 8.4% and 19.3%, respectively. Our entire study demonstrated 26.8% vs. 1.1% of Grade I vs. II hypocalcemia events. However, after correcting the calcium for albumin, hypocalcemia incidence was 0.56% (n = 1). No further workup was done to investigate the etiology as that patient passed away. Our data suggest that the true hypocalcemia incidence after using albumin-corrected calcium values is very low in patients receiving IPCI, even in the presence of calcium altering factors. The percentage of patients with hypocalcemia is much higher and similar to the KEYNOTE-189 and CHECKMATE-067 trials when serum calcium values without albumin correction are used. Thus, the higher reported incidence of hypocalcemia in these trials is likely due to the reporting of serum calcium without albumin correction.

Risk of Future Type 2 Diabetes Mellitus in Patients Developing Steroid-Induced Hyperglycemia During Hospitalization for Chronic Obstructive Pulmonary Disease Exacerbation.

OBJECTIVE: We evaluated the future risk of developing impaired glucose tolerance and type 2 diabetes mellitus (T2DM) in patient without T2DM who develop hyperglycemia with short-term systemic glucocorticoid therapy during hospitalization. METHODS: Retrospective analysis was performed on charts of non-diabetic patients admitted with COPD exacerbation and treated with a course of high dose systemic corticosteroid during hospitalization. Patients with BMI over 40 kg/m2, endocrinopathy and on medications that could impair glucose tolerance were excluded. Patient data were collected for 1 year after initial hospitalization. Diagnosis of T2DM or IGT was based on the ADA criteria. 311 charts were reviewed, of which 64 patients met our inclusion criteria. Depending on the blood glucose readings during hospitalization, the patients were categorized into two groups: hyperglycemic (> 140 mg/dL; n = 42) and normoglycemic (≤ 140 mg/dL; n = 22). RESULTS: In the hyperglycemic group, 17/42 (40%) patients developed prediabetes and 5/42 (12%) developed T2DM on follow-up. Interestingly, none of the patients developed IGT or T2DM in the normoglycemic group. Both the groups were well matched in terms of family history of DM, history of hypertension, hyperlipidemia, BMI > 25 kg/m2, weight change, tobacco and alcohol use, corticosteroid therapy duration, and cumulative steroid dose. After adjusting for all these risk factors, on logistic regression analysis, hyperglycemic patients had 37 times higher chance of developing IGT, compared to normoglycemic patients (p = 0.003). CONCLUSIONS: Our study suggests that patients without T2DM with acute exacerbation of COPD who develop steroid-induced hyperglycemia in response to systemic corticosteroid treatment have an increased risk for developing future IGT or T2DM. Bigger studies are needed to support our findings since results drawn from our study have the limitations of smaller sample size (wider confidence interval) in a single center.

Thyrotoxicosis after massive triiodothyronine (LT3) overdose: a coast-to-coast case series and review.

Excessive exogenous thyroid hormone ingestion may lead to severe thyrotoxicosis and cause potential harm. We have reviewed the literature and suggested that thyroid hormone supplementation should not be used to alleviate nonspecific complaints in patients with normal endogenous thyroid function. Failure to do so may cause serious harm, as demonstrated in one of the cases described here. In addition, treatment based on symptom relief only without biochemical measure may lead to overmedication - as reported from academic hospitals both in Canada and the United States. Given the risk of severe thyrotoxicosis from potential compounding errors, pharmacies providing a compounding service should be subject to more rigorous monitoring by the food and drug administration. Clinicians should also use local biochemical markers when titrating thyroid hormone supplements even though the normal thyroid function reference range has its limitation, failure to do so may result in iatrogenic thyrotoxicosis.

DOES T STAGE AFFECT PROGNOSIS IN PATIENTS WITH STAGE IV B DIFFERENTIATED THYROID CANCER?

Objective: Differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, has a relatively good prognosis. The 8th edition of the American Joint Committee on Cancer (AJCC) pathologic tumor-node-metastasis (T [primary tumor size], N [regional lymph nodes], M [distant metastasis]) staging system did not take the T stage into consideration in stage IV B DTC patients. We evaluated the prognostic value of the T stage for advanced DTC survival. Methods: DTC cases that were considered stage IV B in the AJCC 8th edition were extracted from the Surveillance, Epidemiology, and End Results database. T stage (AJCC 6th standard) was categorized into T0-2, T3 and T4. We analyzed overall survival (OS) and cancer specific survival (CSS) in the overall group as well as in pathologic subgroups. We used the Kaplan-Meier method and log-rank test for univariate analysis and the Cox regression model for multivariate analysis. Results: A total of 519 cases were extracted. Patients with earlier T stages showed significantly better OS and CSS in univariate analysis. T stage was an independent prognostic factor for both OS and CSS in multivariate analysis. Subgroup analysis in papillary and follicular thyroid cancer showed that T4 was an independent prognostic factor for both OS and CSS. Conclusion: AJCC 8 stage IV B DTC patients could be further stratified by T stage. Further studies with larger samples and AJCC 8 T stage information are necessary. Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; CSS = cancer specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid carcinoma; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = surveillance, epidemiology, and end results database.

Metformin, arterial contrast and acute kidney Injury.

BACKGROUND AND AIM OF THE WORK: We aim to respond to interesting article in your journal by Namazi et al. regarding metformin use in patients undergoing coronary angiography and risk of developing metformin associated lactic acidosis. We share our experience regarding patients using metformin undergoing urgent coronary angiography and risk of developing contrast induced nephropathy. METHODS: A retrospective chart review of 154 patients who underwent emergency coronary angiography (CAG) with arterial contrast exposure. The study was approved by the institution review board (Metrowest Medical Center IRB, Framingham Massachusetts, USA). RESULTS: 154 patients admitted with acute coronary syndrome during months of January 2014 - December 2014; 67 patients used metformin (100% had diabetes mellitus) whereas 87 were not on metformin (31% had diabetes mellitus). Our study revealed no difference in contrast induced nephropathy (CIN) between the two groups (p=0.29), when compared at 48 hours after arterial contrast exposure. Higher serum creatinine may be have precluded the use of metformin in the control group. CONCLUSIONS: Our single center, small observational study showed no difference in the incidence of CIN in patients who continued to be on metformin after arterial contrast exposure compared to the control group.