A Rare Co-association of Autoimmune Thyroiditis and Idiopathic Retroperitoneal Fibrosis.

Retroperitoneal fibrosis is a rare fibroinflammatory disease that is reported to be associated with other autoimmune conditions. Here, we report the case of a 51-year-old Caucasian female with a history of autoimmune thyroiditis and Hashimoto's hypothyroidism who presented with symptoms of fever, chills, and hot flashes for three weeks associated with nausea, vomiting, frequent thirst, and frequent urination. On examination, the patient had elevated blood pressure and an excoriated rash on the forearms. Laboratory evaluation showed elevated blood urea nitrogen and creatinine with a hypertensive emergency. Renal ultrasound showed bilateral hydronephrosis suggestive of obstructive uropathy. Computerized tomography of the abdomen and pelvis was suggestive of extensive retroperitoneal fibrosis. The patient was diagnosed with idiopathic retroperitoneal fibrosis without an identifiable secondary cause. Treatment was focused on relieving the ureteral obstruction, managing renal functions, and optimizing blood pressure, following which immunomodulatory agents were used.

Pure Androgen-Secreting Radiologically Suspicious Adrenal Mass: Benign or Malignant?

Pure androgen-secreting adrenocortical tumors (PASATs) are rare entities. Their clinical presentations include virilizing features that vary based on age and gender. The pathogenesis of this tumor is still unclear, with around 50% of such tumors being malignant. Imaging characteristics of the tumor on CT/MRI including size, heterogenicity, and contrast wash-out time are used to predict malignancy. Surgical excision is recommended for all functional adrenal tumors. In this report, we discuss a case of a 68-year-old postmenopausal female presenting with hyperandrogenism and was found to have a 7-cm, PASAT that raised suspicion for malignancy on CT scan, but was determined to be benign on surgical pathology.

Association of Obesity With COVID-19 Severity and Mortality: An Updated Systemic Review, Meta-Analysis, and Meta-Regression.

Background: Obesity affects the course of critical illnesses. We aimed to estimate the association of obesity with the severity and mortality in coronavirus disease 2019 (COVID-19) patients. Data Sources: A systematic search was conducted from the inception of the COVID-19 pandemic through to 13 October 2021, on databases including Medline (PubMed), Embase, Science Web, and Cochrane Central Controlled Trials Registry. Preprint servers such as BioRxiv, MedRxiv, ChemRxiv, and SSRN were also scanned. Study Selection and Data Extraction: Full-length articles focusing on the association of obesity and outcome in COVID-19 patients were included. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used for study selection and data extraction. Our Population of interest were COVID-19 positive patients, obesity is our Intervention/Exposure point, Comparators are Non-obese vs obese patients The chief outcome of the study was the severity of the confirmed COVID-19 positive hospitalized patients in terms of admission to the intensive care unit (ICU) or the requirement of invasive mechanical ventilation/intubation with obesity. All-cause mortality in COVID-19 positive hospitalized patients with obesity was the secondary outcome of the study. Results: In total, 3,140,413 patients from 167 studies were included in the study. Obesity was associated with an increased risk of severe disease (RR=1.52, 95% CI 1.41-1.63, p<0.001, I2 = 97%). Similarly, high mortality was observed in obese patients (RR=1.09, 95% CI 1.02-1.16, p=0.006, I2 = 97%). In multivariate meta-regression on severity, the covariate of the female gender, pulmonary disease, diabetes, older age, cardiovascular diseases, and hypertension was found to be significant and explained R2 = 40% of the between-study heterogeneity for severity. The aforementioned covariates were found to be significant for mortality as well, and these covariates collectively explained R2 = 50% of the between-study variability for mortality. Conclusions: Our findings suggest that obesity is significantly associated with increased severity and higher mortality among COVID-19 patients. Therefore, the inclusion of obesity or its surrogate body mass index in prognostic scores and improvement of guidelines for patient care management is recommended.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

A Case of Acute Pancreatitis in a Patient Receiving High-Dose Steroids for Optic Neuritis.

Although rare, drug-induced pancreatitis is an important cause of acute pancreatitis. The diagnosis of drug-induced pancreatitis remains a challenge for clinicians. Steroids are one of the frequently used drugs in hospitals for many acute illnesses. Patients presenting with signs and symptoms of acute pancreatitis, with a recent history of steroid use, in the absence of other potential causes, should be approached with a high suspicion for steroid-induced pancreatitis to ensure a timely diagnosis. We describe a case of a 57-year-old female treated for optic neuritis of the left eye with high doses of Methylprednisolone for five days, who presented to the emergency room with acute abdominal pain within 24 hours of discharge. A detailed evaluation of the patient's medical history and exclusion of other probable etiologies confirmed the diagnosis of steroid-induced pancreatitis. Withdrawal of the offending agent and supportive care resolved the underlying acute pancreatitis.

Daily Intake and Serum Levels of Copper, Selenium and Zinc According to Glucose Metabolism: Cross-Sectional and Comparative Study.

Trace elements play an important role in metabolism. We compared the daily intake and serum concentrations of copper (Cu), selenium (Se), and zinc (Zn) across a spectrum of glucose tolerance status in a representative U.S. population. Daily intake and serum concentrations of Cu, Zn and Se in 5087 adults from the 2011-2016 National Health and Nutrition Examination Survey (NHANES) were examined and compared to normal (NGT) and abnormal (AGT) glucose tolerance and the presence of diabetes mellitus (DM). Other than Zn deficiency (21.15%), the prevalence of Zn, Se, and Cu excess and Se and Cu deficiency were low (<4.00%). As compared to the NGT group, Cu and Se supplementation was higher in the AGT and DM groups (p < 0.0001 for all). Serum Se and Zn, but not Cu, concentrations were highly correlated with daily intake (p < 0.0001 for both). As compared to the NGT group, serum Cu concentration was highest in the AGT group (p = 0.03), serum Se concentration was highest in the DM group (p < 0.0001), and serum Zn concentration was highest in the AGT group (p < 0.0001). Serum Se and Zn concentration was correlated with daily Se and Zn intake. Even within the reference range for serum Cu, Se, and Zn concentrations, a higher serum concentration of Cu, Se, and Zn was associated with abnormal glucose metabolism. Although the casual relationship remains to be elucidated, these data suggest caution in Cu, Se and Zn supplementation in non-deficient individuals.

A Review of the Quiz, as a New Dimension in Medical Education.

Over the years, medical education delivery has seen a change from teacher-centric to student-centric teaching-learning methods. Educators are constantly looking to develop interactive and innovative teaching-learning tools. One such supplementary tool is the use of the quiz for medical education. The Quiz has been used traditionally as a feedback assessment tool, but lately, it has found its way into the medical curriculum, mostly informally. The few available documented studies on the Quiz as a teaching and learning tool illustrate its acceptance and impact on the stakeholders. It could be one of the solutions to the endless search for a student-centric and engaging tool to deliver the medical curriculum. Commonly, the format for medical quiz is either on a case-based or image-based approach. Such an approach helps bridge the gap between traditional classroom teaching and clinical application. The Quiz is a readily acceptable tool that complements didactic lectures and improves students' learning and comprehension. Being an interactive student-centric tool, it enhances active student participation and encourages regular feedback mechanisms. It promotes healthy competition and peer-assisted learning by encouraging active discussion among students, hence improving student performance in standard examination techniques, along with teacher satisfaction. This literature review aims to enumerate the various formats of the Quiz, their role in improving the understanding and retention of knowledge among the students and assess their acceptability among the stakeholders.

Genomics in medicine: A new era in medicine.

The sequencing of complete human genome revolutionized the genomic medicine. However, the complex interplay of gene-environment-lifestyle and influence of non-coding genomic regions on human health remain largely unexplored. Genomic medicine has great potential for diagnoses or disease prediction, disease prevention and, targeted treatment. However, many of the promising tools of genomic medicine are still in their infancy and their application may be limited because of the limited knowledge we have that precludes its use in many clinical settings. In this review article, we have reviewed the evolution of genomic methodologies/tools, their limitations, and scope, for current and future clinical application.

Autoimmune Myasthenia, Primary Adrenal Insufficiency, and Progressive Hypothyroidism Due to Pembrolizumab and Axitinib Combination Regimen.

Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have been among the increasingly used antineoplastic agents for advanced cancers including renal cell carcinoma (RCC). Although these antineoplastic agents have broad range of efficacy, rare adverse events - mild and fatal, acute and chronic, immune and non-immune mediated - have been reported. We report a case of a 73-year-old Caucasian male patient with stage IV right-sided clear cell RCC who was treated with a pembrolizumab-axitinib combination regimen and suffered life-threatening, acute onset immune-related myasthenia gravis (MG), subsequently progressive hypothyroidism, and primary adrenal insufficiency.

An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma.

Adrenal incidentalomas (AIs) are common incidental findings in medical practice with clinical significance. Although most AIs are nonsecretory and nonmalignant, they require a short course of follow-up over one to two years to rule out malignancy or hormonal secretion according to clinical practice guidelines. However, this can result in some adrenocortical carcinomas (ACCs) being missed if they transform at a later stage or evolve slowly. Here, we report one such case of an AI, which although remained indolent, eventually transformed into an ACC many years after the initial detection.

Lithium-Induced Hyperparathyroidism: An Ill-defined Territory.

Lithium is the gold standard treatment for bipolar disorder. Studies have shown an association between lithium and hyperparathyroidism. However, there is limited data regarding the management of lithium-induced hyperparathyroidism. We present a clinical conundrum which physicians frequently encounter-an excellent lithium responder refractory to other treatments who developed lithium-induced hyperparathyroidism. Medical treatment with cinacalcet was successful in management of hyperparathyroidism without discontinuing lithium maintenance therapy.

It's All Due to the Thyroid: Lessons Learnt From a Patient's Perspective.

Symptoms associated with thyroid pathology can mimic and overlap with a myriad of other diagnostic possibilities. Based on the patient's educational status, underlying fear, anxiety, online medical search, the patient can erroneously attribute various symptoms to thyroid pathology. We present a case of a 79-year-old female with a history of Hashimoto's hypothyroidism, meningioma, who erroneously attributed many of her symptoms to hypothyroidism despite having normal thyroid labs. The patient had symptoms of fatigue, dysphagia, and proximal muscle weakness. Surprisingly the patient already had an existing diagnosis of dermatomyositis and Zenker's diverticulum which could clearly explain her above symptoms. Moreover, the patient did not follow up for whole body scan and other tests that were ordered for cancer screening, which is the standard practice for dermatomyositis. The patient helped us identify the deficiencies in the current health system regarding patient counseling. We identified factors that could act as communication barriers if not properly addressed which include: (1) patient's prior medical knowledge, (2) patient's own underlying fears about their health conditions, (3) use of effective patient education tools, (4) minimizing or avoiding use of medical jargon, (5) role switching to verify patient's understanding, (6) repetition of relevant information, and (7) involvement of the patient in shared decision making. It is important to recognize that thyroid gland dysfunction is the most commonly self-diagnosed condition by patients and the blame can be shifted to thyroid despite evidence to the contrary if effective patient education and counseling are lacking. Understanding the psychological state of the patient along with addressing the underlying fears, and effective patient education with repetition is the key for patient compliance and management.

Atypical Thyroid Function Tests and Thyroid Hormone Resistance.

Clinical interpretation of thyroid labs is usually straightforward. However, there are rare instances when the atypical profile of thyroid labs warrants systematic investigation to determine the underlying cause. We report the case of a 90-year-old Caucasian male with a chronic history of atrial fibrillation with chronic pacemaker dependence who presented with significantly elevated free thyroxine level (>7.77 ng/dL) but normal thyroid-stimulating hormone level (2.15 µIU/mL). After ruling out pituitary tumors and artifactual errors due to lab interference, the diagnosis of thyroid hormone resistance was made.

Recurrent, refractory hypokalemia as a diagnostic clue to thyrotoxic periodic paralysis in a patient with acute kidney injury and suspected Guillain-Barre syndrome.

When clinical presentation is atypical, especially in a non-Asian population, the finding of recurrent and refractory hypokalemia can serve as a key diagnostic clue for timely diagnoses and management of thyrotoxic periodic paralysis. In suspected cases, complete thyroid laboratory panel should be measured so that T3 toxicosis is not missed.

Infection risk with the use of interleukin inhibitors in hospitalized patients with COVID-19: A narrative review.

INTRODUCTION: To date, only corticosteroids and interleukin-6 (IL-6) inhibitors have been shown to reduce mortality of hospitalized patients with COVID-19. In this literature review, we aimed to summarize infection risk of IL inhibitors, with or without the use of corticosteroids, used to treat hospitalized patients with COVID-19. METHODS: A literature search was conducted using the following evidence-based medicine reviews: Cochrane Central Register of Controlled Trials; Cochrane Database of Systematic Reviews; Embase; Ovid Medline; and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions 1946 to April 28, 2021. All relevant articles were identified using the search terms COVID-19 or SARS-coronavirus-2, infections, interleukins, inpatients, adults, and i ncidence. RESULTS: We identified 36 studies of which 2 were meta-analyses, 5 were randomized controlled trials, 9 were prospective studies, and 20 were retrospective studies. When anakinra was compared with control, 2 studies reported an increased risk of infection, and 3 studies reported a similar or decreased incidence of infection. Canakinumab had a lower associated incidence of infection compared with placebo in one study. When sarilumab was compared with placebo, one study reported an increased risk of infection. Nine studies comparing tocilizumab with placebo reported decreased or no difference in infection risk (odds ratio [OR] for the studies ranged from 0.39-1.21). Fourteen studies comparing tocilizumab with placebo reported an increased risk of infection, ranging from 9.1% to 63.0% (OR for the studies ranged from 1.85-5.04). Infection most commonly presented as bacteremia. Of the 6 studies comparing tocilizumab and corticosteroid use with placebo, 4 reported a nonsignificant increase toward corticosteroids being associated with bacterial infections (OR ranged from 2.76-3.8), and 2 studies reported no increased association with a higher infection risk. CONCLUSIONS: Our literature review showed mixed results with variable significance for the association of IL-6 inhibitors with risk of infections in patients with COVID-19.

Phenytoin- Medication That Warrants Deviation From Standard Approach for Thyroid Lab Interpretation.

Long-term treatment with antiepileptic drugs like phenytoin has been reported to alter the thyroid hormone levels. It makes interpretation of thyroid labs hard for clinicians. We report a case of 48-year-old Caucasian female on phenytoin since year 1996 with stable seizure control, who was referred to endocrinology clinic in 2016 for evaluation of suspected central hypothyroidism due to discordant results in thyroid lab panel. Labs showed decreased free T4 level of 0.68ng/dL (reference range 0.89-1.76ng/dL) in the setting of normal thyroid stimulating hormone (TSH) 1.76 µIU/mL (reference range 0.46-4.68 µIU/mL). Clinically patient was euthyroid. Free T3 level was normal -3.82 pg/mL (reference range 2.77-5.27 pg/mL). Phenytoin was identified as the cause of the artifactual lowering of free T4 on routine assays. Therefore subsequent thyroid monitoring was done with TSH measurements. Continued follow-up of TSH remained normal over the subsequent follow-up of four years.

Bexarotene: A Rare Cause of Misleading Thyroid Function Tests.

Bexarotene is a very rare cause of central hypothyroidism (CH) and its effects have been reported to be dose-dependent; however, the available data in the literature on dose-dependent effects are variable. The standard practice of monitoring thyroid function using thyroid-stimulating hormone (TSH) to adjust levothyroxine (LT4) dose does not apply to bexarotene since it causes CH. In CH, TSH is not reliable. Hence free tetraiodothyronine (fT4) level is used to monitor and adjust the LT4 dose. We report a case of an 81-year-old Caucasian male with cutaneous T-cell lymphoma (CTCL) who was treated with bexarotene. His pre-treatment TSH was normal at 1.6 µIU/mL (reference range: 0.46-4.68 µIU/mL). Post-bexarotene, the total tetraiodothyronine (T4) level was within the reference range, but a downward trend was noted. Eventually, total triiodothyronine (T3) dropped to a low level of 0.61 ng/mL (reference range: 0.97-1.69 ng/mL), and LT4 was initiated. Bexarotene dose was increased, but LT4 was not increased by the primary physician who relied on TSH level, which was low, and hence the existing LT4 dose was maintained. The patient had persistent symptoms of hypothyroidism and, eventually, a diagnosis of CH was made. The symptoms of hypothyroidism improved after normalizing fT4, with an increase in the LT4 dose. This case represents an example of missed CH due to bexarotene, -which led to suboptimal LT4 replacement impacting the quality of life for the patient.

Effect of Atorvastatin and Pioglitazone on Plasma Levels of Adhesion Molecules in Non-Diabetic Patients With Hypertension or Stable Angina or Both.

BACKGROUND: It was to study the effect of atorvastatin, pioglitazone and their combination on plasma levels of adhesion molecules in patients with hypertension or stable angina or both. METHODS: It was an open-label, randomized parallel-group study. Forty-five atorvastatin-naive patients with hypertension or stable angina or both, were randomized to receive either atorvastatin (19 patients; 10 mg OD for 12 weeks) or pioglitazone (26 patients; 30 mg OD for 12 weeks). Another group of 30 patients who were already on atorvastatin were put on add-on pioglitazone therapy (pioglitazone (15 mg OD) + atorvastatin (10 mg OD) for 12 weeks). Plasma high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were measured at baseline and after 12 weeks of therapy. RESULTS: Atorvastatin monotherapy significantly reduced plasma sICAM-1, but pioglitazone monotherapy did not produce any significant effect. Addition of pioglitazone in patients already receiving atorvastatin also significantly reduced plasma sICAM-1 level. However, there was no significant change in plasma hsCRP and sVCAM-1 levels in any of the groups after 12 weeks of therapy. CONCLUSION: There is therapeutic advantage of combining pioglitazone and atorvastatin on plasma sICAM-1 levels.

Paranoid personality masking an atypical case of frontotemporal dementia.

Frontotemporal dementia (FTD) is a debilitating disease that is well described in the "Diagnostic and statistical manual of mental disorders, fifth edition (DSM-5)", and typically presents with memory impairment, progressive decline in cortical functioning, and behavioral changes. Age of onset is generally in the late fifties, and usually the first presentation involves a change in behavior and emotional blunting. Treatment of FTD involves management of any neurobehavioral symptoms while trials of atypical antipsychotics are ongoing but suggest some efficacy. We present a case of a patient who first presented with severe paranoid personality traits and frank persecutory delusions. This atypical presentation of our patient first led to her incorrect diagnosis of a psychotic disorder and paranoid personality disorder. As a result of this diagnosis, she was treated unsuccessfully. A subsequent magnetic resonance imaging (MRI) then showed atrophy of frontal and temporal lobes bilaterally (left more prominent than right) which confirmed the diagnosis of FTD. The importance of this case involves the atypical presentation of paranoia and delusions, and our patient's incorrect diagnosis based on her clinical presentation led to a trial of unsuccessful treatment. Only after performing an MRI, which showed atrophy, was the patient appropriately treated and deemed medically stable. This case report illustrates the importance of considering a rare presentation of frontotemporal lobe dementia with patients who are in the typical age range and present with paranoia and delusions.