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.

Hepatic 11ß-hydroxysteroid dehydrogenase type 1 activity in obesity and type 2 diabetes using a novel triple tracer cortisol technique.

AIMS/HYPOTHESIS: Dysregulation of 11ß-hydroxysteroid dehydrogenase (11ß-HSD) enzyme activities are implicated in the pathogenesis of obesity and insulin resistance. The aim of the study was to determine whether hepatic 11ß-HSD type 1 (11ß-HSD-1) enzyme activity differs in people with and without obesity and type 2 diabetes. METHODS: We measured hepatic 11ß-HSD-1 activity in the overnight fasted state in 20 lean non-diabetic participants (LND), 21 overweight/obese non-diabetic participants (OND) and 20 overweight/obese participants with type 2 diabetes (ODM) using a non-invasive approach. One mg doses of [9,12,12-(2)H3]cortisol (D cortisol) and [4-(13)C]cortisone ([(13)C]cortisone) were ingested, while [1,2,6,7-(3)H]cortisol ([(3)H] cortisol) was infused intravenously to enable concurrent measurements of first-pass hepatic extraction of ingested D cortisol and hepatic conversion of ingested [(13)C]cortisone to C13 cortisol derived from the ingested cortisone (a measure of 11ß-HSD-1 activity in the liver) using an isotope dilution technique. One-way ANOVA models and Kruskal-Wallis tests were used to test the hypothesis. RESULTS: Plasma D cortisol and C13 cortisol concentrations were lower in OND than in LND (p < 0.05) over 6 h of the study. There was no difference (p = 0.15) in C13 and D cortisol concentrations between OND and ODM and between LND and ODM for the same study period. Hepatic conversion of [(13)C]cortisone to C13 cortisol was similar between groups. CONCLUSIONS/INTERPRETATION: Hepatic conversion of [(13)C]cortisone to C13 cortisol did not differ between the groups studied. We conclude that hepatic 11ß-HSD-1 activity is similar in individuals who are overweight/obese or who have type 2 diabetes.

Splenic infarction caused by a rare coinfection of Epstein-Barr virus, cytomegalovirus, and Mycoplasma pneumoniae.

Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Mycoplasma pneumoniae are common pathogens of respiratory infection among children and young adults. Although single infection of 1 of these pathogens is common enough, their coinfection has been rarely reported. A 19-year-old woman presented with severe upper abdominal pain for 5 hours as well as flu-like symptoms and jaundice for 2 to 3 weeks. Initial tests found pancytopenia, abnormal liver functions, and presence of atypical lymphocytes in blood smear; the computed tomography of the abdomen revealed para-aortic lymphadenopathy, splenomegaly, and a wedge-shaped focal hypodensity lesion at the periphery of the spleen that was later diagnosed as splenic infarction. Her presentation raised suspicion of infectious mononucleosis. Nevertheless, monospot test, human immunodeficiency virus screening, and hepatitis viral serology were all negative, except that her M pneumoniae immunoglobulin M was found positive. Azithromycin was promptly given, but her fever and abdominal pain persisted. A strong suspicion of mononucleosis led to serological tests for EBV and CMV, which confirmed coinfection of EBV and CMV. By hospital day 7, her fever and abdominal pain had subsided and her liver function became normal. This case exemplifies the challenges in the diagnosis of coinfection of multiple respiratory pathogens and its associated complications. Greater awareness among clinicians would ensure an earlier and more accurate diagnosis of coinfection of EBV/CMV with other respiratory pathogen(s).

Acute hyperglycemia reduces myocardial blood flow reserve and the magnitude of reduction is associated with insulin resistance: a study in nondiabetic humans using contrast echocardiography.

The effect of acute hyperglycemia per se on coronary perfusion in humans is undefined. We evaluated the effects of short-term hyperglycemia on myocardial blood flow reserve (MBFR) in healthy nondiabetic volunteers. Twenty-one nondiabetic volunteers (76 % females, mean ± SD, age 48 ± 5 years) had noninvasive MBFR assessment while exposed to pancreatic clamp with somatostatin and replacement glucagon and growth hormone infusions, with frequent interval plasma glucose (PG) monitoring. Insulin was infused at 0.75 mU/kg/min to mimic postprandial plasma insulin concentrations, and glucose was infused to maintain euglycemia (PG 93.9 ± 7.3 mg/dl) followed by hyperglycemia (PG 231.5 ± 18.1 mg/dl). Myocardial contrast echocardiography (MCE) was performed during each glycemic steady state using continuous infusion of Definity at rest and during regadenoson (Lexiscan 5 ml (400 µg) intravenous bolus) infusion to quantify myocardial blood flow (MBF) and determine MBFR. Insulin resistance (IR) was assessed by glucose infusion rate (GIR; mg/kg/min) at euglycemia. Median stress MBF, MBFR, and ß reserve were significantly reduced during acute hyperglycemia versus euglycemia (stress MBF 3.9 vs 5.4, P = 0.02; MBFR 2.0 vs 2.7, P < 0.0001; ß reserve 1.45 vs 2.4, P = 0.007). Using a median threshold GIR of 5 mg/kg/min, there was a correlation between GIR and hyperglycemic MBFR (r = 0.506, P = 0.019). MBFR, as determined noninvasively by MCE, is significantly decreased during acute hyperglycemia in nondiabetic volunteers, and the magnitude of this reduction is modulated by IR.

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.

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.

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.

Transaldolase exchange and its effects on measurements of gluconeogenesis in humans.

The deuterated water method is used extensively to measure gluconeogenesis in humans. This method assumes negligible exchange of the lower three carbons of fructose 6-phsophate via transaldolase exchange since this exchange will result in enrichment of carbon 5 of glucose in the absence of net gluconeogenesis. The present studies tested this assumption. ²H2O and acetaminophen were ingested and [1-¹³C]acetate infused in 11 nondiabetic subjects after a 16-h fast. Plasma and urinary glucuronide enrichments were measured using nuclear magnetic resonance spectroscopy before and during a 0.35 mU·kg FFM⁻¹·min⁻¹ insulin infusion. Rates of endogenous glucose production measured with [3-³H]- and [6,6-²H2]glucose did not differ either before (14.0 ± 0.7 vs. 13.8 ± 0.7 µmol·kg⁻¹·min⁻¹) or during the clamp (10.4 ± 0.9 vs. 10.9 ± 0.7 µmol·kg⁻¹·min⁻¹), consistent with equilibration and quantitative removal of tritium during triose isomerase exchange. Plasma [3-¹³C] glucose-to-[4-¹³C]glucose and urinary [3-¹³C] glucuronide-to-[4-¹³C]glucuronide ratios were <1.0 (P < 0.001) in all subjects both before (0.66 ± 0.04 and 0.60 ± 0.04) and during (059 ± 0.05 and 0.56 ± 0.06) the insulin infusion, respectively, indicating that ∼35-45% of the labeling of the 5th carbon of glucose by deuterium was due to transaldolase exchange rather than gluconeogenesis. When corrected for transaldolase exchange, rates of gluconeogenesis were lower (P < 0.001) and glycogenolysis higher (P < 0.001) than uncorrected rates both before and during the insulin infusion. In conclusion, assuming negligible dilution by glycerol and near-complete triose isomerase equilibration, these data provide strong experimental evidence that transaldolase exchange occurs in humans, resulting in an overestimate of gluconeogenesis and an underestimate of glycogenolysis when measured with the ²H2O method. Use of appropriate ¹³C tracers provides a means of correcting for transaldolase exchange.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.