Diagnosis of Graves' Disease and Methimazole-Induced Lupus Erythematosus in an Adolescent Male During the COVID-19 Era: A Case Report.

Graves' disease is the most common form of hyperthyroidism in the pediatric population. Methimazole is the recommended regimen that is well-tolerated in most patients. Treatment with methimazole leading to drug-induced lupus erythematosus (DILE) is not well reported in the pediatric population, especially in the COVID-19 era. We present a case of a 14-year-old Caucasian male who presented with concerns of long COVID due to shortness of breath, hypertension, and fatigue. He was not noted to have significant weight loss, exophthalmos, or sleeping difficulties. He was followed by his general pediatrician, pediatric endocrinologist, cardiologist, and rheumatologist. Laboratory tests confirmed the diagnosis of Graves' disease, and treatment was initiated with methimazole and atenolol. One month into treatment, the patient developed polyarthritis, urticarial rash, and difficulty with gait. Based on clinical suspicion and antibody panels, he was diagnosed with DILE secondary to treatment with methimazole. The patient was then started on a potassium iodide (Lugol) solution to promote the euthyroid state and proceed with total thyroidectomy. Post surgery, the patient developed hypothyroidism, which was managed with oral levothyroxine, to which the patient responded well. By discussing the clinical presentation and treatment of this patient, the goal is to raise awareness and increase clinical suspicion in diagnosing Graves' and DILE in adolescents with upper respiratory presentations.

Brain functional connectivity in hyperthyroid patients: systematic review.

Introduction: Functional connectivity (FC) is the correlation between brain regions' activities, studied through neuroimaging techniques like fMRI. It helps researchers understand brain function, organization, and dysfunction. Hyperthyroidism, characterized by high serum levels of free thyroxin and suppressed thyroid stimulating hormone, can lead to mood disturbance, cognitive impairment, and psychiatric symptoms. Excessive thyroid hormone exposure can enhance neuronal death and decrease brain volume, affecting memory, attention, emotion, vision, and motor planning. Methods: We conducted thorough searches across Google Scholar, PubMed, Hinari, and Science Direct to locate pertinent articles containing original data investigating FC measures in individuals diagnosed with hyperthyroidism. Results: The systematic review identified 762 articles, excluding duplicates and non-matching titles and abstracts. Four full-text articles were included in this review. In conclusion, a strong bilateral hippocampal connection in hyperthyroid individuals suggests a possible neurobiological influence on brain networks that may affect cognitive and emotional processing. Systematic Review Registration: PROSPERO, CRD42024516216.

Predictive value of bone turnover markers and thyroid indicators for bone metabolism in GD patients after treatment.

Purpose: To investigate the relationship between bone turnover markers (BTMs) and thyroid indicators in Graves' disease (GD) and to further assess predictive value of changes in early stage retrospectively. Methods: We studied 435 patients with GD and 113 healthy physical examiners retrospectively and followed up these two groups of patients after 6 months. We investigated the correlations between BTMs and other 15 observed factors, and analyzed the predictive value of FT3 and FT4 before and after treatment (FT3-P/FT3-A, FT4-P/FT4-A) on whether BTMs recovered. Results: The levels of thyroid hormones and BTMs in GD group were significantly higher than those in control group (P < 0.05) and decreased after 6 months of treatment. FT3, W, Ca and ALP were independent factors in predicting the elevation of OST. Duration of disease, FT3, TSH and ALP were independent factors in predicting the elevation of P1NP. Age, duration of disease, TRAb and ALP were independent factors in predicting the elevation of CTX-1. The AUC of FT3-P/FT3-A and FT4-P/FT4-A for predicting OST recovery were 0.748 and 0.705 (P < 0.05), respectively, and the cut-off values were 0.51 and 0.595. There was no predictive value for P1NP and CTX-1 recovery (P > 0.05). Conclusion: BTMs were abnormally elevated in GD and were significantly correlated with serum levels of FT3, FT4, TRAb, Ca, and ALP. FT3 decreased more than 51% and FT4 dropped more than 59.5% after 6 months of treatment were independent predictors for the recovery of BTMs in GD.

New-Onset Graves' Disease With Thyroid Storm After COVID-19 Infection.

COVID-19 has been a known cause of triggering autoimmune conditions. Previous literature demonstrates an increase in the incidence of Graves' disease during the COVID-19 pandemic. The virus is thought to affect genetics, leading to a cascade of events that cause hyperthyroidism. In our case, an 81-year-old male presented with symptoms of palpitations, tremors, dizziness, diarrhea, and fatigue. He was found to be in atrial fibrillation with rapid ventricular response, and his workup was consistent with hyperthyroidism. Based on his Burch-Wartofsky score, the diagnosis of thyroid storm was made. There are a limited number of case reports with new-onset Graves' disease after COVID-19 infection. Interestingly, our patient was also in a thyroid storm. He was treated with hydrocortisone cholestyramine, potassium, and propylthiouracil. After treatment, his symptoms resolved, and his thyroid studies improved. We chose to present this case because it demonstrates one of the many autoimmune effects that COVID-19 has been linked to.

Case report: Thyroid storm in a three-year-old girl presenting with febrile status epilepticus and hypoglycemia.

Thyroid storm, though extremely rare in toddlers, requires prompt diagnosis and treatment because it can be fatal if left untreated. However, thyroid storm is not often considered in the differential diagnosis of a febrile convulsion due to its rarity in children. Herein, we report the case of a 3-year-old girl with thyroid storm who presented with febrile status epilepticus. Although the seizure was stopped by diazepam administration, her tachycardia and widened pulse pressure persisted, and severe hypoglycemia was observed. Based on the findings of thyromegaly, a history of excessive sweating and hyperactivity, and a family history of Graves' disease, she was eventually diagnosed with a thyroid storm. The patient was successfully treated with thiamazole, landiolol, hydrocortisone, and potassium iodide. Propranolol, a non-selective ß-blocker, has been used to manage tachycardia during thyroid storm. However, a cardio-selective ß1-blockers, landiolol hydrochloride, was used in our case to avoid worsening hypoglycemia. Febrile status epilepticus is one of the most common medical emergencies in childhood; it is necessary to rule out treatable underlying critical diseases such as septic meningitis and encephalitis. Thyroid storm should be considered in children presenting with prolonged febrile convulsion accompanied by findings that are not usually observed with febrile convulsions.

Thyrotoxic Crisis in the Absence of Risk Factors: A Case Report.

Thyrotoxic crisis is a severe, life-threatening form of thyrotoxicosis characterized by elevated circulating thyroid hormone that can lead to profound complications. Early diagnostic interventions include a thorough physical examination, laboratory assessments of thyroid hormone levels, and the utilization of quantifying assessment tools to grade the severity of the condition. A targeted therapeutic regimen involving a combination of thioamides, beta-blocking agents, and iodide therapies is administered to combat each stage of the physiological process involved in a thyroid storm. The prompt recognition of clinical manifestations and systemic complications of thyrotoxic crisis is of paramount significance to prevent therapeutic delay and reduce patient mortality. Here, we report an atypical case of a new-onset thyrotoxic crisis in a patient without apparent underlying predisposing factors.

Clinical phenotypes of euthyroid, hyperthyroid, and hypothyroid thyroid-associated ophthalmopathy.

OBJECTIVE: To compare the demographic and clinical phenotypes of thyroid-associated ophthalmopathy (TAO) with euthyroidism (Eu-TAO), hyperthyroidism (Hr-TAO), and hypothyroidism (Ho-TAO). METHODS: We enrolled 2158 TAO patients in this retrospective study and assessed their demographics, clinical manifestations, activity, and severity. RESULTS: Among the enrolled patients, 526 (24.37%) had Eu-TAO, 1544 (71.55%) had Hr-TAO, and 88 (4.08%) had Ho-TAO. Compared to Hr-TAO (2.02) and Ho-TAO (2.52) patients, Eu-TAO (1.57) patients had the lowest female-to-male ratio (p = 0.026). The mean ages of Eu-TAO, Hr-TAO, and Ho-TAO patients were 43.11 ± 12.05, 42.23 ± 13.63, and 47.39 ± 13.28 years, respectively (p = 0.001). Patients with Eu-TAO had more unilateral involvement (50% vs. 14.38% vs. 21.59%, p < 0.001) than Hr-TAO or Ho-TAO patients. Clinically active TAO patients presented 8.56% in euthyroid vs. 13.86% in hyperthyroid vs. 11.36% in hypothyroid (p = 0.006). Regarding the severity of the European Group on Graves' Orbitopathy (EUGOGO) classification among euthyroid, hyperthyroid, and hypothyroid patients, mild TAO was present in 67.68, 54.27, and 72.72% of participants, moderate-to-severe TAO in 31.18, 42.49, and 26.14%, and sight-threatening TAO in 1.14, 3.24, and 1.14%, respectively. Eu-TAO was positively correlated with unilateral involvement (OR = 5.671, p < 0.001) and age (OR = 1.013, p = 0.003) and negatively correlated with the female-to-male ratio (OR = 0.656, p < 0.001) and TAO severity (OR = 0.742, p < 0.01). CONCLUSIONS: Eu-TAO patients are older and less likely to be female, and show more unilateral and milder clinical phenotypes than hyper/hypothyroid TAO patients.

Hyperthyroidism leads learning and memory impairment possibly via GRIN2B expression alterations.

The hippocampus as an important structure for learning and memory functions contains a high level of thyroid hormone receptors. Although there are numerous studies investigating the effects of thyroid hormones on cognitive dysfunction and psychiatric symptoms, the underlying molecular processes of these disorders have not yet been fully elucidated. In the present study, 24 male adult rats (4 months) were divided into 3 groups: control group, sham group and hyperthyroid group. Hyperthyroid group and sham group were treated with l-thyroxine or saline for 21 days. Each group was exposed to Morris water maze testing (MWMT), measuring their performance in a hidden-platform spatial task. After learning and memory tests, intracardiac blood was taken from the rats for serum thyroxine levels. Following blood collection, the rats were decapitated to isolate hippocampal tissue. GRIN2A, GRIN2B, BDNF, cFOS, Cdk5, cdk5r1 (p35), and cdk5r2 (p39) gene expression were evaluated using quantitative reverse transcriptase-PCR. Serum thyroxine level was found to be higher in hyperthyroid rats than in the control and sham groups. According to our MWMT findings, the memory performance of the hyperthyroid group was significantly impaired compared to the control and sham groups (p < 0.05). In the hippocampus, the GRIN2A gene expression level was decreased in the sham group, and the GRIN2B gene expression level was decreased in the sham and hyperthyroid groups compared to the control group (p < 0.05). There was no significant difference in other genes (p > 0.05). Hyperthyroidism impaired hippocampus-dependent spatial memory. Hyperthyroidism caused decreased level of GRIN2B gene expression in the hippocampus.

Laboratory Diagnosis of Thyroid and Adrenal Disease.

Diagnosis of thyroid and adrenal disease can be confusing. Whereas the definitive diagnosis of hyperthyroidism and hypoadrenocorticism are relatively straightforward, hypothyroidism and naturally occurring Cushing's syndrome (NOCS) are more complicated. In a patient with compatible clinical signs, a single increased tT4 is enough to confirm hyperthyroidism, but a low tT4 alone is never enough to confirm hypothyroidism. A flatline result (post-stimulation cortisol <2 ug/dL) on an ACTH stimulation test (ACTHst) confirms hypoadrenocorticism, but not all dogs with NOCS have increased ACTHst results. This article explains which diagnostics should be pursued for these endocrinopathies, and how to interpret them.

The Intertwined Relationship Between an Overactive Thyroid and an Overactive Mind: A Case Report and Review of Literature.

This case report presents the clinical scenario of a 45-year-old male patient who exhibited acute psychiatric symptoms as the initial manifestation of Graves' disease, a common etiology of hyperthyroidism. The patient presented with severe agitation, persecutory delusions, and auditory hallucinations, raising concerns about his mental health. Detailed diagnostic evaluations revealed thyroid dysfunction characterized by markedly low thyroid-stimulating hormone (TSH) levels, elevated free T4 levels, and increased total T3 levels, indicative of thyrotoxicosis. Elevated thyroid-stimulating immunoglobulin (TSI) levels further confirmed the diagnosis of Graves' disease. The patient received treatment with methimazole and propranolol to manage the hyperthyroidism, leading to the resolution of psychiatric symptoms. This case emphasizes the importance of considering thyroid function in patients presenting with acute psychiatric disturbances. This literature review explores the intricate relationship between hyperthyroidism, a condition characterized by the excessive production of thyroid hormones, and its impact on psychological and cognitive processes. Understanding the connection between an overactive thyroid and an overactive mind is crucial for clinicians and researchers to provide comprehensive care and treatment for affected individuals.

Fluctuating Hyperthyroidism and Hypothyroidism in Graves' Disease: The Swinging Between Two Clinical Entities.

Autoimmune thyroid disorders are frequently encountered in clinical practice and consist of a spectrum ranging from Graves' hyperthyroidism to Hashimoto's hypothyroidism. Generally, patients with autoimmune thyroid disorders will lean towards one end of the spectrum or the other, with fluctuations between hyper- and hypothyroidism rarely seen. This is especially the case when persistent hyperthyroidism occurs after a prolonged period of hypothyroidism. Here, we present a case of a young female patient initially presenting with Graves' disease with a previous history of hypothyroidism.

Severe Cardiovascular Effects of Prolonged Untreated Hyperthyroidism Manifesting As Thyroid Storm.

A thyroid storm is a rare but life-threatening manifestation of thyrotoxicosis. It still remains a diagnostic challenge as there are no specific laboratory investigations or universally accepted criteria for diagnosing thyroid storms. Diagnosis is mainly based on clinical findings, evidence of hyperthyroidism, and life-threatening symptoms. A thyroid storm has a high risk of mortality mostly due to multi-organ failure and heart failure. Cardiovascular manifestations are the most common presentation of hyperthyroidism; cardiac involvement also has the potential to be the most serious complication. Management of cardiovascular manifestations should be managed aggressively to prevent long-term myocardial damage. A high index of suspicion should be maintained in young adults presenting with heart failure and arrhythmia. We present a case of potentially life-threatening cardiovascular effects of thyroid storm and management in the ICU.

Unprovoked Isolated Pulmonary Embolism and Graves' Disease in a Patient With Dyspnea: A Case Report.

Graves' disease is a commonly diagnosed disease with a plethora of manifestations that can lead to its diagnosis. One of the rarer presentations of Graves' disease is hypercoagulability with the development of spontaneous venous thrombosis. In patients presenting with unprovoked pulmonary embolism, we suggest evaluating the patient's thyroid function tests as a potential underlying cause. To bring this issue to attention, we are presenting a rare case of isolated spontaneous pulmonary embolism development secondarily to underlying Graves' disease.

Case report: Hyperthyroid hypokalemic periodic paralysis.

Introduction and importance: HHPP is a rare type of hypokalemic PP that can occur when there is hyperthyroidism.Thyrotoxic periodic paralysis is due to increased influx of potassium into skeletal muscle cells which leads to profound hypokalemia and paralysis. Insulin and Epinephrine are also responsible for stimulating the Na-K-ATPase pumps which are over expressed during hyperthyroid state. Laboratory hypokalemia in the background of hyperthyroidism with sudden symmetric paralysis point toward the diagnosis. Case: We present a case of 25 year old male with limb weakness for 3hours following heavy dinner.He felt weakness after waking up in the morning where he could not move his both lower limbs. He also had difficulty moving upper limbs. Clinical findings and investigations: Examination revealed proximal muscle weakness with power of 2/5, decreased muscle tone, diminished deep tendon reflexes in all four limbs and equivocal plantar reflex bilaterally. Investigation sent were Total Leukocyte count, Hemoglobin, Renal function test, Liver Function test,Thyroid function test, Vitamin B12, Serology, ACTH, Serum calcium, Serum phosphate, Serum magnesium, Urine R/ME and Stool R/ME. Intervention and outcome: Patient is treated with 10mEq/L/hr infusion of potassium chloride, methimazole and beta-blockers. He is stable and is in regular followup in medicine OPD. Relevance and impact: Early diagnosis of HHPP is very essential to prevent fatal complications (cardiac and respiratory).It can be treated by timely potassium supplementation, methimazole and beta-blockers.Clinicians must be concerned about Hyperkalemia while supplementing Potassium in bed side.

CaMKII inhibition protects against hyperthyroid arrhythmias and adverse myocardial remodeling.

Hyperthyroidism can potentiate arrhythmias and cardiac hypertrophy, whereas Ca2+/calmodulin-dependent kinase II (CaMKII) promotes maladaptive myocardial remodeling. However, it remains unclear whether CaMKII contributes to the progression of hyperthyroid heart disease (HHD). This study demonstrated that CaMKII inhibition can relieve adverse myocardial remodeling and reduce sinus tachycardia, isoproterenol-induced atrial fibrillation, and ventricular arrhythmias in hyperthyroid mice with preserved heart function. Hyperthyroid cardiac hypertrophy was promoted by CaMKII upregulation-induced HDAC4/MEF2a activation. Briefly, CaMKII inhibition benefits HHD management greatly in mice by preventing arrhythmias and maladaptive remodeling.

Randomised clinical trial evaluating the effect of a single preappointment dose of gabapentin on signs of stress in hyperthyroid cats.

OBJECTIVES: The aim of this study was to evaluate the efficacy of gabapentin as an anxiolytic in hyperthyroid cats. METHODS: Cats (n = 47) with confirmed hyperthyroidism were successfully enrolled. The cat owner allocated a temperament score and a transport stress score at their first visit. For the second visit the cat owner (blinded to treatment) administered either liquid gabapentin 20 mg/kg (n = 22) or an indistinguishable placebo solution (n = 25) 1 h prior to leaving home. A second transport score was allocated by the cat owner at this visit. Upon admission a compliance score was independently assigned by two veterinary nurses blinded to treatment. Excess blood from routine blood draw was analysed for gabapentin plasma concentration from cats in the gabapentin group. RESULTS: There were no significant differences in baseline transport score between groups (P = 0.13), but significant differences were noted in the second visit transport score between cats medicated with gabapentin compared with placebo (P = 0.018). Mean compliance scores were significantly different between cats in the treatment group compared with placebo (P = 0.019). Further sedation was required to complete the procedures in 24% of cats in the placebo group compared to 9% in the gabapentin group (P = 0.25). Mean plasma gabapentin concentrations were 10.1 mg/l (range 1.7-22.7) in the gabapentin group within a 1-3 h time frame post-administration. CONCLUSIONS AND RELEVANCE: Hyperthyroid cats medicated with 20 mg/kg gabapentin 1 h prior to leaving home were more relaxed during transport and more compliant with veterinary procedures than cats administered a placebo solution.

A Case of Severe Dilated Cardiomyopathy and Hyperthyroidism.

Hyperthyroidism often leads to heart failure when left untreated, specifically high output heart failure and left ventricular (LV) hypertrophy. A very minimal portion of those develop severe LV dysfunction. We report a case of a 65-year-old male who presented with signs and symptoms of heart failure and was found to have hyperthyroidism, severe systolic dysfunction, and severe dilated cardiomyopathy. The patient is a 65-year-old African American male with a history of hypertension (HTN) who presented with complaints of dyspnea on exertion and bilateral lower limb edema of one-week duration. A review of systems revealed paroxysmal nocturnal dyspnea, orthopnea, palpitations, fatigue, and weight loss. Physical exam showed tachycardia but otherwise no exophthalmos, no thyromegaly, no thyroid nodules, clear lungs, normal heart sounds, regular heart rhythm, normal reflexes, and 2+ edema of bilateral lower extremities up to the knees. Labs showed elevated B-natriuretic peptide, severely suppressed thyroid-stimulating hormone, elevated free triiodothyronine (FT3), and free thyroxine (FT4). Electrocardiogram (EKG) revealed sinus tachycardia, incomplete left bundle branch block, and non-specific T wave abnormality. Echocardiography revealed abnormal (LV) structure and function, with moderate to severe dilatation without LV hypertrophy, severe LV systolic dysfunction with ejection fraction (EF) 30-35%, and an abnormal LV diastolic function. The patient was managed with diuresis for acute onset heart failure and with beta-blocker and methimazole for symptomatic hyperthyroidism. Thyroid assessment is an important step in evaluating any patient with suspected heart failure. This case highlights the balance that should exist between treating hyperthyroidism symptoms and managing disease states such as acute heart failure.

Analysis of Thermogenesis Experiments with CalR.

Modern indirect calorimetry systems allow for high-frequency time series measurements of the factors affected by thermogenesis: energy intake and energy expenditure. These indirect calorimetry systems generate a flood of raw data recording oxygen consumption, carbon dioxide production, physical activity, and food intake among other factors. Analysis of these data requires time-consuming manual manipulation for formatting, data cleaning, quality control, and visualization. Beyond data handling, analyses of indirect calorimetry experiments require specialized statistical treatment to account for differential contributions of fat mass and lean mass to metabolic rates.Here we describe how to use the software package CalR version 1.2, to analyze indirect calorimetry data from three examples of thermogenesis, cold exposure, adrenergic agonism, and hyperthyroidism in mice, by providing standardized methods for reproducible research. CalR is a free online tool with an easy-to-use graphical user interface to import data files from the Columbus Instruments' CLAMS, Sable Systems' Promethion, and TSE Systems' PhenoMaster. Once loaded, CalR can quickly visualize experimental results and perform basic statistical analyses. We present a framework that standardizes the data structures and analyses of indirect calorimetry experiments to provide reusable and reproducible methods for the physiological data affecting body weight.

Birthweight and subsequent risk for thyroid and autoimmune conditions in postmenopausal women.

The objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women's Health Initiative (n = 80,806) were used to examine the associations between birthweight category (<6 lbs., 6-7 lbs. 15 oz, 8-9 lbs. 15 oz, and ≥10 lbs.) and prevalent thyroid (underactive and overactive thyroid and goiter) and autoimmune (lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis/Crohn's disease) conditions. Follow-up questionnaire data were used to examine the associations between birthweight and incident underactive and overactive thyroid, lupus, and RA. Logistic and Cox proportional hazards regression models were used to estimate crude and adjusted odds (OR) and hazards ratios (HR), respectively. Overall, women born weighing ≥10 lbs. had an increased risk for underactive thyroid [OR 1.14 (95% CI 1.02, 1.28)] and incident lupus [HR 1.51 (95% CI 1.12, 2.03)] and a decreased risk for overactive thyroid [OR 0.67 (95% CI 0.50, 0.92)] compared to women born weighing 6-7.99 lbs., after adjustment for adult BMI, demographic variables, and lifestyle factors. Further, women born weighing <6 lbs. were at increased risk for underactive thyroid [OR 1.13 (95% CI 1.04, 1.22)]. Birthweight was not associated with other thyroid or autoimmune disorders. High birthweight was associated with later-life thyroid and autoimmune conditions while low birthweight was associated with underactive thyroid. Preconception and prenatal interventions aimed at reducing the risk of both high and low birthweights may reduce the burden of later-life thyroid and autoimmune conditions.