Thyroid abscess associated with thyrotoxicosis caused by Yersinia enterocolitica subsp. palearctica in a patient with follicular adenoma of the thyroid gland.

BACKGROUND: Yersinia enterocolitica is a gram-negative zoonotic bacterial pathogen that is typically transmitted via the fecal-oral route. The most common clinical manifestation of a Y. enterocolitica infection is self-limited gastroenteritis. Although various extraintestinal manifestations of Y. enterocolitica infection have been reported, there are no reports of thyroid abscesses. CASE PRESENTATION: An 89-year-old Japanese man with follicular adenoma of the left thyroid gland was admitted to our hospital with a 2-day history of fever and left neck pain. Laboratory tests revealed low levels of thyroid stimulating hormone and elevated levels of free thyroxine 4. Contrast-enhanced computed tomography showed low-attenuation areas with peripheral enhancement in the left thyroid gland. He was diagnosed with thyroid abscess and thyrotoxicosis, and treatment with intravenous piperacillin-tazobactam was initiated after collecting blood, drainage fluid, and stool samples. The isolated Gram-negative rod bacteria from blood and drainage fluid cultures was confirmed to be Y. enterocolitica. He was diagnosed with thyroid abscess and thyrotoxicosis due to be Y. enterocolitica subsp. palearctica. The piperacillin-tazobactam was replaced with levofloxacin. CONCLUSION: We report a novel case of a thyroid abscess associated with thyrotoxicosis caused by Y. enterocolitica subsp. palearctica in a patient with a follicular thyroid adenoma.

Hyperthyroidism.

Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.

Exploring synthesis as a vital cognitive skill in complex clinical diagnosis.

Clinicians employ two main cognitive approaches for diagnoses, depending on their expertise. Novices typically use linear hypothetico-deductive methods, while experts rely more on intuitive pattern recognition. These closely correspond to System 1 and System 2 thinking described in behavioral economics. We propose that complex cases additionally require the cognitive skill of synthesis, to visualize and understand the connections between various elements. To illustrate the concept, we describe a 60-year-old individual with a 6 h history of chest pain, fever, cough, accompanying chronic heart failure, atrial fibrillation, COPD, thyrotoxicosis, and ischemic heart disease. Faced with such a scenario, a bedside approach adapted by clinicians is to generate a list of individual diagnoses or pathways of pathogenesis, and address them individually. For example, this cluster could include: smoking causing COPD, IHD leading to chest pain and heart failure, and thyrotoxicosis causing atrial fibrillation (AF). However, other interconnections across pathways could be considered: smoking contributing to IHD; COPD exacerbating heart failure; IHD and pneumonia triggering atrial fibrillation; thyrotoxicosis and AF, independently worsening heart failure; COPD causing hypoxemia and worsening ventricular function. The second cluster of explanation offers a richer network of relationships and connections across disorders and pathways of pathogenesis. This cognitive process of creatively identifying these relationships is synthesis, described in Bloom's taxonomy of the cognitive domain. It is a crucial skill required for visualizing a comprehensive and holistic view of a patient. The concept of synthesis as a cognitive skill in clinical reasoning warrants further exploration.

Atypical Clinical Courses of Graves' Disease Confound Differential Diagnosis of Hyperthyroidism.

BACKGROUND: This study examined the appropriateness of the current paradigm for differential diagnosis of painless thyroiditis and Graves' disease (GD) in patients with thyrotoxicosis. METHODS: We retrospectively evaluated the clinical course of 343 consecutive patients with hyperthyroidism diagnosed by Tc-99m pertechnetate thyroid uptake (TcTU) testing at our hospital from January 2011 to December 2017. RESULTS: Of the 263 patients with normal or high TcTU levels (≥1.0%), 255 (97%) had unequivocal GD and 5 had spontaneous remission GD or atypical GD. Of the 10 patients with low TcTU levels (<1.0% and ≥0.5%), 7 had GD, while others had subclinical GD, spontaneous remission GD with later relapse, and painless thyroiditis. Of those with very low TcTU levels (<0.5%), most had thyroiditis (painless thyroiditis, 33/67 [49%]; subacute thyroiditis, 29/67 [43%]), and some were positive for anti-TSH receptor antibodies. CONCLUSION: Given that atypical GD may confound the diagnosis of thyrotoxicosis, it is essential to follow the patient as a tentative diagnosis, whatever the diagnosis. This is the first report clearly demonstrating that so far there is no gold standard for the diagnosis of GD. It is therefore urgent to establish a consensus on the definition of GD so that the specificity and sensitivity of future diagnostic tests can be determined.

Fetal Thyrotoxicosis due to Maternal TSH Receptor Stimulating Antibodies Causes Infant Central Hypothyroidism.

INTRODUCTION: Women with a current diagnosis or past history of Graves' disease (GD) are at risk of developing fetal thyrotoxicosis (FT) during pregnancy when they are inadequately treated, or because of placental passage of TSH receptor antibodies (TRAb). It is known that FT induced by high maternal thyroid hormone concentrations may result in infant (central) hypothyroidism. CASE PRESENTATION: In a euthyroid woman with a history of GD treated with radioactive iodide (I131), persistently high levels of maternal TRAb resulted in recurrent FT during two separate pregnancies, followed by neonatal hyperthyroidism and infant central hypothyroidism. DISCUSSION: This case demonstrates the novel insight that FT due to high fetal thyroid hormone concentrations stimulated by high maternal TRAb levels might also result in (central) hypothyroidism, requiring long-term evaluation of the hypothalamus-pituitary-thyroid axis in these children.

Short review: novel concepts in the approach to patients with amiodarone-induced thyrotoxicosis.

INTRODUCTION: Amiodarone-induced thyrotoxicosis is associated with high morbidity and mortality rates. The approach to this condition is widely variable across different medical specialists and even among expert endocrinologists. As a matter of fact, the approach to amiodarone-induced thyrotoxicosis has always been considered difficult, due to diagnostic uncertainties easily resulting in missteps, and therapeutic challenges easily resulting in unresponsiveness or slow-responsiveness to the administered drugs. PURPOSE: Our purpose is to review novelties emerged during the last years about this condition, with the aim to provide novel insights on the diagnostic and therapeutic management of this challenging condition.

Encephalitis as an initial presentation of type 2 amiodarone-induced thyrotoxicosis.

We report a case of a woman in her mid-20s presenting with encephalitis as the initial presentation of type 2 amiodarone-induced thyrotoxicosis (AIT). She was on amiodarone in view of a history of hypertrophic cardiomyopathy. Symptomatology included acute personality change and focal myoclonic jerks.Cerebrospinal fluid analysis showed a non-specific protein count elevation with negative microbiology, virology, autoimmune screen and onconeural antibodies. The electroencephalogram was consistent with a generalised cerebral dysrhythmia. An MRI of the head revealed symmetrical oedema within the motor cortices and a high T2 signal within the cerebellar dentate nuclei, with no restricted diffusion. Blood investigations confirmed thyrotoxicosis with negative antithyroid antibodies. She did not fulfil the criteria for a thyroid storm. Other possible causes of encephalitis were excluded.There was an excellent clinical, laboratory and radiological response to glucocorticoids, suggesting a diagnosis of steroid-responsive encephalitis secondary to type 2-AIT in the absence of a thyroid storm.

Thyrotoxic periodic paralysis presenting with quadriparesis and hyperreflexia.

Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that manifests as painless flaccid paralysis. An East Asian man in his late 20s presented to the emergency department with an acute onset of quadriparesis associated with hypertonia and hyperreflexia. His initial symptoms and signs suggested involvement of the brain and spinal cord; however, MRI of the neuroaxis was normal. His serum potassium concentration was low, and thyroid test results were consistent with hyperthyroidism. The patient was diagnosed with TPP associated with Graves' disease and was treated with potassium supplementation, propranolol and methimazole. Motor strength improved to his baseline level of power; bulk was normal, and tone was increased. Although flaccid paralysis is a typical presentation of TPP, brisk reflexes and muscle spasticity cannot rule out this condition. This case highlights the importance of considering TPP as a possible diagnosis in patients presenting with acute quadriparesis.

A machine learning-assisted system to predict thyrotoxicosis using patients' heart rate monitoring data: a retrospective cohort study.

Previous studies have shown a correlation between resting heart rate (HR) measured by wearable devices and serum free thyroxine concentration in patients with thyroid dysfunction. We have developed a machine learning (ML)-assisted system that uses HR data collected from wearable devices to predict the occurrence of thyrotoxicosis in patients. HR monitoring data were collected using a wearable device for a period of 4 months in 175 patients with thyroid dysfunction. During this period, 3 or 4 thyroid function tests (TFTs) were performed on each patient at intervals of at least one month. The HR data collected during the 10 days prior to each TFT were paired with the corresponding TFT results, resulting in a total of 662 pairs of data. Our ML-assisted system predicted thyrotoxicosis of a patient at a given time point based on HR data and their HR-TFT data pair at another time point. Our ML-assisted system divided the 662 cases into either thyrotoxicosis and non-thyrotoxicosis and the performance was calculated based on the TFT results. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of our system for predicting thyrotoxicosis were 86.14%, 85.92%, 52.41%, and 97.18%, respectively. When subclinical thyrotoxicosis was excluded from the analysis, the sensitivity, specificity, PPV, and NPV of our system for predicting thyrotoxicosis were 86.14%, 98.28%, 94.57%, and 95.32%, respectively. Our ML-assisted system used the change in mean, relative standard deviation, skewness, and kurtosis of HR while sleeping, and the Jensen-Shannon divergence of sleep HR and TFT distribution as major parameters for predicting thyrotoxicosis. Our ML-assisted system has demonstrated reasonably accurate predictions of thyrotoxicosis in patients with thyroid dysfunction, and the accuracy could be further improved by gathering more data. This predictive system has the potential to monitor the thyroid function status of patients with thyroid dysfunction by collecting heart rate data, and to determine the optimal timing for blood tests and treatment intervention.

Thyrotoxicosis as a rare presentation in acute suppurative thyroiditis: a case report.

BACKGROUND: Acute suppurative thyroiditis is a rare and potentially life-threatening disease. A few cases of acute suppurative thyroiditis associated with thyrotoxicosis have been reported in adults. We report a case of acute suppurative thyroiditis that was associated with thyrotoxicosis. CASE PRESENTATION: We report the case of a 49-year-old Iranian female presented with a painful neck swelling for a week. Computed tomography showed a well-defined gas-filled collection in the left thyroid lobe with an enhancing margin. The patient underwent two-phase surgery, first left thyroid abscess drainage and then total thyroidectomy. The result of histopathology examination was multinodular goiter with abscess formation without malignancy. CONCLUSION: Abscess formation and thyrotoxicosis is a very rare condition that occurs at the same time in acute suppurative thyroiditis. Despite antibiotic therapy being the first line of treatment, surgery is also required when antibiotic therapy fails.

Hyperthyroidism: A Review.

Importance: Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. Observations: The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Conclusions and Relevance: Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.

Acute Thyrotoxic Myopathy Combined with Neck Pain: A Case Report.

INTRODUCTION: Acute thyrotoxic myopathy (ATM) is a rare and potentially lethal complication of thyrotoxicosis. The typical clinical symptoms of ATM are characterized by bulbar paralysis. Reports of the successful treatment of ATM are sporadic due to its low incidence. However, no English literature has reported Chinese patients with ATM and neck pain. Here, we report for the first time a Chinese patient with ATM and neck pain who recovered through large doses of systemic glucocorticoids and one intrathyroidal steroid injection. CASE REPORT: A 23-year-old woman visited our hospital with a two-year history of progressive weakness of her bulbar muscles, hoarseness, cough when swallowing, dysphagia, and a one-month history of recurrent painful swelling of the thyroid gland. She was diagnosed with ATM, chronic thyrotoxic myopathy (CTM), and Graves' ophthalmopathy (GO) due to Graves' disease (GD). After she was treated with a combination of low-dose glucocorticoids, antithyroid drugs (ATDs), propranolol, and ultrasound-guided percutaneous intrathyroidal injection of glucocorticoids, her bulbar paralysis, proximal myopathy, and neck pain simultaneously improved without recurrence during follow-up. To our knowledge, this is the first case report of a patient with ATM, CTM, GD, GO and neck pain treated by administering a combination of low-dose glucocorticoids, one intrathyroidal steroid injection and antithyroid agents. CONCLUSIONS: Clinicians should consider ATM and intervene with aggressive glucocorticoid therapy, and this is the key to reversing the progression of ATM when a patient has bulbar paralysis and thyrotoxic symptoms. Our case report references the clinical diagnosis and treatment of such cases.

Endogenous and Exogenous Thyrotoxicosis and Risk of Incident Cognitive Disorders in Older Adults.

Importance: Thyroid hormone is among the most common prescriptions in the US and up to 20% may be overtreated. Endogenous hyperthyroidism may be a risk factor for dementia, but data are limited for iatrogenic thyrotoxicosis. Objective: To determine whether thyrotoxicosis, both endogenous and exogenous, is associated with increased risk of cognitive disorders. Design, Setting, and Participants: This cohort study performed a longitudinal time-varying analysis of electronic health records for patients receiving primary care in the Johns Hopkins Community Physicians Network between January 1, 2014, and May 6, 2023. Patients 65 years and older with at least 2 visits 30 days apart to their primary care physicians were eligible. None of the 65 931 included patients had a history of low thyrotropin (TSH) level or cognitive disorder diagnoses within 6 months of their first visit. Data analysis was performed from January 1 through August 5, 2023. Exposure: The exposure variable was a low TSH level, characterized based on the clinical context as due to endogenous thyrotoxicosis, exogenous thyrotoxicosis, or unknown cause, excluding those attributable to acute illness or other medical factors such as medications. Main Outcomes and Measures: The outcome measure was cognitive disorders, including mild cognitive impairment and all-cause dementia, to improve sensitivity and account for the underdiagnosis of dementia in primary care. Results: A total of 65 931 patients were included in the analysis (median [IQR] age at first visit, 68.0 [65.0-74.0] years; 37 208 [56%] were female; 46 106 [69.9%] were White). Patients exposed to thyrotoxicosis had cognitive disorder incidence of 11.0% (95% CI, 8.4%-14.2%) by age 75 years vs 6.4% (95% CI, 6.0%-6.8%) for those not exposed. After adjustment, all-cause thyrotoxicosis was significantly associated with risk of cognitive disorder diagnosis (adjusted hazard ratio, 1.39; 95% CI, 1.18-1.64; P < .001) across age groups. When stratified by cause and severity, exogenous thyrotoxicosis remained a significant risk factor (adjusted hazard ratio, 1.34; 95% CI, 1.10-1.63; P = .003) with point estimates suggestive of a dose response. Conclusions and Relevance: In this cohort study among patients 65 years and older, a low TSH level from either endogenous or exogenous thyrotoxicosis was associated with higher risk of incident cognitive disorder. Iatrogenic thyrotoxicosis is a common result of thyroid hormone therapy. With thyroid hormone among the most common prescriptions in the US, understanding the negative effects of overtreatment is critical to help guide prescribing practice.

Thyrotoxicosis.

Hyperthyroidism is a diagnosis existing along a spectrum of severity. Patients present with a variety of signs and symptoms: tachycardia, elevated heart rate, anxiety, changes in mental status, gastrointestinal disturbances, and hyperthermia. Management of subclinical hyperthyroidism and thyrotoxicosis without thyroid storm is heavily dependent on outpatient evaluation. Thyroid storm is the most severe form of hyperthyroidism with the highest mortality. Management of thyroid storm follows a stepwise approach, with resuscitation and detection of the precipitating cause being paramount. Special attention should be paid to cardiac function in patients with thyroid storm before treatment, as these patients may develop cardiac collapse.

The value of FT4/TSH ratio in the differential diagnosis of Graves' disease and subacute thyroiditis.

Objective: To explore the value of the FT4/TSH ratio in the etiological diagnosis of newly diagnosed patients with thyrotoxicosis. Methods: The retrospective study was conducted on 287 patients with thyrotoxicosis (122 patients with subacute thyroiditis and 165 patients with Graves' disease) and 415 healthy people on their first visit to our hospital. All patients underwent thyroid function tests including the measurement of T3, T4, FT3, FT4, TSH, T3/TSH, and T4/TSH. The receiver operating characteristic (ROC) curve was employed to evaluate the value of FT4/TSH in the differential diagnosis of Graves' disease and subacute thyroiditis, and compared with other related indicators. Results: The area under the curve of FT4/TSH for diagnosing Graves' disease and thyroiditis was 0.846, which was significantly larger than the area under the curve of T3/T4 ratio (P< 0.05) and FT3/FT4 ratio (P< 0.05). When the cut-off value of the FT4/TSH ratio was 5731.286 pmol/mIU, the sensitivity was 71.52%, the specificity was 90.16%, the positive predictive value was 90.77% and the negative predictive value was 70.06%. The diagnostic accuracy was 79.44%. Conclusion: FT4/TSH ratio can be used as a new reference index for the differential diagnosis of thyrotoxicosis.

Limited Utility of Free Triiodothyronine Testing.

BACKGROUND: Free triiodothyronine (fT3) testing is most useful when thyroid stimulating hormone (TSH) is suppressed, and free thyroxine (fT4) is normal or decreased. These laboratory values in a symptomatic patient are referred to as T3 thyrotoxicosis. Standards for fT3 reflex testing have not been established. Herein, we examined the clinical utility of fT3 with the goal of identifying a TSH cutoff in the context of normal/decreased fT4 that maximizes the utility of measuring fT3. METHODS: TSH, fT4, and fT3 results between January 2016 and October 2021 were extracted from the laboratory information system and grouped if resulted on the same day for the same patient. Frequency of biochemical T3 thyrotoxicosis was evaluated at different TSH cutoffs and in outpatient vs inpatient settings. RESULTS: Of the 4366 TSH-fT4-fT3 results, 70 (1.6%) were consistent with biochemical T3 thyrotoxicosis. The common reasons were previously diagnosed hyperthyroidism on antithyroid medication (n = 28) or hypothyroidism on thyroid medication (n = 18) and newly diagnosed hyperthyroidism (n = 20, 0.5%). The likelihood of detecting T3 thyrotoxicosis increased with lower TSH cutoff (<0.3 µIU/mL, 10.3% vs <0.0 1µIU/mL, 27.6%). All patients with newly diagnosed hyperthyroidism had TSH <0.01 µIU/mL. Higher frequency of T3 thyrotoxicosis was observed in the outpatient setting (34%) relative to the inpatient setting (14%, P < 0.001) when TSH < 0.01 µIU/mL. CONCLUSIONS: T3 thyrotoxicosis is a relatively rare diagnosis and fT3 measurement has limited utility in the vast majority of patients. A fT3 reflex for patients with TSH <0.01 µIU/mL and normal/low fT4 may improve clinical utility and reduce unnecessary testing, especially in the outpatient setting.