Paraneoplastic Hyperthyroidism Secondary to a Chemotherapy-Induced Surge in ß-hCG in a Patient with Non-Seminomatous Germ Cell Tumor.

Thyrotoxicosis as the presenting syndrome of an underlying ß-hCG-secreting malignancy is well described. It has been previously theorized, but not reported, that the surge of ß-hCG secondary to chemotherapy induction may inadvertently trigger thyrotoxicosis. After thorough review, this is the first documented case of such event in peer-reviewed medical literature published in the English language. This is a case of a 21-year-old male with stage IIIc non-seminomatous germ cell tumor who developed paraneoplastic hyperthyroidism within 4 days of the first cycle of chemotherapy. Management considerations are suggested based on this case and review of the literature.

[Type 2 amiodarone-induced thyrotoxicosis: efficacy of glucocorticoid therapy, a retrospective analysis].

BACKGROUND: Type 2 amiodarone-induced thyrotoxicosis remains a significant problem of endocrinology and cardiology. Due to the increase a life expectancy of the population, the prevalence of cardiac arrhythmias and prescribing of amiodarone are increasing. Thyrotoxicosis aggravates the existing cardiovascular disease in patients, leads to the progression of left ventricular dysfunction, relapses of arrhythmias, increasing the risk of adverse outcomes. The tactic of further management of patients is complicated: it is necessary to resolve the issue of canceling or continuing the use of antiarrhythmic drugs necessary for a patient with a history of cardiac arrhythmia, as well as competent therapy of the thyroid pathology that has arisen. Oral glucocorticoids are the first-line drugs for the treatment of patients with moderate and severe type 2  amiodarone-induced thyrotoxicosis. Despite the appearance of clinical recommendations, opinions on the management of patients are differ, both among cardiologists and among endocrinologists. Often thyrostatics are prescribed to patients simultaneously with glucocorticoids, although it doesn't have pathogenetic basis. AIM: To evaluate the efficacy of various therapy options in patients with type 2 amiodarone-induced thyrotoxicosis. MATERIALS AND METHODS: The retrospective study included 38 patients (20 men and 18 women aged 35 to 85 years) with type 2 amiodarone-induced thyrotoxicosis. All patients underwent an analysis of anamnestic, anthropometric data, complex laboratory and instrumental diagnostics. According to the treatment options, 3 groups were retrospectively formed: without therapy (n=19), taking glucocorticoids (n=11) and combination of glucocorticoids and thyrostatics (n=8). The follow-up period was 6-18 months, including the treatment. The efficacy of treatment in the groups was evaluated by the time of reaching euthyroidism on the background of glucocorticoid therapy and duration of thyrotoxicosis; the search was conducted for potential predictors of delayed response to glucocorticoid therapy and long-term course of thyrotoxicosis. RESULTS: The average age was 62.0 [52.9; 66.3] years. The level of free thyroxine was significantly decreased after 1 month from the start of therapy in both groups: from 38.1 [32.1; 58.4] to 23.4 [19.6; 29.3] pmol/l (p<0.001) in the group taking glucocorticoids; from 73.9 [42.2; 75.6] to 39.3 [22.4; 47.2] pmol/l (p<0.001) in the combination therapy group. The time of reaching euthyroidism was longer in the combination therapy group (p=0.047), didn't depend on the dose (p=0.338) and duration of taking thiamazole (p=0.911), the delayed response to therapy correlated with age (p=-0.857; p=0.007) and time interval from the appearance of clinical symptoms of thyrotoxicosis to the start of glucocorticoid therapy (p=0.881; p<0.001). CONCLUSION: The results demonstrate the dependence of glucocorticoid response on the age of the patient and start time of therapy relative to the duration of thyrotoxicosis, inexpediency of additional prescribing thyrostatics in type 2 amiodarone-induced thyrotoxicosis.

Monitoring thyroid function during amiodarone use.

Amiodarone is an antiarrhythmic drug used to treat cardiac tachyarrhythmias. It has many adverse effects, with thyroid dysfunction one of the most notable. Through various mechanisms, both thyrotoxicosis and hypothyroidism can occur secondary to amiodarone therapy. There are two types of amiodarone-induced thyrotoxicosis: type 1 occurs in those with pre-existing thyroid disease and is treated with thionamide, whereas type 2 occurs in those without and is treated with glucocorticoids. Patients with amiodarone-induced hypothyroidism may be given levothyroxine to replace thyroid hormone, but in some cases, the appropriate management may be cessation of amiodarone.

The roles of thyroidectomy in patients with amiodarone-induced thyrotoxicosis: A systematic review.

The principal management of Amiodarone-induced-thyrotoxicosis (AIT) is balancing cardiac-thyroid conditions. However, the role of thyroidectomy is still contentious. This systematic review aims to provide insights into the roles of thyroidectomy in the management of AIT. This systematic review encompasses 303 AIT patients who underwent thyroidectomy from 14 studies. The indication of thyroidectomy can be due to cardiac factors, thyrotoxicosis conditions, and patient-physician considerations. Thyroidectomy is more effective in improving thyroid hormone status, cardiac function, and mortality compared to optimal medical therapy, especially in those with left ventricular ejection fraction < 40 %. Thyroidectomy is effective in improving cardiac function and mortality due to shorter duration for achieving euthyroid. Thyroidectomy and medical therapy have comparable side effects. However, the identification of high-risk patients may reduce thyroidectomy complications. Thus, thyroidectomy should not be viewed as the last resource and should be performed immediately when indicated.

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.

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.

Incidence of Endocrine-Related Dysfunction in Patients Treated with New Immune Checkpoint Inhibitors: A Meta-Analysis and Comprehensive Review.

BACKGRUOUND: This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs. METHODS: We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published. RESULTS: A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone. CONCLUSION: Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.

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.

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.

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.

Povidone-iodine-induced transient triiodothyronine thyrotoxicosis in a Japanese patient with prolonged habitual gargling: A case report and literature review.

RATIONALE: Iodine-induced hyperthyroidism and triiodothyronine (T3) thyrotoxicosis in patients who routinely gargle with povidone-iodine (PVP-I) gargling solution are rare in Japan. PATIENT CONCERNS: A 50-year-old man presented to our hospital for a close examination of an enlarged thyroid, which was noted during a complete health checkup. The thyroid was slightly enlarged with no palpable nodules. He had an increased appetite but no weight gain. He had been routinely gargling with PVP-I gargling solution 4 times daily for >10 years. He had no history of thyroid disease. DIAGNOSES: Test results revealed suppressed thyroid-stimulating hormone, normal free thyroxine, and increased free triiodothyronine levels, leading to the diagnosis of T3 thyrotoxicosis. INTERVENTIONS: The patient agreed to stop gargling with PVP-I gargle solution. OUTCOMES: The free triiodothyronine and thyroid-stimulating hormone levels returned to normal at 18 and 21 weeks, respectively, after discontinuation of PVP-I gargling. After an improvement in thyroid function, he gained 5 kg in 1 year. LESSONS: To our knowledge, this is the first case report that describes PVP-I gargle-induced T3 thyrotoxicosis in a healthy individual without thyroid disease. In Japan, which is an iodine-sufficient country, considering the possibility of high-dose iodine intake-induced thyrotoxicosis due to long-term PVP-I gargling or other causes is necessary, even in individuals with no history of thyroid disease.

Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland.

Immune checkpoint inhibitors (ICIs) are used for various malignancies, although they frequently cause immune-related adverse events involving the thyroid gland (thyroid irAEs). We conducted a retrospective cohort study to elucidate thyroid function outcomes. Fifty of 639 patients who received PD-1 blockade therapy met criteria and were divided into the following groups: thyrotoxicosis with subsequent hypothyroidism (Toxic-Hypo, n = 21); thyrotoxicosis without subsequent hypothyroidism (Toxic, n = 9); and hypothyroidism without prior thyrotoxicosis (Hypo, n = 20). The Toxic-Hypo group developed thyroid irAEs earlier than the Toxic group (26 vs. 91 days; p < 0.001), and had higher serum free T4 levels (3.210 vs. 1.880 ng/dL; p = 0.011). In addition, positive anti-thyroglobulin antibodies (TgAbs) at thyroid irAE onset were more common in the Toxic-Hypo group (93.3%) than in the Toxic group (0.0%; p = 0.005) and Hypo group (44.4%; p = 0.007). The Toxic-Hypo group developed severe hypothyroidism and required larger levothyroxine (LT4) doses than the Hypo group (75 vs. 25 µg/day; p = 0.007). We predicted that patients with positive TgAbs who developed severe thyrotoxicosis within 4 weeks after the first ICI administration would develop subsequent hypothyroidism. We treated 4 such patients with prompt LT4 replacement, characterized by LT4 initiation after thyrotoxicosis improvement and quick dose titration. Their euthyroid state was successfully maintained, in contrast with patients receiving conventional replacement. In conclusion, rapid-onset severe thyrotoxicosis in patients with TgAbs correlated with a high likelihood of subsequent hypothyroidism. Accordingly, prompt LT4 replacement is suggested to prevent a severely hypothyroid state.

Concurrent Subacute Thyroiditis and Graves' Disease After COVID-19: A Case Report.

There are many reports of subacute thyroiditis (SAT) that occurred after the coronavirus disease 2019 (COVID-19), but no such case has been reported in Korea. Moreover, the simultaneous occurrence of SAT and Graves' disease (GD) is rare. Here, we describe a patient who developed SAT and GD after the second episode of COVID-19. A 27-year-old woman with no known history of thyroid disease presented with fever, upper respiratory tract symptoms, and painful neck swelling. Thyroid function tests revealed thyrotoxicosis, and thyroid ultrasound showed heterogeneous echogenicity of enlarged thyroid glands. Her initial clinical presentation was consistent with SAT after viral infection, with typical neck tenderness and spontaneous improvement of thyrotoxicosis without antithyroid drug use. However, this case had some atypical features, such as an elevated thyroid-stimulating immunoglobulin level, relapse of thyrotoxicosis in short-term follow-up, and increased Tc-99m pertechnetate uptake, suggesting the coexistence of GD. About two months after methimazole (15 mg/day) was prescribed, she was lost to follow up again. We report the first case of unusual co-occurrence of SAT and GD following COVID-19.

Recurrent hypokalemic paralysis in hypothyroidism.

Hypothyroidism, a commonly encountered thyroid disorder, usually manifests with readily recognizable typical features. However, an unusual presentation of a classic thyroid disorder may hinder accurate diagnosis in certain instances. One such rare initial presentation of hypothyroidism is recurrent hypokalemic paralysis, and existing reports in the literature are sparse. It has been more commonly reported in thyrotoxicosis. We report the case details and clinical outcomes of two middle-aged individuals (a 34-year-old male and a 37-year-old female) with recurrent episodes of hypokalemic paralysis. Their clinical examination revealed pure motor hyporeflexia quadriparesis with hypotonia and diminished deep tendon reflexes without any autonomic dysfunction. They had no significant previous medical history. Biochemical findings revealed hypokalemia in both cases (1.4 and 1.9 mEq/L, respectively) with elevated levels of thyroid­stimulating hormone and thyroid­related antibodies in both individuals, thus, confirming the diagnosis of autoimmune hypothyroidism. Immediate treatment with intravenous and oral potassium correction helped in the recovery. Thyroxine supplementation was considered a follow-up treatment, and for a one-year follow-up period there were no complaints of limb weakness reported in both individual.

Unique Presentation of Thyrotoxic Periodic Paralysis With Urticarial Dermographia.

Thyrotoxic periodic paralysis (TPP) is an acute complication of hyperthyroidism. Thyrotoxic periodic paralysis is treatable, and the management consists of potassium correction, beta-blockers, and antithyroid drug (ATD) therapy. While TPP is well described in the literature, we describe a case of TPP with urticarial dermographia (UD) that resolved with a short course of antihistamines while continuing ATD therapy. To the best of our knowledge, this is the first reported case of UD after methimazole (MMI) therapy in a TPP patient. A 25-year-old Cambodian active duty male with no significant past medical history presented to the emergency department with acute loss of lower extremity muscle tone with hypokalemia in the setting of previously undiagnosed Graves' disease (GD). He was started on MMI but within 2 weeks developed a rash consistent with UD. This was successfully treated with a second-generation antihistamine while continuing his MMI. Thyrotoxic periodic paralysis is primarily treated by controlling the underlying thyroid disease causing paralysis. Methimazole is commonly chosen as a treatment due to its rapid efficacy and long duration of action. However, adverse effects like UD can occur. Current recommendations are that minor cutaneous reactions can be treated with antihistamines for the management of Graves' disease. However, this case and others show that even moderate reactions can be managed in this manner. In a patient with TPP with UD after treatment with MMI, it is reasonable to attempt a trial of antihistamine before changing to another ATD.

Vitamin D inhibits bone loss in mice with thyrotoxicosis by activating the OPG/RANKL and Wnt/ß-catenin signaling pathways.

Objective: Vitamin D and thyroid hormones have crucial roles in bone metabolism. This study aims to explore the effects of vitamin D on bone metabolism in mice with thyrotoxicosis and its mechanisms. Methods: 12-week-old mice were randomly divided into 6 groups (6 mice/group), the control (CON) group, vitamin D (VD) group, low-dose LT4 (Low LT4) group, low-dose LT4+VD (Low LT4+VD) group, high-dose LT4 (High LT4) group, high-dose LT4+VD (High LT4+VD) group, LT4 was provided every day and vitamin D3 every other day for 12 weeks. Thyroid function, 25-hydroxy vitamin D, type I collagen carboxy-terminal peptide (CTX), and type I procollagen amino-terminal peptide were determined. In addition, microcomputed tomography, bone histology and histomorphometry, a three-point bending test, and the mRNA expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and ß-catenin in bone were conducted. Results: The BMD of lumbar vertebrae and femur decreased and the bone microstructure was destroyed significantly in thyrotoxicosis mice. Addition of vitamin D improved the BMD and bone microstructure only in the low LT4+VD group. Mice with thyrotoxicosis had a significantly higher level of CTX (P<0.05), which was decreased by treatment with vitamin D (P<0.05). The eroded surface per bone surface (Er. S/BS) of the cancellous bone and elongated surface/endocortical perimeter (Er. S/E Pm) of the cortical bone significantly increased in the Low LT4 and High LT4 groups (P<0.05). Treatment with vitamin D significantly decreased the Er. S/BS and Er. S/E Pm. But, treatment with vitamin D did not significantly improve the toughness and rigidity of bones. The ratio of OPG to RANKL and mRNA expression of ß-catenin in the Low LT4+VD group were higher than that in the Low LT4 group (P<0.05). Conclusion: In mice with thyrotoxicosis, treatment with vitamin D can inhibit bone resorption and improve the BMD and trabecular bone architecture by increasing the ratio of OPG to RANKL and upregulating the expression of Wnt/ß-catenin.

Thyrotoxicosis Due to Acute Suppurative Thyroiditis in a Pediatric Patient: A Case Report.

Acute suppurative thyroiditis is a rare and potentially life-threatening cause of thyroid inflammation requiring prompt recognition and management. There are few reported cases of thyrotoxicosis due to acute suppurative thyroiditis. We are reporting the case of a 9-year-old boy who presented to the emergency room with fevers, neck pain and swelling, night terrors, and emotional lability. He was hemodynamically stable with initial lab work remarkable for neutrophilia without leukocytosis, elevated inflammatory markers, and hyperthyroidism. Imaging of the neck revealed a heterogenous collection in the region of the left thyroid concerning for suppurative thyroiditis and adenitis. He was admitted to the hospital and initiated on intravenous antibiotics. Given lack of significant improvement in pain, he was taken to the operating room for drainage on hospital day 4 with remarkable clinical improvement in pain. He was discharged on oral antibiotics. Lab work obtained on postoperative day 15 showed resolution of hyperthyroidism and decreasing inflammatory markers. Subsequent imaging following resolution of the acute illness did not reveal any anatomic abnormality that may have predisposed him to developing acute suppurative thyroiditis. Thyrotoxicosis as a complication of acute suppurative thyroiditis is a rare occurrence, and is thought to be due to the release of preformed thyroid hormone from damaged thyroid follicles. The thyrotoxic state is often transient and resolves with appropriate management of acute suppurative thyroiditis. This complication is important to recognize, as failure to appropriately diagnose and treat acute suppurative thyroiditis can lead to poor outcomes, such as airway compromise and death.

Iatrogenic hyperthyroidism in primary congenital hypothyroidism: prevalence and predictive factors.

OBJECTIVES: Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4 dosage. Currently, information regarding iatrogenic hyperthyroidism and predictive factors for permanent hypothyroidism (P-CH) among Thai patients is lacking. The aim of this study is to determine the prevalence and factors for predicting iatrogenic hyperthyroidism at one month after LT4 initiation and for predicting P-CH in primary CH infants. METHODS: This retrospective cohort study involved 87 infants with primary CH. Patients were classified by thyroid status at one month after LT4 initiation. At 3 years, patients were reevaluated after LT4 cessation and assigned as P-CH or transient CH (T-CH). Differences between groups were analyzed. RESULTS: One month after LT4 initiation, 35.6% of patients were classified as having iatrogenic hyperthyroidism. An initial LT4 dose of 10.2 µg/kg/day (sensitivity 64.5%, specificity 71.4%) was a suitable cutoff value for predicting iatrogenic hyperthyroidism, wherein 55.6 and 21.6% of patients were treated with initial doses of ≥10.2 and <10.2 µg/kg/day, respectively (p=0.004). Initial LT4 dose was the only predictive factor for thyroid status after initial treatment. At reevaluation, 47.4% of patients were diagnosed with P-CH. LT4 dosage at 3 years of age was significantly higher in patients with P-CH (3.3 vs. 2.85 µg/kg/day, p=0.02) and the only relevant factor for predicting P-CH. CONCLUSIONS: Iatrogenic hyperthyroidism is common among infants with primary CH when treated with the recommended LT4 dosage. LT4 dose was the only factor for predicting iatrogenic hyperthyroidism after LT4 initiation and the diagnosis of P-CH.

Immune Related Adverse Events of the Thyroid - A Narrative Review.

Immune checkpoints are small molecules present on the cell surface of T-lymphocytes. They maintain self-tolerance and regulate the amplitude and duration of T-cell responses. Antagonism of immune checkpoints with monoclonal antibodies (immune checkpoint inhibitors) is a rapidly evolving field of anti-cancer immunotherapy and has become standard of care in management of many cancer subtypes. Immune checkpoint inhibition is an effective cancer treatment but can precipitate immune related adverse events (irAEs). Thyroid dysfunction is the most common endocrine irAE and can occur in up to 40% of treated patients. Both thyrotoxicosis and hypothyroidism occur. The clinical presentation and demographic associations of thyrotoxicosis compared to hypothyroidism suggest unique entities with different etiologies. Thyroid irAEs, particularly overt thyrotoxicosis, are associated with increased immune toxicity in other organ systems, but also with longer progression-free and overall survival. Polygenic risk scores using susceptibility loci associated with autoimmune thyroiditis predict development of checkpoint inhibitor associated irAEs, suggesting potentially shared mechanisms underpinning their development. Our review will provide an up-to-date summary of knowledge in the field of thyroid irAEs. Major focus will be directed toward pathogenesis (including genetic factors shared with autoimmune thyroid disease), demographic associations, clinical presentation and course, treatment, and the relationship with cancer outcomes.