Elevated Free Thyroxine Research Articles

6492 Novel compound heterozygous mutations in the SBP2 gene

Abstract Disclosure: H. Jeong: None. Mutations in the selenocysteine insertion sequence binding protein 2 gene (SECISBP2 also known as SBP2) result in a multisystemic disorder. A 4-year-old Korean girl presented with atypical thyroid function test result, characterized by normal TSH 2.13 μIU/mL, decreased T3 0.51 ng/mL, free T3(FT3) 1.71 (pg/mL), and elevated free thyroxine (FT4) 4.28 ng/dL. Additionally, she exhibited short stature below 2 standard deviations and delayed bone age. She has not yet begun speaking, and her waking ability commenced only recently. She conceived twins through natural pregnancy, but tragically, her twin sibling passed away in utero at 8 weeks of gestation.A targeted next-generation sequencing panel revealed compound heterozygous mutation in SBP2 gene (p.Arg120Ter/p.Arg672Ter) and in TPO gene (p.Glu413Gln).Her serum selenium level was relatively low,, easuring at 6.94 ng/dL. She underwent T3 supplementation and received a daily selenium supplement of 20mcg. Subsequently, her thyroid function tests normalized. Presentation: 6/2/2024

9396 Deciphering The Enigma: A Case Report On New-onset Graves Disease Presenting As Thyroid Storm In The First Trimester Of Pregnancy, Managed In The Intensive Care Setting

Abstract Disclosure: M. Zeb: None. S.W. Salari: None. A. Tiwari: None. A. Vadher: None. A. Dabaja: None. S. Kambhatla: None. Graves' disease, an autoimmune disorder characterized by hyperthyroidism, presents unique challenges when manifesting as thyroid storm during pregnancy. We report a case of a 27-year-old African American woman at 9 weeks gestation who presented with palpitations, agitation, and fever. On examination, she exhibited fever, tachycardia, tremors in hands, and mild bilateral exophthalmos. Thyroid function tests revealed markedly elevated free thyroxine and suppressed thyroid-stimulating hormone levels. Thyroid ultrasound confirmed diffuse thyroid enlargement with increased vascularity, consistent with Graves' disease. Pelvic ultrasound estimated the gestational age at 9 weeks and 2 days, with a serum β-hCG level of 135,037 mIU/mL. An electrocardiogram revealed sinus tachycardia, and a complete metabolic panel indicated mild hypokalemia. The Thyroid Stimulation Immunoglobulin (TSI) and Thyrotropin receptor antibodies were tested positive. The Burch-Warsofsky point score of 45, supported the diagnosis of thyroid storm. The patient received intensive care treatment including intravenous fluids, hydrocortisone, beta-blockers, Lugol’s iodine, propylthiouracil, and potassium replacement. Following treatment, thyroid function stabilized within 48 hours, and her hyperthyroid symptoms resolved. The patient was discharged on oral labetalol and propylthiouracil. Thyroid storm, characterized by severe manifestations of hyperthyroidism, is a rare but potentially life-threatening condition, especially during pregnancy. Prompt recognition and intervention are crucial due to associated maternal and fetal morbidity and mortality. A multidisciplinary approach, involving endocrinology, obstetrics, and critical care, is essential to optimize outcomes. The unique physiologic changes of pregnancy, such as increased thyroid hormone production and altered thyroid hormone-binding globulin levels, can complicate the diagnosis and management of hyperthyroidism. Our case underscores the importance of vigilance for thyroid dysfunction in pregnant women, even in the absence of prior thyroid disease. Additionally, the potential impact of hyperthyroidism and thyroid storm on pregnancy outcomes highlights the need for early recognition and intervention. Long-term management of Graves' disease during pregnancy may also require adjustment of antithyroid medication dosage and monitoring of thyroid function to maintain euthyroidism while minimizing fetal exposure to medication. Further research is warranted to refine diagnostic criteria, treatment protocols, and long-term management strategies for thyroid storm in pregnancy. Increased awareness among healthcare providers about the risks and management strategies for this rare but serious complication is also necessary. Presentation: 6/3/2024

Hypercalcaemic Crisis Associated with Hyperthyroidism: A Rare and Challenging Presentation

A 51-year-old female with a history of multinodular goitre presented with vomiting, abdominal discomfort, and generalized tiredness. Investigations revealed hypercalcemia (ionized calcium 1.41 mmol/L), hypokalaemia, suppressed parathyroid hormone, and significantly elevated free thyroxine (> 7.77 ng/dL) with a suppressed thyroid-stimulating hormone level consistent with hyperthyroidism. Further, the workup confirmed Graves’ disease as the underlying aetiology. Hyperthyroidism is occasionally associated with mild to moderate hypercalcemia, but severe hypercalcemia or hypercalcaemic crisis is an extremely rare complication. Prompt recognition and treatment are crucial to prevent life-threatening complications. The patient was treated with intravenous fluids, a low-calcium diet, zoledronic acid, carbimazole, and a beta-blocker, leading to improvement in her condition. This case highlights a rare occurrence of hypercalcaemic crisis in a patient with thyrotoxicosis due to Graves’ disease. Hyperthyroidism-induced hypercalcemia requires prompt recognition and multidisciplinary management involving endocrinologists, internists, and critical care specialists to prevent potentially life-threatening complications. Healthcare providers should consider the hypercalcaemic crisis in the differential diagnosis of hypercalcemia in the context of hyperthyroidism.

Thyroid psychosis: when your hormones take over your mind: a case report

IntroductionHyperthyroidism, characterized by excessive production of thyroid hormones, is a common endocrine disorder that affects various body systems. While most commonly recognized for its classic symptoms such as weight loss, tremors, and palpitations, it is important to acknowledge that hyperthyroidism can also lead to a rare but significant complication: psychosis. Psychosis in the context of hyperthyroidism refers to the presence of delusions, hallucinations, and disordered thinking, which can significantly impact an individual’s mental health and overall well-being.ObjectivesThis case report aims to describe a rare case of hyperthyroidism-related psychosis in a patient including the clinical presentation, diagnosis, and management. Additionally, we aim to increase awareness of and promote further research into this condition.MethodsWe present a comprehensive case report detailing the clinical course of a 29-year-old male patient with no previous medical or psychiatric history, who sought urgent psychiatric evaluation at the Razi Hospital La Manouba’s emergency department due to escalating symptoms of agitation and paranoia persisting for three days. The patient, identified as Mr. S.O., a Tunisian male, presented with severe agitation and paranoia necessitating the use of restraints upon admission to the psychiatric emergency department. The initial physical examination revealed no notable abnormalities, except for the presence of tachycardia, which was subsequently confirmed on an electrocardiogram, arousing suspicion of a primary psychiatric illness.ResultsWhile the standard blood workup yielded unremarkable findings, the endocrine workup revealed decreased levels of thyroid-stimulating hormone (TSH) and elevated free thyroxine (FT4). Further laboratory investigations demonstrated elevated anti-thyroid-stimulating hormone receptor antibodies, leading to the diagnosis of Graves’ disease. Collaborative consultation with an endocrinologist resulted in the initiation of a treatment regimen consisting of methimazole, propranolol, and risperidone. Notably, within three days of the initiated therapy, the patient exhibited significant improvement in terms of reduced agitation, coherent speech, and the development of self-reflection regarding the episode, ultimately leading to his discharge on the seventh day of hospitalization. This case report serves to highlight the complexity of psychiatric presentations associated with underlying endocrine disorders and underscores the importance of interdisciplinary collaboration in achieving optimal patient outcomes.ConclusionsWhile mental health factors play a significant role in the development of psychosis, it is essential to recognize that underlying medical conditions may also contribute to its onset or exacerbation.Disclosure of InterestNone Declared

Stress-Induced Graves Disease: Spontaneous Recovery After Stress Relief.

Emotional stress is a precipitating factor for Graves disease (GD). However, the influence of stress relief on the course of GD is unknown. Here, we present a series of patients diagnosed with stress-induced GD in whom stress relief alone led to remission of GD. We report on 11 patients in whom hyperthyroid symptoms started just after severe emotional stress. All patients had suppressed thyroid-stimulating hormone (TSH) levels and elevated free thyroxine (FT4; 22.2-49.5 pmol/L) and TSH-receptor antibody (TRAb; 0.57-40 U/L) levels and were subsequently diagnosed with stress-induced GD. However, all patients declined antithyroid drug treatment. Surprisingly, clinical and biochemical remission was observed in 9 out of 11 patients after 1 to 3 and 2 to 7 months of self-reported stress relief, respectively. Five patients showed long-lasting remission (median follow-up 2.3 years). In 4 patients, remission was initially achieved, but GD relapsed 1 to 4 years afterwards. In 2 patients, treatment with antithyroid drugs was initiated because of rapidly increasing FT4 levels. Baseline FT4 and TRAb levels tended to be higher in patients who did not achieve remission. Furthermore, patients without long-lasting remission were more frequently known to have prior thyroid disease. We report on a series of patients with stress-induced GD in whom stress relief alone led to remission of GD (thus without antithyroid drugs). This may indicate that clinicians could consider stopping antithyroid drug treatment or at least shortening the treatment period after stress relief in patients with stress-induced GD.

Approach to the Patient With Raised Thyroid Hormones and Nonsuppressed TSH.

Measurement of free thyroid hormones (THs) and thyrotropin (TSH) using automated immunoassays is central to the diagnosis of thyroid dysfunction. Using illustrative cases, we describe a diagnostic approach to discordant thyroid function tests, focusing on entities causing elevated free thyroxine and/or free triiodothyronine measurements with nonsuppressed TSH levels. Different types of analytical interference (eg, abnormal thyroid hormone binding proteins, antibodies to iodothyronines or TSH, heterophile antibodies, biotin) or disorders (eg, resistance to thyroid hormone β or α, monocarboxylate transporter 8 or selenoprotein deficiency, TSH-secreting pituitary tumor) that can cause this biochemical pattern will be considered. We show that a structured approach, combining clinical assessment with additional laboratory investigations to exclude assay artifact, followed by genetic testing or specialized imaging, can establish a correct diagnosis, potentially preventing unnecessary investigation or inappropriate therapy.

SAT538 Thyrotoxicosis in the Setting of Metastatic Poorly Differentiated Thyroid Carcinoma, a Marker of Disease Progression?

Abstract Disclosure: B.L. Chang: None. M.A. Fernandez: None. K.M. Shikuma Lee: None. Background: Thyrotoxicosis is a rare manifestation of thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) causing thyrotoxicosis has even more rarely been reported. Here, we report a case of PDTC with thyrotoxicosis developing in a previously euthyroid individual with longstanding untreated follicular neoplasm. Clinical Case: A 79-year-old veteran presented to routine endocrine follow up with new symptoms of thyrotoxicosis. Although previously euthyroid, the evaluation revealed new findings of low serum thyrotropin (TSH) (<0.01 uIU/mL, n=0.34 – 5.60 uIU/mL), elevated free thyroxine (FT4) (2.6 ng/dL, n=0.58 – 1.64 ng/dL), and high total T3 (TT3) levels (223 ng/dL, n=76 – 181 ng/dL). Thyroid stimulating immunoglobulin antibodies (TSI) were positive (214, n<140). Patient has a nine-year history of a fine needle aspiration (FNA) of a large right-sided thyroid nodule with cytology suspicious for follicular neoplasm but declined surgical removal. Thyroid uptake and scan showed heterogeneous uptake throughout the right lobe with a relative photopenic region centrally and spots of more increased activity in areas within the right lobe. The left thyroid lobe showed uniformly low uptake. PET-CT evaluation confirmed spotty FDG-avid areas within the right thyroid mass but did not show other areas of hyperactivity. Methimazole was started with clinical and biochemical improvement. Patient underwent total thyroidectomy, and histopathologic examination showed PDTC with extensive angioinvasion involving the majority of the right thyroid lobe with the left lobe containing a mix of benign thyroid tissue and PDTC fragments. Areas of hyperintensity on the uptake scan correlated to pathological PDTC locations within the right lobe. Within three weeks of thyroidectomy, patient developed recurrent hyperthyroidism. Laboratory studies showed low TSH (0.04 uIU/mL) and elevated FT4 (2 ng/dL). In contrast to pre-operative studies, repeat TSI was below the reference range. Levothyroxine (LT4) was held in anticipation of radioactive iodine therapy, but four weeks later the TSH remained suppressed. 131I was administered which showed accumulation within small thyroid remnants and a single left level three 131I-avid lymph node without other metastases. Following 131I treatment, patient returned to a euthyroid state on standard LT4. Conclusion: Hyperthyroidism has rarely been associated with PDTC, although previous reports have linked more aggressive, multifocal, and locally invasive thyroid cancers to concurrent Graves’ disease or productive bulky metastatic disease. Even without bulky metastatic disease, clinicians should be aware that hyperproductivity may indicate development of autoimmune thyrotoxicosis within PDTC. Presentation Date: Saturday, June 17, 2023

THU667 Severe Hypothyroidism With Paradoxically Elevated Direct Free T4 Due To Anti-thyroxine Antibodies

Abstract Disclosure: O. Magvanjav: None. M.J. McPhaul: None. I. Choucair: None. E. Holt: None. Introduction Laboratory interference may cause abnormal thyroid function test (TFT) results, leading to misdiagnosis and inappropriate patient care. There are several major types of interference. Here, we describe a hypothyroid patient with an elevated thyroid stimulating hormone (TSH) level with a paradoxically elevated direct free thyroxine (FT4) level caused by interference from anti-thyroxine autoantibodies (THAAB). Clinical Case Our patient is a 38-year-old man who was found to have markedly elevated TSH and FT4 levels during an outpatient workup for Lyme disease. The patient was overall well-appearing but reported some symptoms suggestive of hypothyroidism including excessive fatigue, non-pitting edema, and dry skin. Physical exam was notable elevated blood pressure (systolic blood pressure of 150 mmHg and diastolic blood pressure of 95 mmHg), normal temperature, normal heart rate (72 bpm), regular heart rhythm, and normal body mass index. He had non-tender thyromegaly without nodules, non-pitting edema of bilateral hands and legs, decreased leg hair over bilateral shins, and coarse, dry skin of his hands. Initial TSH level was >150 mIU/ml, with a paradoxically elevated direct FT4 of 10 ng/dl (normal range 0.80-1.70 ng/dL). The FT4 level by equilibrium dialysis was <0.2 ng/dl. Outside laboratory testing to eliminate the effect of heterophile antibodies using two different assays again returned with elevated FT4 levels. Screening for macro TSH confirmed the markedly elevated TSH level. Further investigations at a second outside laboratory revealed that he had THAAB. A repeat FT4 level by dialysis confirmed the markedly low FT4 levels. He was empirically started on low dose levothyroxine and after increasing the levothyroxine dose, he showed improvement in clinical symptoms and the expected decline in TSH. Conclusions Here we present a rare case of THAAB that caused laboratory interference during thyroid function testing, leading to falsely elevated thyroid hormone levels on immunoassays. This case shows the importance of suspecting interference when there is a discrepancy between clinical symptoms and laboratory results or between results obtained from different testing methods. Our patient likely had a genetic predilection for autoimmunity, and Lyme disease is a known trigger for various autoimmune conditions. Our case also emphasizes the importance of taking a systematic approach to investigate the cause of the laboratory interference. This will help prevent misdiagnosis of thyroid disorders that may lead to additional unnecessary testing and treatment. Presentation: Thursday, June 15, 2023

Elevated Free Thyroxine Levels Might Alter the Effect of the Lipid Profile on Insulin Resistance in Type 2 Diabetes Mellitus.

Previous studies have shown that hyperthyroidism is associated with heightened insulin resistance and dyslipidemia. Therefore, in this study, we aim to explore the relationship between elevated thyroid hormone levels and the lipid profile in insulin resistance in patients with type 2 diabetes mellitus (T2DM) with hyperthyroidism. A total of 177 participants were included and grouped according to diagnosis. The serum test results demonstrated that free thyroxine (FT4) increased the insulin resistance index (HOMA-IR) by positively correlating with triglyceride (TG) levels (p = 0.005, r2 = 0.35). In patients with T2DM with hyperthyroidism, the decreasing high-density lipoprotein levels showed an association with HOMA-IR (p = 0.005). Among all the patients, with different levels of FT4, the areas under the ROC curve (AUCs) of the TG level, TG/high-density lipoprotein ratio, and HOMA-IR were 0.620 (95% CI: 0.536 to 0.698), 0.614 (95% CI: 0.530 to 0.692), and 0.722 (95% CI: 0.645 to 0.791), respectively. Our results suggest that elevated FT4 levels due to hyperthyroidism could alter the association with the lipid profile and insulin resistance in patients with T2DM. We also suggest that among all the included patients with T2DM, irrespective of the presence of hyperthyroidism, FT4 levels are positively correlated with insulin resistance.

Diagnosis ofResistance to Thyroid Hormone due toa Rare Mutation inthe Thyroid Hormone Receptor Beta Gene ina Patient Previously Presumed to Have Graves' Disease.

Clinicians may confuse an impaired sensitivity to thyroid hormone with hyperthyroidism and offer an inappropriate treatment. We report a diagnosis of resistance to thyroid hormone (RTH) caused by a rare mutation in the thyroid hormone receptor beta gene in a patient previously presumed to have Graves' disease. We have found only one published case of a novel point mutation, c.749T>C (p.Ile250Thr variant) associated with 50% reduction in thyroid hormone receptor binding affinity for triiodothyronine in the I250T mutant; it was found in this patient. A 66-year-old male veteran, with a history of non-ischemic cardiomyopathy and arrhythmias, was referred by a cardiologist with concerns for a possible thyrotropin (TSH) adenoma on account of elevated TSH and free thyroxine (FT4) levels. Pituitary imaging was negative. He was previously treated with radioiodine for presumptive Graves' disease in the civilian sector. Examination revealed a goiter with no nodules. Repeat TSH and FT4 levels were elevated and also free triiodothyronine (FT3) and reverse triiodothyronine. These findings and other test results were consistent with RTH, which was confirmed by genetic testing. Mutation analysis showed the patient to be heterozygous for the p.Ile250Thr variant. He later developed hypothyroidism. Resistance to thyroid hormone can be misdiagnosed as hyperthyroidism with consequent inappropriate treatment. Treatment is not needed in most RTH-beta patients. Thyroid ablation should generally be avoided. Clinicians must be cautious whenever they encounter concurrent elevation of TSH, FT4, and FT3. This RTH-beta patient has a rare I250T mutant of the thyroid hormone receptor beta gene, the second reported case in the literature.

Thyrotoxic periodic paralysis in a Caucasian man without identifiable genetic predisposition: a case report

BackgroundThyrotoxic periodic paralysis (TPP) is a rare condition characterized by muscle paralysis, thyrotoxicosis, and hypokalemia. It presents with paralysis of both proximal and distal musculature in upper and lower limbs and may affect respiratory musculature and the cardiac conduction system. Early diagnosis is essential, as the condition is potentially reversible by oral or intravenous potassium treatment, leading to rapid resolution without lasting weakness. Overlooking the diagnosis may result in respiratory failure and cardiac arrhythmias including QT prolongation, Torsades de points, and ventricular arrhythmias.Case presentationA 19-year-old Caucasian man was admitted acutely with paralysis in upper and lower limbs and tachycardia. Over several months, he had experienced anxiousness, sweating more than usual, had daily palpitations, shortness of breath on exertion, and loose stools, and had lost 21 kg over the last year. Initial blood gas showed very low potassium of 1.4 mM, and blood tests showed decreased Thyroid-stimulating hormone (TSH) < 0.01 × 10− 3 IU/L, elevated free thyroxine (fT4) of 63.5 pM (reference interval (RI): 12.0–22.0 pM), and elevated total triiodothyronine (T3) of 8.2 nM (RI: 1.0–2.6 nM). He was diagnosed with TPP and treated with liquid oral potassium chloride (30 mmol every 30 minutes) and propylthiouracil (initial dose of 400 mg followed by 200 mg three times daily). TSH-receptor antibodies (TRAB) and thyroid-peroxidase antibodies (TPO-ab) were highly elevated. Thyroid ultrasound showed a normal-sized gland and color Doppler sonography showed increased vascularity throughout the gland, compatible with Graves’ disease. He was discharged on day 4 with a normal potassium level and followed in the outpatient clinic where he received standard care for Graves’ disease. Genetic testing using whole-genome sequencing found no genetic variants in genes previously associated with TPP.ConclusionTPP is very rare in Caucasians but more often affects young men in East Asian populations. The case presents a Caucasian man with TPP where genetic testing of CACNA1S, KCNJ18, SCN4A, KCNJ2, KCNE3, and ABCC8 shows no pathogenic variants in genes previously associated with TPP.

Subacute Thyroiditis Developing Within 2 Days of Vaccination Against COVID-19 with BNT162b2 mRNA

A 32-year-old woman presented to the outpatient clinic with persistent fever, anterior neck pain, and palpitations over the past week which developed 2 days after she had received the first dose of the Pfizer/BioNTech SARS-CoV-2 mRNA vaccine. On examination, the patient’s heart rate was 140 beats per minute and the thyroid gland was tender on palpation. Laboratory studies showed a low serum TSH level with elevated free thyroxine. Thyroid ultrasound revealed low-echoic lesions compatible with the site of tenderness. The patient was diagnosed with subacute thyroiditis and treatment was initiated with acetaminophen and propranolol, which resulted in symptom resolution within 2 weeks. Clinicians should be aware that subacute thyroiditis may occur within a few days following COVID-19 vaccination, especially in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations, because differentiating them from early non-specific adverse reactions can be challenging.

Subacute Thyroiditis Developing Within 2 Days of Vaccination Against COVID-19 with BNT162b2 mRNA.

Cases of subacute thyroiditis after vaccination, including against COVID-19, have been increasingly reported.Subacute thyroiditis should be considered in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations after COVID-19 vaccination because these can be diagnostic clues.It is important to note that this condition can occur as early as a few days after vaccination, in order to avoid diagnostic pitfalls.

PSAT239 Pregnant Patient With a History of Methimazole-Induced Agranulocytosis Presenting With Hyperthyroidism: A Case Report

Abstract Background Pregnancy has a profound impact on the thyroid gland and its function. Severe thyrotoxicosis can lead to many complications and endanger the mother or fetus. Antithyroid drug (ATD), at its lowest possible dose, should be given. However, one of the complications of treatment include agranulocytosis which is a rare but serious allergic event with a prevalence of 0.1 to 0.5 percent. Thus, alternative treatment should be prescribed because a cross-reaction between ATDs was observed in 15.2% of patients in a study. Insufficient data is available regarding the use of these medications in pregnant patients with history of drug-induced adverse reactions. There are other feasible alternative treatments but are contraindicated in pregnancy. Case We report a 29-year old patient gravida 5 para 4 at 10 weeks age of gestation at the time of consult presenting with palpitations. She is a known case of Graves’ disease for 7 years and maintained on Methimazole. She was admitted a year prior consult as a case of impending thyroid storm; Methimazole-induced agranulocytosis. Initially, maintained on Lithium but shifted back to Methimazole without a physician's advice and later on, discontinued the medication upon knowledge of pregnancy. She presented on her first trimester of pregnancy with palpitations and elevated free thyroxine (T4) at 71.29 pM (normal range: 11-24 pM). She was started on Propylthiouracil 50 mg/tablet 1 tablet three times a day. On her second trimester, no reported symptoms of hyperthyroidism and/or agranulocytosis such as fever or sore throat. Thyroidectomy was offered at this time explaining the risks and benefits but she strongly refused. Free T4 was then maintained at a value slightly above the upper normal limit. Propylthiouracil was also shifted to Methimazole 5 mg/tablet 1 tablet once daily and revised to 1 tablet every other day on the third trimester of pregnancy. Delivery was uneventful and the newborn was evaluated by a pediatrician with unremarkable findings. Four weeks postpartum, no noted symptoms of hyperthyroidism and/or agranulocytosis. Free T4 was noted within the normal range at 18.84 pM. Alternative treatment was offered due to the risk of ATD-induced agranulocytosis. Conclusion Hyperthyroidism in pregnancy is associated with a variety of complications for the mother and fetus. Three effective treatment options include ATD, thyroidectomy or RAI therapy. But, not all are relatively safe for pregnancy. In initiating ATD, cross-reaction between medications should be considered especially for patients with history of adverse reaction, such as agranulocytosis, which can be life-threatening. However, there are limited studies in the management of this specific case. Treating physician and patient should discuss each of the options, including the benefits, drawbacks and side effects. Keywords: Hyperthyroidism, Graves’ disease, Pregnancy, Agranulocytosis Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

RF35 | PSAT304 A Case of COVID-19 Infection; COVID-19 mRNA-Based Vaccine Induced Human Anti-Mouse Antibodies (HAMA) Interfering With TSH Testing

Abstract A 71-year-old male presented to the endocrine clinic for evaluation of hypothyroidism which has recently been difficult for his primary care physician to control. He initially developed hypothyroidism in 1990 after neck radiation for squamous cell carcinoma of his sternocleidomastoid muscle. He was previously controlled for many years on levothyroxine 150mcg daily with TSH readings in the normal reference range. Patient was infected with COVID-19 in 2020 and was hospitalized for 10 days. He was treated with 5 days of Remdesivir and 10 days of Decadron. 6 months after the infection he received mRNA COVID-19 vaccination. Upon his first visit to the endocrine clinic post COVID-19 infection and vaccination, his TSH was elevated at 90 uIU/mL with a free thyroxine that was elevated at 1.8 ng/dL even after multiple attempts by his primary care physician to increase his Levothyroxine which was up to 225 mcg daily before he was referred to endocrinology. He is compliant with his levothyroxine and takes it on an empty stomach first thing in the morning without any of his other medications. He is not taking iron supplements, biotin or any other supplements or new medications. TSH values had been normal 1 month prior to his COVID-19 infection and was first noted to be abnormal 8 months after his COVID-19 infection and 2 months after his mRNA COVID-19 vaccine. There was no TSH drawn between when he had COVID-19 and when he received his vaccine. It was suspected that he may have a factitious elevation in his TSH due to antibody interference. Labs were drawn for a TSH with human anti-mouse antibodies (HAMA) treatment which resulted with a markedly suppressed TSH at 0.007 uIU/mL with an elevated free thyroxine of 1.94 ng/dL. HAMA antibodies came back elevated at 552 ng/mL. Reference Klee, G., 2000. Human Anti-Mouse Antibodies. Archives of Pathology &amp; Laboratory Medicine, 124(6), pp.921-923. Koshida, S., Asanuma, K., Kuribayashi, K., Goto, M., Tsuji, N., Kobayashi, D., Tanaka, M. and Watanabe, N., 2010. Prevalence of human anti-mouse antibodies (HAMAs) in routine examinations. Clinica Chimica Acta, 411(5-6), pp.391-394. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.

RF23 | PSAT300 The Curious Case of Abnormal Thyroid Function Tests: Think Streptavidin Interference

Abstract Interpretation of abnormal thyroid function tests (TFTs) is routine in endocrine practice. However, when there is a discrepancy between biochemical parameters and the clinical picture, sleuthing is necessary to provide appropriate care.A 34-year-old woman was evaluated by an outside endocrine clinic for abnormal TFTs in the setting of worsening anxiety, night sweats, and menstrual irregularities. These showed elevated free thyroxine (FT4) levels (7.3; ref: 0.9-1.7 ng/dL), free triiodothyronine (FT3) levels (13.9; ref: 2.3-4.1 pg/mL) and total triiodothyronine (T3) (186; ref: 94-170 ng/dL) with normal TSH (0.65; ref: 0.27-4.20 mIU/L), negative microsomal and thyroid receptor antibodies. She denied use of contraceptives, biotin, lithium, glucocorticoids, prior radiation, or recent intravenous contrast. Mother and maternal aunt had unspecified thyroid disease. No physical signs of overt hyperthyroidism/hypothyroidism were noted. Our workup also showed elevated FT4 (1.8 ng/dL), FT3 (13.3 pg/mL), total thyroxine (T4) (24.8; ref: 5.5-10.2 µg/dL), T3 (&amp;gt;651; ref: 79-165 ng/dL), normal TSH (0.71; ref: 0.4-5.5 mIU/L), and normal gonadotropin alpha subunit; ultrasound showed no nodules nor evidence of thyroiditis. FT4 by equilibrium dialysis and liquid chromatography-mass spectrometry was normal (1.3; ref: 0.8-2.0 ng/dL). Human anti-mouse antibodies (HAMA) treated TSH was within normal limits (1.4; ref: 0.4-4.5 mIU/L; Siemens). Leading differential diagnosis was initially thyroid hormone resistance; however subsequent labs, done by PCP for non-specific symptoms, revealed a suppressed parathyroid hormone (PTH) (&amp;lt;6; ref 15-65 pg/mL) with normal serum calcium levels. Given no clinical correlate, lab interference was considered. All the testing, with the exception of the FT4 by mass spectrometry and HAMA TSH, were analyzed utilizing Roche Diagnostics (electrochemiluminescent immunoassays). To evaluate vendor-specific interferences, labs were analyzed utilizing Siemens (chemiluminescent immunoassay) which showed normal T4, T3, FT3, and PTH levels. Unlike the Siemens assays, Roche depends on the formation of a biotin-streptavidin complex during measurement and a ruthenium complex to produce a signal. HAMA and polyethylene glycol treatment also returned differing results from untreated samples possibly indicating the interference was a heterophilic antibody to an unknown target. An investigation by Roche Diagnostics showed evidence of streptavidin antibodies. Streptavidin is a common reagent in endocrine assays. The endogenous streptavidin antibody produces an unintended competition between streptavidin-biotin and streptavidin-antibody in the assay; resulting in falsely-low results for sandwich assays (e.g. PTH) and falsely-high results for competitive assays (e.g. FT3 and T4). The impact to the individual analyte is variable due to assay formulation (e.g. TSH).Interference from anti-streptavidin antibodies is a rare phenomenon and may cause unnecessary diagnostics or treatment. Analytical interference should be considered when clinically suspicious of results, and lab consultation is recommended. The patient was advised to obtain a Medic-Alert bracelet. She was also provided a letter detailing the findings so that providers may consult the laboratory prior to testing. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m.

Delayed Release of Amiodarone Causing Late-Onset Thyrotoxicosis

Introduction: Amiodarone is an antiarrhythmic medication associated with a wide range of adverse effects, including thyroid dysfunction.1 Thyrotoxicosis without underlying Graves' disease or nodules is classified as Type II, or destructive, amiodarone-induced thyrotoxicosis (AIT).2 However, few cases have been reported in whom AIT occurs months after cessation of medication use. We describe a case of late-onset Type II AIT, diagnosed in the setting of atrial fibrillation (AF), 10 months after last known dose of amiodarone. Description of the Case: A 51-year-old man presented with palpitations and an electrocardiogram showing AF with rapid ventricular response. His history was notable for a diagnosis of AF, treated with ablation and multiple courses of amiodarone, most recently 1 year prior with a cumulative dose of 22.4 g for 12 weeks. Serum laboratory tests showed newly suppressed thyroid-stimulating hormone <0.02 (0.3–4.7 mcIU/mL) and elevated free thyroxine 1.9 (0.8–1.7 ng/dL). Thyroid autoantibodies to thyroid peroxidase and thyrotropin receptor and thyroid-stimulating immunoglobulins were absent. He had no recent exposure to biotin or iodinated contrast and reported no recent viral illness or neck pain. He had a 9 kg weight loss in the preceding few months secondary to decreased appetite. Family history was significant for mother and nephew with autoimmune thyroid disease. Thyroid ultrasonography showed no nodules. An iodine-123 uptake scan showed homogeneous bilateral decreased uptake most consistent with destructive thyroiditis. Methimazole treatment, started empirically at presentation, was discontinued. Thyroid function tests normalized within 3 months with no therapy needed. Discussion: Delayed-onset AIT may occur after cessation of amiodarone therapy. To our knowledge, only one case series of eight patients has been reported in whom late-onset thyrotoxicosis occurred after amiodarone cessation.3 Amiodarone contains a significant amount of iodine and releases about 100 to 300 times of the recommended daily intake. It is a lipophilic complex primarily stored within adipose tissue, with a long half-life of up to 100 days. Our patient's rapid weight loss may have contributed to a delayed release of amiodarone from lipid stores, thereby triggering Type II AIT. This case emphasizes the importance of considering AIT in all patients with history of amiodarone use, even months after cessation of therapy, when supported by presentation and diagnostic tests. Patient Consent: Authors have received and archived patient consent for video recording/publication in advance of video recording of procedure. No competing financial interests exist for any of the authors. Runtime of video: 4 mins 12 secs

Thyroidectomy and uncontrolled graves' disease - Multidisciplinary approach prevents unnecessary cancellation.

Dear Editor, Thyroidectomy is the definitive treatment for thyrotoxicosis for patients resistant to medical treatment and performed preferably when the patient is euthyroid.[1] Sometimes it may not be possible to render a patient euthyroid for various reasons leading to postponement or deferment of surgery.[2] A 35-year-old woman, was suffering from Graves’ disease, confirmed by a low thyroid-stimulating hormone (<0.005 miliunits/L), markedly elevated free thyroxine (>100 nanograms/dL), and positive thyroid receptor antibodies. Thionamide (carbimazole) therapy was started to lower the circulating thyroid hormone levels and beta-blockers added to reduce her hyper-adrenergic symptoms. She developed adverse drug effects resulting in agranulocytosis which necessitated discontinuing thionamide therapy. A multidisciplinary team consisting of an endocrinologist, endocrine surgeon, and anaesthetist was convened and a consensus view emerged for urgent total thyroidectomy. In preparation for surgery Lugol’s iodine and oral propranolol 20 mg 8 hourly administered to control tachycardia. Intravenous hydrocortisone 100 mg 8 hourly was started 1 week prior to planned operation to reduce peripheral conversion of free thyroxine to free triiodothyronine. General anaesthesia was administered with target-controlled infusion (TCI) of propofol and remifentanil with intubating dose of atracurium. Neural integrity monitor (NIM) electromyogram tracheal tube was used for intraoperative recurrent laryngeal nerve function monitoring. No further dose of atracurium was used. Anaesthesia was maintained with total intravenous anaesthesia (TIVA) using TCI devices and depth of anaesthesia was monitored with bispectral index (BIS monitor). Total thyroidectomy with parathyroid preservation was uneventful. After a brief observation in the post-anaesthesia recovery unit, she was transferred to the high dependency unit for monitoring. The postoperative course was complicated by severe hypocalcaemia (0.82 mg/dL) due to transient postsurgical hypoparathyroidism. This was confirmed by inappropriately normal parathyroid hormone levels post-surgery despite severe hypocalcaemia. Prolonged and severe stimulation of thyroid hormone is known to induce a high bone turnover state described as thyrotoxic osteodystrophy.[34] The high incidence of hypocalcaemia after thyroidectomy in thyrotoxic patients suggests that rapid loss and sudden removal of T3 and T4 hormone stimulation and inadequate parathyroid hormone response resulting in transient post-thyroidectomy hypocalcaemia. The calcium levels stabilized over the next 3 days with intravenous calcium replacement; subsequently, she was discharged with oral calcium and vitamin D supplements. Thyroidectomy may be the last option in some patients with Graves’ thyrotoxicosis refractory to medical treatment who cannot be optimized by medical treatment. A multidisciplinary team approach may help in appropriate preparation of patients prior to thyroidectomy avoiding unnecessary cancellation or postponement of surgery. Close postoperative monitoring of serum-ionized calcium is also recommended. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Association of subtle alterations in thyroid function with presarcopenia in patients with type 2 diabetes mellitus.

ABSTRACTAims/IntroductionTo investigate the association of subtle alterations in thyroid function with presarcopenia among patients with type 2 diabetes mellitus.Materials and MethodsA total of 1,865 adult patients with type 2 diabetes mellitus were enrolled in this cross‐sectional study, excluding patients with overt thyroid dysfunction. Skeletal muscle mass measured by dual energy X‐ray absorptiometry was used to assess presarcopenia. Logistic regression models were used to estimate the effects of thyroid hormones on presarcopenia, and subgroup analyses were carried out in different strata of age, sex and body mass index, respectively.ResultsCompared with the euthyroid group (Euthy), the subclinical hyperthyroidism group had an increased odds of presarcopenia (multivariate‐adjusted odds ratio 1.99, 95% confidence interval 1.09–3.63), but the subclinical hypothyroidism group did not (P > 0.05). In the subclinical hyperthyroidism group, age and body mass index <24 kg/m2 were independent risk factors for presarcopenia. In the overall Euthy group, an increased odds of presarcopenia was correlated with the elevated free thyroxine : free triiodothyronine ratio (all P for trend <0.05), whereas not with increment in free triiodothyronine level (P for trend >0.05). Additionally, in Euthy subgroup analyses stratified by middle‐age, sex and body mass index, a similar association was noted (all P for trend <0.05), but not in the older‐aged patients (P for trend >0.05).ConclusionsSubclinical hyperthyroidism was an independent risk factor for presarcopenia in patients with type 2 diabetes mellitus, but subclinical hypothyroidism was not. In the Euthy group with type 2 diabetes mellitus, a high free thyroxine : free triiodothyronine ratio was a good index of presarcopenia in addition to older age.

Meeting Program and Abstracts

Graves' disease is an autoimmune condition characterized by hyperthyroidism due to higher levels of circulating autoantibodies that bind to and activate the thyrotropin receptors (TSH receptors) on the surface of thyroid follicular cells. We report a unique case of Graves' disease after the cytokine surge due to an infection with COVID-19. We present a case of a 45-year-old male with a past medical history of hypertension who developed graves' disease after being diagnosed with COVID-19, a highly infectious viral disease caused by SARS- COV 2. Physical examinations showed, patient to be tachycardiac, with an irregular pulse of 155 beats per minute. The patient had a mild resting bilateral hand tremor but did not have any sign of Graves' ophthalmopathy or dermopathy. Electrocardiogram tracing showed the heart rhythm in atrial fibrillation, and the Burch-Wartofsky Point Scale indicated a score of 25 reflecting an impending thyroid storm. Laboratory work-up conducted on the same day showed an undetectable TSH level with elevated free thyroxine (FT4) and free triiodothyronine (FT3). The patient was then started on medical therapy with Propranolol and Methimazole. This is a case of COVID-19 followed by graves hyperthyroidism. This case raises the possibility of triggering of autoimmunity due to cytokine surge seen in genetically susceptible COVID-19 patients. Hence one needs to recognize and treat the autoimmune conditions that might be seen in COVID-19 patients.