scholarly journals MON-478 Impaired Sensitivity to Thyroid Hormone - A Diagnostic and Therapeutic Challenge

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jorge Pedro ◽  
Vanessa Gorito ◽  
Cristina Ferreras ◽  
Ferreira João Silva Maria ◽  
Sofia Ferreira ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
Thyroid Function Tests ◽  
Pediatric Endocrinology ◽  
Free T4 ◽  
Peripheral Tissues ◽  
Free T3 ◽  
Function Tests ◽  
Trh Stimulation ◽  
History Of

Abstract Background: Impaired sensitivity to thyroid hormone refers to any process that negatively affects its action, including defects in its transport, metabolism and action on the receptor. Resistance to thyroid hormone due to beta-receptor mutations (RTH-beta) is the most common form of this entity and is characterized by reduced response of peripheral tissues to the action of thyroid hormone. The genetic variability of cofactors involved in the action of thyroid hormone explains the heterogeneity of resistance among affected individuals. Generally, patients with this disorder, have increased levels of free T4 and free T3 in association with normal or high TSH. Clinical case: 11-year-old boy, with personal history of Attention-deficit/hyperactivity disorder (ADHD). A pediatric endocrinology consultation was requested to evaluate abnormalities in his thyroid function tests. A few months earlier, his father was referred to endocrinology consultation because of thyroid function tests abnormalities: TSH - 3.01 μIU / mL (N: 0.35 - 4.94); Free T4 1.7 ng / dL (N: 0.7-1.48); Free T3 4.77 pg / mL (N: 1.71-3.71). Initially, two diagnostic hypotheses were considered: central hyperthyroidism or impaired sensitivity to thyroid hormone. The adult underwent pituitary magnetic resonance, which raised the hypothesis of a pituitary microadenoma, and TRH stimulation test, whose result was strongly suggestive of the second diagnostic possibility. A genetic study was requested and the presence of the c700 G> A variant (p. Ala 324 trh) in the THRB gene was identified, which confirmed the most likely hypothesis. At the time of the pediatric endocrinology consultation, the 11-year-old boy had the results of his lab tests: TSH - 6.67 μIU / mL (N: 0.35 - 5); T4L 2.27 ng / dL (N: 0.88-1.58); T3L 7.79 pg / mL (N: 2-4.20). Given his perfect height and weight evolution and the absence of symptoms suggestive of hypo or hyperthyroidism, it was decided not to start any medication, keeping only periodic surveillance. Conclusion: This case exemplifies unusual thyroid function tests. This discordance between serum thyroid hormone and TSH concentrations should raise the possibility of impaired sensitivity to thyroid hormone. In this condition, patients may present with symptoms of hypo or hyperthyroidism and the etiology of thyroid function tests abnormalities are not easily recognized. This can lead to misdiagnosis and consequently unnecessary treatment.

scholarly journals MON-481 Remarkable Euthyroid Hyperthyroxinemia Mistaken for Thyrotoxicosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Annavi Baghel ◽  
Joshua D Maier
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
Clinical Status ◽  
Thyroid Function Tests ◽  
Thyroid Disorder ◽  
Diagnostic Challenge ◽  
Free T4 ◽  
Free T3 ◽  
History Of ◽  
Euthyroid Hyperthyroxinemia

Abstract CLINICAL CASE A 46 year old caucasian female with past medical history of menorrhagia was referred from primary care for evaluation of thyrotoxicosis. Thyroid function was assessed in the context of menometrorrhagia. She did not have any history of thyroid disorder or abnormal thyroid function tests. Per outside records, recent labs demonstrated TSH 0.88 uIU/mL (0.36-3.74), Free T4 > 8.00 ng/dL (0.76-1.46), Free T3 2.9 pg/mL (2.18-3.98). All other labs were within normal limits. Thyroid ultrasound revealed normal parenchyma and volume. She did not take any medications or supplements including biotin. She denied heat intolerance, anxiety, palpitations, dyspnea, tremors, hyperdefecation, or change in hair, skin, or mood. No epiphora, diplopia, or eye irritation was reported. Her father had been diagnosed with hyperthyroidism, mother with hypothyroidism. Repeat labs at our visit revealed normal TSH of 1.05 uIU/mL (0.358- 3.74), normal Free T3 2.58 pg/mL (2.18- 3.98), normal Total T3 136 ng/dL (80-200), elevated Free T4 >8.00 ng/dL (0.76-1.46) and elevated Total T4 11.6 ug/dL (4.5-10.5). These lab values were not consistent with patient’s euthyroid clinical status, prompting assessment of Free T4 by dialysis, normal at 1.5 ng/dL (0.9-2.2) and T3 uptake, high at 40% (24-39%). This picture was consistent with Familial Dysalbuminemic Hyperthyroxenemia (FDH). The decision was made not to treat the patient with anti-thyroid medications and to perform a confirmatory genetic testing to test for mutations in the ALB (albumin) gene. DISCUSSION The free T4 assay used by our institution is performed on the Siemens Dimension Vista platform using a two-step chemiluminescent immunoassay. While in theory two-step assays should not yield abnormal results in FDH, several two-step assays are known to yield falsely high results in patients with FDH (1, 2, 3). Other potential etiologies for discordant Free T4 levels include thyroid hormone autoantibodies, heterophile antibodies, biotin use, and anti-streptavidin antibodies (3). CONCLUSION Recognition of laboratory error in the workup of thyroid disease is essential. Clinicians must ensure thyroid function labs are consistent with each other and with the patient’s presentation. In such cases misdiagnosis of hyperthyroidism or thyroid hormone resistance may lead to unnecessary testing and inappropriate treatment (3). References 1. Cartwright D et al. Familial dysalbuminemic hyperthyroxinemia: a persistent diagnostic challenge. Clin Chem. 2009 May;55(5):1044-6 2. Ross HA et al. Spuriously high free thyroxine values in familial dysalbuminemic hyperthyroxinemia. Clin Chem. 2011 Mar;57(3):524-5 3. Favresse J et al. Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm. Endocr Rev. 2018 Oct 1;39(5):830-850.

scholarly journals SUN-504 A Case of T3 Thyrotoxicosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Isabelle Daneault Peloquin ◽  
Matthieu St-Jean
Keyword(s):  
Thyroid Function ◽  
Thyroid Function Test ◽  
Nutritional Supplement ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Endocrine Society ◽  
Product Consumption ◽  
Function Tests ◽  
History Of ◽  
Receptor Antibodies

Abstract Clinical vignette ENDOCRINE SOCIETY 2020 Title: A case of T3 thyrotoxicosis induced by a dietary supplement. A 24 yo man consulted for a 2 weeks history of diaphoresis, fatigue, insomnia, palpitations and headache associated with a 20 pounds lost. The patient didn’t have a goiter or any signs of orbitopathy. The results revealed a free T3 level of 45.8 pmol/L upon arrival (normal (N) 3.4- 6.8 pmol/L), free T4 level of 6.4 pmol/L (N 11.0–22.0 pmol/L) and TSH level less than 0.005 mUI/L (N: 0.35 to 3.50 mUI/L). Facing those results, a complete review of the patient medication and natural product consumption was done. The patient revealed that he was using, since a month, a vegetable extracts nutritional supplement that didn’t included iodine. He was asked to stop the nutritional supplement and propranolol 10 mg twice daily was prescribed. Thyroid function tests were done 3 days after. The results demonstrate a fT3 level of 4.6 pmol/L, a fT4 level of 5.6 pmol/L and a TSH that still suppressed. A thyroid scintigraphy was performed 7 days later and showed a homogeneous uptake of 18.5% (N 7.0% – 35.0%). We saw the patient 2 weeks later and we ordered another thyroid function test with TSH receptor antibodies, TPO antibodies and thyroglobulin. The results were the following: fT3 of 5.1 pmol/L, fT4 of 12.1 pmol/L, TSH of 2.31 mUI/L, thyroglobulin of 19.8 ug/L (N: 1.4 – 78) and normal levels of antibodies against TPO and TSH receptors. To confirm the contamination of the nutritional supplement by fT3 we used a plasma pool of normal patients in which we measured thyroid function tests at baseline and after we have added the nutritional supplement powder to reflect the dose suggested by the manufacturer. The results showed that fT3 level increased by 36.5%, fT4 by 11.2% and TSH didn’t changed. The powder was then analyzed by an external laboratory that wasn’t able to demonstrate the presence of fT3 nor fT4. The two diagnostic possibility facing those results were that the powder induced an interference with immunoassay used to measure fT3 and fT4 but not TSH or thyrotoxicosis induced by the nutritional supplement with limitation in the technique that tried to identify fT3 in the powder. Given the presentation of the patient, we are convinced that this case represents a thyrotoxicosis induced by a nutritional supplement. In conclusion, Graves’ disease is responsible for 60–80% of the cases of hyperthyroidism. However, there are few cases reports of thyrotoxicosis induced by nutritional supplement1,2, but some studies demonstrate the presence of thyroid hormone in significant amounts in some commercially available health supplements3. This case highlights the importance of verifying exposition to medications and natural products when confronted to cases of thyrotoxicosis. 1.Regina A et al. MMWR Morb Mortal Wkly Rep. 2016 2. Panikkath R et al. Am J Ther. 2014 3. Kang GY et al. Thyroid. 2013

scholarly journals SAT-477 Melanoma Treated with Pembrolizumab Leading to Thyroiditis and Subsequent Hypothyroidism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Heather Fishel
Keyword(s):  
Thyroid Function ◽  
T Cell Activation ◽  
Thyroid Dysfunction ◽  
Subsequent Development ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Specific Patient ◽  
Normal Thyroid ◽  
Free T3 ◽  
History Of

Abstract Background: Pembrolizumab (PD-1) is an immune checkpoint inhibitor used for treating melanoma and has been associated endocrine immune-related adverse events. Case Presentation: 76-year-old Caucasian male presented for evaluation of abnormal thyroid labs. Significant co-morbidities included recurrent melanoma, heart failure, atrial fibrillation, coronary artery disease, type 2 diabetes, hypertension. Patient’s melanoma was being treated with Pembrolizumab. Further history revealed no family/personal history of thyroid disease but a history of mouth cancer treated with radiation over 30 years ago. He denied any recent glucocorticoid or biotin use. Symptoms included worsening fatigue, weight loss, and diarrhea. He was afebrile and vitally stable. Physical exam was unremarkable. Prior to this year, patient had normal thyroid labs. Recent thyroid labs showed TSH of 0.01 uIU/mL (normal 0.34-4.94 uIU/mL), confirmed with repeat labs a week later (TSH: < 0.01, Free T4: 2.23 ng/dL, normal Free T4: 0.7-1.48 ng/dL). There was a high suspicion that these labs were related to Pembrolizumab, but other etiologies were evaluated. Completed thyroid uptake and scan showed no evidence of increased activity (4-hour uptake: 1.6%, 24-hour update: 1.2%). Repeat thyroid labs indicated recovering thyroid function with a TSH: 0.14 uIU/mL, Free T4: 0.49 ng/dL, Free T3: 1.5 pg/mL (normal Free T3 2.3-4.2 pg/mL), TSI: 96% (normal < 140%), TPO Ab: 111 IU/mL (normal TPO Ab < 9 IU/mL). One month later thyroid tests resulted as TSH: 72.81 uIU/mL, Free T4: < 0.40. He was started on levothyroxine, which was titrated over several weeks. Discussion: Pembrolizumab (PD-1) is an IgG4 programmed cell death 1-directed monoclonal antibody, whose mechanism of action is to inhibit cancer cells ability impede T-cell activation. However, because of this mechanism, some T-cells, will remain activated, leading to autoimmune diseases. PD-1 has been associated with thyroid dysfunction, with an incidence rate as high as 14-20%. The clinical presentation varies from isolated thyrotoxicosis to overt hypothyroidism. In our patient, he developed thyrotoxicosis with subsequent development of hypothyroidism. Generally, the timing of thyroid dysfunction after the initiation of PD-1 ranges from 3 to 40 weeks, with the median onset at week 6. Baseline TSH and free T4 should be obtained with rechecking of these labs monthly for the first 6 months. For patients who present with thyrotoxicosis, Grave’s disease should be ruled out, and initial treatment should include beta-blockers. Hypothyroidism should be treated with levothyroxine with titration to normal thyroid function tests. What remains to be determined is the mechanism in which PD-1 causes thyroid dysfunction and if specific patient characteristics, such as thyroid antibodies, can be used to risk stratify the likelihood of a patient developing thyroid dysfunction.

scholarly journals MON-470 Biotin Masquerading as Subclinical Hyperthyroidism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anita Eapen ◽  
Hooman Oktaei
Keyword(s):  
Thyroid Function ◽  
Clinical Endocrinology ◽  
Thyroid Function Test ◽  
Graves Disease ◽  
Endocrine Disorders ◽  
Thyroid Function Tests ◽  
Medication History ◽  
Free T4 ◽  
Function Tests ◽  
History Of

Abstract Introduction: Thyroid conditions are among the most common endocrine disorders. Diagnosis is dependent on interpretation of laboratory tests. The challenge comes when the clinical picture is discordant with laboratory results. Case Report: Patient is a 53-year-old male with history of cardiac transplantation, type 2 diabetes mellitus, history of amiodarone-induced hyperthyroidism. He was noted to have labs indicative of hyperthyroidism, while taking amiodarone, in 2016-2017, which was treated with methimazole. He was then noted to have abnormal thyroid function tests with low TSH to 0.3 IU/L, normal T3 and normal T4 levels. Thyroid stimulating immunoglobulin had been checked multiple times, and was normal, which is inconsistent with Graves’ disease. Prior radioactive iodine uptake scan, while off amiodarone, was noted to be normal. He was also scheduled for thyroidectomy at another hospital, which was cancelled due to normalization of thyroid function tests. Consultation was received for suppressed TSH to 0.323 IU/L, without symptoms of hyperthyroidism. He had been taking biotin during this time, which he subsequently stopped taking. Repeat TSH following discontinuation of biotin, was within normal range, most recent TSH 2.48 IU/L, free T4 1.03 ng/dL, free T3 2.7 pg/mL. Discussion: Thyroid function tests are commonly ordered. Interpretation of these tests relies on the provider’s understanding of thyroid physiology in addition to interferences with medications and other conditions. High doses of biotin, which people take as supplements for multiple sclerosis, or metabolic disorders, or for healthy nails and hair, can cause thyroid function test abnormalities. Streptavidin and biotin are used in some immunoassay platforms to capture antigens (TSH, free T4) or antibodies. High levels of serum biotin can inhibit the formation of T4 antibody complex, which results in a falsely high free T4 result. Conclusion: Thyroid Function tests should be interpreted very cautiously, especially in the setting of discordant clinical findings. Prior to ordering these tests, should attempt to obtain a detailed history of medications including over-the-counter supplements, which are commonly not reported during medication history. References:Elston, Marianne S., et al. “Factitious Graves’ Disease Due to Biotin Immunoassay Interference—A Case and Review of the Literature.” The Journal of Clinical Endocrinology & Metabolism, vol. 101, no. 9, 30 June 2016, pp. 3251-3255., doi:10.1210/jc.2016-1971. Koehler, Viktoria F., et al. “Fake News? Biotin Interference in Thyroid Immunoassays.” Clinica Chimica Acta, vol. 484, 30 May 2018, pp. 320-322., doi:10.1016/j.cca.2018.05.053. Soh, Shui-Boon, and Tar-Choon Aw. “Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility.” Annals of Laboratory Medicine, vol. 39, no. 1, 13 Jan. 2019, pp. 3-14., doi:10.3343/alm.2019.39.1.3.

scholarly journals DIAGNOSTIC DILEMMA IN DISCORDANT THYROID FUNCTION TESTS DUE TO THYROID HORMONE AUTOANTIBODIES

2017 ◽  
Vol 3 (1) ◽  
pp. e22-e25 ◽  
Author(s):  
Panudda Srichomkwun ◽  
Neal H. Scherberg ◽  
Jasminka Jakšić ◽  
Samuel Refetoff
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Function ◽  
Thyroid Function Tests ◽  
Diagnostic Dilemma ◽  
Thyroid Hormone Autoantibodies ◽  
Function Tests

scholarly journals THERAPY OF ENDOCRINE DISEASE: T4 + T3 combination therapy: is there a true effect?

2017 ◽  
Vol 177 (6) ◽  
pp. R287-R296 ◽  
Author(s):  
Wilmar M Wiersinga
Keyword(s):  
Combination Therapy ◽  
Thyroid Function ◽  
Healthy Subjects ◽  
Randomized Clinical Trials ◽  
Peripheral Tissue ◽  
Thyroid Function Tests ◽  
Peripheral Tissues ◽  
Persistent Symptoms ◽  
Function Tests ◽  
Number Of Patients

About 5%–10% of hypothyroid patients on T4 replacement therapy have persistent symptoms, despite normal TSH levels. It was hoped that T4 + T3 combination therapy might provide better outcomes, but that was not observed according to a meta-analysis of 11 randomized clinical trials comparing T4 monotherapy with T4 + T3 combination therapy. However, the issue is still subject of much research because normal thyroid function tests in serum may not necessarily indicate an euthyroid state in all peripheral tissues. This review evaluates recent developments in the field of T4 + T3 combination therapy. T4 monotherapy is associated with higher serum FT4 levels than in healthy subjects, and subnormal serum FT3 and FT3/FT4 ratios are observed in about 15% and 30% respectively. T4 + T3 combination therapy may mimic more closely thyroid function tests of healthy subjects, but it has not been demonstrated that relatively low serum FT3 or FT3/FT4 ratios are linked to persistent symptoms. One study reports polymorphism Thr92Ala in DIO2 is related to lower serum FT3 levels after thyroidectomy, and that the D2-Ala mutant reduces T4 to T3 conversion in cell cultures. Peripheral tissue function tests such as serum cholesterol reflect thyroid hormone action in target tissues. Using such biochemical markers, patients who had a normal serum TSH during postoperative T4 monotherapy, were mildly hypothyroid, whereas those with a TSH 0.03–≤0.3 mU/L were closest to euthyroidism. Peripheral tissue function tests suggest euthyroidism more often in patients randomized to T4 + T3 rather than that to T4. Preference for T4 + T3 combination over T4 monotherapy was dose-dependently related to the presence of two polymorphisms in MCT10 and DIO2 in one small study. It is not known if persistent symptoms during T4 monotherapy disappear by switching to T4 + T3 combination therapy. The number of patients on T4 + T3 therapy has multiplied in the last decade, likely induced by indiscriminate statements on the internet. Patients are sometimes not just asking but rather demanding this treatment modality. It creates tensions between patients and physicians. Only continued research will answer the question whether or not T4 + T3 combination therapy has true benefits in some patients.

When thyroid labs do not add up, physicians should ask patients about biotin supplements

2020 ◽  
Vol 13 (3) ◽  
pp. e231337
Author(s):  
Michael S Lundin ◽  
Ahmad Alratroot ◽  
Fawzi Abu Rous ◽  
Saleh Aldasouqi
Keyword(s):  
Thyroid Function ◽  
Dose Adjustment ◽  
Radioactive Iodine ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Medication List ◽  
Function Tests ◽  
Extensive Evaluation ◽  
History Of ◽  
Radioactive Iodine Ablation

A 69-year-old woman with a remote history of Graves’ disease treated with radioactive iodine ablation, who was maintained on a stable dose of levothyroxine for 15 years, presented with abnormal and fluctuating thyroid function tests which were confusing. After extensive evaluation, no diagnosis could be made, and it became difficult to optimise the levothyroxine dose, until we became aware of the recently recognised biotin-induced lab interference. It was then noticed that her medication list included biotin 10 mg two times per day. After holding the biotin and repeating the thyroid function tests, the labs made more sense, and the patient was easily made euthyroid with appropriate dose adjustment. We also investigated our own laboratory, and identified the thyroid labs that are performed with biotin-containing assays and developed strategies to increase the awareness about this lab artefact in our clinics.

scholarly journals SUN-425 Indiscriminate Thyroid Function Testing on Acute Hospital Admissions Reveals a High Abnormality Rate Requiring Follow Up

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Robert P McEvoy ◽  
Anthony O’Riordan ◽  
Mark J Hannon
Keyword(s):  
Thyroid Function ◽  
American Thyroid Association ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Patient Age ◽  
Function Tests ◽  
Patient Âgé ◽  
Thyroid Function Testing ◽  
Function Testing

Abstract The population attending the Medical Assessment Unit at our hospital comprises patients attending electively for investigation and acutely unwell patients presenting for unscheduled care. The standard panel of blood tests taken on arrival includes thyroid function tests (TFTs, i.e. TSH and free-T4), despite a recent review questioning the clinical utility of this practice [1]. We performed a retrospective audit to determine what proportion of our patients had abnormal thyroid function on presentation, and whether these abnormal test results were being followed up. Using the iSoft Clinical Manager software, a list was generated of all patients who attended the hospital between January 2018 and June 2018 inclusive. For each attendance, we recorded the date, medical record number, patient age, gender, and TFT result. Abnormal TFT results were classified as overt or subclinical hyper- or hypothyroid, or non-thyroid illness syndrome (NTIS), based on their admission TSH and free-T4. We then examined the hospital and primary care records of patients with abnormal TFTs to determine if they had ongoing thyroid follow up post discharge. In total, 2,298 patients attended over the 6-month study period. The mean patient age was 67.2 years, and 49% were female. Thyroid function tests were ordered on the day of attendance for 1,688 patients (73%). Of these, 181 results (11%) were abnormal: 20 overt hyperthyroid (11%), 72 subclinical hyperthyroid (40%), 12 overt hypothyroid (7%), 35 subclinical hypothyroid (19%), and 42 NTIS (23%). Twenty of these patients died within 3 months of the abnormal TFT result (4 overt hyperthyroid, 3 subclinical hyperthyroid, 3 overt hypothyroid, 6 subclinical hypothyroid, and 4 NTIS). Of the remaining 161 patients, 74 (46%) had not been followed up within 3 months (4 overt hyperthyroid, 34 subclinical hyperthyroid, 3 overt hypothyroid, 15 subclinical hypothyroid, and 18 NTIS). The low percentage of abnormal TFTs (11%) in this audit is in keeping with similar studies where thyroid function testing was performed on unselected hospital populations [1]. Subclinical hyperthyroidism was by far the most common abnormality found. A high percentage of abnormal tests (46%) were not followed up, with poor compliance with thyroid management guidelines [2]. Future work will investigate adoption of an ‘opt-in’ order system [3] and electronic alerts to flag abnormal results for follow-up. [1] Premawardhana LD. Thyroid testing in acutely ill patients may be an expensive distraction. Biochemia medica. 2017; 27(2): 300-307. [2] Ross DS et al. 2016 American Thyroid Association Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016 Oct; 26(10):1343-1421. [3] Leis B et al. Altering standard admission order sets to promote clinical laboratory stewardship: a cohort quality improvement study. BMJ Qual Saf. 2019; 28(10): 846-52.

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