scholarly journals Diverse Genotypes and Phenotypes of Three Novel Thyroid Hormone Receptor-α Mutations

2016 ◽  
Vol 101 (8) ◽  
pp. 2945-2954 ◽  
Author(s):  
Korcan Demir ◽  
Anja L. M. van Gucht ◽  
Muammer Büyükinan ◽  
Gönül Çatlı ◽  
Yavuz Ayhan ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Motor Development ◽  
Thyroid Hormone Receptor ◽  
Clinical Phenotype ◽  
Case Series ◽  
Detailed Knowledge ◽  
Thyroid Function Tests ◽  
Free T4 ◽  
Serum Free ◽  
Free T3

Context: Recently several patients with resistance to thyroid hormone (RTH)-α due to T3 receptor-α (TRα) mutations were identified. The phenotype of these patients consists of varying degrees of growth impairment, delayed bone, mental and motor development, constipation, macrocephaly, and near-normal thyroid function tests. Objective: The objective of the study was to describe the clinical phenotype of three new families with RTHα and thereby gain more detailed knowledge on this novel syndrome. Design, Setting, and Participants: RTHα was suspected in three index patients from different families. Detailed clinical and biochemical assessment and imaging and genetic analyses were performed in the patients and their relatives. In addition, functional consequences of TRα mutations were investigated in vitro. Results: We studied 22 individuals from three families and identified 10 patients with heterozygous TRα mutations: C380fs387X, R384H, and A263S, respectively. The frame-shift mutation completely inactivated TRα, whereas the missense mutations produced milder defects. These mutations were associated with decreasing severity of the clinical phenotype: the patient in family 1 showed severe defects in growth, mental, and motor development, whereas the seven patients in family 3 had only mild clinical features. The most frequent abnormalities were anemia, constipation, and a delay in at least one of the developmental milestones. Serum free T3 ranged from high-normal to high and serum free T4 and rT3 from normal to low. TSH levels were normal in all patients. Conclusions: This large case series underlines the variation in the clinical phenotype of RTHα patients. RTHα should be suspected in subjects when even mild clinical and laboratory features of hypothyroidism are present along with high/high-normal free T3, low/normal free T4, and normal TSH.

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 Rescue pre-operative treatment with Lugol’s solution in uncontrolled Graves’ disease

2017 ◽  
Vol 6 (4) ◽  
pp. 200-205 ◽  
Author(s):  
Jan Calissendorff ◽  
Henrik Falhammar
Keyword(s):  
Heart Rate ◽  
Thyroid Hormone ◽  
Side Effects ◽  
Definitive Treatment ◽  
Graves Disease ◽  
Free T4 ◽  
Hormone Levels ◽  
Free T3 ◽  
Adherence To Medication ◽  
Thyroid Hormone Levels

Background Graves’ disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol’s solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported. Methods All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005–2015 and treated with Lugol’s solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency. Results Twenty-seven patients were included. Lugol’s solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5–9 days of iodine therapy (free T4 53–20 pmol/L, P = 0.0002; free T3 20–6.5 pmol/L, P = 0.04; heart rate 87–76 beats/min P = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n = 2, rash and vomiting n = 1, swelling of fingers n = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications. Conclusion Treatment of uncontrolled hyperthyroidism with Lugol’s solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol’s solution could be recommended pre-operatively in Graves’ disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred.

Comparison of a new ultrafiltration method for serum free T4 and free T3 with two RIA kits in eight groups of patients

1985 ◽  
Vol 8 (6) ◽  
pp. 495-500 ◽  
Author(s):  
Yuh-Shyun Wang ◽  
A. E. Pekary ◽  
M. L. England ◽  
Jerome M. Hershman
Keyword(s):  
Free T4 ◽  
Serum Free ◽  
Free T3

scholarly journals Thyroid hormone resistance detected by routine neonatal screening

2010 ◽  
Vol 54 (8) ◽  
pp. 723-727 ◽  
Author(s):  
Léa Maria Zanini Maciel ◽  
Patrícia Künzle Ribeiro Magalhães
Keyword(s):  
Thyroid Hormone ◽  
Neonatal Screening ◽  
Thyroid Hormone Receptor ◽  
Direct Sequencing ◽  
Receptor Gene ◽  
Confirmatory Test ◽  
Free T4 ◽  
Laboratory Findings ◽  
Normal Delivery ◽  
Brazilian Patient

We report the clinical and laboratory findings, and molecular analysis of a Brazilian patient with resistance to thyroid hormone syndrome (RTH) detected by neonatal screening. The index case was born at term by normal delivery with 2,920 g and 45 cm. TSH of the neonatal screening test performed on the 5th day of life was of 13.1 µU/mL (cut-off = 10 µU/mL). In a confirmatory test, serum TSH level was 4.3 µU/mL, total T4 was 19 µg/dL (confirmed in another sample, Total T4 = > 24.0 µg/dL), free T4 was 3.7 ηg/dL, and free T3 was 6.7 pg/mL. Direct sequencing of the beta thyroid hormone receptor gene revealed mutation c.1357C>A (P453T), confirming the diagnosis of RHT. Family study demonstrated the presence of RTH in his 1-year-and-3-month-old sister, in his 35-year-old father, and in his 68-year-old paternal grandfather. All of them had goiter and only his father had received an erroneous diagnosis of hyperthyroidism. The present case shows that clinical evaluation and a judicious interpretation of total T4/free T4 concentrations in a newborn recalled due to slightly altered neonatal TSH can contribute to the diagnosis of RTH.

scholarly journals STUDY OF INSULIN RESISTANCE AND THYROID PROFILE IN WOMEN WITH SPONTANEOUS ABORTIONS

2020 ◽  
pp. 1-3
Author(s):  
Annapoorani R ◽  
Nagasudha D
Keyword(s):  
Insulin Resistance ◽  
Thyroid Dysfunction ◽  
Previous History ◽  
Oral Glucose ◽  
Study Group ◽  
Thyroid Function Tests ◽  
Model Assessment ◽  
Spontaneous Abortions ◽  
Free T4 ◽  
Free T3

Thyroid dysfunction and insulin resistance are important endocrinological causes of spontaneous abortions. This study is resistancewith spontaneous abortions Thyroid dysfunction and Insulin resistance are common endocrinological causes of abortions.The present study is a case control study where 75 patients with spontaneous abortions below 20 weeks were taken as cases and 75 patients with normal on going pregnancy without previous history of miscarriage were taken as controls. Thyroid Function Tests (Free T3 ,Free T4,TSH) ,Oral Glucose Tolerance Test following 75 mg glucose load were done in cases and controls. Fasting glucose and insulin levels were measured and Insulin resistance was calculated using homeostatic model assessment method (HOMA- IR).Free T3 levels were signicantly lower and TSH levels were signicantly higher in study group indicating the presence of hypothyroidism in the abortus group. The HOMA-IR insulin resistance scores were apparently higher in the study group than in the controls, but it was not statistically signicant.

scholarly journals Familial Dysalbuminemic Hyperthyroxinemia: An Underdiagnosed Entity

2020 ◽  
Vol 9 (7) ◽  
pp. 2105
Author(s):  
Xavier Dieu ◽  
Nathalie Bouzamondo ◽  
Claire Briet ◽  
Frédéric Illouz ◽  
Valérie Moal ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Clinical Symptoms ◽  
Free T4 ◽  
Biochemical Alterations ◽  
Upper Limit ◽  
Albumin Gene ◽  
Thyroid Hormone Receptor Β ◽  
Index Cases

Resistance to thyroid hormone (RTH) is a syndrome characterized by impaired sensitivity of tissues to thyroid hormone (TH). The alteration of TH-binding proteins, such as in Familial Dysalbuminemic Hyperthyroxinemia (FDH), can mimic the abnormal serum thyroid tests typical of RTH. We aimed to characterize a population referred to our center with suspected RTH and estimate the proportion of patients with FDH. For 303 different families, we collected clinical and hormonal data and sequenced the thyroid hormone receptor β gene (THRB) and exon 7 of the albumin gene (ALB). We found 56 THRB variants (i.e., 38% of the 303 index cases, called RTHβ group). Among the samples screened for FDH variants, 18% had the variant R218H in ALB (FDH group); in addition, 71% of the cases had neither variant (non-FDH/RTHβ group). Patients with FDH had significantly lower free T3 (fT3) and free T4 (fT4) levels and more often an isolated elevation of fT4 than RTHβ patients. Clinically, patients with FDH had fewer symptoms than patients with RTHβ. Our study suggests that FDH should be systematically considered when examining patients suspected of having RTH. In most cases, they present no clinical symptoms, and their biochemical alterations show an elevation of fT4 levels, while fT3 levels are 1.11 times below the upper limit of the assay.

Specificity of thyroid hormone receptor subtype and steroid receptor coactivator-1 on thyroid hormone action

2003 ◽  
Vol 284 (1) ◽  
pp. E36-E46 ◽  
Author(s):  
Peter M. Sadow ◽  
Olivier Chassande ◽  
Karine Gauthier ◽  
Jacques Samarut ◽  
Jianming Xu ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Steroid Receptor ◽  
Receptor Subtype ◽  
Thyroid Function Tests ◽  
Hormone Action ◽  
Peripheral Tissues ◽  
Steroid Receptor Coactivator ◽  
Thyroid Hormone Action

Isoforms of the thyroid hormone receptor ( TR) α and TRβ genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1-mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRα and SRC-1, as well as in TRβ and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRα or TRβ, SRC-1 is important for normal growth; 2) SRC-1 modulates TRα and TRβ effects on heart rate; 3) two new TRβ-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRα-deficient mice.

scholarly journals Thyroid Hormone Resistance With Concurrent Papillary Thyroid Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A961-A962
Author(s):  
Dhivya Pahwa ◽  
Michael Howard Shanik
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Thyroid Hormone Receptor ◽  
Hormone Resistance ◽  
Papillary Thyroid ◽  
Free T4 ◽  
Thyroid Hormone Resistance ◽  
History Of

Abstract Introduction: Thyroid hormone resistance is a genetic mutation resulting in decreased receptor responsiveness. We present a case of thyroid hormone resistance with concurrent papillary thyroid cancer. Clinical Case: A 34-year-old man with a history of papillary thyroid carcinoma status post total thyroidectomy and radioactive iodine. He had transferred his care after moving to our area. He presented with persistently elevated TSH despite ongoing treatment with Levothyroxine 400 mcg daily. Upon presentation the patient reported intermittent palpitations and tremor. Vital signs revealed height of 74 inches, weight of 235 pounds, blood pressure of 112/64, and heart rate of 48. Physical examination revealed a well -healed scar on the neck without palpable lymphadenopathy. Bloodwork revealed TSH of 15.28 mIU/L and Free T4 of 2.8 ng/dL. The patient was maintained on Levothyroxine 400 mcg daily and educated on proper administration of the medication. Two months later, bloodwork revealed a TSH of 9.22 mIU/L with a Free T4 of 3.3 ng/dL. MRI of the pituitary revealed a 4mm hyper-intensity which likely represented a microadenoma. Resistance Thyroid Hormone (RTH) Mutation analysis was ordered which revealed a heterozygous mutation for the Thyroid Hormone Receptor (THR)-Beta gene. The mutation was detected at pArg438His indicating a single nucleotide substitution leading to the replacement of arginine by histidine at the p.438 of the translated protein on exon 10. The patient was maintained on Levothyroxine at 400 mcg daily. Discussion: Thyroid hormone resistance describes a constellation of symptoms from decreased tissue responsiveness to thyroid hormones. Literature reveals the prevalence of THR to be 1 in 40,000 individuals. It occurs due to mutation on the thyroid hormone receptor, most often found on the alpha or beta subunit. Frequently patients present with tachycardia and hyperactivity but it can also present with symptoms suggestive of hypothyroidism and goiter. Risk factors include family history of RTH mutation often with an autosomal dominant inheritance pattern. Patients with an elevated Free T4 with a non-suppressed TSH should be investigated with a genetic analysis of Resistance Thyroid hormone. A positive mutation would confirm the diagnosis. Close monitoring of symptoms as well as thyroid function tests should guide treatment. The concurrent diagnosis of thyroid hormone resistance in conjunction with papillary thyroid carcinoma in our patient is unique and makes management a challenge. The literature reveals few cases reported. Reference: DynaMed. (2018, November 30). Thyroid Hormone Resistance. Retrieved October 2, 2020, from https://www-dynamed-com.arktos.nyit.edu/topics/dmp~AN~T912485 Igata M, et al. Coexistence of resistance to thyroid hormone and papillary thyroid carcinoma. Endocrinol Diabetes Metab Case Rep. 2016;2016:160003. doi:10.1530/EDM-16-0003

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