scholarly journals Thyroid hormone resistance syndrom: difficulties in differential diagnosis

2018 ◽  
Vol 14 (1) ◽  
pp. 39-46
Author(s):  
Lyudmila A. Ruyatkina ◽  
Aguniya A. Molchanova ◽  
Alina S. Ruyatkina ◽  
Lyudmila Y. Rozhinskaya
Keyword(s):  
Differential Diagnosis ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Thyroid Hormone Receptor ◽  
Signs And Symptoms ◽  
Thyroid Stimulating Hormone ◽  
Heterozygous Mutation ◽  
Hormone Resistance ◽  
Thyroid Hormone Resistance ◽  
Free Thyroid Hormones

Thyroid hormone resistance syndrome (RTH) is a rare disorder characterized by reduced peripheral tissue responses to thyroid hormones (TH) and elevated levels of circulating free thyroid hormones. Resistance to thyroid hormone is caused by mutations of the thyroid hormone receptor beta (THRB) gene. In this article, we present case of 26-years-old women who presented with unclear signs and symptoms. Thyroid morphology and function were evaluated with standard ultrasound of the thyroid, scintigraphy and cytological specimen obtained by FNAB. The features of the basic assessment of thyroid status with an emphasis on the concept of “±feedback” of thyroid-stimulating hormone (TSH) and TH. A differential diagnosis of TSH-secreting pituitary adenoma and RTH was discussed. Heterozygous mutation p.P453T in the THRB gene was detected. Thus, the given clinical case demonstrates the necessity of the thorough examination of patients in identifying disorders of the principle of “±feedback”. The observation in dynamics is recommended.

scholarly journals Thyroid Hormone Resistant Syndrome

2020 ◽  
pp. 6-10
Author(s):  
Karo Gyurjian ◽  
Vishwanath Venketaraman
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Receptor Gene ◽  
Signs And Symptoms ◽  
Thyroid Stimulating Hormone ◽  
Hormone Resistance ◽  
Thyroid Receptor ◽  
Thyroid Hormone Levels ◽  
Beta Gene ◽  
Receptor Beta

Thyroid hormone resistance (THR), also known as resistance to thyroid hormone (RTH), is an inherited condition characterized by reduced end-organ responsiveness to thyroid hormone, caused by mutations in the thyroid hormone receptor gene. Patients typically present with elevated thyroid hormone levels (T3 and T4) with normal, or slightly elevated thyroid-stimulating hormone (TSH) levels.1 In a majority of cases, the disease is caused by a mutation in the thyroid receptor beta (TR-beta) gene. Patients can present with signs and symptoms of hypothyroidism or hyperthyroidism or can be asymptomatic. We present a case of a 16-year-old male who was referred for endocrinologic evaluation after abnormal findings in the thyroid function panel.

scholarly journals The Mutant Thyroid Hormone Receptor Beta R320P Causes Syndrome of Resistance to Thyroid Hormone

2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Tetsuya Kimura ◽  
Yoshitaka Hayashi ◽  
Yuka Tsukamoto ◽  
Yasuyuki Okamoto
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Elevated Serum ◽  
Index Patient ◽  
Serum Levels ◽  
Heterozygous Mutation ◽  
Hormone Resistance ◽  
Thyroid Hormone Resistance ◽  
First Case ◽  
Thyroid Hormone Resistance Syndrome

A 31-year-old Japanese male patient with a history of atrial fibrillation showed elevated serum levels of free thyroxine and triiodothyronine and a normal level of thyrotropin. The same abnormal hormone pattern was also found in his son. These data indicated that the index patient and the son have thyroid hormone resistance syndrome. Exon sequencing using DNA from these two patients revealed that both patients harbored a heterozygous mutation in the THRB gene: G1244C in exon 9, which results in R320P substitution. Therefore, thyroid hormone resistance syndrome caused by THRB mutation (RTHβ) was diagnosed. The mutation of the 320th arginine to proline has not been found to date. In conclusion, herein, we have described the first case of RTHβ that is associated with R320P mutation.

scholarly journals Thyroid Hormone Resistance Syndrome Presenting as Exercise Induced Asthma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A707-A708
Author(s):  
Joshua D Umscheid ◽  
Naim Mitre ◽  
Fadi Jamil Odeh Al Muhaisen
Keyword(s):  
Genetic Testing ◽  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Receptor Gene ◽  
Target Tissue ◽  
Hormone Resistance ◽  
Color Flow ◽  
Thyroid Hormone Resistance ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Abstract Background: Pathogenic variants in the thyroid hormone receptor (THRB) gene are associated with thyroid hormone resistance. Over 85% of the genetic mutations are in the beta TR gene. The disorder is characterized mainly by elevated thyroid hormone levels, unsuppressed levels of TSH, and goiter. Clinical case: An 11-year-old male initially seen at the PCP office for tachycardia and chest discomfort, especially during school exercise. He reported shortness of breath. His symptoms will resolve at rest. He was diagnosed initially with asthma and was put on Singular, Pulmicort, and albuterol as needed. His symptoms did not improve with this treatment, and he reported symptoms worsened with albuterol. He had a normal Echocardiogram and chest X-ray. A mild goiter was noted on his physical exam. Thyroid ultrasound showed an enlarged thyroid gland. An ovoid echogenic focus in the inferior thyroid lobe measuring 4 X 7 X 8mm was identified. The nodule was wider than tall, with a solid appearance with no internal color flow. Evaluation in our clinic showed normal TSH at 1.624mcIU/mL (0.35-5.5). FT4 was high at 1.54ng/dL (0.82-1.40), and FT3 elevated at 6.3pg/mL (3.3-4.8). Thyroid antibodies and thyroid-stimulating immunoglobulin (TSI) were normal. A 24 hour I-123 thyroid uptake was approximately 55% (10-30%) with no focal increased or decreased uptake. Given his elevated thyroid hormone levels with unsuppressed TSH in the context of goiter and tachycardia, genetic testing for the Thyroid receptor gene was done. He was found to be heterozygous for a pathogenic variant in THRB, c.1286G>A (p.Arg429Gln). This genotype is consistent with a diagnosis of autosomal dominant Thyroid hormone resistance. The patient was started on Atenolol, given his elevated heart rate, and he reported improvement in his symptoms during exercise. Conclusion: Thyroid hormone resistance was first described as a clinical entity in 1967. The phenotype can vary among individuals. It is characterized by a reduced responsiveness of target tissue to thyroid hormone and binding affinity. The disease can present with goiter, behavioral issues, abnormal growth, and tachycardia. Affected individuals may have attention deficit-hyperactivity disorders (ADHD) and language difficulties. Thyroid hormone resistance can be misdiagnosed, as in our patient. He was diagnosed with asthma and was put on unnecessary medications that worsened his symptoms. Thyroid hormone resistance can also be misdiagnosed with Graves’ disease, given the elevated thyroid hormone. It is essential to highlight the importance of genetic testing in these cases, as an accurate diagnosis will prevent unnecessary treatments with potentially serious side effects.

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

scholarly journals Correlations of Free Thyroid Hormones Measured by Tandem Mass Spectrometry and Immunoassay with Thyroid-Stimulating Hormone across 4 Patient Populations

2009 ◽  
Vol 55 (7) ◽  
pp. 1380-1388 ◽  
Author(s):  
Jacqueline Jonklaas ◽  
Natasa Kahric-Janicic ◽  
Offie P Soldin ◽  
Steven J Soldin
Keyword(s):  
Mass Spectrometry ◽  
Thyroid Hormone ◽  
Tandem Mass Spectrometry ◽  
Thyroid Hormones ◽  
Thyroid Stimulating Hormone ◽  
Free Thyroxine ◽  
Tandem Mass ◽  
Free Triiodothyronine ◽  
Free Thyroid Hormones ◽  
Free Thyroid Hormone

Abstract Background: Accurate measurement of free thyroid hormones is important for managing thyroid disorders. Ultrafiltration liquid chromatography tandem mass spectrometry (LC-MS/MS) can reliably measure the concentrations of small molecules, including thyroid hormones. Our study was designed to compare free thyroid hormone measurements performed with immunoassay and LC-MS/MS. Methods: We studied the performance of LC-MS/MS in 4 different populations comprising pediatric patients, euthyroid adults, and healthy nonpregnant and pregnant women. The samples obtained from each population numbered 38, 200, 28, and 128, respectively. Free thyroxine, free triiodothyronine, and thyroid-stimulating hormone (TSH) concentrations were documented. Results: LC-MS/MS measurement of free thyroid hormones provided better correlation with log-transformed serum TSH in each population and also the populations combined. The correlations between free thyroxine measured by LC-MS/MS and log TSH in the pediatric outpatients and healthy adults were −0.90 and −0.77, respectively. The correlations for immunoassay were −0.82 and −0.48. The correlations between free triiodothyronine measured by LC-MS/MS and TSH for both pediatric and healthy adult populations were −0.72 and −0.68, respectively. Conclusions: Free thyroid hormone concentrations measured by LC-MS/MS correlate to a greater degree with log TSH values compared to concentrations measured by immunoassay. This correlation was maintained across the patient populations we studied and may reflect the accuracy and specificity of LC-MS/MS. The superior ability of LC-MS/MS to enable documentation of the well-known thyroid hormone–TSH relationship supports the use of this measurement technique in a variety of clinical situations.

A new mutation in thyroid hormone resistance

2016 ◽  
Vol 62 (5) ◽  
pp. 78-79
Author(s):  
Ana Filipa Martins ◽  
João Martin Martins ◽  
Sónia Do Vale ◽  
Gabriel Miltenberger-Miltenyi
Keyword(s):  
Thyroid Hormone ◽  
Medical Treatment ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thyroid Hormone Receptor ◽  
Clinical Course ◽  
Thyroid Function Tests ◽  
Hormone Resistance ◽  
New Mutation ◽  
Thyroid Hormone Resistance

Introduction. Thyroid Hormone Resistance (THR) is a rare syndrome with a variable and fluctuating clinical course depending on complex genetic and molecular defects.Case report. SCPR, a caucasian female patient aged 23, was referred to outpatient endocrine department because of increased T4 levels. There was no evidence of thyroid dysfunction or goiter. Past medical history was negative with normal growth and neurophysiological development and regular menstrual cycles. There was no family history of thyroid disease. Analytical evaluation revealed T4 – 17.9 µg/dL [Reference Value (RV): 4.5-12.5], T3 – 247 ng/mL (RV: 72-170), TSH – 4.9 µU/mL (RV: 0.4-4.0), FT3 – 7.8 pg/mL (RV: 1.8-4.2), FT4 – 2.6 ng/dL (RV: 0.8-1.9), TPOAb 11 U/mL (RV: <35), TgAb < 20 U/mL (RV: <40), TRAb < 1 (RV: <2). The TRH test (200 µg, ev) revealed a normal but high TSH response up to 23 µU/mL (5-25) and a sellar NMR scan showed no abnormalities. No medical treatment was prescribed. Over the follow up period of 10 years thyroid function fluctuated with borderline high FT4 and TSH. Clinical course was marked by the development of obesity, depressive syndrome and the diagnosis of chronic fatigue syndrome with two uneventful pregnancies. Over that period, either Hyperthyroidism or Hypothyroidism were diagnosed and treated at other institutions. Recently genetic testing revealed a new mutation on exon 10 of the β thyroid hormone receptor form c790G>T (p.Val264Phe) with unknown significance.Discussion. Several important points are illustrated by this case. 1) thyroid function tests may fluctuate over time, only sometimes with clear evidence of THR. 2) clinical manifestations of the syndrome are multiform and the relation to thyroid hormone levels is far from clear with abnormalities of growth and neurophysiological development, infertility, obesity, psychiatric disorders or subtle symptoms suggesting thyroid dysfunction variably reported; 3) interpretation of analytical abnormalities may be difficult with thyroid dysfunction commonly misdiagnosed; 4) medical treatment is controversial; 5) More than 100 mutations have been reported and the particular complexity of thyroid hormone effects – several isoforms of the receptor, homo- or heterodimerization of the receptor with the retinoid X receptor and dominant negative effects making the interpretation of the functional significance of new mutations difficult. 

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