scholarly journals Challenging diagnosis of resistance to thyroid hormone in a patient with pituitary adenoma

2019 ◽  
Vol 12 (7) ◽  
pp. e229430
Author(s):  
Nelson Carvalho Cunha ◽  
Leonor Gomes ◽  
Margarida Bastos
Keyword(s):  
Pituitary Adenoma ◽  
Thyroid Hormone ◽  
Correct Diagnosis ◽  
Pituitary Surgery ◽  
Pituitary Hormones ◽  
Young Female ◽  
Left Lobe ◽  
Antithyroid Drugs ◽  
Resistance To Thyroid Hormone ◽  
Normal Ranges

The elevation of thyroid hormone with a normal or elevated thyroid-stimulation hormone (TSH) occurs uncommonly. This set a diagnosis challenge between TSH-secreting pituitary adenoma and resistance to thyroid hormone (RTH). We report a case of a young female patient with palpitations, with elevated thyroid hormone and non-suppressed TSH. TSH receptor antibody was undetectable. Thyroid ultrasound revealed mild heterogeneous goitre, and MRI revealed a microadenoma with 7.5 mm length in pituitary’s left lobe. Pituitary hormones were within normal ranges. The thyrotropin-releasing hormone stimulation test showed normal TSH elevation, consistent with RTH. The genetic test revealed a mutation in heterozygosity in THRB gene (G344R) confirming RTH-beta. No pituitary surgery or thyroidectomy was performed nor were prescribed any antithyroid drugs. Inappropriate secretion of TSH requires a high level of clinical suspicion and the proper laboratory, genetic and radiological studies to conduct a correct diagnosis and prevent unnecessary and potential harmful therapies.

scholarly journals SAT-434 Phenotype and Genotype Analysis of Patients with Resistance to Thyroid Hormone β: A Single-Center Experience

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Karn Wejaphikul ◽  
Prapai Dejkhamron ◽  
Stefan Groeneweg ◽  
W Edward Visser ◽  
Kevalee Unachak ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mutation Analysis ◽  
Novel Mutation ◽  
Family Members ◽  
Antithyroid Drugs ◽  
Thyroid Function Tests ◽  
Resistance To Thyroid Hormone ◽  
The Mean ◽  
The Impact

Abstract Introduction Resistance to thyroid hormone β (RTHβ) is caused by mutations in THRB, the gene that encodes thyroid hormone receptor β. The clinical phenotype is variable and may include goiter, tachycardia, and learning disability with or without hyperactive behavior. The biochemical hallmark of RTHβ is elevated T4 and T3 with non-suppressed TSH concentrations. We here describe the phenotype and genotype of three Thai patients diagnosed with RTHβ in a pediatric referral center. Patients had previously been misdiagnosed and inappropriately treated with antithyroid drugs (ATDs). Methods Clinical features and thyroid function tests (TFTs) of three unrelated RTHβ patients were retrospectively reviewed. Genomic DNA of the RTHβ patients and affected family members was amplified for exon 7-10 of the THRB gene and sequenced to identify mutation by Sanger sequencing. The impact of the p.L341V novel mutation on the affinity for T3 and T3-induced transcriptional activity was previously determined in vitro. Results Three female patients were diagnosed with RTHβ. All of them had been misdiagnosed with hyperthyroidism and treated with ATDs prior to referral. The mean age at diagnosis was 8 years. The main presenting symptoms were diffuse goiter and tachycardia. The mean duration of ATD treatment was 3 years. During the treatment, patients had fluctuating thyroid hormone and increased TSH levels. An older sister and mother of one patient also had similar TFTs abnormalities, for which the mother had undergone a subtotal thyroidectomy. RTHβ was diagnosed based on the high FT3 and FT4 with normal (non-suppressed) TSH concentrations and confirmed by mutation analysis. Anti-thyroid peroxidase, anti-thyroglobulin, and TSH receptor antibody (TRAb) were negative, excluding autoimmune thyroid disease. Heterozygous missense mutations of the THRB gene were identified in all patients and affected family members. Two mutations had been previously reported (p.R243W and p.L456F), and one mutation was novel (p.L341V). In vitro studies confirmed an important role of Leu341 in T3 binding of the TRβ and functional impairment of the p.L341V novel mutation and were reported separately. According to available literature, only nine Thai RTHβ patients (in three families) carrying three different mutations (p.G251V, p.M313T, and p.A317T) had been previously reported. Goiter was the most common clinical finding, and almost all patients had a history of receiving unnecessary treatment with ATDs. Conclusion We report a series of RTHβ patients carrying THRB gene mutations, including one novel mutation (p.L341V). Clinicians should be alert that RTHβ can be found in patients with goiter and tachycardia. Elevated T4 and T3 with non-suppressed TSH concentration is the main diagnostic clue for this disease. Mutation analysis allows definitive diagnosis of RTHβ and may help to avoid potential misdiagnosis and improper treatment.

Serum copper as a novel biomarker for resistance to thyroid hormone

2012 ◽  
Vol 443 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Jens Mittag ◽  
Thomas Behrends ◽  
Kristina Nordström ◽  
Joao Anselmo ◽  
Björn Vennström ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Large Scale ◽  
Hormone Receptors ◽  
Correct Diagnosis ◽  
Serum Copper ◽  
Serum Selenium ◽  
Mrna Levels ◽  
Resistance To Thyroid Hormone ◽  
Screening Parameter ◽  
Specific Regulation

Thyroid hormone action is mediated by the thyroid hormone receptors TRα1 and TRβ. Defects in TRβ lead to RTH (resistance to thyroid hormone) β, a syndrome characterized by high levels of thyroid hormone and non-suppressed TSH (thyroid-stimulating hormone). However, a correct diagnosis of RTHβ patients is difficult as the clinical picture varies. A biochemical serum marker indicative of defects in TRβ signalling is needed and could simplify the diagnosis of RTHβ, in particular the differentiation to TSH-secreting pituitary adenomas, which present with clinically similar symptoms. In the present paper we show that serum copper levels are regulated by thyroid hormone, which stimulates the synthesis and the export of the hepatic copper-transport protein ceruloplasmin into the serum. This is accompanied by a concerted reduction in the mRNA levels of other copper-containing proteins such as metallothioneins 1 and 2 or superoxide dismutase 1. The induction of serum copper is abolished in genetically hyperthyroid mice lacking TRβ and human RTHβ patients, demonstrating an important role of TRβ for this process. Together with a previously reported TRα1 specific regulation of serum selenium, we show that the ratio of serum copper and selenium, which is largely independent of thyroid hormone levels, volume changes or sample degradation, can constitute a valuable novel biomarker for RTHβ. Moreover, it could also provide a suitable large-scale screening parameter to identify RTHα patients, which have not been identified to date.

Innapropriate TSH secretion: the challenging diagnosis

2016 ◽  
Vol 62 (5) ◽  
pp. 79-80 ◽  
Author(s):  
Nélson Cunha ◽  
Leonor Gomes ◽  
Luís Cardoso ◽  
Nuno Vicente ◽  
Diana Martins ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Thyroid Hormone ◽  
Genetic Test ◽  
Elevated Serum ◽  
Hormone Resistance ◽  
Free T4 ◽  
Resistance To Thyroid Hormone ◽  
Thyroid Hormone Resistance ◽  
Free T3 ◽  
Tsh Secretion

Background. The elevation of thyroid hormone with a normal or elevated TSH occurs uncommonly. This has different causes and pose a diagnosis challenge namely between TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone. The accurate diagnosis is essential, because delayed diagnosis of TSHoma can lead to tumour growth and poor surgical cure rates, whereas medical, surgical or radioablative treatments in patients with resistance to thyroid hormone are usually unnecessary and potentially harmful.Case Report. A 23-years-old women with palpitations, fatigue, insomnia and exophthalmia with elevated serum free T4 and TSH, medicated with methimazole 5mg 3id was sent to evaluation in endocrinology department. She did not report headaches or visual problems. Patient’s laboratory tests at admission: TSH 9,6 µUI/mL (0,4–4,0 µUI/mL), Free T4 2,1 pg/dL (0,8–1,9 pg/dL). After stopping anti-thyroid drug presented TSH 2,9 µUI/mL (0,4-4,0 µUI/mL), Free T4 3,7 pg/dL (0,8–1,9 pg/dL), Free T3 11 pg/mL (1,8–4,2 pg/mL); antithyroid peroxidase and antithyroglobulin antibodies and thyroid stimulating immunoglobulin were undetectable; thyroid ultrasound revealed small heterogeneous goiter; thyroid technetium scintigraphy showed diffuse glandular hyperfunctioning; Magnetic resonance imaging revealed a microadenoma with 7,5mm in the left side of pituitary. Remaining anterior pituitary hormones were within normal ranges. The thyrotropin-releasing hormone stimulation test was performed and revealed TSH at 0’ 1,7 µUI/mL, 20’ 14 µUI/mL and 60’ 11 µUI/mL, with free T4 2,3 pg/dL and free T3 5,9 pg/mL, which was consistent with thyroid hormone resistance syndrome. In this clinical setting genetic test was performed and revealed mutation in heterozygosity in THRβ gene: c.1030G>A, p.Gly344Arg. Patient’s mother was also tested and no mutation was found. Her father was not available to do the genetic test. No pituitary surgery or thyroidectomy was performed, nor were prescribed any anti-thyroid drugs.Conclusions. In this case, an innapropriate TSH secretion was identified and the clinical, biochemical and genetic investigations were consistent with resistance to thyroid hormone. Known that as many as 15% non-ill people may have a small, nonfunctioning pituitary adenoma, patients with thyroid hormone resistance may have incidentally abnormal imaging findings. The high level of clinical suspicion and the proper laboratory, genetic and radiological studies, conduct to a correct diagnosis and prevent unnecessary and potential harmful therapies.

Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma

2002 ◽  
Vol 41 (04) ◽  
pp. 178-183 ◽  
Author(s):  
V. Fidler ◽  
K. Zaletel ◽  
S. Gaberšček ◽  
S. Hojker ◽  
E. Pirnat
Keyword(s):  
Thyroid Hormone ◽  
Antithyroid Drugs ◽  
Prospective Clinical Study ◽  
Hormone Concentration ◽  
Toxic Adenoma ◽  
Free Triiodothyronine ◽  
Thyroid Cells ◽  
131I Treatment ◽  
Before And After ◽  
Thyroid Hormone Concentration

Summary Aim: In spite of extensive use of 131I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether 131I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. Patients and methods: 30 consecutive patients were treated with 925 MBq 131I. Serum concentration of thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of 131I. Results: After application of 131I no clinical worsening was observed. FT4 and fT3 concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p <0.0001). Slight and clinically irrelevant increase in the level of the two thyroid hormones was observed in 9 patients. Furthermore, we observed a prolonged increase in Tg concentration and a transient increase in IL-6 concentration. Conclusion: Neither evidence of any clinical aggravation of hyperthyroidism nor any significant increase in thyroid hormone concentration by 131I induced necrosis of thyroid cells was found. Therefore, the application of 131I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma.

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