scholarly journals An Update on the Pathophysiology and Diagnosis of Inappropriate Secretion of Thyroid-Stimulating Hormone

2021 ◽  
Vol 22 (12) ◽  
pp. 6611
Author(s):  
Kenji Ohba
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Elevated Serum ◽  
Thyroid Stimulating Hormone ◽  
Free Triiodothyronine ◽  
Related Condition ◽  
Important Indicator ◽  
Inappropriate Secretion ◽  
Hpt Axis ◽  
Stimulating Hormone

Inappropriate secretion of thyroid-stimulating hormone (IST), also known as central hyperthyroidism, is a clinical condition characterized by elevated free thyroxine and triiodothyronine concentrations concurrent with detectable thyroid-stimulating hormone (TSH) concentrations. Similarly, the term syndrome of IST (SITSH) is widely used in Japan to refer to a closely related condition; however, unlike that for IST, an elevated serum free triiodothyronine concentration is not a requisite criterion for SITSH diagnosis. IST or SITSH is an important indicator of resistance to thyroid hormone β (RTHβ) caused by germline mutations in genes encoding thyroid hormone receptor β (TRβ) and TSH-secreting pituitary adenoma. Recent evidence has accumulated for several conditions associated with IST, including RTH without mutations in the TRβ gene (non-TR-RTH), the phenomenon of hysteresis involving the hypothalamus-pituitary-thyroid axis (HPT-axis), methodological interference, and Cushing’s syndrome after surgical resection. However, little information is available on the systematic pathophysiological aspects of IST in previous review articles. This report presents an overview of the recent advances in our understanding of the etiological aspects of IST that are relevant for diagnosis and treatment. Moreover, the report focuses on the potential mechanism of IST caused by hysteresis in the HPT-axis (lagging TSH recovery) in terms of epigenetic regulation.

scholarly journals Low free thyroxine and normal thyroid-stimulating hormone in infants and children: possible causes and diagnostic work-up

2021 ◽  
Author(s):  
Peter Lauffer ◽  
A. S. Paul van Trotsenburg ◽  
Nitash Zwaveling-Soonawala
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Thyroid Stimulating Hormone ◽  
Free Thyroxine ◽  
Infants And Children ◽  
Clinical Algorithm ◽  
Hpt Axis ◽  
In Infants And Children ◽  
Stimulating Hormone

AbstractScreening for hypo- or hyperthyroidism in adults is generally done by measuring the serum thyrotropin (thyroid-stimulating hormone, TSH) concentration. This is an efficient approach in case of suspected acquired thyroid disease. However, in infants and children, congenital hypothalamus-pituitary-thyroid (HPT) axis disorders also need to be considered, including primary and central congenital hypothyroidism, and even rarer thyroid hormone receptor and transporter defects. In primary congenital hypothyroidism, TSH will be elevated, but in the other congenital HPT axis disorders, TSH is usually within the normal range. Free thyroxine (FT4) assessment is essential for the diagnosis in these conditions.Conclusion: Here we discuss a number of rare congenital HPT axis disorders in which TSH is normal, but FT4 is low, and provide a clinical algorithm to distinguish between these disorders. What is Known:• A single thyroid-stimulating hormone (TSH) measurement is an appropriate screening method for primary hypothyroidism.• For central hypothyroidism and rare thyroid hormone receptor and transporter defects a free thyroxine (FT4) measurement is essential for the diagnosis because TSH is usually normal. What is New:• Here we present a new problem-oriented clinical algorithm including a diagnostic flow-chart for low FT4 and normal TSH in infants and children.

scholarly journals Painless destructive thyroiditis in a patient with resistance to thyroid hormone: a case report

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Tomoko Nagamine ◽  
Jaeduk Yoshimura Noh ◽  
Naoya Emoto ◽  
Takahito Kogai ◽  
Akira Hishinuma ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Complete Suppression ◽  
Free Triiodothyronine ◽  
General Physician ◽  
Resistance To Thyroid Hormone ◽  
Tsh Suppression ◽  
Stimulating Hormone

Abstract Background Resistance to thyroid hormone (RTH) usually features a syndrome of inappropriate secretion of thyroid-stimulating hormone (SITSH) without suppression of the typical high thyroid hormone levels. However, some patients with RTH show thyroid-stimulating hormone (TSH) suppression due to thyrotoxicosis. We report a case of painless thyroiditis in a patient with RTH that was misdiagnosed as Graves’ disease because of TSH-suppressed thyrotoxicosis. Case presentation A sixteen-year-old boy consulted a local general physician for fatigue. He had a goiter, and biochemical analysis showed TSH < 0.1 μIU/mL, free triiodothyronine (FT3) of 2.70 pg/mL, and free thyroxine (FT4) of 3.6 ng/dL. He was diagnosed with Graves’ disease and was treated with 20 mg thiamazole. One year later, he was referred to the department of endocrinology because of SITSH. He was finally diagnosed with RTH due to the finding of a heterozygous missense mutation (methionine 334 threonine) in the thyroid hormone receptor β gene. Three years after cessation of thiamazole, his hyperthyroxinemia showed marked exacerbation with TSH suppression. We diagnosed him with painless destructive thyroiditis because of low technetium-99 m (Tc-99 m) uptake in the thyroid. Extreme hyperthyroxinemia was ameliorated, with a return to the usual SITSH levels, within 1 month without any treatment. Conclusion The present case demonstrates that diagnosing RTH is difficult when patients show hyperthyroxinemia with complete suppression of TSH to undetectable levels, and the data lead to misdiagnosis of RTH as Graves’ disease. The initial diagnosis is important, and Tc-99 m scintigraphy is useful for the differential diagnosis of thyrotoxicosis accompanying RTH.

scholarly journals Misleading results from immunoassays of serum free thyroxine in the presence of rheumatoid factor

1997 ◽  
Vol 43 (6) ◽  
pp. 957-962 ◽  
Author(s):  
Anthony G W Norden ◽  
Rodwin A Jackson ◽  
Lorraine E Norden ◽  
A Jane Griffin ◽  
Margaret A Barnes ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Rheumatoid Factor ◽  
Equilibrium Dialysis ◽  
Thyroid Stimulating Hormone ◽  
Normal Serum ◽  
Free Thyroxine ◽  
Free Triiodothyronine ◽  
Serum Free ◽  
Serum Free Thyroxine ◽  
Stimulating Hormone

Abstract A novel interference with measurements of serum free thyroxine (FT4) caused by rheumatoid factor (RhF) is described. We found misleading, sometimes gross, increases of FT4 results in 5 clinically euthyroid elderly female patients with high RhF concentrations. All 5 patients had high FT4 on Abbott AxSYM® or IMx® analyzers. “NETRIA” immunoassays gave misleading results in 4 of the 5 patients; Amerlex-MAB® in 2 of 4 patients; AutoDELFIA®in 2 of the 5; and Corning ACS-180® and Bayer Diagnostics Immuno 1® in 1 of the 5. BM-ES700® system results for FT4 in these women remained within the reference range. Results for serum T4, thyroid-stimulating hormone, free triiodothyronine, thyroid-hormone-binding globulin, and FT4 measured by equilibrium dialysis were normal in all 5 patients. Drugs, albumin-binding variants, and anti-thyroid-hormone antibodies were excluded as interferences. Addition to normal serum of the RhF isolated from each of the 5 patients increased the apparent FT4 (Abbott AxSYM). Screening of 83 unselected patients demonstrated a highly significant positive correlation between FT4 (Abbott AxSYM) and RhF concentrations. Discrepant, apparently increased FT4 with a normal result for thyroid-stimulating hormone should lead to measurement of the patient’s RhF concentration.

scholarly journals Molecular dynamics approach to the I431V mutational impact on thyroid hormone receptor-beta

BIBECHANA ◽  
2018 ◽  
Vol 16 ◽  
pp. 79-91
Author(s):  
Tika Ram Lamichhane ◽  
Sharma Paudel ◽  
Binod Kumar Yadav ◽  
Hari Prasad Lamichhane
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Point Mutations ◽  
Binding Pocket ◽  
Accessible Surface Area ◽  
Thyroid Stimulating Hormone ◽  
Solvent Accessible Surface Area ◽  
Free Triiodothyronine ◽  
Receptor Beta

The point mutations like I431V on thyroid hormone receptor-beta (THR-β) gene cause resistance to thyroid hormones (RTH) with the clinical diagnosis of elevated free triiodothyronine (T3) and free thyroxin (T4) but not suppressed thyroid stimulating hormone (TSH) on the blood serum. Some ultrasonographic (USG) reports of the patients with RTH show thyroid gland disorder with goiter or nodule(s) or cyst(s) and some USG reports even with RTH are normal. I431V-mutant causes more steric hindrance while binding T3 into THR-β than the native wild type THRT3. The residue on the 431-codon is dynamic in nature showing its flexibility over the course of entry and release of T3-hormone into/from the ligand binding pocket. The more increased solvent accessible surface area of I431V-mutant than that of native I431-residue makes the partial unfolding of the globular THR-β protein. The smaller height of radial distribution function between I431-mutant and T3 shows the decrease in probability of finding the atomic particles nearby T3-hormone in THRT3-MT than in THRT3-WT. The electrostatic interaction energy between native I431 and T3 is negative, but it is positive between I431V and T3. Moreover, the internal energy of I431V-mutant has been found smaller than that of native I431-residue in THRT3 systems.BIBECHANA 16 (2019) 79-91

scholarly journals Coexistence of Autoimmune Hyper- and Hypothyroidism in a Kindred with Reduced Sensitivity to Thyroid Hormone

2020 ◽  
Vol 9 (5) ◽  
pp. 263-268
Author(s):  
Yasmine Abdellaoui ◽  
Dimitra Magkou ◽  
Sofia Bakopoulou ◽  
Ramona Zaharia ◽  
Marie-Laure Raffin-Sanson ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Thyroid Stimulating Hormone ◽  
Graves Disease ◽  
Free Triiodothyronine ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Autoimmune Hypothyroidism ◽  
First Time ◽  
Receptor Antibodies

Introduction: Resistance to thyroid hormone beta (RTHβ) is a rare disease with an autosomal dominant transmission. Diagnosis may be challenging especially in patients with hyper- or hypothyroidism. Case Presentation: A 31-year-old male patient with suppressed thyroid-stimulating hormone (TSH), elevated free thyroxine and free triiodothyronine, along with high thyroid receptor antibodies was diagnosed with Graves’ disease. Benzylthiouracil was started. One month later, reduced sensitivity to thyroid hormones was suspected because of persistently high thyroid hormone levels contrasting with high TSH level. Molecular analysis highlighted a 10c.1357C>T p.P453S mutation in the thyroid hormone receptor beta gene (THRB). RTHβ was diagnosed. Several relatives also had RTHβ (the mother, the young son, and 2 out of 3 siblings). Autoimmune hypothyroidism was present in the mother, whereas 2 out of 3 siblings had asymptomatic autoimmunity. Discussion/Conclusion: Both Graves’ disease and autoimmune hypothyroidism were described in patients with RTHβ. We show here for the first time that autoimmune hypo- and hyperthyroidism may coexist in kindred with RTHβ. Seven previously published cases of Graves’ disease and RTHβ were retrieved and analyzed. Treatments and thyroid hormone level targets are discussed as well as the possible link between RTHβ and autoimmune thyroid diseases.

scholarly journals ThyrotropinomA: Diagnosing a Rare Cause of Hyperthyroidism

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A968-A968
Author(s):  
Monica Bhanot ◽  
Chase Dean Hendrickson
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Equilibrium Dialysis ◽  
Elevated Serum ◽  
Sex Hormone Binding Globulin ◽  
Molar Ratio ◽  
Graves Disease ◽  
Free Triiodothyronine ◽  
Α Subunit ◽  
Free Thyroid Hormones

Abstract Case: The patient is a 40-year-old male who presented for evaluation of hyperthyroidism with symptoms including palpitations, increased bowel movements, anxiety, and worsening tremor. With a family history of Graves’ disease and an ultrasound showing a hyperemic thyroid, there was initial suspicion for Graves’ disease. Although a radioactive iodine thyroid scan showed diffuse uptake that was elevated, 21.4% at 4 hours and 33.1% at 24 hours, lab evaluation appeared inconsistent with Graves’ disease revealing: TSH 1.65 µU/mL (upper limit of normal [ULN] 4.5), free thyroxine (FT4) 1.99 ng/dL (ULN 1.17), free triiodothyronine 6.16 ng/dL (ULN 3.98), thyroid stimulating immunoglobulin 92% (ULN 122), and thyroid receptor antibodies less than 1.0 IU/L (ULN 1.75). Lab results were reproducible with elevated FT4 even by equilibrium dialysis at 3.9 ng/dL (ULN 2.4) and high-normal TSH with serial dilution that ruled out assay interreference. Given these findings, our focus turned to rare causes of hyperthyroidism including thyrotropinoma and thyroid hormone resistance (RTH). Unique to the diagnosis of thyrotropinoma is an elevated serum α subunit in 50-85% of cases (1). Therefore, we obtained an α subunit level which was 0.35 ng/mL (ULN 0.55) with a molar ratio of 2.2 (ULN 2.4). Since the α subunit level was normal, the patient obtained genetic testing for mutations in the thyroid hormone receptor β gene seen in 85% of RTH cases (1). However, no sequence variants were identified. Since initial lab and genetic analyses were undifferentiating, additional tests were obtained including an insulin-like growth-factor 1 level of 209 ng/mL (ULN 237) and prolactin level of 10.1 ng/mL (ULN 20) which can be elevated in 30% of mixed thyrotropinoma cases (1). The first evidence to suggest a thyrotropinoma was a mildly elevated sex-hormone binding globulin at 102 nmol/L (ULN 80). Further evaluation with pituitary magnetic resonance imaging showed a 6-milimeter lesion. Although the pituitary lesion is suggestive of a thyrotropinoma, it is not definitive, as they are present in 20% of RTH cases (1). Therefore, with increased suspicion of a thyrotropinoma, we pursued the more robust T3 suppression test which showed 56% suppression of TSH consistent with a thyrotropinoma. The patient had pituitary surgery with pathology confirming weak immunoreactivity for TSH. Post-operatively, his symptoms improved and free thyroid hormones normalized. Discussion: It is important to distinguish between thyrotropinoma and RTH as the treatment is different with 80% of thyrotropinoma cases achieving euthyroidism after surgery (1). In our case, the diagnosis was initially unclear thus it was important to broaden the lab and genetic evaluation considering the limitations of the studies. One such limitation is the α subunit may not be elevated in microadenomas as occurred in our case. 1. Beck-Peccoz et al. J Endocrinol Invest. 2019; 42:1401-6

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