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Friday, 29 November 2013

Thyroid Disease : Thyroid hormone resistance syndrome – The Misdiagnosis and Diagnosis

Thyroid disease is defined as a condition of malfunction of thyroid. Hyperthyroidism is a condition in which the thyroid gland is over active and produces too much thyroid hormones. Hypothyroidism is a condition in which the thyroid gland is under active and produces very little thyroid hormones. Thyroid cancer is defined as condition in which the cells in the thyroid gland have become cancerous.
Thyroid hormone resistance syndrome
Thyroid hormone resistance syndrome is defined as a condition of which affected individuals have elevated serum thyroid hormone levels and inappropriately normal or elevated thyroid-stimulating hormone (TSH) but are usually clinically euthyroid and require no treatment. Selective pituitary resistance to thyroid hormone (PRTH) is characterized by resistance in the pituitary gland but not in peripheral tissues(a).
D. Misdiagnosis and Diagnosis
D.1. Misdiagnosis
1. Hyperthyroidism
There is a report of an isolated case of RTH initially misdiagnosed as hyperthyroidism, and detail the investigations which ultimately led to the correct diagnosis(23).
2. Falsely diagnnosis
There is a report of a 63-year-old woman was referred because of suspected SITSH. Laboratory tests showed a normal TSH (0.52 μIU/L; normal range: 0.5-5.0) measured by sandwich Elecsys, and elevated FT4 (3.8 ng/dL; normal range: 0.9-1.6) and FT3 (7.6 pg/mL; normal range: 2.3-4.0), determined by competitive Elecsys. To exclude possible assay interference, aliquots of the original samples were retested using a different method (ADVIA Centaur), which showed normal FT4 and FT3 levels. Eight hormone levels, other than thyroid function tests measured by competitive or sandwich Elecsys, were higher or lower than levels determined by an alternative analysis. Subsequent examinations, including gel filtration chromatography, suggested interference by substances against ruthenium, which reduced the excitation of ruthenium, and resulted in erroneous results(24). Other suggested that patients with TSH-secreting pituitary tumors(TSHoma) also manifest SITSH. Thus, the differential diagnosis of RTH vs. TSHoma is sometimes difficult and challenging. In this review article, the etiology of RTH and diagnostic approach for SITSH are explained and an algorithm for differential diagnosis of RTH vs. TSHoma is proposed(25).
3. Coexistence of mutation genes
There is a report of the coexistence of THRB and TBG gene mutations in the same individual (mother of the proband), whereas other affected family members had only 1 of the 2 genes mutated. The case illustrates the difficulty that might be encountered in the interpretation of thyroid function tests when different genetic defects affecting thyroid function coexist(26).
4. Grave’s disease
RTH is often misdiagnosed as Graves’ disease. However, these disorders can coexist, and the concurrent presence of both disorders in a patient can present diagnostic challenges. A previous report of a patient with Graves’ disease associated with RTH was published before gene sequencing could be used to confirm diagnosis of RTH. There is a report of a patient with Graves’ disease and concurrent RTH that was confirmed by gene sequencing, showing a mutation in the thyroid hormone receptor beta gene(27).
D.2. Diagnosis
If you are experience certain symptoms of the above and your doctor suspects that you have developed acute thyroiditis, after recording the past and present history and completing a physical exam, the tests which your doctor orders may include
1. Urinary test
Urinary cortisol metabolites are altered both quantitatively and qualitatively in thyroid dysfunction. According to the study by the Showa University, the ratio of the urinary concentrations of cortisol metabolites, THE/THF, appears to be a good marker for peripheral thyroid hormone resistance(28).
2. Blood test
Unfortunately, the blood test results of the disorder can also be found in other disorders such as TSH-oma (pituitary adenoma), or other pituitary disorders. According to the study by the Nagoya University, almost all patients with RTH manifest unsuppressed thyrotropin (TSH) despite elevated free-T4 and free-T3 levels. This abnormal finding in the thyroid function test is termed “syndrome of inappropriate secretion of TSH” (SITSH) or “central hyperthyroidism”. Patients with TSH-secreting pituitary tumors(TSHoma) also manifest SITSH. Thus, the differential diagnosis of RTH vs. TSH-oma is sometimes difficult and challenging(29)
3. Identifying a mutation of the thyroid receptor
Resistance to thyroid hormone (RTH) is a rare condition usually diagnosed in patients with classic thyroid function tests (TFTs) of elevated thyroid hormone levels with nonsuppressed TSH. According to the study by the, At least six major steps are required for secreted thyroid hormone (TH) to exert its action on target tissues. Mutations interfering with three of these steps have been so far identified. The first recognized defect, which causes resistance to TH, involves the TH receptor β gene and has been given the acronym RTH(30).
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Sources
(23) http://www.ncbi.nlm.nih.gov/pubmed/16445164
(24) http://www.ncbi.nlm.nih.gov/pubmed/22673200
(25) http://www.ncbi.nlm.nih.gov/pubmed/23214067
(26) http://www.ncbi.nlm.nih.gov/pubmed/23633200
(27) http://www.ncbi.nlm.nih.gov/pubmed/20151830
(28) http://www.ncbi.nlm.nih.gov/pubmed/8257864
(29) http://www.ncbi.nlm.nih.gov/pubmed/23214067
(30) http://www.bprcem.com/article/S1521-690X%2807%2900026-7/abstract