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Thyroid disease is defined as a condition of malfunction of thyroid gland.
Thyroid disease: Thyroid hormone resistance syndrome
Thyroid hormone resistance syndrome is a condition affected individuals with elevated serum thyroid hormone levels and inappropriately normal or elevated thyroid-stimulating hormone (TSH) usually required no treatment(a). Thyroid hormone resistance syndrome affects approximately 1 in 40,000 live births involved over 100 differently identified mutations.
1. Hyperactivity, emotional lability, a below average intelligence quotient, and short stature
Thyroid hormone resistance mutations are associated with a wide variety of symptoms. including hyperactivity, emotional lability, a below average intelligence quotient, and short stature(1).
2. Hyperthyroid symptoms
People with resistance to thyroid hormone may be experience hyperthyroid symptoms, such as sudden weight loss, rapid heartbeat (tachycardia), increased appetite, nervousness, anxiety and irritability, tremor, etc., if they were born to a mother with Graves' disease and treated with methimazole and iodine(2)(3).
3. Psychiatric disorders
Children born in families with resistance to thyroid hormone (RTH)may develop psychiatric symptoms(4).
4. Other symptoms
According to the study by the Northwestern University Medical School, resistance to thyroid hormone can cause, delayed bone maturation, hyperactivity, learning disabilities, and hearing defects, as well as variable features of hyper- and hypothyroidism(5), failure to thrive, growth retardation and attention-deficit hyperactivity disorder in childhood, and goitre and thyrotoxic cardiac symptoms in adults(5a).
Thyroid hormone resistance of genetic mutation, such as THRbeta gene, A317T(7) and E333D(8), MCT8(9) and SECISBP2(9) has showed to effect (9) the thyroid hormone receptor in causation of reduced hormone binding affinity, concentration of free thyroid hormone in the circulation(6).
Syndromes of reduced sensitivity to thyroid hormone due to gene mutation may also affect the movement of ions and enzyme involved in the activation or deactivation of thyroid hormones, according to the University of Chicago. In rare case, patients may also explicit impaired thyroid hormone production involved two rare congenital disorders, such as lingual ectopy of the thyroid gland and resistance to thyroid hormone (RTH)(10).
B.2. Risk factors
1. Dominant inheritance
Resistance to thyroid hormone (RTH) is an inherited syndrome of reduced tissue in response to production of thyroid hormone due to effect of mutations in the thyroid hormone receptor beta (TR beta) gene in induced impairment of T3-mediated function( (11). Gene R243W mutation in thyroid hormone receptor β in father, without showing any symptom but not the mother, was also detected in the offspring(12).
2. Graves' disease
In thyroid hormone receptor β mutations, usually inherited in an autosomal-dominant pattern may also present in baby with hyperthyroid symptoms born to a mother with Graves' disease and treated with methimazole and iodine(12).
3. Minor alterations at the DNA level
Mutations in the thyroid hormone receptor (TR) beta gene is found to be associated with 122 different mutations of resistance to thyroid hormone (RTH), in induction of minor alterations at the DNA level, according to the study by the Stoke Mandeville Hospital(13).
C. Complications and diseases associated to Thyroid hormone resistance
1. Growth retardation/short stature and skeletal dysplasia
Resistance to thyroid hormone (RTH) has shown to responsible for growth retardation/short stature, skeletal dysplasia, constipation, and defective thyroid receptor α (TRα) in children(14).
Resistance to thyroid hormone (RTH) is an uncommon inherited cause of hyperthyroxinemia due to inappropriate secretion of TSH, according to the study by the University of Cambridge, Addenbrooke's Hospital, United Kingdom(15).
3. Cardiovascular risk
Patients with resistance to thyroid hormone (RTH) are shown to be associated with arterial stiffness and elevated LDL-cholesterol levels, the causation of increased cardiovascular risk(16).
C.2. Diseases associated to Thyroid hormone resistance
1. Differentiated thyroid cancer (DTC)
Thyroid hormone resistance patients may be at increased risk to develop thyroid cancer(17), including papillary thyroid carcinoma(19).
2. A pituitary tumor
Inappropriate TSH secretion of resistance to thyroid hormone (RTH) may have an inclination for the development of pituitary hyperplasia and adenoma(18).
3. Immune thrombocytopenic purpura (ITP)
High-dose thyroid hormone replacement in treatment of patients with resistance to thyroid hormone (RTH) may induce ameliorated the features of hypothyroidism but decreased number of circulating platelets (Immune thrombocytopenic purpura (ITP))(20).
4. Postpartum thyroiditis
Although it is rare, woman affected by resistance to thyroid hormone (RTH) caused by mutation V283A in THRB genes, may also experience to postpartum thyroiditis (PPT) after pregnancies(21).
5. Chronic thyroiditis
Coincidence of resistance to thyroid hormone (RTH) and chronic thyroiditis is rare, but it can occur in patients with RTH, according to a report of the five-year medical history of a Japanese woman and her father with RTH (22).
D. Misdiagnosis and Diagnosis
Resistance to thyroid hormone (RTH) in some incidences may be initially misdiagnosed as hyperthyroidism(23).
2. Falsely diagnosis
Differential diagnosis of RTH vs. TSHoma is sometimes difficult and challenging as both syndromes show similarity of inappropriate secretion of TSH(SITSH).(25).
3. Coexistence of mutation genes
Coexistence gene mutations, such as of THRB and TBG in the same individual may complicate the interpretation of thyroid function tests because of different genetic defects in affecting thyroid function(26).
4. Grave's disease
RTH is often misdiagnosed as Graves' disease. Gene mutation differentiation in the thyroid hormone receptor beta may reduce risk of misdiagnosis(27).
If you are experience certain symptoms of the above and your doctor suspects that you have developed abnormal thyroid function, after recording the past and present history and completing a physical exam, the tests may include
1. Urinary test
The aim of the test is to analyze the cortisol metabolites in urine. The alternation of both quantitatively and qualitatively have been found to be associated to thyroid dysfunction. The abnormal ratio of the urinary concentrations of cortisol metabolites appears to be a good marker for peripheral thyroid hormone resistance, according to Showa University(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), making the differential diagnosis of RTH vs. TSH-oma 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. Gene mutation diagnosis is always necessary for correct differentiation(30).
Table. Suggested therapeutic approaches for resistance to thyroid hormone (RTH) patients.
|Drugs||Untoward effects and limitations|
|TRIAC||Effective in almost all patients|
|D-T4||Effective in almost all patients|
|T3||Production of daily peaks of very high T3 concentrations, which|
|contribute to maintain clinical hyperthyroidism|
|Transient effect owing to TSH escape from inhibition|
|Sms analog||Transient effect owing to TSH escape from inhibition|
|Corticosteroid||Cause of severe inhibition of hypothalamic-pituitary-adrenal axis function and cushingoid features|
|Antithyroid drugs||Cause of further increase in TSH circulating level with consequent increase of goiter size and to hyperplasia at pituitary thyrotroph level|
|b-blockers||Effects limited to b-adrenergic blockade.
Propranolol inhibits peripheral conversion of T4 to T3, causing a
worsening of tissue hypometabolic state. Cardiac selective compounds,
such as atenolol devoid of effect on peripheral T4 conversion, appear to
be more useful(31).|
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