Thyroid hormone resistance
Encyclopedia
Thyroid hormone resistance describes a rare syndrome
where the thyroid hormone
levels are elevated but the thyroid stimulating hormone (TSH) level is not suppressed, or not completely suppressed as would be expected.
s of the β (beta) form (THRB gene) of the thyroid hormone receptor
, of which over 100 different mutations have been documented.
Mutations in MCT8 and SECISBP2
have also been associated with this condition.
s, even between members of the same family harboring the same mutation. Typically most or all tissues are resistant to thyroid hormone, so despite raised measures of serum thyroid hormone the individual may appear euthyroid
(have no symptoms of over- or underactivity of the thyroid gland). The most common symptoms are goiter and tachycardia
. It has also been linked to some cases of attention deficit hyperactivity disorder (ADHD), although the majority of people with that diagnosis have no thyroid problems.
An association with depression
has been proposed.
results for this disorder can also be found in other disorders (for example TSH-oma (pituitary adenoma
), or other pituitary disorders). The diagnosis may involve identifying a mutation of the thyroid receptor, which is present in approximately 85% of cases.
Yet, since discovery of resistance to thyroid hormones in the absence of thyroid hormone receptor beta mutations, lack of a mutation in a patient does not rule out resistance.
to thyroid hormones. Antibodies to thyroid hormones quite commonly occur in such disorders, and may interfere with the normal clinical assays used in monitoring such disorders, and in unusual cases may have further independent clinical significance.
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
where the thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
levels are elevated but the thyroid stimulating hormone (TSH) level is not suppressed, or not completely suppressed as would be expected.
Causes
The most common cause of the syndrome are mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s of the β (beta) form (THRB gene) of the thyroid hormone receptor
Thyroid hormone receptor
The thyroid hormone receptor is a type of nuclear receptor that is activated by binding thyroid hormone.-Function:Amongst the most important functions of thyroid hormone receptors are regulation of metabolism and heart rate...
, of which over 100 different mutations have been documented.
Mutations in MCT8 and SECISBP2
SECISBP2
SECIS-binding protein 2 is a protein that in humans is encoded by the SECISBP2 gene.- Function :The incorporation of selenocysteine into a protein requires the concerted action of an mRNA element called a sec insertion sequence , a selenocysteine-specific translation elongation factor and a SECIS...
have also been associated with this condition.
Incidence
Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births.Presentation
The syndrome can present with variable symptomSymptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s, even between members of the same family harboring the same mutation. Typically most or all tissues are resistant to thyroid hormone, so despite raised measures of serum thyroid hormone the individual may appear euthyroid
Euthyroid
Euthyroid is the state of having normal thyroid gland function.Examples of a nonfunctioning thyroid gland may be hypothyroidism, hyperthyroidism, or thyroiditis....
(have no symptoms of over- or underactivity of the thyroid gland). The most common symptoms are goiter and tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
. It has also been linked to some cases of attention deficit hyperactivity disorder (ADHD), although the majority of people with that diagnosis have no thyroid problems.
An association with depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
has been proposed.
Diagnosis
The characteristic blood testBlood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
results for this disorder can also be found in other disorders (for example TSH-oma (pituitary adenoma
Pituitary adenoma
Pituitary adenomas are tumors that occur in the pituitary gland, and account for about 15% of intracranial neoplasms. Tumors which exceed 10 mm in size are defined as macroadenomas, and those smaller than 10 mm are referred to as microadenomas...
), or other pituitary disorders). The diagnosis may involve identifying a mutation of the thyroid receptor, which is present in approximately 85% of cases.
Yet, since discovery of resistance to thyroid hormones in the absence of thyroid hormone receptor beta mutations, lack of a mutation in a patient does not rule out resistance.
Terminology
Sometimes the phrase thyroid hormone resistance is used to identify cases where patients with autoimmune thyroid disorders respond poorly to normal doses of replacement thyroid hormone. This is thought to occur where patients have developed antibodiesAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
to thyroid hormones. Antibodies to thyroid hormones quite commonly occur in such disorders, and may interfere with the normal clinical assays used in monitoring such disorders, and in unusual cases may have further independent clinical significance.