Mental retardation

Mental retardation (MR) is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors. It has historically been defined as an Intelligence Quotient score under 70.[1] Once focused almost entirely on cognition, the definition now includes both a component relating to mental functioning and one relating to individuals' functional skills in their environment. As a result, a person with a below-average intelligence quotient (BAIQ) may not be considered mentally retarded. Syndromic mental retardation is intellectual deficits associated with other medical and behavioral signs and symptoms. Non-syndromic mental retardation refers to intellectual deficits that appear without other abnormalities.

Thyroid dwarf

Cretinism cretinism , condition produced in infants and children due to lack of thyroid hormone. It usually results from a congenital defect (e.g., absence of the thyroid, presence of only a rudimentary gland, inability of the gland to produce thyroxine). ..... Click the link for more information. is a type of dwarfism accompanied by mental retardation and distortion of the body, resulting from an insufficiency of thyroid hormone.

Thyroxine, or 3,5,3',5'-tetraiodothyronine (often abbreviated as T4), a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland. Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.[1][2]

Regulation of thyroid hormone levels

TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3).[4] TSH production is controlled by thyrotropin-releasing hormone (TRH), which is manufactured in the hypothalamus and transported to the anterior pituitary gland via the hypothalamo-hypophyseal portal system, where it increases TSH production and release. Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary production of TSH, decreasing or inhibiting its release. The level of thyroid hormones (T3 and T4) in the blood has an effect on the pituitary release of TSH; when the levels of T3 and T4 are low, the production of TSH is increased, and, on the

converse, when levels of T3 and T4 are high, TSH production is decreased. This effect creates a regulatory negative feedback loop.
[edit] Subunits

TSH is a glycoprotein and consists of two subunits, the alpha and the beta subunit.
The (alpha) subunit (i.e., chorionic gonadotropin alpha) is nearly identical to that of human chorionic gonadotropin (HCG), luteinizing hormone (LH), folliclestimulating hormone (FSH). The subunit is thought to be the effector region responsible for stimulation of adenylate cyclase (involved the generation of cAMP). The chain has a 92-amino acid sequence The (beta) subunit (TSHB) is unique to TSH, and therefore determines its receptor specificity. The chain has a 118-amino acid sequence.

[edit] The TSH receptor

The TSH receptor is found mainly on thyroid follicular cells.[5] Stimulation of the receptor increases T3 and T4 production and secretion. Stimulating antibodies to this receptor mimic TSH and cause Graves' disease.

Applications
[edit] Diagnostic Further information: Thyroid function tests

TSH levels are tested in the blood of patients suspected of suffering from excess (hyperthyroidism), or deficiency (hypothyroidism) of thyroid hormone. In general, a standard reference range for TSH for adults is between 0.4 and 3.0 IU/mL (equivalent to mIU/L), but values vary slightly among labs. The therapeutic target range TSH level for patients on treatment ranges between 0.3 to 3.0 IU/mL.[6] The interpretation depends also on what the blood levels of thyroid hormones (T3 and T4) are. TSH levels for children normally start out much higher. In 2002, the National Academy of Clinical Biochemistry (NACB) in the United States recommended age-related reference limits starting from about 1.3 to 19 IU/mL for normal-term infants at birth, dropping to 0.610 IU/mL at 10 weeks old, 0.47.0 IU/mL at 14 months and gradually dropping during childhood and puberty to adult levels, 0.44.0 IU/mL.[7] The NACB also stated that it expected the normal (95%) range for adults to be reduced to 0.4 2.5 IU/mL, because research had shown that adults with an initially measured TSH level of over 2.0 IU/mL had "an increased odds ratio of developing hypothyroidism over the [following] 20 years, especially if thyroid antibodies were elevated".[8]

Source of pathology

TSH level

Thyroid hormone level

Disease causing conditions Benign tumor of the pituitary (adenoma) or thyroid hormone resistance Hypopituitarism Hyperthyroidism or Graves' disease Congenital hypothyroidism (cretinism), hypothyroidism or Hashimoto's thyroiditis

Hypothalamus/pitui High High tary Hypothalamus/pitui Low tary Thyroid Thyroid Low Low High

High Low

A TSH assay is now also the recommended screening tool for thyroid disease. Recent advances in increasing the sensitivity of the TSH assay make it a better screening tool than free T4.[