Natural History of Thyroid Function Disorders

• INCLUSION CRITERIA:

The categories of subjects eligible to participate in this study include:

1. Patients with known or suspected thyroid abnormalities (e.g. hypothyroidism,hyperthyroidism, extreme iodine deficiency, and inherited forms of hypothyroidismresulting from abnormalities in the expression of genes coding for the TSH- betasubunit, Pax-8, TTF-2, Pit-I, Tg, PDS, and NIS.

2. Patients with thyroid function test (TFT) abnormalities due to:

• Non-thyroidal illness

• Abnormalities of serum TH binding proteins leading to euthyroidhyperthyroxinemia or hypotriiodothyronemia.

• Genetic deficiency of thyroxine-binding globulin (TBG).

• Antibodies to mouse immunoglobulins leading to an artifactual elevation in theTSH ultrasensitive ("3rd generation") assay which may mimic "inappropriate"secretion of TSH.

Inclusion and exclusion criteria for each group of subjects are given below.

Patients with known or suspected thyroid abnormalities will be eligible to p rticipate if the individual meets all of the following criteria:

1. Stated willingness to comply with all study procedures and availability for theduration of the study.

2. Male or female, aged 6 months+.

Hyperthyroid states include but are not restricted to:

1. Graves' disease (GD) thought to result from thyroid-stimulating immunoglobulins (TSIg's), a subclass of which also stimulate eye muscle and fatty tissue producingexophthalmos (Graves' ophthalmopathy), as well as the skin in the pretibial areacausing pretibial myxedema (Graves' dermopathy);

2. Subacute thyroiditis (SAT), a painful inflammation thought to result from viralinfection with Coxsackie, as well as other viruses;

3. Silent thyroiditis, a painless inflammation thought to result from autoimmune attackof thyrocytes by antimicrosomal antibodies directed against thyroid peroxidase (TPO), as well as antithyroglobulin(anti-Tg) antibodies;

4. Single or multiple hyperfunctioning thyroid nodules of unknown etiology, probablyresulting from the activation of certain thyroid oncogenes and/or growth factors,such as the thyrotropin (TSH) receptor (TSHR) and the a-subunit of the G protein (Ga);

5. Iodide-induced hyperthyroidism of unknown etiology;

6. Surreptitious administration of thyroid hormone (TH), usually present in patientswith underlying psychiatric disease or occasionally related to patients with obesityand other eating disorders

7. Trophoblastic neoplasms, thought to result from high levels of hCG secretion, which,because of its structural similarity to TSH, causes "spillover" of action at theTSHR level;

8. "Inappropriate" secretion of TSH, which may be present either in patients with TSH-producing pituitary tumors (TSHomas) or from a non-neoplastic cause, i.e. pituitaryresistance to the action of thyroid hormone (3,4).

Hypothyroid states include but are not restricted to:

1. Primary (or thyroidal) hypothyroidism, usually resulting from auto-antibodies tothyroid proteins, such as antimicrosomal antibodies to TPO usually associated withlymphocytic (Hashimoto's) thyroiditis (HT) or atrophic thyroiditis, or blockingantibodies to the TSHR, usually in the context of non-goitrous hypothyroidism;

2. Secondary (or pituitary) hypothyroidism, usually resulting from tumors of thepituitary of non-thyrotropic origin such, as growth hormone (GH)-secreting tumors orprolactinomas;

3. Tertiary (or hypothalamic) hypothyroidism, usually resulting from a deficiency inthe hypothalamic hormone thyrotropin-releasing hormone (TRH), either of unknownetiology or secondary to a pituitary tumor;

4. Bio-inactive TSH, either relating to an endogenous abnormality of hypothalamichormones or secondary to pituitary tumors (and usually related to abnormalglycosylation patterns of the TSH molecule);

5. Generalized resistance to thyroid hormone (RTH), a disease which has been shown tobe due to abnormalities in the TH receptor, c-erbA-beta (or TR- beta).

The above are the principal disorders under study, but we may also investigate other abnormalities, such as extreme iodine deficiency, and inherited forms of hypothyroidism resulting from abnormalities in the expression of genes coding for the TSH- beta subunit, Pax-8, TTF-2, Pit-I, Tg, PDS, and NIS (among others).

EXCLUSION CRITERIA:

There are no exclusion criteria for subjects with known or suspected thyroid abnormalities.