Study Criteria

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 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.

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

       -  Non-thyroidal illness

       -  Abnormalities of serum TH binding proteins leading to euthyroid hyperthyroxinemia
          or hypotriiodothyronemia.

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

       -  Antibodies to mouse immunoglobulins leading to an artifactual elevation in the
          TSH 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 the
     duration 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 producing
     exophthalmos (Graves' ophthalmopathy), as well as the skin in the pretibial area
     causing pretibial myxedema (Graves' dermopathy);

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

  3. Silent thyroiditis, a painless inflammation thought to result from autoimmune attack
     of 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, probably
     resulting 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 patients with
     underlying psychiatric disease or occasionally related to patients with obesity and
     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 the TSHR
     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. pituitary
     resistance 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 to
     thyroid proteins, such as antimicrosomal antibodies to TPO usually associated with
     lymphocytic (Hashimoto's) thyroiditis (HT) or atrophic thyroiditis, or blocking
     antibodies to the TSHR, usually in the context of non-goitrous hypothyroidism;

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

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

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

  5. Generalized resistance to thyroid hormone (RTH), a disease which has been shown to be
     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.