Subjects of any age with known or suspected thyroid abnormalities are actively recruited to this natural history protocol. The disorders studied can be broadly defined as hyper- or hypothyroid states and laboratory abnormalities. Hyperthyroid states include but are not restricted to Graves'disease with or without extrathyroidal manifestations;subacute thyroiditis;silent thyroiditis;single or multiple hyperfunctioning thyroid nodules;iodide-induced hyperthyroidism;surreptitious administration of thyroid hormone;trophoblastic neoplasms;""""""""inappropriate"""""""" secretion of TSH arising from TSH- producing pituitary tumors or from a non-neoplastic cause, i.e. pituitary resistance to the action of thyroid hormone. Hypothyroid states include primary thyroid failure due to agenesis, autoimmunity or iatrogenic causes;secondary (or pituitary) hypothyroidism, usually resulting from tumors of the pituitary of non-thyrotropic origin such, as growth hormone (GH)-secreting tumors or prolactinomas;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;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); generalized resistance to thyroid hormone (RTH), a disease which has been shown to be due to abnormalities in the TH receptor. Additionally, conditions or states that result in abnormal thyroid function tests are studied including non-thyroidal illness;abnormalities of serum TH binding proteins leading to euthyroid hyperthyroxinemia or hypertriiodothyronemia; genetic deficiency of thyroxine-binding globulin (TBG); antibody interference in TSH or other thyroid hormone assays. Since TRH in no longer commercially available in the United States, to ensure a continuous source of TRH available for clinical use and research studies, the Pharmaceutical Development Service located in the Clinical Center Pharmacy Department, has produced pharmaceutical grade TRH for human use. Tests of the safety and activity of this new preparation of TRH was conducted healthy volunteers between the ages of 18 and 65 under an IND and this preparation is now used for clinical diagnostics and experimental studies at the NIH.

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