Evaluation of Patients With Thyroid Disorders
Evaluation of Patients With Thyroid Disorders
Participants in this study will be patients diagnosed with or suspected to have a thyroid
 function disorder. These conditions may include: hypothyroidism, hyperthyroidism, thyroid
 hormone resistance, Graves' Dermopathy, and thyroid-stimulating hormone (TSH) secreting
 pituitary adenomas.

 The main purpose of this study is to further understand the natural history, clinical
 presentation, and genetics of thyroid function disorders. Many of the tests performed are in
 the context of standard medical care that is offered to all patients with thyroid function
 disorders. In addition, blood and tissue samples may be taken for research and genetic
 studies.
Patients with thyroid function abnormalities (hyperthyroidism, hypothyroidism) are studied
 and treated in this protocol. Patients undergo routine history and physical examination,
 standard endocrine blood and urine tests, a standard TRH test, thyroid nuclear medicine
 scans, thyroidal radioiodine (RAI) or technetium (99mTc) uptake measurements, as well as
 X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) studies or other standard
 diagnostic procedures, as clinically indicated.

 The goals of this study are:

 -  1. To understand the pathophysiology and various causes of thyroid function
 abnormalities (e.g., hyperthyroidism, hypothyroidism).

 -  2. To longitudinally follow the effects of standard therapies for patients with abnormal
 thyroid functions.

 -  3. To create a repository of clinical data and biospecimens for future research of
 thyroid disorders.

 Our objective will be accomplished by obtaining clinical data and biospecimens during
 standard care procedures and tests performed on enrolled subjects being evaluated as an
 outpatient in the clinic or as an inpatient at the NIH Clinical Center.
-  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.