Overview
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.
Description
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.
Eligibility
- INCLUSION CRITERIA:
The categories of subjects eligible to participate in this study include:
- 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.
- 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.