Protocol Number: 06-DK-0133

Title:

Thyroid Hormone-Induced Lipolysis: An In Vivo Microdialysis Study

Number:

06-DK-0133

Summary:

This study will use a technique called microperfusion to examine how thyroid hormones are involved in fat metabolism. The thyroid gland produces two kinds of hormones: T3 and T4. Some of the T4 is changed to T3 in various organs after leaving the thyroid. The T3 stimulates the body to burn fat. People have different rates at which they can change T4 to T3, and this may lead to differences in body fat among different people.

Microperfusion is based on the exchange of substances across tiny holes of a small plastic tube called a "probe," which is inserted after numbing the skin over a fat pad. Through these openings, the fat pad is continuously rinsed with small amounts of fluid, and an exchange of substances occurs. The fluid drips from the other opening of the probe and is collected in a vial. Small amounts of study drugs are infused and the amount of substances released by the fat pad in response to them are measured.

Healthy normal volunteers 18 years of age and older may be eligible for this study. Candidates are screened with a medical history, physical examination and blood tests.

Participants undergo microperfusion. A needle is placed in an arm vein for collecting blood samples before and at the end of the experiment for measuring thyroid hormones and other substances in the blood. The skin over the fat pad next to the umbilicus (navel) is numbed and two microperfusion probes are inserted. A salt water solution is infused into the fat pad for one hour and the substances in the fluid are measured as the fluid leaves the fat pad. After 1 hour isoproterenol, a drug that aids in energy production by fat, is added to help determine the level of fat metabolism. After an additional hour small amounts of thyroid hormone are added to the fluid and samples are collected as they leave the body. Two catheters are inserted during each experiment. Small volumes of sterile fluid are circulated continuously in the tubing and samples are collected at regular intervals.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

- Age greater than or equal to 18 years, male or female.

- Written informed consent.

EXCLUSION CRITERIA:

- Hypo- or hyper-thyroid (history or TSH greater than 5.0 or less than 0.4 miU/L)

- Blood pressure greater than 140/90 mmHg [17] or current antihypertensive therapy

- History of cardiovascular disease

- BMI less than or equal to 20 or greater than or equal to 30 Kg/m(2).

- Diabetes mellitus (serum glucose greater than or equal to 126 mg/dL).

- Hypercholesterolemia (serum levels greater than or equal to 240 mg/dL), hypertriglyceridemia (plasma levels greater than or equal to 220 mg/dL) and/or use of antilipemic therapy.

- Liver disease or ALT serum level greater than two fold the upper laboratory reference limit.

- Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min (Cockcroft method).

- History of illicit drug or alcohol abuse within the last 5 years; current use of drugs (by history) or alcohol (CAGE greater than 3).

- Psychiatric conditions or behavior that would be incompatible with safe and successful participation in this study

- Current use of medications/dietary supplements/alternative therapies known to alter thyroid function.

- Allergy to ethanol, levothyroxine, liothyronine, isoproterenol, lidocaine.

- Pregnancy/breastfeeding.

- Current smoker

All subjects will be fully informed of the aim, nature, and risks of the study prior to giving written informed consent.

Special Instructions:

Currently Not Provided

Keywords:

Deiodinase

Levothyroxine

Liothyronine

Lipid Metabolism

Recruitment Keyword(s):

Healthy Volunteer

HV

Condition(s):

Healthy Volunteers

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Elks ML, Manganiello VC. Effects of thyroid hormone on regulation of lipolysis and adenosine 3',5'-monophosphate metabolism in 3T3-L1 adipocytes. Endocrinology. 1985 Sep;117(3):947-53.

Germack R, Starzec A, Perret GY. Regulation of beta 1- and beta 3-adrenergic agonist-stimulated lipolytic response in hyperthyroid and hypothyroid rat white adipocytes. Br J Pharmacol. 2000 Feb;129(3):448-56.

Mentuccia D, Proietti-Pannunzi L, Tanner K, Bacci V, Pollin TI, Poehlman ET, Shuldiner AR, Celi FS. Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes. 2002 Mar;51(3):880-3.

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