T3 Uptake - Kresser Institute Membership Site

Marker Name: T3 uptake

REFERENCE RANGES FOR T3 (TRIIODOTHYRONINE) UPTAKE:

Laboratory reference range:
Male and Female: 24–39%

Functional reference ranges:
Male: 30–38%
Female: 28–35%

DESCRIPTION:

Triiodothyronine (T3) uptake, or T3 resin uptake, estimates the saturation of thyroid hormone molecules on serum-binding proteins (mostly thyroxine-binding globulin, or TBG).^1,2 T3 uptake was developed to determine whether abnormal thyroxine (T4) levels are due to differences in free thyroid hormone levels or abnormal TBG levels.¹

According to the free hormone hypothesis, only free hormone (i.e., hormone that is not bound to serum proteins) can be taken up by cells and affect nuclear thyroid hormone receptors.^1,4 Less than 0.5 percent of serum T3 is “free”; 80 percent of T3 is bound to TBG, 15 percent is bound to albumin and lipoproteins, and 5 percent is bound to transthyretin (TTR).³ Given that the majority of thyroid hormone is bound, the levels of serum proteins can have a substantial effect on bound thyroid hormone levels, and therefore total thyroid hormone levels in blood.^1,3 Importantly, serum protein levels do not alter free hormone concentrations or the absolute rates of thyroid hormone metabolism.³ While total and free thyroid hormone levels can often provide an accurate picture of thyroid function, total thyroid hormone levels are decidedly inaccurate if serum-binding proteins are deficient or present in excess.^1,5 The T3 uptake test can provide clarity in these cases.

Utility of the T3 resin uptake test can be best understood through clinical examples. A person with an abnormally high T4 level may either have true hyperthyroidism or an elevated serum TBG level.⁶ The T3 resin uptake test can distinguish between the two clinical situations; uptake will be high in hyperthyroidism or low in a state of TBG excess. The converse is also true. A low T4 level may indicate hypothyroidism or diminished TBG. In hypothyroidism, T3 uptake will also be low. However, if TBG levels are abnormally low, T3 uptake will be abnormally high.⁶

Clinical Status	Total T4	T3 resin uptake
Hyperthyroidism	High	High
Hypothyroidism	Low	Low
High TBG	High	Low
Low TBG	Low	High

Any illness that depletes TBG levels will increase T3 uptake.⁶ This depletion of TBG may be due to a lack of serum protein production (e.g., liver cirrhosis) or through protein excretion by the kidney (e.g., nephrotic syndrome). Any serious illness can reduce TBG levels and increase T3 uptake. TBG levels are sensitive to the presence of other circulating hormones either in the context of disease (e.g., acromegaly, Cushing syndrome) or from exogenous administration (e.g., corticosteroids, androgens).

An increase in TBG in serum will decrease T3 uptake.⁶ While liver disease is usually associated with a drop in serum proteins (e.g., albumin), hepatitis and porphyria actually increase TBG levels.^7,8 Normal pregnancy may result in an increase in serum TBG. TBG levels are also related to circulating estrogens, including pharmacological doses of estrogens such as those found in oral contraceptives.

T3 resin uptake is only meaningful in the context of other thyroid function testing, particularly T4 levels. Therefore, it is essential to measure T3 uptake, T4 levels, and TSH levels together or temporally near each other.^1,5,6

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^5,10

Hyperthyroidism
Cushing disease
Acromegaly
Serious illness (i.e., reduced TBG)
Diabetic ketoacidosis
Cirrhosis
Nephrotic syndrome
X-linked decreased thyroid-binding globulin
Drugs
- Corticosteroids (e.g., prednisone)
- Androgens (e.g., anabolic steroids)
- Salicylates
- Asparaginase
- Danazol
- Niacin

Low in:^5,7,9

Pregnancy
Hypothyroidism
Hepatitis
Primary biliary cirrhosis
Malnutrition
Porphyria
X-Linked increased thyroid-binding globulin
Drugs
- Estrogens (e.g., oral contraceptives)
- Perphenazine
- Fluorouracil
- Clofibrate

FUNCTIONAL RANGE INDICATIONS:

High in:

Testosterone replacement
PCOS
Salicylate use
Heparin therapy

Low in:

Estrogen replacement
Heparin therapy

References: