Endocrine Metabolism IV: Thyroid Gland
The lodothyronine Deiodinases
5 -deiodination (outer ring)
5 -deiodination (outer ring)
5-deiodination (inner ring)
rT3 > T4 > T3
T4 > rT3
T3 > T4
Liver, kidney, thyroid, et al.
Brain, pituitary, skin, brown fat
Liver, kidney, et al.
Affinity (Km) for T4
Low (~1 jtiM)
High (~1 nM)
High (~40 nM)
High carbohydrate diet
*Iopanoic acid (3-amino-a-ethyl-2,4,6-?n/o4o-hydrocinnamic acid) is a radiopaque iodine compound used as a contrast medium in cholecystography.
**Amiodarone (2-butyT3-benzofuranyl) [4- [2- (diethylamino) ethoxyl]-3,5-d//orfo-phenyl] methanone) is a coronary vasodilator used in the con-
trol of ventricular arrhythmias, and in the management of angina pectoris.
*The physiologic rise in cortisol levels at about the time of birth stimulates 5'-deiodinase and causes a rise in T3 and fall in rT3. The effect of physi-
ologic levels of cortisol on 5-deiodinase in adults is unclear.
T4, both involving the removal of the inner ring 5-iodide.
The type III enzyme is widely distributed among tissues
and is responsible for the formation of almost all (95%)
of the circulating rT3. Its activity is not altered by most
of the factors or conditions that inhibit the activity of
types I or II deiodinases, and this explains why there is
a reciprocal relationship between the plasma levels of T
Not all metabolic processing of iodothyronines involves
deiodination, although it is the major metabolic route for
T4, T3, and rT3, accounting for about 80% of the fate
of each compound. The remaining 20% is conjugated in
the liver with sulfate or glucuronide, and/or processed by
oxidative deamination and decarboxylation to form thy-
roacetic acid derivatives with minimal biological activity
Inorganic iodide liberated from deiodinations enter the
extracellular compartment and is excreted in the urine
(~488 /zg/d) or stool (~12 /xg/d via bile), or is reabsorbed
by the thyroid gland (~108 /zg/d) for resynthesis of thy-
roid hormones. At the average daily intake of ~500 /xg
inorganic iodide, this amounts to no net change in the
iodide status, although the small amount of iodide that
is lost through the skin and gastrointestinal tract would
place the body in a negative iodide balance unless intake
is adjusted accordingly.
33.4 Biological Actions of Thyroid Hormones
Mechanism of Action and Latency Period
All but a few of the thyroid effects that have been identi-
fied occur at the level of gene transcription, mediated by
nuclear thyroid hormone receptors (Chapter 30). These ef-
fects have a longer latency period than for most steroids;
some of the relatively early responses show a latency
period of several hours.
Thyroid hormone enhances cardiac contractility and ex-
erts a positive chronotropic effect on the heart, increas-
ing heart rate by a mechanism that may involve more
than a potentiation of the
-adrenergic effect. In the