ERFA® 2 grain (Thyroid)

The principal pharmacologic effect of exogenous thyroid hormones is to increase the metabolic rate of body tissues.

The normal thyroid gland contains approximately 200 μg of levothyroxine (T4)/g of gland, and 15 μg of triiodothyronine (T3)/g. The ratio of these two hormones in the circulation does not represent the ratio in the thyroid gland, since about 80% of peripheral triiodothyronine comes from monodeiodination of the outer ring of levothyroxine. Peripheral monodeiodination of levothyroxine at the 5 position (inner ring) also results in the formation of reverse triiodothyronine (r T3), which is calorigenically inactive. These facts would seem to advocate levothyroxine as the treatment of choice for the hypothyroid patient and to mitigate against the administration of hormone combinations which while normalizing thyroxine levels, may produce triiodothyronine levels in the thyrotoxic range.

Triiodothyronine (T3) level is low in the fetus and newborn, in old age, in chronic caloric deprivation, hepatic cirrhosis, renal failure, surgical stress, and chronic illnesses representing what has been called the “low triiodothyronine syndrome.”

Pharmacokinetics:

Animal studies have shown that T4 is only partially absorbed from the gastrointestinal tract. The degree of absorption is dependent on the vehicle used for its administration and by the character of the intestinal contents, the intestinal flora, including plasma protein, soluble dietary factors, all of which bind thyroid and thereby make it unavailable for diffusion. Only 41% is absorbed when given in a gelatin capsule as opposed to a 74 percent absorption when given with an albumin carrier.

Depending on other factors, absorption has varied from 48 to 79% of the administered dose.

Fasting increases absorption. Malabsorption syndromes, as well as dietary factors (children’s soybean formula, concomitant use of anionic exchange resins such as cholestyramine), cause excessive fecal loss. T3 is almost totally absorbed, (95% in 4 hours). The hormones contained in the natural preparations are absorbed in a manner similar to the synthetic hormones.

More than 99% of circulating hormones are bound to serum proteins, including thyroid-binding globulin (TBg), thyroid-binding prealbumin (TBPA), and albumin (TBa), whose capacities and affinities vary for the hormones. The higher affinity of levothyroxine (T4) for both TBg and TBPA as compared to triiodothyronine (T3) partially explains the higher serum levels and longer half-life of the former hormone. Both protein-bound hormones exist in reverse equilibrium with minute amounts of free hormone, the latter accounting for the metabolic activity.

Deiodination of levothyroxine (T4) occurs at a number of sites, including liver, kidney, and other tissues. The conjugated hormone, in the form of glucuronide or sulfate, is found in the bile and gut where it may complete an enterohepatic circulation. Eighty-five percent of levothyroxine (T4) metabolized daily is deiodinated.