Topic 47 Thyroid hormones

Figure 2.6 Dorzolamide 16, a topically active carbonic anhydrase inhibitor, resulted from a structure-based ligand design it is used for the treatment of glaucoma. Sulfaguanidine 17 inhibits thyroid hormone biosynthesis. A phenylog of sulfanilamide 11 (Figure 2.4), dapsone 18, is used for the treatment of leprosy.

Steroid hormones are lipid-soluble molecules that act by a different mechanism. Once a steroid hormone has diffused into a cell, it binds to a specific receptor protein in the cytoplasm. The hormone-receptor complex moves into the nucleus, where it binds to specific sites on DNA. Steroid-receptor complexes alter a cell s pattern and rate of gene transcription and, ultimately, protein synthesis. (This topic is discussed in Chapter 18.) The thyroid hormones act similarly. 

The available data from in vivo, as well as from in vitro, experiments clearly demonstrate that soy isoflavones act as inhibitors of TPO and thus may influence iodine incorporation in thyroid hormone biosynthesis. On the other hand, most of the cfinical trials, including our own, have shown only modest and transitory effects of soy isoflavones on circulating thyroid hormone levels. However, they may be important in the case of insufficient iodine supply. Besides thyroid hormone biosynthesis, soy isoflavones may influence other events involved in thyroid function, such as iodine transport, thyroid hormone deiodination, and signaling pathways. So far, the data available on these topics is scarce and more experiments addressing these issues are needed. 

Topical methimazole is used as a skin depigmenting agent for conditions that include epidermal melasma. In 20 patients who used this treatment once daily for 6 weeks there were no significant changes in circulating thyroid hormone or thyroid-stimulating hormone (TSH) and no significant cutaneous adverse reactions [33 ]. 

Uses Despite the presence of thyroid hormone receptors on hair follicles and associated cells [16 ] and the success of topical T3 as a stimulate of hair growth in animals [17 ], topical treatment of alopecia areata with T3 (3.8 gg T3/30 gg of vehicle Novasome A) for 12 weeks in 10 patients in a double-blind placebo-controlled trial was found to be safe but ineffective in restoring hair growth [18 ]. 

Small lipophilic (lipid-soluble) hormones diffuse across the plasma membrane and then interact with intracellular receptors in the cytosol or nucleus. The resulting hormone-receptor complex often binds to regions of the DNA and affects the transcription of certain genes (see Topic G7). Small lipophilic hormones with intracellular receptors include the steroid hormones which are synthesized from cholesterol (see Topic K5) (e.g. the female sex hormones estrogen and progesterone), thyroxine which is produced by thyroid cells and is the principal iodinated compound in animals, retinoic acid which is derived from vitamin A, and vitamin D which is synthesized in the skin in response to sunlight (see Topic K5). 

Iodine I2 (elemental Iodine) term also used generically for all chemical forms of Iodine Possibly an Intermediate In the synthesis of hormone within thyroid cells Used as topical disinfectant. No use In IDD control... 

Hamburgh M, The role of thyroid and growth hormone in neurogenesis, in "Current Topics in Developmental Biology", Moscona AA, Monroy A (eds) Academic Press, New York, vol 4 109 (1969)... 

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