Thyroid and the Skin

Thyroid hormones influence the differentiation, maturation, and growth of many different body tissues; the total energy expenditure of the organism; and the turnover of nearly all substrates, vitamins, and other hormones. Thus, it is not surprising that the thyroid gland plays an important role in both skin development and the maintenance of normal cutaneous function. In general, the biologic effects of thyroid hormones require binding to specific nuclear receptors with subsequent alteration of gene transcription and stimulation of messenger RNA synthesis. It is postulated that, in addition to nuclear receptors, subcellular receptors exist in mitochondria and plasma membranes. It has been clearly demonstrated that thyroid activity directly affects oxygen consumption, protein synthesis, mitosis, and the thickness of the epidermis. Thyroid activity is also considered essential for the formation and growth of hair, and for sebum secretion. Dermal effects are less well defined.

The impact of thyroid hormone activity on the integument, however, is more notable during deficiency or excess states than during normal physiologic processes. The prevalence of hypothyroidism is 4.6% and that of hyperthyroidism is 1.3%, therefore, the clinician will frequently observe these findings in practice. With several important exceptions (discussed later), the majority of cutaneous changes accompanying thyroid disease are neither unique nor pathognomonic. However, in patients with thyroid dysfunction, even such nonspecific cutaneous findings and associations often provide important clues that aid in the diagnosis of previously unsuspected thyroid disease. Finally, some syndromes with cutaneous or mucosal lesions are associated with an increased risk for thyroid tumors (e.g., Cowden’s disease, multiple mucosal neuroma syndromes, Gardner’s syndrome, Carney’s complex, and Werner’s syndrome).

The thyroid gland, which weighs an average of 20 to 25 g in adults, actively secretes thyroxine (T ₄ ) and triiodothyronine (T ₃ ) from the intraluminal thyroglobulin of its follicular cells. The follicular cells are derived primarily from median midpharyngeal tissue during embryologic development. T ₃ is more active than its precursor T ₄ . It is worth noting that about 80% of the T ₃ produced daily actually results from hepatic and renal deiodination of T ₄ , rather than from direct thyroid secretion. Thyroxine has a lower metabolic clearance rate and longer serum half-life than T ₃ because it binds more tightly to serum-binding proteins than does T ₃ . The half-life of T ₃ is less than a day, whereas the half-life of T ₄ is about 7 days. Furthermore, although only 0.02% of the total plasma T ₄ and 0.30% of the total plasma T ₃ are free (i.e., not protein bound), the free forms both determine the thyroid “status” and maintain the negative feedback regulatory system involving the hypothalamic–pituitary–thyroid axis.

Calcitonin is secreted from thyroid parafollicular cells (C cells). This hormone is involved in the metabolism of calcium and phosphorus, leading to decreasing serum calcium by inhibiting osteoclast bone resorption. In comparison, parathyroid hormone increases bone resorption. The parafollicular cells are derived embryologically from the neural crest, becoming incorporated within the ultimobranchial pharyngeal pouch.

Thyroid evaluation should commence with a physical examination of the gland. Laboratory tests of direct thyroid function include total and free T ₄ and T ₃ , free T ₄ index, T ₃ or T ₄ resin uptake (now termed the thyroid hormone-binding ratio), and radioactive iodine uptake. An evaluation of thyroid gland function is characteristically based on thyrotropin levels (thyroid-stimulating hormone—TSH), being elevated in patients with primary causes of hypothyroidism (e.g., Hashimoto’s thyroiditis) or reduced in patients with primary forms of hyperthyroidism (e.g., Graves’ disease). The thyroid may undergo anatomic evaluation by a thyroid scan, ultrasonography, fine-needle aspiration, or surgical biopsy. Finally, tests for autoimmune thyroid disease include serum thyroid peroxidase (antimicrosomal), thyroid-stimulating, or antithyroglobulin antibody determination. Following thyroidectomy for carcinoma, increases in serum thyroglobulin are considered suspicious for recurrent disease. Table 25-1 shows the differences in laboratory tests for Graves’ disease and Hashimoto’s thyroiditis.

The cutaneous manifestations of thyroid disease may be categorized as follows: (1) specific lesions that contain thyroid tissue; (2) signs and symptoms of hyperthyroid and hypothyroid states; and (3) other skin or systemic disorders associated with thyroid disease.