Thyroid and the Skin


Key Points

  • When evaluating cysts and nodules of the head and neck, consider thyroglossal ductal cysts and thyroid carcinoma metastases.

  • There are many syndromes associated with thyroid cancer with dermatologic manifestations (e.g., Cowden’s disease, multiple mucosal neuroma syndromes, Gardner’s syndrome, Carney’s complex, and Werner’s syndrome).

  • Urticaria has been associated with papillary carcinoma and autoimmune thyroid disease although the pathogenesis remains to be elucidated.

  • Pretibial myxedema, Graves’ ophthalmopathy, and thyroid acropachy often exist as a triad in patients with Graves’ disease.

  • Hypothyroid states are characterized by myxedema and mucin deposition.

  • Hair and nail changes often serve as important clues in thyroid disease (e.g., madarosis with hypothyroidism and Plummer nails in hyperthyroidism).

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.

TABLE 25-1
Thyroid Function Tests
Graves’ Disease Hashimoto’s Thyroiditis
Thyroid stimulating hormone (TSH) Decreased Increased
T 4 , T 3 , free T 4 Increased Decreased
Thyroglobulin antibody 12–30% 50–60%
Anti-TSH receptor assay 80–100% 6%
Radioiodine uptake Increased Decreased

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.

Specific Lesions

Thyroglossal Duct Cysts

During embryonic life, the developing thyroid gland descends in the neck while possibly maintaining its connection to the tongue by a narrow tube of undifferentiated epithelium, the thyroglossal duct. Thyroglossal duct cysts can present anywhere from the tongue to the diaphragm. Movement of the cyst with tongue protrusion is only seen if the connection to the tongue is preserved. This structure may activate later in life, and the cells then differentiate into columnar, ciliated, or squamous epithelium, or even into overt glandular tissue. Thyroglossal duct cysts account for 70% of the congenital cystic abnormalities of the neck. They usually present in the first decade of life as a cystic midline mass containing mucoid material. Occasionally, part of the duct will form a sinus tract extending to the skin surface at, or just lateral to, the midline. This may present as a bullous lesion. These anomalies are classified according to their location with respect to the hyoid bone: 65% are infrahyoid; 20% are suprahyoid; and 15% are juxtahyoid. Thyroglossal duct cysts are usually mobile and nontender, unless complicated by infection. Dysphagia may occur with lesions beneath the tongue and superior vena cava syndrome may occur with lesions that are retrosternal. Malignancies develop within these structures in less than 1% of cases; 80% of such neoplasms are papillary adenocarcinomas. It is essential that clinicians be certain that these cysts are distinguished from ectopic thyroid tissue, which may be the only functioning thyroid tissue present in 75% of ectopic thyroid patients. Ectopic tissue can be detected by ultrasound or radionuclide scans. Possible treatment modalities include excision of a portion of the hyoid bone along with the cyst (the “Sistrunk” procedure decreases recurrence rate compared to simple excision) and endoscopic CO 2 laser for those lesions extending into the respiratory tract.

Cutaneous Metastases

Thyroid cancer accounts for 3.8% of new cancers and 0.3% of cancer deaths. Although the incidence of thyroid cancer has been increasing, much of this may be attributable to increased detection by ultrasound screening procedure. Papillary thyroid carcinoma accounts for the majority of thyroid malignancies in early life. It metastasizes to regional lymph nodes, but only rarely distantly (including to the skin). By contrast, follicular carcinoma usually appears in middle-aged or elderly individuals, and distant metastases are more frequent. Anaplastic tumors—the giant or spindle cell subtypes—occur almost without exception in those over 60 years of age, grow rapidly, and possess a propensity for both nodal and distant metastases. Albeit rare, all histologic types of thyroid cancer have been reported to metastasize to the skin. Such metastatic lesions tend to favor the head and neck region, may be either solitary or multiple, and are generally painless. In this respect, metastases from thyroid neoplasms do not differ significantly from those originating in other sites. Seeding of the skin has been reported after percutaneous needle biopsy. Thyroid cancer metastases have been reported from 2 to 10 years after the discovery of the primary tumor. Although such lesions usually occur in patients with a known history of malignancy, they may be the initial presentation of a cancer. In those cases where a biopsy was performed and the routine histology is equivocal, immunohistochemical stains (i.e., thyroid transcription factor and thyroglobin for most tumors, with calcitonin, synaptophysin, chromogranin, and CD56 being specific for medullary carcinoma) may allow for a precise diagnosis.

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