Thyroid disease and the skin

Cutaneous manifestations of thyroid disease are protean in nature and can be divided into specific lesions such as the thyroglossal duct cyst and cutaneous metastases from thyroid malignancy, nonspecific signs secondary to thyroid hormone imbalance, and associated dermatologic and systemic disorders. This review represents a summary and update of thyroid disease and the skin.     

Pretibial myxoedema associated with Hashimoto''s thyroiditis

Pretibial myxoedema is a cutaneous mucinosis typically associated with Graves' disease, although it may also develop in subjects with non-thyrotoxic thyroid pathologies. This report presents a rare case of pretibial myxoedema occurring in a 58-year-old woman with biopsy-proven Hashimoto's thyroiditis. The hypothetical pathogenetic link between the two disorders is discussed with particular attention to the role of thyroid stimulating hormone receptor antibodies.     

Primary hypothyroidism with exuberant dermatological manifestations

Thyroid hormone has effects on the skin. Patients with hypothyroidism have changes such as dry, scaly and rough skin. Increase carotene in the dermis becomes a yellowish tone to the skin of the patient with hypothyroidism. There is an increase in capillary cycle (anagen phase) and nail growth and a reduction in eccrine gland secretion. It is a case of primary hypothyroidism with nail manifestations associated with dermatologic disorders and successful treatment with levothyroxine. Receptors for thyroid hormone have already been found in keratinocytes, fibroblasts, hair follicles and sebaceous glands. Genes responsive to thyroid hormones and elements of the hypothalamic–pituitary–thyroid axis were identified on the skin. This report highlights the importance of cutaneous manifestations as markers of thyroid disease.     

Carcinoma erysipeloides associated with anaplastic thyroid carcinoma

Cutaneous metastases from carcinoma of the thyroid gland are rare and carcinoma erysipeloides is even rarer. We present the clinical, histological, and immunohistochemical features of inflammatory erysipeloid metastases arising from an anaplastic carcinoma of the thyroid gland. In this case the anaplastic carcinoma probably transformed from a pre-existing, long-standing papillary carcinoma of the thyroid gland. Although visible inflammation is a hallmark of many benign skin disorders, it is not commonly present in cutaneous malignant metastases. As a result, the significance of a marked inflammatory changes in association with metastatic skin disease may not be recognized. Dermatologists need to be aware of the potential for inflammatory manifestations in cutaneous metastases from a thyroid carcinoma.     

Cutaneous manifestations of thyroid disease.

Cutaneous manifestations of thyroid disease are protean in nature and affect all age groups. This review focuses on normal thyroid gland physiology, specific cutaneous/thyroid lesions such as the thyroglossal duct cyst and metastatic thyroid malignancies, nonspecific cutaneous alterations of the hyperthyroid and hypothyroid states, and the numerous associations of thyroid disease with other cutaneous and/or systemic disorders.     

Cutaneous manifestations of thyroid disease

The diagnosis of thyroid disease can often first be identified by recognizing various cutaneous manifestations associated with an imbalance of circulating thyroid hormone. This article reviews the pathophysiology of thyroid disease, characteristic cutaneous findings of the hypothyroid and hyperthyroid states, and cutaneous conditions associated with thyroid disease.     

Menopause and the skin

Women live one-third of their lives in the post-menopausal state. Significant hormonal alterations occur at the time of menopause, leading to a range of physiological disorders affecting multiple organ systems in the body. The effects of menopause on the skin have been underresearched. Many skin changes occur at the time of menopause and the cutaneous effects of hormone replacement therapy are significant. Menopausal changes in hormones may alter the biomechanical properties of the skin and certain disorders are more common in menopausal women, such as lichen sclerosus, atrophic vulvovaginitis, flushing and dysaesthetic vulvodynia. Hair and oral changes may also be associated. As the average life expectancy increases, dermatologists need to be familiar with skin diseases affecting women in this age group.     

Cutaneous mucinosis associated with thyroid dysfunction

An unusual case of pruritic, papular cutaneous mucinosis in conjunction with hypothyroidism is described. Resolution of this disorder followed thyroid hormone supplementation. The various cutaneous mucinoses and the pathogenesis of mucin deposition are reviewed.     

Abnormal lipogenesis in thyroid hormone-deficient epidermis

Striking skin changes can accompany hypothyroidism, among them a scaly ichthyosis. The pathogenesis of these disorders is unknown. Since altered sterol metabolism has been associated with other scaling dermatoses, we tested the hypothesis that altered epidermal lipogenesis may accompany hypothyroidism and induce the observed scaling. Thyroidectomized (TX) rats were sacrificed 53 days postthyroidectomy, and the rate of incorporation of the radiolabeled precursor, [14C]acetate, into epidermal lipids was determined. Approximately 2-fold decreases in incorporation of precursor into both polar and neutral lipids were observed in the TX epidermis; the most significant decreases, however, were in the neutral lipids, particularly the sterol and sterol-ester moieties. Total cholesterol pool size was also reduced in the TX epidermis. Similar decreases in sterol biosynthesis were noted in human keratinocytes cultivated in medium devoid of thyroid hormone. These findings demonstrate that lipid metabolism, and notably sterol synthesis, is altered in epidermal keratinocytes deprived of thyroid hormone, and suggest that, as in other scaling disorders, this abnormal sterologenesis may lead to the clinically observed ichthyosis that can accompany hypothyroidism.     

ALOPECIA AREATA AND AUTOIMMUNITY: A CLINICAL STUDY

Alopecia areata (AA) frequently occur in association with other autoimmune diseases such as thyroid disorders, anemias and other skin disorders with autoimmune etiology. Despite numerous studies related to individual disease associations in alopecia areata, there is paucity of literature regarding comprehensive studies on concomitant cutaneous and systemic diseases. The present study has been designed to determine if there is a significant association between alopecia areata and other autoimmune diseases. This study covers 71 patients with the diagnosis of alopecia areata as the case group and 71 patients with no evidence of alopecia areata as the control group. Among the cutaneous diseases associated with AA, atopic dermatitis (AD) showed maximum frequency with an O/E ratio of 2.5, which indicates that it is two to three times more common in patients with alopecia areata. In our study, thyroid disorders showed the highest frequency with on O/E ratio of 3.2 and a P value of 0.01, which is statistically highly significant. Among the thyroid disorders, hypothyroidism was the most frequent association (14.1%) in our study. Since systemic involvement is not infrequent in patients with alopecia areata, it is imperative to screen these patients for associated disorders, particularly atopy, thyroid diseases, anemias and other autoimmune disorders, especially if alopecia areata is chronic, recurrent and extensive.     

The rash in life-threatening metabolic and endocrine disorders

Recognizing the skin manifestations of metabolic and endocrine disorders, many of which may have potentially lethal complications, is important for dermatologists and other clinicians. The skin can be a window into a patient’s internal health, and cutaneous manifestations can facilitate early diagnosis and intervention of potentially life-altering systemic disorders with associated morbidity and mortality. This contribution provides an overview of the diverse rashes associated with potentially lethal, acquired metabolic and endocrine disorders of the pituitary, thyroid, parathyroid, pancreas, adrenals, and blood, as well as neuroendocrine and nutritional disease.     

Nails: diagnostic clue to genodermatoses

Nails are cutaneous appendages mostly involved in mechanical functions. However, nails may reflect presence of various systemic disorders evidenced by alteration of their shape, size, color or texture. Genodermatoses are multisystem disorders with cutaneous involvement. Many of the genodermatoses present with nail changes and some of these may be the clinical pointers to the diagnosis. Diagnostic clues to various genodermatoses derived from nail findings have been discussed.     

Dermatologic aspects of thyroid disease

Thyroid disorders commonly have dermatologic manifestations. The purpose of the present chapter is to review and emphasize potential clinical dermatologic findings that can occur with Graves' disease, hypothyroidism and thyroid cancer. In autoimmune diseases such as Graves' disease and Hashimoto's thyroiditis the skin manifestations may be related to either thyroid hormone levels themselves or to the associated T and/or B cell abnormalities. Thyroid cancer may be associated with various syndromes that could have significant skin manifestations.     

Cutaneous consequences of accelerated thyroid function

General and specific cutaneous findings associated with hyperthyroidism are reviewed. Familiarity with these findings may aid the practitioner in the early diagnosis of thyroid diseases. Several normally idiopathic cutaneous diseases can occasionally be controlled if underlying thyroid disease is considered as a cause, and appropriate testing performed.     

Rare syndromes

Dermatologists may also encounter patients presenting with skin lesions that reflect an underlying endocrine disorder not commonly seen in daily practice. Some of these endocrine disorders include glucagonoma, neurofibromatosis type 1, McCune-Albright syndrome, multiple endocrine neoplasia, the Carney complex, carcinoid tumors, and mastocytosis. The clinical syndrome classically associated with glucagonoma includes necrolytic migratory erythema, weight loss, diabetes mellitus, anemia, cheilitis, venous thrombosis, and neuropsychiatric symptoms. The hallmarks of neurofibromatosis type 1 are the multiple café-au-lait spots and associated cutaneous neurofibromas. Other presenting features include freckling, peripheral neurofibromas, Lisch nodules, bone abnormalities, tumors, neurologic abnormalities and hypertension. McCune-Albright syndrome is characterized by café-au-lait spots, polyostotic fibrous dysplasia, sexual precocity, and hyperfunction of multiple endocrine glands. Multiple endocrine neoplasia type 2A is characterized by medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. In some patients with multiple endocrine neoplasia type 2A, cutaneous lichen amyloidosis may also be present. Multiple endocrine neoplasia type 2B is characterized by medullary thyroid cancer and pheochromocytoma but not hyperparathyroidism. The syndrome also includes mucosal neuromas, typically involving the lips and tongue, intestinal ganglioneuromas and a marfanoid habitus. Multiple endocrine neoplasia type 1 is an autosomal dominant predisposition to tumors of the parathyroid glands (four-gland hyperplasia), anterior pituitary, and pancreatic islet cells; hence, the mnemonic device of the "3 Ps"; multiple cutaneous lesions (angiofibromas and collagenomas) are frequent in patients with multiple endocrine neoplasia type 1. Carney complex may be viewed as a form of multiple endocrine neoplasia because affected patients often have tumors of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (some with Cushing's syndrome), pituitary adenoma, testicular neoplasms, thyroid adenoma or carcinoma, and ovarian cysts. Additional unusual manifestations include psammomatous melanotic schwannoma, breast ductal adenoma, and a rare bone tumor, osteochondromyxoma. Carcinoid syndrome is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors; the major manifestations are diarrhea, flushing, bronchospasm, and cardiac valvular lesions. Mast cell diseases include all disorders of mast cell proliferation. These diseases can be limited to the skin, referred to as "cutaneous mastocytosis," or involve extracutaneous tissues, called "systemic mastocytosis." Patients present with urticaria pigmentosa, mastocytoma, or diffuse cutaneous mastocytosis. Systemic involvement may be gastronintestinal, hematologic, neurologic, and skeletal.     

Cutaneous manifestations of thyroid disease

Of all the endocrinopathies that may have cutaneous findings, thyroid disease is probably the one most likely to be seen by the practicing physician since the skin readily reflects the functional capacity of the thyroid gland. Cutaneous findings may be the only clue to otherwise silent thyroid disease. Skin changes may precede other clinical and laboratory evidence of thyroid malfunction by months or years. Thus, the skin not only aids in the diagnosis of thyroid dysfunction, but also helps the physician select those high-risk patients in whom thyroid abnormalities may later develop.     

Reticular erythematous mucinosis and acral papulokeratotic lesions associated with myxoedema due to Hashimoto thyroiditis.

A case is described of a patient with generalized myxoedema due to Hashimoto thyroiditis involving lesions of reticular erythematous mucinosis and acral papulokeratotic lesions with 'church spire' histological pattern. Substitutive treatment with thyroid hormone led to a rapid regression of the cutaneous lesions. The infrequent association of reticular erythematous mucinosis lesions and other forms of cutaneous mucinoses with hypothyroidism is discussed, with special emphasis on the fact that the underlying thyroid disease in all cases was Hashimoto thyroiditis. The association of distal keratotic papules with hypothyroidism has not been previously reported in the literature.     

Investigation and management of cutaneous arterial insufficiency of the extremities*

The effects of arterial disease may be identified most readily by examination of the skin, and that of the digits often shows the most pronounced changes. The skin may be ischaemic as part of the general arterial insufficiency to a limb or, particularly as with vasospastic disorders, may show the most exaggerated changes whilst other tissues are relatively spared. The spectrum of arterial conditions causing cutaneous arterial insufficiency is wide and ranges from vasospastic disorders, without permanent tissue damage, to conditions where there is necrosis of tissue with loss of function and leading on to gangrene.     

Granulomatous vasculitides and the skin

Wegener's granulomatosis, lymphomatoid granulomatosis, and Churg-Strauss granulomatosis may all have cutaneous involvement. The morphology of cutaneous lesions in these disorders varies from macular erythema to frank gangrenous ulceration. Most often lesions are located on the extremities; however, truncal or facial involvement has been reported, the latter especially in Wegener's granulomatosis. A common histologic finding in these cutaneous lesions is necrotizing vasculitis. However, it is also possible to see Churg-Strauss extravascular granulomas and even periarteritis. Cutaneous involvement with these three forms of systemic granulomatosis generally parallels the systemic course. The treatment for the cutaneous lesions is dictated by the treatment for the systemic vasculitis. It is important to recognize that the cutaneous extravascular granuloma and cutaneous granulomatous vasculitis can be associated with other disorders in addition to systemic granulomatosis. These disorders include most importantly lymphoproliferative diseases, inflammatory disorders such as arthritis, autoimmune diseases, and other inflammatory disorders such as sarcoidosis. Cutaneous involvement with giant cell or temporal arteritis is not common, but ulcerative temporal-parietal scalp lesions are distinctive. Although not common in the United States, Takayasu's arteritis may have several cutaneous manifestations, including erythema nodosum-like lesions. Granulomatous vasculitides have a myriad of cutaneous manifestations. Knowledge of these manifestations may allow for prompt diagnosis in many cases and increased surveillance in other cases for associated systemic illnesses.     

Cutaneous manifestations of endocrine-metabolic disease and nutritional deficiency in the elderly

This article explores cutaneous manifestations of endocrine-metabolic disease and nutritional deficiency in the elderly. Topics covered include the following: diabetes mellitus, thyroid disorders, adrenal dysfunction, pituitary disorders, parathyroid disease, nutritional deficiencies, menopause, and HIV.