Cutaneous Manifestations of Endocrine Disorders - Endocrinology Advisor

Cutaneous Manifestations of Endocrine Disorders

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  • In more than 99% of patients, this disorder is caused by excess growth hormone (GH) resulting from an adenoma of the pituitary gland.2 Dermatologic manifestations include coarsening of facial features, macroglossia, macrocheilia, gingival hyperplasia, cutis verticis gyrate, hyperpigmentation (affects 40% of patients), acanthosis nigricans, hyperhidrosis, hypertrichosis, and platonychia. First-line treatment is generally transsphenoidal excision of the adenoma, followed by somatostatin analogs for residual disease and adjuvant therapies such as dopamine agonists. In 50% of patients, medical therapy is linked to complete reversal of most features.3

    Acromegaly

    In more than 99% of patients, this disorder is caused by excess growth hormone (GH) resulting from an adenoma of the pituitary gland.2 Dermatologic manifestations include coarsening of facial features, macroglossia, macrocheilia, gingival hyperplasia, cutis verticis gyrate, hyperpigmentation (affects 40% of patients), acanthosis nigricans, hyperhidrosis, hypertrichosis, and platonychia.

    First-line treatment is generally transsphenoidal excision of the adenoma, followed by somatostatin analogs for residual disease and adjuvant therapies such as dopamine agonists. In 50% of patients, medical therapy is linked to complete reversal of most features.3

  • The most common cause of hyperthyroidism is Graves' disease, which is estimated to affect more than 3 million Americans.4 The "binding of the thyrotropin antibody to mesenchymal tissue receptors results in soft tissue proliferation and overgrowth," as explained in the review. Dermatologic manifestations include facial flushing, palmar erythema, hyperhidrosis of soles and palms, downy hair texture on scalp with diffuse thinning, soft shiny nails with onycholysis, and pretibial myxedema (affects 4% of patients with Graves' disease).2 Common approaches to treat the underlying disease include antithyroid medications, radioactive ablation, and thyroidectomy. For persistent pretibial myxedema, intralesional corticosteroid injections have demonstrated efficacy.5

    Hyperthyroidism

    The most common cause of hyperthyroidism is Graves' disease, which is estimated to affect more than 3 million Americans.4 The "binding of the thyrotropin antibody to mesenchymal tissue receptors results in soft tissue proliferation and overgrowth," as explained in the review. Dermatologic manifestations include facial flushing, palmar erythema, hyperhidrosis of soles and palms, downy hair texture on scalp with diffuse thinning, soft shiny nails with onycholysis, and pretibial myxedema (affects 4% of patients with Graves' disease).2

    Common approaches to treat the underlying disease include antithyroid medications, radioactive ablation, and thyroidectomy. For persistent pretibial myxedema, intralesional corticosteroid injections have demonstrated efficacy.5

  • In the United States, hyperthyroidism is most commonly caused by chronic lymphocytic thyroiditis (Hashimoto's thyroiditis).2 Reductions in basal metabolic rate and sympathetic nervous system response result from decreased sensitivity of alpha- and beta-adrenergic receptors to catecholamine signaling. Dermatologic manifestations include dry, cold, and mottled skin; carotenemia; myxedema (most often of hands, face, pretibial, and periorbital areas); macroglossia; loss of lateral third of eyebrows; rough, brittle hair; diffuse, partial alopecia; and hydrotrichosis of back and shoulders (pediatric population). Treatment typically involves supplementation with L-thyroxine, which reverses the cutaneous signs of hypothyroidism.

    Hypothyroidism

    In the United States, hyperthyroidism is most commonly caused by chronic lymphocytic thyroiditis (Hashimoto's thyroiditis).2 Reductions in basal metabolic rate and sympathetic nervous system response result from decreased sensitivity of alpha- and beta-adrenergic receptors to catecholamine signaling. Dermatologic manifestations include dry, cold, and mottled skin; carotenemia; myxedema (most often of hands, face, pretibial, and periorbital areas); macroglossia; loss of lateral third of eyebrows; rough, brittle hair; diffuse, partial alopecia; and hydrotrichosis of back and shoulders (pediatric population).

    Treatment typically involves supplementation with L-thyroxine, which reverses the cutaneous signs of hypothyroidism.

  • Diabetes mellitus (DM) is characterized by hyperglycemia as a result of insulin dysfunction. The "insulin-dependent increase in [insulin-like growth factor 1 (IGF-1)] and activation of the IGF-1 signaling pathway promotes cellular growth and differentiation and mediates the subsequent development of some of the cutaneous findings," according the paper.6 Dermatologic manifestations include diabetic dermopathy (affects 70% of adult with DM7), increased susceptibility to skin infections, necrobiosis lipoidica diabeticorum (affects 0.3%-1.6% of patients with DM6), diabetic bullae, scleredema adultorum, and acanthosis nigricans. Examples of specific treatments for the cutaneous features of DM include topical and intralesional corticosteroids for necrobiosis lipoidica diabeticorum, topical or systemic retinoids and keratolytic agents to help manage acanthosis nigricans, and wound care for the management of diabetic dermopathy and diabetic bullae.

    Diabetes Mellitus

    Diabetes mellitus (DM) is characterized by hyperglycemia as a result of insulin dysfunction. The "insulin-dependent increase in [insulin-like growth factor 1 (IGF-1)] and activation of the IGF-1 signaling pathway promotes cellular growth and differentiation and mediates the subsequent development of some of the cutaneous findings," according the paper.6

    Dermatologic manifestations include diabetic dermopathy (affects 70% of adult with DM7), increased susceptibility to skin infections, necrobiosis lipoidica diabeticorum (affects 0.3%-1.6% of patients with DM6), diabetic bullae, scleredema adultorum, and acanthosis nigricans.

    Examples of specific treatments for the cutaneous features of DM include topical and intralesional corticosteroids for necrobiosis lipoidica diabeticorum, topical or systemic retinoids and keratolytic agents to help manage acanthosis nigricans, and wound care for the management of diabetic dermopathy and diabetic bullae.

  • Most cases of Cushing syndrome result from hypocortisolemia caused by "pituitary (Cushing's disease) or ectopic hypersecretion of adrenocorticotropic hormone (ACTH), adrenal overproduction of cortisol, or iatrogenic administration of glucocorticoids," wrote the authors. It is believed that excess glucocorticoid levels reduce proliferation of keratinocytes and dermal fibroblasts, and these "changes abate the formation of collagen and other components of the extracellular matrix and ultimately contribute to skin atrophy and fragility." Dermatologic manifestations include moon facies, dorsocervical fat pad, and supraclavicular fat pad caused by deposition of adipose tissue; easy bruising and delayed wound healing; dermal atrophy; striae distensae (up to 35% of girls and 15% of boys aged 9-16 years8); hyperpigmentation; acanthosis nigricans; and steroid acne. Treatment options for Cushing syndrome include surgery for tumor removal, chemotherapy, radiation, and steroid synthesis inhibitors. Most dermatologic manifestations resolve after treatment.

    Cushing Syndrome

    Most cases of Cushing syndrome result from hypocortisolemia caused by "pituitary (Cushing's disease) or ectopic hypersecretion of adrenocorticotropic hormone (ACTH), adrenal overproduction of cortisol, or iatrogenic administration of glucocorticoids," wrote the authors. It is believed that excess glucocorticoid levels reduce proliferation of keratinocytes and dermal fibroblasts, and these "changes abate the formation of collagen and other components of the extracellular matrix and ultimately contribute to skin atrophy and fragility."

    Dermatologic manifestations include moon facies, dorsocervical fat pad, and supraclavicular fat pad caused by deposition of adipose tissue; easy bruising and delayed wound healing; dermal atrophy; striae distensae (up to 35% of girls and 15% of boys aged 9-16 years8); hyperpigmentation; acanthosis nigricans; and steroid acne.

    Treatment options for Cushing syndrome include surgery for tumor removal, chemotherapy, radiation, and steroid synthesis inhibitors. Most dermatologic manifestations resolve after treatment.

  • Addison disease is characterized by low cortisol production and is often mediated by autoimmune mechanisms. As part of its pathophysiology, elevated levels of melanocyte-stimulating hormone stimulate synthesis of melanin by epidermal melanocytes.9 Dermatologic manifestations include bronze hyperpigmentation (67% of pediatric patients and nearly all adult patients9), hair and mucosal hyperpigmentation, loss of axillary and pubic hair, longitudinal hyperpigmented bands on nails, and vitiligo. Treatment consists of cortisol replacement therapy.

    Addison Disease/Primary Adrenal Insufficiency

    Addison disease is characterized by low cortisol production and is often mediated by autoimmune mechanisms. As part of its pathophysiology, elevated levels of melanocyte-stimulating hormone stimulate synthesis of melanin by epidermal melanocytes.9

    Dermatologic manifestations include bronze hyperpigmentation (67% of pediatric patients and nearly all adult patients9), hair and mucosal hyperpigmentation, loss of axillary and pubic hair, longitudinal hyperpigmented bands on nails, and vitiligo.

    Treatment consists of cortisol replacement therapy.

  • Polycystic ovary syndrome (PCOS) is characterized by excess androgen (resulting from elevated luteinizing hormone and insulin) and chronic anovulation that is not caused by pituitary or adrenal pathology. Dermatologic manifestations include hirsutism, acne vulgaris, androgenetic alopecia, acanthosis nigricans, and seborrheic dermatitis. Treatment options include weight loss and lifestyle modifications, oral contraceptives, and metformin. Anti-androgen treatment may reduce hirsutism and acne; laser hair removal, electrolysis, and topical eflornithine may improve hirsutism; and topical minoxidil and spironolactone may improve androgenetic alopecia in PCOS.

    Polycystic Ovary Syndrome

    Polycystic ovary syndrome (PCOS) is characterized by excess androgen (resulting from elevated luteinizing hormone and insulin) and chronic anovulation that is not caused by pituitary or adrenal pathology. Dermatologic manifestations include hirsutism, acne vulgaris, androgenetic alopecia, acanthosis nigricans, and seborrheic dermatitis.

    Treatment options include weight loss and lifestyle modifications, oral contraceptives, and metformin. Anti-androgen treatment may reduce hirsutism and acne; laser hair removal, electrolysis, and topical eflornithine may improve hirsutism; and topical minoxidil and spironolactone may improve androgenetic alopecia in PCOS.

  • These autosomal dominant disorders are characterized by benign or malignant neoplasms of multiple endocrine tissues. Dermatologic manifestations of MEN1, angiofibromas (observed in 88% of patients10), lipomas, café-au-lait spots, collagenomas, and necrolytic migratory erythema. In MEN2A, lichen amyloidosis is the most significant cutaneous feature. In MEN2B, cutaneous features may include mucosal neuromas, most commonly on the eyelids, conjunctiva, lips, and tongue, as well as café-au-lait macules. Although treatment of MEN syndromes varies by case, surgical excision may be used for benign skin tumors, topical rapamycin and laser therapy may reduce the number and size of angiofibromas, and case reports suggest that corticosteroids, retinoids, phototherapy, and laser therapy may be effective in treating lichen amyloidosis.11

    Multiple Endocrine Neoplasia (MEN) Syndromes

    These autosomal dominant disorders are characterized by benign or malignant neoplasms of multiple endocrine tissues.

    Dermatologic manifestations of MEN1, angiofibromas (observed in 88% of patients10), lipomas, café-au-lait spots, collagenomas, and necrolytic migratory erythema. In MEN2A, lichen amyloidosis is the most significant cutaneous feature. In MEN2B, cutaneous features may include mucosal neuromas, most commonly on the eyelids, conjunctiva, lips, and tongue, as well as café-au-lait macules.

    Although treatment of MEN syndromes varies by case, surgical excision may be used for benign skin tumors, topical rapamycin and laser therapy may reduce the number and size of angiofibromas, and case reports suggest that corticosteroids, retinoids, phototherapy, and laser therapy may be effective in treating lichen amyloidosis.11

  • These immune-mediated disorders are defined by inadequate function of at least 2 endocrine organs. Dermatologic manifestations include chronic mucocutaneous candidiasis, alopecia areata, and vitiligo, as well as dry, scaly, hyperkeratotic skin and brittle nails. Along with treatment addressing the endocrine abnormalities of APS, antifungal agents, such as azoles and amphotericin, are used to treat the cutaneous features of APS.

    Autoimmune Polyendocrine Syndromes

    These immune-mediated disorders are defined by inadequate function of at least 2 endocrine organs. Dermatologic manifestations include chronic mucocutaneous candidiasis, alopecia areata, and vitiligo, as well as dry, scaly, hyperkeratotic skin and brittle nails.

    Along with treatment addressing the endocrine abnormalities of APS, antifungal agents, such as azoles and amphotericin, are used to treat the cutaneous features of APS.

In addition to the direct effects of endocrine disorders, patients with these conditions often experience dermatologic manifestations resulting from the dysregulation of endocrine hormones. These cutaneous changes, which may be the first sign of endocrine disease in some cases, are associated with significant morbidity and reduced quality of life.

Noting that the “skin serves as a window for clinicians to understand, diagnose, and monitor endocrine disease,” the authors of a recent review published in Translational Pediatrics reviewed the dermatologic manifestations of various endocrinopathies.1

References

  1. Lause M, Kamboj A, and Fernandez Faith E. Dermatologic manifestations of endocrine disorders. Transl Pediatr. 2017;6(4):300-312.
  2. Jabbour SA. Cutaneous manifestations of endocrine disorders: a guide for dermatologists. Am J Clin Dermatol. 2003;4(5):315-331.
  3. Mishra A, Tehrani H, Hancock K, et al. Management of primary cutis verticis gyrata with tissue expansion and hairline lowering foreheadplasty. J Plast Reconstr Aesthet Surg. 2010;63(6):1060-1061.
  4. Jacobson DL, Gange SJ, Rose NR, et al. Epidemiology and estimated population burden of selected autoimmune diseases in the United States. Clin Immunol Immunopathol. 1997;84(3):223-243.
  5. Lan C, Li C, Chen W, et al. A randomized controlled trial of intralesional glucocorticoid for treating pretibial myxedema. J Clin Med Res. 2015;7(11):862-872.
  6. Brzezinski P, Chiriac AE, Pinteala T, et al. Diabetic dermopathy (“shin spots”) and diabetic bullae (“bullosis diabeticorum”) at the same patient. Pak J Med Sci. 2015;31(5):1275-1276.
  7. Van Hattem S, Bootsma AH, Thio HB. Skin manifestations of diabetes. Cleve Clin J Med. 2008;75(11):772, 774, 776-777.
  8. Mancini AJ, Goldsmith L, Paller A. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. New York: Elsevier/Saunders; 2016.
  9. Erickson QL, Faleski EJ, Koops MK, et al. Addison’s disease: the potentially life-threatening tan. Cutis. 2000;66:72-74.
  10. Darling TN, Skarulis MC, Steinberg SM, et al. Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. Arch Dermatol. 1997;133(7):853-857.
  11. Vasani RJ. Response to oral acitretin in lichen amyloidosis. Indian Dermatol Online J. 2014;5(Suppl2):S92-S94.
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