[Reiew Article]a Guide for Dermatologists - Cutaneous Manifestations of Endocrine Disorders

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Am J Clin Dermatol 2003; 4 (5): 315-331THERAPY IN PRACTICE 1175-0561/03/0005-0315/$30.00/0 Adis Data Information BV 2003. All rights reserved.

Cutaneous Manifestations of Endocrine DisordersA Guide for Dermatologists

Serge A. Jabbour

Division of Endocrinology, Diabetes and Metabolism, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Contents

Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3161. Thyrotoxicosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316

1.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317

1.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3171.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3182. Hypothyroidism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318

2.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3182.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3192.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319

3. Autoimmune Thyroid Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3193.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3193.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3203.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320

4. Cushing Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3214.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3214.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3224.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322

5. Addison Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3225.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3225.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3235.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323

6. Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3236.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3236.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3246.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324

7. Androgen-Related Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3247.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3247.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3247.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325

8. Hypopituitarism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325

8.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3268.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3268.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326

9. Parathyroid Hormone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3269.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3279.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3279.3 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327

10. Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32710.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32710.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328


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10.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32911. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329

Dermatologists may commonly see skin lesions that reflect an underlying endocrine disorder. Identifying theAbstractendocrinopathy is very important, so that patients can receive corrective rather than symptomatic treatment. Skindiseases with underlying endocrine pathology include: thyrotoxicosis; hypothyroidism; Cushing syndrome;Addison disease; acromegaly; hyperandrogenism; hypopituitarism; primary hyperparathyroidism; hypoparathy-roidism; pseudohypoparathyroidism and manifestations of diabetes mellitus.

Thyrotoxicosis may lead to multiple cutaneous manifestations, including hair loss, pretibial myxedema,onycholysis and acropachy. In patients with hypothyroidism, there is hair loss, the skin is cold and pale, withmyxedematous changes, mainly in the hands and in the periorbital region.

The striking features of Cushing syndrome are centripetal obesity, moon facies, buffalo hump, supraclavicu-lar fat pads, and abdominal striae. In Addison disease, the skin is hyperpigmented, mostly on the face, neck andback of the hands.

Virtually all patients with acromegaly have acral and soft tissue overgrowth, with characteristic findings, likemacrognathia and enlarged hands and feet. The skin is thickened, and facial features are coarser.

Conditions leading to hyperandrogenism in females present as acne, hirsutism and signs of virilization(temporal balding, clitoromegaly).

A prominent feature of hypopituitarism is a pallor of the skin with a yellowish tinge. The skin is also thinner,resulting in fine wrinkling around the eyes and mouth, making the patient look older.

Primary hyperparathyroidism is rarely associated with pruritus and chronic urticaria. In hypoparathyroidism,the skin is dry, scaly and puffy. Nails become brittle and hair is coarse and sparse. Pseudohypoparathyroidismmay have a special somatic phenotype known as Albright osteodystrophy. This consists of short stature, shortneck, brachydactyly and subcutaneous calcifications.

Some of the cutaneous manifestations of diabetes mellitus include necrobiosis lipoidica diabeticorum,diabetic dermopathy, scleredema adultorum and acanthosis nigricans.

Hormones are known to be essential in regulating physiologicprocesses in each system of the body, including the skin. Endo-crine diseases, through excess or deficiencies of hormones, resultin changes in cutaneous function and morphology. This paperreviews many endocrinopathies and their associated skin condi-tions. The overall clinical presentation is also discussed, as are theappropriate diagnostic tests, and a brief overview of the treatmentsrelated to these endocrine disorders.

1. Thyrotoxicosis

Thyrotoxicosis may be due to several conditions. The mostcommon cause is Graves disease (autoimmune disease); its fre-quency ranging from 6090% of all thyrotoxic patients in differentregions of the world. Most of the remaining etiologies are causedby a single toxic adenoma, a toxic multinodular goiter, severaltypes of thyroiditis (subacute thyroiditis, silent thyroiditis) orexcessive exogenous thyroid hormone ingestion. These other

Table I. Major symptoms and signs of thyrotoxicosis

Symptoms Signs

Fatigue Diffuse goiter (Graves), solitary nodule ormultinodular goiter

Heat intolerance Muscle weakness

Hyperactivity Ophthalmopathy (Graves)

Increased appetite Pretibial myxedema, acropachy(Graves)

Increased perspiration Stare, lid lag and eyelid retraction

Menstrual disturbance Systolic hypertension

Neck pain (Subacute Tachycardia or atrial arrhythmiathyroiditis)

Nervousness Thyroid tenderness(subacute thyroiditis)

Palpitation Tremor and hyperreflexia

Tremor Warm, moist, smooth skin

Weakness

Weight losscauses are rare. [1-3] The symptoms and signs of thyrotoxicosis aresummarized in table I. [4]

Adis Data Information BV 2003. All rights reserved. Am J Clin Dermatol 2003; 4 (5)


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Cutaneous Manifestations of Endocrine Disorders 317

In addition to the aforementioned cutaneous features of thethyrotoxic state, patients with Graves disease may have distinctcutaneous manifestations such as pretibial myxedema and ac-ropachy. Pretibial myxedema or thyroid dermopathy (figure 2) isalmost always associated with Graves ophthalmopathy, [25] but iwas also reported in patients with Hashimoto thyroiditis. [26] Ioccurs in a small percentage of patients with Graves disease(0.54%), most frequently on the anterior tibia and dorsa of thefeet, and consists of nonpitting scaly thickening and induration of the skin; it can also present as few well-demarcated pink, flesh-colored or purple-brown papules or nodules. [8,27] Thyroid ac-ropachy (figure 3) is a triad consisting of digital clubbing, softtissue swelling of the hands and feet, and periosteal new boneformation. [8] It occurs in 0.11% of patients with Graves dis-

Fig. 1. Plummers nail, or onycholysis, is a separation of the nail plate fromthe nail bed. The separated portion is white and opaque, in contrast to thepink translucence of the attached portion. ease. [28] It almost always occurs in association with

ophthalmopathy and pretibial myxedema.[29]

1.1 Cutaneous Manifestations

1.2 DiagnosisIn patients with thyrotoxicosis, the skin is usually warm, ery-thematous and moist, with a smooth, silky texture. [5-7] The warmth, The diagnosis of thyrotoxicosis is made by measuring serumcaused by increased cutaneous blood flow and peripheral vasodila- thyroid-stimulating hormone (TSH) level, which is the most cost-tion, may be responsible for episodic facial flushing and palmar effective screening test. [30] A normal TSH almost excludes thyro-erythema. [8] toxicosis, except in the rare case of TSH-secreting pituitary adeno-

The epidermis is thin but not atrophic. [9] Generalized hyperhi- ma, where TSH is normal to high. [30,31] If TSH is suppressed todrosis may be noted, but it is usually more prominent on the palms below 0.1 IU/ml, free T4 (thyroxine) and free T3 (triiodothyro-and soles. [8,9] Scalp hair is fine and soft, and holds a permanent nine) should then be obtained. Because serum levels of total T4wave poorly. [5,8] Diffuse loss of scalp hair occurs in 2040% of and total T3 can be affected by some binding proteins (mostlythyrotoxic patients, although the severity of the loss is not directly thyroxine-binding globulin), free levels are more accurate andrelated to the severity of the endocrine abnormality. [10] Alopecia reflect the patients true thyroid state. Some patients may also haveareata and loss of axillary, pubic, body and eyebrow hair may also T3-toxicosis, producing mainly T3; for this reason, free T3 shouldbe noted. [11] The nails become shiny, soft and friable. Many always be measured, especially if TSH is suppressed and free T4 ispatients develop onycholysis (figure 1), that is, distal separation of normal. [30,31]nail plate from its underlying bed with upward curvature, so-called After a laboratory diagnosis of hyperthyroidism is made, aPlummers nail; it usually begins under the distal central portion of 24-hour radioiodine uptake and scan is usually done to define thethe fourth fingernail, but may eventually involve any of the fingerand toe nails. [12,13] Onycholysis is not specific to thyrotoxicosisand may be observed in patients with hypothyroidism, psoriasis,trauma or allergic contact dermatitis. [14] Such nail changes are lesscommon in patients over 60 years of age. [15] Hyperpigmentation

has been noted in thyrotoxic patients from 2% to as high as 40% of large series. [2,16] The hyperpigmentation can be diffuse or local-ized, sometimes in a pattern similar to patients with Addisondisease. [8]

Vitiligo of variable extent occurs in a substantial portion of patients, and is seen especially in Graves disease, as a marker of the autoimmune disease. [17-19]

Other less frequently reported cutaneous changes are pruri-tus, [20] eczematous dermatitis, [21] dermographism and urticaria, [22]

purpura and erythematous eruptions, [23] and xanthelasma. [24]Fig. 2. Pretibial myxedema, a localized violaceous induration that usuallyoccurs on the shins.



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locytosis. [33] The different types of thyroiditis are usually self-limited and do not necessitate radioactive iodine or antithyroidagents. [34]

2. Hypothyroidism

Worldwide, iodine deficiency is the most common cause of hypothyroidism. [35] In areas where iodine intake is adequate, themost common causes are chronic autoimmune thyroiditis (goitroustype or Hashimotos thyroiditis and atrophic type or primarymyxedema), radiation-induced thyroiditis (mostly after 131 I therapy for thyrotoxicosis) and post-surgical hypothyroidism. [35] Otherare causes are drug-induced (lithium, iodine), central hypothy-roidism (pituitary or hypothalamic disease), and the hypothyroidphase of certain thyroiditis (subacute, silent). [35] The symptomsand signs of hypothyroidism are summarized in table II. [36]


In hypothyroidism, the skin is cold and pale, due to cutaneousvasoconstriction and reduced core temperature. [9] In over 80% ofpatients with primary hypothyroidism, the epidermis is thin, dry,rough, hyperkeratotic and covered with fine superficial scales. [37

These abnormalities are much less frequent in central hypothy-roidism (


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conversion of beta-carotene to vitamin A. Scleral sparing is a clueto hypercarotenemia as opposed to jaundice. [40]

The most striking skin change is due to dermal accumulation of mucopolysaccharides (myxedema), and is most marked in thehands and in the periorbital region. The facial changes are almostpathognomonic (figure 4). There is a non-pitting swelling orpuffiness around the eyes, with a very characteristic loss of theouter third of the eyebrows. A drooping of the upper lid may occursecondary to decreased sympathetic stimulation. The nose isbroadened, and the lips are thickened. The tongue is large. Theface lacks expressiveness; and changing emotions are registeredslowly. [8,9,37]

The hair is dull, coarse and brittle, in part due to diminishedsebum secretion. Hair loss has been noted in up to 50% of hypothyroid patients, resulting in a diffuse, partial alopecia. [8,37]

There is also loss of genital and beard hair. Nail deformities arereported in many patients with myxedema. [37,41] The nails are thin,brittle and striated, with both longitudinal and transversegrooves. [42] Other manifestations include vitiligo, alopecia areata,and dermatitis herpetiformis. [8,43]

2.2 Diagnosis

The diagnosis of hypothyroidism is made by measurement of serum TSH, which is above normal in these patients. If the level isnormal, hypothyroidism is almost excluded, except in the rareoccurrence of central hypothyroidism, where TSH can be normalor low; in this case, the diagnosis is made by adding free T4 levelto TSH. [44,45] When TSH is high, free T4 is also measured, but it Fig. 4. Hypothyroidism. This patient has many typical features of hypothy-

roidism: puffiness of the face with dry and pale skin.may be normal in the early stages of hypothyroidism (subclinicalhypothyroidism). Antithyroid peroxidase antibodies (anti-TPO)

time, there is no cause-effect relationship demonstrated, but theare obtained to document the diagnosis of Hashimoto thyroidi-association is probably part of the same immune dysfunction.tis. [44,45] 24-hour thyroid uptake and scan is neither necessary norThese associations may be in the patients or in other familyuseful in patients with hypothyroidism.members. [47]

2.3 Treatment3.1 Cutaneous Manifestations

L-thyroxine is given in a maintenance dose of 1.6 g/kg/day topatients with hypothyroidism, except in patients with underlying The most common clinical association of autoimmune thyroidcardiac disease or older people (>60 years), where treatment is

disease is dyschromia, which generally has an autoimmune etiolo-started at 25 g/day and increased progressively by 25 g every gy. The most frequent hyperchromia is melasma, a localized caf e24 weeks until the maintenance dose is reached. TSH levels are au-lait hyperpigmentation over the forehead, upper lips, cheeks,measured 6 weeks after the treatment is started or after any change and chin. There is a strong association between thyroid autoim-in dose. [46] Titration in dosage is made every 6 weeks until TSH munity (microsomal thyroid autoantibodies) and melasma, mostlyreaches a normal level of around 12 IU/ml. in women whose melasma develops during pregnancy or after

ingestion of oral contraceptive drugs. [48] Among hypochromias,3. Autoimmune Thyroid Diseasethe main expression is vitiligo, characterized by achromic areas

Many skin disorders can be seen in patients with autoimmune with hyperpigmented margins, located mainly in the back of thethyroid disease, independently of thyroid function. Most of the hands, face, neck, folds and genitals. The prevalence of vitiligo in



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Graves disease; the prevalence of TSHR-Ab varies from 70to100%, being higher in patients with hyperthyroidism. [53]

Of course, TSH is also measured, as discussed in sections 1 and2. If TSH is normal, but thyroid autoantibodies are present, thepatients is at higher risk of developing thyroid dysfunction; there-fore, follow-up testing with yearly TSH measurements would beindicated.

3.3 Treatment

If the patient has hyper- or hypothyroidism, then treatment isaimed at correcting thyroid function (see sections 1 and 2). If thepatient is euthyroid, but has thyroid autoantibodies, treatment of the autoimmune thyroid disease is not usually indicated. However,a few investigators have reported patients with urticaria and

angioedema that resolved after L-thyroxine therapy, even if TSHwas initially within normal limits. [51,52] Therefore, in these pa-tients, especially if they do not respond to other treatments, L-thyroxine could be tried for 48 weeks; [51,52] care should be taken

Table III. Symptoms and signs of Cushing syndrome

Symptom or sign Reported incidence(%)

Abdominal striae 5171

Acne, oily skin 2680

Ankle edema 2860

Backache, vertebral collapse, fracture 4050

Centripetal obesity 7997

Easy bruisability 2384

Facial plethora 5094

Glucose intolerance 3990

Headache 047

Hirsutism 6481

Hyperpigmentation 416

Hypertension 7487

Impotence 5580Oligomenorrhea or amenorrhea 5580

Polydipsia, polyuria 2544

Psychological changes 3186

Renal calculi 1519

Weakness, proximal myopathy 2990

patients with Graves disease is 67%, whereas it is only 12% inthe general population. [49]

Besides dyschromia, alopecia areata is classically associatedwith thyroid diseases; [50] the main features are circumscribed bald

patches in the scalp or beard. Also, in patients with diffusealopecia, autoimmune thyroid disease is found in almost 60% of the cases. [47]

Other skin disorders described in patients with autoimmunethyroid diseases are pemphigus, bullous pemphigoid, dermatitisherpetiformis, lupus erythematosus, scleroderma, and Sj ogrensyndrome.

The association of chronic urticaria and angioedema with thy-roid autoimmunity has also been observed, and resolution of chronic urticaria was achieved after L-thyroxine treatment, even ineuthyroid patients. [51,52]

3.2 Diagnosis

The presence of one or more of the skin disorders previouslylisted in section 3.1 should prompt the screening for autoimmunethyroid disease by the use of antithyroid peroxidase antibodies,which replaced the former antithyroid microsomal and an-tithyroglobulin antibodies. These antibodies are present in almost9598% of patients with Hashimoto thyroiditis and in almost 80%of patients with Graves disease. A more expensive test, autoan-tibodies against the TSH receptor (TSHR-Ab), is more specific for Fig. 5. Plethoric moon facies in Cushing syndrome.



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skin eventually becomes fragile and, in extreme case, peels off after being covered with adhesive tape (Liddle sign). [61] Minowounds heal slowly. [55] Loss of subcutaneous connective tissueresults in easy bruising after minimal trauma. [61]

One sign that is virtually pathognomonic for Cushing syndromeis the presence of purple (violaceous) striae >1cm in diameter(figure 7). They are most commonly seen on the abdomen andlower flanks but can also occur on the upper arms, shoulders,axillae, breasts, hips, buttocks and upper thighs. These violaceousstriae must be differentiated from those often seen in obese orpregnant patients, which are pink, reddish or silvery, less pig-mented and thinner. [56]

Fig. 6. Buffalo hump and supraclavicular fat pad in Cushing syndrome.Hyperpigmentation is also seen and is dependent upon both the

duration and the degree of increase in ACTH secretion. [55] Inot to render the patient thyrotoxic by titrating L-thyroxine inoccurs most often in patients with the ectopic ACTH syndrome,

order to keep the TSH in the lower range of normal. less often with pituitary hypersecretion of ACTH, and not at allwith adrenal Cushing syndrome. [55] It may be generalized, but is4. Cushing Syndromemost evident in areas exposed to light (face, neck, back of the

Defined as the constellation of clinical signs and symptoms hands) or to chronic mild trauma or pressure (shoulders, midriff,resulting from chronic glucocorticoid excess, Cushing syndrome waist, elbows, knuckles, spine, knees). Patchy pigmentation maycan be caused mainly by pituitary hypersecretion of adrenocortico- occur on the inner surface of lips and the buccal mucosa along thetropic hormone (ACTH) [Cushing disease], ectopic secretion of line of dental occlusion. [55,61] As in any condition that causesACTH by non-pituitary tumors, adrenal hypersecretion of hyperinsulinism and insulin resistance, acanthosis nigricans mayglucocorticoids or exogenous administration of corticosteroids. be found in Cushing syndrome. [62,63] The axillae are the mostOther etiologies are very rare. [54] The clinical manifestations of frequent sites, but also the sides of the neck, under the breasts, theCushing syndrome are summarized in table III. [55,56] belt line and the groin. [56]

The most common change in body hair in Cushing syndrome is4.1 Cutaneous Manifestationsthe development of villous hypertrichosis of the forehead andupper cheeks. [56] When there is concomitant androgen excessOne of the striking features of glucocorticoid excess is the(most common with carcinomas), women with Cushing diseasechange in the appearance and body habitus. The most commonshow signs of hirsutism, oily facial skin, acneiform rash on thefeature is progressive central (centripetal) obesity, usually involv-face, neck and shoulders, temporal balding and other signs of ing the face, neck, trunk, abdomen and internally, the mesenteryvirilization. [55,56]and mediastinum. [55] Significant fat deposits may also appear in

the cheeks resulting in moon facies often accompanied by pleth-ora over the cheeks, anterior neck, and sun-exposed chest (figure5), in the dorsocervical area known as buffalo hump (figure 6), orin the supraclavicular fossae (figure 6) resulting in supraclavicu-

lar fat pads.[56]

Retro-orbital fat deposition may result in exoph-thalmos. [57]

The centripetal obesity is accompanied by wasting of the ex-tremities. [9] Corticosteroids inhibit epidermal cell division, [58] anddecrease collagen synthesis. [59] The stratum corneum is thinnedand there is loss of subcutaneous fat in the extremities. [60] Thesealterations in skin cell physiology lead to several dermatologicalchanges, including cutaneous atrophy, which is often promi-nent. [56] On physical examination, a fine cigarette paper wrin-kling may be seen on the dorsum of the hand and the elbow. [56] The Fig. 7. Abdominal striae (wide and purple) in Cushing syndrome.



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ing, adrenal carcinoma) or drugs which block steroid synthesis(ketoconazole, metyrapone, aminoglutethimide).

5. Addison Disease

The most common cause of chronic primary adrenal insuffi-ciency (Addison disease) was formerly tuberculous adrenalitis, butnow it is autoimmune adrenalitis (slow destruction of the adrenalsby cytotoxic lymphocytes). [66] Other etiologies (infection, hemor-rhage, neoplasia) are less common. Addison disease should not beconfused with secondary adrenal insufficiency, where the damageis in the hypothalamic/pituitary axis (tumors, chronic steroid in-take, etc.). The clinical manifestations are shown in table IV. [66-68


The most striking cutaneous change of chronic primary adrenalinsufficiency is hyperpigmentation (figure 8 and figure 9), whichoccurs almost uniformly, [9] with some exceptions. [69] In many

Table IV. Clinical manifestations of Addison disease

Amenorrhea

Anorexia

Associated autoimmune disorders (vitiligo, Hashimotos thyroiditis etc.)

Decreased axillary and pubic hair

Diarrhea

Hyperpigmentation

Hypoglycemia

Hyponatremia, hyperkalemia and acidosis

Hypotension

Loss of libido

Lymphocytosis, eosinophilia

Mild normocytic anemia

Myalgias and arthralgias

Nausea and vomiting

Psychiatric manifestations

Tiredness and weakness

Weight losspatients, it may be the first sign of the disease. [70] It is caused byincreased melanin content in the skin, due to the melanocyte-

4.2 Diagnosisstimulating activity of the high plasma ACTH concentration. [71,72

The hyperpigmentation is generalized, but is most conspicuous inWhen the index of suspicion is high for Cushing syndrome, the areas exposed to light (such as face, neck, back of hands), areas

screening test of choice is a 24-hour urinary free cortisol (UFC). A exposed to chronic pressure (elbows, knees, spine, knuckles,level of at least three times the upper limit of normal is diagnostic waist, midriff, shoulders), in the palmar creases and in sexual areasof Cushing syndrome. [64,65] Intermediate values necessitate repeat- (nipples, areolae, axillae, perineum and genitalia). [9,67,68] Patchying the test. The UFC is 95100% sensitive and specific. [65] pigmentation also appears on mucosal surfaces, especially theAnother screening test is the overnight dexamethasone suppres- buccal mucosa, inner surfaces of lips, gums and tongue. [9] Genera-sion test, where 1mg of dexamethasone is given at 11.00pm and a lized buccal, vaginal and anal mucosal membrane hyperpigmenta-serum cortisol is obtained the next morning at 8.00am. A value of tion is usually seen only in patients whose skin is normally>3 g/dl is abnormal. This test is only 80% specific, because it pigmented, such as African Americans and native Americans. [67carries many false positives, especially in certain psychiatric con- Scars acquired after the onset of Addison disease are permanentlyditions like major depression. [65] For this reason, even when abnor- pigmented. Hair may darken and longitudinal pigmented bandsmal, the overnight dexamethasone suppression test needs to beconfirmed by doing a UFC. [64,65] After the diagnosis of Cushingsyndrome is made, serum ACTH should be measured to define thesource, either adrenal (low ACTH), pituitary (normal to highACTH), or ectopic (very high ACTH). Subsequently, appropriateimaging is performed. [64,65] Sometimes, the ACTH level is not verydiagnostic, and further sophisticated tests are necessary (beyondthe scope of this article).

4.3 Treatment

The treatment of Cushing syndrome is directed at the source.Surgery on the pituitary, adrenal or ectopic tumor (if not metastat-ic) is performed. Occasionally, it may be necessary to use radiationtherapy (pituitary tumor), chemotherapy (metastatic ectopic Cush-

Fig. 8. Hyperpigmentation, mostly marked on areas exposed to light, suchas face and neck in Addison disease.



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normal in 1050% of these women. [83,84] PCOS is the associationof androgenism (biochemical or clinical) with chronic anovulationin women without specific underlying disease of the adrenal orpituitary glands. [85] Less common causes include congenital adre-nal hyperplasia (CAH), ovarian and adrenal tumors, and drugs(anabolic steroids, progestogens, danazol). [83,84] Certain drugs, likeminoxidil, cyclosporine and penicillamine may rarely causehypertrichosis, or diffusely increased total body hair; which doesnot represent true hirsutism. [83,84] The major clinical findings inwomen with androgen-related disorders are summarized in tableVI. [83,84]

7.1 Cutaneous ManifestationsFig. 10. Acromegaly, showing coarse facial features and macrognathia.

The skin becomes thickened and coarse in patients with andro-ous. [78] Hair growth increases and some women (


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pituitary hormones. The most common cause is a pituitary tumor,

although infiltrative, vascular, cranial radiation therapy, hypotha-

lamic tumors and other disorders also cause hypopituitarism. [86

Most of the symptoms and signs are similar to those that occurwith a primary deficiency of that gland. ACTH deficiency results

in adrenal insufficiency (see previous section), except that

hyperpigmentation is absent. TSH deficiency results in symptoms

and signs of hypothyroidism (see previous section). Luteinizing

hormone (LH) and follicle-stimulating hormone (FSH) deficien-

cies lead to amenorrhea in females and erectile dysfunction with

hypogonadism in males. Loss of GH results in lack of vigor,

decreased tolerance to exercise and decreased social functioning.

Table VI. Clinical findings in women with androgen-related disorders

Acanthosis nigricans and obesity (especially in PCOS)

Acne vulgaris and seborrhea

Clitoromegaly

Deepening of voice

Galactorrhea (hyperprolactinemia)

Hirsutism (see section 7.1); androgenetic alopecia (diffuse)

Increased muscle mass

Irregular periods

Loss of female body contour

Striae, thin skin, bruising, truncal obesity (Cushing syndrome seesection 4)

Temporal balding

PCOS = polycystic ovary syndrome.

PRL (prolactin) is the only hormone under tonic inhibition in

suspected, and ovarian imaging (transvaginal ultrasound) should normal conditions; in hypopituitarism, it becomes elevated andbe performed. If DHEA-S is more than 23 times the upper limit results in galactorrhea. [86] Less commonly, deficiency in arginineof normal, imaging of the adrenals (CT scan) is done to exclude a

vasopressin (AVP) results in diabetes insipidus.virilizing adrenal mass. Prolactin is measured in women who,besides hirsutism, have irregular menses, to exclude hyperprolac-tinemia; [84] slightly elevated prolactin levels may be seen in wo-men with PCOS, moderately elevated values (>40 ng/dl) shouldprompt a search for other etiologies (hypothalamic/pituitary dis-ease, renal or liver disease, primary hypothyroidism, and drugs,mainly neuroleptics).

The diagnosis of PCOS does not require the presence of poly-

cystic ovaries on ultrasound, because 20% of normal ovulatorywomen may have polycystic ovaries and up to 20% of women withPCOS may have normal ovaries.

Testing for late-onset CAH (due to 21-hydroxylase deficiency)should be considered in women with early onset of hirsutism or afamily history of CAH. Diagnosis is best established by measuringserum 17-hydroxyprogesterone before and 60 minutes after 250 gof cosyntropin. A 60-minute value above 1000 ng/dl is diagnostic.

7.3 Treatment

In women who have PCOS or idiopathic hirsutism, oral contra-ceptives, frequently in combination with antiandrogens (like spiro-nolactone) are effective in controlling the hirsutism and regulatingthe periods in most women. [83-85] Of course, hirsutism can also betreated by physical methods (electrolysis, laser removal etc.).Adrenal or ovarian tumors should be resected. In CAH, treatmentmight include glucocorticoids and genetic counseling. [85]

8. Hypopituitarism

Hypopituitarism results from a variety of conditions that com-promise the anterior pituitary and therefore the elaboration of all Fig. 12. Facial acne, hirsutism and greasy skin.



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volume, osmolarity and specific gravity; serum electrolytes arealso measured. Some of these tests have limitations, the discussionof which is beyond the scope of this paper. [86] A pituitary MRI isalso performed to rule out the possibility of tumor or other destruc-tive process in the sellar region.

8.3 Treatment

Treatment of hypopituitarism is directed at the underlyingprocess resulting in hypopituitarism. Most commonly, it is apituitary macroadenoma that needs to be removed surgically. [86

Hormonal deficiencies should also be replaced (thyroid hormones,glucocorticoids, sex steroids, GH, and occasionally AVP). [86]

9. Parathyroid Hormone

Primary hyperparathyroidism (hypersecretion of parathyroidhormone [PTH] by parathyroid adenoma or hyperplasia) is notassociated with any cutaneous manifestations except, rarely, pruri-tus and deposition of calcium. [9] In few case reports, chronicurticaria was the initial manifestation of primary hyperpara-thyroidism. [87]

Hypoparathyroidism (failure of parathyroid glands) may be theresult of surgery, infiltrative disorders, autoimmune conditions, oridiopathic. The clinical presentation of hypoparathyroidism isshown in table VII. [88]

Pseudohypoparathyroidism is a heritable disorder of target-organ unresponsiveness to parathyroid hormone. It mimics hy-

poparathyroidism, with hypocalcemia and hyperphosphatemia,Fig. 13. Enlargement of the clitoris. but the PTH level is elevated. [89] Many of these patients have


Pallor of the skin with a yellowish tinge is a prominent featurein patients with hypopituitarism, but mucous membranes retaintheir normal hue unless the patient is anemic. The skin is dry butsofter than in primary hypothyroidism. The face may be puffy andless expressive because of a reduction in skin folds. Thinness of the skin and subcutaneous tissues results in fine wrinkling aroundthe eyes and mouth making the patient look older. [9]

Loss of body hair occurs in all patients. Scalp hair tends to befine and dry. Sebaceous secretions and sweating also decrease. [9]

8.2 Diagnosis

Screening studies include measurement of prolactin, TSH, freeT4, morning cortisol and ACTH, FSH, LH, testosterone (inmales), and dynamic testing for GH deficiency. In the right setting(polyuria, polydipsia and absence of diabetes mellitus), screeningfor diabetes insipidus is done by a 24-hour urine collection for

Table VII. Clinical manifestation of hypoparathyroidism

Abnormal dentition

Cataracts

Chvostek sign (twitching of the circumoral muscles in response totapping the facial nerve, just anterior to the ear)

Coarse brittle hair, alopecia

Dry, rough skin

Extrapyramidal signs

Laryngospasm and bronchospasm

Muscle cramps

Paresthesias

Personality disturbances

Prolonged Q-T interval on EKG

Pseudopapilledema

Seizures

Tetany

Trousseau sign (carpal spasm elicited by inflation of a blood pressurecuff to 20mm Hg above the patients systolic pressure for 3 minutes)



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9.2 Diagnosis

The diagnosis of hypoparathyroidism (low calcium, high phos-phorus and low PTH), pseudohypoparathyroidism (low calcium,

high phosphorus and high PTH) and primary hyperparathyroidism(high calcium and high PTH) can be made by measuring serumionized calcium, phosphorus and intact PTH. [88]

9.3 Treatment

In patients with symptomatic primary hyperparathyroidism,surgery should be performed. [91] In asymptomatic patients, indica-tions for surgery include: 400 mg/day, decreased kidney function, nephrocalci-nosis, and low serum levels of 25-hydroxyvitamin D. [91] Whensurgery is not performed, patients should stay well hydrated, andkeep a daily calcium intake of no more than 600800mg.

In patients with hypoparathyroidism and pseudohypoparathy-roidism, calcium and calcitriol (1,25-hydroxyvitamin D) are usedin combination. [90]

10. Diabetes Mellitus

Diabetes mellitus is a group of metabolic diseases characterizedby hyperglycemia resulting from defects in insulin secretion (type1 diabetes), insulin action or both (type 2 diabetes). The classicsymptoms are polyuria, polydipsia and unexplained weightloss. [92] Other manifestations of diabetes mellitus are shown intable VIII. [92]

10.1 Cutaneous ManifestationsFig. 14. Albright hereditary osteodystrophy: short stature, round face, shortneck and brachydactyly (short digits).

Certain skin disorders are more frequently associated withAlbright hereditary osteodystrophy. Pseudopseudohypoparathy-

diabetes mellitus. The best example of such an association isroidism is the presence of Albright hereditary osteodystrophy necrobiosis lipoidica diabeticorum (NLD) [figure 16]. Occurringwithout any disorder of calcium metabolism. [89] in 0.3% of patients with diabetes mellitus, these lesions are distinc-


In hypoparathyroidism and pseudohypoparathyroidism, theskin is dry, scaly, hyperkeratotic, and puffy. Nails become opaque,brittle and develop transverse ridges. Hair becomes coarse andsparse. Eczematous dermatitis, hyperkeratotic and maculopapulareruptions have been reported. [9] Autoimmune hypoparathyroidismmay be associated with chronic mucocutaneous candidiasis. [90]

Many patients with pseudohypoparathyroidism and all patientswith pseudopseudohypoparathyroidism have Albright hereditaryosteodystrophy (figure 14 and figure 15), which consists of shortstature, short neck, brachydactyly (short digits, mainly fourth andfifth metacarpals), and subcutaneous ossifications. [89]

Fig. 15. Brachydactyly in a patient with Albright hereditary osteodystrophy:most often, there is shortening of the fourth and fifth metacarpals.



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328 Jabbo

does not pit on pressure. It occurs mainly in obese patients withdiabetes mellitus with evidence of vascular complications. It maynot remit after a long period of time. [99,100]

As many as one-third of patients with diabetes (both type 1 andtype 2) have tight, thickened, and waxy skin over the dorsa of thehands. [101] Other cutaneous manifestations include reddening of the face (rubeosis faciei) and of the extremities in patients withlong-standing diabetes mellitus, with occasional necrosis and de-struction of the underlying bone, [102] bullous lesions of the feet,xanthomatosis (secondary to hyperlipidemia, common in diabetesmellitus), infections (most frequent are staphylococcal pyodermas,candidiasis, erythrasma and epidermophytosis). [9]

10.2 Diagnosis

There are three possible ways to diagnose diabetes mellitus,

and each must be confirmed, on a subsequent day, by one of the

Table VIII. Clinical manifestations in diabetes mellitus

Atherosclerotic heart disease (myocardial infarction, heart failure) andperipheral vascular disease (lower extremity amputation)

Autonomic neuropathy (postural hypotension, gastroparesis, diarrhea,

neurogenic bladder, sexual dysfunction)Intertriginous candidiasis (common in the obese) and oral candidiasis(uncommon)

Neuropathic foot ulcers with secondary infections and diabetic Charcotsfoot (degenerative change of the bony structure of the foot)

Peripheral neuropathy (sensory deficit, burning and tingling sensations)

Polyuria, polydipsia, polyphagia

Renal failure

Retinopathy (blurred vision, decreased visual acuity, visual loss)

Skin lesions and infections (see section 10.1)

Strokes

Unexplained weight loss

Vaginitis (usually due to monilial infection)other two methods. The three methods are: (i) fasting plasmaglucose at least 7.0 mmol/l (126 mg/dl); (ii) symptoms of diabetes

tive, oval or irregularly shaped, indurated plaques with centralatrophy and yellow pigmentation; peripherally along the marginsthere is either red-brown or violaceous pigmentation. The lesionsusually occur on the anterior and lateral surfaces of the lowerlegs. [9] The differential diagnosis includes granuloma annulare,which presents as asymptomatic annular red plaques on the dor-sum of the extremities or posterior neck, but lacking a yellowdiscoloration. Even histologically, it might be difficult to differen-tiate between NLD and granuloma annulare. NLD occurs in pa-tients with both type 1 and type 2 diabetes. The majority of patients have diabetes mellitus when NLD develops; in most of therest, diabetes mellitus appears later. [93]

Progression of lesions does not correlate with normalization of hyperglycemia. [9] Acanthosis nigricans has been associated withtype 2 diabetes, type A and type B syndromes of insulin-resistance(in type A, there is a defect in insulin receptor; in type B, there areblocking antibodies to the insulin receptor). [62,63,94] Acanthosisnigricans (figure 17) consists of diffuse velvety thickening andhyperpigmentation of the skin, chiefly in the axillae, neck, in-framammary folds, groin, perineum, and less often, nipples and

areolae.[95]

Vitiligo occurs with greater than expected incidence inpatients with diabetes, either type 1 [96] or type 2. [97] Diabeticdermopathy consists of asymptomatic, irregularly shaped patchesoccurring on the anterior lower legs; their surfaces are depressedand they are a light brown color. [98] They are often accompaniedby significant microangiopathy elsewhere. [9] Scleredemaadultorum consists of induration of the skin beginning on theposterior and lateral neck. This painless swelling may graduallyspread to the face, shoulders, anterior neck, and upper torso; it mayeventually involve the abdomen, arms and hands. The hard skin

Fig. 16. Necrobiosis lipoidica diabeticorum with multiple lesions showingan atrophic and necrotic center with a raised brownish-red border.



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4. Dabon-Almirante CLM, Surks MI. Clinical and laboratory diagnosis of thyrotoxi-cosis. Endocrinol Metab Clin North Am 1998; 27 (1): 25-35

5. Mullin GE, Eastern JS. Cutaneous signs of thyroid disease. Am Fam Physician1986; 34 (4): 93-8

6. Holt PJA, Lazarus J, Marks R. The epidermis in thyroid disease. Br J Dermatol1976; 95: 513-8

7. Rosen T, Kleman GA. Thyroid and the skin. In: Callen JP, Jorizzo JL Greer KE, etal., editors. Dermatologic signs of internal disease. 2nd ed. Philadelphia: WBSaunders, 1995: 189

8. Heymann WR. Cutaneous manifestations of thyroid disease. J Am Acad Dermatol1992; 26: 885-902

9. Freinkel RK. Cutaneous manifestations of endocrine diseases. In: Fitzpatrick TB,Eisen AZ, Wolff K, et al., editors. Dermatology in general medicine. 4th ed.New York: McGraw-Hill, 1993: 2113-31

10. Rook A. Endocrine influences on hair growth. BMJ 1965; 1: 609-1411. Rook A, Dawber R. Diseases of the hair and scalp. 2nd ed. Oxford: Blackwell

Scientific Publications, 1991: 14712. Norton LA. Disorders of the nails. In: Moschella SL, Hurley HJ, editors. Dermatol-

ogy. 3rd ed. Philadelphia: WB Saunders, 1992: 1574Fig. 17. Acanthosis nigricans with the typical velvety hyperpigmented skinof the neck and axillae.

13. Locke W. Unusual manifestations of Graves disease. Med Clin North Am 1967;51 (4): 915-24

plus casual plasma glucose at least 11.1 mmol/l (200 mg/dl); and 14. Mullin GE, Eastern JS. Cutaneous consequences of accelerated thyroid function.Cutis 1986; 37: 109-14(iii) 2-hour plasma glucose at least 11.1 mmol/l (200 mg/dl) during

15. Davis PJ, Davis FB. Hyperthyroidism in patients over the age of 60 years.an oral glucose tolerance test. [92] Medicine 1974; 53 (3): 161-8116. Heymann WR. The skin in thyrotoxicosis. In: Braverman LE, Utiger RD, editors.

The thyroid. 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2000: 593-510.3 Treatment17. Ortonne J-P, Mosher DB, Fitzpatrick TB. Vitiligo and other hypomelanoses of hair

and skin. New York: Plenum, 1983: 182Treatment of diabetes mellitus always includes lifestyle modifi-18. Cunliffe WJ, Hall R, Newell DJ, et al. Vitiligo, thyroid disease and autoimmunity.

cations. In type 1 diabetes, insulin is given as 34 injections a day Br J Dermatol 1968; 80: 135-9(combination of long- and short-acting insulins). [103] In type 2 19. Shong YK, Kim JA. Vitiligo in autoimmune thyroid disease. Thyroidology 1991;

3: 89-91diabetes, oral agents (secretagogues, metformin, thiazolidinedion-20. Kantor GR, Bernhard JD. Investigation of the pruritic patient in daily practice.

es and -glucosidase inhibitors) can be used as monotherapy or in Semin Dermatol 1995; 14: 290-6combination. [104] Insulin may be added in patients who have not 21. Readett MD. Constitutional eczema and thyroid disease. Br J Dermatol 1964; 76:

126-39had sufficient disease response with oral agents.

[104]

22. Collet E, Petit J-M, LaCroix M, et al. Chronic urticaria and thyroid auto-immunity.Ann Dermatol Venereol 1995; 122 (6-7): 413-6

11. Conclusion 23. Pegum JS, Grice K. Unusual skin eruptions with eosinophilia associated withhyperthyroidism. Br J Dermatol 1973; 88 (3): 295-301

24. Thomson JA. Xanthelasma associated with thyrotoxicosis. J Clin EndocrinolMany cutaneous manifestations may be caused by an underly-Metab 1965 (Pt 1); 25: 758-60ing endocrine disorder. Dermatologists should be able to recognize

25. Fatourechi V, Pajouhi M, Fransway AF. Dermopathy of Graves disease (pretibialthese patients, and perform the basic screening tests before refer- myxedema): review of 150 cases. Medicine 1994; 73 (1): 1-7

26. Horiuchi Y. Pretibial myxedema associated with chronic thyroiditis [letter]. Archring them to endocrinologists, in order to complete the work-upDermatol 1985; 121 (4): 451and receive corrective rather than symptomatic treatment.

27. McDougall IR. Graves disease: current concepts. Med Clin North Am 1991; 75:79-95

28. Moule B, Grant MC, Boyle IT, et al. Thyroid acropachy. Clin Radiol 1970; 21:Acknowledgements329-33

29. Solanki SV, Shah SS, Kothari UR. Thyroid acropachy. Indian J Med Sci 1973; 27:No sources of funding were used to assist in the preparation of this708-10manuscript. The author has no conflicts of interest that are directly relevant to

30. Ross DS. Serum thyroid-stimulating hormone measurement for assessment of the content of this manuscript.thyroid function and disease. Endocrinol Metab Clin North Am 2001; 30 (2):245-64

31. Ladenson PW. Diagnosis of thyrotoxicosis. In: Braverman LE, Utiger RD, editors.ReferencesWerner and Ingbars the thyroid. 7th ed. Philadelphia: Lippincott-Raven, 1996:1. Brownlie BE, Wells JE. The epidemiology of thyrotoxicosis in New Zealand:708-12incidence and geographical distribution in North Canterbury, 1983-1985. Clin

32. Kaplan MM, Meier DA, Dworkin HJ. Treatment of hyperthyroidism with radioac-Endocrinol 1990; 33 (2): 249-59tive iodine. Endocrinol Metab Clin North Am 1998; 27 (1): 205-232. Reinwein D, Benker G, Konig MP, et al. The different types of hyperthyroidism in

33. Cooper DS. Antithyroid drugs for the treatment of hyperthyroidism caused byEurope: results of a prospective study of 924 patients. J Endocrinol Invest 1988;Graves disease. Endocrinol Metab Clin North Am 1998; 27 (1): 225-4711 (3): 193-200

3. Williams I, Ankrett VO, Lazarus JH, et al. Aetiology of hyperthyroidism in 34. Ross DS. Syndromes of thyrotoxicosis with low radioactive iodine uptake. En-Canada and Wales. J Epidemiol Community Health 1983; 37 (3): 245-8 docrinol Metab Clin North Am 1998; 27 (1): 169-85



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94. Cruz PD, Hud JA. Excess insulin binding to insulin-like growth factor receptors: 101. Clark CV, Pentland B, Ewing DJ, et al. Decreased skin wrinkling in diabetesproposed mechanism for acanthosis nigricans. J Invest Dermatol 1992; 98 (6 mellitus. Diabetes Care 1984; 7 (3): 224-7Suppl.): 82S-5S 102. Lithner F. Lesions of the legs in diabetics and in patients with familial amyloidosis

95. Matsuoka LY, Wortsman J, Goldman J. Acanthosis nigricans. Clin Dermatol 1993; and polyneuropathy. Acta Med Scand Suppl 1976; 589: 1-2311: 21-5

103. McCulloch DK. Basic insulin regimens in diabetes mellitus. UpToDate 2003; 1196. Macaron C, Winter RJ, Traisman HS, et al. Vitiligo and juvenile diabetes mellitus.

(1): 1-6Arch Dermatol 1977; 113 (11): 1515-7104. Jabbour SA, Goldstein BJ. Improving disease management with new treatments for97. Dawber RPR. Vitiligo in mature-onset diabetes. Br J Dermatol 1968; 80 (5): 275-8

type 2 diabetes mellitus. Clin Geriatr 2001; 9 (5): 157-6898. Stawiski MA, Voorhees JJ. Cutaneous signs of diabetes mellitus. Cutis 1976; 18(3): 415-21

99. Fleischmajor R, Lara JV. Scleredema adultorum: a histochenical and biochemicalCorrespondence and offprints: Dr Serge A. Jabbour, 211 South 9th Street, Stestudy. Arch Dermatol 1965; 92: 643-52600, Philadelphia, PA 19107, USA.100. Cohen BA, Wheeler CE, Briggman RA. Scleredema of Buschke and diabetes

mellitus. Arch Dermatol 1970; 101: 27-35 E-mail: [email protected]


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