THERAPY IN PRACTICE

Am J Clin Dermatol 2003; 4 (5): 315-331

1175-0561/03/0005-0315/$30.00/0
Adis Data Information BV 2003. All rights reserved.

Cutaneous Manifestations of Endocrine Disorders

A Guide for Dermatologists
Serge A. Jabbour
Division of Endocrinology, Diabetes and Metabolism, Thomas Jefferson University, Philadelphia, Pennsylvania, USA

Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
1. Thyrotoxicosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
1.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
1.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317
1.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
2. Hypothyroidism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
2.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318
2.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
2.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
3. Autoimmune Thyroid Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
3.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
3.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
3.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
4. Cushing Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
4.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321
4.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
4.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
5. Addison Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
5.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322
5.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
5.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
6. Acromegaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
6.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 323
6.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
6.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
7. Androgen-Related Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
7.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
7.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324
7.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
8. Hypopituitarism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
8.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
8.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
8.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
9. Parathyroid Hormone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
9.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
9.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
9.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
10. Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
10.1 Cutaneous Manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
10.2 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328

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10.3 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329

11. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329

Abstract

Dermatologists may commonly see skin lesions that reflect an underlying endocrine disorder. Identifying the
endocrinopathy is very important, so that patients can receive corrective rather than symptomatic treatment. Skin
diseases with underlying endocrine pathology include: thyrotoxicosis; hypothyroidism; Cushing syndrome;
Addison disease; acromegaly; hyperandrogenism; hypopituitarism; primary hyperparathyroidism; hypoparathyroidism; 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, with
myxedematous changes, mainly in the hands and in the periorbital region.
The striking features of Cushing syndrome are centripetal obesity, moon facies, buffalo hump, supraclavicular fat pads, and abdominal striae. In Addison disease, the skin is hyperpigmented, mostly on the face, neck and
back of the hands.
Virtually all patients with acromegaly have acral and soft tissue overgrowth, with characteristic findings, like
macrognathia 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. Pseudohypoparathyroidism
may have a special somatic phenotype known as Albright osteodystrophy. This consists of short stature, short
neck, 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 physiologic

processes in each system of the body, including the skin. Endocrine diseases, through excess or deficiencies of hormones, result
in changes in cutaneous function and morphology. This paper
reviews many endocrinopathies and their associated skin conditions. The overall clinical presentation is also discussed, as are the
appropriate diagnostic tests, and a brief overview of the treatments
related to these endocrine disorders.
1. Thyrotoxicosis
Thyrotoxicosis may be due to several conditions. The most
common cause is Graves disease (autoimmune disease); its frequency ranging from 6090% of all thyrotoxic patients in different
regions of the world. Most of the remaining etiologies are caused
by a single toxic adenoma, a toxic multinodular goiter, several
types of thyroiditis (subacute thyroiditis, silent thyroiditis) or
excessive exogenous thyroid hormone ingestion. These other
causes are rare.[1-3] The symptoms and signs of thyrotoxicosis are
summarized in table I.[4]
Adis Data Information BV 2003. All rights reserved.

Table I. Major symptoms and signs of thyrotoxicosis

Symptoms

Signs

Fatigue

Diffuse goiter (Graves), solitary nodule or

multinodular 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

thyroiditis)

Tachycardia or atrial arrhythmia

Nervousness

Thyroid tenderness
(subacute thyroiditis)

Palpitation

Tremor and hyperreflexia

Tremor

Warm, moist, smooth skin

Weakness
Weight loss

Am J Clin Dermatol 2003; 4 (5)

Cutaneous Manifestations of Endocrine Disorders

Fig. 1. Plummers nail, or onycholysis, is a separation of the nail plate from

the nail bed. The separated portion is white and opaque, in contrast to the
pink translucence of the attached portion.

1.1 Cutaneous Manifestations

In patients with thyrotoxicosis, the skin is usually warm, erythematous and moist, with a smooth, silky texture.[5-7] The warmth,
caused by increased cutaneous blood flow and peripheral vasodilation, may be responsible for episodic facial flushing and palmar
erythema.[8]
The epidermis is thin but not atrophic.[9] Generalized hyperhidrosis may be noted, but it is usually more prominent on the palms
and soles.[8,9] Scalp hair is fine and soft, and holds a permanent
wave poorly.[5,8] Diffuse loss of scalp hair occurs in 2040% of
thyrotoxic patients, although the severity of the loss is not directly
related to the severity of the endocrine abnormality.[10] Alopecia
areata and loss of axillary, pubic, body and eyebrow hair may also
be noted.[11] The nails become shiny, soft and friable. Many
patients develop onycholysis (figure 1), that is, distal separation of
nail plate from its underlying bed with upward curvature, so-called
Plummers nail; it usually begins under the distal central portion of
the fourth fingernail, but may eventually involve any of the finger
and toe nails.[12,13] Onycholysis is not specific to thyrotoxicosis
and may be observed in patients with hypothyroidism, psoriasis,
trauma or allergic contact dermatitis.[14] Such nail changes are less
common 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 localized, sometimes in a pattern similar to patients with Addison
disease.[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 pruritus,[20] eczematous dermatitis,[21] dermographism and urticaria,[22]
purpura and erythematous eruptions,[23] and xanthelasma.[24]
Adis Data Information BV 2003. All rights reserved.

317

In addition to the aforementioned cutaneous features of the

thyrotoxic state, patients with Graves disease may have distinct
cutaneous manifestations such as pretibial myxedema and acropachy. Pretibial myxedema or thyroid dermopathy (figure 2) is
almost always associated with Graves ophthalmopathy,[25] but it
was also reported in patients with Hashimoto thyroiditis.[26] It
occurs in a small percentage of patients with Graves disease
(0.54%), most frequently on the anterior tibia and dorsa of the
feet, and consists of nonpitting scaly thickening and induration of
the skin; it can also present as few well-demarcated pink, fleshcolored or purple-brown papules or nodules.[8,27] Thyroid acropachy (figure 3) is a triad consisting of digital clubbing, soft
tissue swelling of the hands and feet, and periosteal new bone
formation.[8] It occurs in 0.11% of patients with Graves disease.[28] It almost always occurs in association with
ophthalmopathy and pretibial myxedema.[29]
1.2 Diagnosis

The diagnosis of thyrotoxicosis is made by measuring serum

thyroid-stimulating hormone (TSH) level, which is the most costeffective screening test.[30] A normal TSH almost excludes thyrotoxicosis, except in the rare case of TSH-secreting pituitary adenoma, where TSH is normal to high.[30,31] If TSH is suppressed to
below 0.1 IU/ml, free T4 (thyroxine) and free T3 (triiodothyronine) should then be obtained. Because serum levels of total T4
and total T3 can be affected by some binding proteins (mostly
thyroxine-binding globulin), free levels are more accurate and
reflect the patients true thyroid state. Some patients may also have
T3-toxicosis, producing mainly T3; for this reason, free T3 should
always be measured, especially if TSH is suppressed and free T4 is
normal.[30,31]
After a laboratory diagnosis of hyperthyroidism is made, a
24-hour radioiodine uptake and scan is usually done to define the

Fig. 2. Pretibial myxedema, a localized violaceous induration that usually

occurs on the shins.
Am J Clin Dermatol 2003; 4 (5)

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Jabbour

locytosis.[33] The different types of thyroiditis are usually selflimited and do not necessitate radioactive iodine or antithyroid
agents.[34]
2. Hypothyroidism
Worldwide, iodine deficiency is the most common cause of
hypothyroidism.[35] In areas where iodine intake is adequate, the
most common causes are chronic autoimmune thyroiditis (goitrous
type or Hashimotos thyroiditis and atrophic type or primary
myxedema), radiation-induced thyroiditis (mostly after 131I therapy for thyrotoxicosis) and post-surgical hypothyroidism.[35] Other
rare causes are drug-induced (lithium, iodine), central hypothyroidism (pituitary or hypothalamic disease), and the hypothyroid
phase of certain thyroiditis (subacute, silent).[35] The symptoms
and signs of hypothyroidism are summarized in table II.[36]
2.1 Cutaneous Manifestations

Fig. 3. Acropachy or clubbing of the nail.

etiology, either Graves (high uptake, homogenous goiter), toxic

nodule(s) [high uptake, hot nodule(s)], or thyroiditis (low/suppressed uptake, cold scan).[30,31]
1.3 Treatment

Patients with symptomatic thyrotxicosis can be given a betaadrenoreceptor antagonist (beta-blocker), unless contraindicated
(such as patients with asthma). The definite treatment of hyperthyroidism depends on the etiology. In Graves disease and toxic
nodule(s), radioactive iodine is the favorite option for most endocrinologists, because it has a good safety profile and is very
effective.[32] However, it may lead to post-ablative hypothyroidism
and weight gain. In Graves disease, when patients refuse radioactive iodine, antithyroid agents (methimazole, propylthiouracil) are
another option,[33] but induce a remission in only 3040% of
patients after a treatment period of 18 months. They also have
adverse effects that include rash, pruritus, urticaria, arthralgias,
fever, nausea and vomiting; but the most serious effect is agranu Adis Data Information BV 2003. All rights reserved.

In hypothyroidism, the skin is cold and pale, due to cutaneous

vasoconstriction and reduced core temperature.[9] In over 80% of
patients 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 hypothyroidism (<10%).[38] Fine wrinkling imparts a parchment-like quality to the skin, especially in hypothyroidism secondary to pituitary
failure.[9] A malar flush is seen in 50% of patients.[37] Yellowish
discoloration of the skin, especially the palms, soles and nasolabial
folds, is caused by accumulation of carotene in stratum corneum,
secondary to carotenemia,[39] attributed to a hepatic defect in the
Table II. Major symptoms and signs of hypothyroidism
Symptoms

Signs

Arthralgia

Ascites

Cold intolerance

Bradycardia

Constipation

Carotenemia

Decreased appetite

Diastolic hypertension

Decreased perspiration

Diffuse or nodular goiter

Depression

Dry, coarse skin

Dry skin

Hoarseness

Fatigue and lethargy

Hyporeflexia and delayed relaxation of

reflexes

Hoarseness

Loss of lateral third of eyebrows

Menstrual disturbances

Nonpitting edema (myxedema)

Mental impairment

Pleural effusions

Paresthesia

Puffy face

Sleepiness

Slow movements

Weight gain

Slow speech

Am J Clin Dermatol 2003; 4 (5)

Cutaneous Manifestations of Endocrine Disorders

319

conversion of beta-carotene to vitamin A. Scleral sparing is a clue

to hypercarotenemia as opposed to jaundice.[40]
The most striking skin change is due to dermal accumulation of
mucopolysaccharides (myxedema), and is most marked in the
hands and in the periorbital region. The facial changes are almost
pathognomonic (figure 4). There is a non-pitting swelling or
puffiness around the eyes, with a very characteristic loss of the
outer third of the eyebrows. A drooping of the upper lid may occur
secondary to decreased sympathetic stimulation. The nose is
broadened, and the lips are thickened. The tongue is large. The
face lacks expressiveness; and changing emotions are registered
slowly.[8,9,37]
The hair is dull, coarse and brittle, in part due to diminished
sebum 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 are
reported in many patients with myxedema.[37,41] The nails are thin,
brittle and striated, with both longitudinal and transverse
grooves.[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 is
normal, hypothyroidism is almost excluded, except in the rare
occurrence of central hypothyroidism, where TSH can be normal
or low; in this case, the diagnosis is made by adding free T4 level
to TSH.[44,45] When TSH is high, free T4 is also measured, but it
may be normal in the early stages of hypothyroidism (subclinical
hypothyroidism). Antithyroid peroxidase antibodies (anti-TPO)
are obtained to document the diagnosis of Hashimoto thyroiditis.[44,45] 24-hour thyroid uptake and scan is neither necessary nor
useful in patients with hypothyroidism.

Fig. 4. Hypothyroidism. This patient has many typical features of hypothyroidism: puffiness of the face with dry and pale skin.

time, there is no cause-effect relationship demonstrated, but the

association is probably part of the same immune dysfunction.
These associations may be in the patients or in other family
members.[47]

2.3 Treatment

L-thyroxine is given in a maintenance dose of 1.6 g/kg/day to

patients with hypothyroidism, except in patients with underlying
cardiac disease or older people (>60 years), where treatment is
started at 25 g/day and increased progressively by 25g every
24 weeks until the maintenance dose is reached. TSH levels are
measured 6 weeks after the treatment is started or after any change
in dose.[46] Titration in dosage is made every 6 weeks until TSH
reaches a normal level of around 12 IU/ml.
3. Autoimmune Thyroid Disease
Many skin disorders can be seen in patients with autoimmune
thyroid disease, independently of thyroid function. Most of the
Adis Data Information BV 2003. All rights reserved.

3.1 Cutaneous Manifestations

The most common clinical association of autoimmune thyroid

disease is dyschromia, which generally has an autoimmune etiology. The most frequent hyperchromia is melasma, a localized cafeau-lait hyperpigmentation over the forehead, upper lips, cheeks,
and chin. There is a strong association between thyroid autoimmunity (microsomal thyroid autoantibodies) and melasma, mostly
in women whose melasma develops during pregnancy or after
ingestion of oral contraceptive drugs.[48] Among hypochromias,
the main expression is vitiligo, characterized by achromic areas
with hyperpigmented margins, located mainly in the back of the
hands, face, neck, folds and genitals. The prevalence of vitiligo in
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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

5580

Oligomenorrhea or amenorrhea

5580

Polydipsia, polyuria

2544

Psychological changes

3186

Renal calculi

1519

Weakness, proximal myopathy

2990

Graves disease; the prevalence of TSHR-Ab varies from 70

to100%, being higher in patients with hyperthyroidism.[53]
Of course, TSH is also measured, as discussed in sections 1 and
2. If TSH is normal, but thyroid autoantibodies are present, the
patients is at higher risk of developing thyroid dysfunction; therefore, follow-up testing with yearly TSH measurements would be
indicated.
3.3 Treatment

If the patient has hyper- or hypothyroidism, then treatment is

aimed at correcting thyroid function (see sections 1 and 2). If the
patient 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 TSH
was initially within normal limits.[51,52] Therefore, in these patients, especially if they do not respond to other treatments, Lthyroxine could be tried for 48 weeks;[51,52] care should be taken

patients with Graves disease is 67%, whereas it is only 12% in

the general population.[49]
Besides dyschromia, alopecia areata is classically associated
with thyroid diseases;[50] the main features are circumscribed bald
patches in the scalp or beard. Also, in patients with diffuse
alopecia, autoimmune thyroid disease is found in almost 60% of
the cases.[47]
Other skin disorders described in patients with autoimmune
thyroid diseases are pemphigus, bullous pemphigoid, dermatitis
herpetiformis, lupus erythematosus, scleroderma, and Sjogren
syndrome.
The association of chronic urticaria and angioedema with thyroid autoimmunity has also been observed, and resolution of
chronic urticaria was achieved after L-thyroxine treatment, even in
euthyroid patients.[51,52]
3.2 Diagnosis

The presence of one or more of the skin disorders previously

listed in section 3.1 should prompt the screening for autoimmune
thyroid disease by the use of antithyroid peroxidase antibodies,
which replaced the former antithyroid microsomal and antithyroglobulin antibodies. These antibodies are present in almost
9598% of patients with Hashimoto thyroiditis and in almost 80%
of patients with Graves disease. A more expensive test, autoantibodies against the TSH receptor (TSHR-Ab), is more specific for
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Fig. 5. Plethoric moon facies in Cushing syndrome.

Am J Clin Dermatol 2003; 4 (5)

Cutaneous Manifestations of Endocrine Disorders

321

skin eventually becomes fragile and, in extreme case, peels off

after being covered with adhesive tape (Liddle sign).[61] Minor
wounds heal slowly.[55] Loss of subcutaneous connective tissue
results in easy bruising after minimal trauma.[61]

Fig. 6. Buffalo hump and supraclavicular fat pad in Cushing syndrome.

not to render the patient thyrotoxic by titrating L-thyroxine in

order to keep the TSH in the lower range of normal.
4. Cushing Syndrome
Defined as the constellation of clinical signs and symptoms
resulting from chronic glucocorticoid excess, Cushing syndrome
can be caused mainly by pituitary hypersecretion of adrenocorticotropic hormone (ACTH) [Cushing disease], ectopic secretion of
ACTH by non-pituitary tumors, adrenal hypersecretion of
glucocorticoids or exogenous administration of corticosteroids.
Other etiologies are very rare.[54] The clinical manifestations of
Cushing syndrome are summarized in table III.[55,56]
4.1 Cutaneous Manifestations

One of the striking features of glucocorticoid excess is the

change in the appearance and body habitus. The most common
feature is progressive central (centripetal) obesity, usually involving the face, neck, trunk, abdomen and internally, the mesentery
and mediastinum.[55] Significant fat deposits may also appear in
the cheeks resulting in moon facies often accompanied by plethora over the cheeks, anterior neck, and sun-exposed chest (figure
5), in the dorsocervical area known as buffalo hump (figure 6), or
in the supraclavicular fossae (figure 6) resulting in supraclavicular fat pads.[56] Retro-orbital fat deposition may result in exophthalmos.[57]
The centripetal obesity is accompanied by wasting of the extremities.[9] Corticosteroids inhibit epidermal cell division,[58] and
decrease collagen synthesis.[59] The stratum corneum is thinned
and there is loss of subcutaneous fat in the extremities.[60] These
alterations in skin cell physiology lead to several dermatological
changes, including cutaneous atrophy, which is often prominent.[56] On physical examination, a fine cigarette paper wrinkling may be seen on the dorsum of the hand and the elbow.[56] The
Adis Data Information BV 2003. All rights reserved.

One sign that is virtually pathognomonic for Cushing syndrome

is the presence of purple (violaceous) striae >1cm in diameter
(figure 7). They are most commonly seen on the abdomen and
lower flanks but can also occur on the upper arms, shoulders,
axillae, breasts, hips, buttocks and upper thighs. These violaceous
striae must be differentiated from those often seen in obese or
pregnant patients, which are pink, reddish or silvery, less pigmented and thinner.[56]
Hyperpigmentation is also seen and is dependent upon both the
duration and the degree of increase in ACTH secretion.[55] It
occurs most often in patients with the ectopic ACTH syndrome,
less often with pituitary hypersecretion of ACTH, and not at all
with adrenal Cushing syndrome.[55] It may be generalized, but is
most evident in areas exposed to light (face, neck, back of the
hands) or to chronic mild trauma or pressure (shoulders, midriff,
waist, elbows, knuckles, spine, knees). Patchy pigmentation may
occur on the inner surface of lips and the buccal mucosa along the
line of dental occlusion.[55,61] As in any condition that causes
hyperinsulinism and insulin resistance, acanthosis nigricans may
be found in Cushing syndrome.[62,63] The axillae are the most
frequent sites, but also the sides of the neck, under the breasts, the
belt line and the groin.[56]
The most common change in body hair in Cushing syndrome is
the development of villous hypertrichosis of the forehead and
upper cheeks.[56] When there is concomitant androgen excess
(most common with carcinomas), women with Cushing disease
show signs of hirsutism, oily facial skin, acneiform rash on the
face, neck and shoulders, temporal balding and other signs of
virilization.[55,56]

Fig. 7. Abdominal striae (wide and purple) in Cushing syndrome.

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Table IV. Clinical manifestations of Addison disease

Amenorrhea

ing, adrenal carcinoma) or drugs which block steroid synthesis

(ketoconazole, metyrapone, aminoglutethimide).

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

5. Addison Disease
The most common cause of chronic primary adrenal insufficiency (Addison disease) was formerly tuberculous adrenalitis, but
now it is autoimmune adrenalitis (slow destruction of the adrenals
by cytotoxic lymphocytes).[66] Other etiologies (infection, hemorrhage, neoplasia) are less common. Addison disease should not be
confused with secondary adrenal insufficiency, where the damage
is in the hypothalamic/pituitary axis (tumors, chronic steroid intake, etc.). The clinical manifestations are shown in table IV.[66-68]

Mild normocytic anemia

Myalgias and arthralgias

5.1 Cutaneous Manifestations

Nausea and vomiting

Psychiatric manifestations
Tiredness and weakness
Weight loss

4.2 Diagnosis

When the index of suspicion is high for Cushing syndrome, the

screening test of choice is a 24-hour urinary free cortisol (UFC). A
level of at least three times the upper limit of normal is diagnostic
of Cushing syndrome.[64,65] Intermediate values necessitate repeating the test. The UFC is 95100% sensitive and specific.[65]
Another screening test is the overnight dexamethasone suppression test, where 1mg of dexamethasone is given at 11.00pm and a
serum cortisol is obtained the next morning at 8.00am. A value of
>3 g/dl is abnormal. This test is only 80% specific, because it
carries many false positives, especially in certain psychiatric conditions like major depression.[65] For this reason, even when abnormal, the overnight dexamethasone suppression test needs to be
confirmed by doing a UFC.[64,65] After the diagnosis of Cushing
syndrome is made, serum ACTH should be measured to define the
source, either adrenal (low ACTH), pituitary (normal to high
ACTH), or ectopic (very high ACTH). Subsequently, appropriate
imaging is performed.[64,65] Sometimes, the ACTH level is not very
diagnostic, and further sophisticated tests are necessary (beyond
the scope of this article).

The most striking cutaneous change of chronic primary adrenal

insufficiency is hyperpigmentation (figure 8 and figure 9), which
occurs almost uniformly,[9] with some exceptions.[69] In many
patients, it may be the first sign of the disease.[70] It is caused by
increased melanin content in the skin, due to the melanocytestimulating activity of the high plasma ACTH concentration.[71,72]
The hyperpigmentation is generalized, but is most conspicuous in
areas exposed to light (such as face, neck, back of hands), areas
exposed to chronic pressure (elbows, knees, spine, knuckles,
waist, midriff, shoulders), in the palmar creases and in sexual areas
(nipples, areolae, axillae, perineum and genitalia).[9,67,68] Patchy
pigmentation also appears on mucosal surfaces, especially the
buccal mucosa, inner surfaces of lips, gums and tongue.[9] Generalized buccal, vaginal and anal mucosal membrane hyperpigmentation is usually seen only in patients whose skin is normally
pigmented, such as African Americans and native Americans.[67]
Scars acquired after the onset of Addison disease are permanently
pigmented. Hair may darken and longitudinal pigmented bands

4.3 Treatment

The treatment of Cushing syndrome is directed at the source.

Surgery on the pituitary, adrenal or ectopic tumor (if not metastatic) is performed. Occasionally, it may be necessary to use radiation
therapy (pituitary tumor), chemotherapy (metastatic ectopic Cush Adis Data Information BV 2003. All rights reserved.

Fig. 8. Hyperpigmentation, mostly marked on areas exposed to light, such

as face and neck in Addison disease.
Am J Clin Dermatol 2003; 4 (5)

Cutaneous Manifestations of Endocrine Disorders

323

going surgery or a major procedure, stress dose corticosteroids

must be given.[76]
6. Acromegaly
Acromegaly is the clinical syndrome that results from excessive secretion of growth hormone (GH). More than 99% of cases
result from a pituitary adenoma.[77] The clinical features of acromegaly are summarized in table V.[77,78]
6.1 Cutaneous Manifestations

Fig. 9. On the left, hand of a patient with Addison disease, showing a

darker skin and hyperpigmented knuckles. On the right, hand of the patients mother.

appear on the nails.[9] Decreased axillary and pubic hair is common in women, in whom androgen production primarily occurs in
the adrenal glands.[73] Patchy, often bilaterally symmetrical areas
of vitiligo, the result of autoimmune destruction of dermal melanocytes, occur on the trunk or extremities in 1020% of patients with
autoimmune-based disease but not those with other causes of
adrenal insufficiency.[67,74]
5.2 Diagnosis

The diagnosis of Addison disease is made by performing a

short cosyntropin (synthetic ACTH) stimulation test: A baseline
serum cortisol is obtained, then the patient is injected with cosyntropin 0.25mg intramuscularly or intravenously; 1 hour later,
another serum cortisol is obtained. A normal response is a 1-hour
cortisol value of at least 20 g/dl. If it is <20 g/dl it is diagnostic
of adrenal insufficiency, either primary or secondary.[75] Additionally, plasma ACTH is elevated (>100 ng/L) in patients with
Addison disease, while it is normal (952 ng/L) or low in patients
with secondary adrenal insufficiency. Typical routine laboratory
tests in Addison disease show hyponatremia, hyperkalemia and
hyperchloremic metabolic acidosis.[75] After the diagnosis of Addison disease is made, imaging of the adrenals (computed tomography [CT] scan) is done to exclude any hemorrhage, infection and
metastatic cancer.

Virtually all patients with acromegaly have acral and soft tissue
overgrowth, although the extent of the overgrowth varies. The
characteristic findings (figure 10 and figure 11) are an enlarged
jaw (macrognathia), and enlarged, swollen hands and feet, which
result in increasing shoe and glove size and the need to enlarge
rings.[78] The skin is thickened and has a doughy feel. Furrowing
and accentuation of folds contributes to the coarsening of the facial
features. Deepening of creases on the forehead and nasolabial
folds gives the patients a scowling, somber expression.[9] Eyelids
are thick, the lower lip is enlarged and there is macroglossia.[78]
Folds of skin over bony prominences on the hands are accentuated.
The pads of the digits become fleshy, and fingers assume a blunted
shape. The heel pads on the feet are thickened.[9] The overgrowth
of fibrous tissue leads to production of small fibromas that are
found in 2030% of patients.[79] Nails become thick and hard.
Hyperhidrosis is present in 50% of patients, and is often malodorTable V. Clinical manifestations of acromegaly
Acral overgrowth (enlarged hands and feet)
Amenorrhea in females, impotence and loss of libido in males
Arthralgias
Cardiomyopathy, left ventricular hypertrophy, arrhythmias
Carpal tunnel syndrome
Deepening of the voice
Excessive sweating
Glucose intolerance
Hyperphosphatemia
Hypertension
Increased risk of colonic polyps and gastrointestinal malignancies
Kidney stones

5.3 Treatment

Treatment of Addison disease consists of replacing glucocorticoids (prednisone 57.5 mg/day or hydrocortisone 1520mg in the
morning and 510mg in the evening) and mineralocorticoids
(fludrocortisone 0.050.1 mg/day). During minor illnesses, patients should double/triple their glucocorticoid dose. When under Adis Data Information BV 2003. All rights reserved.

Macroglossia
Macrognathia, enlargement of nose and frontal bones
Malocclusion
New skin tags
Osteoporosis (if hypogonadism present)
Sleep apnea

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normal in 1050% of these women.[83,84] PCOS is the association

of androgenism (biochemical or clinical) with chronic anovulation
in women without specific underlying disease of the adrenal or
pituitary glands.[85] Less common causes include congenital adrenal hyperplasia (CAH), ovarian and adrenal tumors, and drugs
(anabolic steroids, progestogens, danazol).[83,84] Certain drugs, like
minoxidil, cyclosporine and penicillamine may rarely cause
hypertrichosis, or diffusely increased total body hair; which does
not represent true hirsutism.[83,84] The major clinical findings in
women with androgen-related disorders are summarized in table
VI.[83,84]
Fig. 10. Acromegaly, showing coarse facial features and macrognathia.

ous.[78] Hair growth increases and some women (<10%) complain

of hirsutism.[78] Hyperpigmentation has been observed in about
40%. The increase in color is generalized but not marked.[9]
Acanthosis nigricans is associated with acromegaly in at least 10%
of patients.[80]
6.2 Diagnosis

The diagnosis of acromegaly can be done by measurement of

serum insulin-like growth factor (IGF-1) which is GH-dependent,
and serum GH after a glucose load. Serum IGF-1 is elevated in
virtually all patients with acromegaly and provides excellent discrimination from unaffected individuals.[81] However, poorly controlled diabetes mellitus, starvation, and hepatic failure result in
false underestimation of IGF-1 levels. In these cases, measurement
of serum GH after a glucose load is the most specific dynamic test;
acromegalics do not suppress their GH levels to <1 g/L (measured by immunoradiometric [IRMA] assay) after ingestion of
75100g of an oral glucose solution.[82] When the laboratory
diagnosis is made, a pituitary magnetic resonance imaging (MRI)
is done to define the size and extension of the tumor.

7.1 Cutaneous Manifestations

The skin becomes thickened and coarse in patients with androgen-related disorders. Pores on the face enlarge, and there is
excessive oiliness. Typically, acne vulgaris and seborrhea develop
(figure 12). Androgenetic alopecia may be seen, typically with
diffuse hair loss; alopecia is rarely complete. Hirsutism (increase
in androgen-dependent terminal hair) occurs on the lip, chin, chest,
areolae, abdomen, linea alba, lower back, buttock, inner thighs and
external genitalia.[83,84] Acanthosis nigricans can also be seen,
especially in women with PCOS.[62,63] In addition, in patients with
severe hyperandrogenism (virilization), we can see temporal balding, deepening of the voice, increased muscle mass, loss of female
body contour and clitoromegaly[83] (figure 13).
7.2 Diagnosis

The tests that provide the most useful information in patients

with androgen-related disorders are measurements of serum total
testosterone, dehydroepiandrosterone-sulfate (DHEA-S) and prolactin, although other tests may be indicated in selected patients.[84]
If total testosterone is greater than 200 ng/dl, an ovarian tumor is

6.3 Treatment

Treatment of acromegaly consists essentially in resecting the

pituitary tumor.[82] If surgery is not curative, somatostatin analogues can be used postoperatively.[82] Occasionally, radiation
therapy may offer some benefit.[82]
7. Androgen-Related Disorders
Androgen-related disorders are most commonly due to increased sensitivity of the pilosebaceous unit to normal plasma
levels of androgens with normal menstrual cycles.[83] When there
is androgen excess, polycystic ovary syndrome (PCOS) is the most
common cause, although plasma levels of androgens may be
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Fig. 11. Same patient with acromegaly (see figure 10) with enlarged hands
and fingers.
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Cutaneous Manifestations of Endocrine Disorders

325

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

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

Acanthosis nigricans and obesity (especially in PCOS)

although infiltrative, vascular, cranial radiation therapy, hypotha-

Acne vulgaris and seborrhea

lamic tumors and other disorders also cause hypopituitarism.[86]

Clitoromegaly
Deepening of voice
Galactorrhea (hyperprolactinemia)

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

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

in adrenal insufficiency (see previous section), except that

Increased muscle mass

hyperpigmentation is absent. TSH deficiency results in symptoms

Irregular periods

and signs of hypothyroidism (see previous section). Luteinizing

Loss of female body contour

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

Striae, thin skin, bruising, truncal obesity (Cushing syndrome see

section 4)

cies lead to amenorrhea in females and erectile dysfunction with

Temporal balding

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

PCOS = polycystic ovary syndrome.

decreased tolerance to exercise and decreased social functioning.

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

suspected, and ovarian imaging (transvaginal ultrasound) should

be performed. If DHEA-S is more than 23 times the upper limit
of normal, imaging of the adrenals (CT scan) is done to exclude a
virilizing adrenal mass. Prolactin is measured in women who,
besides hirsutism, have irregular menses, to exclude hyperprolactinemia;[84] slightly elevated prolactin levels may be seen in women with PCOS, moderately elevated values (>40 ng/dl) should
prompt a search for other etiologies (hypothalamic/pituitary disease, renal or liver disease, primary hypothyroidism, and drugs,
mainly neuroleptics).
The diagnosis of PCOS does not require the presence of polycystic ovaries on ultrasound, because 20% of normal ovulatory
women may have polycystic ovaries and up to 20% of women with
PCOS 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 a
family history of CAH. Diagnosis is best established by measuring
serum 17-hydroxyprogesterone before and 60 minutes after 250g
of cosyntropin. A 60-minute value above 1000 ng/dl is diagnostic.

normal conditions; in hypopituitarism, it becomes elevated and

results in galactorrhea.[86] Less commonly, deficiency in arginine
vasopressin (AVP) results in diabetes insipidus.

7.3 Treatment

In women who have PCOS or idiopathic hirsutism, oral contraceptives, frequently in combination with antiandrogens (like spironolactone) are effective in controlling the hirsutism and regulating
the periods in most women.[83-85] Of course, hirsutism can also be
treated by physical methods (electrolysis, laser removal etc.).
Adrenal or ovarian tumors should be resected. In CAH, treatment
might include glucocorticoids and genetic counseling.[85]
8. Hypopituitarism
Hypopituitarism results from a variety of conditions that compromise the anterior pituitary and therefore the elaboration of all
Adis Data Information BV 2003. All rights reserved.

Fig. 12. Facial acne, hirsutism and greasy skin.

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volume, osmolarity and specific gravity; serum electrolytes are

also measured. Some of these tests have limitations, the discussion
of which is beyond the scope of this paper.[86] A pituitary MRI is
also performed to rule out the possibility of tumor or other destructive process in the sellar region.
8.3 Treatment

Treatment of hypopituitarism is directed at the underlying

process resulting in hypopituitarism. Most commonly, it is a
pituitary 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

Fig. 13. Enlargement of the clitoris.

8.1 Cutaneous Manifestations

Pallor of the skin with a yellowish tinge is a prominent feature

in patients with hypopituitarism, but mucous membranes retain
their normal hue unless the patient is anemic. The skin is dry but
softer than in primary hypothyroidism. The face may be puffy and
less expressive because of a reduction in skin folds. Thinness of
the skin and subcutaneous tissues results in fine wrinkling around
the eyes and mouth making the patient look older.[9]
Loss of body hair occurs in all patients. Scalp hair tends to be
fine and dry. Sebaceous secretions and sweating also decrease.[9]
8.2 Diagnosis

Screening studies include measurement of prolactin, TSH, free

T4, morning cortisol and ACTH, FSH, LH, testosterone (in
males), and dynamic testing for GH deficiency. In the right setting
(polyuria, polydipsia and absence of diabetes mellitus), screening
for diabetes insipidus is done by a 24-hour urine collection for
Adis Data Information BV 2003. All rights reserved.

Primary hyperparathyroidism (hypersecretion of parathyroid

hormone [PTH] by parathyroid adenoma or hyperplasia) is not
associated with any cutaneous manifestations except, rarely, pruritus and deposition of calcium.[9] In few case reports, chronic
urticaria was the initial manifestation of primary hyperparathyroidism.[87]
Hypoparathyroidism (failure of parathyroid glands) may be the
result of surgery, infiltrative disorders, autoimmune conditions, or
idiopathic. The clinical presentation of hypoparathyroidism is
shown in table VII.[88]
Pseudohypoparathyroidism is a heritable disorder of targetorgan unresponsiveness to parathyroid hormone. It mimics hypoparathyroidism, with hypocalcemia and hyperphosphatemia,
but the PTH level is elevated.[89] Many of these patients have
Table VII. Clinical manifestation of hypoparathyroidism
Abnormal dentition
Cataracts
Chvostek sign (twitching of the circumoral muscles in response to
tapping 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 pressure
cuff to 20mm Hg above the patients systolic pressure for 3 minutes)

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327

9.2 Diagnosis

The diagnosis of hypoparathyroidism (low calcium, high phosphorus and low PTH), pseudohypoparathyroidism (low calcium,
high phosphorus and high PTH) and primary hyperparathyroidism
(high calcium and high PTH) can be made by measuring serum
ionized calcium, phosphorus and intact PTH.[88]
9.3 Treatment

In patients with symptomatic primary hyperparathyroidism,

surgery should be performed.[91] In asymptomatic patients, indications for surgery include: <50 years of age, bone disease, urine
calcium >400 mg/day, decreased kidney function, nephrocalcinosis, and low serum levels of 25-hydroxyvitamin D.[91] When
surgery is not performed, patients should stay well hydrated, and
keep a daily calcium intake of no more than 600800mg.
In patients with hypoparathyroidism and pseudohypoparathyroidism, calcium and calcitriol (1,25-hydroxyvitamin D) are used
in combination.[90]
10. Diabetes Mellitus
Diabetes mellitus is a group of metabolic diseases characterized
by hyperglycemia resulting from defects in insulin secretion (type
1 diabetes), insulin action or both (type 2 diabetes). The classic
symptoms are polyuria, polydipsia and unexplained weight
loss.[92] Other manifestations of diabetes mellitus are shown in
table VIII.[92]
Fig. 14. Albright hereditary osteodystrophy: short stature, round face, short
neck and brachydactyly (short digits).

Albright hereditary osteodystrophy. Pseudopseudohypoparathyroidism is the presence of Albright hereditary osteodystrophy

without any disorder of calcium metabolism.[89]

10.1 Cutaneous Manifestations

Certain skin disorders are more frequently associated with

diabetes mellitus. The best example of such an association is
necrobiosis lipoidica diabeticorum (NLD) [figure 16]. Occurring
in 0.3% of patients with diabetes mellitus, these lesions are distinc-

9.1 Cutaneous Manifestations

In hypoparathyroidism and pseudohypoparathyroidism, the

skin is dry, scaly, hyperkeratotic, and puffy. Nails become opaque,
brittle and develop transverse ridges. Hair becomes coarse and
sparse. Eczematous dermatitis, hyperkeratotic and maculopapular
eruptions have been reported.[9] Autoimmune hypoparathyroidism
may be associated with chronic mucocutaneous candidiasis.[90]
Many patients with pseudohypoparathyroidism and all patients
with pseudopseudohypoparathyroidism have Albright hereditary
osteodystrophy (figure 14 and figure 15), which consists of short
stature, short neck, brachydactyly (short digits, mainly fourth and
fifth metacarpals), and subcutaneous ossifications.[89]
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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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Table VIII. Clinical manifestations in diabetes mellitus

Atherosclerotic heart disease (myocardial infarction, heart failure) and
peripheral 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 Charcots
foot (degenerative change of the bony structure of the foot)
Peripheral neuropathy (sensory deficit, burning and tingling sensations)
Polyuria, polydipsia, polyphagia
Renal failure

Jabbour

does not pit on pressure. It occurs mainly in obese patients with

diabetes mellitus with evidence of vascular complications. It may
not remit after a long period of time.[99,100]
As many as one-third of patients with diabetes (both type 1 and
type 2) have tight, thickened, and waxy skin over the dorsa of the
hands.[101] Other cutaneous manifestations include reddening of
the face (rubeosis faciei) and of the extremities in patients with
long-standing diabetes mellitus, with occasional necrosis and destruction of the underlying bone,[102] bullous lesions of the feet,
xanthomatosis (secondary to hyperlipidemia, common in diabetes
mellitus), infections (most frequent are staphylococcal pyodermas,
candidiasis, erythrasma and epidermophytosis).[9]

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

Skin lesions and infections (see section 10.1)

10.2 Diagnosis

Strokes
Unexplained weight loss
Vaginitis (usually due to monilial infection)

tive, oval or irregularly shaped, indurated plaques with central

atrophy and yellow pigmentation; peripherally along the margins
there is either red-brown or violaceous pigmentation. The lesions
usually occur on the anterior and lateral surfaces of the lower
legs.[9] The differential diagnosis includes granuloma annulare,
which presents as asymptomatic annular red plaques on the dorsum of the extremities or posterior neck, but lacking a yellow
discoloration. Even histologically, it might be difficult to differentiate between NLD and granuloma annulare. NLD occurs in patients with both type 1 and type 2 diabetes. The majority of
patients have diabetes mellitus when NLD develops; in most of the
rest, diabetes mellitus appears later.[93]
Progression of lesions does not correlate with normalization of
hyperglycemia.[9] Acanthosis nigricans has been associated with
type 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 are
blocking antibodies to the insulin receptor).[62,63,94] Acanthosis
nigricans (figure 17) consists of diffuse velvety thickening and
hyperpigmentation of the skin, chiefly in the axillae, neck, inframammary folds, groin, perineum, and less often, nipples and
areolae.[95] Vitiligo occurs with greater than expected incidence in
patients with diabetes, either type 1[96] or type 2.[97] Diabetic
dermopathy consists of asymptomatic, irregularly shaped patches
occurring on the anterior lower legs; their surfaces are depressed
and they are a light brown color.[98] They are often accompanied
by significant microangiopathy elsewhere.[9] Scleredema
adultorum consists of induration of the skin beginning on the
posterior and lateral neck. This painless swelling may gradually
spread to the face, shoulders, anterior neck, and upper torso; it may
eventually involve the abdomen, arms and hands. The hard skin
Adis Data Information BV 2003. All rights reserved.

There are three possible ways to diagnose diabetes mellitus,

and each must be confirmed, on a subsequent day, by one of the
other two methods. The three methods are: (i) fasting plasma
glucose at least 7.0 mmol/l (126 mg/dl); (ii) symptoms of diabetes

Fig. 16. Necrobiosis lipoidica diabeticorum with multiple lesions showing

an atrophic and necrotic center with a raised brownish-red border.
Am J Clin Dermatol 2003; 4 (5)

Cutaneous Manifestations of Endocrine Disorders

Fig. 17. Acanthosis nigricans with the typical velvety hyperpigmented skin
of the neck and axillae.

plus casual plasma glucose at least 11.1 mmol/l (200 mg/dl); and
(iii) 2-hour plasma glucose at least 11.1 mmol/l (200 mg/dl) during
an oral glucose tolerance test.[92]
10.3 Treatment

Treatment of diabetes mellitus always includes lifestyle modifications. In type 1 diabetes, insulin is given as 34 injections a day
(combination of long- and short-acting insulins).[103] In type 2
diabetes, oral agents (secretagogues, metformin, thiazolidinediones and -glucosidase inhibitors) can be used as monotherapy or in
combination.[104] Insulin may be added in patients who have not
had sufficient disease response with oral agents.[104]
11. Conclusion
Many cutaneous manifestations may be caused by an underlying endocrine disorder. Dermatologists should be able to recognize
these patients, and perform the basic screening tests before referring them to endocrinologists, in order to complete the work-up
and receive corrective rather than symptomatic treatment.
Acknowledgements
No sources of funding were used to assist in the preparation of this
manuscript. The author has no conflicts of interest that are directly relevant to
the content of this manuscript.

References
1. Brownlie BE, Wells JE. The epidemiology of thyrotoxicosis in New Zealand:
incidence and geographical distribution in North Canterbury, 1983-1985. Clin
Endocrinol 1990; 33 (2): 249-59
2. Reinwein D, Benker G, Konig MP, et al. The different types of hyperthyroidism in
Europe: results of a prospective study of 924 patients. J Endocrinol Invest 1988;
11 (3): 193-200
3. Williams I, Ankrett VO, Lazarus JH, et al. Aetiology of hyperthyroidism in
Canada and Wales. J Epidemiol Community Health 1983; 37 (3): 245-8
Adis Data Information BV 2003. All rights reserved.

329

4. Dabon-Almirante CLM, Surks MI. Clinical and laboratory diagnosis of thyrotoxicosis. Endocrinol Metab Clin North Am 1998; 27 (1): 25-35
5. Mullin GE, Eastern JS. Cutaneous signs of thyroid disease. Am Fam Physician
1986; 34 (4): 93-8
6. Holt PJA, Lazarus J, Marks R. The epidermis in thyroid disease. Br J Dermatol
1976; 95: 513-8
7. Rosen T, Kleman GA. Thyroid and the skin. In: Callen JP, Jorizzo JL Greer KE, et
al., editors. Dermatologic signs of internal disease. 2nd ed. Philadelphia: WB
Saunders, 1995: 189
8. Heymann WR. Cutaneous manifestations of thyroid disease. J Am Acad Dermatol
1992; 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: 609-14
11. Rook A, Dawber R. Diseases of the hair and scalp. 2nd ed. Oxford: Blackwell
Scientific Publications, 1991: 147
12. Norton LA. Disorders of the nails. In: Moschella SL, Hurley HJ, editors. Dermatology. 3rd ed. Philadelphia: WB Saunders, 1992: 1574
13. Locke W. Unusual manifestations of Graves disease. Med Clin North Am 1967;
51 (4): 915-24
14. Mullin GE, Eastern JS. Cutaneous consequences of accelerated thyroid function.
Cutis 1986; 37: 109-14
15. Davis PJ, Davis FB. Hyperthyroidism in patients over the age of 60 years.
Medicine 1974; 53 (3): 161-81
16. Heymann WR. The skin in thyrotoxicosis. In: Braverman LE, Utiger RD, editors.
The thyroid. 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2000: 593-5
17. Ortonne J-P, Mosher DB, Fitzpatrick TB. Vitiligo and other hypomelanoses of hair
and skin. New York: Plenum, 1983: 182
18. Cunliffe WJ, Hall R, Newell DJ, et al. Vitiligo, thyroid disease and autoimmunity.
Br J Dermatol 1968; 80: 135-9
19. Shong YK, Kim JA. Vitiligo in autoimmune thyroid disease. Thyroidology 1991;
3: 89-91
20. Kantor GR, Bernhard JD. Investigation of the pruritic patient in daily practice.
Semin Dermatol 1995; 14: 290-6
21. Readett MD. Constitutional eczema and thyroid disease. Br J Dermatol 1964; 76:
126-39
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
23. Pegum JS, Grice K. Unusual skin eruptions with eosinophilia associated with
hyperthyroidism. Br J Dermatol 1973; 88 (3): 295-301
24. Thomson JA. Xanthelasma associated with thyrotoxicosis. J Clin Endocrinol
Metab 1965 (Pt 1); 25: 758-60
25. Fatourechi V, Pajouhi M, Fransway AF. Dermopathy of Graves disease (pretibial
myxedema): review of 150 cases. Medicine 1994; 73 (1): 1-7
26. Horiuchi Y. Pretibial myxedema associated with chronic thyroiditis [letter]. Arch
Dermatol 1985; 121 (4): 451
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:
329-33
29. Solanki SV, Shah SS, Kothari UR. Thyroid acropachy. Indian J Med Sci 1973; 27:
708-10
30. Ross DS. Serum thyroid-stimulating hormone measurement for assessment of
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.
Werner and Ingbars the thyroid. 7th ed. Philadelphia: Lippincott-Raven, 1996:
708-12
32. Kaplan MM, Meier DA, Dworkin HJ. Treatment of hyperthyroidism with radioactive iodine. Endocrinol Metab Clin North Am 1998; 27 (1): 205-23
33. Cooper DS. Antithyroid drugs for the treatment of hyperthyroidism caused by
Graves disease. Endocrinol Metab Clin North Am 1998; 27 (1): 225-47
34. Ross DS. Syndromes of thyrotoxicosis with low radioactive iodine uptake. Endocrinol Metab Clin North Am 1998; 27 (1): 169-85
Am J Clin Dermatol 2003; 4 (5)

330

35. Braverman LE, Utiger RD. Introduction to hypothyroidism. In: Braverman LE,
Utiger RD, editors. Werner and Ingbars the thyroid. 7th ed. Philadelphia:
Lippincott-Raven, 1996: 736-7
36. Larsen PR, Davies TF, Hay ID. The thyroid gland. In: Wilson JD, Foster DW,
Kronenberg HM, et al, editors. Williams textbook of endocrinology. 9th ed.
Philadelphia: WB Saunders, 1998: 460-6
37. Bernhard JD, Freedberg IM, Vogel LN. The skin in hypothyroidism. In:
Braverman LE, Utiger RD, editors. Werner and Ingbars the thyroid. 7th ed.
Philadelphia: Lippincott-Raven, 1996: 792-5
38. Wayne EJ. Clinical and metabolic studies in thyroid disease. BMJ 1960; 1: 78-90
39. Diven DG, Gwinup G, Newton RC. The thyroid. Dermatol Clin 1989; 7: 547-58
40. Al-Jubouri MA, Coombes EJ, Young RM, et al. Xanthoderma: an unusual
presentation of hypothyroidism. J Clin Pathol 1994; 47 (9): 850-1
41. Orteu CH, Rustin MH. 20 thickened, fragile nails. Lancet 1996; 347 (9002): 662
42. Tosti A, Baran R, Dawber RPR. The nail in systemic diseases and drug-induced
changes. In: Baran R, Dawber RPR, editors. Diseases of the nails and their
management. 2nd ed. Oxford: Blackwell Scientific Publications, 1994: 175
43. Cunningham MJ, Zone JJ. Thyroid abnormalities in dermatitis herpetiformis:
prevalence of clinical thyroid disease and thyroid autoantibodies. Ann Intern
Med 1985; 102 (2): 194-6
44. Stockigt JR. Free thyroid hormone measurement. Endocrinol Metab Clin North
Am 2001; 30 (2): 265-89
45. Ladenson PW. Diagnosis of hypothyroidism. In: Braverman LE, Utiger RD,
editors. Werner and Ingbars the thyroid. 7th ed. Philadelphia: LippincottRaven, 1996: 878-82
46. Brent GA, Larsen PR. Treatment of hypothyroidism. In: Braverman LE, Utiger
RD, editors. Werner and Ingbars the thyroid. 8th ed. Philadelphia: LippincottRaven, 2000: 853-8
47. Niepomniszcze H, Huaier AR. Skin disorders and thyroid diseases. J Endocrinol
Invest 2001; 24: 628-38
48. Lutfi RJ, Fridmanis M, Misiunas AL, et al. Association of melasma with thyroid
autoimmunity and other thyroidal abnormalities and their relationship to the
origin of the melasma. J Clin Endocrinol Metab 1985; 61 (1): 28-31
49. Hegedus L, Heidenheim M, Gervil M, et al. High frequency of thyroid dysfunction
in patients with vitiligo. Acta Derm Venereol 1994; 74: 120-3
50. McDonagh AJ, Messenger AG. The pathogenesis of alopecia areata. Dermatol Clin
1996; 14: 661-70
51. Leznoff A, Sussman GL. Syndrome of idiopathic chronic urticaria and angioedema
with thyroid autoimmunity: a study of 90 patients. J Allergy Clin Immunol
1989; 84 (1): 66-71
52. Rumbyrt JS, Katz JL, Schocket AL. Resolution of chronic urticaria in patients with
thyroid autoimmunity. J Allergy Clin Immunol 1995; 96 (6): 901-5
53. Orgiazzi J. Anti-TSH receptor antibodies in clinical practice. Endocrinol Metab
Clin North Am 2000; 29 (2): 339-55
54. Findling JW, Aron DC, Tyrrell JB. Glucocrticoids and adrenal androgens. In:
Greenspan FS, Strewler GJ, editors. Basic & clinical endocrinology. 5th ed.
Connecticut: Appleton & Lange, 1997: 343-54
55. Findling JW, Raff H. Diagnosis and differential diagnosis of Cushings syndrome.
Endocrinol Metab Clin North Am 2001; 30 (3): 729-47
56. Yanovski JA, Cutler GB. Glucocorticoid action and the clinical features of Cushings syndrome. Endocrinol Metab Clin North Am 1994; 23 (3): 487-509
57. Panzer SW, Patrinely JR, Wilson HK. Exophthalmos and iatrogenic Cushings
syndrome. Ophthal Plast Reconstr Surg 1994; 10 (4): 278-82
58. Fisher B, Maibach HF. The effect of corticosteroids on human epidermal mitotic
activity. Arch Dermatol 1971; 103: 39-43
59. Rokowski K, Sheehy J, Cutroneo KR. Glucocorticoid-mediated selective reduction
of functioning collagen messenger ribonucleic acid. Arch Biochem Biophys
1981; 210: 74-7
60. Ferguson JK, Donald RA, Wetson TS, et al. Skin thickness in patients with
acromegaly and Cushings syndrome and response to treatment. Clin Endocrinol 1983; 18 (4): 347-53
61. Orth DN, Kovacs WJ. The adrenal cortex. In: Wilson JD, Foster DW, Kronenberg
HM, et al, editors. Williams textbook of endocrinology. 9th ed. Philadelphia:
WB Saunders, 1998: 565-9
62. Matsuoka LY, Gavin JR, Goldman J. Spectrum of endocrine abnormalities associated with acanthosis nigricans. Am J Med 1987; 83: 719-25
Adis Data Information BV 2003. All rights reserved.

Jabbour

63. Winkelmann RK, Scheen RS, Underhal LO. Acanthosis nigricans and endocrine
disease. JAMA 1960; 174 (9): 1145-52
64. Findling JW, Raff H. Newer diagnostic techniques and problems in Cushings
disease. Endocrinol Metab Clin North Am 1999; 28 (1): 191-210
65. Meier CA, Biller BMK. Clinical and biochemical evaluation of Cushings syndrome. Endocrinol Metab Clin North Am 1997; 26 (4): 741-62
66. Oelkers W. Adrenal insufficiency: current concepts. N Engl J Med 1996; 335 (16):
1206-12
67. Findling JW, Aron DC, Tyrrell JB. Disorders of adrenocortical insufficiency. In:
Greenspan FS, Strewler GJ, editors. Basic & clinical endocrinology. 5th ed.
Connecticut: Appleton & Lange, 1997: 334-43
68. Dunlop D. Eighty-six cases of Addisons disease. BMJ 1963; 1: 887-91
69. Barnett AH, Espiner EA, Donald RA. Patients presenting with Addisons need not
be pigmented. Postgrad Med J 1982; 58: 690-2
70. Soffer LJ, Dorfman RI, Gabrilove JL. The human adrenal gland. Philadelphia: Lea
and Febiger, 1961: 256-75
71. Mountjoy KG. The human melanocyte stimulating hormone receptor has evolved
to become super-sensitive to melanocortin peptides. Mol Cell Endocrinol
1994; 102 (1-2): R7-11
72. Hunt G, Todd C, Kyne S, et al. ACTH stimulates melanogenesis in cultured human
melanocytes. J Endocrinol 1994; 140 (1): R1-3
73. Parker LN. Addisons disease and Cushings syndrome. In: Parker LN, editor.
Adrenal androgens in clinical medicine. San Diego: Academic Press, 1989:
158-74
74. Zelissen PMJ, Bast EJEG, Croughs RJM. Associated autoimmunity in Addisons
disease. J Autoimmun 1995; 8: 121-30
75. Grinspoon SK, Biller BM. Laboratory assessment of adrenal insufficiency. J Clin
Endocrinol Metab 1994; 79: 923-31
76. Malchoff CD, Carey RM. Adrenal insufficiency. In: Bardin CW, editor. Current
therapy in endocrinology and metabolism. 6th ed. St Louis: Mosby-Year Book
Inc, 1997: 142-6
77. Thorner MO, Vance ML, Laws ER, et al. The anterior pituitary. In: Wilson JD,
Foster DW, Kronenberg HM, et al, editors. Williams textbook of endocrinology. 9th ed. Philadelphia: WB Saunders, 1998: 295-307
78. Melmed S. Clinical manifestations of acromegaly. UpToDate 1998; 6 (1): 1-5
79. Davidoff LM. Studies in acromegaly: III. the anamnesis ans symptomatology in
one hundred cases. Endocrinology 1926; 10: 461-83
80. Brown J, Winkelmann RK. Acanthosis nigricans: a study of 90 cases. Medicine
1968; 47 (1): 33-51
81. Melmed S. Diagnosis of acromegaly. UpToDate 1997; 6 (1): 1-4
82. Ezzat S. Acromegaly. Endocrinol Metab Clin North Am 1997; 26 (4): 703-23
83. Carr BR. Disorders of the ovaries and female reproductive tract. In: Wilson JD,
Foster DW, Kronenberg HM, et al, editors. Williams textbook of endocrinology. 9th ed. Philadelphia: WB Saunders, 1998: 795-9
84. Taylor AE. Polycystic ovary syndrome. Endocrinol Metab Clin North Am 1008; 27
(4): 877-902
85. Franks S. Polycystic ovary syndrome. N Engl J Med 1995; 333 (13): 853-61
86. Vance ML. Hypopituitarism. N Engl J Med 1994; 330 (23): 1651-62
87. Dagher HN, Aboujaoude ZC, Jabbour SA. Chronic urticaria: an unusual initial
manifestation of primary hyperparathyroidism. Endocr Pract 2002; 8 (1): 47-9
88. Goltzman D. Hypoparathyroidism. In: Favus MJ, editor. Primer on the metabolic
bone diseases and disorders of mineral metabolism. 3rd ed. Philadelphia:
Lippincott-Raven, 1996: 220-3
89. Strewler GJ. Mineral metabolism & metabolic bone disease. In: Greenspan FS,
Strewler GJ, editors. Basic & clinical endocrinology. 5th edn. Connecticut:
Appleton & Lange, 1997: 288-9
90. Sutphin A, Fuller A, McCune DJ. Five cases (three in siblings) of idiopathic
hypoparathyroidism associated with moniliasis. J Clin Endocrinol 1943; 3:
625-34
91. Bilezikian JP. Primary hyperparathyroidism: when to observe and when to operate.
Endocrinol Metab Clin North Am 2000; 29 (3): 465-78
92. American Diabetes Association. Report of the expert committee on the diagnosis
and classification of diabetes mellitus. Diabetes Care 1998; 21 (S1): S5-S19
93. Muller SA, Winkelman RK. Necrobiosis lipoidica diabeticorum, a clinical and
pathological investigation of 171 cases. Arch Dermatol 1966; 93 (3): 272-81
Am J Clin Dermatol 2003; 4 (5)

Cutaneous Manifestations of Endocrine Disorders

94. Cruz PD, Hud JA. Excess insulin binding to insulin-like growth factor receptors:
proposed mechanism for acanthosis nigricans. J Invest Dermatol 1992; 98 (6
Suppl.): 82S-5S
95. Matsuoka LY, Wortsman J, Goldman J. Acanthosis nigricans. Clin Dermatol 1993;
11: 21-5
96. Macaron C, Winter RJ, Traisman HS, et al. Vitiligo and juvenile diabetes mellitus.
Arch Dermatol 1977; 113 (11): 1515-7
97. Dawber RPR. Vitiligo in mature-onset diabetes. Br J Dermatol 1968; 80 (5): 275-8
98. 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 biochemical
study. Arch Dermatol 1965; 92: 643-52
100. Cohen BA, Wheeler CE, Briggman RA. Scleredema of Buschke and diabetes
mellitus. Arch Dermatol 1970; 101: 27-35

Adis Data Information BV 2003. All rights reserved.

331

101. Clark CV, Pentland B, Ewing DJ, et al. Decreased skin wrinkling in diabetes
mellitus. Diabetes Care 1984; 7 (3): 224-7
102. Lithner F. Lesions of the legs in diabetics and in patients with familial amyloidosis
and polyneuropathy. Acta Med Scand Suppl 1976; 589: 1-23
103. McCulloch DK. Basic insulin regimens in diabetes mellitus. UpToDate 2003; 11
(1): 1-6
104. Jabbour SA, Goldstein BJ. Improving disease management with new treatments for
type 2 diabetes mellitus. Clin Geriatr 2001; 9 (5): 157-68

Correspondence and offprints: Dr Serge A. Jabbour, 211 South 9th Street, Ste
600, Philadelphia, PA 19107, USA.
E-mail: serge.jabbour@mail.tju.edu

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