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The obesity syndrome and acanthosis nigricans. Acanthosis nigricans is a common cosmetic problem providing epidemiological clues to the obesity syndrome, the insulin-resistance syndrome, the thrifty metabolism, dyslipidaemia, hypertension and diabetes mellitus type II.

Obesity and its consequences are arguably the chief public health problems facing the developed world. Obesity causes many fatal diseases, in particular cerebrovascular and cardiovascular disease. Acanthosis nigricans (AN) is a common cosmetic disability in pigmented ethnic groups. It may present with periorbital darkening or darkening of the neck or knuckles as well as acrochordons (skin tags) around eyelids, neck or axillae. The more classical AN of axillae and groins is less often a cosmetic disability, although it is an important physical sign. AN is very common in pigmented populations throughout the world, irrespective of domicile. It is rare in whites. AN is closely associated with all the features of the insulin-resistance syndrome (IRS), especially obesity. AN and IRS share a similar prevalence and epidemiology. IRS (also known as syndrome X or the deadly quartet) is characterized by insulin resistance (IR) and its associated conditions, including obesity, dyslipidaemia, hypertension and diabetes mellitus (DM) type II. The sequelae of IRS are cardiovascular and cerebrovascular disease. The origins of insulin resistance and its sequel, IRS, are debated. Insulin resistance can result from obesity. Also obesity usually presents before AN, hypertension or DM II. For these reasons it may be more helpful to recognize instead an obesity syndrome. The obesity syndrome is characterized by a genetically determined thrifty metabolism that protects subjects in famine conditions but which, in conditions of plenty, leads to weight gain with all its consequences, including hyperlipidaemia, hypertension, IR with DM II, and, in due course, cerebrovascular and cardiovascular disease. In pigmented races, AN is an important early manifestation of the obesity syndrome. AN helps identify persons at particular risk of developing the obesity syndrome, dyslipidaemia, hypertension and IR with DM II. Recognition of AN, therefore, offers important opportunities for health screening and preventative medicine.

Journal Article↗

Spectrum of endocrine abnormalities associated with acanthosis nigricans.

Acanthosis nigricans is a marker for disorders of insulin action, endocrine abnormalities, and cancer of internal organs. To evaluate the clinical significance of this marker the systemic alterations and clinical features of 26 patients with acanthosis nigricans seen at two institutions were reviewed. Most subjects affected by acanthosis nigricans were female (20 patients), Caucasian (22 patients), in the third decade of life (13 patients), and overweight (24 patients greater than 120 percent ideal body weight). Gonadal disease, present in 17 patients, was expressed as polycystic ovary syndrome (11 cases), disorders of prolactin secretion (two cases, one with polycystic ovary syndrome), streak gonads (one case), and hypogonadism of the male (four cases). Thyroid disease and tinea versicolor were present in four patients each. Three patients were receiving insulin therapy for diabetes mellitus, and in two additional patients diabetes mellitus was detected during the diagnostic workup. All patients had elevated fasting insulin levels; most of them also had an exaggerated insulin response to a glucose load. Two of 18 patients tested had antibodies against the insulin receptor in the circulation. Skin biopsy of acanthosis nigricans lesions from all 26 patients showed a typical pattern of hyperkeratosis, acanthosis, and epidermal papillomatosis. Colloidal iron staining showed glycosaminoglycan infiltration of the papillary dermis (21 of 21 cases), consisting mainly of hyaluronic acid. It is concluded that: (1) hyperinsulinenemia and local dermal glycosaminoglycan deposition are regular features in acanthosis nigricans and (2) patients with acanthosis nigricans should be screened for diabetes mellitus, gonadal disease, and hypothyroidism.

Acanthosis Nigricans↗

Acanthosis nigricans.

Acanthosis nigricans is a lesion affecting localized areas of the skin in persons with obesity and/or hyperinsulinemia. Roughening of the skin correlates with histological papilomatosis and the apparent darkening is due to hyperkeratosis. Biochemical mechanisms for developing this hyperplastic lesion are unclear, but likely involve local cutaneous growth factors. Cross sectional surveys of unselected populations have demonstrated that young children have low prevalences of obesity and acanthosis nigricans, but the prevalences of both increase with increasing age until plateaus are reached after the age of ten. Nearly 40% of Native American teenagers have acanthosis nigricans, whereas about 13% of African American, 6% of Hispanic, and less than 1% of white, non-Hispanic children aged 10-19 have clinically apparent acanthosis nigricans. We conclude that the presence of this skin lesion is a clinical surrogate of laboratory-documented hyperinsulinemia. Acanthosis nigricans identifies a subgroup within an ethnic group who have the highest insulin concentration, the most severe insulin resistance, and thus the highest risk for the development of type 2 diabetes.

Acanthosis Nigricans↗

Screening for type 2 diabetes in children with acanthosis nigricans.

Acanthosis nigricans is a physical finding of the skin that appears to be a marker for insulin resistance. Because of the association of insulin resistance and type 2 diabetes, acanthosis nigricans may also be a marker for type 2 diabetes. Some states have recommended statewide screening for acanthosis nigricans. However, this has led to a large referral of children to pediatric endocrinologists. Presented is a schema for primary care physicians and school nurses to use as a guideline for referral of children with acanthosis nigricans.

Acanthosis Nigricans↗

Antibodies against the insulin receptor in paraneoplastic acanthosis nigricans.

Acanthosis nigricans is a skin disorder associated with endocrine abnormalities, autoimmune disease, and systemic malignancies. Insulin resistance is a common accompaniment of the nonmalignant varieties of acanthosis nigricans. A 44-year-old man is described with a functioning metastatic pheochromocytoma, acanthosis nigricans, and insulin-resistant diabetes mellitus. Studies of insulin action showed a low titer of anti-insulin antibodies and a very high titer of antibodies against the insulin receptor. This case documents for the first time insulin resistance due to anti-insulin receptor antibodies in a paraneoplastic variety of acanthosis nigricans.

Acanthosis Nigricans↗

Acanthosis nigricans.

Acanthosis nigricans is a mucocutaneous eruption that occurs in a strikingly exuberant form as a marker for a highly malignant and rapidly fatal internal cancer. Recently, it has been recognized that acanthosis nigricans may also be a relatively common marker for increased long-term risk of the less dramatic but potentially serious systemic disorders associated with insulin resistance and compensatory increased insulin secretion.

Acanthosis Nigricans↗

[Clinical types of acanthosis nigricans].

Acanthosis nigricans is a rare disease, occurring with the same frequency in females and males. Eight clinically practical types of this disease have been presented. Authors also observed a coexistence of this disease with neoplasms, which obligates doctors to perform more accurate diagnosis of the patient. The clinically practical scale of the intensification of skin lesions in acanthosis nigricans has been also presented. This scale is helpful in therapy monitoring.

Acanthosis Nigricans↗

Conjunctival involvement in malignancy-associated acanthosis nigricans.

Acanthosis nigricans classically presents with pigmented skin lesions over the neck, groin and axillae. It may involve the mucosal surfaces, particularly the oral mucosa. Conjunctival involvement is very rare, especially in the variety associated with malignancy. We report a case of acanthosis nigricans associated with squamous cell carcinoma of the bronchus where bilateral papillary conjunctivitis, progressing to hypertrophic papillary conjunctival and lid margin lesions, was the presenting feature. Topical treatment with corticosteroid and artificial tear drops resulted in the partial improvement of the ocular symptoms.

Acanthosis Nigricans↗

Acanthosis nigricans.

Acanthosis nigricans is thickened, velvety, hyperpigmented skin associated with a variety of endocrine disorders, malignancies and medications.

Acanthosis Nigricans↗

Acanthosis nigricans.

Acanthosis nigricans (AN) is a dermopathy with a distinctive appearance that facilitates its diagnosis. Although an external condition, it is associated with a wide variety of less obvious internal conditions, either benign or malignant. Insulin resistance figures prominently in its benign associations and plays a primary role in its development. The development of AN in malignant conditions remains to be explained. AN rarely requires treatment, although the underlying condition usually does.

Acanthosis Nigricans↗

Acanthosis nigricans.

Acanthosis nigricans (AN) is a well-defined skin disorder characterized by velvety hyperkeratotic macules that can be accompanied by various degrees of pigmentation. Other manifestations of AN are marked papillomatous growths and deep skin markings. These changes can affect the entire skin but preferentially are observed in the axilla, neck, genitals, and oral cavity. The presence of AN around and within the oral cavity as well as its well-known association with internal malignant conditions, especially adenocarcinoma of the stomach, and/or its association with insulin resistance, has prompted this review article, which emphasizes the oral manifestations of AN.

Acanthosis Nigricans↗

Genes, growth factors and acanthosis nigricans.

Acanthosis nigricans (AN) occurs most commonly in association with hyperinsulinaemia and more rarely as a paraneoplastic syndrome. It is also a feature of several genetic disorders. Indirect evidence suggests a role for tyrosine kinase growth factor receptor signalling in the pathogenesis of AN. Defects in the insulin receptor gene causing insulin resistance and AN are well recognized, but recent data in several other syndromes of this association, including lipodystrophic disorders, have identified causative defects in other pathways. The mechanism of AN due to insulin resistance is most probably direct or indirect activation of the insulin-like growth factor 1 receptor by high levels of circulating insulin. However, more direct evidence for abnormal tyrosine kinase receptor signalling in AN has been provided by studies of craniosynostosis and skeletal dysplasia syndromes with AN, which have identified activating mutations in fibroblast growth factor receptors.

Acanthosis Nigricans↗

Neuropeptides in the pathogenesis of obesity-associated benign acanthosis nigricans.

The association of acanthosis nigricans with pituitary tumors and insulin-resistant diabetes suggests that a pituitary peptide may promote papillomatosis and acanthosis characteristic of acanthosis nigricans. Although such a peptide has not been isolated, it may derive by sequential cleavage from the 31,000-dalton precursor peptide to ACTH and beta-lipotropin (beta-LPH). In order to evaluate the role of pituitary peptides in the pathogenesis of acanthosis nigricans, we compared plasma levels of beta-endorphin (beta-EP) and ACTH in plasma of 8 fasting patients with obesity-associated benign acanthosis nigricans and 7 fasting normal controls utilizing sensitive radioimmunoassay procedures. Mean plasma beta-EP levels for the acanthosis nigricans and control subjects were not significantly different (90 pg/ml vs. 140 pg/ml), nor was any significant difference observed between plasma ACTH levels of the 2 groups (42.3 and 31.2 pg/ml, respectively.) Our data indicate that plasma levels of the pituitary-derived peptides ACTH and beta-EP are not increased in obesity-associated benign acanthosis nigricans, and suggest that its proposed hormonal mediator might originate independently from the large peptide precursor of ACTH, beta-LPH and their fragments.

Acanthosis Nigricans↗