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PubMed1997

Hyperinsulinemia and acanthosis nigricans in African Americans.

Compared with the US white, non-Hispanic population, the African-American population has a nearly two-fold higher prevalence of noninsulin-dependent diabetes mellitus (NIDDM). Obesity, which usually precedes NIDDM, is associated with the skin lesion acanthosis nigricans in African Americans. This study was undertaken to determine what the relationship of acanthosis nigricans was to hyperinsulinemia, a major risk factor for NIDDM. Eighty-nine African-American subjects with acanthosis nigricans and 25 others without the skin lesion were evaluated using oral glucose tolerance testing and responsiveness to insulin. Noninsulin-dependent diabetes mellitus was present in 19 of the subjects with acanthosis nigricans. The prevalence of NIDDM in this group increased with increasing age, reaching 50% among those in their 40s. Fasting plasma insulin concentration was in direct proportion to the severity of the acanthosis nigricans involvement of the neck. These data suggest that among African Americans, this skin lesion is a marker for hyperinsulinemia and insulin resistance. Furthermore, the presence of acanthosis nigricans identifies a subset with a much higher prevalence of NIDDM than is present in African Americans in the general population.

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PubMed1986

Acanthosis nigricans, hypothyroidism, and insulin resistance.

Acanthosis nigricans has been associated with multiple endocrinopathies. The common denominator appears to be insulin resistance. Three patients are described (one woman and two men) who presented with hypothyroidism and acanthosis nigricans. All the patients had elevated insulin levels in the fasting state and in response to an oral glucose load. The mechanism for the resistance to insulin was a post-receptor binding defect or a structural abnormality in circulating insulin, since glucose tolerance and plasma cortisol, somatomedin, growth hormone, and insulin receptor concentrations in peripheral monocytes were all normal. Antibodies to insulin or the insulin receptor were absent. Neither insulin resistance nor acanthosis nigricans diminished following correction of the hypothyroidism. It is concluded that hypothyroidism may be associated with acanthosis nigricans, that hyperinsulinemia is a regular correlate of the skin disorder, and that treatment of the hypothyroidism does not resolve the hyperinsulinemia or the acanthosis nigricans.

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PubMed2001

Association of acanthosis nigricans with risk of diabetes mellitus, and hormonal disturbances in arabian females: case-control study.

OBJECTIVE: To aim of the present study is to determine the association of acanthosis nigricans(AN) with risk of diabetes mellitus, and hormonal levels in female subjects from the United Arab Emirates (UAE). DESIGN: Matched case-control study. SETTING: Tawam Teaching Hospital of Faculty of Medicine and Health Sciences. SUBJECTS: 184 female subjects (92 females with AN and 92 females without AN); (age range 16-65 years) were recruited. METHODS: Height, weight, and sitting blood pressure were recorded on 184 female subjects with AN and without AN. Fasting blood samples were obtained for measurement of uric acid, glucose, cholesterol, HDL-cholesterol, and triglyceride levels. MAIN OUTCOME MEASURE: Risk factors were investigated. Analysis was based on univariate and multivariate analysis. RESULTS: The present study showed that BMI, family history of DM, fasting glucose, HDL-cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significantly higher in obese women in acanthosis and non acanthosis groups. The results revealed that BMI, family history of DM, total cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significant higher in diabetic women in non-acanthosis. Furthermore, systolic blood pressure, total cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significantly higher in diabetic women in acanthosis groups. Overall, DM subjects had significantly higher values for hormone levels of TSH, FSH, LH, progesterone, testosterone, cortisol, prolactin, GH, and ferritin. CONCLUSION: The conclusion has been stated as follows: patients in the UAE who have AN have a high prevalence of DM and insulin resistance. Since AN is rather prevalent in the UAE, identifying this skin lesion can help detect those subjects with a higher risk of DM and hormonal disturbances.

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PubMed2005

Acanthosis nigricans: clinical predictor of abnormal glucose tolerance in Asian women with polycystic ovary syndrome.

The aim of this retrospective study was to assess whether acanthosis nigricans is a predictive factor for abnormal glucose tolerance (AGT) in Asian women with polycystic ovary syndrome (PCOS). Data from the record forms and electronic form of 121 PCOS women who consecutively attended the Reproductive Endocrinology and Infertility Unit were reviewed. In accordance with the unit's guidelines, all women received a physical examination, had anthropometric measurements taken and underwent as a 75-g oral glucose tolerance test after diagnosis. Their age, body mass index (BMI) and waist/hip ratio (WHR) was 29.1+/-6.1 years, 27.4+/-6.8 kg/m2 and 0.84+/-0.6 (mean+/-standard deviation), respectively. The prevalence of AGT was 42.9%, with 1.6% having impaired fasting glucose, 32.3% having impaired glucose tolerance and 9.1% having type 2 diabetes mellitus. The PCOS women with acanthosis nigricans had significantly higher BMI, WHR, fasting glucose, 2-h post-load glucose, fasting insulin, 2-h post-load insulin and prevalence of AGT compared with those without acanthosis nigricans. By logistic regression analysis, acanthosis nigricans and WHR were independent predictors for AGT, with an odds ratio (95% confidence interval) of 2.7 (1.1-7.1) and 10.1 (1.8-20.7), respectively. In conclusion, acanthosis nigricans was demonstrated as a predictive factor for AGT in Asian women with PCOS.

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PubMed1998

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.

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PubMed1976

Insulin resistance and acanthosis nigricans. Report of a case with antibodies to insulin receptors.

A 64-year-old black man presented with the syndrome of acanthosis nigricans and insulin-resistant diabetes mellitus requiring up to 3000 units of insulin per day. The patient's plasma contained circulating antibodies to insulin receptors thought to be responsible for the insulin resistance. The marked insulin resistance, the manifestations of acanthosis nigricans, the evidence of immunologic dysfunction by the absence of expected circulating antibodies to insulin, and the demonstration of circulating antibodies to insulin receptors put this patient in Kahn's category B of insulin resistance and acanthosis nigricans. There was no evidence of malignancy, lipodystrophy, or endocrine abnormality. The occurrence of acanthosis nigricans with insulin resistance due to binding of cell membrane insulin receptors by antibodies has been reported exclusively in women. This case report is the first description of a male patient with the syndrome of insulin resistance and acanthosis nigricans and focuses attention on features that might mislead one to suspect other causes of insulin resistance.

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PubMed2000

Acanthosis nigricans in obese patients: Presentations and implications for prevention of atherosclerotic vascular disease.

Acanthosis nigricans is traditionally characterized by hyperpigmented, velvety plaques of body folds. Involvement of other areas occurs as well. The condition is caused by hyperinsulinemia, a consequence of insulin resistance that occurs associated with obesity. As the frequency and degree of obesity increase in the population, a concomitant increase in acanthosis nigricans can be expected. The dermatologist has an important role in identifying the subset of obese patients with acanthosis nigricans. These patients have hyperinsulinemia and may be at greater risk of consequent atherosclerotic cardiovascular disease. It is essential for dermatologists to recognize the many presentations of acanthosis nigricans to identify patients at risk for associated medical conditions. This article illustrates a variety of presentations of acanthosis nigricans associated with insulin resistance.

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PubMedDate not supplied

Diabetic ketoacidosis in association with acanthosis nigricans.

OBJECTIVE: To report the occurrence of diabetic ketoacidosis in three patients with acanthosis nigricans. METHODS: Case reports with clinical and laboratory data are presented, and the syndrome of acanthosis nigricans is discussed. RESULTS: Three obese male patients--two American Indians and one Polynesian man--sought medical attention because of symptoms of diabetic ketoacidosis and were noted to have acanthosis nigricans. No factor was identified that could have precipitated the diabetic ketoacidosis, which was resolved by treatment with insulin. CONCLUSIONS: The unexpected association of diabetic ketoacidosis and acanthosis nigricans is documented in these three cases. The hyperinsulinemia associated with acanthosis nigricans results from insulin resistance, and when insulin resistance occurs in combination with impaired insulin secretion, diabetic ketoacidosis can result.

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PubMed2001

A study of insulin resistance in subjects with acanthosis nigricans.

AIM: To study the prevalence of insulin resistance (IR) and its sequelae in patients with acanthosis. METHODOLOGY: Thirty six patients (28 females; eight males) with biopsy proven acanthosis nigricans and eight controls were evaluated for insulin sensitivity (IS) by estimating (a) the glucose and insulin responses to a 75 gm glucose load (Oral glucose tolerance test-OGTT), (b) the glucose disposal rate (GDR) during an intravenous insulin tolerance test (ITT). Serum androgen levels (testosterone--Te, androstenedione--ASD, Dehydro-epiandrosterone sulphate--DHEAS) were estimated in the basal state and 60 min after a bolus of insulin. Thyroid function tests (tri-iodo-thyronine--T3, thyroxine--T4, thyroid stimulating hormone--TSH) were performed in all subjects. RESULTS: The acanthotic population, overall had insignificant hyperglycemia (Area under curve of glucose--AUC-G : 17,745.5 +/- 847.5 v/s 11,051.3 +/- 274.5 mg/dl/min) and hyperinsulinemia (Area under curve of insulin -AUC-I: 20,825.2 +/- 1,287.7 v/s 6,340.1 +/- 984.2 microlU/ml/min) compared to controls during OGTT. Eight patients with acanthosis nigricans had impaired glucose tolerance and eight had overt diabetes using WHO criteria. 69.4% of the acanthotic subjects were obese and 13.9% (5/36) were hypertensive. Thyroid dysfunction was present in three (one had hypothyroidism and two had thyrotoxicosis). Reproductive disorders--menstrual irregularity (46.5%), amenorrhea (21.4%), hirsuitism (21.4%) and infertility (3.6%) was encountered in a significant number of acanthotics. Acanthotics overall had statistically higher levels of androgens; Te (females)--0.74 +/- 0.09 v/s 0.27 +/- 0.09 ng/ml (p < 0.005), ASD--1.8 +/- 0.21 v/s 0.94 +/- 0.2 ng/ml (p < 0.005) and DHEAS--1,880.8 +/- 216.3 v/s 772.8 +/- 210.4 ng/ml (p < 0.005). An elevated DHEAS correlated positively to body mass index (BMI) and android obesity. Serum Te levels correlated positively with GDR. Serum insulin levels increased progressively with obesity and acanthosis. Serum insulin was associated with progressive worsening of hyperandrogenism (as seen in non-obese controls, non-obese and obese acanthotics). CONCLUSIONS: Subjects with acanthosis nigricans should be screened for insulin resistance and its clinical and metabolic sequelae. Thyroid dysfunction should be sought in these subjects as it can be easily treated.

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PubMed2004

[Acral acanthosis nigricans paraneoplastic: about one case].

The paraneoplastic acanthosis nigricans occurs in association with visceral neoplasms. We report a case of acanthosis nigricans that seat at a dorsal face of the second, third and fourth right toe of a 63 year-old patient. The exploration has been put in evidence a carcinoma of the right lung. The acanthosis nigricans has been nearly disappeared after resection of the pulmonary lobe. The relapses of the acanthosis nigricans in a same sit after five years has been reveal a carcinoma of the bladder. The resection of the bladder tumour has been followed by disappearance of the acanthosis nigricans.

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PubMed1992

Prevalence and significance of acanthosis nigricans in an adult obese population.

BACKGROUND AND DESIGN: Acanthosis nigricans develops commonly in obese individuals, yet its prevalence and significance in an unselected adult obese population has not been determined. To address these issues, 34 patients enrolled in the Adult Obesity Clinic at Parkland Memorial Hospital (Dallas, Tex) were chosen at random and examined. RESULTS: Acanthosis nigricans was observed in fully 74% of patients; its prevalence correlated positively with severity of obesity. Black obese patients demonstrated a greater propensity for manifesting the cutaneous disorder than did white obese individuals. Patients with acanthosis nigricans exhibited fasting plasma insulin levels that were markedly higher than those of nonacanthotic cohorts. CONCLUSIONS: Obesity is a significant risk factor for the development of acanthosis nigricans. Conversely, acanthosis nigricans is a reliable cutaneous marker of hyperinsulinemia in obese individuals.

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PubMed1988

Malignant acanthosis nigricans associated with non-Hodgkin's lymphoma. Report of 2 cases.

Two cases of malignant acanthosis nigricans associated with non-Hodgkin's lymphoma are presented. A 61-year-old negro male with a diffuse large cell non-Hodgkin's lymphoma presented extensive acanthosis nigricans, pachydermatoglyphy and florid cutaneous papillomatosis. No viral particles were observed by electron microscopic studies of the wart-like lesions. Acanthosis nigricans disappeared under chemotherapy. The second case was a 21-year-old caucasian male with non T non B diffuse large cell non-Hodgkin's lymphoma. Very few cases of acanthosis nigricans associated with non-Hodgkin's lymphoma have been reported in the literature, since to our knowledge these two are only the fourth and fifth. Pachydermatoglyphy and florid cutaneous papillomatosis are markers of malignant acanthosis nigricans.

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PubMed1981

Ovarian pathology associated with insulin resistance and acanthosis nigricans.

Insulin resistance and the skin lesions of acanthosis nigricans are not commonly seen by the gynecologist, but the ovarian pathology that can be associated with insulin resistance and acanthosis nigricans is well known. The clinical course of disease in a patient with virilization-amenorrhea associated with insulin resistance and acanthosis nigricans is presented to illustrate the association. Hyperthecosis was the ovarian pathology demonstrated; testosterone levels were in excess of 400 ng/gl. Postoperative testosterone levels were normal at 62 ng/dl. Additional ovarian pathology reported in association with insulin resistance and acanthosis nigricans includes polycystic ovary disease alone, in association with stromal luteomas, or with bilateral dermoid cysts. Furthermore, masculinizing ovarian neoplasms such as hilar cell tumors have been reported in association with ovarian hyperthecosis. When evaluating patients with androgen excess, it would be worthwhile to keep in mind the association with abnormal carbohydrate metabolism and acanthosis nigricans.

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PubMed1992

Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha.

The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.

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PubMed1987

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.

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PubMed1991

Acanthosis nigricans and a rectal carcinoid.

Malignant acanthosis nigricans is often related to adenocarcinomas of the gastrointestinal tract, but it has also been found to coexist with tumors of the amine precursor uptake and decarboxylation system. It can precede, accompany, or follow the appearance of the underlying tumor. Evaluation of our patient's new-onset acanthosis nigricans led to the discovery of an asymptomatic rectal carcinoid tumor. To our knowledge, this is the first report of acanthosis nigricans associated with a carcinoid tumor of the rectum. It emphasizes the importance of considering underlying malignancy in the evaluation of patients with acanthosis nigricans.

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PubMed1992

Esophageal acanthosis nigricans in association with adenocarcinoma from an unknown primary site.

A case of acanthosis nigricans with esophageal involvement is presented. Six months after the patient's initial examination, metastatic adenocarcinoma from an unknown primary site was discovered. This represents the ninth reported case of esophageal acanthosis nigricans; six of the eight previously described cases were in association with malignancy localized to the gastrointestinal tract. Esophageal acanthosis nigricans may be a more specific marker for associated malignancy than cutaneous or oral mucosal manifestations. If present, esophageal acanthosis nigricans may serve as an indication for an extensive search for occult malignancy.

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PubMed1989

Prevalence of acanthosis nigricans in an unselected population.

PURPOSE: The intent of this study was to determine, in an unselected population, the prevalence of the hyperinsulinemia-associated skin lesion, acanthosis nigricans. SUBJECTS AND METHODS: The posterior neck of every child in the sixth and eighth grades of the public schools of Galveston, Texas, was personally examined by the investigators during a state-mandated school health survey. A total of 1,412 children were examined. RESULTS: The data for each child examined included the absence or presence of acanthosis nigricans, height, weight, age, sex, and ethnic background. A subset of the children with the skin lesion also had fasting plasma insulin levels measured. Acanthosis nigricans was present in 7.1% of the 1,412 children examined. The skin lesion was equally distributed between boys and girls and was most common among children with severe obesity. The condition was present in two of 440 white non-Hispanics, 19 of 343 Hispanics, and 80 of 601 blacks examined. The fasting plasma insulin concentrations measured in some of these children and in previously evaluated subjects strongly correlate with the presence and severity of the acanthosis nigricans skin lesion. CONCLUSIONS: This skin lesion is much more common than previously believed and has a dramatic ethnic predisposition. We conclude that the high prevalence of this skin lesion further suggests that insulin resistance and hyperinsulinemia, with all of their serious medical implications, are also highly prevalent.

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