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PubMed2004

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↗
PubMed2002

Acanthosis nigricans with endometrial carcinoma: case report and review of the literature.

BACKGROUND: Acanthosis nigricans is classified into benign and malignant forms on the basis of clinical associations. The main interest in acanthosis nigricans has been based on its association with malignancy because of the dramatic clinical appearance of the skin lesions and the usually rapidly fatal nature of the underlying disease. "Tripe palms" is a descriptive term of acanthosis nigricans of the palms. It more often is associated with internal malignancy. Most importantly, it often precedes the diagnosis of a new or recurrent tumor. Malignant acanthosis nigricans is most commonly associated with intra-abdominal malignancies. There are very few reports in the literature of malignant acanthosis nigricans associated with gynecological malignancies. Only five cases of endometrial carcinoma associated with acanthosis nigricans and/or tripe palms have been reported in the literature. CASE: A 69-year-old African-American female presented with skin changes consistent with the diagnosis of acanthosis nigricans and tripe palms. More than 14 months later she was found to have endometrial carcinoma. She subsequently underwent total abdominal hysterectomy and salpingo-oophorectomy followed by chemotherapy with paclitaxel and carboplatin. During treatment of the underlying malignancy the skin condition dramatically improved. CONCLUSION: Tripe palms can be associated with endometrial carcinoma and may be the first sign of malignancy. Malignant acanthosis nigricans may improve with treatment of the underlying malignancy. Patients who present with tripe palms may need to undergo workup to search for underlying malignancy.

Acanthosis Nigricans↗
PubMed2001

The autosomal dominant trait of obesity, acanthosis nigricans, hypertension, ischemic heart disease and diabetes type 2.

OBJECTIVE: Among obese subjects, acanthosis nigricans in both males and females is not as uncommon as previously thought. Whereas this finding was extensively evaluated in females, mostly in the context of polycystic ovaries syndrome, little attention has been paid to obese males with acanthosis nigricans. As acanthosis seems to be a marker for insulin resistance, the present study was designed to evaluate the hypothesis that the clinical syndrome of obesity and acanthosis would take a different clinical course than that of simple obesity. METHODS: To characterize the course of acanthosis nigricans and obesity in males, we examined 22 children and adolescents with this complex, together with their parents and grandparents and found them to follow a detrimental sequence of the metabolic syndrome. We compared the findings to 13 age-matched males with obesity but no clinical apparent acanthosis nigricans. We analyzed the clinical course, fat distribution, glucose, insulin and C-peptide and lipoproteins. RESULTS: Onset of obesity in the metabolic syndrome group was at a mean age of 6.4 years, as compared to 2.3 years in the controls. The metabolic syndrome patients had a truncal (android) distribution of fat and their fasting blood glucose was significantly higher. HDL/total cholesterol was lower. Examination of the pedigrees suggested autosomal dominant inheritance of the obesity and acanthosis nigricans complex, extending to hypertension and ischemic heart disease in the parents' generation, and further extending to include diabetes type 2 in the grandparents' generation. CONCLUSIONS: This metabolic syndrome is inherited as an autosomal dominant trait, with onset of truncal obesity at age 6-7 years, acanthosis nigricans during childhood or adolescence, extending to hypertension and ischemic heart disease during young adulthood, and further extending to include diabetes type 2 in late adulthood. It is recommended that such children should be followed up as an 'at-risk' group, and would probably benefit from intensive weight reduction, which may prevent the later manifestations of the syndrome.

Acanthosis Nigricans↗
PubMedDate not supplied

Prevalence of acanthosis nigricans in newly-diagnosed type 2 diabetes.

OBJECTIVE: To determine the prevalence of acanthosis nigricans in a population of patients with newly-diagnosed type 2 diabetes mellitus. METHODS: Chart review of men and women treated for newly diagnosed type 2 diabetes at the University Diabetes Treatment Center at Parkland Health and Hospital System in Dallas, Texas between January 1998 and December 1999. The presence of acanthosis nigricans was evaluated on the posterior neck of each individual. RESULTS: Of 216 patients identified with newly diagnosed type 2 diabetes, 78 individuals (36.1%) presented with acanthosis nigricans involving the back of the neck. Most subjects were obese, with the mean BMI of the subject population at 32.7 +/- 5.8 kg/m2 (mean +/- SD). Prevalence of acanthosis nigricans increased with degree of obesity, with fully 54.1% of the population with a BMI of > or = 30 kg/m2 manifesting the skin lesion. The prevalence of acanthosis nigricans differed notably among ethnic groups, as the lesion occurred in 50 (52.6%) of 95 African-American subjects and 28 (35.9%) of 78 Latin-American subjects. Patients with acanthosis nigricans required markedly higher insulin doses (82.3 +/- 7.2 units/day) to achieve euglycemia compared to those without the disorder (50.2 +/- 5.7 units/day). CONCLUSION: These results suggest that acanthosis nigricans is a readily visible marker of hyperinsulinemia and is frequently encountered in patients with type 2 diabetes. Prevalence of acanthosis nigricans is influenced by ethnicity and BMI in this patient population.

Acanthosis Nigricans↗
PubMed2004

[Clinical significance of pancreatic beta-cell function in obese children with acanthosis nigricans].

OBJECTIVE: The strong relation between type 2 diabetes mellitus and obesity with acanthosis nigricans is widely concerned. This study investigated the pancreatic beta-cell function in obese children with acanthosis nigricans, so as to find out the role of insulin secretion and insulin resistance in obese children with acanthosis nigricans. METHODS: Thirty-five obese children with acanthosis nigricans (19 males and 16 females with mean age 12.8 +/- 1.5 years) were enrolled in this study. Thirty-eight obese children (21 boys and 17 girls with mean age 11.9 +/- 2.6 years) and 39 normal children (20 boys and 19 girls with mean age 11.2 +/- 2.2 years) were recruited as obese and normal control groups. The levels of serum fasting insulin, C-peptide, proinsulin and true insulin were measured in all the subjects. The ratios of proinsulin/insulin and proinsulin/C-peptide were calculated. Homeostasis model assessment was applied to assess the status of insulin resistance and basic function of pancreatic beta-cell. RESULTS: The levels of fasting insulin, C-peptide proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index of obese children with acanthosis nigricans, obese control children and normal control children were: 18.5 (5.0-60.5) pmol/L, 12.4 (6.1-35.8) pmol/L and 5.1 (2.0-32.8) pmol/L; 3.9 (1.3-14.0) microg/L, 2.4 (1.1-4.0) microg/L and 1.1 (1.0-4.2) microg/L; 28.8 (9.9-64.2) pmol/L, 9.5 (2.2-34.5) pmol/L and 4.2 (2.0-16.0) pmol/L; 33.0 (6.2-66.0) pmol/L, 10.6 (4.8-29.4) pmol/L and 4.5 (1.3-30.1) pmol/L; 1.2 (0.4-8.9), 0.9 (0.2-1.9) and 0.8 (0.4-2.0); 6.9 (2.5-36.6), 4.7 (1.2-12.3) and 3.6 (1.2-9.6); 5.0 (0.8-14.1), 2.6 (1.3-8.1) and 1.2(0.4-6.9); 303.3 (52.2-1,163.8), 213.6 (84.6-572.0) and 51.1 (19.1-561.4). The levels of fasting insulin, C-peptide, proinsulin, true insulin, the ratios of proinsulin/insulin and proinsulin/C-peptide, insulin resistance index and insulin secretion index in obese children with acanthosis nigricans were significantly higher than those in obese children (P < 0.001) and normal children (P < 0.001). CONCLUSION: Obese children with acanthosis nigricans had higher insulin resistance and pancreatic beta-cell dysfunction; acanthosis nigricans may be a skin sign of high risk of type 2 diabetes mellitus.

Acanthosis Nigricans↗
PubMed2004

[Obese children with benign acanthosis nigricans and insulin resistance: analysis of 19 cases].

OBJECTIVE: The prevalence of obesity and of type 2 diabetes mellitus in children have increased in the Chinese population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with hyperinsulinemia and impaired glucose tolerance are well accepted as being at high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has not been systematically evaluated in obese children. In order to further explore the relationship between obese childhood with benign acanthosis nigricans and insulin resistance and type 2 diabetes mellitus, we examined 19 obese children with benign acanthosis nigricans. METHODS: Nineteen of seventy six obese children (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin biopsies were performed in these 19 obese children with acanthosis nigricans for final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were measured on fasting blood specimens and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined. Oral glucose tolerance tests were also performed in these 19 children with benign acanthosis nigricans. RESULTS: Anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index as well as fasting insulin level in acanthosis nigricans group were significantly higher than that of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these 19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating apparent insulin resistance. One of them was diagnosed as type 2 diabetes mellitus and ten of them showed impaired oral glucose tolerance. CONCLUSION: Childhood benign acanthosis nigricans is tightly associated with obesity, hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be used as a reliable index of insulin resistance.

Acanthosis Nigricans↗
PubMed2006

Acanthosis Nigricans, insulin resistance (HOMA) and dyslipidemia among Native American children.

OBJECTIVE: It is controversial whether acanthosis nigricans is an independent marker of insulin resistance. In this study, we evaluated whether insulin resistance (as reflected by HOMA) was associated with acanthosis nigricans, Native American heritage, BMI, fasting insulin, and plasma lipids in Native American children and adolescents. DESIGN/METHODS: Retrospective chart review of Native American children (3.6 to 17.8 yrs) seen in 4 tribal or Indian Health Service clinics after referral for exceptionally high type 2 diabetes risk (family history, extreme obesity, and/or severe acanthosis nigricans). RESULTS: All but 2 had a family history of type 2 diabetes in at least one first or second degree relative, all but 3 had acanthosis nigricans (12 severe and 11 mild/not severe), and all but 2 were obese (BMI Z score of +3 to +8). Those with severe acanthosis nigricans had higher BMI and fasting insulin levels and lower HDL-C (p < 0.05) than those with acanthosis nigricans that was not severe. HDL-C correlated with BMI Z-score (p = 0.046) and approached significance with fasting insulin. HOMA correlated with BMI (p = 0.0005), with 82.4% of males and 33.3% of females having a HOMA greater than the 90th percentile for normal children. A multiple regression model indicated that acanthosis nigricans severity remained a predictor (p = 0.015) of HOMA after association of BMI Z score, Native American blood quantum, and gender were removed. CONCLUSIONS: These data indicate that among Native American children at high risk for developing type 2 diabetes, acanthosis nigricans is an independent marker of insulin resistance (as reflected by HOMA).

Acanthosis Nigricans↗
PubMed1997

Malignant acanthosis nigricans and tripe palms in a patient with endometrial adenocarcinoma--a case report and review of literature.

BACKGROUND: In the world literature, uterine carcinoma associated with paraneoplastic malignant acanthosis nigricans and tripe palms has been mentioned in two review articles. Endometrial adenocarcinoma associated with malignant acanthosis nigricans without tripe palms has been cited in three case reports, and endometrial adenocarcinoma associated with tripe palms without malignant acanthosis nigricans has been cited in one case report. We present the case of a patient with endometrial adenocarcinoma associated with acanthosis nigricans and tripe palms which we have been following for the past 7 years. METHODS: Our 54-year-old patient had been operated for moderately differentiated endometrial adenocarcinoma. She had also received postoperative radiotherapy. RESULTS: Three years after surgery, tripe palms and acanthosis nigricans with generalized pruritus occurred. After treatment with etretinate, the skin symptoms were somewhat mitigated while the pruritus persisted. Six years after gynecologic treatment, a solitary inguinal metastatic lymph node of endometrial carcinoma was detected. Following lymphadenectomy there was additional but not complete mitigation of skin symptoms including pruritus. CONCLUSIONS: In clinical practice the association of malignant acanthosis nigricans and tripe palms with endometrial adenocarcinoma is found extremely rarely. Although the survival time of adenocarcinoma patients with malignant acanthosis nigricans is short, our patient has been treated and followed for more than 7 years.

Acanthosis Nigricans↗
PubMed1987

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↗
PubMed1983

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↗
PubMed1985

Acanthosis nigricans in obese women with hyperandrogenism. Characterization of an insulin-resistant state distinct from the type A and B syndromes.

Acanthosis nigricans and hyperandrogenism are commonly found in patients with extreme target cell resistance to insulin, as in the type A and B syndromes of insulin resistance. However, the significance of concurrent acanthosis nigricans and hyperandrogenism in other clinical settings is not clear. We observed acanthosis nigricans to be present in 5% (15 of 300) of patients being evaluated for hyperandrogenism, and carried out studies of insulin binding and action in a group (7) of these women. Although none were diabetic, all were insulin resistant as assessed by hyperinsulinemia when fasting and after oral glucose administration. All patients were obese (mean IBW, 169%). However, when matched to hyperandrogenized women of similar body weight, patients with acanthosis nigricans were clearly more hyperinsulinemic. Insulin binding to monocytes and red cells was decreased in patients with acanthosis, and the extent of decrease was predicted by the fasting insulin level. There was also marked resistance to exogenous insulin during euglycemic insulin clamp studies in the two patients so tested. Anti-insulin receptor antibodies were not detectable, ruling out the type B syndrome. Unlike the type A syndrome, insulin binding to monocytes of these patients increased after acute (2/2) and chronic (1/1) caloric restriction. In the latter patient, acanthosis nigricans remitted as insulin resistance and the insulin binding defect improved. We conclude that acanthosis nigricans is present in as many as 5% of women with clinically significant hyperandrogenism. These women, although not diabetic, have fairly marked insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthosis Nigricans↗
PubMed1989

[Inhibition of pancreatic beta-cell secretion during a "glucose-clamp" in subjects with acanthosis nigricans].

It has long been known that acanthosis nigricans is accompanied by insulin resistance. In certain insulin-resistant states, including obesity, a more sluggish response to the insulin/insulin inhibition feedback normally present in pancreatic beta cells has been documented. Some have claimed a sort of beta-cell insulin resistance "parallel" to that of the peripheral tissues. The present study assesses the efficiency of the insulin/insulin feedback in acanthosis nigricans patients, measuring the inhibition of the production of C-peptide (the indicator of beta cell secretion) induced by the administration of exogenous insulin during glucose clamping. This was done in order to compare the roles of the peripheral tissues and the beta cells in producing the insulin resistance typical of acanthosis nigricans. The study using the glucose-insulin clamp technique was conducted on 4 Acanthosis Nigricans patients with normal glucose tolerance and 4 healthy controls, the drop in C-peptide levels after the administration of exogenous insulin being assessed in the course of both steady states. The results showed that the acanthosis nigricans patients retained a beta cell response to the exogenous insulin through their peripheral tissues presented a reduced sensitivity to insulin as revealed by the glucose-insulin clamp. It therefore seems reasonable to attribute the endocrine metabolic alteration found in Acanthosis Nigricans to a peripheral receptor and/or post receptor alteration rather than central alterations in the beta cells that have yet to be demonstrated. It is concluded that in acanthosis nigricans the peripheral insulin resistance is primarily independent phenomenon and not "parallel" to insulin/insulin feedback.

Acanthosis Nigricans↗
PubMed1988

Role of obesity and hyperinsulinemia in the insulin resistance of obese subjects with the clinical triad of polycystic ovaries, hirsutism and acanthosis nigricans.

The insulin resistance of 4 nonobese and 8 obese patients with polycystic ovaries, hirsutism and benign acanthosis nigricans, and of 6 'obese normal' apart from obesity and 10 normal female subjects was evaluated by means of an intravenous insulin tolerance test and by measuring basal and insulin responses to an oral glucose load. The patients with polycystic ovaries, hirsutism and acanthosis had a decreased hypoglycemic response to exogenous insulin. The subjects with polycystic ovaries presented a significantly greater mean glucose response area for the same or greater mean insulin response area than the obese or nonobese normal subjects. The insulin resistance in the patient with polycystic ovaries, hirsutism and acanthosis nigricans could not be exclusively ascribed to a reduced receptor number, but also appeared to be due to a simultaneous postbinding defect probably related to the high insulin levels in patients with polycystic ovaries be they obese or not. The elevated plasma androgens and the presence of acanthosis found in these patients are likely also related to the hyperinsulinemia. To evaluate the influence of obesity, obese and nonobese patients with acanthosis nigricans and polycystic ovaries were compared. Higher insulin levels were found in the thin subjects, which could explain their greater insulin resistance and more severe hyperandrogenism. The comparison between obese patients with and those without acanthosis nigricans and polycystic ovaries suggested that, despite similar insulin levels, the greater known duration of obesity (probably also of the hyperinsulinemia) of the former was a possible explanation for their more intense insulin resistance and higher testosterone levels.

Acanthosis Nigricans↗
PubMed1988

Oral acanthosis nigricans: report of a case and comparison of oral and cutaneous pathology.

Malignant acanthosis nigricans is usually associated with adenocarcinomas of the digestive tract. The lesions of acanthosis nigricans commonly run a parallel course to the associated malignancy, producing hyperpigmented, roughened plaques on the skin and, sometimes, verruca-like papules on the oral mucosa. The clinical differences between cutaneous and oral acanthosis nigricans are mirrored by the marked differences in the histopathology. Because oral acanthosis nigricans is uncommon, recognizing histologic features may be difficult. The oral lesions have a true acanthosis and epithelial papillary hyperplasia while the cutaneous forms show slight irregular acanthosis that alternates with areas of epidermal atrophy and dermal papillomatosis.

Acanthosis Nigricans↗