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PubMed1987

Ketoconazole reverses hyperandrogenism in a patient with insulin resistance and acanthosis nigricans.

We administered ketoconazole to a young woman with ovarian hyperandrogenism, insulin resistance, and acanthosis nigricans. While taking ketoconazole, her serum testosterone, androstenedione, dehydroepiandrosterone, and cortisol levels declined, while serum progesterone, 17-hydroxyprogesterone, and 11-deoxycortisol rose. Serum LH, FSH, and estradiol levels were intermittently higher during ketoconazole treatment, although LH and FSH responsiveness to GnRH did not change. Basal and stimulated serum insulin concentrations were high before and during ketoconazole therapy, while fasting glucose levels and glucose disappearance rate constants were normal throughout the study. A dramatic improvement in hirsutism occurred, and menses resumed after a 6-yr hiatus. Adverse drug effects or clinical evidence of adrenal insufficiency were not encountered. These results support a role for ketoconazole in the therapy of ovarian hyperandrogenism.

Acanthosis Nigricans↗
PubMed1990

Bimodal correlation between the circulating insulin level and the production rate of dehydroepiandrosterone: positive correlation in controls and negative correlation in the polycystic ovary syndrome with acanthosis nigricans.

The objective of this study was to define the relationship among the circulating insulin level (IRI), the MCR of dehydroepiandrosterone (MCR-D), and the production rate of DHEA (PR-D) in 10 women with the polycystic ovary syndrome and acanthosis nigricans (PCOS-AN). Seven normal weight and 10 obese women served as controls. Measurement of the MCR-D and PR-D was accomplished by iv saline infusion (0.9% NaCl solution) on day 1 as a control and a 4-h iv dehydroepiandrosterone (unlabeled) infusion (1 mg/h) was performed on day 2. Mean MCR-D was more than 2-fold higher in the obese controls compared to the normal weight controls. However, the plasma concentration of DHEA(PC-D) was not significantly different in the normal and obese control women, since the PR-D was increased proportionately to the MCR-D. The MCR-D and the PR-D were coupled through insulin in the control women, and their correlation coefficients with IRI were positive and identical (0.77 and 0.73, respectively). In contrast, IRI was negatively correlated with PR-D in the PCOS-AN women. Also, unlike the control women, there was minimal or no change in the MCR-D across a broad range of IRI in the PCOS-AN women. Thus, the MCR-D and PR-D were not coupled in these women.

Acanthosis Nigricans↗
PubMed1990

Defect in tyrosine kinase activity of the insulin receptor from a patient with insulin resistance and acanthosis nigricans.

We report here a defect in tyrosine kinase activity of the insulin receptor from an insulin-resistant patient with acanthosis nigricans using cultured Ebstein-Barr virus (EBV)-transformed B-lymphocytes. As judged by affinity labeling and immunoblotting, the alpha- and beta-subunits of insulin receptors from the patient's lymphocytes exhibited the same mol wt as those from control subjects. Lectin-purified extracts from lymphocytes of the patient and the control subjects containing the same insulin-binding capacity were assayed for autophosphorylation and the ability to phosphorylate histone H2B. The degree of insulin-dependent autophosphorylation and the tyrosine kinase activity of the insulin receptor from the patient's lymphocytes were decreased to 15% and 13%, respectively, in a cell-free system. The insulin-dependent autophosphorylation of the insulin receptor was also impaired in intact EBV lymphocytes from the patient. Consistent with these results, we found that one of this patient's alleles had a mutation in which valine is substituted for Gly996, the third glycine in the conserved Gly-X-Gly-X-X-Gly motif in the kinase domain. Thus, it seems likely that the defect in tyrosine kinase activity of the insulin receptor cause the insulin resistance in this patient. The EBV lymphocyte can be a good system to detect genetically determined abnormalities in the insulin receptor.

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PubMed1991

Acanthosis Nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings.

Acanthosis nigricans (AN) is a frequent clinical finding in hyperandrogenic women. Its presence has been used to subgroup such women. We performed this study in order to determine the actual histological prevalence of AN and its relationship to sex hormone levels and insulin action. Insulin-mediated glucose disposal was determined by the euglycemic clamp technique, and neck or axillary skin biopsies were graded blind for the presence and severity of AN in lean and obese women with the polycystic ovary syndrome (PCO) and in age- and weight-matched normal ovulatory controls. AN was present on clinical examination in 11 of 13 obese PCO, 3 of 6 lean PCO, 4 of 14 obese normal, and 0 of 4 lean normal women. AN was present on histological examination in 13 of 13 obese PCO, 5 of 6 lean PCO, 13 of 14 obese normal, and 1 of 4 lean normal women. The severity of histological AN was most highly correlated with insulin-mediated glucose disposal (r = -0.61; P less than 0.001) rather than fasting (r = 0.46; P less than 0.05) or glucose-stimulated insulin levels (r = 0.48; P less than 0.01). The only sex steroid correlated with histological AN was dehydroepiandrosterone sulfate (r = 0.46; P less than 0.01). We conclude that 1) clinical skin examination was very insensitive for detecting AN; 2) the best biochemical correlate of histological AN was decreased insulin action, rather than insulin or androgen levels per se; and 3) AN is a very common epiphenomenon of insulin resistance, and its clinical presence should not be used as a criterion for stratifying hyperandrogenic women.

Acanthosis Nigricans↗
PubMed1995

Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans.

Benign premature adrenarche (PA) is the term used to refer to girls with the early development of pubic hair before the age of 8 yr and is characterized by mild hyperandrogenism. Hyperandrogenism in adult women is often not as benign and has been associated with insulin resistance, acanthosis nigricans (AN), and the polycystic ovary syndrome. We have seen a group of young girls with PA who have also been found to have AN. The purpose of this study was to determine whether there are any clinical and biochemical differences in those girls with PA with and without AN. Twelve girls with PA were divided into two groups at the time of evaluation: group I, those without AN (n = 5); and group II, those with AN (n = 7). Adrenal androgen levels were determined in all subjects by a 60-min ACTH stimulation test. Insulin sensitivity was measured by the frequently sampled iv glucose tolerance test with tolbutamide and was assessed using the modified minimal model. Mean chronological age, bone age, and weight for length index were similar in the two groups. The baseline and stimulated levels of adrenal androgens were also not significantly different between the two groups. The group I girls (without AN) had an insulin sensitivity index of 6.75 +/- 1.31, which was in the normal prepubertal range. This was significantly different from that in group II (with AN), who had an insulin sensitivity index of 3.69 +/- 1.29. Therefore, many girls with premature adrenarche can have AN and decreased insulin sensitivity. Whether these girls have a truly benign course or are at risk of ovarian dysfunction or carbohydrate intolerance needs to be assessed.

Acanthosis Nigricans↗
PubMed1976

Radiological manifestations of oesophageal involvement in acanthosis nigricans.

Radiologic features of two cases of acanthosis nigricans with oesophageal involvement are reported. The first case demonstrated diffuse, granular shadows throughout the oesophagus which were difficult to differentiate from oesophageal moniliasis. Another case showed many discrete and tiny elevations resembling pseudopolyposis of the colon. Emphasis is placed on radiological differential diagnosis from moniliasis and leukoplakia of the oesophagus.

Acanthosis Nigricans↗
PubMed1982

[Insulin resistance with acanthosis nigricans: a case report].

We described a 12 7/12-year-old boy presenting the syndrome of insulin resistance and acanthosis nigricans Type A. Insulin levels at fasting state and after glucose loading were 149 +/- 63 microunits/ml (mean +/- SD) and over 1000 microunits/ml, respectively, while fasting levels of blood glucose were 77.7 +/- 8.9 mg/dl (mean +/- SD). A marked resistance to exogenous insulin was observed. Circulating levels of insulin antagonists such as growth hormone, cortisol and glucagon, were within the normal range. Proinsulin was less than 5% of the total radioimmunoassayable insulin. Insulin antibody and anti-receptor antibody were not detected. Insulin binding to mononuclear cells were decreased to about 50% of controls. Analysis of membrane receptors demonstrated the normal average affinity, dissociation kinetics and negative cooperativity with a decreased number of receptors. After two days fasting, plasma IRI levels decreased to 27 microunits/ml, however insulin binding kinetics were not affected. This might suggesting that the receptor decrease was not secondary to hyperinsulinemia. These findings indicate that a decreased number of receptors was one of the causes for insulin resistance in the patient.

Acanthosis Nigricans↗
PubMed2002

Association of acanthosis nigricans with race and metabolic disturbances in obese women.

Acanthosis nigricans (AN) has been recognized as a marker of insulin resistance and diabetes mellitus. We have compared frequency of race and metabolic disturbances in obese women with several degrees of AN (AN group, N = 190) to a group without AN (non-AN group, N = 61) from a mixed racial population. The groups were similar regarding age and body mass index. All patients (except the diabetic patients) underwent an oral glucose tolerance test (75 g). The racial distribution of this population was 35.1% white, 37.8% mulatto and 27.1% black and the frequency of AN was 62.5, 82.1 and 83.8%, respectively, higher in black versus white (P = 0.003) and mulatto versus white (P = 0.002) women. The frequencies of diabetes mellitus and impaired glucose tolerance were 5.8 and 12.6% in the AN group and 1.6 and 8.2% in the non-AN group, respectively (P>0.05). Fasting glucose, beta cell function determined by the homeostasis model of assessment (HOMA), fasting insulin and insulin area under the curve were similar for the AN and non-AN groups. A higher HOMA insulin resistance was observed in the AN group compared to the non-AN group (P = 0.02) and in the subgroup of highest degree of AN compared to those with other degrees. The mean lipid levels and the frequency of dyslipidemia were similar for the two groups. AN was strongly associated with the black or mulatto rather than the white race, even after taking into account the effect of age, body mass index and HOMA insulin resistance.

Acanthosis Nigricans↗
PubMed1984

A case of insulin resistance associated with acanthosis nigricans.

We described here a 12-year-old male patient with the syndrome of insulin resistance and acanthosis nigricans type A. Insulin levels at fasting state and after glucose loading were 149 +/- 63 microU/ml (mean +/- S.D.) and over 1,000 microU/ml respectively, while the fasting level of blood glucose was 77.7 +/- 8.9 mg/ml (mean +/- S.D.). A marked resistance to exogenous insulin was observed. Circulating levels of insulin antagonists such as growth hormone, cortisol and glucagon were within the normal range. Proinsulin was less than 5% of the radioimmunoassayable insulin. No insulin antibody or antireceptor antibody was detected. Insulin binding to mononuclear cells was decreased to about 50% of the controls. Analysis of membrane receptors demonstrated the normal average affinity, dissociation kinetics and negative cooperativity with a decreased number of receptors. After two days fasting, plasma IRI levels decreased to 27 microU/ml, while insulin binding kinetics were not affected; which suggests that the receptor decrease was not secondary to hyperinsulinemia. These findings indicate that the decreased number of receptors was one of the causes for insulin resistance in this patient.

Acanthosis Nigricans↗
PubMed2001

Oral Acanthosis nigricans as a marker of internal malignancy. A case report.

BACKGROUND: Acanthosis nigricans (AN) is a rare mucocutaneous condition that can involve the oral tissues. There are 2 clinical forms of AN: benign and malignant. Benign AN is related to systemic diseases such as diabetes and obesity or can be induced by drugs such as systemic corticosteroids, nicotinic acid, estrogens, insulin, and fusidic acid. Malignant AN appears in association with tumors such as lung, ovarian, breast, and gastric carcinoma. METHODS: A rare case of malignant AN that initially manifested in the oral cavity of a 73-year-old patient is reported. RESULTS: A bladder and lung carcinoma were detected following the diagnosis of AN. CONCLUSIONS: The diagnostic importance of oral AN is emphasized because, in our patient, its recognition led to the detection of 2 occult malignant tumors.

Acanthosis Nigricans↗
PubMed1986

Familial insulin resistance and acanthosis nigricans. Presence of a postbinding defect.

Type A insulin resistance, associated with acanthosis nigricans and menstrual irregularity, has been ascribed to a decreased concentration of insulin receptors. We now report four affected females from one family, a mother and three daughters (including identical twins) who appear to have the type A syndrome. Two of the kindred had no apparent ovarian dysfunction, while the other two had hyperprolactinemia without other findings of polycystic ovary disease, suggesting a genetic disease with variable penetrance. All had normal erythrocyte and monocyte insulin binding. Insulin dose-response studies to assess glucose metabolism and insulin sensitivity were performed in the affected twins. The dose response to insulin was shifted to the right with a decrease in maximal response. These results are consistent with a postbinding defect in insulin action in these patients.

Acanthosis Nigricans↗
PubMed1989

Autophosphorylation of cultured skin fibroblast insulin receptors from patients with severe insulin resistance and acanthosis nigricans.

The severe insulin resistance with acanthosis nigricans seen in young women without insulin-receptor autoantibodies is characterized by hyperinsulinemia and decreased in vivo responsiveness to insulin. We evaluated the potential cellular defects in insulin-receptor binding and autophosphorylation in 12 subjects with this syndrome. When evaluated as a group, insulin binding to freshly isolated monocytes was 55% that of controls. Specific binding of insulin to skin fibroblasts in monolayer culture was 49% that of controls. Maximal insulin-stimulated receptor autophosphorylation was only 27% that of controls. Individual data demonstrated that the diminished autophosphorylation activity was out of proportion to the diminished fibroblast insulin binding in cell lines from most subjects and was less than 50% of the predicted activity in 6 of the 12 studied cell lines. These data are consistent with genetically determined defects leading to diminished numbers of cell surface insulin receptors with intact tyrosine kinase autophosphorylation in many of our cell lines. However, in at least half, there appeared to be an additional defect beyond insulin binding, resulting in a disproportionate decrease in insulin-sensitive phosphorylation of the insulin-receptor beta-subunit.

Acanthosis Nigricans↗
PubMed1999

A quantitative scale of acanthosis nigricans.

OBJECTIVE: To develop and validate a scale for acanthosis nigricans (AN). RESEARCH DESIGN AND METHODS: Subjects were participants from the San Antonio Family Diabetes Study and the San Antonio Family Heart Study. A total of 406 subjects were independently examined for AN by at least two observers. Five locations were examined: the neck, axilla, elbows, knuckles, and knees. Interobserver concordance and kappa statistics were calculated to determine replicability of the scale. Comparisons of diabetes-related risk factors by AN score were also calculated. RESULTS: Only the neck had consistently high kappa statistics, and thus, other locations were excluded from further analyses. Elevated AN was strongly associated with elevated fasting insulin and BMI in both diabetic and nondiabetic subjects. Elevated AN was also strongly associated with elevated fasting glucose, systolic blood pressure, and diastolic blood pressure, and with decreased HDL in nondiabetic subjects. In diabetic subjects, elevated AN was associated with elevated total cholesterol. CONCLUSIONS: We have developed a scale for AN that is easy to use, has high interobserver reliability in Mexican Americans, and correlates well with fasting insulin and BMI. This scale will permit longitudinal and cross-sectional evaluation of AN and will permit the evaluation of AN as a trait in genetic studies.

Acanthosis Nigricans↗
PubMed2002

Association of acanthosis nigricans with hyperinsulinemia compared with other selected risk factors for type 2 diabetes in Cherokee Indians: the Cherokee Diabetes Study.

OBJECTIVE: To report prevalence rates of acanthosis nigricans (AN) and hyperinsulinemia and the association of AN with hyperinsulinemia compared with other known or suspected risk factors for type 2 diabetes in young American Indians. RESEARCH DESIGN AND METHODS: A random sample of Cherokee Nation members aged 5-40 years was invited to participate in the Cherokee Diabetes Study, a cross-sectional study of type 2 diabetes and its risk factors in a young American Indian population. Data were collected by personal interview, medical history, physical examination (including anthropometric and blood pressure measurements and examination of the neck for AN), and laboratory analyses of blood specimens. Levels of insulin, lipids, and glucose were measured on fasting blood specimens. Diabetes status was determined according to the American Diabetes Association criteria. RESULTS: A total of 2,205 participants were examined. Overall prevalence rates for AN and hyperinsulinemia were 34.2 and 47.2%, respectively. In general, the rates for both increased with age and degree of Indian heritage and were higher in female subjects, overweight/obese individuals, those with type 2 diabetes, and those with a parental history of type 2 diabetes. In addition, both had significantly higher age- and sex-adjusted means for selected known or suspected risk factors for type 2 diabetes. AN remained significantly associated with hyperinsulinemia (P = 0.0001) in multivariate analysis. CONCLUSIONS: AN is independently associated with hyperinsulinemia and therefore may be useful as an early indicator of high risk for diabetes.

Acanthosis Nigricans↗
PubMed2004

Relation between acanthosis nigricans and insulin sensitivity in overweight Hispanic children at risk for type 2 diabetes.

OBJECTIVE: To investigate in a population of Hispanic children if 1) the presence of acanthosis nigricans (AN) is related to insulin sensitivity (S(i)) independent of adiposity and 2) scale scoring AN severity adds to the clinical estimation of insulin sensitivity, above and beyond the presence or absence AN alone. RESEARCH DESIGN AND METHODS: The study population, 131 Hispanic overweight children (mean BMI percentile 97.0 +/- 3.1, 72 boys, 59 girls, ages 8-13 years, mean Tanner stage 2.4 +/- 1.5) with a family history of type 2 diabetes, underwent a physical examination of the neck to determine AN absence or presence (0-1), AN extent score (0-4 scale), AN texture score (0-3 scale), and an AN combined score (extent + texture; 0-7 scale). S(i) was measured by the frequently sampled intravenous glucose tolerance test and minimal modeling. Multivariate linear regression analysis was used to determine the role of BMI and AN in predicting S(i). RESULTS: BMI was the main predictor of S(i), explaining approximately 41% of the variance. The presence of AN explained an additional 4% of the variability in S(i); scale scoring of AN extent or texture did not significantly improve the prediction. CONCLUSIONS: Although AN is an independent risk factor for insulin resistance in overweight Hispanic children at risk for type 2 diabetes, body adiposity is the primary determinant of insulin sensitivity. In addition, scale scoring AN seems of minimal usefulness in clinically estimating the severity of insulin resistance over and above assessing the presence or absence of AN and calculating BMI.

Acanthosis Nigricans↗
PubMed1996

A case of severe hyperandrogenism, acanthosis nigricans and over diabetes: the use of non-invasive methods for diagnosis, pathogenesis and management.

Hyperandrogenism is characterized clinically by hirsutism, acne, androgens-dependent alopecia and elevated serum concentrations of androgens (testosterone and androstenedione). Polycystic ovary syndrome is the most frequent cause of hyperandrogenism. Nevertheless, the differential diagnosis includes androgen-secreting tumors of the ovary or adrenal gland. Although rare, it is important to consider this diagnosis in patients with serum testosterone concentrations greater than 7 nmol/l. A 35-year-old woman who presented with hirsutism, amenorrhea and acanthosis nigricans is described. The endocrine abnormalities included a serum testosterone concentration of 9 nmol/l and overt type II diabetes mellitus. Imaging studies, including magnetic resonance imaging and Doppler ultrasonography, did not disclose a secreting tumor. After cyproterone acetate was prescribed the serum testosterone concentration returned to normal. The recent application of modern, high-resolution diagnostic ultrasonography and magnetic resonance imaging enabled a morphologically based diagnosis in a case of severe hyperandrogenism, with no need for invasive procedures. The therapeutic response to antiandrogens is reassuring.

Acanthosis Nigricans↗
PubMedDate not supplied

Malignant acanthosis nigricans with liver secondaries from an occult primary adenocarcinoma of gastrointestinal tract.

A 38-year-old female presented with hyperpigmented velvety plaques on the nape and the sides of the neck with diffuse pigmentation of the face and flexures suggestive of acanthosis nigricans. The dorsa of both the hands showed increased rugosity, hyperpigmentation and hyperkeratosis of the palms, suggestive of tripe palms. Investigations revealed multiple secondaries in the liver. Histopathology showed the secondaries to be from adenocarcinoma of the gastrointestinal tract.

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