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PubMed1985

Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: pediatric perspective and natural history.

We studied the syndrome of acanthosis nigricans, obesity, insulin resistance, and hyperandrogenemia in 22 patients. Although isolated case reports in adolescents have appeared, this syndrome has not received full recognition as a pediatric entity. Our patients (17 girls, five boys) had a mean weight 5.7 SD above the mean for age, although mean height was only 0.5 SD above the mean for age. All patients had acanthosis nigricans. Their insulin resistance was significantly greater than that in a control group with comparable obesity. Fasting insulin concentration was 5.25 microU/ml in lean controls, 19.6 microU/ml in obese controls, and 49.8 microU/ml in study patients (P less than 0.002). Mean glucose disappearance rate during an insulin tolerance test was 6.7%/min in lean controls, 5.19%/min in obese controls, and 2.35%/min in study patients (P less than 0.02). After menarche, mean plasma testosterone concentration was 106 ng/dl, compared with less than 50 ng/dl in all lean and obese control patients. Data derived from our series of patients lead us to conclude that (1) this is a genetic syndrome, although the exact mode of inheritance is unclear; (2) the natural history of the syndrome invariably begins with the onset of obesity, followed by acanthosis nigricans that worsens with progressive weight gain; (3) acanthosis nigricans is thus a marker for hyperinsulinemia, which occurs before hyperandrogenemia; (4) hyperandrogenemia occurs only after menarche. Identification of this syndrome should permit monitoring for the development of hyperandrogenemia during puberty and determination of other affected family members.

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PubMed1989

Acanthosis nigricans: a cutaneous marker of tissue resistance to insulin.

Tissue resistance to insulin is a major feature underlying the development of acanthosis nigricans in many patients. We report two unusual cases of acanthosis nigricans with contrasting forms of insulin resistance and propose an algorithm for the evaluation of patients with acanthosis nigricans. Further, we present a schematic framework that emphasizes the role of insulin and insulin growth factors in the pathogenesis of acanthosis nigricans.

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PubMed1994

Case report: defective beta and alpha cell regulation in patients with hyperinsulinemia and acanthosis nigricans.

Beta cell hypersecretion is associated with the syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans. It is unknown whether concomitant alpha cell secretory dysfunction occurs in patients with this syndrome. The authors evaluated the gastroenteropancreatic hormones in four family members with varying degrees of the hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome. Gastroenteropancreatic hormones were measured during oral glucose tolerance test with and without subcutaneous octreotide injection. The study revealed that the administration of subcutaneous octreotide resulted in suppression of beta cell function (insulin and c-peptide) but had no effect or a delayed effect on alpha cell secretion (glucagon). Furthermore, the severity of glucagon abnormalities paralleled that of beta cell hypersecretion and the clinical and phenotypic manifestations of acanthosis nigricans in our four patients. We speculate that this alpha cell aberration could potentially be involved in the altered glucose homeostasis and perhaps the skin manifestations of this syndrome. Therefore, glucagon levels should be evaluated in the hormonal studies in patients with hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome.

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PubMed1992

Assessment of patients with acanthosis nigricans skin lesion for hyperinsulinemia, insulin resistance and diabetes risk.

Acanthosis nigricans is a skin lesion characterized by thickening and apparent darkening of the keratin layer of the skin, usually on the neck and axillae. Recent studies reveal that this disorder is directly associated with hyperinsulinemia. A major implication of hyperinsulinemia is insulin resistance--a primary factor in the development of type II diabetes mellitus. Prolonged hypersecretion of insulin presumably leads to pancreatic exhaustion and subsequent glucose intolerance that can progress to type II diabetes. Prospective studies of individuals with acanthosis nigricans have shown very high prevalence rates of type II diabetes. Prevalence studies among adolescents have shown that the lesion appears early in life and is a common finding in some ethnic groups. These data suggest that acanthosis nigricans is an easily detected empirical marker for elevated risk of type II diabetes. The lesion can appear long before the onset of glucose intolerance. Thus, including acanthosis nigricans screening in a comprehensive disease-prevention program can help identify people at risk for type II diabetes prior to the actual onset of glucose intolerance, as well as individuals with undiagnosed diabetes. Interventions that reduce insulin resistance include weight loss and regular physical activity.

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PubMed2005

Eyelid involvement in acanthosis nigricans: the importance of systemic screening.

A 53-year-old man presented with thickening and hyperpigmentation of the eyelids. After the diagnosis of acanthosis nigricans was made, further investigation of a possible underlying disorder, including biochemical and instrumental examinations, indicated the presence of glucose intolerance, which had been diagnosed 3 years after the clinical appearance of acanthosis nigricans. Eyelid involvement in acanthosis nigricans is rare. Ophthalmologists should be aware of the possibility that acanthosis nigricans can exist in the periocular area and perform a systemic assessment of the patient for the presence of an underlying condition.

Acanthosis Nigricans↗

PubMed1992

An association of acanthosis nigricans and Crouzon syndrome.

An 11-year-old Japanese female having acanthosis nigricans associated with Crouzon syndrome is reported. Crouzon syndrome is a craniostenotic craniofacial malformation associated with premature closure of selective calvarial sutures, exophthalmos, maxillary hypoplasia, and a beak-shaped nose. It is an autosomal dominant inherited disorder. Crouzon syndrome is one of the syndromes which may be associated with acanthosis nigricans. The association of acanthosis nigricans with Crouzon syndrome is assumed to be a rare abnormality, although the true frequency is uncertain. We have reviewed the reported cases of acanthosis nigricans associated with Crouzon syndrome and characteristics were discussed.

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PubMed1990

Acanthosis nigricans in obese women with the polycystic ovary syndrome: disease spectrum not distinct entity.

Fasting and stimulated insulin concentrations in four patients with acanthosis nigricans and polycystic ovary syndrome were compared with four patients, matched for weight and ovarian morphology, without acanthosis. The median fasting serum insulin concentrations were 114.2 and 25.1 mU/l in the respective groups (P = 0.02). One additional patient was investigated before and after an 18% increase in weight which resulted in a 170% increase in fasting insulin concentrations and the development of acanthosis nigricans. These observations suggest that there is variation between individuals in the degree of obesity that results in the development of acanthosis and that obese patients with this skin condition represent the severe end of the spectrum of the polycystic ovary syndrome.

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PubMed1994

Acanthosis nigricans caused by nicotinic acid: case report and review of the literature.

Drug-induced acanthosis nigricans has been reported in the literature. We present a patient with familial combined hyperlipidemia who developed nicotinic-acid-induced acanthosis nigricans. The literature on the cutaneous side effects of nicotinic acid as well as on the medications that can cause acanthosis nigricans is reviewed. Some hypotheses on the pathogenesis of nicotinic-acid-induced acanthosis are presented.

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PubMed1991

Coexistent urticaria pigmentosa, acromegaly and acanthosis nigricans.

We report a case of urticaria pigmentosa, acromegaly and acanthosis nigricans in a 25-year-old male. The patient exhibited multiple pigmented papules on the trunk and the extremities. Histological examinations of the papules revealed infiltrates of mast cells in the upper dermis. Ultrastructurally, the mast cells were fully matured and exhibited no atypical features. A typical appearance of acromegaly, frontal bossing, prominence of the jaw and bony overgrowth and cutaneous changes of acanthosis nigricans on the neck, the axillae and the groins were observed. Growth hormone hypersecretion and insulin resistance were detected in the patient. A pituitary tumor was found and resected surgically. After the operation, endocrinological abnormalities and cutaneous manifestations of acanthosis nigricans improved markedly. As far as we know, this is the first report of the coexistence of urticaria pigmentosa, acromegaly and acanthosis nigricans.

Acanthosis Nigricans↗

PubMedDate not supplied

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.

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PubMed1994

Acanthosis Nigricans among Native Americans: an indicator of high diabetes risk.

Prevalence of the skin lesion acanthosis nigricans was determined in two tribal communities in Texas and Nebraska. Thirty-eight percent of the Alabama-Coushatta tribe of Texas had acanthosis nigricans. Nineteen percent of Omaha and Winnebago tribal children had the skin lesion; the youngest children had the least acanthosis nigricans. Among weight-matched Alabama-Coushatta, fasting insulin concentrations were twofold higher in subjects with the lesion. It was concluded that acanthosis nigricans is highly prevalent among Native Americans and that its presence suggests insulin resistance. Thus, it may identify those with the highest risk for non-insulin-dependent diabetes mellitus in this population.

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PubMed1975

[Acanthosis nigricans associated with diffuse esophageal papillomatosis].

Two cases of acanthosis nigricans seen in 2 women, the characteristics of which were those of malignant forms, showed oesophageal involvment, the appearance of which was quite similar to that of the mucosal localisations of the syndrome. The authors discuss the features which distinguish the oesophageal localisation of acanthosis nigricans from other types of oesophageal acanthosis or papillomata. In one case, this type of acanthosis, seven years after its onset, was not associated with any detectable malignant change and in the other the cutaneous lesions were improved following surgery at which the associated gastric tumour was not removed.

Acanthosis Nigricans↗

PubMedDate not supplied

Acanthosis nigricans in association with congenital adrenal hyperplasia: resolution after treatment. Case report.

A case is described of a three-day-old female with salt wasting type of 21-hydroxylase deficient congenital adrenal hyperplasia who presented with acanthosis nigricans of both axillae. Following corticosteroid and mineralocorticoid therapy for disease, the acanthosis nigricans resolved. It is believed that this is the first reported case of acanthosis nigricans occurring in association with congenital adrenal hyperplasia, a phenomenon that resolved after treatment. We speculate that the acanthosis nigricans resulted from hyperandrogenemia or other unknown factors in our patient.

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PubMed2006

Malignant acanthosis nigricans and tripe palms associated with pancreatic adenocarcinoma.

Malignant acanthosis nigricans is a disease that has an abrupt onset and is most commonly associated with gastric adenocarcinoma. It also has occurred as a paraneoplastic phenomenon in other carcinomas. Malignant acanthosis nigricans can occur simultaneously, before, or after the onset of internal malignancy. Malignant acanthosis on the palms is referred to as tripe palms. We describe a rare association of oral malignant acanthosis nigricans and tripe palms secondary to an underlying pancreatic adenocarcinoma.

Acanthosis Nigricans↗

PubMed1988

Improved acanthosis nigricans with lipodystrophic diabetes during dietary fish oil supplementation.

Acanthosis nigricans is well recognized in its clinical association with several types of insulin-resistant syndromes, and skin involvement is usually unresponsive to local treatment or management of diabetes. A young woman with a lipodystrophic form of diabetes, hypertriglyceridemia, and severe generalized acanthosis nigricans was placed on a diet with fat supplementation in the form of omega-3-fatty-acid-rich fish oil. She was observed to have striking improvement in the appearance and extent of acanthosis nigricans while receiving this regimen. This occurred despite continued therapy with niacin (nicotinic acid), an agent associated with acanthosis nigricanslike skin changes.

Acanthosis Nigricans↗

PubMed1985

Acanthosis nigricans and insulin resistance associated with hypothyroidism.

An obese 15-year-old boy with a one-year history of acanthosis nigricans was found to have primary hypothyroidism, with a thyrotropin level in excess of 50 microU/mL. At the same time, he was found to have subclinical insulin resistance. Therapy with thyroxine resulted in weight loss, reversal of hyperinsulinemia, and resolution of the acanthosis nigricans. Hypothyroidism can be added to the list of endocrine diseases associated with acanthosis nigricans. This is unlikely to be a direct effect of the hypothyroid state, but may instead be an indirect action mediated through obesity and subsequent insulin resistance. Insulin resistance and hyperinsulinemia seem to be commonly associated with (and perhaps causative of) the acanthosis nigricans that is seen in many endocrine diseases.

Acanthosis Nigricans↗

PubMed1994

The hyperandrogenic-insulin-resistant acanthosis nigricans syndrome: therapeutic response.

The hyperandrogenic-insulin-resistant acanthosis nigricans syndrome affects between 2% and 5% of hirsute women and is characterized by INS resistance, elevated INS levels, acanthosis nigricans, and androgen excess. These patients' response to therapy is unclear, although long-acting GnRH-a suppression has been proposed. The objective of this study was to determine the success of OC in suppressing the hyperandrogenemia of five patients with the hyperandrogenic-insulin-resistant acanthosis nigricans syndrome and the subsequent response to GnRH-a suppression of those women failing initial therapy. After 6 months of OC and SPA therapy, four patients experienced adequate suppression of free T, an increase in SHBG levels, and a subjective improvement in hair growth rate. Two also reported an improvement in hair texture. The total and free T levels in the fifth patient did not suppress after 8 months of OC therapy. Nevertheless, in this patient the administration of a GnRH-a along with hormonal replacement and SPA adequately suppressed free and total T, increased SHBG, and dramatically decreased the shaving interval. In conclusion, although GnRH-a suppression and hormonal replacement can be helpful in patients not responding to standard therapy, the majority of patients with the hyperandrogenic-insulin-resistant acanthosis nigricans syndrome will respond favorably to OC treatment. It is also clear that although hyperinsulinemia augments LH-stimulated androgen biosynthesis in vivo, it does not appear to be able to initiate or maintain androgen production in the absence of adequate gonadotropin stimulation.

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PubMed1997

[Scleredema, acanthosis nigricans and IgA/Kappa multiple myeloma].

BACKGROUND: Scleredema is an uncommon disease of unknown origin. Characteristic thick skin with symmetrical diffuse induration develops. The infiltration begins on the face and neck then extends to the root of the upper limbs and trunk. There are three clinical types of scleredema. The first is preceded by an upper airway infection and progresses rapidly before regressing spontaneously within a few months. The second type is associated with chronic diabetes. The third type is associated with monoclonal gammapathy, rarely of myelomatous type, and develops insidiously. Acanthosis nigricans can be a paraneoplastic syndrome, often associated with a gastrointestinal cancer. Few cases associating scleredema and acanathosis nigricans have been reported. CASE REPORT: A 56-year old woman had developed scleredema over the last 6 years when acanthosis nigricans appeared together with IgA kappa multiple myeloma. Treatment with melphalan and prednisolone was effective against the myeloma as well as the scleredema and acanthosis nigricans. DISCUSSION: Only five cases of associated scleredema and multiple myeloma have been reported, four with kappa IgG myeloma and one with IgA myeloma. An association between acanthosis nigricans and sclerederma could be coincidental although the fact that the different manifestations regressed together after the myeloma treatment would suggest some relationship between these three diseases.

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