Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In six patients with acanthosis nigricans variable degrees of glucose intolerance, hyperinsulinemia and marked resistance to exogenous insulin were found. Studies of insulin receptors on circulating monocytes suggest that the insulin resistance in these patients was due to a marked decrease in insulin binding to its membrane receptors. When these patients were fasted, there was a fall in plasma insulin but no increase in insulin binding, suggesting that the receptor defect was not secondary to the hyperinsulinemia. The clinical features shared by these cases and several similar ones previously reported may be divided into two unique clinical syndromes: Type A, a syndrome in younger females with signs of virilization or accelerated growth, in whom the receptor defect may be primary, and Type B, a syndrome in older females with signs of an immunologic disease, in whom circulating antibodies to the insulin receptor are found.
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PMID:The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. 17 81

We have previously described a group of young females with virilization, acanthosis nigricans, insulin resistance, and markedly decreased binding of insulin to its receptor (syndrome of insulin resistance and acanthosis nigricans type A). The present report concerns a 15-yr-old female with clinical features indistinguishable from the type A patients, including virilization, acanthosis nigricans, and extreme resistance to endogenous and exogenous insulin. Insulin levels were 400-650 microU/ml while fasting and were over 2200 microU/ml when stimulated. Proinsulin was less than 10% of the total immunoassayable insulin. In distinct contrast to the type A patients, insulin receptors on cells from this patient were entirely normal on the basis of specificity, negative cooperativity, affinity, concentration, and interaction with antiinsulin receptor antibodies. These findings suggest the presence of an intracellular defect as the cause of the observed insulin resistance.
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PMID:Insulin resistance, acanthosis nigricans, and normal insulin receptors in a young woman: evidence for a postreceptor defect. 40 Jul 28

The syndrome of type A insulin resistance is encountered in young women and is characterized by glucose intolerance or frank diabetes mellitus, endogenous hyperinsulinism, insensitivity to insulin administration, acanthosis nigricans and virilization. The insulin resistance is due to reduced cellular insulin binding because of a lack of or defective binding sites and/or because the interaction with the tyrosine kinase of the beta-subunit is hindered. This study was undertaken to find out whether hyperglycaemia in these patients may be influenced by the administration of recombinant human insulin-like growth factor I which exerts insulin-like effects through the insulin receptor as well as the type 1 insulin-like growth factor I receptor. Recombinant human insulin-like growth factor I was intravenously administered in two subsequent doses of 100 micrograms/kg body weight to three women with type A insulin resistance. An immediate but slow fall of blood glucose was observed. The glucose disappearance rate was 28.0 mumol/min, i.e. considerably lower than that seen in healthy subjects. The markedly elevated insulin and C-peptide levels fell in a parallel manner to blood glucose but not to normal levels. The results show that recombinant human insulin-like growth factor I, presumably by reacting with the type 1 insulin-like growth factor receptor, can normalize serum glucose levels in patients with severe insulin resistance at least for several hours. We suggest that the potential or recombinant human insulin-like growth factor I to control hyperglycaemia in type A insulin resistant patients should be explored in more depth.
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PMID:Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance. 195 1

The most common signs of androgen excess in women are acne, alopecia, and hirsutism. Less common manifestations include android obesity, virilization, and acanthosis nigricans. These changes appear to be the result of excessive androgen production or increased target organ sensitivity. To evaluate excessive androgen production, an androgen screening protocol is recommended that includes measurement of dehydroepiandrosterone sulfate, testosterone, androstenedione, prolactin, follicular stimulating hormone, and luteinizing hormone. When androgen excess is confirmed, dexamethasone suppression is recommended to determine the source of the androgen(s). Once excessive androgen production is confirmed, more specific therapies can be administered.
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PMID:Diagnostic approach to androgen disorders in women: acne, hirsutism, and alopecia. 214 37

Thirteen patients with the syndrome of acanthosis nigricans and insulin resistance are described. They all had a combination of dermatoses related to hyperandrogenism (cutaneous virilism): hirsuties (II), acne vulgaris (6), hidradenitis suppurativa (5) and androgenic alopecia (4). In addition, 9 out of 13 had keratosis pilaris. The patients had raised fasting plasma insulin levels compared with matched normal controls (P less than 0.01) and increased insulin resistance (P less than 0.02). Insulin resistance correlated with total serum testosterone (rs = 0.65; P less than 0.02).
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PMID:Acanthosis nigricans, insulin resistance and cutaneous virilism. 329 47

Nine women with acanthosis nigricans and masculinization, who did not appear to have any of the reported syndromes associated with acanthosis nigricans, were studied to characterize the clinical, biochemical, and ovarian morphologic features of their disorders. These patients had the clinical and biochemical profiles of polycystic ovarian disease. All acanthosis nigricans subjects had significant insulin resistance when insulin binding to both circulating monocytes and erythrocytes was compared to the control subjects. Microscopic examination of the ovaries revealed no evidence of recent normal ovulation, sclerosis of the ovarian cortex, follicle cysts, and stromal hyperthecosis. The authors conclude that ovarian stromal hyperthecosis and insulin resistance are consistent findings in the present type of patient. This study provides further evidence supporting a relationship between insulin resistance and human ovarian function.
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PMID:Clinical, biochemical, and ovarian morphologic features in women with acanthosis nigricans and masculinization. 390 Aug 41

The syndrome of type A insulin resistance in nonobese women is characterized by hyperinsulinemia, resistance to exogenous insulin, acanthosis nigricans, polycystic ovaries, and masculinization. Insulin binding to intact circulating monocytes and cultured Epstein-Barr virus-transformed B-lymphocytes derived from these patients is decreased in some patients but normal in others. Insulin receptors consist of two subunits; the alpha-subunit contains the insulin-binding site, and the beta-subunit possesses an insulin-sensitive tyrosine-specific protein kinase activity. Insulin binding to circulating monocytes was decreased in five patients, suggesting a decreased number of alpha-subunits on the surface of cells from the patients with type A insulin resistance. In the present work, we demonstrated that there is a proportional decrease in the function of the beta-subunit (i.e. tyrosine kinase activity) in cells from these subjects. In one patient, insulin binding to circulating monocytes was normal, and the insulin-stimulated tyrosine kinase activity of the receptors was normal as well. In separate studies, using cultured Epstein-Barr virus-transformed lymphocytes from the same six patients with type A extreme insulin resistance, the results were similar, in that the functions of the alpha- and beta-subunits of the receptor from these cells correlated. Though heterogeneity among the six patients with type A extreme insulin resistance at the level of the kinase activity of their insulin receptors was demonstrated, it does not appear that a selective defect in beta-subunit phosphorylation per se can be implicated in the mechanisms of insulin resistance of these patients. These findings are distinct from our previously reported patient with normal binding and very low insulin-stimulated phosphorylation of the beta-subunit of the receptor of circulating monocytes, in whom it was speculated that selective reduction in beta-subunit phosphorylation was responsible for insulin resistance.
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PMID:Tyrosine kinase activity of the insulin receptor of patients with type A extreme insulin resistance: studies with circulating mononuclear cells and cultured lymphocytes. 633 31

[125I]Insulin binding has been studied in two patients with extreme insulin resistance using cultured B-lymphocytes transformed with Epstein-Barr virus. A cell line from a female infant with leprechaunism had insulin binding which was decreased 90% below the lower limit of normal. Lymphocytes from a young woman with type A extreme insulin resistance (associated with acanthosis nigricans and virilization) had insulin binding which was 80% depressed. In both cases, the defect in binding resulted from a decrease in the number of receptors per cell. The remaining receptors had normal properties, including a normal affinity for insulin and a normal specificity for insulin analogs. Insulin binding in cultured lymphocytes from these two insulin-resistant patients was also inhibited normally by antibodies to the insulin receptor. Immunological assays using anti-receptor antibodies confirmed the conclusion that the number of receptors was decreased. Affinity labeling of the leprechaun insulin receptor with [125I]insulin demonstrated the existence of an alpha-subunit with apparently normal molecular weight (130,000 daltons). However, the number of receptor molecules per cell appeared reduced.
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PMID:Decreased insulin binding in cultured lymphocytes from two patients with extreme insulin resistance. 703 23

Hirsutism, polycystic ovaries, and elevated levels of plasma testosterone are characteristic clinical features in women with extreme insulin resistance and acanthosis nigricans. Extreme insulin resistance resulting from autoantibodies to the insulin receptor (type B extreme insulin resistance) had been considered an exception to this generalization. A woman with type B extreme insulin resistance developed clinical evidence of masculinization in association with a markedly elevated level of plasma testosterone (1000 ng/dL). In nine women with autoantibodies to the insulin receptor, excessive ovarian production of testosterone was a common feature among the premenopausal patients. Postmenopausal patients rarely developed elevated levels of plasma testosterone, presumably as a result of ovarian failure. Overproduction of testosterone may result from a direct effect of hyperinsulinemia on the ovary.
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PMID:Insulin resistance associated with androgen excess in women with autoantibodies to the insulin receptor. 714 93

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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PMID:Ovarian pathology associated with insulin resistance and acanthosis nigricans. 730 Dec 47


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