1/210. acanthosis nigricans and wart-like lesions associated with metastatic carcinoma of the stomach. A 63-year-old white man developed malignant acanthosis nigricans one year after a hemigastrectomy for adenocarcinoma of the stomach. Multiple "wart-like" lesions involving the dorsa of the hands, arms and trunk were also present. The malignant acanthosis nigricans in the patient appears to have paralledled the course of the metastatic gastric adenocarcinoma. Discrete verrucous lesions can occur in malignant acanthosis nigricans which histopathologically may show either squamous or basal cell hyperplasia. ( info) |
2/210. pregnancy after treatment with the insulin-sensitizing agent troglitazone in an obese woman with the hyperandrogenic, insulin-resistant acanthosis nigricans syndrome. OBJECTIVE: To report a case of unassisted pregnancy after 5 months of troglitazone treatment in a severely hyperandrogenic, insulin-resistant woman with acanthosis nigricans (hair-AN) previously managed with depot leuprolide acetate (LA) plus oral contraceptive and dexamethasone therapy. DESIGN: Case report. SETTING: Private infertility clinic. PATIENT(S): A 28-year-old African-American woman with excessive obesity (body mass index = 42 kg/m2) and hair-AN syndrome. INTERVENTION(S): Androgen suppression with depot LA plus oral contraceptive and dexamethasone therapy, troglitazone treatment resulting in normalization of fasting insulin and testosterone, spontaneous menses, and an unassisted pregnancy. MAIN OUTCOME MEASURE(S): luteinizing hormone and testosterone concentrations, fasting insulin and glucose levels, insulin-glucose ratios, hCG levels, and ultrasound examinations. RESULT(S): Spontaneous menses followed by an intrauterine pregnancy after 5 months of treatment with troglitazone, an insulin-sensitizing agent, in a woman with severe hair-AN syndrome whose hyperandrogenism previously could be normalized only with depot LA plus oral contraceptive therapy and dexamethasone. CONCLUSION(S): Troglitazone treatment resulted in attenuation of both hyperinsulinemia and hyperandrogenism in an obese woman with hair-AN and resulted in resumption of menses and a spontaneous pregnancy. ( info) |
| We report on a 27-year-old man with acanthosis nigricans (AN) associated with severe obesity, insulin resistance and hypothyroidism. A very low-calorie diet treatment decreased his weight and then ameliorated the insulin-resistant state. These effects were followed by remarkable improvement of the AN prior to the correction of the hypothyroidism. This confirms that AN may be mainly attributed to insulin resistance rather than hypothyroidism per se. ( info) |
4/210. Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. We previously discovered a novel missense mutation (Lys650Met) in the tyrosine kinase domain of the fibroblast growth factor receptor 3 (FGFR3) gene in four unrelated individuals with a condition we called "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) [Tavormina et al., 1999: Am. J. Hum. Genet. 64:722-731]. Here we present a more detailed clinical account of the SADDAN phenotype. The FGFR3 Lys650Met mutation results in severe disturbances in endochondral bone growth that approach and overlap those observed in thanatophoric dysplasia, type I. However, this mutation is most often compatible with survival into adulthood. Other unusual bone deformities, such as femoral bowing with reverse (i.e., posterior apex) tibial and fibular bowing and "ram's horn" bowing of the clavicle, are also seen in some patients. In addition to skeletal dysplasia, progressive acanthosis nigricans, and central nervous system structural anomalies, seizures and severe developmental delays are observed in surviving SADDAN patients. Despite its location within the same FGFR3 codon as the thanatophoric dysplasia type II mutation (Lys650Glu) and a similar effect on constitutive activation of the FGFR3 tyrosine kinase, the Lys650Met is not associated with cloverleaf skull or craniosynostosis. ( info) |
| The presence of insulin receptor antibodies is a rare cause of insulin resistance. patients usually have a combination of hyperglycemia, insulin resistance, acanthosis nigricans, and autoimmune features. We report a patient with systemic lupus erythematosus and severe insulin resistance due to insulin receptor antibodies. The most striking aspect of the clinical presentation is the resistance to insulin therapy, with our patient unresponsive to doses of up to 154,075 units in a day. While on a low-dose glucocorticoid therapy, the patient had clinical improvement, and glucose levels subsequently became normal even without insulin and glucocorticoid. ( info) |
| We present a case of malignant acanthosis nigricans (AN) that initially manifested in the oral cavity. In the present report, the patient had typical clinical and histological findings of oral and esophageal AN, with subtle skin changes, associated with a gallbladder adenocarcinoma. The importance of the clinical oral examination is emphasized because the recognition of oral lesions led to the diagnosis of AN and to the following detection of the internal malignancy. Since the tumours associated with AN are highly malignant, it is of the utmost importance to recognize the skin and mucous membrane changes in adults. ( info) |
| We describe a woman with the syndrome characterised by hyperandrogenism, insulin resistance and acanthosis nigricans (the hair-AN syndrome), and an associated insulinoma (islet B-cell tumour), whose signs and symptoms cleared after partial pancreatectomy. ( info) |
8/210. A gene for congenital generalized lipodystrophy maps to human chromosome 9q34. Congenital generalized lipodystrophy (CGL, Berardinelli-Seip syndrome, OMIM # 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (theta(max) = 0.05). There was evidence for genetic heterogeneity (alpha = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL1 critical region harbors a plausible candidate gene encoding the retinoid x receptor alpha (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue. ( info) |
| acanthosis nigricans is an uncommon skin condition characterized by hyperkeratosis and skin hyperpigmentation. Most causes are benign, but it may also be associated with gastrointestinal and other malignancies. When associated with malignant disease, the skin pathology may be more severe and treatment often unsuccessful. We describe a 66-year-old man with acanthosis nigricans associated with carcinoma of the stomach, with distressing generalized cutaneous, perioral and perineal disease, whose skin condition resolved completely with combination chemotherapy. In patients with malignant acanthosis, chemotherapy may relieve many of the distressing cutaneous symptoms. A close liaison between gastroenterologists, dermatologists and oncologists is required. ( info) |
| The association of acanthosis nigricans (AN) with the sign of Leser-Trelat (LT) and gastric carcinoma is rare. Our patient was a 69-year-old man, who presented with hematemesis; a stage-IV poorly differentiated, diffuse-type, adenocarcinoma of the gastric antrum was diagnosed. The AN was striking, with florid cutaneous papillomatosis that also involved the mucous membranes of the mouth and eyelids, and keratoderma. AN and the sign of LT predated tumor detection by 6 months and regressed after chemotherapy in parallel with reduction of the tumor load, demonstrating the dermatoses as paraneoplastic phenomena. The patient died 7 months after completion of chemotherapy. The coexistence of AN and the sign of LT should prompt a search for underlying malignancy. The pathogenesis of both dermatoses is discussed. ( info) |