1/12. association of metformin and pregnancy in the polycystic ovary syndrome. A report of three cases.BACKGROUND: infertility is a common manifestation of the polycystic ovary syndrome (PCOS), a condition characterized by chronic anovulation, hyperinsulinemia and hyperandrogenism. Hyperinsulinemia leads to increased ovarian androgen production, resulting in follicular atresia and anovulation. metformin, a medication that improves insulin sensitivity and decreases serum insulin levels, restores menstrual cyclicity and ovulatory function and may improve fertility rates in women with PCOS. We present three consecutive cases from our clinic that support this premise. CASES: Three patients were seen in the reproductive endocrinology clinic with documented PCOS, long-standing infertility and clinically diagnosed insulin resistance. The first patient had hyperandrogenic, insulin-resistant acanthosis nigricans syndrome and had been resistant to multiple courses of clomiphene citrate; the second exhibited hypertension, hyperlipidemia and glucose intolerance along with anovulation; and the third presented with poorly controlled type 2 diabetes and a desire to conceive. Each patient received metformin, which led to restoration of menstrual cyclicity and conception in all three cases. CONCLUSION: These three patients reflect the heterogeneous nature of PCOS, and treating their underlying insulin resistance with metformin resulted in pregnancy. These findings suggest that metformin may be a useful adjunct for treatment of infertility in patients with PCOS.- - - - - - - - - - ranking = 1keywords = hyperinsulinemia (Clic here for more details about this article) |
2/12. polycystic ovary syndrome: a case presentation.polycystic ovary syndrome (PCOS) is a disorder of excessive adrenal hormone production that results in characteristic features. It is associated with hyperinsulinemia and, if left untreated, carries a risk for developing such complications as diabetes and heart disease. The clinical features are described here by means of a case presentation. Using the Ferriman-Gallwey score, the degree of hirsutism is identified. Differential diagnoses and recommended treatments are discussed. The role of the advanced practice nurse in the diagnosis and care of patients with PCOS is included.- - - - - - - - - - ranking = 1keywords = hyperinsulinemia (Clic here for more details about this article) |
3/12. insulinoma presenting with hyperandrogenism: a case report and a literature review.An 18-year-old woman presented with a 6-month history of amenorrhoea and hyperandrogenism. Three months later she developed several episodes of fasting hypoglycaemia and was subsequently diagnosed with an insulinoma. Hyperinsulinaemia was observed in association with an elevated serum testosterone level. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS). Polycystic ovarian syndrome is unusual in a patient having an insulinoma. The rarity of this association may be the result of the late age of onset of this type of tumour, intermittent secretion of excessive insulin by the tumour, the degree of hyperinsulinism or other factors extrinsic to the insulin receptor that may facilitate insulin activity. However, we could not discover how our patient differs in having had PCOS from the majority of women with insulinoma who do not. If other patients with insulinoma are subsequently found to have hyperandrogenism, then this tumour might be added to the differential diagnosis of causes of anovulatory cycles and hyperandrogenaemia, although rare the association would be uncommon.- - - - - - - - - - ranking = 0.104320310313keywords = hyperinsulinism (Clic here for more details about this article) |
4/12. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective.The interaction of insulin with its cell surface receptor is the first step in insulin action and the first identified target of insulin resistance. The insulin resistance in several syndromic forms of extreme insulin resistance has been shown to be caused by mutations in the receptor gene. We studied 8 female patients with the type A form of extreme insulin resistance and 3 patients (2 male and 1 female) with the Rabson-Mendenhall syndrome and followed the natural history of these patients for up to 30 years. The 11 patients ranged in age from 7 to 32 years at presentation. All 11 patients had extreme insulin resistance, acanthosis nigricans, and hyperandrogenism in the female patients, and all but 1 were of normal body weight. This phenotype strongly predicts mutations in the insulin receptor: of the 8 patients studied, 7 were found to have mutations. Similar results from the literature are found in other patients with type A and Rabson-Mendenhall syndromes and leprechaunism. The hyperandrogenic state resulting from hyperinsulinemia and insulin resistance in these patients was extreme: 6 of 8 patients had ovarian surgery to correct the polycystic ovarian syndrome and elevation of serum testosterone. By contrast, a larger group of insulin-resistant patients who were obese with hyperandrogenism, insulin resistance, and acanthosis nigricans (hair-AN syndrome) did not have a high probability of mutations in the insulin receptor. The morbidity and mortality of these patients were high: 3 of 11 died, 9 of 11 were diabetic and 1 had impaired glucose tolerance, and 7 of 9 patients had 1 or more severe complication of diabetes. Our literature review revealed that the mortality of leprechaunism is so high that the term leprechaunism should be restricted to infants or young children under 2 years of age. Analogous to patients with the common forms of type 2 diabetes, these patients had a heterogeneous course. In 2 patients who were able to maintain extremely high endogenous insulin production, the fasting blood glucose remained normal even though post-glucose-challenge levels were elevated. Most patients, however, required large doses of exogenous insulin to ameliorate the severe hyperglycemia. Preliminary results of a recent study suggest that recombinant leptin administration may benefit these patients with severe insulin resistance.- - - - - - - - - - ranking = 1keywords = hyperinsulinemia (Clic here for more details about this article) |
5/12. Follow-up study of two sisters with type A syndrome of severe insulin resistance gives a new insight into PCOS pathogenesis in relation to puberty and pregnancy outcome: a case report.We report two sisters with profound insulin resistance associated with a novel heterozygous missense mutation in exon 19 (His1130Arg) of the insulin receptor gene. The eldest was seen after puberty at age 15 and she presented a severe form of polycystic ovary syndrome (PCOS) with biological hyperandrogenism (HA) mimicking a virilizing tumour. However, she has been able to ovulate under clomiphene citrate (CC) and to achieve two uneventful pregnancies. The patient had no glucose tolerance abnormality during pregnancies. The outcome of pregnancy was good except for a low birthweight. The youngest sister was seen earlier in life (at age 11) before puberty. First, she developed polycystic ovaries (PCO), seen under ultrasound scan, and later also developed full PCOS. This second finding gave us the opportunity to observe that PCO developed before and at the beginning of puberty despite low LH levels. We postulate that the development of PCO was the consequence of an LH-independent intra-ovarian HA likely induced by the severe hyperinsulinism in the context of genetic abnormalities.- - - - - - - - - - ranking = 0.104320310313keywords = hyperinsulinism (Clic here for more details about this article) |
6/12. insulin resistance, acanthosis nigricans, and polycystic ovaries associated with a circulating inhibitor of postbinding insulin action.A 21-yr-old moderately obese woman with hirsutism, acanthosis nigricans, and oligomenorrhoea was diagnosed as having polycystic ovary syndrome. Despite hyperinsulinemia, binding of insulin to her red cells was within the range for normal, young adult subjects. Her serum did not bind or degrade [125I]insulin or alter its binding to fat cells, and was negative for insulin receptor antibodies. However, her serum caused a dose-dependent inhibition of insulin-stimulated lipogenesis (conversion of [3-3H]glucose to [3H]lipid) in rat fat cells significantly greater than that produced with control serum (relative potency, 3.5:1) and (at a 1:20 dilution) markedly impaired the response of both lipogenesis and 2-deoxy-D-glucose uptake to maximum concentrations of insulin. After the patient was treated with clomiphene for 4 months, her menses resumed, hair growth slowed, fasting blood glucose and plasma insulin concentrations decreased, and serum inhibitory activity decreased to the control range. serum inhibitory activity was stable to freezing and thawing and to heating at 56 C for 30 min, and could be extracted into acid-ethanol. By dialysis, its mol wt was below 1000, whereas by ultracentrifugation, it was above 3500; both high and low mol wt forms were detected after Sephadex G-50 gel chromatography of serum, suggesting that the inhibitor was of low mol wt but loosely bound to a higher mol wt component in serum. These findings indicate that insulin resistance in this patient with acanthosis nigricans and polycystic ovaries could be attributed to a circulating low mol wt inhibitor of postbinding insulin action.- - - - - - - - - - ranking = 1keywords = hyperinsulinemia (Clic here for more details about this article) |
7/12. Familial hyperinsulinemia complicated by extreme insulin resistance during pregnancy: a probable postreceptor defect.Detailed studies of a family with hyperinsulinemia are reported. The index patient, a 30-yr-old woman with polycystic ovary syndrome, presented with gestational diabetes which was completely resistant to insulin in the presence of severe endogenous hyperinsulinemia. Sensitivity to insulin was regained after delivery. Therapy with cyproterone acetate and ethinyl estradiol for hirsutism exacerbated the hyperinsulinemia toward the levels occurring in pregnancy, with a concomitant deterioration of glucose tolerance. Five other members of her family also were found to have hyperinsulinemia together with high concentrations of circulating c-peptide. Antibodies to insulin and to insulin receptors were not detected, insulin antagonists were not increased, and insulin degradation in the circulation was normal. Insulin extracted from the patient's serum was identical to normal insulin by the criteria of Sephadex chromatography, placental membrane insulin receptor binding, and stimulation of 2-deoxyglucose uptake in isolated rat adipocytes. Although [125I]insulin binding to erythrocytes of all family members and to the patient's placental membranes was markedly reduced, binding to fibroblast cultures from the patient was normal. Insulin-stimulated glucose transport in these fibroblasts also was normal, but there was a mild (20%) reduction in the concentration of cytochalasin b-binding sites in erythrocyte ghosts. insulin resistance in this family may be due to a partial defect distal to the insulin receptor. This is asymptomatic unless metabolic stresses (pregnancy or steroid administration) are superimposed.- - - - - - - - - - ranking = 8keywords = hyperinsulinemia (Clic here for more details about this article) |
8/12. A case of insulin resistant diabetes with possible antibodies to insulin receptors.A case of a 19-year-old, non-obese female with insulin resistant diabetes mellitus and polycystic ovary syndrome was reported. The maximal insulin requirement attained 360 units per day, but a satisfactory control of diabetes did not follow. The patient's serum contained not only anti-insulin antibodies, but also possible anti-insulin receptor antibodies which were demonstrated by the 125I-insulin binding test using insulin receptors derived from human placental plasma membrane. The insulin resistance in this case was assumed to be caused primarily by possible blocking antibodies to insulin receptors and partly by anti-insulin antibodies because of the following observations. First, high serum free insulin (165 microunits/ml) without hypoglycemia indicates the presence of insulin resistance due to other factors than antiinsulin antibodies. Second, the titer of 125I-insulin binding capacity of serum was not unusually higher than those seen in chronically insulin-treated diabetics. Third, immunologically heterospecies insulin (fish insulin) was also ineffective. The clinical features such as absence of ketoacidosis and association with polycystic ovary syndrome resemble those of an unique diabetic syndrome reported previously though acanthosis nigricans and endogenous hyperinsulinemia were not found in this case. Her insulin resistance remitted spontaneously and over the next 18 months' observation, her diabetes remained regulated without insulin therapy.- - - - - - - - - - ranking = 1keywords = hyperinsulinemia (Clic here for more details about this article) |
9/12. insulin resistance with acanthosis nigricans and acral hypertrophy.Two patients are described with obesity, acanthosis nigricans, acral hypertrophy, basal hyperinsulinism and exaggerated insulin responses to oral glucose. One patient, a diabetic female showed features of virilisation due to polycystic ovarian disease and underwent gonadectomy with some resolution of her androgenisation and acanthosis nigricans. Binding of labelled insulin to erythrocytes was significantly decreased in both patients compared with normal or obese control subjects. In contrast, the receptor concentration in adipose tissue obtained from the patient undergoing gonadectomy was higher than seen in obese control subjects. Thus, somatic growth may be stimulated by insulin in some tissues in these hyperinsulinaemic patients due to relative preservation of receptor numbers.- - - - - - - - - - ranking = 0.104320310313keywords = hyperinsulinism (Clic here for more details about this article) |
10/12. Impaired insulin degradation in a patient with insulin resistance and acanthosis nigricans.The kinetics of plasma insulin were studied in a 14 year old girl with the syndrome of insulin resistance and acanthosis nigricans. The clearance of plasma insulin was found to be strikingly reduced (135 ml/min . m2 versus 456 /- 22 in 17 normal control subjects), whereas the basal systemic insulin delivery rate was increased about 10-fold (25.5 mU/min . m2 versus 2.6 /- 0.3 in normal subjects). Thus, reduced insulin clearance and excessive posthepatic delivery of the hormone both contributed to the severe fasting hyperinsulinemia (218 microunits/ml) associated with the other clinical features of the syndrome (glucose intolerance, primary amenorrhea, polycystic ovaries, hirsutism). Following ovarian wedge resection, insulin clearance rose to 264 ml/min . m2, and insulin delivery fell to 9.8 microunits/ml min . m2. The resulting abatement of the patient's hyperinsulinism (fasting plasma insulin = 37 microunits/ml) was accompanied by the appearance of menses, normalization of glucose tolerance, and amelioration of the acanthosis. The improvement in menstrual function and acanthosis, however, was not sustained. This case provides evidence for interdependence of insulin action and insulin degradation in humans.- - - - - - - - - - ranking = 1.104320310313keywords = hyperinsulinemia, hyperinsulinism (Clic here for more details about this article) |
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