[Congenital Hyperinsulinism: review of 12 Tunisian cases]

Congenital hyperinsulinism in infancy [CHI] is a heterogeneous disorder with respect to genetics and response to therapy. Data on CHI are sporadic in North African population. To characterize the clinical features and outcome of 12 Tunisian patients with CHI. data of patients diagnosed with CHI during the period 1989-2007 were retrospectively analyzed. Diagnosis was considered whenever hyperinsulinemia 10 UI/ml was concomitant to hypoglycemia<3mmol/l and/or high insulin to glucose ratio>0.3 and/or positif glucagon test. Transient causes of hypoglycemia, adrenal and growth hormone deficiency were excluded. There were nine infants diagnosed at a median age of 17 months and three newborns. Permanent hyperammoniemia, found in one patient, guided to leucine-sensitive hyperinsulinism. Seven patients presented with seizures, two with psychomotor delay and one with recurrent malaises. Among 42 assays of plasmatic insulin, when in hypoglycemia, 40% only were 10 U/ml. Three patients resisted to diazoxide and underwent subtotal pancreatectomy complicated by diabetes mellitus in two cases and persistent hypoglycemia in one patient. Histological examination concluded to diffuse hyperplasia of pancreatic cells. Diazoxide was discontinued in four out the eight responders patients. Four patients died, seven patients developed variable degrees of mental retardation and five suffered from epilepsy. Early onset forms were, as reported in the literature, mostly resistant to medical therapy. The high proportion of neurological sequelae is related to diagnosis delay or to a late surgery. We focus on the importance of a precocious diagnosis and aggressive treatment of hypoglycemia

[Indication of metformin in the management of hormonal dysfunction secondary to polycystic ovarian syndrome: prospective comparative study about 63 cases]

Polycystic ovarian syndrome [PCOS] is the most common hormonal dysfunction in women. It's a cause of female infertility by oligoanovulation, clinical and biochemical hyperandrogenism and polycystic ovaries. Weight loss, firstly proposed in overweight or obese patient suffering from PCOS, aims to reduce hyperinsulinism and hyperandrogenism. Recently, Metformin, an insulin sensitizer, has been proposed as an alternative first line treatment for polycystic ovarian syndrome by improving hyperinsulinemia and hyperandrogenism in these women. The aim of our study, and through a literature review, is to demonstrate if Metformin should be used as a first-line drug for infertile women with this syndrome or as an adjunction to Clomifene Citrate, the longest established treatment already used in this syndrome. A prospective comparative study including 63 patients with PCOS has been done during 2 years. Women were randomly allocated to clomifene + Metformin [Metformin group, Metformin took during 8 weeks, 850 mg twice a day, plus Clomifene 100 mg per day during five days] or Clomifene only [100 mg per day during five days]. All patients underwent a two- month's diet. The middle age was about 30.63 years and the body mass index [BMI] was about 29.88 kg/ m[2]. We noticed a 6.2% weight loss in both groups [a non significant difference in p=0.04]. The median of infertility period was about 2.49 years. The ovulation rate in the Metformin group was 53.12% [significant difference for inducing ovulation p=0.02] and 32.25% in Clomifene group [non-significant difference 0.07]. There was also a significant difference for ongoing pregnancies [p=0.04]. In fact, 11 on 32 patients [34%] achieved a full-term pregnancy in Metformin group versus only 4 ones on 31 patients [12.9%] in Clomifene group. Our conclusion is that Metformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement, excluding ART cycles

A utilização de agentes hipoglicemiantes no tratamento de pacientes com síndrome dos ovários policísticos / The use of hipoglycemic agents on the treatment of patients with polycystic ovary syndrome

A síndrome dos ovários policísticos é a mais comum afecção endócrina na idade reprodutiva, acometendo 5 a 10 porcento das mulheres. Caracteriza-se por anovulação crônica, anormalidades menstruais e hiperandrogenismo laboratorial e ou clínico. O principal distúrbio na fisiopatologia ainda é desconhecido, mas há importantes evidências de que a resistência insulínica, hiperandrogenismo e alterações na liberação pulsátil das gonadotrofinas estejam envolvidos. Além das gonodatrofinas, fatores de crescimento e outros peptídeos participam da regulação do desenvolvimento folicular ovariano e da esteroidogênese e podem ter participação na SOP. Além disso, sabe-se que muitas mulheres com esta síndrome têm resistência insulínica, que pode ser corrigida pelos agentes sensibilizadores do receptor de insulina. Nesta revisão, analisou-se a ação da tiazolidinediona rosiglitazona em amenizar a sintomatologia na SOP, corrigindo a hiperinsulinemia. Sugere-se, então, que a rosiglitazona é alternativa para a correção da resistência insulínica em mulheres com a síndrome dos ovários policísticos.

The polycystic ovary syndrome is the most common endocrine-gynecological disorder of premenopausal women, affecting 5 - 10 percent of this population. It is characterized by chronic anovulation, menstrual disturbance and laboratorial and or clinic hyperandrogenism. The primary pathophysiological defect is unknown, but important characteristics include insulin resistance, androgen excess and abnormal gonadotropin dynamics. Growth factors, such as IGF-I, and other peptides have also been shown to play an important role in the regulation of ovarian follicular maturation and steroidogenesis. These factors might have important role in PCOS. Furthermore, some patients with PCOS may have insulin resistance and the insulin-sensitizing drugs may correct this condition. In this review, we analyzed the action of the thiazolidinedione rosiglitazone on decreasing SOP symptoms and regulating hyperinsulism. Our review suggests that rosiglitazone is an alternative to ameliorate insulin resistance in women with polycystic ovary syndrome.

Uso de la metformina en pacientes con el síndrome del ovario poliquístico: [revisión] / Use of the metformina in patients with the syndrome of the poliquistic ovary: [review]

La metformina es un medicamento indicado para el tratamiento de la diabetes mellitus tipo II con una función renal normal. Ha sido usada, sin la aprobación de la Administración de Drogas y Alimentos de los EEUU, en pacientes con el síndrome del ovario poliquístico, como regulador del trastorno menstrual, tratamiento del hirsutismo e inductor de ovulación. Desde 1980, Burghen y colaboradores señalaron la asociación entre el hiperandrogenismo y la hiperinsulinemia en el síndrome del ovario poliquístico. El exceso de andrógenos, resultado del aumento de la insulina, deteriora la acción de ésta. Los efectos de la metformina en la disminución de la glucosa son consecuencia de una reducción en la producción de glucosa hepática y un aumento en su empleo. Este medicamento incrementa la mayoría de las acciones biológicas de la insulina en personas con resistencia a la insulina preexistente y disminuye la absorción intestinal de glucosa. Se concluye que la metformina es útil en la regulación el ciclo menstrual en comparación con el placebo; no es un tratamiento de primera elección en el hirsutismo y su uso como monoterapia en la inducción de la ovulación no demuestra sustancialmente mejoría en la tasa de embarazo clínico. La evidencia señala que la metformina asociada con el citrato de clomifeno induce la ovulación y mejora la tasa de embarazo clínico.

Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome

The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS) are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH) and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years) were treated with metformin (500 mg three times daily) for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women) and PCOS women during the late follicular (one sample) and luteal (3 samples) phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA), Duncan's test and Karl Pearson's coefficient of correlation (r). The endocrine study showed low progesterone level (4.9 ng/ml) during luteal phase in the PCOS women as compared with control (21.6 ng/ml). A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01) and between progesterone and LH (r = -0.56; P < 0.05) concentrations, and a positive correlation (r = 0.83; P < 0.001) was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml) in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.

Hiperinsulinismo neonatal persistente: Caso clínico y tratamiento médico con octreotide / Persistent neonatal hypoglycaemia: a clinical case treated with octreotide

El hiperinsulinismo neonatal constituye la causa más común de hipoglicemia persistente en el menor de 1 año. Existe una secreción inapropiada de insulina en condiciones de hipoglicemia debido a una alteración en el receptor de sulfonilurea en la célula beta pancreática. Se describe el caso de un recién nacido prematuro, pequeño para la edad gestacional, que presentó precozmente hipoglicemias de difícil manejo, requiriendo cargas de glucosa de hasta 26 mg/kg/min. Tras confirmar el diagnóstico se inició tratamiento médico con octreotide. Luego de 72 horas de iniciado el tratamiento se logró disminuir el aporte de glucosa endovenosa, suspendiéndolo a las 6 semanas. En el seguimiento no se han presentado complicaciones derivadas del tratamiento, su situación nutricional es adecuada y su desarrollo psicomotor es normal. El uso de octreotide debe ser considerado como alternativa terapéutica en niños con hiperinsulinismo persistente, evitando la cirugía que presenta alta morbimortalidad, especialmente en este grupo etario.

Efecto de la metformina sobre la resistencia insulínica en mujeres obesas y obesas hiperandrogénicas / Effects of metformin on insulin resistance in obese and hyperandrogenic women

Background: Metformin is a biguanide often used in obese diabetics that improves tissue sensitivity to insulin. Aim:To assess the effects of metformin on tissue insulin sensitivity in obese and byperandrogenic women. Patients and methods: Eight obese and eight obese and eight and hyperandrogenic women received metformin 850 mg orally during 12 weeks. Before and at the end of the treatment period, an insulin tolerance test to measure insulin sensitivity was performed and blood was drawn to measure sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), testosterone, triglycerides, total and HDL cholesterol. The free androgen index was calculated for each sample. Results: After metformin treatment, the insulin sensitivity index improved from 0.38 (0.05-0.5) to 0.43 (0.25-0.59) in obese and hyperandrogenic women. SHBG increased and total cholesterol and triglycerides decreased significantly in both groups. No other significant changes were observed. Conclusions: Metformin has a favorable effect on tissue sensitivity to insulin, SHBG and serum lipids in obese and hyperandrogenic women

Efecto contraregulador del glucagon en la hiperinsulinemia inducida / Effect of glucagon in induced hyperinsulinem

Estudiando al glucagon como una alternativa en el tratamiento de la hiperinsulinemia el problema fue si el glucagon exogeno en condiciones de hiperinsulinemia inducida puede producir un efecto contraregulador al de la insulina en un grupo de ratas machos adultos de la Cepa Wistar. Se investigo el comportamiento dosis respuesta en diferentes tratamientos con insulina y glucagon dividiendo 40 ratas en cuatro grupos y aplicando un tratamiento a cada grupo. Las variables evaluadas fueron: Peptido C, glucagon, glucemia y acidos grasos libres plasmaticos. Se concluyo que existe suficiente diferencia en los resultados medios de los niveles de cada parametro analizado en los cuatro grupos.