[High frequency of thyroid abnormalities in polycystic ovary syndrome]. / Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p<0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities (p<0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico / High frequency of thyroid abnormalities in polycystic ovary syndrome

La prevalencia de trastornos tiroideos (TT) no ha sido suficientemente evaluada en mujeres con síndrome de ovario poliquístico (SOP). El propósito de esta investigación fue examinar dicha relación. En este estudio prospectivo de diseño caso-control, se incluyeron 194 mujeres. El grupo SOP consistió en 142 pacientes diagnosticadas por criterios Rotterdam 2003, y el grupo control incluyó a 52 mujeres sanas apareadas por edad. Se extrajeron muestras de sangre en ayuno para dosajes de T4 libre, tirotrofina, anticuerpos antiperoxidasa (ATPO), insulinemia y glucemia y se calculó el índice HOMA. Un total de 52 pacientes con SOP presentó autoinmunidad tiroidea (AIT+) y/o hipotiroidismo subclínico (HSC) (36.6%) (TT+) en comparación con 7 mujeres del grupo de control (13.5%), lo que representa una frecuencia cinco veces mayor de TT en pacientes con SOP en comparación con los controles (odds ratio ajustado: 5.6; IC 95%: 2.1-14.9; p < 0.001). Las pacientes TT+ tuvieron valores de insulinemia y HOMA significativamente más altos que aquellas sin trastornos tiroideos (TT-) (p < 0.05).Este estudio muestra una alta tasa de TT en mujeres con SOP asociada a mayores niveles de insulinemia y HOMA. Teniendo en cuenta que el SOP, el hipotiroidismo y la autoinmunidad tiroidea pueden tener un profundo impacto en la salud reproductiva, nuestros datos sugieren que las pacientes con SOP deberían ser evaluadas para descartar TT.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p < 0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities(p < 0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Heterozygous IGFALS gene variants in idiopathic short stature and normal children: impact on height and the IGF system.

BACKGROUND: In acid-labile subunit (ALS)-deficient families, heterozygous carriers of IGFALS gene mutations are frequently shorter than their wild-type relatives, suggesting that IGFALS haploinsufficiency could result in short stature. We have characterized IGFALS gene variants in idiopathic short stature (ISS) and in normal children, determining their impact on height and the IGF system. PATIENTS AND METHODS: In 188 normal and 79 ISS children levels of IGF-1, IGFBP-3, ALS, ternary complex formation (TCF) and IGFALS gene sequence were determined. RESULTS: In sum, 9 nonsynonymous or frameshift IGFALS variants (E35Gfs*17, G83S, L97F, R277H, P287L, A330D, R493H, A546V and R548W) were found in 10 ISS children and 6 variants (G170S, V239M, N276S, R277H, G506R and R548W) were found in 7 normal children. If ISS children were classified according to the ability for TCF enhanced by the addition of rhIGFBP-3 (TCF+), carriers of pathogenic IGFALS gene variants were shorter and presented lower levels of IGF-1, IGFBP-3 and ALS in comparison to carriers of benign variants. In ISS families, subjects carrying pathogenic variants were shorter and presented lower IGF-1, IGFBP-3 and ALS levels than noncarriers. CONCLUSIONS: These findings suggest that heterozygous IGFALS gene variants could be responsible for short stature in a subset of ISS children with diminished levels of IGF-1, IGFBP-3 and ALS.

[Critical evaluation of the oral glucose tolerance test for the diagnosis of insulin resistance in patients with polycystic ovary syndrome]. / Evaluacion critica del test de tolerancia oral a la glucosa para el diagnostico de resistencia insulinica en pacientes con sindrome de ovario poliquistico.

Oral glucose tolerance test (OGTT) is the most commonly used method to evaluate insulin resistance (IR) in the clinical practice. Our objective was to evaluate the diagnostic utility of fasting tests compared with OGTT tests in women with PCO, and the ability of fasting tests to detect postprandial hyperglycemia. One hundred fourteen women with PCO and 29 normal women were evaluated by a 2 hours OGTT. Fasting plasma insulin (INS) and glucose were measured during the test. GLU:INS ratio (r) (fasting glucose/fasting insulin), HOMA (homeostatic model assessment), QUICKI (quantitative insulin sensitivity check index) (fasting tests), as well as the AUCI (area under the curve of INS) and ISI composite (ISI) (insulin sensitivity index) (OGTT tests), were determined. A significant correlation between fasting tests and OGTT tests was found. Normal fasting tests with abnormal OGTT tests were found in 9 patients. No patient with fasting insulin levels less than 9.9 Ul/ml were IR, and all women with fasting insulin levels over 18.4 UI/ml were classified as having IR. We found glucose levels 120 min post glucose load (G 120) > or = 140 mg/dl in 14 patients (12.2%). Fasting glucose and insulin levels and the fasting tests, were poor predictors of impaired glucose tolerance (IGT) and type 2 diabetes (DBT 2). Thus, fasting tests are useful in the diagnostic of IR in PCO patients. OGTT is necessary when the fasting insulin levels range between 9.9 and 18.4 Ul/ml. Women with PCO should undergo periodic screening for abnormal glucose tolerance.

Evaluación crítica del test de tolerancia oral a la glucosa para el diagnóstico de resistencia insulínica en pacientes con síndrome de ovario poliquístico / Critical evaluation of the oral glucose tolerance test for the diagnosis of insulin resistance in patients with polycystic ovary syndrome

El test de tolerancia oral a la glucosa (TTOG) es el más frecuentemente utilizado en la práctica clínica para el diagnóstico de resistencia insulínica (RI). El objetivo del presente trabajo fue la evaluación de la utilidad de los índices basales e índices TTOG, en mujeres con síndrome de ovario poliquístico (SOP) y del valor predictivo de los índices basales sobre la glucemia a los 120 minutos postprandial (G 120). Se estudiaron 114 pacientes con diagnóstico de SOP y 29 mujeres normales. A todas se les realizó un TTOG. Se dosó insulina y glucosa séricas cada 30 min durante las 2 horas del test y se determinaron los siguientes índices: Indices basales: GLU/lNS (glucemia en ayunas / insulinemia en ayunas), HOMA (modelo homeostático) y QUICKI (índice cuantitativo de sensibilidad insulínica) e índices TTOG: AI (área bajo la curva de insulina) e ISI composite (índice de sensibilidad insulínica). Se observaron correlaciones significativas entre los índices basales y los índices TTOG. Hubo 9 pruebas con índices basales normales que presentaban índice TTOG patológicos. Ninguna paciente con niveles de insulina menores a 9.9 Ul/ml presentó RI, mientras que todas las pacientes con niveles de insulina mayores a 18.4 Ul/ml tuvieron RI. Catorce pacientes (10.5%) presentaron G 120 ³ a 140 mg%. En 4 de los 14 casos (12.2%), los valores basales no hicieron sospechar la posibilidad del diagnóstico de hiperglucemia post prandial. En conclusión, en pacientes con SOP, los índices basales son útiles para diagnosticar RI. Proponemos realizar TTOG para diagnóstico de RI en aquellas pacientes que presenten insulinemias en ayunas entre 9.9 y 18.4 Ul/ml. En pacientes con SOP, se recomienda la evaluación periódica de la G 120. (AU)

Oral glucose tolerance test (OGTT) is the most commonly used method to evaluate insulin resistance (IR) in the clinical practice. Our objective was to evaluate the diagnostic utility of fasting tests compared with OGTT tests in women with PCO, and the ability of fasting tests to detect postprandial hyperglycemia. One hundred fourteen women with PCO and 29 normal women were evaluated by a 2 hours OGTT. Fasting plasma insulin (INS) and glucose were measured during the test. GLU:INS ratio (r) (fasting glucose/fasting insulin), HOMA (homeostatic model assessment), QUICKI (quantitative insulin sensitivity check index) (fasting tests), as well as the AUCI (area under the curve of INS) and ISI composite (ISI) (insulin sensitivity index) (OGTT tests), were determined. A significant correlation between fasting tests and OGTT tests was found. Normal fasting tests with abnormal OGTT tests were found in 9 patients. No patient with fasting insulin levels less than 9.9 UI/ml were IR, and all women with fasting insulin levels over 18.4 UI/ml were classified as having IR. We found glucose levels 120 min post glucose load (G 120) ³ 140 mg/dl in 14 patients (12.2%). Fasting glucose and insulin levels and the fasting tests, were poor predictors of impaired glucose tolerance (IGT) and type 2 diabetes (DBT 2). Thus, fasting tests are useful in the diagnostic of IR in PCO patients. OGTT is necessary when the fasting insulin levels range between 9.9 and 18.4 UI/ml. Women with PCO should undergo periodic screening for abnormal glucose tolerance. (AU)

Evaluación crítica del test de tolerancia oral a la glucosa para el diagnóstico de resistencia insulínica en pacientes con síndrome de ovario poliquístico / Critical evaluation of the oral glucose tolerance test for the diagnosis of insulin resistance in patients with polycystic ovary syndrome

El test de tolerancia oral a la glucosa (TTOG) es el más frecuentemente utilizado en la práctica clínica para el diagnóstico de resistencia insulínica (RI). El objetivo del presente trabajo fue la evaluación de la utilidad de los índices basales e índices TTOG, en mujeres con síndrome de ovario poliquístico (SOP) y del valor predictivo de los índices basales sobre la glucemia a los 120 minutos postprandial (G 120). Se estudiaron 114 pacientes con diagnóstico de SOP y 29 mujeres normales. A todas se les realizó un TTOG. Se dosó insulina y glucosa séricas cada 30 min durante las 2 horas del test y se determinaron los siguientes índices: Indices basales: GLU/lNS (glucemia en ayunas / insulinemia en ayunas), HOMA (modelo homeostático) y QUICKI (índice cuantitativo de sensibilidad insulínica) e índices TTOG: AI (área bajo la curva de insulina) e ISI composite (índice de sensibilidad insulínica). Se observaron correlaciones significativas entre los índices basales y los índices TTOG. Hubo 9 pruebas con índices basales normales que presentaban índice TTOG patológicos. Ninguna paciente con niveles de insulina menores a 9.9 Ul/ml presentó RI, mientras que todas las pacientes con niveles de insulina mayores a 18.4 Ul/ml tuvieron RI. Catorce pacientes (10.5%) presentaron G 120 ³ a 140 mg%. En 4 de los 14 casos (12.2%), los valores basales no hicieron sospechar la posibilidad del diagnóstico de hiperglucemia post prandial. En conclusión, en pacientes con SOP, los índices basales son útiles para diagnosticar RI. Proponemos realizar TTOG para diagnóstico de RI en aquellas pacientes que presenten insulinemias en ayunas entre 9.9 y 18.4 Ul/ml. En pacientes con SOP, se recomienda la evaluación periódica de la G 120.

Oral glucose tolerance test (OGTT) is the most commonly used method to evaluate insulin resistance (IR) in the clinical practice. Our objective was to evaluate the diagnostic utility of fasting tests compared with OGTT tests in women with PCO, and the ability of fasting tests to detect postprandial hyperglycemia. One hundred fourteen women with PCO and 29 normal women were evaluated by a 2 hours OGTT. Fasting plasma insulin (INS) and glucose were measured during the test. GLU:INS ratio (r) (fasting glucose/fasting insulin), HOMA (homeostatic model assessment), QUICKI (quantitative insulin sensitivity check index) (fasting tests), as well as the AUCI (area under the curve of INS) and ISI composite (ISI) (insulin sensitivity index) (OGTT tests), were determined. A significant correlation between fasting tests and OGTT tests was found. Normal fasting tests with abnormal OGTT tests were found in 9 patients. No patient with fasting insulin levels less than 9.9 UI/ml were IR, and all women with fasting insulin levels over 18.4 UI/ml were classified as having IR. We found glucose levels 120 min post glucose load (G 120) ³ 140 mg/dl in 14 patients (12.2%). Fasting glucose and insulin levels and the fasting tests, were poor predictors of impaired glucose tolerance (IGT) and type 2 diabetes (DBT 2). Thus, fasting tests are useful in the diagnostic of IR in PCO patients. OGTT is necessary when the fasting insulin levels range between 9.9 and 18.4 UI/ml. Women with PCO should undergo periodic screening for abnormal glucose tolerance.

Normal growth spurt and final height despite low levels of all forms of circulating insulin-like growth factor-I in a patient with acid-labile subunit deficiency.

BACKGROUND: In a recently described patient with acid-labile subunit (ALS) deficiency, the inability to form ternary complexes resulted in a marked reduction in circulating total insulin-like growth factor (IGF)-I, whereas skeletal growth was only marginally affected. To further study the role of circulating versus locally produced IGF-I in skeletal growth in this patient, we now describe in detail growth changes and their relationship with several components of the circulating IGF system. DESIGN AND METHODS: We followed growth and development up to the final height in a patient with complete ALS deficiency and determined both spontaneous and growth hormone (GH)-stimulated changes in the IGF system, including measurements of total, free and bioactive IGF-I, total IGF-II and insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3. RESULTS: The patient had a delayed growth and pubertal onset. Six months of GH treatment had no effect on growth. At the age of 19.3 years, he spontaneously completed puberty and had a normal growth spurt for a late adolescent (peak height velocity of 8.4 cm/year). A normal final height was attained at 21.3 years (167.5 cm; -0.78 SDS). During as well as after puberty, basal levels of total, free and bioactive IGF-I were low, as were total IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3. GH treatment for 6 months normalized free IGF-I and increased bioactive IGF-I, but had no effect on growth velocity. CONCLUSIONS: This case story shows that in the presence of complete ALS deficiency, a height within normal limits can be obtained despite low levels of all forms of circulating IGF-I. Furthermore, the patient presented a delayed but normal growth spurt without any marked increment of circulating IGF-I.

[Leptin in patients with polycystic ovary syndrome. Direct correlation with insulin resistance]. / Leptina en pacientes con síndrome de ovario poliquístico. Correlacíon directa con la resistencia insulínica.

Up to now it is unclear whether there is a relationship between insulin resistance and circulating leptin levels (LEP) in women with polycystic ovary syndrome (PCOS). To assess the role of LEP in PCOS and to clarify the relationship between plasma LEP levels and insulin resistance (IR) in PCOS patients, we studied 49 women with PCOS and 14 normal premenopausal women. All subjects were evaluated by a 2 hours, 75 g, oral glucose tolerance test. Fasting plasma LEP, insulin, glucose, insulin sensitivity indexes and LEP:body mass index (BMI) were determined. Results were analyzed by ANOVA and the Pearson's correlation test when appropriate. The results indicate that: 1) no differences were found in basal plasma LEP levels (ng/ml) between normal (17.6 +/- 4.9) and PCOS (21.9 +/- 2.8) women; 2) in PCOS patients, a significant (P < 0.01) correlation between plasma LEP levels and BMI and insulin sensitivity indexes were found; and 3) seventeen PCOS patients were insulin resistant (IR) and showed higher basal plasma LEP levels (32.8 +/- 4.3, P < 0.01) and LEP:BMI (0.95 +/- 0.09, P < 0.05) than non insulin resistant (non IR) PCOS subjects (16.2 +/- 3.2 and 0.61 +/- 0.08, respectively). Our results suggest that PCOS seems to be associated with normoleptinemia, however, if IR are analyzed separately from non IR PCOS patients, there is a clear relationship between IR PCOS and hyperleptinemia, regardless of the BMI. The present study strongly supports bi-directional relationship between fat and carbohydrate metabolisms under a very particular physiopathological condition (PCOS).

Leptina en pacientes con síndrome de ovario poliquístico. Correlacíon directa con la resistencia insulínica. / [Leptin in patients with polycystic ovary syndrome. Direct correlation with insulin resistance]

Up to now it is unclear whether there is a relationship between insulin resistance and circulating leptin levels (LEP) in women with polycystic ovary syndrome (PCOS). To assess the role of LEP in PCOS and to clarify the relationship between plasma LEP levels and insulin resistance (IR) in PCOS patients, we studied 49 women with PCOS and 14 normal premenopausal women. All subjects were evaluated by a 2 hours, 75 g, oral glucose tolerance test. Fasting plasma LEP, insulin, glucose, insulin sensitivity indexes and LEP:body mass index (BMI) were determined. Results were analyzed by ANOVA and the Pearsons correlation test when appropriate. The results indicate that: 1) no differences were found in basal plasma LEP levels (ng/ml) between normal (17.6 +/- 4.9) and PCOS (21.9 +/- 2.8) women; 2) in PCOS patients, a significant (P < 0.01) correlation between plasma LEP levels and BMI and insulin sensitivity indexes were found; and 3) seventeen PCOS patients were insulin resistant (IR) and showed higher basal plasma LEP levels (32.8 +/- 4.3, P < 0.01) and LEP:BMI (0.95 +/- 0.09, P < 0.05) than non insulin resistant (non IR) PCOS subjects (16.2 +/- 3.2 and 0.61 +/- 0.08, respectively). Our results suggest that PCOS seems to be associated with normoleptinemia, however, if IR are analyzed separately from non IR PCOS patients, there is a clear relationship between IR PCOS and hyperleptinemia, regardless of the BMI. The present study strongly supports bi-directional relationship between fat and carbohydrate metabolisms under a very particular physiopathological condition (PCOS).

Leptina en pacientes con sindrome de ovario poliquistico: correlacion directa con la resistencia insulinica / Leptin in patients with polycystic ovary syndrome: direct correlation with insulin resistance

La presencia de resistencia insulínica (RI) es un hecho frecuentemente asociado al síndrome de ovario poliquístico (PCO), sin embargo aún no está clara la relación existente entre la RI y los niveles circulantes de leptina en estas pacientes. En este trabajo investigamos los niveles plasmáticos de leptina en pacientes con PCO y evaluamos su relación con la presencia de RI. Se seleccionaron 49 pacientes con PCO y 14 mujeres normales. A todas las pacientes se les realizó un test de tolerancia oral a la glucosa. Se dosó leptina (LEP), insulina y glucosa séricas durante las 2 hs del test y se determinaron los índices de sensibilidad insulínica y relación leptina: índice de masa corporal (LEP:BMI). 1) No observamos diferencias significativas en los niveles séricos de LEP (ng/ ml) entre las pacientes PCO (21.9 ± 2.8) y los controles normales (17.6 ± 4.9). 2) En las pacientes con PCO, los niveles séricos de LEP y el índice LEP:BMI se correlacionaron en forma significativa con el BMI y los índices de sensibilidad insulínica (P<0.01). 3) Diecisiete pacientes con PCO que presentaron RI evidenciaron niveles significativamente mayores de leptina sérica (32.8 ± 4.3 vs. 16.2 ± 3.2, P<0.01) y LEP:BMI (0.95 ± 0.09 vs. 0.61 ± 0.08, P<0.05) que las pacientes sin RI. En conclusión, nuestros resultados evidencian que el síndrome PCO pareceríacursar con normoleptinemia, sin embargo la presencia de RI podría estar relacionada con un aumento de laconcentración de leptina sérica independientemente del BMI. Estos resultados avalan la existencia de una interrelación leptina ¹ insulina en este grupo de pacientes.(AU)

Leptina en pacientes con sindrome de ovario poliquistico: correlacion directa con la resistencia insulinica / Leptin in patients with polycystic ovary syndrome: direct correlation with insulin resistance

La presencia de resistencia insulínica (RI) es un hecho frecuentemente asociado al síndrome de ovario poliquístico (PCO), sin embargo aún no está clara la relación existente entre la RI y los niveles circulantes de leptina en estas pacientes. En este trabajo investigamos los niveles plasmáticos de leptina en pacientes con PCO y evaluamos su relación con la presencia de RI. Se seleccionaron 49 pacientes con PCO y 14 mujeres normales. A todas las pacientes se les realizó un test de tolerancia oral a la glucosa. Se dosó leptina (LEP), insulina y glucosa séricas durante las 2 hs del test y se determinaron los índices de sensibilidad insulínica y relación leptina: índice de masa corporal (LEP:BMI). 1) No observamos diferencias significativas en los niveles séricos de LEP (ng/ ml) entre las pacientes PCO (21.9 ± 2.8) y los controles normales (17.6 ± 4.9). 2) En las pacientes con PCO, los niveles séricos de LEP y el índice LEP:BMI se correlacionaron en forma significativa con el BMI y los índices de sensibilidad insulínica (P<0.01). 3) Diecisiete pacientes con PCO que presentaron RI evidenciaron niveles significativamente mayores de leptina sérica (32.8 ± 4.3 vs. 16.2 ± 3.2, P<0.01) y LEP:BMI (0.95 ± 0.09 vs. 0.61 ± 0.08, P<0.05) que las pacientes sin RI. En conclusión, nuestros resultados evidencian que el síndrome PCO pareceríacursar con normoleptinemia, sin embargo la presencia de RI podría estar relacionada con un aumento de laconcentración de leptina sérica independientemente del BMI. Estos resultados avalan la existencia de una interrelación leptina - insulina en este grupo de pacientes.