Influence of Body Mass Index on the Growth Hormone Response to Provocative Testing in Short Children without Growth Hormone Deficiency

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.

Acromegalia: comparación de los niveles séricos de IGF-I por dos inmunoensayos y su correlación con la prueba de tolerancia oral a la glucosa / Acromegaly: Comparison of serum IGF-1 levels measured by two immunoassays and their correlation with the Oral Glucose Tolerance Test

Introducción: La determinación de IGF-I en suero o plasma es una herramienta esencial en el diagnóstico y seguimiento de la acromegalia. Sin embargo, se deben tener presentes algunos inconvenientes en su medición por diferentes inmunoensayos. Objetivos: Evaluar dos inmunoensayos para la determinación de IGF-I y su correlación con el nadir de GH en el TTOG en pacientes acromegalicos. Materiales y métodos: Se analizaron 37 pacientes acromegálicos, 20 mujeres y 17 hombres. IGF-I fue determinada por Immulite 1000, (IMM) y por IRMA (DSL). Se realizó el TTOG y se determinó glucosa y GH en todos los tiempos (basal, 30, 60, 90 y 120min). Se consideró respuesta normal un nadir de GH <1ng/ml. Nueve pacientes se encontraban bajo tratamiento y 28 sin tratamiento. Análisis estadístico: se utilizaron el test de Wilcoxon, de Bland y Altman y curvas ROC. Se consideró significativa una p<0,05. Resultados: Las concentraciones basales de glucosa fueron 97,86±10,91 mg/dl, de GH 2,8 (1,59-14,4) ng/ml, de IGF-I por IMM 602±318 ng/ml y por DSL 1006±596 ng/ml. IGF-I por IMM y DSL mostró una diferencia significativa con p <0,01 y un bias de - 403,2 ng/ml con valores menores por IMM. IGF-I elevada por IMM y DSL, se encontró en el 84% y en el 97% respectivamente. IGF-I elevada con nadir de GH >1ng/ml se encontró en el 70%, con nadir de GH normal en el 13,5%. IGF-I normal con nadir >1ng/ml en el 2,7% y con nadir de GH normal en el 13,5%. El área bajo las curvas ROC no mostró diferencias significativas. Conclusiones: Los niveles de IGF-I determinados por IMM y DSL fueron significativamente diferentes mostrando un bias negativo para IMM. La mayoría de los valores del nadir de GH fueron consistentes con los niveles de IGF-I observándose una discrepancia en el 30% de los pacientes, estuvieran o no bajo tratamiento.

Introduction: IGF-I determination in serum or plasma is an essential tool in the diagnosis and follow-up of acromegaly. Hepatic production of IGF-I is regulated by GH and circulates bound to several IGF-I binding proteins which extends its half life. IGF-I is not released in a pulsatile pattern and has no significant variability in 24 h. Objective: To evaluate two different methodologies in IGF-I levels determination and their correlation with GH nadir in OGTT in acromegalic patients. Material and methods: We analyzed 37 acromegalic patients, 20 women and 17 men, mean age was 45±12 years. IGF-I levels were assayed by Immulite 1000, DPC (IMM) and DSL-5600 ACTIVE® IGF-I Coated-Tube IRMA (DSL) and OGTTs (at baseline and at 30, 60, 90 and 120 minutes) were performed by measuring plasma glucose and GH assay by immunochemiluminometric assay (Access); we considered a nadir <1ng/ml as normal response. Nine patients were under medical treatment (cabergoline: 4, octeotride: 4, and cabergoline plus octeotrite: 1) and 28 without treatment. Statistical analysis: Wilcoxon and, Bland and Altman tests and ROC curves. Differences were considered significant at p< 0.05. Results: Basal glucose levels were 97.86±10.91 mg/dl and mean GH was 2.8 (1.59-14.4) ng/ml. Mean IGF-I levels performed by IMM were 602±318 ng/ml and 1006±596 ng/ml by DSL. There was a statistically significant difference between both methodologies (p<0.01). Bland and Altman test showed a bias of - 403.2 ng/ml with lower values by IMM. We observed elevated IGF-I levels in 84% by IMM and in 97% by DSL, and only one patient had normal levels with both methodologies. Elevated IGF-I levels and GH nadir >1ng/ml were observed in 70% of the patients, increased IGF-I with normal GH nadir in 13.5%, normal IGF-I with GH nadir >1ng/ml in 2.7% and normal IGF-I with normal GH nadir in 13.5%. Patients under treatment: 3 showed normal GH nadir with elevated IGF-I levels, in 2 of them by both methodologies, and in the other one it was normal by IMM and elevated by DSL; the other 6 showed GH nadir > 1ng/ml, 5 of them presented elevated IGF-I by both methodologies and the other one showed discrepancy in IGF-I levels. The under ROC curve area and confidence interval (CI) of 95% for IGF-I IMM and DSL were 0.96 (0.90-1.00) and 0.91 (0.82-1.00) respectively. Differences between the ROC curves areas were not significant Conclusions: IGF-I levels determined by IMM and DSL were statistically significantly different. IGF-I levels showed a negative bias by IMM. Most of the results of GH nadir were consistent with IGF-I levels but we observed discrepancy in 30% of the patients, regardless of whether they were under treatment or not.

McCune-albright syndrome and acromegaly: hormonal control with use of cabergoline and long-acting somatostatin - case report / Síndrome de McCune-albright associada à acromegalia: controle hormonal com cabergolina e somatostatina de longa duração - relato de caso

OBJECTIVES: The use of drug therapy based on cabergoline, octreotide and long-acting release (LAR) octreotide has presented varying results in the treatment of GH excessive production in patients with McCune-Albright Syndrome. METHODS: We report the case of a 29 year-old female patient presenting McCune-Albright Syndrome and complaint of excessive bone growth. RESULTS: The patient presented a pituitary adenoma involving the right internal carotid artery and excessive secretion of growth hormone (no GH suppression was observed after the oral glucose tolerance test). Due to the presence of diffuse thickness in skull base bones, surgical approach was not considered effective and the patient was submitted to drug therapy with octreotide LAR and cabergoline. At the one year follow-up, GH and IGF-1 levels were normal and no adverse effects were present. CONCLUSION: The use of drug therapy based on the association of cabergoline and octreotide is safe and able to achieve complete hormonal control in the treatment of acromegaly for McCune-Albright patients.

OBJETIVO: O uso de terapia medicamentosa, como cabergolina, octreotide e octreotide de longa duração, tem apresentado resultados variados no tratamento da produção excessiva de hormônio de crescimento (GH) em pacientes com síndrome de McCune-Albright. MÉTODOS: Foi relatado o caso de uma paciente de 29 anos apresentando síndrome de McCune-Albright com queixas de crescimento ósseo excessivo. RESULTADOS: A paciente apresentava adenoma pituitário com envolvimento da artéria carótida interna direita e produção excessiva de GH (sem supressão de GH após o teste de supressão com glicose). Por causa do aumento importante da espessura dos ossos da base do crânio, a abordagem cirúrgica foi considerada pouco efetiva e a paciente foi submetida à terapia medicamentosa com octreotide de longa duração e cabergolina. No seguimento de um ano, os níveis de GH e IGF-1 estavam normais e os efeitos adversos não eram presentes. CONCLUSÃO: A terapia medicamentosa fundamentada na associação de cabergolina e octreotide é segura e capaz de alcançar controle hormonal completo no tratamento de acromegalia na síndrome de McCune-Albright.

Hormona del crecimiento y prolactina en líquido amniótico y plasma materno durante el embarazo normal / Growth hormone and prolactin in maternal plasma and amniotic fluid during normal gestation

Objective. To measure the concentration of human growth hormone (GH) and prolactin (PRL) In maternal plasma (MP) and amniotic fluid (AF) during gestation and to evaluate their correlation. Methods. HC and PRL were measured by radioimmunoassay in 60 healthy women with uncomplicated singleton pregnancies at 16-36 weeks of gestation (WG). Trends of both hormones were estimated throughout pregnancy. The correlation of either hormone measured in different fluids was also estimated. Results. GH in AF (AF-GH) decreased significantly throughout pregnancy; (AF-GH = 21.32 - 0.54 X WG, r = -0.72 [95% confidence intervals (95% CI) -0.57-0.82], p = 0.001), and increased in MP (MP-GH); (MP-GH = 2.73 +0.11 X WG, r = 0.45 [95% CI, 0.21-0.63]p = 0.05). The correlation between MP-GH and AF-GH was, (AF-GH = 16.28 - 1.54 x - M-PGH, r = -0.47 [95% CI, -0.64 --0.21]; p = 0.01). PRL values did not show significant differences neither in AF (AF-PRL / WG, r = 0.06, p = 0.6) nor in MP (MP-PRL / WG, r = 0.25, p = 0.14) during pregnancy, being AF-PRL (mean 151.3 ng/mL, SD 34.2 ng/mL) significantly higher than MP-PRL (mean 119.3 ng/mL, SD 55.4 ng/mL) (p = 0.006) in all the studied period. Conclusion. AF-GH and MP-GH showed a significant negative correlation during pregnancy. PRL measured in AF and PM did not show changes throughout gestation being AF-PRL significantly higher than MP-PRL.

Objetivo. Medir los valores de hormona del crecimiento (HC) y prolactina (PRL) en el líquido amniótico (LA) y en el plasma materno (PM) durante el embarazo normal y analizar sus asociaciones. Métodos. HC y PRL fueron medidas en el LA y en el PM por medio de radioinmunoanálisis en 60 mujeres con embarazo único y sin complicaciones entre 16 y 36 semanas de gestación (SG). Se evaluaron las tendencias de ambas hormonas a lo largo del embarazo y la correlación entre los valores obtenidos en ambos compartimentos. Resultados. La HC en LA (HCLA) disminuyó en forma significativa durante el embarazo (HCLA = 21.32 - 0.54 X SG, r = -0.72 [intervalos de confianza al 95% (IC 95%) -0.57-0.82], p = 0.001) y en PM (HCPM) aumentó (HCPM = 2.73 + 0.11 X SG, r = 0.45 [IC 95%, 0.21-0.63] p = 0.05). La correlación entre los valores de HC en LA y en PM fue: (HCLA = 16.28-1.54 x -HCPM, r = -0.47 [IC 95% -0.64 -0 -0.21]; p = 0.01). La concentración de PRL a lo largo del embarazo tanto en LA (PRL-LA/SG, r = 0.06, p = 0.6) como en PM (PRL-PM/SG r = 0.25, p = 0.14) no cambió y fue significativamente más alta en LA que en PM (LA; media 151.3 ng/mL, DE 34.2 ng/ inL, PM; media 119.3 ng/mL, DE 55.4 ng/mL, respectivamente, p = 0.006). Conclusiones. HC en PM y HC en LA presentan una correlación inversa a lo largo del embarazo, en tanto que los valores de PRL en ambos compartimentos no cambian, siendo significativamente más elevados en el LA.

Acromegalia e doença tiroideana: prevalência de câncer de tireóide / Acromegaly and thyroid disease: prevalence of thyroid cancer

A relação entre câncer e acromegalia tem sido objeto de estudo há muitos anos. A partir de um caso de carcinoma diferenciado de tireóide em um de nossos pacientes acromegálicos, estudamos uma série de 100 outros acromegálicos e encontramos dois outros casos de câncer de tireóide, descritos neste trabalho. A partir daí, levantamos os dados da literatura sobre esta última associação e sua possível patogênese. A prevalência de patologias tireoidianas é aumentada dentre os acromegálicos, às custas, principalmente, do bócio nodular. Esta associação será abordada, assim como a relação entre o fator de crescimento insulina símile I (IGF-I) e câncer, numa tentativa de entender melhor seu significado frente aos nossos casos. Nós concluímos que seria prudente realizar exame ultrassonográfico periódico em acromegálicos, seguido de Punção Aspirativa com Agulha Fina (PAAF) dos nódulos suspeitos.

Niveles de hormona de crecimiento y somatomedina C en niños con desnutrición grave / Malnutrition in children growth and somato medine C

La desnutrición se acompaña de modificaciones importantes en los niveles hormonales plasmáticos como parte de sus mecanismos adaptativos que permiten la sobrevida; devido al alto índice de desnutridos en nuestro medio, la motivación para esta investigación fue conocer como se comportan nuestros pacientes en relación a lo descrito en la literatura. Se evaluaron 20 niños desnutridos graves (13 Kwashiorkor y 7 Marasmo-Kwashiorkor) en edades comprendidas entre un mes y tres años, al ingreso, a los 15 días, al mes y a los dos meses de la recuperación. Las variables estudiadas fueron: edad, antropometría, escore de McLaren, niveles hormonales plasmáticos (Hormona de Crecimiento, IGF-1). Al ingreso los valores de hormona de crecimiento fueron elevados, disminuyendo significativamente (p<0,05) a los dos meses de la rehabilitación nutricional, en contraste los niveles de IGF-1 fueron bajos al ingreso, aumentando significativamente (p<0,05) a los dos meses de la recuperación. Los niveles altos de hormona de crecimiento pudieran ser explicados por la ausencia de retrocontrol ejercido normalmente por los niveles de IGF-1 que se encuentran disminuidos. El mejor entendimiento de los cambios hormonales en la desnutrición podrá conducir al uso terapeútico de ciertas hormonas tanto en la rehabilitación nutricional como en efermedades acompañadas de desnutrición

Macroadenomas näo-funcionantes da hipófise: estudo imuno-histoquímico / Functionless pituitary macroadenomas: immunohistochemical study

Cinqüenta e nove adenomas hipofisários, do tipo nao-funcionante, foram analisados pelo método imuno-histoquímico. Os tumores foram estudados através da técnica da peroxidase - avidina - biotina (ABC) e pesquisados os seguintes hormônios, com anticorpos primários específicos: prolactina (PRL), hormônio do crescimento (HS), corticotrofina (ACTH), gonadotrofinas (HCG) e tireotrofina (TSH). Trinta e oito tumores nao reagiram a nenhum anticorpo, 8 tumores apresentaram imunorreaçao positiva à prolactina, 5 tumores eram imunorreativos ao HS, 6 eram imunorreativos ao ACTH, e 10 tumores eram imunorreativos às gonadrotofinas, sendo que 5 ao LH e 5 ao FSH. Dos tumores que apresentaram imunorreatividade ao hormônio do crescimento e à prolactina houve manifestaçao clínica em apenas um, cujo paciente evoluiu com altas taxas de prolactina sangüínea.