Stimulated GH peak diagnostic performance to identify GH deficiency in children based on adult height
Precisión diagnóstica del pico de GH estimulada en la deficiencia de GH en pediatría basado en la talla final
Author
Teodózio, AC
Halah, MP
Aragon, DC
Elias, PL
Castro, M.
Moreira, AC
Antonini, SR
Abstract
Introduction: Diagnosing GH deficiency (GHD) is a challenge and depends on GH response to GH stimulatory test (GHST), whose cutoff remains unclear. Aims: To identify GH peak cutoff which best diagnoses GHD in short stature (SS) patients. Methods: Retrospective study: 858 children (0-18y) realized 1290 GHST between 2001-2016. Three-hundred-forty patients were classified as isolated SS (ISS = isolated GHD, familial SS, idiopathic SS) or GHD+hypopituitarism (MPHD). In those with known adult height (AH), clinical and biochemical data (median and interquartile range) were compared (Wilcoxon test). ROC curve was used to find discriminating GH peak in the ISS group, considering true GHD those who underwent rhGH treatment, reached AH ≥ -2 SDS and parental corrected adult height (AH – target height *TH+) ≥ -1.6 SDS. Results: Known AH was found in 146 out of 340. At admission: 10.1yrs [6.1; 12.9]; height (H) = -2.7 SDS [-3.4; -2.1]; H-TH = -1.5 SDS [-2.4; -0.7]; height velocity (HV) = -0.3 SDS [-1,3; 1]; plasma IGF1 = -1.6 SDS [-2.1; -0.9], maximum GH peak = 4.2 ng/mL [0.8; 9.1]. Forty-five patients presented MPHD and 101 presented ISS. MPHD patients had lower IGF1 (-2.1 vs. -1.4 SDS; p = 0.01) and GH peak (0.4 vs. 7 ng/mL; p<0.0001). Sixty-five patients received rhGH until reaching AH (MPHD = 24; ISS = 41). Decision for therapy was based on clinical judgment besides GHST. Treated patients were younger (8 vs 12.1yrs; p = 0.001), had lower HV (-1 vs. 0.1 SDS; p = 0.0001), IGF1 (-1.8 vs. -1.4 SDS; p = 0.02), GH peak (1.6 vs. 6.7 ng/ mL; p = 0.02), achieved higher AH (-1.6 vs. -2.2 SDS; p = 0.03) and AH-TH (-0.2 vs. -0.9; p = 0.02). True GHD was identified in 24 ISS. ROC analysis suggested a 6.8 ng/ml GH peak cutoff for ISS patients (AUC = 0.68, low sensitivity = 75%, specificity = 61% and LR = 1.92). Conclusions: In ISS patients, the most discriminative GH peak cutoff to identify GHD is 6.8 ng/ml. However, solely, this test has a poor diagnostic performance. Introducción: El diagnóstico de la deficiencia de GH (DGH) es difícil y depende del test de estimulación de GH (TEGH), cuyo cutoff aún no está claro.Objetivos: Identificar el valor de GH estimulada que mejor diagnostica DGH en niños con talla baja (TB).Métodos: Estudio retrospectivo: 858 niños (0-18a) realizaron 1290 TEGH entre 2001-2016. 340 clasificados como TB aislada (TBA= DGH aislado, TB familiar, TB idiopática) o GHD+hipopituitarismo (TB-MDH). En aquellos con talla final (TF) conocida, se compararon datos clínicos y bioquímicos (test de Wilcoxon; presentados en SDS, mediana y rango intercuartílico). Se empleó análisis ROC para encontrar el valor de GH estimulada que mejor diagnostica DGH en niños TBA, considerando DGH verdadera aquellos tratados con rhGH, con TF≥-2 SDS y TF corregida por la talla media parental (TF-TMP)≥-1,6 SDS.Resultados: TF conocida en 146/340 pacientes. Admisión: edad=10,1a [6,1; 12,9]; talla (T)=-2,7 [-3,4; -2,1]; T-TMP=-1,5 [-2,4; -0,7]; velocidad de crecimiento (VC)=-0,3 [-1,3; 1]; IGF1=-1,6 [-2,1; -0,9]; pico de GH=4,2 ng/ml [0,8; 9,1]. 45 pacientes TB-MDH, 101 TBA. Niños TB-MDH tenían IGF1 (-2,1 vs -1,4; p=0,01) y GH estimulada (0,4 vs 7 ng/ml; p<0,0001) más bajas. La indicación terapéutica no se basó únicamente en TEGH. 65 pacientes fueron tratados con rhGH hasta completar el crecimiento (TB-MDH=24; TBA=41): eran más jóvenes (8 vs 12,1a; p=0,001), presentaban VC (-1 vs 0,1; P=0,0001), IGF1 (-1,8 vs -1,4; p=0,02) y GH estimulada (1,6 vs 6,7 ng/ml; p=0,02) más bajas, alcanzaron mejor TF (-1,6 vs -2,2; p=0,03) y TF-TMP (-0,2 vs -0,9; p=0,02). 24 TBA clasificados como DGH verdadera. El ROC sugirió un cutoff para GH de 6,8 ng/ml en niños TBA [AUC=0,68, baja sensibilidad (75%), especificidad (61%) y LR (1,92)].Conclusiones: En niños TBA, el cutoff de GH que mejor diagnostica DGH es de 6,8 ng/ml. Sin embargo, aisladamente esta prueba tiene una baja precisión.