Serum levels of intact and total IGFBP-4, and stanniocalcin-2 in congenital isolated gh deficiency

Viviane Campos; Aguiar Oliveira Manuel H.; Martin Bidlingmaier; Yuen Kevin CJ; Roberto Salvatori; P. Oliveira Carla R.; Angela Leal; Enaldo Melo; Katharina Schilbach; Jan Frystyk; de Oliveira Longo Schweizer Junia Ribeiro

doi:10.1530/endoabs.110.EP802

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Endocrine Abstracts (2025) 110 EP802 | DOI: 10.1530/endoabs.110.EP802

ECEESPE2025 ePoster Presentations Growth Axis and Syndromes (132 abstracts)

Serum levels of intact and total IGFBP-4, and stanniocalcin-2 in congenital isolated gh deficiency

Viviane Campos ¹ , Manuel H. Aguiar Oliveira ¹ , Martin Bidlingmaier ² , Kevin CJ Yuen ³ , Roberto Salvatori ⁴ , Carla R. P. Oliveira ¹ , Angela Leal ¹ , Enaldo Melo ¹ , Katharina Schilbach ² , Jan Frystyk ⁵ & Júnia Ribeiro de Oliveira Longo Schweizer ²

Author affiliations

¹Federal University of Sergipe, Aracaju, Brazil; ²Ludwig-Maximilians-Universität in Munich, Munich, Germany; ³University Arizona College of Medicine, Phoenix, Phoenix, United States; ⁴Johns Hopkins University, Baltimore, United States; ⁵University of Southern Denmark, Odense, Denmark

JOINT1755

The Itabaianinha cohort is composed of subjects with a homozygous GHRH-R c.57 + 1G →A mutation, causing congenital isolated GH deficiency (IGHD). These subjects exhibit severe short stature, central obesity, hypercholesterolemia, but no premature atherosclerosis, and normal lifespan. They have marked reductions in serum IGF-I, IGFBP-3 and ALS, but normal IGFBP-1 and IGFBP-2 levels. Stanniocalcin-2 (STC2), plasma pregnancy-associated protein A (PAPP-A) and IGFBP-4 are functionally related proteins that in concert regulate IGF-I action, and hence body growth. PAPP-A cleaves IGFBP-4 enzymatically, and liberates bound IGF-I, whereas stanniocalcin-2 inhibits PAPP-A. These proteins have not previously been characterized in GH deficiency, Here, we present data on total and intact IGFBP-4 and Stanniocalcin-2. Table 1 shows that levels of intact IGFBP4 are 4-times higher in IGHD (P <0.0001), with a very large effect size (Mann Whitney Eta-squared =0.539 and a Cohen’s d =2.165), whereas total IGFBP-4 (intact plus fragments) and STC2 are similar to age- and BMI-matched controls. The higher levels of intact IGFBP-4 suggest a role of PAPP-A in mediating IGFBP-4 cleavage, which contributes to the growth reduction in this cohort

Table 1. Clinical and biochemical data in 23 IGHD individuals and 11 controls. Data are expressed as mean (standard deviation), except for glucose, insulin, triglycerides, IGF-1, IGFBP3, and intact IGFBP4 expressed as median (interquartile range)
Parameters	IGHD	Controls	95% CI	P
Age (years)	50.8 (13.7)	44.9 (15.6)	-4.8 to 16.6	0.273
Female sex, n (%)	10 (43.5)	6 (54.5)	-0.5 to 0.3	0.717
Weight (kg)	42.8 (7.0)	72.6 (11.78)	-36.2 to -23.2	<0.0001
Height (m)	1.29 (0.10)	1.65 (0.08)	-0.4 to -0.3	<0.0001
BMI (kg/m²)	25.9 (3.9)	26.1 (5.4)	-3.6 to 3.1	0.879
Glucose (mg/dl)	87.0 (15.0)	89.5 (12.3)	-13.6 to 4.8	0.186
Insulin (µU/ml)	4.2 (1.8)	6.7 (3.9)	-5.0 to -1.1	0.004
HOMA-IR	0.88 (0.44)	1.63 (0.86)	-1.3 to -0.1	0.018
Total cholesterol (mg/dl)	222 (41)	185.4 (42.1)	-6.4.0 to 45.6	0.134
LDL cholesterol (mg/dl)	119.1 (36.3)	102.3 (25.7	-8.0 to 41.8	0.178
HDL cholesterol (mg/dl)	49.7 (8.1)	51.7 (14.1)	-9.7 to 5.7	0.603
Tryglicerides (mg/dl)	139.0 (178.0	77.0 (96)	-44.9 to 106.0	0.424
IGF1 (ng/ml)	11.0 (6.0)	180.5 (76.8)	-163 to -128	< 0.0001
IGFBP-3 (ng/ml)	579 (222)	3458 (1476)	-3258 to -2272	<0.0001
Stanniocalcin-2 (ng/ml)	43.4 (7.4)	47.8 (10.1)	-11.1 to 3.1.	0.191
Total IGFBP-4 (ng/ml)	101.6 (28.1)	96.6 (30.9)	-19.7 to 29.8	0.678
Intact IGFB-4 (ng/ml)	83.9 (22.2)	21.2 (34.2)	39.7 to 64.2	<0.0001