Serum Insulin-Like Growth Factor-1 (IGF-1) Age-Specific Reference Values for Healthy Adult Population of Serbia

M Stojanovic; M Popevic; S Pekic; M Doknic; D Miljic; M Medic-Stojanoska; D Topalov; J Stojanovic; A Milovanovic; M Petakov; S Damjanovic; V Popovic

doi:10.4183/aeb.2021.462

Serum Insulin-Like Growth Factor-1 (IGF-1) Age-Specific Reference Values for Healthy Adult Population of Serbia

Acta Endocrinol (Buchar). 2021 Oct-Dec;17(4):462-471. doi: 10.4183/aeb.2021.462.

Authors

M Stojanovic^{1

2}, M Popevic^{3

4}, S Pekic^{1

2}, M Doknic^{1

2}, D Miljic^{1

2}, M Medic-Stojanoska^{5

6}, D Topalov⁷, J Stojanovic⁸, A Milovanovic^{2

9}, M Petakov^{1

2}, S Damjanovic², V Popovic²

Affiliations

¹ University Clinical Center of Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases - Department of Neuroendocrinology, Belgrade, Serbia.
² Medical Faculty, University of Belgrade, Belgrade, Serbia.
³ University of Defence in Belgrade - Medical Faculty of the Military Medical Academy, Belgrade, Serbia.
⁴ Military Medical Academy - Institute of Occupational Medicine, Belgrade, Serbia.
⁵ Clinical Center of Vojvodina - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Novi Sad, Serbia.
⁶ University of Novi Sad - Medical Faculty, Novi Sad, Serbia.
⁷ Institute for laboratory diagnostics - Konzilijum, Belgrade, Serbia.
⁸ Zvezdara University Medical Center - Division of Endocrinology, Diabetes and Metabolic Disorders, Belgrade, Serbia.
⁹ Serbian Institute of Occupational Health, Belgrade, Serbia.

Abstract

Context: Insulin-like growth factor-1 (IGF-1) is main serum surrogate marker of growth hormone (GH) secretion, used in diagnostics and treatment of GH deficiency (GHD) and acromegaly. Regional, ethnic, racial or nutritional factors obscure cross-population applicability of IGF-1 reference values. Establishment of population- and assay-specific reference values requires sizable representative cohort of healthy subjects.

Subjects and methods: In representative sample of healthy adult population of Serbia (N=1200, 21-80 years, 1:1 male:female) serum IGF-1 was analyzed by Siemens Immulite 2000 assay under uniform laboratory conditions. Upper and lower limit of reference range (5^th - 95^th percentile) were calculated for each of the 12 quinquennial age intervals. IGF-1 distribution was normalized and standard deviation score (SDS) calculated by Logarithmic and LMS methods.

Results: IGF-1 and age correlated significantly, with most prominent decline at 21-50 years, followed by a plateau up to age of 70. Gender differences were not significant overall. Plateau in age-related IGF-1 decline was less prominent in women. Correlations of IGF-1 with body mass index (BMI) or waist to hip ratio (WHR) were insignificant. Superior IGF-1 SDS transformation was achieved with LMS method, while logarithmic method was simpler to use.

Conclusions: Normative age-specific serum IGF-1 reference values were established on a representative cohort of healthy adults in Serbia. Our results support recommendations against necessity for gender-specific or BMI- and WHR-specific reference ranges. Population-based data serve to generate IGF-1 SDS, which is valuable in rational application of consensus guidelines, proper longitudinal follow-up, advancement in efficacy and safety and personalization of treatment targets.

Keywords: Growth hormone; IGF-1; SD-score; Southeast Europe; normal healthy population; normative data; population-based.