J Pediatr Endocrinol Metab 2016; aop *Corresponding author: Susanne E. Stalman, MD, Academic Medical Center, Department of Pediatrics, Meibergdreef 9, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands, Phone: +31 20 5668844, Fax: +31 20 5664440, E-mail: s.e.stalman@amc.uva.nl; and Department of Pediatrics, Tergooi Hospitals, Blaricum, The Netherlands Ilse Hellinga: Department of Pediatrics, Wilhelmina Children’s Hospital, Utrecht, The Netherlands Jan M. Wit: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands Raoul C.M. Hennekam: Department of Pediatrics, Academic Medical Center, Amsterdam, The Netherlands Gerdine A. Kamp and Frans B. Plötz: Department of Pediatrics, Tergooi Hospitals, Blaricum, The Netherlands Susanne E. Stalman*, Ilse Hellinga, Jan M. Wit, Raoul C.M. Hennekam, Gerdine A. Kamp and Frans B. Plötz Growth failure in adolescents: etiology, the role of pubertal timing and most useful criteria for diagnostic workup DOI 10.1515/jpem-2015-0267 Received July 3, 2015; accepted November 23, 2015 Abstract Background: The aim of the study was to evaluate the etiology, the role of pubertal timing and most useful cri- teria for diagnostic workup in adolescents with growth failure. Methods: Adolescents (n = 182) aged 10.0–18.0 years underwent a standardized diagnostic protocol. Constitu- tional delay of growth and puberty (CDGP) was defined as late pubertal onset or a Tanner stage less than –2 SDS. Dutch and Finnish criteria for growth monitoring were retrospectively assessed. Results: In 13 children (7.1%) a specific diagnosis could be established. CDGP was diagnosed in 10% of patients aged  ≥ 13 (girls) or  ≥ 14 years (boys). Sensitivity to detect pathologic causes was 85% and 62% for, respectively Dutch and Finnish criteria for growth monitoring as used in younger children, but specificity was low (55%–59%). Conclusions: In adolescents, pathological causes for growth failure and pubertal delay are common, and we recommend a combination of height SDS, distance to THSDS and growth deflection for deciding on further diagnostic testing. Keywords: adolescents; growth disorders; growth failure; height; height deflection; target height. Introduction Growth failure, including short stature, growth retarda- tion, or short in comparison to target height, is generally considered a relatively early sign of various pathological conditions. The incidence of detectable causes in children below 10 years varies between 3.0% and 9.5% [1–4]. In two countries evidence-based guidelines have been developed to assist primary health workers in their decision to refer a child for specialist care: in the Netherlands validated up to 10.0 years and in Finland up to 18 years. These consist of a combination of short stature for the population, short for genetic background, and growth deflection [5–7]. The Finnish guideline [6, 7] contains complicated algorithms that can only be used if integrated into an electronic health record system and the change in height SDS (ΔHSDS) can only be calculated up to 12 years of age. For adolescents with growth failure, the incidence of detectable pathological causes has been reported as mark- edly lower (1.3%) than in younger children [8]. This can be explained in part by assuming that the majority of congen- ital disorders have been diagnosed at an earlier age and that acquired disorders causing growth failure in adoles- cence are rare. In this age group, it is also more difficult to develop guidelines for referral for specialist care because of the wide variability of the onset and progression of puberty. For example, in case of delayed pubertal devel- opment, growth rate can substantially decrease, leading to a decreasing height standard deviation score (HSDS) and increasing distance to target height SDS (THSDS) [9]. Constitutional delay of growth and puberty (CDGP), the most common cause of delayed puberty [10, 11], is primar- ily characterized by delayed puberty (pubertal onset  > 13 in girls and  > 14 in boys), but also associated with slow growth, delayed bone age and a positive family history for delayed puberty [12–14]. In a recent paper on Danish Brought to you by | University of California - San Diego Authenticated Download Date | 1/30/16 2:55 PM