Constitutional Growth Delay

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Children with constitutional growth delay (CGD), the most common cause of short stature and pubertal delay, [1] typically have retarded linear growth within the first 3 years of life. In this variant of normal growth, linear growth velocity and weight gain slows beginning as young as age 3-6 months, resulting in downward crossing of growth percentiles, which often continues until age 2-3 years. At that time, growth resumes at a normal rate, and these children grow either along the lower growth percentiles or beneath the curve but parallel to it for the remainder of the prepubertal years.

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At the expected time of puberty, the height of children with constitutional growth delay begins to drift further from the growth curve because of delay in the onset of the pubertal growth spurt. Catch-up growth, onset of puberty, and pubertal growth spurt occur later than average, resulting in normal adult stature and sexual development.

However, a report by Rohani et al on males with constitutional growth delay—mean age 15.2 years at presentation and 20 years at study’s end—found that the majority of patients attained neither their target height nor their predicted adult height. The mean final or near-final height reached by the subjects was 165.7 cm, compared with a predicted adult height of 170.7 cm and a target height of 171.8 cm. [2]

Although constitutional growth delay is a variant of normal growth rather than a disorder, delays in growth and sexual development may contribute to psychological difficulties, warranting treatment for some individuals. Studies have suggested that referral bias is largely responsible for the impression that normal short stature per se is a cause of psychosocial problems; nonreferred children with short stature do not differ from those with more normal stature in school performance or socialization.

Constitutional growth delay is a global delay in development that affects every organ system. Delays in growth and sexual development are quantified by skeletal age, which is determined from bone age radiographic studies of the left hand and wrist. Growth and development are appropriate for an individual’s biologic age (skeletal age) rather than for their chronologic age. Timing and tempo of growth and development are delayed in accordance with the biologic state of maturity. Constitutional growth delay may be inherited as an autosomal dominant, recessive, or X-linked trait. [3]

Approximately 15% of patients with short stature referred for endocrinologic evaluation have constitutional growth delay. Individuals with constitutional growth delay and familial short stature represent another 23%. The frequency of constitutional growth delay may be underestimated because individuals with milder delays and those who are not psychologically stressed may not be seen by subspecialists. In a study of 555 (out of 80,000) schoolchildren below the third percentile in height for age with growth rates below normal (< 5 cm/y), twice as many boys as girls were affected. Constitutional growth delay was found in 28% of boys and 24% of girls, and another 18% of boys and 16% of girls had familial short stature in combination with constitutional growth delay.

No racial bias has been identified.

Although the epidemiologic data indicate that all variants of normal growth are twice as common in boys as in girls, referrals for short stature reflect an even more divergent sex ratio. This likely reflects greater concern about males who are shorter than their peers or who have delayed sexual development.

Patterns of growth consistent with constitutional growth delay occur in infants as young as 3-6 months. However, individuals often do not seek medical attention until puberty, when lack of sexual development becomes a concern and discrepancy in height from peers is magnified by the delay in pubertal growth spurt.

Sultan M, Afzal M, Qureshi SM, et al. Etiology of short stature in children. J Coll Physicians Surg Pak. 2008 Aug. 18(8):493-7. [Medline].

Rohani F, Alai MR, Moradi S, Amirkashani D. Evaluation of near final height in boys with constitutional delay in growth and puberty. Endocr Connect. 2018 Mar. 7 (3):456-9. [Medline]. [Full Text].

Banerjee I, Hanson D, Perveen R, Whatmore A, Black GC, Clayton PE. Constitutional delay of growth and puberty is not commonly associated with mutations in the acid labile subunit gene. Eur J Endocrinol. 2008 Apr. 158(4):473-7. [Medline].

Rothermel J, Lass N, Toschke C, Reinehr T. Progressive Decline in Height Standard Deviation Scores in the First 5 Years of Life Distinguished Idiopathic Growth Hormone Deficiency from Familial Short Stature and Constitutional Delay of Growth. Horm Res Paediatr. 2016. 86 (2):117-25. [Medline].

Rogol AD, Hayden GF. Etiologies and early diagnosis of short stature and growth failure in children and adolescents. J Pediatr. 2014 May. 164(5 Suppl):S1-14.e6. [Medline].

Howard SR. Genes underlying delayed puberty. Mol Cell Endocrinol. 2018 Nov 15. 476:119-28. [Medline]. [Full Text].

Gunn KC, Cutfield WS, Hofman PL, Jefferies CA, Albert BB, Gunn AJ. Constitutional delay influences the auxological response to growth hormone treatment in children with short stature and growth hormone sufficiency. Sci Rep. 2014 Aug 14. 4:6061. [Medline].

Bozzola M, Bozzola E, Montalbano C, Stamati FA, Ferrara P, Villani A. Delayed puberty versus hypogonadism: a challenge for the pediatrician. Ann Pediatr Endocrinol Metab. 2018 Jun. 23 (2):57-61. [Medline]. [Full Text].

Rohayem J, Nieschlag E, Kliesch S, Zitzmann M. Inhibin B, AMH, but not INSL3, IGF1 or DHEAS support differentiation between constitutional delay of growth and puberty and hypogonadotropic hypogonadism. Andrology. 2015 Sep. 3 (5):882-7. [Medline].

Varimo T, Miettinen PJ, Kansakoski J, Raivio T, Hero M. Congenital hypogonadotropic hypogonadism, functional hypogonadotropism or constitutional delay of growth and puberty? An analysis of a large patient series from a single tertiary center. Hum Reprod. 2017 Jan. 32 (1):147-53. [Medline].

Giri D, Patil P, Blair J, et al. Testosterone Therapy Improves the First Year Height Velocity in Adolescent Boys with Constitutional Delay of Growth and Puberty. Int J Endocrinol Metab. 2017 Apr. 15 (2):e42311. [Medline]. [Full Text].

Chioma L, Papucci G, Fintini D, Cappa M. Use of testosterone gel compared to intramuscular formulation for puberty induction in males with constitutional delay of growth and puberty: a preliminary study. J Endocrinol Invest. 2018 Feb. 41 (2):259-63. [Medline].

McGrath N, O’Grady MJ. Aromatase inhibitors for short stature in male children and adolescents. Cochrane Database Syst Rev. 2015 Oct 8. 10:CD010888. [Medline].

Harrington J, Palmert MR. Clinical review: Distinguishing constitutional delay of growth and puberty from isolated hypogonadotropic hypogonadism: critical appraisal of available diagnostic tests. J Clin Endocrinol Metab. 2012 Sep. 97(9):3056-67. [Medline].

Krebs A, Moske-Eick O, Doerfer J, Roemer-Pergher C, van der Werf-Grohmann N, Schwab KO. Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature. J Pediatr Endocrinol Metab. 2012. 25(5-6):581-5. [Medline].

Cook DM, Rose SR. A review of guidelines for use of growth hormone in pediatric and transition patients. Pituitary. 2012 Sep. 15 (3):301-10. [Medline].

[Guideline] Wilson TA, Rose SR, Cohen P, et al. Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr. 2003 Oct. 143(4):415-21. [Medline].

Doneray H, Orbak Z. Association between bone turnover markers and bone mineral density in puberty and constitutional delay of growth and puberty. West Indian Med J. 2008 Jan. 57(1):33-9. [Medline].

Wit JM, Oostdijk W. Novel approaches to short stature therapy. Best Pract Res Clin Endocrinol Metab. 2015 Jun. 29 (3):353-66. [Medline].

Pamela A Clark, MD Consulting Staff, McLeod Physician Associates; Consulting Staff, McLeod Pediatric Subspecialists

Pamela A Clark, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children’s Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Sasigarn A Bowden, MD Associate Professor of Pediatrics, Section of Pediatric Endocrinology, Metabolism and Diabetes, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Associate Fellowship Program Director, Division of Endocrinology, Nationwide Children’s Hospital; Affiliate Faculty/Principal Investigator, Center for Clinical Translational Research, Research Institute at Nationwide Children’s Hospital

Sasigarn A Bowden, MD is a member of the following medical societies: American Society for Bone and Mineral Research, Central Ohio Pediatric Society, Endocrine Society, International Society for Pediatric and Adolescent Diabetes, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, Florida Chapter of The American Academy of Pediatrics, Florida Pediatric Society, International Society for Pediatric and Adolescent Diabetes

Disclosure: Nothing to disclose.

Constitutional Growth Delay

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