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Constitutional Growth Delay Workup

  • Author: Pamela A Clark, MD; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Nov 20, 2015
 

Laboratory Studies

Constitutional growth delay (CGD) in children with slow growth or delayed puberty is a diagnosis of exclusion. Evaluation excludes hormonal deficiencies, occult systemic illness, or syndromes associated with growth impairment as potential underlying causes.

Hormonal evaluation

Thyroid function

Thyroxine (T4) and thyroid-stimulating hormone (TSH) levels are within the reference range in patients with constitutional growth delay.

GH production

Random growth hormone (GH) values are of little use because of the pulsatile fashion in which GH is secreted by the pituitary. Rather, levels of insulinlike growth factor-1 (IGF-1) and its major binding protein (IGFBP-3) are measured. They are a reliable reflection of GH production if malnutrition is not a concern. IGF-1 and IGFBP-3 levels are sex and age specific; they should be interpreted using skeletal age (see Radiography) rather than chronologic age. GH production is normal for bone age (biologic age) in constitutional growth delay but may appear decreased if interpreted in the context of chronologic age because of the natural increment in GH production with advancing age and pubertal stage. GH provocative testing may also yield falsely low values in some prepubertal individuals with constitutional growth delay unless they are primed with sex steroids (ie, testosterone, estrogen).[4]

Gonadotropin (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) secretion

LH and FSH are helpful only if the skeletal maturation is advanced to the stage consistent with puberty (ie, at least age 10 y in girls and age 12 y in boys). Low levels of these hormones are expected in young children and adolescents with younger skeletal age. This is defined as physiologic hypogonadotropic hypogonadism. Extremely elevated LH and FSH levels are indicative of gonadal dysfunction (ie, pathologic hypergonadotropic hypogonadism) and convey a poor prognosis for spontaneous pubertal development and future sexual function. Such levels are found in patients with Turner syndrome and in patients with Kallmann syndrome (see below) and gonadal damage from chemotherapy and irradiation.

Routine laboratory studies

Abnormal routine laboratory study findings may suggest the presence of diseases such as inflammatory bowel disease, renal tubular acidosis, occult malignancy, infections, and autoimmune disorders. Routine screening to rule out occult systemic disease as a cause for growth impairment or pubertal delay includes the following tests:

  • CBC count with differential
  • Chemistries including renal and hepatic indices
  • Erythrocyte sedimentation rate
  • Urinalysis

Genetic evaluation

If syndromes are suspected based on physical examination findings or family history, a karyotype or referral for genetic evaluation may be indicated. Syndromes that may mimic constitutional growth delay include, but are not limited to, the following:

  • Turner syndrome (females) - Short stature and gonadal failure; abnormality of X chromosome
  • Noonan syndrome - Turner phenotype but normal karyotype; often with abnormalities of pubertal development
  • Kallmann syndrome - Hyposmia or anosmia and hypogonadotropic hypogonadism
  • Russell-Silver syndrome - Marked growth retardation of prenatal onset
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Imaging Studies

Radiography

A radiographic study of the left hand and wrist to assess skeletal maturation is critical in diagnosing constitutional growth delay. Typically, the bone age begins to lag behind chronologic age during early childhood and is delayed in adolescence by an average of 2-4 years. Because the timing of puberty, the pubertal growth spurt, and epiphyseal fusion are dependent on biologic age (skeletal maturation) rather than chronologic age, all of these events are delayed in accordance with bone age. Lateral skull radiographs are rarely obtained because they are only helpful in the context of intracranial calcifications, such as those associated with craniopharyngiomas.

MRI

MRI of the pituitary gland is indicated if pituitary dysfunction is found upon hormonal evaluation or when physical symptoms (eg, visual changes, severe headaches) are present in the context of growth failure or pubertal delay.

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Contributor Information and Disclosures
Author

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.

Specialty Editor Board

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.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

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.

References
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  15. Racine MS, Symons KV, Foster CM, Barkan AL. Augmentation of growth hormone secretion after testosterone treatment in boys with constitutional delay of growth and adolescence: evidence against an increase in hypothalamic secretion of growth hormone-releasing hormone. J Clin Endocrinol Metab. Jul 2004. 89(7):3326-31. [Medline]. [Full Text].

  16. Yap F, Hogler W, Briody J, et al. The skeletal phenotype of men with previous constitutional delay of puberty. J Clin Endocrinol Metab. Sep 2004. 89(9):4306-11. [Medline]. [Full Text].

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Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.
 
 
 
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