Constitutional Growth Delay Workup

Updated: Jan 08, 2019
  • Author: Pamela A Clark, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Workup

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). [7]

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. [8] 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.

Other

A study by Rohayem et al indicated that inhibin B and anti-Müllerian hormone (AMH) are useful in differentiating between boys with prepubertal constitutional delay of growth and puberty and those with hypogonadotropic hypogonadism. The study found that the former had higher levels of inhibin B and AMH than did the latter. [9]

A retrospective study by Varimo et al suggested that in prepubertal boys, testicular volume, gonadotropin-releasing hormone–induced LH level, and basal inhibin B level are the best markers for differentiating constitutional delay of growth and puberty from congenital hypogonadotropic hypogonadism. [10]

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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