What is the recommended hormonal evaluation for a patient presenting with short stature?

Hormonal Evaluation of Short Stature

Initial Hormonal Assessment

All children with pathologic short stature should undergo thyroid function testing (TSH and free T4) and IGF-1 measurement as the primary hormonal screening tests, with bone age radiograph to guide further evaluation. 1, 2

The hormonal evaluation should be performed after ruling out familial short stature and constitutional delay of growth, which together account for approximately 50% of short stature cases and do not require hormonal testing. 3

Algorithmic Approach to Hormonal Testing

Step 1: Universal Hormonal Screening

• Thyroid function tests (TSH, free T4) - Hypothyroidism is a previously unrecognized endocrine cause identified in approximately 2% of short stature evaluations and must be excluded first. 3
• IGF-1 level - Severely low IGF-1 indicates growth hormone axis dysfunction and is the primary screening tool for growth hormone deficiency. 2
• Bone age radiograph (left wrist and hand) - While not strictly hormonal, this is essential to interpret hormonal findings, as delayed bone age is characteristic of endocrinopathies. 1, 2, 4

Step 2: Growth Hormone Axis Evaluation (If IGF-1 is Low)

• Growth hormone stimulation testing should be performed when IGF-1 is severely low, bone age is delayed, and growth velocity is decreased. 2
• Growth hormone deficiency comprises 44% of endocrine causes of short stature and 13% of all pathologic short stature cases. 5
• IGFBP-3 measurement can provide additional information about GH axis function when IGF-1 results are equivocal. 2

Step 3: Additional Pituitary Hormone Assessment

• FSH and LH levels should be measured to differentiate isolated growth hormone deficiency from multiple pituitary hormone deficiency. 2
• Isolated hormone deficiency pattern (normal TSH, FSH, LH with low IGF-1) suggests isolated GHD rather than panhypopituitarism. 2

Sex-Specific Hormonal Considerations

For Girls with Short Stature

• Karyotype analysis is mandatory even without obvious Turner syndrome features, as chromosomal abnormalities (primarily Turner syndrome) represent 19% of pathologic diagnoses. 3, 1
• Turner syndrome can present with isolated short stature and subtle or absent dysmorphic features, making it a critical diagnostic pitfall. 1

For Boys with Delayed Puberty

• Testosterone levels should be assessed in adolescent boys with constitutional delay to distinguish from hypogonadotropic hypogonadism. 6

Clinical Context That Modifies Hormonal Testing

Proportionate Short Stature with Normal Growth Velocity

• Focus on thyroid function and Turner syndrome screening (in girls), as growth hormone deficiency typically presents with decreased growth velocity. 1, 6

Proportionate Short Stature with Decreased Growth Velocity

• Prioritize complete GH axis evaluation (IGF-1, stimulation testing) and thyroid function, as these endocrinopathies cause growth deceleration. 2, 6

Disproportionate Short Stature

• Hormonal evaluation is lower priority; focus shifts to skeletal survey and genetic testing for skeletal dysplasias and SHOX mutations. 1, 4

Short Stature with Dysmorphic Features

• While chromosomal analysis takes precedence, thyroid function should still be assessed as syndromic patients can have multiple endocrinopathies. 7, 8

Critical Pitfalls to Avoid

• Missing hypothyroidism - Always test thyroid function before attributing short stature to other causes, as it is treatable and can be occult. 3
• Failing to screen girls for Turner syndrome - This is the most common pathologic diagnosis in genetic evaluations and can present without obvious features. 3, 1
• Ordering GH stimulation testing prematurely - IGF-1 should be measured first; normal IGF-1 makes GH deficiency unlikely and avoids unnecessary provocative testing. 2
• Initiating testosterone or GH therapy before obtaining bone age - This risks premature epiphyseal closure and compromised final adult height. 4
• Assuming normal variants without hormonal screening - Even with familial history, approximately 2% have unrecognized endocrine causes. 3

Integration with Growth Velocity Assessment

• Growth velocity documentation over 6 months is essential to interpret hormonal results, as pathologic deceleration (crossing centile lines) indicates likely endocrinopathy requiring full hormonal evaluation. 3, 2
• Normal growth velocity with short stature makes growth hormone deficiency less likely but does not exclude hypothyroidism or Turner syndrome. 1, 6