From the Guidelines
For a patient with normal blood panel but abnormal bone age scan, the workup and treatment plan should focus on identifying and addressing the underlying cause of bone age discrepancy. Initial evaluation should include a thorough history and physical examination, with particular attention to growth patterns, pubertal development, and family history. Additional testing should include thyroid function tests (TSH, free T4), growth hormone stimulation test, IGF-1 levels, and sex hormone levels (LH, FSH, estradiol or testosterone) 1. Imaging studies such as pelvic ultrasound in females or testicular ultrasound in males may be indicated. If the bone age is advanced, consider evaluation for precocious puberty with GnRH stimulation test. If delayed, assess for growth hormone deficiency or hypothyroidism. Treatment depends on the specific diagnosis: GnRH analogs (such as leuprolide acetate 7.5-15 mg IM monthly) for precocious puberty; growth hormone replacement (0.16-0.24 mg/kg/week divided into daily subcutaneous injections) for growth hormone deficiency; or levothyroxine for hypothyroidism. Regular follow-up every 3-6 months is essential to monitor growth velocity, pubertal progression, and repeat bone age studies annually, as recommended by the American College of Radiology for monitoring bone mineral density 1. Early intervention is crucial as bone age discrepancies can significantly impact final adult height, with advanced bone age potentially resulting in premature epiphyseal fusion and compromised height potential. In terms of bone health, DXA scanning is important for both untreated and treated patients, and patients receiving treatment who demonstrate decreasing BMD on follow-up scans may require an adjustment in their pharmacotherapy regimen 1. The monitoring time interval is based on the expected rate of change of bone mineralization and is typically 2 years, unless the patient is at risk for substantial short-term decreases in mineralization, such as patients receiving glucocorticoid therapy, in which case 1-year follow-up is recommended 1. Scan intervals <1 year are discouraged, and it is essential for patients to be scanned on the same DXA scanner as vendor differences in technologies prohibit a direct comparison unless cross-calibration has been performed 1. BMD values, not t scores, are compared between the previous and current scans, and diagnosis is based on t scores, with the WHO defining normal BMD as a t score greater than –1.0, low bone mass or osteopenia as –1.0 to –2.4, and osteoporosis as t scores equal to or less than –2.5 1.
From the Research
Workup and Treatment Plan
For a patient with a normal blood panel but an abnormal bone age scan, the following steps can be considered:
- Evaluate thyroid function, as growth hormone (GH) therapy can affect thyroid axis 2, 3, 4, 5, 6
- Assess the need for GH therapy, as it can impact bone growth and development
- Monitor thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels, as GH therapy can cause changes in these levels 2, 3, 5, 6
- Consider the use of thyrotropin-releasing hormone (TRH) stimulation tests to identify patients at risk of central hypothyroidism 2, 4
Potential Effects of GH Therapy
GH therapy can have various effects on thyroid function, including:
- Increased peripheral conversion of T4 to T3 3, 5
- Decreased serum FT4 concentrations 2, 5, 6
- Increased risk of central hypothyroidism, particularly in patients with organic pituitary disease or multiple pituitary hormone deficiencies 4
- Changes in TSH levels, although these may not always be significant 3, 5
Monitoring and Follow-up
Regular monitoring of thyroid function is recommended for patients on GH therapy, particularly during the first year of treatment 6
- Measure FT4, TSH, and T3 levels at baseline, 6 months, 12 months, and yearly thereafter
- Adjust GH dose according to insulin-like growth factor-I (IGF-I) levels and monitor for signs of hypothyroidism 6