A Clinical Trial of High Dose Growth Hormone in a Patient with a Dominant Negative Growth Hormone Receptor Mutation
Rare patients with short stature and growth hormone (GH) resistance have dominant-negative variants in the GH receptor. We describe a patient with GH resistance due to elevated levels of GH binding protein and demonstrate the potential for a precision medicine intervention. To determine whether high...
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Published in | The journal of clinical endocrinology and metabolism |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
10.04.2024
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Subjects | |
Online Access | Get more information |
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Summary: | Rare patients with short stature and growth hormone (GH) resistance have dominant-negative variants in the GH receptor. We describe a patient with GH resistance due to elevated levels of GH binding protein and demonstrate the potential for a precision medicine intervention.
To determine whether high dose GH can overcome GH resistance in this specific patient resulting in normal IGF-1 levels and improved growth rates.
Single patient trial of ascending doses of GH followed by dose stable phase; total 12 months of treatment.
Patient has a heterozygous variant in GH receptor resulting in elevated levels of GH binding protein manifesting as GH resistance and severe short stature.
Daily subcutaneous GH starting at 50 micrograms/kg/day and escalating to 250 micrograms/kg/day until goal IGF-1 achieved. Subject continued 250 micrograms/kg/day for a total treatment duration of 12 months.
The primary outcome measure was the dose of GH required to achieve an IGF-1 level above the mid-point of the normal range. Secondary endpoints included height velocity and the change in height SDS during the 1st year of treatment.
A dose of GH of 250 micrograms/kg/day achieved the target IGF-1 level. The patient's annualized height velocity was 8.7 cm/year, an increase of 3.4 cm/year from baseline, resulting in a 0.81 SD gain in height.
A precision medicine approach of extremely high dose GH was able to overcome GH resistance in a patient with a dominant-negative variant in the GH receptor resulting in elevated GH binding protein levels. |
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ISSN: | 1945-7197 |
DOI: | 10.1210/clinem/dgae244 |