J Clin Endocrinol Metab. 2024 Apr 10:dgae244. doi: 10.1210/clinem/dgae244. Online ahead of print.
ABSTRACT
CONTEXT: 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.
OBJECTIVE: To determine whether high dose GH can overcome GH resistance in this specific patient resulting in normal IGF-1 levels and improved growth rates.
DESIGN: Single patient trial of ascending doses of GH followed by dose stable phase; total 12 months of treatment.
PATIENT: Patient has a heterozygous variant in GH receptor resulting in elevated levels of GH binding protein manifesting as GH resistance and severe short stature.
INTERVENTIONS: 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.
OUTCOME MEASURES: 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.
RESULTS: 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.
CONCLUSIONS: 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.
PMID:38597155 | DOI:10.1210/clinem/dgae244
