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Abstract Introduction: A 12-year-9-month-old non-Hispanic black male with a history of growth hormone deficiency (GHD), pituitary hypoplasia, pre-diabetes, obesity, hypertension, and hyperlipidemia was initiated on weekly growth hormone (lonapegsomatropin-tcgd) and then transiently developed symptomatic hyperglycemia to 500 mg/dL. We aim to describe this medication effect. Case Presentation: He was born full term and appropriate for gestational age. He was referred to endocrinology at 3.5 years for short stature with a height SDS of -2.48. IGF-1 51.1 ng/mL and IGFBP-3 1.2 ng/mL were low. GH stimulation test noted baseline and peak GH of 0.1 ng/mL. MRI brain showed hypoplastic adenohypophysis, aplastic pituitary stalk, and ectopic neurohypophysis. There had been difficulty with adherence daily GH over the following nine years. BMI trajectory rose to above 180% of the 95th percentile. By age 12, A1c was 6.6%. Metformin was started and increased to 1000 mg twice daily. Subsequent A1c was 6.0%. Due to poor compliance with daily GH, at 12-years-9-months, he was initiated on 22 mg (0.25 mg/kg/week) of weekly lonapegsomatropin-tcgd to improve compliance. The day after his first injection, he developed non-bloody, non-bilious emesis. He denied headaches and endorsed polyuria. Due to concern for increased intracranial pressure, he was sent to the Emergency Department; however, ophthalmologic exam was negative. Initial serum glucose was 500 mg/dL, then 336 mg/dL after one-liter normal saline. Hemoglobin A1c was 5.7%, urine glucose 3+ mg/dL, and urine ketones 2+ mg/dL. Venous pH of 7.379 and bicarbonate of 20.6 mmol/L ruled out diabetic ketoacidosis. Metformin was held during the hospitalization. Hyperglycemia rapidly improved with transient insulin administration. He received one dose of glargine 20 units. He was initiated on lispro carb ratio of 1:8 and correction factor 1:15 for target glucose 150 mg/dL. By day four, glucoses were below 100 mg/dL; lispro was discontinued and he was discharged home. Weekly GH was discontinued with plans to resume daily GH therapy in several months. Conclusion: To conclude, lonapegsomatropin-tcgd offers the convenience of a weekly, rather than daily GH treatment; however, this patient developed a rapid increase in insulin resistance and hyperglycemia requiring insulin. The discrepancy between the glucose of 500 mg/dL and A1c of 5.7%, along with the rapid resolution of hyperglycemia is further consistent with a medication side effect. Close glucose monitoring of patients initiated on weekly growth hormone is crucial, particularly in those with a history of pre-diabetes.

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