Growth Hormone Deficiency as a Cause of Insulin Resistance

Columbus, OH — May 2018

Rohan Henry, MD, and his colleagues in the Section of Endocrinology at Nationwide Children’s Hospital were genuinely puzzled. A 19-year-old woman, treated for medulloblastoma as a 7-year-old, came in after a regular screening of late-onset complications of chemotherapy and radiation therapy. Her hemoglobin A1c was 9.1 percent, clear evidence of diabetes.

Insulin therapy was begun, and doses ultimately reached 2.9 units per kilogram per day (155 units/day), but hemoglobin A1c never dropped below 7.4 percent. What was causing this insulin resistance?

Nothing on the typical differential diagnosis explained it. She was negative for type 1 diabetes antibodies; no chemotherapy drug she had been administered was associated with insulin resistance; liver biopsy ruled out adenomas; she was not obese; she was Caucasian.

A growth hormone stimulation test, though, did show a peak growth hormone level of 0.8 ng/mL. While not normally something an endocrinologist would consider, Dr. Henry was aware of mouse model studies showing that severe growth hormone deficiency can lead to metabolic syndrome. A 1997 publication had also reported on a boy with many pituitary hormone issues who developed a fatty liver. He was treated with hydrocortisone and levothyroxine, but it was not until he was treated with growth hormone that his fatty liver was resolved.

Dr. Henry developed a hypothesis: a fatty liver is hepatic evidence of insulin resistance; the fatty liver was resolved with growth hormone therapy; type 2 diabetes is extreme evidence of insulin resistance; it could be ameliorated with growth hormone as well.

As a poster presented at the 10th International Meeting of Pediatric Endocrinology showed, growth hormone therapy did lead to a significant improvement in the patient’s insulin resistance, ultimately reducing dosage to 1.9 units/kg/day and reducing hemoglobin A1c levels to as little as 5.3 percent.

“Issues of impaired glucose metabolism have been rarely reported in obese patients with growth hormone deficiency, but not in lean patients,” says Dr. Henry, first author on the poster. “We see many patients who have multiple hormone deficiencies after cancer treatment, but we do not always emphasize growth hormone if those patients have finished linear growth. This shows us how important it can be for metabolic reasons.”

This case has a number of other potential implications, says Dr. Henry, who is also an assistant professor of Pediatrics at The Ohio State University College of Medicine. Growth hormone therapy is expensive, and insurance often does not cover it outside of use for linear growth issues – it was a struggle for the patient to receive insurance coverage in this case.

But diabetes and insulin resistance are expensive as well. It may be the case that growth hormone therapy for severely deficient patients should be more readily covered if its deficiency can lead to those other conditions. At the very least, children with growth hormone deficiency should be followed closely with special attention to potential metabolic concerns, says Dr. Henry.

The case also highlights the importance of transitional care for this population.

“Patients who stop growing linearly are more likely to be lost to follow-up, because they no longer think they need to worry about growth hormone therapy,” says Dr. Henry. “This shows that we as providers need to try even harder to ensure they aren’t lost, and also that those who are severely growth hormone deficient are transitioned to adult dosing of growth hormone therapy after the appropriate testing has been performed.”

References:

Henry R, Chaudhari M. Growth Hormone Therapy Ameliorates Insulin Resistance in Severe Growth Hormone Deficiency. 10th International Meeting of Pediatric Endocrinology. 2017 Sept 14-17; Washington D.C.

Takano S, Kanzaki S, Sato M, Kubo T, Seino Y. Effect of growth hormone on fatty liver in panhypopituitarism. Archives of Disease in Childhood. 1997; 76:537-538