Surgical Remission of Acromegaly Resolves Neuroglycopenia and Paradoxical Rise in GH after OGTT

Background: Acromegaly is known to cause insulin resistance through increased gluconeogenesis and reduction in peripheral glucose use; however, hypoglycemia related to acromegaly has not been reported. Clinical Case: A 58-year old man presented for evaluation of several elevated serum IGF1 levels. The patient had reported years of increased body heat but no changes in his hands or feet and no voice deepening. He recently needed 15 dental crowns due to gaps in his teeth. He also had difficult to manage OSA and weight gain. The patient reported neuroglycopenia after a high glycemic meal or drink, although he was never able to objectively measure any low blood glucoses when they occurred; these symptoms improved but did not resolve despite adhering to a low carbohydrate diet. He also had decreased libido and erectile dysfunction. Exam was significant for coarse facial features. Prior testing revealed several elevated IGF1 serum levels, the last one being 227 ng/mL (54-194). One year prior, OGTT resulted in an initial GH level of 0.1 ng/mL with a decrease to <0.1 ng/mL after two hours. Repeat OGTT had an initial GH of 2.98 ng/mL which paradoxically rose to 12 ng/mL. Fasting BG was 90 mg/dL and peaked at 171 mg/dL. Pituitary MRI showed a 5 mm microadenoma, consistent with acromegaly from a GH secreting adenoma. He underwent a TSSC, and his heat intolerance, low libido, and symptom of hypoglycemia resolved completely. Subsequent IGF1 levels and MRI imaging normalized. Postoperatively OGTT showed a peak GH of 0.23 ng/mL with a peak glucose of 134 mg/dL. There was no paradoxical rise in GH. Discussion: Acromegaly is commonly associated with insulin resistance in ~30% of cases; however, there are no reports of associated neuroglycopenia after a carbohydrate-rich meal or OGTT, which in our patient resolved after successful removal of the pituitary microadenoma. His low glucose symptoms could have been a result of reactive hypoglycemia, which is often seen in patients with diabetes or even prediabetes. However this patient had no history of either. He did not have evidence of any tumors causing hypoglycemia and no gastric surgery to suggest a related etiology (e.g, dumping syndrome or nesidioblastosis). Conversely since GH is normally anabolic and stimulates insulin release, the patient’s elevated GH may have caused an abnormal increase in insulin, leading to his hypoglycemia symptoms. Indeed GIP, which stimulates insulin, is thought to be the cause of the paradoxical rise in GH seen in 30% of acromegaly cases. Remarkably, the patient’s hypoglycemia symptoms disappeared after treatment of the acromegaly, which leads us to consider that excess GH was the culprit.