Endocrine Abstracts

Background: Gastrointestinal stromal tumours (GIST) are a rare cause of non-islet cell tumour hypoglycaemia (NICTH), usually due to paraneoplastic secretion of incompletely processed insulin-like growth factor-2 (“big IGF-2”). Glucocorticoids are first-line therapy; somatostatin analogues and diazoxide have variable efficacy.

Case: A 54-year-old woman with GIST and hepatic metastases presented with recurrent symptomatic hypoglycaemia (capillary glucose 1.9–2.8 mmol/l). Thyroid function, adrenal reserve, and hepatic synthetic function were normal. During hypoglycaemia, insulin and C-peptide were suppressed; IGF-2:IGF-1 ratio was elevated at 17.7 (normal < 10), consistent with NICTH. Hypoglycaemia persisted despite continuous carbohydrate supplementation and prednisolone 30 mg daily. Over subsequent weeks, prednisolone was replaced with dexamethasone, short-acting octreotide (100 µg subcutaneously three times daily) was commenced, and diazoxide was added, without benefit. Trans-arterial chemoembolisation (TACE) was performed in an attempt to reduce metastatic burden and IGF-2 secretion, however hypoglycaemia persisted. Recombinant human growth hormone (Somatropin 1 mg subcutaneously daily) was initiated but hypoglycaemia recurred after 5 days; increasing the dose to 1.6 mg daily achieved sustained euglycaemia. Treatment was well tolerated, and euglycaemia has been maintained to date despite ongoing disease progression.

Discussion: This case illustrates GIST-associated NICTH unresponsive to glucocorticoids, somatostatin analogue, diazoxide, and TACE, but resolving with recombinant growth hormone. Benefit likely reflects stimulation of hepatic gluconeogenesis and increased IGF-binding protein concentrations, which sequester “big” IGF-2 and reduce its bioactivity. While glucocorticoids remain the mainstay of NICTH therapy, this case adds to limited evidence supporting growth hormone as an effective salvage option in refractory disease.