Endocrine Abstracts

A 92-year-old man presented with a one-month history of episodic aggression, confusion, urinary incontinence and auditory hallucinations. Episodes lasted 30 - 150 minutes, occurred daily and were abruptly self-terminating. Between episodes he was cognitively intact and lived independently. Initial investigations revealed a plasma glucose of 11.0 millimoles per litre, other biochemical tests were normal.

He was known to have a pleural mass at the left lung base, discovered a year previously when admitted for assessment of breathlessness. Computed tomography had shown a hypervascular mass, measuring 9 x 7 centimetres, consistent with a pleural sarcoma or fibrosarcoma. One year later it measured 15 x 15 centimetres.

EEG during an event suggested a diagnosis of metabolic encephalopathy and simultaneous plasma glucose was 2.2 millimoles per litre. Overnight fasting precipitated a further event when plasma glucose was 1.5 millimoles per litre; insulin: <0.8 milliunits per litre; cortisol 402 nanomoles per litre; IGF-I: 4.0 and IGF-II: 61.0 nanomoles per litre, ratio IGF-II:IGF-I 15.2 (reference range <10).

Non-islet cell tumour hypoglycaemia is caused by over expression of the prepro-IGF-II gene within tumour cells. IGF-II binds to a specific binding protein (IGFBP-3) and an acid labile subunit to form a high molecular weight complex controlling IGF-II hypoglycaemic activity. Abnormal processing of tumour related IGF-II leads to the production of a higher molecular weight form (big IGF-II) binding IGFBP-3 but not ALS. This has high insulin like activity, exerting a hypoglycaemic effect. Glucocorticoids suppress production of big IGF-II and thus hypoglycaemia.

These results therefore suggested non-islet cell tumour hypoglycaemia, secondary to excessive secretion of IGF II. Treatment with 10 milligrams of prednisolone daily has rendered him euglycaemic and symptom free.

This case also clearly demonstrates that patients with episodic confusion should have repeated blood glucose measurements, even if baseline measurements are normal or high.