Non-islet cell tumour hypoglycaemia in adrenocortical carcinoma responding to combined growth hormone and corticosteroid therapy

C E Plowman; O Soruna; J Pittaway; E Goodchild; J Shamash; TT Chung; T E Abdel-Aziz; Drake W M

doi:10.1530/endoabs.100.OC2

Case History: A 26-year-old woman with known metastatic adrenocortical carcinoma (ACC) was transferred to our department with recurrent severe hypoglycaemic episodes. Her ACC was diagnosed in 2018 and a 175 × 130 × 89 mm 1200 g mass was surgically resected (ENS@T stage-II, Weiss score-5, Ki-67 20%, Helsinki score-28). Her disease progressed despite adjuvant radiotherapy, mitotane and three chemotherapy regimens. In January 2023, she began experiencing episodes of profound hypoglycaemia, associated with hypokalaemia. She had loss of hypoglycaemic awareness and had prolonged hospitalisations for collapse and seizures.

Investigations and method: Her diagnostic work up centred on serum samples taken during a hypoglycaemic episode, including c-peptide, insulin, growth hormone (GH), insulin-like growth factor (IGF)-1 and sulphonylurea screen. Subsequent IGF-I and IGF-II assays were done before and after initiating treatment.

Results and treatment: The raised IGF-I:IGF-II ratio (30.3, normal <10) confirmed non-islet cell tumour hypoglycaemia (NICTH). A trial of GH (somatropin 1.2 mg OD subcutaneously) and corticosteroids (dexamethasone 1 mg OD) was started. Her hypoglycaemia and hypokalaemia resolved within days and her IGF-I:IGF-II ratio improved. Unfortunately, her ACC progressed and she died in February 2024.

Results and treatment
Test	Value
Fasting plasma glucose (3.5-6 mmol/l)	1.4
Potassium(3.5-5.3 mmol/l)	2.4
C-peptide(370-1470 pmol/l)	<50
Insulin(2.6-24.9 mU/l)	<1.0
Beta-hydroxybutyrate(mmol/l)	0.02
Urine sulphonylurea screen	negative
Growth Hormone (mg/l)	0.60
IGF-1 (103.3-328.4 mg/l)	39

Table 1.
Test	February-23	April-23	May-23	November-23
IGF-I(11.2-54.5 nmol/l)	2.3	GH and corticosteroids started	11.3	11.2
IGF-II(nmol/l)	69.7		139.4	85.5
IGF-II:IGF-I ratio(<10)	30.3		12.3	7.6

Conclusions: ACCs are rare; although 50-60% are functional they typically produce glucocorticoids and/or mineralocorticoids and/or or androgens. Although many ACCs are associated with overexpression of IGF-II, aberrant expression of the immature form of IGF-II believed to be important in the mechanism of NICTH is very rare. NICTH can be suspected in the context of malignancy with recurrent hypoglycaemia, exclusion of the presence of endogenous/exogenous insulin and is supported by a raised serum IGF-I:IGF-II ratio. After initial stabilisation with glucagon and glucose, management can be surgical or with medical therapy. Treatment options include GH and/or corticosteroids. Somatostatin analogues have been used with varying effect. This is a very rare case of metastatic ACC secreting pro-IGF-II causing NICTH. The hypoglycaemic episodes responded well to combination treatment with corticosteroids and GH. The use of GH in this setting is a risk-benefit decision; the theoretical mitogenic effects of GH on the ACC were offset by the need to treat life-threatening hypoglycaemia.

Endocrine Abstracts

OC2