Increased plasma β-hydroxybutyrate levels during the fasting test in patients with endogenous hyperinsulinaemic hypoglycaemia

Abstract

Objective: The objective of the present study was to determine whether a plasma b-hydroxybutyrate (BOHB) level O2700 mmol/l during the 72-h fasting test is sufficient to rule out the diagnosis of endogenous hyperinsulinaemic hypoglycaemia (EHH). Research design and methods: We retrospectively studied BOHB levels in 39 patients with EHH who had undergone a 72-h fasting test to make the diagnosis of EHH, and we compared EHH patients with BOHB levels O2700 mmol/l (group 1), EHH patients with BOHB levels !2700 mmol/l (group 2) and 59 controls (median glycaemia: 3.2 mmol/l and median BOHB: 6095 mmol/l). Results: During a 72-h fasting test, nine patients (group 1) had BOHB levels O2700 mmol/l (median 6140 and range 2957-7824) and 30 patients (group 2) had BOHB levels !2700 mmol/l (median 542 and range 0-2607). In group 1, four patients had undergone partial pancreatectomy previously and were evaluated for the recurrence of hypoglycaemia, whereas none of the group 2 patients had been operated. The duration of the fasting test was longer in group 1 than in group 2 (P!0.0001), and at the end of the fasting test, plasma glucose concentrations were not significantly different (PZ0.0617), but insulin (PZ0.004), C-peptide (PZ0.0015) and proinsulin (PZ0.0038) levels were significantly lower in group 1 patients than in group 2 patients, suggesting lower insulin secretion and/or impaired glycaemic counter-regulation. Conclusion: During a fasting test, a BOHB level O2700 mmol/l is observed in some EHH patients, suggesting that BOHB levels cannot rule out the recurrence of EHH, in particular, after partial pancreatectomy.European Journal of Endocrinology 169 91-97

Biochemical and Clinical Features of Insulinoma in a Patient with Turner Syndrome

“…Furthermore, we saw markedly elevated BOHB levels. This may seem surprising, since elevated BOHB levels are thought to rule out EHH with 100% sensitivity and specificity [8]; however, as in this case and consistent with previously described cases [9] their diagnostic specificity is much lower when plasma glucose levels drop below 45mg/dl. High BOHB levels may be explained by the combination of modest elevation in insulin levels and increased insulin resistance specific for TS, facilitating the escape of ketogenesis from the inhibitory effects of insulin, as previously described in setting of posthypoglycemia insulin resistance [10].…”

ENETS Consensus Guidelines Update for the Management of Patients with Functional Pancreatic Neuroendocrine Tumors and Non-Functional Pancreatic Neuroendocrine Tumors

“…The use of an insulin cut-off value of ≤3 instead of ≤ 5uIU/mL is supported by a recent study showing that 9% of patients with insulinoma would be missed using the older recommended value of ≥ 5 [81]. Another study [80] demonstrates that some patients with insulinoma (23%), can have plasma β-hydroxybutyrate levels of >2.7 mmol/liter, especially if they have underwent previous partial pancreatectomy and are being evaluated for recurrence [80]. …”

S2k-Leitlinie Neuroendokrine Tumore

“…Eine Bestimmung der ß-Hydroxybutyrat-Spiegel oder Urin-Ketonkörper sollte am Ende des Tests durchgeführt werden, um ein ausreichendes Fasten zu bestätigen [116,119,120]. Niedrige Hydroxybutyrat-Spiegel (< 2,7 mmol/l) im Zusammenhang mit einer nachgewiesenen Hypoglykämie weisen auf eine inadäquate autonome Insulinsekretion hin, auch wenn insbesondere bei Patienten mit Insulinomrezidiv und Z. n. partieller Pankreatektomie auch höhere Hydroxybutyrat-Spiegel beschrieben wurden [123]. Ein Glukagon-Test am Ende der 72-Stunden-Hungerperiode kann zusätzlich durchgeführt werden.…”