Poster Presentation ESA-SRB-APEG-NZSE 2022

Paliperidone induced hypoglycaemia a diagnostic dilemma   (#341)

Naeel Mohammad 1 , Evelyn TAN 1
  1. John Hunter Hospital, Hunter New England Local Health District, Newcastle, NSW, Australia

 

Mr. M. A. is a 36-year-old male with a nomadic lifestyle who was hospitalised with prominent negative symptoms of schizophrenia in August 2021 and started on paliperidone and venlafaxine. A routine metabolic screen in February 2022 revealed a fasting glucose of 2.7mmol/l despite being asymptomatic. He was referred to the closest regional hospital for further investigation of recurrent asymptomatic hypoglycaemia. He completed the full 72-hour fast due to a lack of Whipple’s triad and the results supported a negative test.

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Sulphonylurea screening, insulin antibody, morning cortisol, IGF-1, renal and liver function tests were normal. He is non-alcoholic and eats regularly. There was no family history of hypoglycaemia or pancreatic disorders.

Mr. M.A was transferred to our tertiary service for additional imaging. DOTATATE scans, CT and MRI scans were negative for pancreatic pathology. As hypoglycaemia persisted, he underwent a calcium stimulation test (Table 2), which revealed a 2 to 3 fold increase in insulin levels at the proximal splenic artery at 90s (10.3-->28.3mIU/L), andgastroduodenal artery at 90s (23-->45.6mIU/L). He had started on Diazoxide.

 

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As there were cases of severe hypoglycaemia with risperidone and risperidone analogue paliperidone, discussions with the mental health team led to switching paliperidone to aripriprazole in May 2022. BGLs over the next 2 months ranged between 3.2 and 11.6 mmol/l. Diazoxide was discontinued and regular corn-starch was commenced.

Discussion:

Several cases of hypoglycaemia caused by antipsychotics have been reported [1,2,3]. A fall in blood glucose is normally rapidly detected, and counter-regulatory mechanisms are recruited. The α2-adrenoceptors on pancreatic β-cells inhibit insulin secretion and seem to be critically important for this counter-regulatory response. The α2-adrenoceptor antagonists increase insulin secretion [2,4]. Risperidone has an antagonistic effect on α2-adrenoceptors[2]. Paliperidone, the primary active metabolite of risperidone, has an affinity for α2-adrenoceptors that is slightly stronger than that of risperidone [1,5].

  1. 1. Tsubasa Omi, Keisen Riku, Motoyuki Fukumoto, Koji Kanai, Yumi Omura, Hiromune Takada, Hidenori Matunaga, "Paliperidone Induced Hypoglycemia by Increasing Insulin Secretion", Case Reports in Psychiatry, vol. 2016, Article ID 1805414, 3 pages,2016. https://doi.org/10.1155/2016/1805414.
  2. 2. Nagamine T. Hypoglycemia associated with insulin hypersecretion following the addition of olanzapine to conventional antipsychotics. Neuropsychiatr. Dis. Treat. 2006; 2: 583– 585
  3. 3. Fagerholm V, Haaparanta M, Scheinin M. α2-adrenoceptor regulation of blood glucose homeostasis. Basic Clin. Pharmacol. Toxicol. 2011; 108: 365– 370.
  4. 4. K. Melkersson, “Clozapine and olanzapine, but not conventional antipsychotics, increase insulin release in vitro,” European Neuropsychopharmacology, vol. 14, no. 2, pp. 115–119, 2004.
  5. 5. J. A. Gray and B. L. Roth, “The pipeline and future of drug development in schizophrenia,” Molecular Psychiatry, vol. 12, no. 10, pp. 904–922, 2007