The mechanistic target of rapamycin (mTOR) inhibitor everolimus is an antitumor agent known to cause hyperglycemia. However, the clinical course of everolimus-induced hyperglycemia, its pathophysiological basis, and the treatment strategy are not clear. In this case series report, we present the clinical course of everolimus-induced hyperglycemia in four patients. Hyperglycemia occurred 3-8 weeks after the administration of everolimus irrespective of the body mass index (range, 21.3-29.1 kg/m 2) or pre-existing diabetes. Insulin or insulin secretagogues were required for glycemic control in most of the patients. Of note, the hyperglycemia was reversible in all patients, and none of the patients required anti-diabetic agents to achieve adequate glycemic control after cessation of everolimus therapy. To investigate the underlying mechanism of everolimus-induced hyperglycemia, we assessed insulin secretion and sensitivity by 75 g oral glucose tolerance test, arginine challenge test, and/or hyperinsulinemic-euglycemic clamp study using stable isotope-labeled glucose tracer in two patients. Everolimus did not affect insulin sensitivity in the liver, skeletal muscle, or the adipose tissue. In contrast, everolimus impaired insulin secretion and thereby increased basal hepatic glucose production. These findings further our understanding of the role of mTOR in glucose homeostasis in humans and provide insights for treatment strategies against everolimus-induced hyperglycemia.

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A primary intraventricular haemorrhage (PIVH) usually presents with non-localised neurological symptoms since the haematoma is limited to the ventricles. However, it is sometimes associated with focal neurological signs, whose pathophysiologies are not confirmed. Here, we report on a case of PIVH who showed rare manifestations in the acute stage: upward gaze palsy and convergence insufficiency. The CT and MRI showed intraventricular haematoma without evidence of parenchymal haemorrhage, local mass effect around midbrain or hydrocephalus. There had been bilateral papilloedema, and it resolved along with improvement of the ophthalmic symptoms, suggesting a possible causal relation to increased intracranial pressure. The ophthalmic abnormalities suggested injury of the rostral part of the midbrain, especially the region around the dorsal midbrain tectum. It should be known that PIVH is one of the causes of acutely developing upward gaze palsy and convergence insufficiency.

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