Pembrolizumab-induced fulminant type 1 diabetes with C-peptide persistence at first referral.

SUMMARY: A 72-year-old man with no history of diabetes was referred to our department due to hyperglycemia during pembrolizumab treatment for non-small-cell lung carcinoma. His blood glucose level was 209 mg/dL, but he was not in a state of ketosis or ketoacidosis. Serum C-peptide levels persisted at first, but gradually decreased, and 18 days later, he was admitted to our hospital with diabetic ketoacidosis (DKA). The patient was diagnosed with fulminant type 1 diabetes (FT1D) induced by pembrolizumab. According to the literature, the insulin secretion capacity of a patient with type 1 diabetes (T1D) induced by anti-programmed cell death-1 (anti-PD-1) antibody is depleted in approximately 2 to 3 weeks, which is longer than that of typical FT1D. Patients with hyperglycemia and C-peptide persistence should be considered for hospitalization or frequent outpatient visits with insulin treatment because these could indicate the onset of life-threatening FT1D induced by anti-PD-1 antibodies. Based on the clinical course of this patient and the literature, we suggest monitoring anti-PD-1 antibody-related T1D. LEARNING POINTS: Immune checkpoint inhibitors, such as anti-PD-1 antibodies, are increasingly used as anticancer drugs. Anti-PD-1 antibodies can cause immune-related adverse events, including T1D. FT1D, a novel subtype of T1D, is characterized by the abrupt onset of hyperglycemia with ketoacidosis, a relatively low glycated hemoglobin level and depletion of C-peptide level at onset. In patients being treated with anti-PD-1 antibody, hyperglycemia with C-peptide level persistence should be monitored through regular blood tests. Because of C-peptide persistence and mild hyperglycemia, it is possible to miss a diagnosis of life-threatening FT1D induced by anti-PD-1 antibody. In particular, in patients who have no history of diabetes, hyperglycemia without DKA is likely to be the very beginning of anti-PD-1 antibody-induced T1D. Therefore, such patients must be considered for either hospitalization or frequent outpatient visits with insulin injections and self-monitoring of blood glucose.

Hungry bone syndrome after thyroidectomy for thyroid storm.

A 39-year-old man was admitted to our hospital with the diagnosis of thyroid storm due to Graves' disease. Near-total thyroidectomy was performed after 1 month's pharmacological treatment, and he presented with tetany next morning. Serum corrected calcium value was 5.7 mg/dL. Procollagen type 1 N-terminal propeptide increased considerably, while tartrate-resistant acid phosphatase 5b decreased. These changes indicated that bone formation exceeded bone resorption in reverse after thyroidectomy. Calcium gluconate was administered intravenously for 14 days, before the patient was discharged. Oral administration of calcium and active forms of vitamin D was continued for 4 months. Rapid skeletal uptake of calcium from blood caused severe and persistent hypocalcaemia, which is called hungry bone syndrome. When patients with Graves' disease have severe thyrotoxicosis, high serum alkaline phosphatase levels and low bone mineral densities, they are at high risk for hungry bone syndrome after thyroidectomy, and should be educated for the symptoms of hypocalcaemia.

Tuberculous Addison's disease with increased hydrocortisone requirements due to administration of rifampicin.

A 58-year-old man was referred to our hospital for darkened skin, general fatigue and weight loss. His adrenocorticotropic hormone and cortisol levels indicated a primary adrenal insufficiency. 18Fluorodeoxyglucose positron emission tomography/CT showed bilateral enlargement of the adrenal glands, with 18fluorodeoxyglucose accumulation. Loop-mediated isothermal amplification assays of bronchoalveolar lavage fluid were positive for Mycobacterium tuberculosis The patient was diagnosed with tuberculous Addison's disease and treated with antituberculosis agents, including rifampicin. The patient's fatigue worsened gradually after initiation of rifampicin, and the dosage of hydrocortisone was increased. Serum cortisol level monitoring at 2 hours after administration of hydrocortisone was shown to be clinically useful for determining the optimal dose, especially with concurrent use of rifampicin.