Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB1*04:05-DQB1*04:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes.

Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, they can lead to immune-related adverse events, including immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM). While fulminant T1DM is common in East Asia, ICI-T1DM has predominantly been reported in Western countries. In this report, we present the case of a 66-year-old Japanese man with type 2 diabetes mellitus undergoing dialysis for diabetic nephropathy. The patient was diagnosed with left upper lobe lung cancer, and treatment with nivolumab and ipilimumab was initiated. After 48 days, the patient experienced impaired consciousness and difficulty moving. His blood glucose levels were 815 mg/dL, and metabolic acidosis was detected, leading to a diagnosis of diabetic ketoacidosis. The patient was subsequently treated with continuous intravenous insulin. However, his C-peptide levels rapidly depleted, and new-onset ICI-T1DM was diagnosed. Although most Japanese patients with ICI-T1DM test negative for glutamic acid decarboxylase (GAD) antibodies, this case exhibited a strong positivity. Thus, we reviewed the literature on 15 similar Japanese cases, revealing a mean HbA1c level at onset of 8.7% and a mean time from ICI administration to onset of 9.7 weeks, which was shorter than that in GAD-negative cases. Moreover, human leukocyte antigen typing revealed five cases of DRB1*04:05-DQB1*04:01, including the present case, and one case of DRB1*09:01-DQB1*03:03, both of which were susceptible to T1DM haplotypes. These findings suggest that GAD antibody positivity may be associated with acute onset and disease progression in some cases of Japanese patients with ICI-T1DM. Given that the prediction of new-onset ICI-T1DM is challenging, monitoring GAD antibody levels might be useful. However, further studies with large sample sizes and validation across different racial and ethnic populations are warranted.

Concurrent bacterial liver abscess and mild encephalitis/encephalopathy with reversible splenial lesion in a patient with poorly controlled type 2 diabetes.

A 34-year-old man with poorly controlled type 2 diabetes was admitted to our hospital because of fever, headache, vomiting, and impaired consciousness. His hemoglobin A1c level was as high as 11.0%. Abdominal computed tomography revealed a bacterial liver abscess, while head magnetic resonance imaging simultaneously showed a high-signal lesion on diffusion-weighted imaging and a low-signal lesion on the apparent diffusion coefficient map of the splenium of the corpus callosum. No significant findings were detected in the cerebrospinal fluid. The latter findings led to a diagnosis of mild encephalitis/encephalopathy with reversible splenial lesions. His impaired consciousness resolved on Day 5 after treatment with ceftriaxone and metronidazole infusion and intensive insulin therapy; magnetic resonance imaging on Day 20 showed that the lesion in the splenium of the corpus callosum had disappeared. We propose that when a person with poorly controlled diabetes develops a bacterial infection and presents with impaired consciousness and headache, clinicians should consider the complications of mild encephalitis/encephalopathy with reversible splenial lesion.

Lanreotide and diazoxide have comparable effects on glucose levels in an elderly Japanese insulinoma patient: a case report.

An insulinoma is a pancreatic neuroendocrine tumor that causes hypoglycemia. In the elderly, as surgery is not always possible, drugs are an important alternative. However, the effects of lanreotide on insulinomas have not yet been elucidated. We report the case of an 85-year-old Japanese woman who was admitted for loss of consciousness and hypoglycemia, which was resolved after intravenous glucose infusion. Insulin secretion was not inhibited during hypoglycemia. Enhanced computed tomography and OctreoScan scintigraphy revealed a pancreatic tumor (diameter, 13 mm) with radiotracer accumulation. Thus, clinical insulinoma was confirmed. However, the patient refused further examination and surgery. Diazoxide (150 mg/day) therapy resolved hypoglycemia but caused fluid retention. Consequently, we switched to lanreotide (120 mg/6 weeks). Continuous glucose monitoring revealed that both drugs had comparable effects on interstitial glucose normalization. Furthermore, 447 days after the initiation of lanreotide treatment, the patient had no hypoglycemic symptoms. Therefore, lanreotide may be a useful alternative treatment option for inoperable insulinomas in elderly individuals.

Pendred syndrome with hyperthyroidism.

Objectives: Pendred syndrome is an autosomal recessive disorder characterized by the combination of sensorineural deafness and goiter and is caused by biallelic mutations in the SLC26A4/PDS gene. Thyroid function is generally reported as euthyroid or hypothyroid in this condition. We present a case of Pendred syndrome with hyperthyroidism. Patient: An 83-year-old woman with congenital deaf-mutism presented with complaints of nausea. She developed a large goiter and had hearing impairment. Her hearing level was 105 dB in both ears. She presented with hyperthyroidism and was treated with thiamazole. Results: She had a homozygous mutation in c.1579A>C:p.T527P of the SLC26A4 gene, confirming a diagnosis of Pendred syndrome. Conclusion: Pendred syndrome may develop into hyperthyroidism if the size of the goiter increases. Moreover, a homozygous mutation in c.1579A>C:p.T527P of the SLC26A4 gene, which was previously reported to be associated with nonsyndromic hearing loss with enlarged vestibular aqueduct, may also cause Pendred syndrome.

Autoimmune pancreatitis with spontaneous remission on 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

A 79-year-old man with elevated blood glucose was started on insulin therapy. IgG4 was as high as 1,830 mg/dL, and 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) confirmed diffuse pancreatic enlargement and accumulation of FDG. Based on the above, autoimmune pancreatitis (AIP) was diagnosed, but steroid treatment was not performed. IgG4 later declined, and FDG accumulation in the pancreas disappeared on FDG-PET/CT at the age of 83 years. AIP was thought to have gradually remitted spontaneously over time. FDG-PET/CT is useful for evaluating AIP activity.

Insulin autoimmune syndrome possibly caused by coenzyme Q10.

A 52-year-old woman was transported for reduced consciousness. Her blood glucose was only 19 mg/dL, but her blood immunoreactive insulin and insulin antibody levels were high at 250 µU/mL and 50 U/mL, respectively. She had no history of insulin treatment, but she had been taking coenzyme Q10 supplements for three months. Her human leukocyte antigen serotype was DR4. After stopping coenzyme Q10, her hypoglycemia disappeared and immunoreactive insulin and insulin antibody levels normalized. Based on the above, she was diagnosed with insulin autoimmune syndrome caused by coenzyme Q10. It is necessary to be aware of the onset of insulin autoimmune syndrome due to coenzyme Q10. Its pathogenesis requires clarification.

Late onset adrenal insufficiency after adrenalectomy due to latent nonclassical 21-hydroxylase deficiency: A case report.

RATIONALE: Adrenal incidentaloma is sometimes complicated with 21-hydroxylase deficiency (21-OHD). Latent nonclassical 21-OHD in incidentaloma is difficult to diagnose. Although adrenalectomy in 21-OHD has been conducted when malignancy could not be excluded, adrenal insufficiency sometimes occurs, and it might not be observed immediately after operation. Here, we report a case of a 71-year-old man who experienced adrenal insufficiency over 2 decades postadrenalectomy, leading to a diagnosis of latent nonclassical 21-OHD. PATIENT CONCERNS: A 71-year-old man was admitted to the hospital due to difficulty in movements and a sodium level of 119 mEq/L. His medical history revealed precocious puberty and left adrenalectomy because of an incidentaloma at 49 years of age, diagnosed pathologically as an adenoma. He did not attend follow-up visits because he did not have any symptoms. In 2017, 3 months before hospitalization, he experienced general fatigue. A few days before admittance, he complained of difficulty in moving and visual hallucination of small animals. DIAGNOSES: Laboratory evaluations revealed a high level of adrenocorticotropic hormone (ACTH) and low cortisol level. ACTH-stimulating test revealed a low basal level and low response for cortisol, and a high basal level and low response for 17-hydroxyprogesterone. We analyzed large gene deletion or conversion and the 9 most common micro mutations in the CYP21A2 gene by polymerase chain reaction; micro mutation of I172N and heterozygous large gene deletion or conversion were detected leading to the diagnosis of nonclassical 21-OHD. INTERVENTIONS: Immediately, 100 mg hydrocortisone was administered, followed by daily hydrocortisone and saline. The symptoms and hyponatremia improved in a few days. He was discharged from the hospital on day 34 with a daily dose of 15 mg hydrocortisone. LESSONS: Clinicians should be aware of late onset of adrenal insufficiency after adrenalectomy. In such cases, clinicians should not overlook the latent nonclassical 21-OHD.