Recurrent distal cholangiocarcinoma and humoral hypercalcemia of malignancy: report of a rare case and literature review.

A 61-year-old Japanese woman presented with epigastric pain and jaundice. Imaging showed the presence of primary distal cholangiocarcinoma (DCC). A subtotal stomach-preserving pancreaticoduodenectomy was performed, followed by chemotherapy using S-1. However, second-line chemotherapy with gemcitabine and cis-diamminedichloroplatinum was required for the treatment of hepatic metastasis of the DCC 3 months following the surgery. Nine months after the surgery, the serum calcium and parathyroid hormone-related peptide concentrations were high, at 16.5 mg/dL and 28.7 pmol/L, respectively, which suggested the presence of humoral hypercalcemia of malignancy (HHM) secondary to the DCC. Moreover, marked leukocytosis, with a white blood cell count of 40,400/µL, was also present. The patient died 11 months after the diagnosis of DCC. Because hypercalcemia of malignancy is associated with a poor prognosis, and HHM and leukocytosis caused by DCC are very rare, we have presented the present case in detail and provide a review of the existing literature.

Insulinoma presenting with anti-insulin antibodies.

Summary: An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 µU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 µU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies. Learning points: Insulinoma presenting with concomitant anti-insulin antibodies appears rare. Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome. Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.

Continuous glucose monitoring in a patient with insulinoma presenting with unawareness of postprandial hypoglycemia.

Summary: Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 µU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 µU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery. Learning points: Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Current status of low-density lipoprotein cholesterol for primary prevention of coronary artery disease in late-stage elderly persons with type 2 diabetes mellitus: A retrospective, single-center study.

AIMS/INTRODUCTION: The importance of low-density lipoprotein cholesterol (LDL-C) in the primary prevention of cardiovascular disease has recently been reported in the population aged ≥75 years with hypercholesterolemia. Therefore, the current status of LDL-C management for primary prevention of coronary artery disease in patients aged ≥75 years with type 2 diabetes mellitus was investigated. MATERIALS AND METHODS: A total of 124 patients aged ≥75 years who had type 2 diabetes mellitus, but no coronary artery disease, were investigated. The patients' background characteristics, LDL-C, glycemic status, ankle-brachial index and cardio-ankle vascular index were compared between patients taking and not taking LDL-C-lowering agents, such as hydroxymethylglutaryl-CoA reductase inhibitors (statins) and ezetimibe. The details of the antihyperlipidemic and antidiabetic agents used in the present study were also examined. RESULTS: LDL-C was significantly lower in patients taking LDL-C-lowering agents (LDLCLT[+]) than in patients not taking them (LDLCLT[-]), although LDL-C was maintained <120 mg/dL in both groups (93.0 mg/dL vs 102.1 mg/dL). Approximately half of the cases in the LDLCLT(+) group received moderate-intensity statins, with pitavastatin being the most prescribed statin. Glycated hemoglobin was significantly lower in the LDLCLT(+) group than in the LDLCLT(-) group (6.9% vs 7.3%). Sodium-glucose transporter 2 inhibitors were more frequently used in the LDLCLT(+) group than in the LDLCLT(-) group. The ankle-brachial index/cardio-ankle vascular index did not differ between the groups. CONCLUSION: Low-density lipoprotein cholesterol was properly managed for primary prevention of coronary artery disease in patients aged ≥75 years with type 2 diabetes mellitus regardless of the presence or absence of LDL-C-lowering agents.

Serial assessments of anterior pituitary hormones in a case of mixed histiocytosis representing Langerhans cell histiocytosis overlapping with Erdheim-Chester disease.

SUMMARY: A 61-year-old man developed central diabetes insipidus caused by mixed histiocytosis (MH) representing Langerhans cell histiocytosis overlapping with Erdheim-Chester disease. Bone, skin, vascular, and retroperitoneal involvements were also observed. Dynamic hormonal testing showed normal responses for anterior pituitary hormones, except for impaired secretion of growth hormone (GH). MRI of the brain showed thickening of the pituitary stalk with slightly reduced signal hyperintensity in the posterior pituitary lobe on T1-weighted imaging. During 2 years of follow-up without radical treatment for MH, imaging studies suggested extension of vascular and retroperitoneal involvements. In contrast, brain MRI did not show any particular interval changes, except for the disappearance of hyperintense signalling in the posterior pituitary lobe. Moreover, no other anterior pituitary dysfunctions beyond GH deficiency emerged during the 2 years of follow-up. The natural history of MH in this case is described, focusing on serial assessments of pituitary functions using dynamic tests. LEARNING POINTS: Erdheim-Chester disease and Langerhans cell histiocytosis overlapping as MH was described, focusing on pituitary functions. MH caused both GH deficiency and central diabetes insipidus. Despite a lack of radical therapy for MH, no other anterior pituitary dysfunctions emerged for 2 years. Radiological images showed no particular interval changes in pituitary stalk lesions, while vascular and retroperitoneal involvements extended.

Comparison of glucose monitoring between Freestyle Libre Pro and iPro2 in patients with diabetes mellitus.

AIMS/INTRODUCTION: Flash and continuous glucose monitoring systems are becoming prevalent in clinical practice. We directly compared a flash glucose monitoring system (FreeStyle Libre Pro [FSL-Pro]) with a continuous glucose monitoring system (iPro2) in patients with diabetes mellitus. MATERIALS AND METHODS: Glucose concentrations were simultaneously measured using the FSL-Pro, iPro2 and self-monitoring blood glucose in 10 patients with diabetes mellitus, and agreement among them was assessed. RESULTS: Parkes error grid analysis showed that the 92.9 and 7.1% of glucose values measured using the FSL-Pro fell into areas A and B, respectively, and that 96.3, 2.8 and 0.9% of those determined using iPro2 fell into areas A, B and C, respectively. The median absolute relative differences compared with self-monitoring blood glucose were 8.1% (3.9-12.7%) and 5.0% (2.6-9.1%) for the FSL-Pro and iPro2, respectively. Analysis of 5,555 paired values showed a close correlation between FSL-Pro and iPro2 glucose values (ρ = 0.96, P < 0.01). Notably, 65.3% of all glucose values were lower for the FSL-Pro than the iPro2. Median glucose values also decreased by 3.3% for the FSL-Pro compared with the iPro2 (177.0 [133.0-228.0] vs 183.0 [145.0-230.0] mg/dL, P < 0.01). The difference in glucose values between the two systems was more pronounced in hypoglycemia. The median absolute relative difference between FSL-Pro and iPro2 during hypoglycemia was much larger than that during euglycemia and hyperglycemia. CONCLUSIONS: Both the FSL-Pro and iPro2 systems are clinically acceptable, but glucose values tended to be lower when measured using the FSL-Pro than the iPro2. Agreement was not close between these systems during hypoglycemia.

Bacteremic renal stone-associated urinary tract infection caused by nontypable Haemophilus influenzae: A rare invasive disease in an immunocompetent patient.

Haemophilus species are known to colonize the upper respiratory tract and can cause infections. However Haemophilus influenzae has been rarely described as a cause of genitourinary tract infection. We report a 44-year-old nonimmunocompromised Japanese man with bacteremic pyelonephritis caused by a nontypable H. influenzae associated with a left ureteral calculus. The organism was isolated from both blood and urine cultures. Treatment consisted of 14 days of intravenous ceftriaxone and oral amoxicillin one after than other and insertion of a left ureteral stent. After discharge, he underwent extracorporeal shock wave lithotrity for the left ureteral calculus. He had no recrudescence of the symptoms. H. influenzae should be considered as a genitourinary pathogen among patients with certain risk factors such as anatomical or functional abnormality of genitourinary tract. Collaboration between clinicians and microbiology laboratory personnel is essential for correct identification of the organism and appropriate therapy for genitourinary tract infections due to this organism.

Reversible splenial lesion syndrome with a hyperosmolar hyperglycemic state and neuroleptic malignant syndrome caused by olanzapine.

A 27-year-old woman with panic disorder taking 20 mg olanzapine daily for 4 months was admitted to Mito Kyodo General Hospital, Mito, Ibaraki, Japan, because of disturbed consciousness with fever, hyperglycemia, hyperosmolarity and elevated creatine phosphokinase. She was diagnosed with a hyperosmolar hyperglycemic state and neuroleptic malignant syndrome. Brain magnetic resonance imaging showed transiently restricted diffusion in the splenium of the corpus callosum, with a high signal intensity on diffusion-weighted imaging. The neurological abnormalities disappeared along with improvement of metabolic derangements, and the follow-up magnetic resonance imaging carried out on the 26th day of admission showed complete resolution of the lesions in the splenium of the corpus callosum. These clinical and radiological features are highly suggestive of clinically mild encephalitis/encephalopathy with a reversible splenial lesion. The first case of mild encephalitis/encephalopathy with a reversible splenial lesion caused by olanzapine-induced hyperosmolar hyperglycemic state and neuroleptic malignant syndrome is reported.

Acute-onset type 1 diabetes mellitus caused by nivolumab in a patient with advanced pulmonary adenocarcinoma.

A case of acute-onset type 1 diabetes mellitus concomitant with pneumonitis and vitiligo is described.