Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report.

BACKGROUND: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. CASE PRESENTATION: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. CONCLUSIONS: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.

A case of MODY5-like manifestations without mutations or deletions in coding and minimal promoter regions of the HNF1B gene.

Pancreatic tail hypoplasia is a common manifestation of maturity onset diabetes of the young (MODY) 5 that can cause reno-genito-urinary malformations such as renal cysts and bicornuate uterus. A 69-year-old female was admitted to our hospital for consultation on her relatively high HbA1c value. At age 20, she was diagnosed with uterus bicornis. At age 68, she was diagnosed with pancreas tail hypoplasia, renal cysts and non-functioning pancreatic neuroendocrine tumor (NET) in addition to right hydronephrosis due to multiple ureteral bladder carcinomas. She received total right nephrectomy, ureterectomy and partial cystectomy for multiple ureteral bladder carcinomas [non-invasive papillary urothelial carcinoma, low grade (G1), pTa, LV10, u-rtx, RM0, and pN0 (0/8)]. She also received distal pancreatomy for pancreatic NET [NET G1]. She then was referred to our department at age 69 due to increase in her HbA1c value from 6.2 to 7.2%; 75 g oral glucose tolerance test revealed impaired glucose tolerance. Her clinical characteristics (uterus bicornis, pancreas hypoplasia, and renal cysts) closely resembled the phenotype of MODY5, in which mutations in the HNF1B gene have been reported. Our genetic testing failed to detect any mutation or microdeletion in the coding or minimal promoter regions of the HNF1B gene. Although there remains a possibility that genetic mutations in introns and regulatory regions of the HNF1B gene might cause the MODY5-like manifestations in this patient, these results might suggest involvement of genes other than HNF1B in the pathogenesis of our patient's disease.

Hypoglycemic coma in an elderly adult switched from twice-daily vildagliptin to once-daily glimepiride to improve drug adherence.

BACKGROUND: Elderly adults with diabetes are at increased risk of severe hypoglycemia and hypoglycemic coma due to various conditions including decline in cognitive function, reduced activity of daily living (ADL) and reduced renal function; special cautions are, therefore, recommended to avoid these life-threatening events. CASE PRESENTATION: A 92-year-old female was admitted to our institution because of severe coma. Upon arrival, her serum C-peptide was 1.64 ng/mL despite low plasma glucose (24 mg/dL) and serum glimepiride (40.85 ng/mL). She had past history of compression fracture of her lumbar spine, which substantially affected her ADL. Her score on the dementia assessment sheet for community-based integrated care system-8 items (DASC-8) was 26 points. She had been receiving 12 oral medications for diabetes, essential hypertension, chronic gastritis and constipation from her nearby clinic. Her physician-in-charge had found that she was not taking her medications properly and simplified her prescription regimen to 3 oral medications with vildagliptin 50 mg twice daily replaced by glimepiride 3 mg once daily and asked her son to assist in taking the drugs 6 days before her admission to our hospital. While her consciousness level was improved to some extent, she was transferred to a long-term care bed hospital because it had become too difficult to care for her at home. CONCLUSIONS: It is important to note that anti-diabetes drugs should be carefully selected based on each patient's cognitive function and ADL, and that the reasoning should be shared with the general practitioners involved to avoid severe hypoglycemic events. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00510-9.

Effects of ChREBP deficiency on adrenal lipogenesis and steroidogenesis.

Carbohydrate response element-binding protein (ChREBP) is critical in the regulation of fatty acid and triglyceride synthesis in the liver. Interestingly, Chrebp-/- mice show reduced levels of plasma cholesterol, which is critical for steroid hormone synthesis in adrenal glands. Furthermore, Chrebp mRNA expression was previously reported in human adrenal glands. Thus, it remains to be investigated whether ChREBP plays a role directly or indirectly in steroid hormone synthesis and release in adrenal glands. In the present study, we find that Chrebp mRNA is expressed in mouse adrenal glands and that ChREBP binds to carbohydrate response elements. Histological analysis of Chrebp-/- mice shows no adrenal hyperplasia and less oil red O staining compared with that in WT mice. In adrenal glands of Chrebp-/- mice, expression of Fasn and Scd1, two enzymes critical for fatty acid synthesis, was substantially lower and triglyceride content was reduced. Expression of Srebf2, a key transcription factor controlling synthesis and uptake of cholesterol and the target genes, was upregulated, while cholesterol content was not significantly altered in the adrenal glands of Chrebp-/- mice. Adrenal corticosterone content and plasma adrenocorticotropic hormone and corticosterone levels were not significantly altered in Chrebp-/- mice. Consistently, expression of genes related to steroid hormone synthesis was not altered. Corticosterone secretion in response to two different stimuli, namely 24-h starvation and cosyntropin administration, was also not altered in Chrebp-/- mice. Taking these results together, corticosterone synthesis and release were not affected in Chrebp-/- mice despite reduced plasma cholesterol levels.

SGLT2 Inhibitor and GLP-1 Receptor Agonist Combination Therapy Substantially Improved the Renal Function in a Patient with Type 2 Diabetes: Implications for Additive Renoprotective Effects of the Two Drug Classes.

A 72-year-old man had type 2 diabetes (T2D) that had been diagnosed at 54 years old. Macroalbuminuria was first detected at age 64. While his HbA1c had been kept below 7%, his estimated glomerular filtration rate (eGFR) was declining rapidly. At 70 years old, his eGFR dropped below 50 mL/min/1.73 m2. A renal biopsy revealed diabetic nephropathy. Sodium glucose transporter 2 inhibitors (SGLT2i)/glucagon-like peptide-1 receptor agonists (GLP-1RA) combination therapy substantially improved his eGFR and urinary albumin level, and the renoprotective effect persisted for the two-year study period. These findings suggest that SGLT2i and GLP-1RA can additively improve the renal function in patients with T2D.

Sodium-glucose cotransporter 2 inhibitor and sarcopenia in a lean elderly adult with type 2 diabetes: A case report.

A 70-year-old woman with type 2 diabetes was admitted to Gifu University Hospital, Gifu, Japan, because of ketosis. She was diagnosed with type 2 diabetes at age 49 years and started insulin therapy at age 57 years, which restored glycemic control. Insulin therapy was discontinued and oral antidiabetes drugs, including sodium-glucose cotransporter 2 inhibitor dapagliflozin, were initiated at age 69 years. Thereafter, her bodyweight declined from 40.0 kg to 29.8 kg in 12 months; glycated hemoglobin remained >8.0%. On admission to our hospital, her laboratory tests and computed tomography scan showed ketosis, insulinopenia, and the presence of dehydration and bacterial pneumonia. She also lost substantial bodyweight and developed sarcopenia. The current case shows the importance of patient assessment before sodium-glucose cotransporter 2 inhibitor initiation in the elderly.

A rare case of autoimmune polyglandular syndrome with Sjögren's syndrome and primary hypoparathyroidism.

A 31-year-old woman experienced tetany and was diagnosed with Hashimoto thyroiditis and hypoparathyroidism. At 33 years of age, her renal function gradually decreased. At 39 years of age, she moved to our hospital and was diagnosed with tubulointerstitial nephritis by renal biopsy. Simultaneously, she was diagnosed with Sjögren's syndrome by autoantibodies and salivary gland biopsy. At 40 years of age, based on hypoglycaemia and eosinophilia, she was suspected of adrenal insufficiency, and was diagnosed with primary adrenal insufficiency by both corticotropin stimulation and corticotropin-releasing hormone stimulation test. She was diagnosed as autoimmune polyglandular syndrome (APS) (Hashimoto thyroiditis and possible primary adrenal insufficiency) as well as primary hypoparathyroidism and Sjögren's syndrome, which are very rarely complicated in APS-2. Therefore, in this patient, it was helpful to pay attention for new onset of other autoimmune diseases.