Hyperosmia and Hypergeusia As Potential Clues in Diagnosing Adrenal Insufficiency: A Case Report.

Adrenal insufficiency often presents with nonspecific symptoms, physical findings, and laboratory results, leading to diagnostic challenges. However, reports have indicated that specific symptoms such as hypergeusia (hypersensitivity to taste) and hyperosmia (hypersensitivity to smell) can also occur. We report the case of a 60-year-old male with loss of appetite, fatigue, and polyarthralgia, where a detailed medical history revealed the cause of anorexia to be hypergeusia and hyperosmia. These specific symptoms led to the diagnosis of adrenal insufficiency. Treatment with oral steroids for secondary adrenal insufficiency resulted in the improvement of his diverse symptoms. This case illustrates that in patients presenting with chronic nonspecific symptoms, inquiring about heightened taste and smell sensitivity can prompt suspicion of adrenal insufficiency. Moreover, this case serves as a reminder that careful medical history taking in patients with nonspecific symptoms can uncover specific findings that may be diagnostic clues.

A case of NASH with genetic predisposition successfully treated with an SGLT2 inhibitor: a possible involvement of mitochondrial dysfunction.

Summary: In this study, we herein describe a 47-year-old Japanese woman who manifested inheritable non-alcoholic steatohepatitis (NASH) and severe dyslipidemia. Interestingly, her NASH progression was ameliorated by treatment with a sodium-glucose co-transporter 2 (SGLT2) inhibitor. This inheritability prompted us to comprehensively decode her genomic information using whole-exome sequencing. We found the well-established I148M mutation in PNPLA3 as well as mutations in LGALS3 and PEMT for her NASH. Mutations in GCKR may contribute to both NASH and dyslipidemia. We further mined gene mutations potentially responsible for her manifestations that led to the identification of a novel M188fs mutation in MUL1 that may be causally associated with her mitochondrial dysfunction. Our case may provide some clues to better understand this spectrum of disease as well as the rationale for selecting medications. Learning points: While the PNPLA3 I148M mutation is well-established, accumulation of other mutations may accelerate susceptibility to non-alcoholic steatohepatitis (NASH). NASH and dyslipidemia may be intertwined biochemically and genetically through several key genes. SGLT2 inhibitors emerge as promising treatment for NASH albeit with interindividual variation in efficacy. Genetic background may explain the mechanisms behind the variation. A novel dysfunctional mutation in MUL1 may lead to metabolic inflexibilities through impaired mitochondrial dynamics and function.

A case of early-onset diabetes with impaired insulin secretion carrying a PAX6 gene Gln135* mutation.

Summary: A paired homeodomain transcription factor, PAX6 (paired-box 6), is essential for the development and differentiation of pancreatic endocrine cells as well as ocular cells. Despite the impairment of insulin secretion observed in PAX6-deficient mice, evidence implicating causal association between PAX6 gene mutations and monogenic forms of human diabetes is limited. We herein describe a 33-year-old Japanese woman with congenital aniridia who was referred to our hospital because of her uncontrolled diabetes with elevated hemoglobin A1c (13.1%) and blood glucose (32.5 mmol/L) levels. Our biochemical analysis revealed that her insulin secretory capacity was modestly impaired as represented by decreased 24-h urinary C-peptide levels (38.0 µg/day), primarily explaining her diabetes. Intriguingly, there was a trend toward a reduction in her serum glucagon levels as well. Based on the well-recognized association of PAX6 gene mutations with congenital aniridia, we screened the whole PAX6 coding sequence, leading to an identification of a heterozygous Gln135* mutation. We tested our idea that this mutation may at least in part explain the impaired insulin secretion observed in this patient. In cultured pancreatic ß-cells, exogenous expression of the PAX6 Gln135* mutant produced a truncated protein that lacked the transcriptional activity to induce insulin gene expression. Our observation together with preceding reports support the recent attempt to include PAX6 in the growing list of genes causally responsible for monogenic diabetes. In addition, since most cases of congenital aniridia carry PAX6 mutations, we may need to pay more attention to blood glucose levels in these patients. Learning points: PAX6 Gln135* mutation may be causally associated not only with congenital aniridia but also with diabetes. Blood glucose levels may deserve more attention in cases of congenital aniridia with PAX6 mutations. Our case supports the recent attempt to include PAX6 in the list of MODY genes, and Gln135* may be pathogenic.

Starvation Ketoacidosis With Hypoglycemia in a Patient With Chronic Pancreatitis.

Chronic pancreatitis is a pancreatic inflammation that can result in endocrine pancreatic insufficiency. We present a case of starvation ketoacidosis in a 44-year-old Japanese man with chronic alcoholic pancreatitis. On admission, he exhibited hypoglycemia and severe acidosis. Intravenous glucose and vitamin B1 were administered in the emergency department, and nutritional management for presumed starvation ketoacidosis was begun. Because the patient did not have diabetes mellitus, his insulin secretion and insulin resistance were examined. A diagnosis of pancreatic diabetes caused by chronic pancreatitis was made based on decreased insulin secretion, normal insulin resistance, and negative anti-glutamic acid decarboxylase antibody. Intensive insulin therapy was initiated, and he was discharged 15 days after hospitalization. Although starvation rarely causes hypoglycemia and severe ketoacidosis, they can be induced by short-term fasting in patients with decreased pancreatic function.