Rare Case of Pseudohypoparathyroidism With Normocalcemia Because of a Novel GNAS Mutation.

PTH resistance is characterized by hypocalcemia and hyperphosphatemia in the presence of elevated PTH concentrations, resulting in pseudohypoparathyroidism, which is subdivided into different types according to its different pathogenesis and phenotype. PTH receptor is the alpha subunit of stimulatory G protein (Gsα)-coupled receptor. Pathogenic variants of GNAS gene, encoding for Gsα, lead to reduced Gsα function and PTH resistance. We report a patient with PHP type 1a, with no documented evidence of hypocalcemia, presenting with AHO phenotype and multihormone resistance to PTH, TSH, and GnRH. Her genetic testing showed a novel heterozygous pathogenic variants, a c.934T > G change in exon 11 in adenylate cyclase stimulatory G protein that has not been reported in the literature so far.

A Recurrent Episode of Dermatomyositis Associated with Papillary Thyroid Cancer.

OBJECTIVE: It is uncommon for dermatomyositis to be associated with papillary thyroid cancer. We report an unusual case of papillary thyroid cancer presenting with dermatomyositis. METHODS: The case history, imaging and laboratory data is reviewed. RESULTS: We report the case of a 62-year-old female with a prior history of dermatomyositis and breast cancer who presented with a recurrent episode of dermatomyositis. Extensive evaluation of the cause of the dermatomyositis recurrence revealed no recurrence of the breast cancer but a thyroid nodule was identified. The nodule was biopsied and the patient was noted to have papillary thyroid cancer. The patient subsequently underwent total thyroidectomy and had gradual improvement in her dermatomyositis. CONCLUSION: It is very uncommon for dermatomyositis to be associated with papillary thyroid cancer.

"Hyper-warburgism," a cause of asymptomatic hypoglycemia with lactic acidosis in a patient with non-Hodgkin's lymphoma.

CONTEXT: In cancer cells, the Warburg effect is defined as the avid consumption of glucose through the glycolytic pathway with concomitant lactate production, even under aerobic conditions. CASE: We report a 64-yr-old woman who was referred to our institution for pancytopenia and hypoglycemia. Physical examination demonstrated hepatosplenomegaly and petechiae. She had no clinical manifestation of neuroglycopenia, despite serum glucose of 26 mg/dl (1.4 mmol/liter) and serum lactate of 28.5 mmol/liter (normal range, 0.5-3.4 mmol/liter). Bone marrow biopsy demonstrated diffuse large B-cell lymphoma. Staging (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography showed increased FDG avidity in an enlarged spleen and absent FDG uptake in the brain. Despite dextrose infusions up to 30 g/h, there was no increase in serum glucose, but there was a paradoxical increase in serum lactate. Immunochemotherapy improved the hematological and metabolic abnormalities. Follow-up FDG-positron emission tomography/computed tomography showed a decrease in splenic avidity and an increase in brain FDG avidity. The patient refused further chemotherapy and died 1 wk after discharge. METHODS: Literature review of cases of lymphoma with lactic acidosis, with and without hypoglycemia, demonstrated that these combinations occurred in multiple categories of B- and T-cell lymphoma. There was no difference in the mortality rate in those with (75%) or without (74%) concomitant hypoglycemia. CONCLUSION: This case represents an exaggerated Warburg effect, or "hyper-warburgism," characterized by excessive lactate production and overwhelming glucose consumption. We speculate that the decreased brain FDG uptake, despite the lack of neuroglycopenic symptoms, supports the hypothesis that lactate served as a fuel for the brain, thus protecting against hypoglycemia.

Topiramate treatment protects blood-brain barrier pericytes from hyperglycemia-induced oxidative damage in diabetic mice.

Diabetes mellitus causes cerebral microvasculature deterioration and cognitive decline. The specialized endothelial cells of cerebral microvasculature comprise the blood-brain barrier, and the pericytes (PC) that are in immediate contact with these endothelial cells are vital for blood-brain barrier integrity. In diabetes, increased mitochondrial oxidative stress is implicated as a mechanism for hyperglycemia-induced PC loss as a prerequisite leading to blood-brain barrier disruption. Mitochondrial carbonic anhydrases (CA) regulate the oxidative metabolism of glucose and thus play an important role in the generation of reactive oxygen species and oxidative stress. We hypothesize that the inhibition of mitochondrial CA would reduce mitochondrial oxidative stress, rescue cerebral PC loss caused by diabetes-induced oxidative stress, and preserve blood-brain barrier integrity. We studied the effects of pharmacological inhibition of mitochondrial CA activity on streptozotocin-diabetes-induced oxidative stress and PC loss in the mouse brain. At 3 wk of diabetes, there was significant oxidative stress; the levels of reduced glutathione were lower and those of 3-nitrotyrosine, 4-hydroxy-2-trans-nonenal, and superoxide dismutase were higher. Treatment of diabetic mice with topiramate, a potent mitochondrial CA inhibitor, prevented the oxidative stress caused by 3 wk of diabetes. A significant decline in cerebral PC numbers, at 12 wk of diabetes, was also rescued by topiramate treatment. These results provide the first evidence that inhibition of mitochondrial CA activity reduces diabetes-induced oxidative stress in the mouse brain and rescues cerebral PC dropout. Thus, mitochondrial CA may provide a new therapeutic target for oxidative stress related illnesses of the central nervous system.

Management of inpatient hyperglycemia: assessing knowledge and barriers to better care among residents.

To identify areas that should be targeted for improvement, we surveyed residents for their knowledge and barriers regarding management of inpatient hyperglycemia. One hundred thirty-five residents from 4 teaching hospitals completed a questionnaire to assess their knowledge about the different types of insulin, the perceived barriers toward managing inpatient hyperglycemia, and the problems they face when dealing with this commonly encountered problem. The majority of participants thought that managing inpatient hyperglycemia was very important in the critically ill and perioperative patients, whereas only 65% thought that it was very important for noncritically ill patients. Most residents reported that they will target blood glucose levels that are inconsistent with the current recommendations. Half of them reported that they were very comfortable with managing inpatient hyperglycemia and hypoglycemia. Of the participants, 46% said they will use a stand-alone insulin sliding scale for patients with difficult to control blood glucose and 43% thought that physicians still use it because of their unfamiliarity with ordering prandial and basal insulin. Unpredictable changes in patient diet and mealtimes, along with the risk of causing patient hypoglycemia, were the most frequently chosen as barriers to better management of inpatient hyperglycemia. Most participants lack important inpatient hyperglycemia knowledge, specifically about insulin types and pharmacokinetics. This study demonstrated the gap in knowledge about management of inpatient hyperglycemia among residents and illustrated the need to develop certain policies and to implement educational programs directed toward residents that reflect the current guidelines.