Background
Familial Hypocalciuric Hypercalcemia (FHH) is a rare autosomal dominant genetic disorder which causes impaired calcium sensing receptor (CaSR) function which is located in the parathyroid ...and kidneys. This disorder leads to hypercalcemia, hypocalciuria and normal to moderately elevated parathyroid hormone (PTH). Here we present a case of asymptomatic FHH diagnosed in the seventh decade of life. Case description
A 63-year old Caucasian female was referred to the endocrinology clinic for evaluation of her hypercalcemia. Patient had elevated blood calcium levels (ranging from 10.5-11 mg/dl) since the age of 55. She denied any history of kidney stones, osteoporosis, fracture or malignancy. There was no family history of hypercalcemia. Her other medical history included diabetes mellitus type 2, hypertension, hyperlipidemia and depression. Medications were Metformin, insulin, enalapril, simvastatin, fluoxetine. Laboratory workup revealed calcium 10.1mg/dl, PTH 77.3 pg/ml, 25 OH Vit D 22 ng/ml, Initial urine 24-hour calcium 0mg/24 hr, creatinine 1.2 mg/dl, 24-hour urine creatinine 1.1 mg/dl. DEXA scan with normal bone mineral density. Vitamin D was supplemented and subsequent repeat urine 24-hour calcium had improved but was still low at 29mg/24 hour with urine calcium/creatinine ratio of 0.029. Follow-up blood calcium levels showed fluctuations ranging from 9.4-10.3. Patient was subsequently referred for genetic testing which returned positive for heterozygous mutation in the CASR gene. Discussion
FHH is an inherited disorder with prevalence of 1 in 78,000 and presents as benign, lifelong, persistent hypercalcemia and hypocalciuria without hypercalcemic related complications. Patients are mostly asymptomatic but there have been cases of pancreatitis, gall stones and chondrocalcinosis noted in literature from FHH. Conclusion
Distinguishing FHH from primary hyperparathyroidism is important as the former is benign and does not require any surgical intervention while latter is cured with parathyroidectomy. This case identifies the role of primary care physicians in timely detection of hypercalcemia and subsequent diagnosis which can prevent unnecessary parathyroid surgical procedures as well as complications from hypercalcemia in patients with primary hyperparathyroidism.
Insulin resistance can arise when pathological levels of free fatty acids (FFAs) and proinflammatory cytokines disrupt insulin signaling. Protein kinase C delta (PKCδ) is a FFA- and a proinflammatory ...cytokine-regulated protein kinase that is associated with inhibition of insulin signaling and action. To gain insight into the role of PKCδ in insulin resistance, PKCδ activation was studied in a genetic model of obesity-linked insulin resistance. PKCδ was found to be activated in the liver of obese insulin-resistant Zucker rats and in isolated cultured hepatocytes. PKCδ was further studied in PKCδ-null mice and their wild-type littermates fed a high-fat or control diet for 10 weeks. PKCδ-null mice on a high-fat diet had improved insulin sensitivity and hepatic insulin signaling compared to wild-type littermates. Additionally, the deleterious effect of a high-fat diet on glucose tolerance in wild-type mice was completely blocked in PKCδ-null mice. To directly test the role of PKCδ in cellular insulin resistance, primary hepatocytes from the high-fat diet mice were isolated and stimulated with insulin. Primary hepatocytes from PKCδ-null mice had improved insulin-stimulated Akt and FOXO phosphorylation compared to hepatocytes from wild-type littermates. Consistent with this result, tumor necrosis factor alpha-mediated inhibition of insulin signaling was blocked in PKCδ knockdown primary hepatocytes. These results indicate that PKCδ plays a role in insulin resistance and is consistent with the hypothesis that PKCδ is a negative regulator of insulin signaling and thus may be a therapeutic target for the treatment of type 2 diabetes.
This article is aimed at providing a practical up-to-date review of the precipitating factors, diagnosis, management and secondary prevention of hyperglycemic emergencies (diabetic ketoacidosis (DKA) ...and hyperglycemic hyperosmolar state (HHS) to assist critical care physicians and hospitalists caring for these patients. Limitations of various guidelines include implementation in settings with an infrastructure different from that specified in the guidelines of a respective country, state, region or community. Appropriate individualized acute management of these conditions typically results in satisfactory clinical outcomes and may decrease the mortality rate from up to 20% in type 2 diabetics with hyperglycemic hyperosmolar state vs less than 2% in patients with DKA. DKA may be the first manifestation of type 1 diabetes and can also occur in type 2 diabetics depending on the state of insulin sufficiency/secretion. For type 1 diabetics, the transition period from adolescence to adulthood is particularly critical to prevent repetitive hospital admissions. Hyperglycemic emergencies are usually preventable but do depend on patient compliance and adherence as well as medical infrastructure. Patients of all ages should be both appropriately educated and assured continuous access to health care to prevent recurrences of these conditions.
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