Glucagonoma is a very rare tumor of the pancreatic alpha cells that results in the overproduction of the hormone, glucagon. Typically associated with a rash called necrolytic migratory erythema, weight loss, and mild diabetes mellitus, most people with glucagonoma contract it spontaneously. However, about 10% of cases are associated with multiple endocrine neoplasia type 1 (MEN-1) syndrome. Causes
Although the cause of glucagonoma is unknown, some genetic factors may lead to the condition. A family history of multiple endocrine neoplasia type 1 (MEN1) is a risk factor. Additionally, those with Mahvash disease have an increased risk for glucagonoma, as glucagon receptor gene (GCGR) is mutated. Mechanism
Glucagonoma results from the overproduction of glucagon, a peptide hormone located in the pancreatic alpha cells. Classic symptoms include, but are not limited to, necrolytic migratory erythema (NME), diabetes mellitus, and weight loss. NME presents in about 70% of cases of glucagonoma, and is characterized by erythematous lesions over the distal extremities and the groin area. NME has occasionally been observed in people who do not have glucagonoma. People who develop glucagonoma from Mahvash disease also do not develop NME, implying that working glucagon receptors are needed in order for NME to be present in a person. Weight loss, the most commonly associated effect with glucagonoma, results from the glucagon hormone, which prevents the uptake of glucose by somatic cells. Diabetes is not present in all cases of glucagonoma, but does frequently result from the insulin and glucagon imbalance.
Structural damage to hair cells (primarily the outer hair cells) will result in hearing loss that can be characterized by an attenuation and distortion of incoming auditory stimuli. During hair cell death scars develop, which prevent potassium rich fluid of the endolymph from mixing with the fluid on the basal domain. The potassium rich fluid is toxic to the neuronal endings and can damage hearing of the entire ear. If the endolymph fluid mixes with the fluid on the basal domain the neurons become depolarized, causing complete hearing loss. In addition to complete hearing loss, if the area is not sealed and leakage continues further tissue damage will occur. The scars that form to replace the damaged hair cell are caused by supporting hair cells undergoing apoptosis and sealing the reticular lamina, which prevents fluid leakage. The cell death of two supporting hair cells rapidly expands their apical domain, which compresses the hair cell beneath its apical domain. Nerve damage
Recent studies have investigated additional mechanisms of NIHL involving delayed or disabled electrochemical transmission of nerve impulses from the hair cell to and along the auditory nerve. In cases of extreme acute acoustic trauma, a portion of the postsynaptic dendrite (where the hair cell transfers electrochemical signals to the auditory nerve) can rupture from overstimulation, temporarily stopping all transmission of auditory input to the auditory nerve. This is known as excitotoxicity. Usually, this sort of rupture heals within about five days, resulting in functional recovery of that synapse.