Peer-reviewed veterinary case report
GNAS gene mutations in dogs with cortisol-secreting adrenal tumors
By Kool, M M J et al.·Published in Journal of veterinary internal medicine·2013·Department of Clinical Sciences of Companion Animals, Netherlands·View original on PubMed →
PetCaseFinder translated the abstract of this peer-reviewed paper into plain English so pet owners can read it. We do not publish original research — every detail traces back to the citation above. How we work →
Original publication title: Activating mutations of GNAS in canine cortisol-secreting adrenocortical tumors.
- Species:
- dog
Plain-English summary
A group of dogs with Cushing's syndrome, which causes symptoms like excessive thirst, increased urination, and a pot-bellied appearance, were found to have tumors in their adrenal glands that were producing too much cortisol. Researchers discovered that about one-third of these tumors had a specific genetic mutation that causes the tumors to secrete cortisol independently of the usual regulatory hormones. This finding suggests that these mutations may play a significant role in the development of these tumors and the resulting hormone imbalance. Understanding these mutations could help veterinarians better diagnose and treat dogs with Cushing's syndrome.
People also search for: dog Cushing's syndrome symptoms · dog adrenal tumor treatment · why is my dog drinking so much water
Abstract
BACKGROUND: Cushing's syndrome or hypercortisolism is a common endocrinopathy in dogs. In approximately 15% of cases, the disorder is caused by adrenocorticotropin (ACTH)-independent hypersecretion of cortisol by an adrenocortical tumor (AT). Without other explanation, the cortisol hypersecretion has been referred to as autonomous. OBJECTIVES: To investigate whether ACTH-independent hypersecretion of cortisol may be associated with aberrant activation of the melanocortin 2 receptor (MC2R)-cyclic AMP (cAMP)-protein kinase A (PKA) pathway. ANIMALS: All analyses were performed on 44 cortisol-secreting ATs (14 adenomas and 30 carcinomas) derived from dogs diagnosed with ACTH-independent hypercortisolism. METHODS: Mutation analysis was performed of genes encoding the stimulatory G protein alpha subunit (GNAS), MC2R, and PKA regulatory subunit 1A (PRKAR1A) in all ATs. RESULTS: Approximately one-third of all ATs harbored an activating mutation of GNAS. Missense mutations, known to result in constitutive activation, were present in codon 201 in 11 ATs, in codon 203 (1 AT), and in codon 227 (3 ATs). No functional mutations were found in MC2R and PRKAR1A. CONCLUSIONS AND CLINICAL IMPORTANCE: Activation of cAMP signaling is a frequent event in canine cortisol-secreting ATs and may play a crucial role in both ACTH-independent cortisol production and tumor formation. To the best of our knowledge, this is the first report of potentially causative mutations in canine cortisol-secreting ATs.
Find similar cases for your pet
PetCaseFinder finds other peer-reviewed reports of pets with the same symptoms, plus a plain-English summary of what was tried across them.
Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/24112376/