endocrinology (disorders of growth hormone secretion) Flashcards
Feline acromegaly
What is the etiology of acromegaly
The predominant cause of feline acromegaly is a functional somatotropic adenoma in the pars distalis of the anterior pituitary gland resulting in excessive growth hormone secretion
Somatotropic hyperplasia has been suggested for occasional acromegaalic cats
A study found that higher levels of organohalogenated chemicals, which can be found in any household and can induce pituitary oncogenesis, were present in the plasma of acromegalic household cats
what is the pathophysiology of feline acromegaly
Production of GH and IGF-1 is normally finely regulated thanks to feedback mechanisms
In the case of a GH-producing pituitary adenoma, feedback mechanisms tend to fail to control GH and, in turn, IGF-1 production
The syndrome of acromegaly results from a generalised overexposure of tissues to not only GH, but also IGF-1, the latter because of a significant elevation in GH-induced production, predominantly by the liver
The classical signs of acromegaly are the result of the anabolic and catabolic effects of GH, the anabolic effects of IGF-1, and in some cases, the additional effect of a gradually expanding pituitary tumor
GH is an important modulator of insulin sensitivity thus it seems logical that almost all reported cats with acromegaly have concurrent insulin-resistant diabetus mellitus
What is the signalment for feline acromegaly
Male-neutered middle-aged to older DSH with insulin-resistant diabetus mellitus
Median insulin dose 7 IU BID
When is a high index of suspicion warranted
1/ Historical signs
- PU/PD
- Polyphagia
- Weight gain
- Prognathia inferior
- NB: the absence of a typical acromegalic appearance (i.e. prognathia inferior, increase in paw size) should not decrease the index of suspicion in an insulin-resistant cat
2/ Clinical signs
- Abdominal organomegaly (liver and kidneys)
- Broad facial features
- Respiratory stridor due to generalised thickening of oropharyngeal tissues
- Heart anomalies (e.g. murmur, galop rythm, periods of open-mouth breathing and tachypnoea when stressed)
3/ Once the presence of true insulin resistance is established in a cat, acromegaly must be considered
- Any weight gain in the light of poor diabetic control should further increase the suspicion of the presence of acromegaly
How would you confirm a suspicion of feline acromegaly?
1/ Routine clinical pathology
- Only total protein levels are significantly elevated in the acromegalic cats
2/ IGF-1 measurement
- When elevated, it indicates that further testing is warranted because there are false-positive and false-negative
- Elevated IGF-1 levels have been reported in apparently non-acromegalic diabetic cats
- A cut-off of 1000 ng/ml has a positive predictive value of 95 %
3/ GH measurement
- A validated feline GH radio-immunoassay proved useful in distinguishing normal cats from acromegalic cats with no overlap
- Not readily available for cats
- The pulsatile secretion pattern of this hormone can lead to false-positive in non-acromegalic cats
4/ Intracranial imaging
- Once IGF-1 or feline GH determination suggest acromegaly, intracranial imaging is indicated
- Contrast-enhanced CT and MRI are useful
What are the possible treatment approaches for feline acromegaly
Radiotherapy
Hypophysectomy
Medical therapy
What are the advantages/disadvantages of radiotherapy for acromegaly
Radiotherapy is probably the best treatment option that can currently be offered
However, not all patients will respond to radiotherapy, with some showing improvement of diabetes mellitus but persistence of other acromegalic signs
What are the advantages/disadvantages of hypophysectomy
Transphenoidal hypophysectomy has been employed as a treatment method for pituitary tumors in cats at the university of Utrecht
It is a highly specialised procedure which is not without risk
What are the advantages/disadvantages of medical therapy
1/ Pasireotide
- A somatostatin analog given once-monthly
- It causes a significant decrease in IGF-1 and GH levels, shrinkage of the GH-secreting pituitary tumor, and improves diabetic control (with remission in some cats)
- Unacceptable diarrhea occurs in a reasonable number of cats
- High cost
2/ Conservative (insulin) treatment
- It represents a genuine alternative treatment when definitive treatment is not possible
- Monitoring blood glucose concentration before each dose of insulin can be considered in order to reduce the risk of clinical hypoglycemia
- Monitoring for negative glucosuria might prove a more acceptable alternative for some owners
3/ Cabergoline
- Potent D2 receptor dopamine agonist
- Highly available and economical
- A dose of 10 µg/kg every 48 h can show a reduction of IGF-1, fructosamine and insulin requirements along with resolution of clinical signs within 6 months
- It has antiproliferative and proapoptotic effects on corticotropinoma, somatotropinoma and prolactinoma neoplastic cells, both in humans and dogs
Explain why IGF-1 can be falsely normal in an acromegalic cat
Portal insulin is required for hepatic IGF-1 production
Since endogenous insulin concentrations can be low in feline DM, a low IGF-1 reading could be obtained when sampling takes place prior to initiation of exogenous insulin treatment despite the presence of excess groth hormone due to acromegaly
