Serum N‐Terminal Type III Procollagen Propeptide: An Indicator of Growth Hormone Excess and Response to Treatment in Feline Hypersomatotropism

Abstract

BackgroundN‐terminal type III procollagen propeptide (PIIINP) is a biomarker of soft tissue proliferation. Hypersomatotropism (HS) is associated with soft tissue proliferation.HypothesisSerum PIIINP is increased in cats with HS and decreases with effective treatment, and may be an additional tool in the diagnosis and treatment of feline HS.AnimalsCats with uncomplicated diabetes mellitus (DM; n = 30) and with HS‐induced DM (HSDM; n = 30). Pre‐ and posttreatment samples were available from 5 cats undergoing radiotherapy (RT) and 16 cats undergoing hypophysectomy (HPX).MethodsRetrospective and prospective cross‐sectional study. Analytical performance of a serum PIIINP ELISA was assessed and validated for use in cats. PIIINP and insulin‐like growth factor 1 (IGF‐1) radioimmunoassays (RIA) were performed pre‐ and post‐treatment in cats with DM and HSDM. PIIINP and IGF‐1 were compared between cats treated by RT and HPX.ResultsSerum PIIINP concentrations were significantly higher (P < .001) in HSDM cats (median, 19.6 ng/mL; range, 1.7–27.9) compared to DM cats (median, 5.0 ng/mL; range, 2.1–10.4). A cut‐off of 10.5 ng/mL allowed differentiation between DM and HSDM cats with 87% sensitivity and 100% specificity (area under the curve [AUC], 0.91; 95% confidence interval [CI], 0.82‐1). After RT, PIIINP increased significantly (P = .043) with no significant change in IGF‐1 concentrations. After HPX, serum PIIINP (P = .034) and IGF‐1 concentrations (P < .001) decreased significantly.Conclusion and clinical importance PIIINP concentrations are increased in cats with untreated HSDM compared to those with DM, demonstrating the effect of excess GH on soft tissue. PIIINP concentrations decreased after HPX in most HSDM cats.

Time spent with cats is never wasted: Lessons learned from feline acromegalic cardiomyopathy, a naturally occurring animal model of the human disease

“…Interstitial fibrosis is considered a characteristic histopathological finding in HCM in both humans and cats [ 1 ], and has also been described in both human [ 25 ] and feline [ 28 ] patients with acromegaly. Increased collagen turnover has also been demonstrated both in the cat [ 69 ] and human [ 70 ] with acromegaly. One previous study in humans found that myocardial fibrosis increases with age [ 71 ], so the presence of fibrosis in itself may not always indicate disease.…”

Efficacy of hypophysectomy for the treatment of hypersomatotropism‐induced diabetes mellitus in 68 cats

“…There was a consistent and marked reduction in serum IGF‐1 concentration after hypophysectomy in the current study. Normalization of serum IGF‐1 concentration to <300 ng/mL within 4 weeks of surgery occurred in 44 of 55 cats (80.0%), in contrast to variable serum GH and IGF‐1 concentration reductions after radiation therapy 8,16,18 . Normalization of IGF‐1 is an important biomarker for identifying those who have achieved normalization of endogenous GH.…”

“…7,8 Stereotactic radiation therapy for the treatment of 53 cats with HST and DM achieved reduced insulin requirements in 39 (95%) and diabetic remission in 13 (32%) of 41 cats. 9 Even if glycemic control improves, serum IGF-1 does not reduce significantly with hypofractionated radiotherapy regardless of changes in glycemic control, 8,16 resulting in progressive acromegalic features. 17 The single study to date on the use of stereotactic radiation therapy on cats with HST and DM did not report serum IGF-1 concentrations after treatment.…”