Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Abstract

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6–28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90–100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2–28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease.

What's in a Name? Classification of Diabetes Mellitus in Veterinary Medicine and Why It Matters

“…Of these cats, 63 (20%) were further evaluated, including intracranial imaging, postmortem evaluation, or both. Based on these 63 cats, IGF‐1 had a positive predictive value of 95%, confirming the prevalence of hypersomatotropism among UK diabetic cats to be 25% . Interestingly, only 1 in 4 attending clinicians originally strongly suspected hypersomatotropism in cats subsequently diagnosed with the disease, suggesting that many affected cats present with DM but otherwise lack readily identifiable signs of acromegaly.…”

“…In contrast, hypersomatotropism‐induced DM is common. Recently, 1,221 diabetic cats were screened in first opinion practices in the United Kingdom and 26% were found to have serum insulin‐like growth factor‐1 concentrations (IGF‐1) > 1,000 ng/mL . Of these cats, 63 (20%) were further evaluated, including intracranial imaging, postmortem evaluation, or both.…”

“…Interestingly, only 1 in 4 attending clinicians originally strongly suspected hypersomatotropism in cats subsequently diagnosed with the disease, suggesting that many affected cats present with DM but otherwise lack readily identifiable signs of acromegaly. The investigators suggested use of the term hypersomatotropism over acromegaly because the latter implies the presence of physical features indicative of GH excess …”

Evaluation of the safety of daily administration of capromorelin in cats

“…This situation is markedly different from that of cats with hypersomatotropism, in which the pituitary tumour persistently secretes GH, resulting in chronically elevated serum GH in addition to elevated IGF‐1 levels (Berg et al., ; Peterson et al., ). An IGF‐1 measurement >1000 ng/ml is generally used to aid in the diagnosis of hypersomatotropism (Niessen et al., , ; Tschour et al., ). Some capromorelin‐treated cats in Study 2 had IGF‐1 levels >1000 ng/ml at some time points, with a maximum value of 1498 ng/ml recorded in this study (predosing on day 30).…”

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

“…Hypersomatotropism (HS), excess production of growth hormone (GH) by a functional somatotrophic adenoma, carcinoma or hyperplasia of the pituitary gland, and the resulting syndrome acromegaly are thought to be relatively common among diabetic cats . Feline HS now is hypothesized to cause diabetes in as many as 1 in 4 diabetic cats .…”