Combined treatment of pegvisomant and cabergoline in a cat with hypersomatotropism: insulin-like growth factor 1 normalization and control of comorbidities

Abstract

Case summary

A 19-year-old, spayed female domestic shorthair cat was referred with diabetes mellitus and difficulties in achieving glycemic control. Hypersomatotropism (HST) was diagnosed based on clinical signs compatible with acromegaly (prognathia inferior, broad facial features and abdominal enlargement), increased serum insulin-like growth factor 1 (IGF-1) concentration (4430 ng/ml) and pituitary enlargement (height 4.7 mm). Serum IGF-1 concentrations, biochemical analysis and urinalysis were performed at the time of HST diagnosis and after 10, 20, 30, 60, 120 and 180 days of pegvisomant treatment (PEGV, Somarvet; Pfizer). The cat received PEGV (1 mg/kg SC q24h) in combination with cabergoline (10 μg/kg PO q48h). Serum IGF-1 concentrations decreased abruptly to 396 ng/ml on day 10 of PEGV treatment and blood glucose concentrations also decreased rapidly. Insulin was no longer required after 7 days of PEGV. From day 30 (IGF-1 286 ng/ml), PEGV was administered q48h and the same therapeutic response was maintained after 60 days of treatment (IGF-1 290 ng/ml and diabetic remission). From day 120, PEGV was administered once weekly and normal IGF-1 concentrations (270 ng/ml) were observed after 180 days of treatment. The cat also showed improvements in echocardiographic variables and in her quality of life (QoL) score.

Relevance and novel information

This is the first reported case of PEGV plus cabergoline treatment in a cat with HST. The results suggest that the combined treatment of PEGV and cabergoline was associated with normalization of IGF-1 concentrations, diabetic remission, and improvement of cardiovascular function and QoL over a short period.

Plain language summary

Successful use of combined treatment of pegvisomant and cabergoline to treat a cat with excess growth hormone

A 19-year-old female cat was presented with diabetes mellitus that was difficult to control. Physical examination revealed features suggestive of a growth hormone disorder, such as an enlarged lower jaw, broad facial features and abdominal distension. Further testing confirmed hypersomatotropism (excess growth hormone) based on high serum insulin-like growth factor 1 (IGF-1) levels and an enlarged pituitary gland. The cat was treated with cabergoline and pegvisomant, a drug that blocks the action of growth hormone. After starting treatment, blood glucose levels decreased rapidly, and insulin therapy was discontinued within 1 week. IGF-1 levels dropped sharply within 10 days and remained within the normal range throughout the 6 months of treatment. Frequency of pegvisomant dosing was gradually reduced from daily to once weekly while maintaining good control. In addition to diabetic remission, improvements in heart function and overall quality of life were observed. This case represents the first report of pegvisomant used in combination with cabergoline in a cat with hypersomatotropism and suggests that this therapy can effectively normalize hormone levels, resolve diabetes, and improve clinical condition and quality of life in affected cats.

Keywords

Pegvisomant GH excess diabetic remission acromegaly

Case description

This study was approved by the Ethics Committee of the School of Veterinary Science at the University of Buenos Aires (protocol 2022/66), in accordance with the Argentinian laws on animal testing and the World Health Organization’s guidelines. Written informed consent was obtained from the cat owners before enrollment.

A 19-year-old, spayed female domestic shorthair cat, weighing 5.7 kg and with a body condition score of 4/5, was referred to the Veterinary Science Center (Maimonides University, Argentina) with polyuria, polydipsia, polyphagia and difficulties in glycemic control in the context of diabetes mellitus (DM). Since being diagnosed with DM 3 months prior, the cat had been receiving increasing doses of insulin glargine (100 IU/ml, 2 IU/kg q12h) alongside a commercial diet for diabetic cats.

The physical examination revealed prognathia inferior, broad facial features and abdominal enlargement (Figure 1). Serum biochemical analysis and urinalysis showed hyperglycemia, increased serum fructosamine concentration and glucosuria (Table 1). The average systolic blood pressure (SBP) was 165 mmHg. The clinical findings, together with the lack of response to increasing insulin doses, led to the suspicion of different endocrine causes of insulin resistance (Table 1).¹ Hypersomatotropism (HST) was diagnosed based on phenotypic changes consistent with acromegaly and a markedly increased serum insulin-like growth factor 1 (IGF-1) concentration (4430 ng/ml, radioimmunoassay [RIA]; Immuno-Biological Laboratories),^2
–4 as well as pituitary enlargement on CT (Figure 2). An abdominal ultrasound revealed increased thickness in both adrenal glands (0.6 cm). In addition, a hypertrophic cardiomyopathy (HCM) phenotype was identified via echocardiography (Table 2).

Figure 1

A 19-year-old, female domestic shorthair cat at the time of presentation, when hypersomatotropism was diagnosed. Note the prognathia inferior and broad facial features

Table 1

Clinicopathologic findings, hormone analysis and insulin doses at diagnosis of hypersomatotropism (HST), during cabergoline and pegvisomant (PEGV) treatment

	Diagnosis of HST	Cabergoline	PEGV
	Diagnosis of HST	Month 1	Day 10	Day 20	Day 30	Day 60	Day 120	Day 180	RI
Glycemia (mmol/l)	28	24	6.3	5.8	5.5	5.6	4.9	5.3	4.4–6.6
ALT (U/l)	57	67	459	307	147	99	77	64	<80
AST (U/l)	27	26	86	87	54	40	38	53	<80
ALP (U/l)	31	36	64	71	58	44	40	39	<100
Fructosamine (μmol/l)	749	537	518	459	377	387	390	395	200–380
Glucosuria (mmol/l)	60	60	0	0	0	0	0	0	0
IGF-1 (ng/ml)	4430	4501	369	484	285	290	267	270	<700
TT4 (μg/dl)	2.2	–	–	–	–	–	–	–	1–4
UCCR (×10⁻⁶)	14	–	–	–	–	–	–	–	<36
Insulin dose (IU/kg)	2	2.7	0	0	0	0	0	0	–
Frequency of PEGV administration	–	–	q24h	q24h	q24h	q48h	q3.5d	q7d	–

ALT = alanine aminotransferase; ALP = alkaline phosphatase; AST = aspartate aminotransferase; IGF-1 = serum insulin-like growth factor 1; RI = reference interval; TT4 = total thyroxine; UCCR = urinary cortisol:creatinine ratio

Figure 2

Pituitary enlargement in CT cross section (blue arrow indicating pituitary height 4.7 mm)

Table 2

Echocardiographic measurements and systolic blood pressure (SBP) before and after 180 days of pegvisomant (PEGV) treatment

Variable	Pre-PEGV	180 days after PEGV
IVSd (mm)	6.1	4.7
Diastolic diameter of the LV (mm)	15.4	14.7
Posterior wall of the LV in diastole (mm)	5.9	4.8
Left ventricular mass (g)	17.7	11.5
LA (mm)	16.7	14
LA:Ao ratio	1.77	1.25
Left atrial shortening fraction (%)	13	25.7
SBP (mmHg)	165	131

IVSd = interventricular septum thickness at end-diastole; LA = left atrium; LA:Ao = left atrium:aortic ratio; LV = left ventricle

Initially, cabergoline (10 μg/kg PO q48h, Dostinex; Pfizer) was prescribed.⁴ The owners and the veterinary team monitored the cat’s clinical signs and glucose levels at home. Glucose assessments were performed using a continuous glucose monitoring system (CGMS, FreeStyle Libre) in combination with a glucometer (FreeStyle Optium). No relevant changes in interstitial/blood glucose concentrations or serum IGF-1 concentration (4501 ng/ml) were observed while cabergoline was administered alone. After 1 month of cabergoline monotherapy, a combined treatment with pegvisomant (PEGV, Somarvet; Pfizer) was prescribed (1 mg/kg SC q24h). On day 10 of PEGV + cabergoline treatment, serum IGF-1 concentrations decreased abruptly to 396 ng/ml and fell within the reference interval (RI) for RIA (RI 200–700) (Table 1).³ Interstitial/blood glucose concentrations also decreased rapidly, and insulin administration was progressively reduced, becoming unnecessary after 7 days of PEGV + cabergoline treatment. Two episodes of asymptomatic hypoglycemia (2.8–3.2 mmol/l) were recorded during the first week without insulin. From day 30 (IGF-1 286 ng/ml), PEGV was administered q48h and cabergoline was continued at 10 μg/kg q48h. The same therapeutic response was maintained after 60 days of treatment (blood/interstitial glucose concentration 4.4–6.6 mmol/l and IGF-1 290 ng/ml). After 45 days of observing normal interstitial/blood glucose concentrations without insulin, the CGMS was discontinued and monitoring continued with blood glucose tests q6h/q8h and weekly urinalysis. From day 60, PEGV was administered twice weekly and cabergoline was continued at 10 μg/kg q48h; normal IGF-1 concentrations (267 ng/ml) were observed after 120 days of treatment. From day 120, PEGV was administered once weekly and cabergoline was continued at 10 μg/kg q48h; normal IGF-1 concentrations (270 ng/ml) were observed after 180 days of treatment. Similarly, fasting blood glucose concentrations remained unchanged (4.4–6.6 mmol/l) and there were no clinical signs of DM or glucosuria at any time after insulin was withdrawn. Serum fructosamine concentrations decreased markedly with PEGV + cabergoline treatment but did not reach normal values, remaining slightly above the RI (Table 1).

On day 180 of PEGV treatment, improvements in SBP and echocardiographic variables were observed (Table 2). Likewise, the owner’s perception of the cat’s quality of life (QoL) was assessed using a scale ranging from 1 (poor) to 5 (excellent) before and after 180 days of PEGV treatment.⁵ The QoL score was 2 before treatment and 5 after treatment. A transient increase in alanine and aspartate aminotransferases was observed during the first 3 months (Table 1). No other side effects were reported during the study period.

Discussion

In this case report, the safety and efficacy of PEGV were evaluated in a diabetic cat with HST. This is the first reported case of PEGV used in combination with cabergoline in a domestic cat (Felis catus). The results are highly promising, suggesting that a combination of PEGV and cabergoline treatment could successfully control HST and its comorbidities (DM and HCM). In this clinical case, the combined treatment normalized serum IGF-1 concentrations within 10 days, promoted diabetic remission within 1 week, and improved cardiovascular function and QoL over the 6-month follow-up period.

HST is a metabolic disorder caused by the hypersecretion of growth hormone (GH).⁶ In domestic cats, it is caused by a functioning somatotropinoma or hyperplasia of the pars distalis of the pituitary gland.⁷ HST has primarily been described in diabetic cats, with prevalence rates in the range of 15–25%;^3,8 however, it can also develop in non-diabetic cats.^9,10

Although HST is a relatively common endocrinopathy in cats, studies on medical treatment are lacking. PEGV, a genetically modified analog of GH, binds to GH receptors without activating signal transduction. Thus, it acts as a competitive GH receptor antagonist.^11
–13 This blockade prevents JAK2–STAT5 downstream signaling and leads to a reduction in hepatic IGF-1 secretion, independently of circulating GH concentrations.^11
–13 In humans with acromegaly, PEGV is widely used as a second-line option for patients with resistance or intolerance to somatostatin receptor ligands (SRLs) and it achieves IGF-1 normalization in most cases.^11
–15 The drug has also been shown to improve insulin sensitivity, reduce cardiovascular risk and improve QoL.^16,17 PEGV improved glycemic control in 56.6% of patients with acromegaly and prediabetes/DM who were resistant to first-generation SLRs.¹⁸ However, PEGV does not shrink the pituitary tumor, and MRI monitoring is recommended because tumor enlargement has been reported in a minority of patients.^12
–17

It is important to note that PEGV has never been tested in cats. In the case presented, the therapeutic response of the combined treatment of PEGV and cabergoline was remarkable. Serum IGF-1 concentration decreased notably from above 4400 ng/ml to within the RI over a period of 10 days of combination therapy. Furthermore, normal IGF-1 concentrations were maintained throughout successive rechecks during the study, even with the decreasing frequency of PEGV administration. In addition, insulin treatment was discontinued after 7 days of PEGV + cabergoline treatment. According to the Agreeing Language in Veterinary Endocrinology (ALIVE) criteria, a feline patient previously diagnosed with DM is said to be in diabetic remission if they cease to receive insulin and show no evidence of DM after 4 weeks.¹⁹ The cat in this report fulfilled this criterion. After insulin was withdrawn, the cat showed no clinical signs of DM, fasting hyperglycemia or glucosuria. Diabetic remission has been previously described in cats with HST that were treated with hypophysectomy, radiotherapy, pasireotide and cabergoline.^20
–23

Since there are no published reports on the use of PEGV in cats, the dosing strategy was extrapolated from preclinical and clinical studies. Notably, differences in sensitivity to PEGV has been documented across species (mice, primates and humans).^24,25 An interesting finding in this case report was the possibility of tapering PEGV administration. It is relevant to highlight that cabergoline was still in use, and the dosage and frequency were ongoing. After the initial daily dose of PEGV, the interval was extended to q48h, then to twice weekly and ultimately to once weekly, while maintaining diabetic remission and an IGF-1 concentration within the RI. This probably suggests that PEGV exhibits prolonged receptor occupancy and sustained biological effects in cats. In human acromegaly, PEGV is titrated individually based on serum IGF-1 concentration, often in combination with SRLs to reduce dose requirements.²⁶ Whether similar protocols could be applied in cats remains to be explored, but the results of this case report suggest that individualized approaches are feasible.

Interestingly, serum fructosamine concentration did not normalize despite diabetic remission. There are different hypotheses that could explain this finding: (1) changes in protein composition: increased presence of proteins that are more easily glycated; and (2) borderline average glycemia: the blood glucose concentrations of the present case are at the upper limit of RI. In cats, there is a lack of evidence on prediabetes,^19,27 and it is possible that the cat in this report could be included in this condition.

In humans, PEGV treatment has been associated with reversible elevations in transaminases and rare cases of clinical hepatotoxicity.^12
–18 In the present case, a marked increase in transaminase activity occurred during the first 3 months of PEGV treatment, coinciding with more frequent weekly administrations. However, the increase was self-limiting and was not associated with any clinical signs or biochemical evidence of hepatic dysfunction.

Although cabergoline monotherapy has been shown to normalize serum IGF-1 concentrations in 26% of diabetic cats with HST and induce diabetic remission in 35% of cases, it did not achieve these therapeutic goals in this cat.⁴ In the present case, treatment with cabergoline (in combination with PEGV) was continued in an attempt to control the growth/proliferation of the somatotropinoma. Combination therapy with PEGV and cabergoline has been investigated in human acromegaly as an effective strategy to enhance biochemical control in patients partially resistant to monotherapy.^28,29 The dopaminergic suppression of GH secretion by cabergoline complements the blockade of peripheral GH receptors, allowing further reductions in IGF-1 and lowering the required dose of PEGV.^28,29 In addition, continued cabergoline administration may help prevent pituitary tumor enlargement, as PEGV alone does not exert antiproliferative effects on somatotroph cells.^28,29

After 180 days of treatment with PEGV and cabergoline, most of the echocardiographic changes were reversed, as has been observed after hypophysectomy.³⁰ In humans with acromegaly, successful treatment has been associated with significant echocardiographic improvements, including reductions in left ventricular hypertrophy and chamber size, as well as improved diastolic function. This suggests that acromegalic cardiomyopathy may be partially reversible.^31,32

This case report has limitations. First, pituitary imaging was not repeated during the follow-up period, meaning that tumor size evolution could not be assessed. The results and conclusions are also limited by the fact that this is a single-case report with a relatively short follow-up period. Other limitations include discontinuing the CGMS after achieving remission and not performing glucose tolerance tests. Although these tests have not been validated in cats, they could have provided a clearer indication of a potential prediabetic state.

Conclusions

This is the first reported case of PEGV + cabergoline treatment in a cat with HST. The results suggest that the combined treatment of PEGV and cabergoline was associated with a rapid normalization of serum IGF-1 concentrations, diabetic remission, and improvements in cardiovascular function and QoL over a short period. Despite its high cost, PEGV could be considered a novel, safe and promising treatment option for controlling feline HST and its comorbidities (DM and HCM), alongside other medical options, such as radiotherapy or hypophysectomy. Further research should focus on treating more cats, determining optimal dosage regimens and testing combined treatment protocols to control HST more effectively.

Footnotes

Accepted: 3 February 2026

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals and procedures that differed from established internationally recognized high standards (‘best practice’) of veterinary clinical care for the individual patient. The study therefore had prior ethical approval from an established (or ad hoc) committee as stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers) for all procedure(s) undertaken (prospective or retrospective studies). For any animals or people individually identifiable within this publication, informed consent (verbal or written) for their use in the publication was obtained from the people involved.

ORCID iD

Diego Miceli

Juan P Rey Amunategui

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