Feline Comorbidities: Hypersomatotropism-induced diabetes in cats.

PRACTICAL RELEVANCE: Diabetes mellitus is the second-most common feline endocrinopathy, affecting an estimated 1/200 cats. While the underlying causes vary, around 15-25% of cats with diabetes mellitus develop the condition secondarily to progressive growth hormone (GH)-induced insulin resistance. This typically results in a form of diabetes that is challenging to manage, whereby the response to insulin is very variable or high doses are required to achieve even minimal diabetic control. CLINICAL CHALLENGES: Although uncontrolled chronic excessive GH may result in phenotypic changes that raise suspicion for acromegaly, many cats with hypersomatotropism (HST) do not have these changes. In these situations, a clinician's index of suspicion may be increased by the presence of less dramatic changes such as marked polyphagia, stertor or uncontrolled diabetes mellitus. The current diagnostic test of choice is demonstration of a markedly increased serum insulin-like growth factor 1 (IGF1) concentration, but some affected cats will have only a marginal increase; additionally, chronic insulin administration in cats results in an increase in serum IGF1, making the diagnosis less clear cut and requiring additional confirmatory tests. EVIDENCE BASE: Over the past two decades, HST has increasingly been recognised as an underlying cause of diabetes mellitus in cats. This review, which focuses on diagnosis and treatment, utilises data from observational studies, clinical trials and case series, as well as drawing on the experience of the authors in managing this condition.

Transsphenoidal hypophysectomy for the treatment of hypersomatotropism secondary to a pituitary somatotroph adenoma in a dog.

Pituitary-dependent hypersomatotropism is rarely diagnosed in dogs and surgical treatment is not reported. A 6-year-10-month male neutered Patterdale Terrier presented with polyuria, polydipsia, progressive pharyngeal stertor, excessive hair growth and widened facial features and paws. Serum insulin-like growth factor-1 concentration via radioimmunoassay was consistent with hypersomatotropism (1783 ng/mL). A pituitary mass was identified on magnetic resonance and computed tomography imaging. Six weeks later, glucosuria, starved hyperglycemia and serum fructosamine above the reference range (467.6 µmol/L, RI 177-314) were documented, consistent with diabetes mellitus. Transsphenoidal hypophysectomy was performed under general anesthesia without complications. Pituitary histopathology identified an acidophil neoplasm, with positive immunostaining for growth hormone. Postoperatively, there was rapid resolution of clinical, biochemical and morphologic changes of hypersomatotropism with persistence of diabetes mellitus. This case demonstrates successful resolution of hypersomatotropism with ongoing diabetes mellitus in a dog after surgical treatment by transsphenoidal hypophysectomy.

Hypersomatotropism and Other Causes of Insulin Resistance in Cats.

True insulin resistance should be differentiated from management-related difficulties (eg, short insulin duration, inappropriate insulin injection, inappropriate storage). Hypersomatotropism (HST) is the number one cause of insulin resistance in cats, with hypercortisolism (HC) occupying a more distant second place. Serum insulinlike growth factor-1 is adequate for screening for HST, and screening at the time of diagnosis, regardless of presence of insulin resistance, is advocated. Treatment of either disease centers on removal of the overactive endocrine gland (hypophysectomy, adrenalectomy) or inhibition of the pituitary or adrenal glands by using drugs such as trilostane (HC), pasireotide (HST, HC) or cabergoline (HST, HC).

Pathophysiology of Prediabetes, Diabetes, and Diabetic Remission in Cats.

Diabetes mellitus (DM) has a heterogenous cause, and the exact pathogenesis differs between patients. Most diabetic cats have a cause similar to human type 2 DM but, in some, DM is associated with underlying conditions, such as hypersomatotropism, hyperadrenocorticism, or administration of diabetogenic drugs. Predisposing factors for feline DM include obesity, reduced physical activity, male sex, and increasing age. Gluco(lipo)toxicity and genetic predisposition also likely play roles in pathogenesis. Prediabetes cannot be accurately diagnosed in cats at the current time. Diabetic cats can enter remission, but relapses are common, as these cats might have ongoing, abnormal glucose homeostasis.

Prevalence of hypersomatotropism and hyperthyroidism in cats with diabetes mellitus from referral centers in Buenos Aires (2020-2022).

OBJECTIVES: The aim of this study was to estimate the prevalence of hypersomatotropism (HST) and hyperthyroidism in cats with diabetes mellitus (DM) from referral centers in Buenos Aires, Argentina. METHODS: This was a prospective study. Systematic screening of serum insulin-like growth factor 1 (IGF-1) and total thyroxine was performed in all cats diagnosed with DM at referral centers in Buenos Aires between February 2020 and February 2022. RESULTS: In total, 154 diabetic cats were evaluated (99 males and 55 females; median age 12 years [range 3-21]; mean body weight 5 kg [range 2-12]). Altogether, there were 115 (75%) domestic shorthairs and one domestic longhair; the remaining 38 cats were purebred (mainly Siamese, n = 25 [16%]). Twenty (12.9%) cats had IGF-1 concentrations >1000 ng/ml, and three (1.9%) had IGF-1 concentrations between 800 and 1000 ng/ml along with pituitary enlargement on CT, resulting in a 14.9% HST prevalence rate in diabetic cats. Intracranial imaging was performed in all cats with HST; median pituitary dorsoventral height was 5.8 mm (range 3.1-9.5). Fourteen of 23 (61%) cats had phenotypic changes consistent with acromegaly at the time of diagnosis of HST. Four of 154 (2.5%) cats had concurrent hyperthyroidism. CONCLUSIONS AND RELEVANCE: To date, this is the first study outside of Europe to have evaluated the prevalence of HST and hyperthyroidism in cats with DM. In Buenos Aires referral centers, feline HST is the most common concurrent endocrinopathy in cats with DM but with a lower prevalence than has previously been reported. Hyperthyroidism is a rare concurrent endocrinopathy in diabetic cats from referral centers in Buenos Aires.

Endocrine response and outcome in 14 cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (17 Gy).

OBJECTIVE: To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS). ANIMALS: 14 client-owned cats. PROCEDURES: Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time. RESULTS: Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status. CLINICAL RELEVANCE: The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.

Serum insulin-like growth factor-1 concentrations in healthy cats before and after weight gain and weight loss.

BACKGROUND: Measurement of serum concentrations of insulin-like growth factor (IGF)-1 is used to diagnose acromegaly in cats. HYPOTHESIS: Changes of body weight do not affect serum concentrations of IGF-1 in cats. ANIMALS: Ten healthy purpose-bred cats. METHODS: Prospective study. In lean cats, food availability was stepwise increased during the first week and given ad libitum for a total of 40 weeks to increase their body weight. From week 41 to week 60, food access was limited to reach a weight loss of 1% to 2% each week. Measurement of IGF-1 was performed at week 0, 16, 40, and 60. Insulin-like growth factor-1 was measured by radioimmunoassay. Body weight and IGF-1 were compared among the 4 time points. RESULTS: Body weight increased by 44% from week 0 (4.5 ± 0.4 kg) to week 40 (6.5 ± 1.2 kg) (P < .001) and decreased by 25% from week 40 to week 60 (4.9 ± 0.7 kg) (P < .001). Serum IGF-1 concentrations did not differ during the study period (week 0, 16, 40, 60: 500 ± 188, 479 ± 247, 470 ± 184, 435 ± 154 ng/mL, respectively; P = .38). Correlations with body weight were not observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Insulin-like growth factor-1 might not be influenced by changes of body weight in healthy cats, possibly suggesting that the latter is unimportant when interpreting IGF-1 results in this species.

Acromegaly in dogs and cats.

Acromegaly is an endocrine disease that leads to elevated production and secretion of growth hormone (GH). It can occur in adult and aged cats and is usually associated with neoplasms, such as functional pituitary macroadenoma of somatotropic cells. In dogs it is usually related to an increase in serum progesterone that induces production of GH by the mammary glands. The main clinical signs are related to insulin resistance and the anabolic effect induced by GH: polyuria, polydipsia, polyphagia, increased tissue growth, weight gain, prognathism, and other changes. The condition can be diagnosed from clinical signals and imaging associated to measurement of serum concentrations of GH and insulin-like growth factor 1 (IGF-1, also known as somatomedin C). The main therapeutic modalities are radiotherapy, hypophysectomy, and several drugs such as somatostatin analogs, dopaminergic agonists and GH receptor antagonists. The present review aims to provide a relevant animal model of acromegaly with an update on the therapeutic approach that may help clinicians to consider the GH axis-IGF-1 system, its pathogenesis and the clinical signs induced by this hormonal disorder.

Increased insulin-like growth factor 1 concentrations in a retrospective population of non-diabetic cats diagnosed with hypertrophic cardiomyopathy.

OBJECTIVES: The aim of the study was to document whether a proportion of non-diabetic cats with left ventricular hypertrophy (LVH) previously diagnosed with hypertrophic cardiomyopathy (HCM) have elevated circulating insulin-like growth factor 1 (IGF-1) concentrations. METHODS: A retrospective analysis of residual blood samples obtained at the time of echocardiographic diagnosis of HCM from a population of 60 non-diabetic cats were analysed for circulating IGF-1 concentrations using a validated radioimmunoassay and compared with a control group of 16 apparently healthy cats without LVH. Clinical and echocardiographic data for cats with an IGF-1 level >1000 ng/ml were compared with those with an IGF-1 level <800 ng/ml. RESULTS: In total, 6.7% (95% confidence interval 1.8-16.2%) of cats with HCM had an IGF-1 level >1000 ng/ml. The prevalence of an IGF-1 level >1000 ng/ml in the control group was zero. CONCLUSIONS AND RELEVANCE: A small proportion of non-diabetic cats previously diagnosed with HCM had an IGF-1 concentration at a level that has been associated with feline hypersomatotropism (fHS) in the diabetic cat population. Further prospective research is required to confirm or refute the presence of fHS in non-diabetic cats with LVH and increased IGF-1.

Evaluation of hypophysectomy for treatment of hypersomatotropism in 25 cats.

BACKGROUND: Successful treatment of cats with hypersomatotropism by transsphenoidal hypophysectomy is described in small numbers of cats. OBJECTIVES: To describe the endocrine profile, survival, and remission rates of hypersomatotropism and diabetes mellitus in a cohort of cats with hypersomatotropism that underwent hypophysectomy between 2008 and 2020. ANIMALS: Twenty-five client-owned cats with spontaneous hypersomatotropism. METHODS: Retrospective study. Diagnosis of hypersomatotropism was based on clinical signs, plasma insulin-like growth factor-1 (IGF-1) concentration, and imaging of the pituitary gland. Growth hormone (GH) and IGF-1 concentrations were measured repeatedly after surgery. Survival times were calculated based on follow-up information from owners and referring veterinarians. RESULTS: Median postoperative hospital stay was 7 days (range, 3-18 days). One cat died within 4 weeks of surgery. Median plasma GH concentration decreased significantly from 51.0 ng/mL (range, 5.0-101.0 ng/mL) before surgery to 3.8 ng/mL (range, 0.6-13.0 ng/mL) at 5 hours after surgery. Remission of hypersomatotropism, defined as normalization of plasma IGF-1 concentration, occurred in 23/24 cats (median, 34 ng/mL; range, 14-240 ng/mL) and 22/24 cats entered diabetic remission. Median survival time was 1347 days (95% confidence interval, 900-1794 days; range, 11-3180 days) and the overall 1-, 2-, and 3-year all-cause survival rates were 76%, 76%, and 52%, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: This study shows the beneficial outcome of hypophysectomy in cats with hypersomatotropism, marked by low death rate and a high percentage of diabetic remission and definitive cure.

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

BACKGROUND: Hypersomatotropism (HST) is an increasingly recognized endocrinopathy in cats and is mostly described associated with diabetes mellitus (DM). OBJECTIVES: To evaluate the efficacy and safety of transsphenoidal hypophysectomy in treating HST and DM in cats. ANIMALS: Sixty-eight client-owned cats with HST and DM treated by transsphenoidal hypophysectomy. METHODS: Retrospective cohort study. Medical records were reviewed for glycemic control and serum insulin-like growth factor-1 (IGF-1) concentrations. Postoperative complications, death within 4 weeks, and proportion achieving diabetic remission were recorded. Survival times and DM-free intervals were calculated. RESULTS: Fifty-eight cats (85.3%) were alive 4 weeks postoperatively with 10 (15%) postoperative deaths. Complications included hypoglycemia (n = 9), electrolyte imbalance (n = 9), and transient congestive heart failure (n = 5). Fifty-five cats (95% of 58 surviving cats [81% of all cats undergoing surgery]) had improved control of diabetes. Diabetic remission occurred in 41 cats (71% of 58 surviving cats [60% of all cats]) with insulin administration discontinued after a median of 9 days (range, 2-120). Postoperative 4-week serum IGF-1 concentration nadir was significantly lower in cats achieving diabetic remission (median 20 ng/mL [15-708] than those that did not (324 ng/mL [15-1955]; P = .03). All cats received long-term levothyroxine and hydrocortisone PO, alongside desmopressin (conjunctival) in 38 of 53 cats (72%). Recurrence of DM occurred in 5 of 41 cats (12%) after a median of 248 days (range, 84-1232). Median survival time of all cats was 853 days (range, 1-1740). CONCLUSIONS AND CLINICAL IMPORTANCE: Transsphenoidal hypophysectomy is an effective treatment for cats with HST and DM, with a long-term outcome that compares favorably to existing options.

Pilot study assessing the use of cabergoline for the treatment of cats with hypersomatotropism and diabetes mellitus.

OBJECTIVES: An affordable and effective treatment is needed to manage feline hypersomatotropism. The aim of this study was to assess whether treatment with oral cabergoline for 90 days in cats with hypersomatotropism and diabetes mellitus improved diabetic and insulin-like growth factor 1 (IGF-1) control. METHODS: This was a prospective cohort non-blinded pilot study enrolling client-owned cats with spontaneously occurring diabetes mellitus and hypersomatotropism. Cats received oral cabergoline (5-10 µg/kg q24h) for 90 consecutive days. Serum IGF-1 and fructosamine concentrations were measured on days 1, 30 and 90. Quality of life was determined using the DIAQoL-pet questionnaire on days 1 and 90. RESULTS: Nine cats were enrolled and eight completed the study. There was no significant change in the following: IGF-1 (day 1 median 2001 ng/ml [range 890-2001 ng/ml]; day 30 median 2001 ng/ml [range 929-2001 ng/ml]; day 90 median 1828 ng/ml [range 1035-2001 ng/ml]; χ2(2) = 0.667, P = 0.805); fructosamine (day 1 median 499 µmol/l [range 330-887 µmol/l], day 30 median 551 µmol/l [range 288-722 µmol/l], day 90 median 503 [range 315-851 µmol/l]; χ2(2) = 0.581, P = 0.764); or DIAQoL-pet score (median on day 1 -2.79 [range -4.62 to -0.28], median on day 90 -3.24 [range -4.41 to -0.28]; P = 0.715). There was a significant change of insulin dose (χ2(2) = 8.667, P = 0.008) with cats receiving higher insulin doses at day 90 compared with day 1 (median on day 1 was 0.98 [range 0.63-1.49] and median on day 90 was 1.56 [range 0.49-2.55] units/kg q12h; P = 0.026). CONCLUSIONS AND RELEVANCE: Cabergoline did not improve diabetic control or normalise insulin-like growth factor concentration, or improve patient quality of life.

Feline Pituitary Adenomas: Correlation of Histologic and Immunohistochemical Characteristics With Clinical Findings and Case Outcome.

Pituitary glands from 141 feline autopsy cases were reviewed histologically. Adenoma and hyperplasia were the most common lesions at 13 cases each. Pituitary adenoma was more likely than hyperplasia to be associated with clinical evidence of endocrinopathy or an intracranial mass (P < .001). A histochemical and immunohistochemical panel was applied to 44 autopsy- or hypophysectomy-derived pituitary adenomas in 43 cats from 2 diagnostic laboratories. Adenomas were differentiated from hyperplasia by the presence of disrupted reticulin fibers. One cat had a double (somatotroph and melanotroph) adenoma. Twenty somatotroph adenomas consisted of periodic acid-Schiff (PAS)-negative acidophils that expressed growth hormone; 16/20 had hypersomatotropism; 17/20 had diabetes mellitus. Eleven melanotroph adenomas consisted of PAS-positive basophils or chromophobes that expressed melanocyte-stimulating and adrenocorticotrophic hormones; 5/11 had hypercortisolism; 6/11 had diabetes mellitus. Eleven gonadotroph adenomas consisted of PAS-negative chromophobes that expressed follicle-stimulating and/or luteinizing hormones. Two thyrotroph adenomas consisted of PAS-negative basophils or chromophobes that expressed thyroid-stimulating hormone. Pituitary-dependent disease was not recognized in cats with gonadotroph or thyrotroph adenomas. The Ki-67 proliferation index in hypophysectomy specimens was lower in somatotroph than in melanotroph adenomas. Fourteen cats with hypophysectomy-treated somatotroph or melanotroph adenoma had an 899-day median survival time versus 173 days in 17 nonsurgical cases. After adjusting for age, adenoma size and type, hypophysectomized cats had an overall better survival time than nonsurgical cases (P = .029). The study results underscore the value of hypophysectomy and trophic hormone immunohistochemistry in the treatment and classification of feline pituitary adenomas.

Clinical diabetes mellitus in association with diestrus-induced acromegaly in 2 bitches.

Two intact bitches aged 9 and 11 years were referred due to chronic polyuria, polydipsia, vomiting, anorexia and progressive lethargy. On clinical examination, signs of tissue overgrowth (large paws, widened interdental space, pharyngeal stridor) were noticed. Diabetes mellitus (DM) was diagnosed in one dog (case 1) and diabetic ketoacidosis (DKA) in the other (case 2). There were increased IGF-1 values suggestive of hypersomatotropism. Progesterone values and pathological findings of the ovaries and uterus indicated diestrus. Diagnosis of diestrus-induced hypersomatotropism was made and ovariohysterectomy was performed in both dogs. Dog 1 also had multiple mammary neoplasms treated with bilateral mastectomy. Treatment resulted in diabetic remission in case 1 and improved glycaemic control in case 2. Overall, diestrus-induced hypersomatotropism is rare but should be considered in any intact diabetic bitch with acromegalic features. Ovariohysterectomy is recommended and associated with a fair to good prognosis.

Long-term management and postmortem examination in a diabetic cat with acromegaly treated with two courses of radiation therapy.

A 12-year-old, castrated male cat with diabetes mellitus was diagnosed with acromegaly and examined with magnetic resonance imaging (enlarged pituitary gland, 8 mm); serum hormone concentrations were measured. After the first course of radiation therapy (4 Gy, 12 fractions), insulin administration was not required from day 420 after diagnosis. Enlarged pituitary tumor (8 mm) recurred, and insulin dosage amount of the cat was increased on day 1,065. The second course of radiation therapy (6 Gy, 4 fractions) was performed on day 1,201 and insulin administration was again discontinued. However, the cat died from lymphoma on day 1,397. Postmortem examination revealed pituitary adenoma. Most tumor cells were positive for chromogranin A, synaptophysin, and growth hormone immunohistochemistry. The pancreatic islet cells revealed diffuse hyperplasia. We achieved long-term successful management of an acromegalic cat with two courses of RT. However, a protocol for a second course of RT for feline recurrent pituitary tumor should be further discussed.

Anaesthetic management and complications during hypophysectomy in 37 cats with acromegaly.

OBJECTIVES: The aim of this study was to describe the anaesthetic management and perianaesthetic complications encountered during hypophysectomy surgery in acromegalic cats. We explored relationships between animal demographic data, the anaesthetic protocol used and presence of perioperative complications. METHODS: Cats having undergone hypophysectomy surgery for the treatment of feline acromegaly at a single veterinary referral hospital were identified from hospital records. The anaesthesia records and clinical notes of these animals were retrospectively reviewed. Descriptive statistics were produced and binary logistic regression run to assess for any relationship between patient factors, anaesthetic management and complications during the perioperative period. RESULTS: Perianaesthetic complications identified included hypothermia, hypotension, bradycardia and airway obstruction. Mortality at 24 h post-anaesthesia was 8%. The use of alpha (α)2 agonists was associated with a lower incidence of hypotension. Fentanyl infusion was associated with a higher incidence of airway obstruction compared with remifentanil. Subjectively assessed anaesthetic recovery quality had an association with the number of days spent in the intensive care ward postoperatively. CONCLUSIONS AND RELEVANCE: The anaesthetic management described seems effective for hypophysectomy surgery in cats. Intraoperative complications were common and, while not apparently associated with 24 h patient outcome, drugs and equipment to manage these complications should be available.

Radiotherapy and pasireotide treatment of a growth hormone producing pituitary tumor in a diabetic dog.

An 8-year-old castrated male border terrier dog was diagnosed with acromegaly resulting from a growth hormone secreting pituitary tumor. Sixteen daily fractions of radiation therapy were delivered followed, approximately 1 year later, by administration of pasireotide. The aforementioned treatment was considered effective and should be further evaluated in similar cases.

Radiothérapie et traitement au pasiréotide pour une tumeur pituitaire produisant une hormone de croissance chez un chien diabétique. Un chien Terrier-Border castré âgé de 8 ans a été diagnostiqué avec de l'acromégalie découlant d'une tumeur pituitaire secrétant une hormone de croissance. Seize fractions quotidiennes de radiothérapie ont été administrées et ont été suivies, environ un an plus tard, de l'administration du pasiréotide. Le traitement précédemment mentionné a été considéré efficace et devrait être étudié de plus près dans des cas similaires.(Traduit par Isabelle Vallières).

Pasireotide Long-Acting Release Treatment for Diabetic Cats with Underlying Hypersomatotropism.

BACKGROUND: Long-term medical management of hypersomatotropism (HS) in cats has proved unrewarding. Pasireotide, a novel somatostatin analogue, decreases serum insulin-like growth factor 1 (IGF-1) and improves insulin sensitivity in cats with HS when administered as a short-acting preparation. OBJECTIVES: Assess once-monthly administration of long-acting pasireotide (pasireotide LAR) for treatment of cats with HS. ANIMALS: Fourteen cats with HS, diagnosed based on diabetes mellitus, pituitary enlargement, and serum IGF-1 > 1000 ng/mL. METHODS: Uncontrolled, prospective cohort study. Cats received pasireotide LAR (6-8 mg/kg SC) once monthly for 6 months. Fructosamine and IGF-1 concentrations, and 12-hour blood glucose curves (BGCs) were assessed at baseline and then monthly. Product of fructosamine concentration and insulin dose was calculated as an indicator of insulin resistance (Insulin Resistance Index). Linear mixed-effects modeling assessed for significant change in fructosamine, IGF-1, mean blood glucose (MBG) of BGCs, insulin dose (U/kg) and Insulin Resistance Index. RESULTS: Eight cats completed the trial. Three cats entered diabetic remission. Median IGF-1 (baseline: 1962 ng/mL [range 1051-2000 ng/mL]; month 6: 1253 ng/mL [524-1987 ng/mL]; P < .001) and median Insulin Resistance Index (baseline: 812 µmolU/L kg [173-3565 µmolU/L kg]; month 6: 135 µmolU/L kg [0-443 µmolU/L kg]; P = .001) decreased significantly. No significant change was found in mean fructosamine (baseline: 494 ± 127 µmol/L; month 6: 319 ± 113.3 µmol/L; P = .07) or MBG (baseline: 347.7 ± 111.0 mg/dL; month 6: 319.5 ± 113.3 mg/dL; P = .11), despite a significant decrease in median insulin dose (baseline: 1.5 [0.4-5.2] U/kg; 6 months: 0.3 [0.0-1.4] U/kg; P < .001). Adverse events included diarrhea (n = 11), hypoglycemia (n = 5), and worsening polyphagia (n = 2). CONCLUSIONS AND CLINICAL IMPORTANCE: Pasireotide LAR is the first drug to show potential as a long-term management option for cats with HS.

Feline hypersomatotropism and acromegaly tumorigenesis: a potential role for the AIP gene.

Acromegaly in humans is usually sporadic, however up to 20% of familial isolated pituitary adenomas are caused by germline sequence variants of the aryl-hydrocarbon-receptor interacting protein (AIP) gene. Feline acromegaly has similarities to human acromegalic families with AIP mutations. The aim of this study was to sequence the feline AIP gene, identify sequence variants and compare the AIP gene sequence between feline acromegalic and control cats, and in acromegalic siblings. The feline AIP gene was amplified through PCR using whole blood genomic DNA from 10 acromegalic and 10 control cats, and 3 sibling pairs affected by acromegaly. PCR products were sequenced and compared with the published predicted feline AIP gene. A single nonsynonymous SNP was identified in exon 1 (AIP:c.9T > G) of two acromegalic cats and none of the control cats, as well as both members of one sibling pair. The region of this SNP is considered essential for the interaction of the AIP protein with its receptor. This sequence variant has not previously been reported in humans. Two additional synonymous sequence variants were identified (AIP:c.481C > T and AIP:c.826C > T). This is the first molecular study to investigate a potential genetic cause of feline acromegaly and identified a nonsynonymous AIP single nucleotide polymorphism in 20% of the acromegalic cat population evaluated, as well as in one of the sibling pairs evaluated.

Evaluation of insulin-like growth factor-1, total thyroxine, feline pancreas-specific lipase and urinary corticoid-to-creatinine ratio in cats with diabetes mellitus in Switzerland and the Netherlands.

Objectives The aim of the study was to evaluate circulating insulin-like growth factor-1 (IGF-1), feline pancreas-specific lipase (fPLI) and total thyroxine (TT4) concentrations and urinary corticoid-to-creatinine ratio (UCCR) as indicators for the prevalence of acromegaly, pancreatitis, hyperthyroidism and hypercortisolism in cats with diabetes mellitus. Methods Blood and urine samples were collected from diabetic cats treated in primary care clinics in Switzerland and the Netherlands. Standardised questionnaires and physical examination forms provided clinical information from owners and veterinarians. Laboratory testing included serum biochemistry profile analysis and measurement of circulating fructosamine, IGF-1, fPLI, and TT4 concentrations and UCCR. CT of the pituitary gland was performed using a multidetector computed tomography scanner. Results Blood samples were available from 215 cats and urine samples were collected at home from 117 cats. Age ranged from 2-18 years (median 12 years) and body weight from 2.7-12.3 kg (median 5.5 kg). Sixty-five percent of the cats were castrated male and 35% were female (33% spayed); 82% were domestic shorthair cats. Eighty percent of cats received a porcine insulin zinc suspension, 19.5% insulin glargine and 0.5% a human neutral protamine hagedorn insulin. Thirty-six of 202 (17.8%) cats had IGF-1 concentrations >1000 ng/ml. Serum fPLI, and TT4 concentrations and UCCR were increased in 86/196 (43.9%), 9/201 (4.5%) and 18/117 cats (15.3%), respectively. Prevalence did not differ between countries. Conclusions Hyperthyroidism is rare, whereas increased fPLI concentration, possibly reflecting pancreatitis, is common in diabetic cats. The high UCCR may reflect activation of the hypothalamus-pituitary-adrenal axis, which also occurs in diabetic humans. The percentage of cats with increased IGF-1 was high but lower than reported in recent studies.