Overview

• Syndrome resulting from growth hormone (somatotropin) hypersecretion by tumorous or hyperplastic somatotrophs in the anterior pituitary.
• Clinical signs are due to growth hormone's direct catabolic/diabetogenic effects and its indirect anabolic effects mediated through insulin-like growth factor I, which is secreted by the liver in response to growth hormone stimulation.
• Elevated IGF1 activity induces excessive soft tissue growth, visceral organomegaly, bone remodeling and thickening (especially in bones formed from membranous ossification) resulting in arthropathy, broad facial features, and enlarged “clubbed” paws.
• Myocardial hypertrophy occurs in many cats, but heart failure is uncommon.
• The catabolic actions of GH result from insulin antagonism leading eventually to pancreatic cell exhaustion and DM. Between 25 and 33% of diabetic cats may have acromegaly.
• Like most diabetic cats the potential for remission remains if the excessive GH production can be normalized; likelihood of remission is inversely related to the duration of DM.

Signalment

• Cat
• Median age-11 years (range of 6–17 years)
• Approximately 80% are males

Signs

• Initial signs relate to unregulated DM with the vast majority of cases presenting with polyuria, polydipsia, and often profound polyphagia accompanied with concurrent weight gain (weight loss has also been reported).
• Many patients gain weight and have increased body size due to increased bone and soft tissue mass, not from increased adipose tissue. Weight gain in an unregulated diabetic cat strongly suggests acromegaly.
• Broadening of facial features, prognathia inferior, and increased paw size reflect long-standing or severe disease.
• Organomegaly-most commonly bilateral renomegaly and hepatomegaly.
• Murmur and/or gallop rhythm occasionally present; signs of heart failure uncommon.
• Lameness may develop.
• Neurologic signs referable to intracranial disease through an expanding pituitary mass lesion possible.
• Recent reports suggest the majority of acromegalic cats are indistinguishable phenotypically from non-acromegalic diabetic cats.

Causes & Risk Factors

• GH hypersecretion.
• Progestins do not cause GH secretion and acromegaly in cats as they do in dogs.

Differential Diagnosis

• Uncomplicated DM or DM secondary to hyperadrenocorticism
• Pituitary-dependent hyperadrenocorticism and acromegaly can both produce insulin-resistant DM with an associated pituitary mass lesion. Differentiation may require use of a low-dose dexamethasone suppression test to rule out PDH.
• Acromegaly and PDH can occur concurrently.
• Other disorders causing weight loss with polyphagia, polyuria, and polydipsia such as hyperthyroidism are not usually associated with significant glucose intolerance.
• Insulin-resistant DM (>2.0 U of insulin/kg/12h) is to be expected in all acromegalic cats and the dose tends to increase over time, with doses of 12–50 U/cat/12h not uncommon.
• Acromegaly should be suspected in any diabetic cat demonstrating signs of otherwise unexplained insulin resistance.

CBC/Biochemistry/Urinalysis

• Most abnormalities attributed to poorly controlled DM-hyperglycemia, glucosuria, and elevated fructosamine levels are consistent findings in most acromegalic cats.
• Hyperproteinemia.
• Traditionally associated with renal failure and hypertension, but more recent studies suggest this is not the case.

Other Laboratory Tests

• IGF1-diabetic cats receiving insulin can have higher IGF1 levels than normal; hence there is significant potential for overlap between acromegalic and non-acromegalic diabetic cats; however, dramatically elevated IGF1 levels (e.g., >1,000 ng/ml) are strongly suggestive of the acromegaly.
• IGF1 is well preserved across the species, so valid assays are commonly available.
• GH-elevated basal serum levels are diagnostic. However, as GH is not well preserved across the species, a validated fGH assay has limited availability.

Imaging

• Intracranial imaging to demonstrate a pituitary mass lesion; MRI is more sensitive than contrast-enhanced CT, although the difference is modest and from a cost-benefit perspective CT is generally preferred.
• Echocardiographic abnormalities may include left atrial enlargement, asymmetric septal and left ventricular free-wall thickening, systolic anterior motion of the mitral valve, and diastolic dysfunction.
• Radiographic changes include increased oropharyngeal soft tissue, degenerative arthropathy with periarticular osteophytosis, spinal spondylosis deformans, and variable abdominal organomegaly.

Radiotherapy

• The only currently available means of reducing autonomous overproduction of GH from the anterior pituitary. Unfortunately, radiotherapy is more suited to reducing the size of the tumor than achieving clinically significant reductions in GH secretion.
• A total dose of between 3,500 and 5,500 cGY, administered in variably fractionated doses is often suggested. Recent reports suggest that the greatest success may be achieved with a total dose of 3,700 cGy administered as an incremental hypofractionated dosage protocol of 10 doses. Using this method, 13 of 14 acromegalic cats had markedly improved diabetic control.

Surgery

• Hypophysectomy is considered the treatment of choice in human hypersomatotropism. It has also proven to be the only consistently effective and reliable method to cure HS in cats.
• An experienced neurosurgeon and appropriate pre-, peri- and postoperative care are essential for success. A transsphenoidal approach is currently preferred (incising the soft palate).
• In the long run, cats need to be supplemented with thyroid hormone and a glucocorticoid; synthetic ADH (DDAVP) supplementation can often be ceased 6–8 weeks postoperatively. When performed early in the disease process, diabetic remission is a realistic outcome and often occurs within 2 months after the procedure.

Palliative Treatment

• When definitive treatment is not possible, the focus should lie on gaining more control of the diabetes mellitus and treating possible comorbidities.
• Eventually most cats tend to need high dosages of insulin and/or combinations of short-acting and long-acting insulin types to ensure an adequate quality of life for both pet and owner.
• Nevertheless, a minority achieve an adequate quality of life.
• Regular veterinary assessment is recommended.
• Iatrogenic hypoglycemia is a major concern given the pulsatile nature of GH secretion (and therefore associated insulin resistance).