Feline acromegaly: Treatment options

Feline acromegaly is a disease characterized by excessive growth hormone released from a functional pituitary adenoma, resulting in a wide array of clinical signs and, commonly, insulin-resistant diabetes. For information on the pathophysiology, clinical signs, and diagnosis of feline acromegaly, see the article on page 467. This article provides an overview of the many treatment options for this disease.

MEDICAL TREATMENT

Medical options for treating acromegaly range from increasing a patient's insulin dosage to manage the diabetogenic effects of acromegaly to instituting treatment with a somatostatin analogue, dopamine agonist, or growth hormone receptor antagonist. Several of these treatments are common in human medicine but have not been studied widely in veterinary medicine.

Somatostatin analogues

Somatostatin is a hypothalamic hormone that acts on the pituitary gland to inhibit growth hormone release. Somatostatin analogues are commonly administered in people with acromegaly and have efficacy rates of 50% to 60%. In addition to acting centrally by suppressing growth hormone release and peripherally by interfering with growth hormone receptor binding on hepatocytes, somatostatin analogues are also thought to result in tumor shrinkage of pituitary adenomas by promoting apoptosis.1

The somatostatin analogue octreotide has been evaluated in a few cats with acromegaly with limited success. In a study of four cats with acromegaly, no change in serum growth hormone concentration was noted after treatment with octreotide.2 Another study, which measured the short-term effects of octreotide in five cats with acromegaly, found a decrease in growth hormone concentrations for up to 90 minutes after octreotide administration.3 However, a recent study evaluating a long-acting somatostatin analogue (Sandostatin LAR Depot—Novartis) showed no benefit in cats treated for three to six months.4

The failure of these drugs to inhibit growth hormone release may be related to differences in somatostatin receptor subtypes found on pituitary adenomas. Future studies to identify the somatostatin receptor subtypes in feline growth hormone-secreting pituitary tumors are required to determine if these subtypes are similar to the ones found in people and if human somatostatin analogue therapy, at least in theory, may be beneficial in cats with acromegaly.

Dopamine agonists and growth hormone receptor antagonists

Dopamine agonists and, more recently, growth hormone receptor antagonists are also given to people to treat acromegaly.

Growth hormone receptor antagonist therapy has not been reported in cats, but in people, response rates have been reported to be as high as 90%.1 However, it has been noted that these medications have no effect on tumor size (do not result in tumor shrinkage) and, thus, would not benefit patients with neurologic signs.

A single case study on the treatment of feline acromegaly with a dopamine agonist (L-deprenyl) showed that the medication had no effect on reducing insulin requirements or clinical signs of disease.5 In people, dopamine agonists are typically only 10% to 20% effective but are often combined with other medications.1

Increasing insulin

Increasing the dosage of insulin to improve glycemic control and clinical signs of diabetes is the most conservative—and most common—method for managing insulin-resistant diabetic acromegalic cats. While helping to control the clinical signs of the diabetes, raising the insulin dose has no effect on growth hormone secretion, progression of the clinical signs of acromegaly, or continued growth of the pituitary tumor.

In addition, some patients treated with high doses of insulin unpredictably and inexplicably become sensitized to the effect of the insulin, resulting in hypoglycemic crises.6,7 The timing of the insulin sensitization and occurrence of hypoglycemic episodes was extremely variable. In one study, several acromegalic cats were euthanized after experiencing hypoglycemic comas.6

SURGICAL TREATMENT

Surgically removing the pituitary tumor (adenectomy) is the treatment of choice in people with acromegaly. The procedure can be performed in cats and dogs but typically results in the complete removal of the pituitary gland (hypophysectomy). Complications associated with the surgery include hemorrhage and incision dehiscence. After surgery, patients require treatment with cortisone, L-thyroxine, with or without desmopressin, to compensate for the loss of pituitary function. Because of this, only patients that are easily medicated should be considered for this procedure.

Few case reports exist for the treatment of feline acromegaly with transsphenoidal hypophysectomy. In one case, a patient was receiving 25 U of insulin detemir (Levemir—Novo Nordisk) four times a day before surgery, and three weeks after surgery, the patient no longer required insulin therapy.8 Up to one year later, the patient's insulin-like growth factor-1 (IGF-1) and growth hormone concentrations remained normal.

In a case we treated at VCA West Los Angeles Animal Hospital, a 13-year-old castrated male domestic shorthaired cat with acromegaly underwent transsphenoidal hypophysectomy. The patient had a history of insulin-resistant diabetes mellitus and was receiving 15 U of insulin glargine every 12 hours. The patient's diabetes mellitus resolved two weeks after the surgery and remained in remission for eight months, at which time the cat was euthanized for an unrelated issue.

Availability of this procedure is limited in the United States, and as of this writing, the procedure is only available at the VCA West Los Angeles Animal Hospital, although other institutions may soon be able to offer this option.

RADIATION

Radiation therapy is another option for the treatment of feline acromegaly, especially if the tumor is inoperable or surgical treatment is not available in the area. In human medicine, radiation therapy is regarded as a second-line treatment since beneficial effects may take years to develop and patients typically experience undesired late-term central nervous system radiation effects.

Most studies that have been performed in veterinary medicine focus on radiation treatment of pituitary masses regardless of functional status. There is no standard treatment protocol for pituitary masses, and varying methods have been used, including both single- and multiple-dose fractions, administering total doses from 1,500 to 4,500 cGY.9-14 Most of the cats included in these studies had insulin-resistant diabetes (suspected acromegaly or Cushing's disease) or neurologic signs.

Radiation therapy has been shown in these studies to be successful in improving both insulin resistance and neurologic signs. Neurologic improvement was generally seen within weeks to months. Improved insulin response was seen within the first month; however, most patients still required insulin therapy. In cases in which repeat imaging was available, a decrease in tumor size was also noted.

Disadvantages of radiation therapy are the early and delayed effects of radiation, repeated anesthesia, and expense. Early effects from radiation therapy include hair loss, skin pigmentation, and otitis externa.12,14 Reported late-term side effects include brain necrosis, tumor regrowth, loss of vision, and hearing impairment.11,12

In one study, 12 cats with pituitary tumors were treated with a coarse fractionated radiation protocol, delivering a total dose of 37 Gy in five once-weekly doses.9 Eight of these cats had insulin-resistant diabetes mellitus secondary to acromegaly. After radiation therapy, five of the eight cats no longer required insulin therapy, two became stable diabetics, and one required less insulin. In addition, three of four cats had improved neurologic signs. The mean survival time of cats in this study was about 18 months.

In another study, 14 cats with confirmed acromegaly and insulin-resistant diabetes mellitus were treated with a total dose of 3,700 cGy divided into 10 fractions (three a week).10 Thirteen of the 14 cats had improved insulin responses, with an average insulin dosage reduction of about 75%. Six of the cats went into complete diabetic remission, and three of the six remained in remission at the time of this writing. The median survival time of cats in this study was 28 months.

CONCLUSION

Many options exist for treating feline acromegaly. However, clinical studies on their long-term safety and efficacy are limited and often lack controls. Until more work is done evaluating medical treatments such as somatostatin analogues and growth hormone antagonists, most patients are best treated with radiation therapy or surgery to control growth hormone concentrations and neurologic signs, or with increased insulin doses to improve glycemic control.

When making your recommendation regarding treatment, be sure to consider the patient's clinical status (state of diabetes control, any coexisting diseases, whether or not it is a candidate for anesthesia), the availability of treatments in your area, and the advantages and disadvantages of each treatment modality.

Justin Wakayama, DVM Department of Veterinary Clinical Sciences College of Veterinary Medicine University of Minnesota St. Paul, MN 55108

David S. Bruyette, DVM, DACVIM VCA West Los Angeles Animal Hospital 1900 S. Sepulveda Blvd. West Los Angeles, CA 90025

Veterinary Diagnostic Investigation and Consultation 26205 Fairside Road Malibu, CA 90256