Feline Acromegaly- Treatments

So now that we know that Merry has Acromegaly... then you probably know I decided to treat him by giving him 2 insulins and controlling it that way. My vet and I discussed the radiation therapy but I chose to not go in that direction.   I asked my vet the other day what will happen when it's the end of his life.  How will I know when the disease is too much.  She told me that he will start having seizures.  I am pretty scared about that.  I just hope it isn't bad and that I make the decision to put him down when the time is right.  Sometimes I wish I was one of the lucky people who come home and find that their cats have passed away and they don't have to make the decision about when the time is right to put them down.  Anyways...

My vet gave me their new magazine Veterinary Medicine which has an excellent article on Acromegaly.  That is a link to the article but incase someone finds this post out there in the world of the internet and it is gone I would like to repost it here for information.  I don't have permission to do this but hope that the magazine doesn't mind so we can spread the information out (just incase the link is ever pulled).  

Feline acromegaly: Treatment options

Somatostatin analogues, dopamine agonists, and growth hormone receptor antagonists are commonly used to treat people with acromegaly. Should you be giving them to your patients?

Oct 1, 2013 By: Justin Wakayama, DVM, David S. Bruyette, DVM, DACVIM VETERINARY MEDICINE

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

Feline Acromegaly

Recently when I went into the vet for my crazy cat Pippin (who is doing well after being on all the meds but tonight he eye looks crazy.. what's next???), the vet gave me their new magazine Veterinary Medicine which has an excellent article on Acromegaly.  That is a link to the article but incase someone finds this post out there in the world of the internet and it is gone I would like to repost it here for information.  I don't have permission to do this but hope that the magazine doesn't mind so we can spread the information out (just incase the link is pulled).   In my next post... I'll post what they say about treatments so be sure to look for that.

Feline acromegaly: The keys to diagnosis

Caused by excessive growth hormone secretion, this likely underdiagnosed endocrinopathy may be lurking in your feline patients—especially older, poorly controlled diabetic males. Here's a look at which diagnostic tests can help you detect it.

Oct 1, 2013 By: Justin Wakayama, DVM, David S. Bruyette, DVM, DACVIM VETERINARY MEDICINE

Feline acromegaly is a disease characterized by excessive growth hormone secretion, leading to a wide array of clinical signs caused by the hormone's effects on multiple organ systems. These effects can be divided into two major classes: catabolic and anabolic. The catabolic actions of growth hormone include insulin antagonism and lipolysis, with the net effect of promoting hyperglycemia. The slow anabolic (or hypertrophic) effects of growth hormone are mediated by insulin-like growth factors. Growth hormone stimulates the production of insulin-like growth factors in several tissues throughout the body. Insulin-like growth factor-1 (IGF-1), which is produced in the liver, is thought to be the key factor that facilitates the anabolic effects of growth hormone that are responsible for the characteristic appearance of people, dogs, and cats with acromegaly.
Similar to its etiology in people, acromegaly in cats is the result of a functional adenoma of the pituitary gland that releases excessive growth hormone despite negative feedback.¹
 

ANATOMY AND PHYSIOLOGY Growth hormone is produced in an anterior lobe of the pituitary gland, specifically by cells called somatotrophs. The regulation of growth hormone is complex, and many factors—both environmental and endogenous—are responsible for its control. The two most important regulators of growth hormone production and release are growth hormone-releasing hormone (GHRH) and somatostatin, which are produced in the hypothalamus. While growth hormone release is stimulated by GHRH, it is inhibited by somatostatin as well as by negative feedback from itself and IGF-1.¹
 
SIGNALMENT
Feline acromegaly is an uncommon disease, although it is thought to be underdiagnosed. It most commonly affects middle-aged and older, male castrated cats. In one study, 13 of 14 cats with acromegaly were males, with an average age of 10.2 years.² This association may be biased, however, as most cats in which acromegaly is diagnosed are presented for complications associated with diabetes mellitus, which is also common in older, male castrated cats. Based on available data, no known breed association for feline acromegaly exists. 

CLINICAL SIGNS

1. This domestic shorthaired cat with presumptive acromegaly is exhibiting a broadened face, a physical change commonly associated with feline acromegaly. The cat was presented for unregulated diabetes.

Cats with acromegaly are commonly presented for insulin-resistant diabetes mellitus (insulin doses dependent on insulin type) with concurrent weight gain rather than weight loss.² Other clinical signs vary because of the wide range of effects the disease has on the body. Physical changes associated with feline acromegaly include increased body weight, a broadened face, enlarged feet, protrusion of the mandible (prognathia inferior), increased interdental spacing, organomegaly, and a poor coat (Figures 1-3).

2. The same cat as in Figure 1 exhibiting another physical change associated with feline acromegaly—protrusion of the mandible.

Respiratory disease may result from excessive growth of the soft palate and laryngeal tissues, leading to stertorous breathing and even upper airway obstruction. Cardiovascular signs include the presence of a heart murmur, hypertension, arrhythmia, and congestive heart failure associated with hypertrophic cardiomyopathy.³ Neurologic disease associated with feline acromegaly is uncommon but can occur with large pituitary adenomas. Neurologic signs that have been observed with acromegaly include dullness, lethargy, abnormal behavior, circling, and blindness.

3. This close-up of the cat's teeth (the same cat as in Figures 1 & 2) highlights increased interdental spacing, another physical change associated with feline acromegaly.

Glomerulopathy and secondary renal failure have also been associated with feline acromegaly. Histologic evaluation of the kidneys of cats with acromegaly has revealed thickening of the glomerular basement membrane and Bowman's capsule, periglomerular fibrosis, and degeneration of the renal tubules.² Because of an associated degenerative arthropathy and peripheral (diabetic) neuropathy, lameness has also been noted in cats with acromegaly.

Gallbladder and Pancreatitis

Another day, another problem.  My cat Pippin was so sick last night.  Lots of throwing up... this throw up was even the color of blood and stunk really really bad.  It was Nasty!  Poor guy... I stayed up with him in the bathroom most of the night till it settled down.  I called the vet first thing in the morning and brought him up there.  I knew it was going to be his pancreas again.

 

I walked out of the vet today with a $900 bill!!!  WHAT!  I was not expecting that.  I mean .. WHAT!  So the vet did two blood tests... one is the normal panel and I guess the other one was to check the pancreas.  Then it was all this meds... and a urine test and a $50 vet visit charge.  And then they did an ultra sound since there was blood in the vomit.  Turns out that the gallbladder has some gunk in it which we discovered with a ultra sound. So Pippin now has to take Denosyl to help him out. 

Today sucked as far as money that is for sure.  Pippin is now on a steroid for life.  Which isn't great for cats with diabetes because now we will probably have to up his insulin (3 units of Prozinc).  He will be taking a narcotic for 5 days, nausea pills for 5 days, novifit, his insulin meds, and his steroid.  The cost of today's visit was a tough one.  Now we also know we will have to spend an additional $30 a month on steroid pills for Pippin.    Just a tough day all around.  Though I am glad we figured out his gallbladder isn't well and have time to correct it.

For those of you wondering whether or not to get a pet... remember they aren't cheap!