Therapy of Concurrent Diabetes Mellitus and Cushing's Syndrome
(with o,p'-DDD/Lysodren)
from the veterinary textbook,
Canine and Feline Endocrinology and Reproduction, 2nd Edition,
by Edward C. Feldman and Richard W. Nelson, 1996.

Page manager's note:
As with everything contained in the Cushing's web pages,
this information is intended to supplement
-- not replace or supersede --
the guidance of your veterinarian.

Initial Diagnosis and Treatment. If a dog is diagnosed as having diabetes mellitus and hyperadrenocorticism, one must treat both disorders. While completing the diagnostic evaluation for hyperadrenocorticism and awaiting test results, insulin therapy should be initiated. Most of these dogs require large doses of insulin. Dogs with hyperadrenocorticism that require a conservative or low dose of insulin are occasionally seen. These latter dogs are the best candidates for weaning from insulin following Lysodren therapy. No attempt is made to achieve perfect glycemic control; rather a dosage of insulin adequate to prevent ketoacidosis is advised (0.5 U/kg of NPH or Lente insulin BID is a conservative initial dosage). Attempts at extremely good control of the diabetic condition should not be undertaken until the hyperadrenocorticism is controlled or the Cushing's diagnosis is refuted.

Lysodren Dosage. Approximately 5-10% of dogs with Cushing's syndrome also have diabetes mellitus (i.e., persistent fasting hyperglycemia and glycosuria). These dogs should be treated in the same manner as other dogs with Pituitary-Dependent Hyperadrenocorticism (Lysodren at 50 mg/kg/day and no glucocorticoids). However, it is recognized that Cushing's syndrome causes insulin antagonism. Successful reduction of circulating cortisol concentrations should reduce the insulin requirement by diminishing insulin resistance. Failure to plan for this enhanced insulin effectiveness could result in hypoglycemic reactions.

Treatment and Monitoring Protocol. The treatment of the diabetic dog with Cushing's syndrome requires more work by both owner and veterinarian. These dogs often receive more than 2.0 U/kg/day of insulin. The complicated nature of treating this combination of diseases should be carefully explained to the owner. Both owner and veterinarian must be aware that as the dog receives Lysodren, the Cushing's syndrome should progressively resolve, and the diabetes management usually changes as well as insulin resistance resolves. Both diseases must be monitored. Owners should be asked to obtain a urine sample from their pet at least two or three times daily during the "loading dose" phase of Lysodren therapy. Each sample is checked for glucose. Any time a urine sample is found to be negative for glucose, the subsequent insulin dose should be reduced by at least 10-20%. The hyperadrenocorticism in most of these dogs in controlled in the expected 5 to 9 days. The ACTH stimulation test should be rechecked within 7 days of initiating Lysodren to recognize the end point and to avoid overdose. The recheck protocol for these dogs should proceed as follows: 1) the owner feeds the dog at home; 2) the dog is brought to the veterinary hospital in the morning between 7 and 9 a.m.; 3) the blood glucose is measured and the owner is observed as insulin is administered; 4) the blood glucose is monitored every 1-2 hours throughout the day; 5) 1 to 2 hours before the owner picks up the pet in the late afternoon, and ACTH stimulation test is completed. This protocol provides an opportunity to answer two critical questions: 1) what effect has Lysodren therapy had on glycemic control (blood glucose, insulin dosage) and 2) what effect has Lysodren had on the hyperadrenocorticism?

Prognosis. Approximately 5-10% of dogs diagnosed with this combination of diseases require no insulin following successful Lysodren therapy. An additional 70-80% require significantly less insulin and their diabetes mellitus is easier to control. The insulin dose in the remaining dogs is minimally reduced by control of the Pituitary-dependent Hyperadrenocorticism, but the insulin is more effective in lowering blood glucose concentrations. If none of these three results is observed, the original diagnosis of hyperadrenocorticism should be questioned.

Page manager's note:
This article reflects only the treatment regimens which had been approved as of late 1995. After the publication of this text, Anipryl was approved for use with Cushing's. The absence of information on Anipryl should not be interpreted to mean that it is not a treatment option.