An adult female bottlenose dolphin was presented with complaint of severe obesity. Her daily fish ration had been lowered in attempt to reduce her weight. This resulted in what appeared as muscle wasting and not blubber reduction. Blood tests including complete blood counts, erythrocyte sedimentation rate, serum chemistries and thyroid hormone levels were considered normal except for significant elevation of the liver enzyme - gamma glutamyl transferase, mild elevation in cholesterol and triglycerides and an eosinopenia.

Banked serum samples were sent to Auburn University's College of Veterinary Medicine for thyroid and cortisol assays. The thyroid levels were considered low normal, but the cortisol levels were three to four times above our controls. Adrenocorticotropic hormone (ACTH) assays were performed on plasma and the results showed levels ten times higher than the controls. The data indicated chronic elevation of circulating plasma glucocorticoid concentrations, with a pituitary dependent etiology, a condition called Cushing's disease.

There are four drugs currently utilized to reduce cortisol levels. It was decided that Ketaconazole (Nizoral) would be the best approach. The initial dose was 5 mg/kg divided B.I.D. for the first two weeks and then was increased to 7.5mg/kg divided T.I.D. Her caloric intake was maintained at approximately 6,500 calories per day. In seven months time she lost 44kg (216 to 172kg) which was considered ideal weight for a 237cm adult female dolphin. During this time the GGT levels declined to the normal range. Cholesterol and triglyceride levels were also reduced. The dolphin continues to do well after 18 months of ketaconzole therapy. Periodic blood tests and body weight are within normal limits.

"Princess" is a female bottlenose dolphin (Tursiops truncatus) approximately 27 years old. She has been at the Gulfarium for the past 20 years. She delivered a male calf on May 10, 1989, her first calf. The calf named "Cody" was clinically normal until he was found dead in the pool on September 25, 1989. The cause of death was acute peri-cerebral hemorrhage, a result of disseminated brain abscess. The primary lesion was found at the umbilicus with multiple caseous granulomatous lesions throughout the pulmonary system. Cultures of abscesses revealed Clostridium Perfringens and Actinomyces. At the ninth month of the gestation she weighed 475 pounds. A year later her weight was 390 pounds. Since that time, she had a gradual weight gain to a weight of 476.5 pounds on August 20, 1991.

She is 237 cm in length, her ideal weight is 359 pounds (163.2 kg). Her calorie intake was 7605 Kcal/day. It was calculated the minimum daily caloric intake at 40 Kcal/kg/day for her ideal weight should be 6527 Kcal/day. Calculations were made from the diet of zoo herring and capelin she received to adjust her daily intake to 6527Kcal/day. This was the second time attempts were made to reduce her daily caloric intake. On both occasions, the trainers complained that she was loosing her muscle mass below her dorsal fin and not the blubber layer.

On June 30, 1991, her blubber fat was measured using ultrasonography. Measurements were abnormally high with many measurements in the mid 30mm range. My previous experience with measuring dolphins, blubber had ranges in the mid to high teens. Serum chemistries taken that month (6-14-91 and 6-30-91) showed mildly elevated cholesterol and triglycerides. The liver enzyme GGT was significantly elevated. Hypothyroidism was considered as a differential diagnosis. Serum samples are routinely frozen from this parks animals for future testing; therefore, we were able to look at samples from 1987, 1988, and 1990. These samples were sent to Auburn University endocrine diagnostic service for thyroid hormone analysis. The results were somewhat low compared to the control samples and other published data, but the thyroid levels were considered low normals and had actually increased in the more recent samples. Her clinical signs as well as her hepatopathy indicated possible Cushing's syndrome. Serum cortisol levels were requested and these samples were 3-4 times higher then our controls.

Auburn University endocrine diagnostic service was consulted and they suggested measuring ACTH levels to further determine the etiology of the abnormally high cortisol levels. When compared to the initial control values, The ACTH levels were ten times above the controls. These results indicated that the increased cortisol was pituitary or hypothalamic dependent. This condition of excess cortisol stimulation is known as Cushing's disease.

There are four drugs to reduce cortisol levels; OPDDD (Lysodren), Isoconazole, Miconazole, and Ketoconazole (Nizoral). Ketoconazole was determined to be the drug of choice for this case.

The initial dose was 5mg/kg divided BID (25% of the recommended canine dose); however, after two weeks the continued high cholesterol and triglyceride levels suggested the dose was too low, the ACTH/cortisol assays were pending. The dose was increased to 7.5mg/kg divided TID. In retrospect, the 5mg/kg dose appeared to be adequate after receiving the ACTH/cortisol assays. However, the 7.5mg/kg divided TID dose was maintained for 18 months.

During the first seven months, Princess lost 100 pounds while maintained on approximately 6,50OKcal/day. Also, during this period, and at the present time, her liver enzyme GGT, cholesterol and triglycerides have returned to normal.

Serum ketaconazole levels were determined during the 5mg/kg/day and 7.5mg/kg/day dosage schedules and are reported in the results. There was some concern that the drug would be metabolized at a faster rate with continuous drug administration.

It was suggested that the serum aldosterone levels would be useful to further investigate the disease origin. ACTH in dolphins not only causes increased serum cortisol but also significant increases in serum aldosterone. The serum aldosterone levels were elevated prior to and at the first blood sample taken two weeks after beginning therapy and after that, the aldosterone levels have been significantly reduced.

These results are somewhat confusing in that ketoconazole has minimal effects on aldosterone concentrations in normal human subjects. The ACTH results initially were greatly reduced but rebounded and have become variable during therapy. Aldosterone levels (under the control of ACTH) have had a downward trend during therapy.

The electrolytes have been considered within normal limits prior to and throughout therapy. The elevated liver enzyme gamma glutamyl transferase gradually came back to normal during the therapy. The elevation of cholesterol and triglycerides also decreased to normal. Cushing's disease is often accompanied by fatty liver syndrome, which was my assessment of the serum chemistries. Complete blood counts indicated deceased eosinophils prior to therapy and have become more normal as the serum cortisol levels have been reduced.

At the time of writing this case report, the Ketaconazole dose has been reduced to 500mg BID (6mg/kg/day). Plans are to reduce the dose gradually, monitoring closely the serum chemistries, complete blood counts, cortisol, ACTH, and aldosterone.