Improving Treatments for Atypical Hyperadrenocorticism

Melatonin and Phytoestrogens – A Potent Combination?

Hyperadrenocorticism in dogs is caused by problems with the adrenal system that lead the overproduction of one or more hormones. Symptoms are many. Some of the most common include excessive hunger and thirst, a need to urinate frequently, poor heat tolerance, skin problems, and muscle weakness. However, the specific symptoms of hyperadrenocorticism vary both by the dog and by which hormones are affected, which can sometimes make it difficult to diagnose and treat.

Although veterinarians are generally familiar with the most common presentation of hyperadrenocorticism, where levels of the stress hormone cortisol are increased, there is less understanding of a condition known as atypical hyperadrenocorticism. Dogs with this disease actually have normal levels of cortisol but show increased levels of various other steroid hormones – including the sex hormones estradiol and progesterone. These hormones are produced not just in the adrenal gland, but throughout the body, which can significantly complicate treatment.

However, there is hope. With the help of the AKC Canine Health Foundation, scientists from the University of Tennessee, Knoxville have begun to look for a treatment that could effectively help dogs with the atypical form of hyperadrenocorticism. Working with cultured human adrenal tumor cells, since canine cell lines aren’t available, they have identified a combination of two compounds – melatonin and lignan – which in preliminary studies looks like they might be able to bring many cases of atypical hyperadrenocorticism under control.

• Melatonin is often thought of as the “sleep hormone,” but it would be more accurate to call it the “light hormone.” Production is affected by the changes in light levels that take place across different seasons as well as throughout the day, and it plays a role in the formation of circadian rhythms. However, and more importantly for dogs with hyperadrenocorticism, melatonin also regulates sexual reproduction in animals that only breed seasonally. In other words, it has an effect on the same sex hormones that cause problems in dogs with atypical hyperadrenocorticism.

• Lignan is shorthand for “lignan phytoestrogen” – a group of compounds found in plants (phyto-) that stimulate sex hormone receptors (-estrogen). The two most common lignans found in humans and other animals are the so called “mammalian lignans” ENL and END, which get their name because our intestinal bacteria form them from the raw material lignans found in the nuts, grains, vegetables, and seeds that we eat.

When the two substances were combined and applied to adrenal tumor cells, the scientists were pleased to discover that the treatment did largely what they’d hoped. It reduced the amounts of cortisol, estradiol, and androstenedione, three important hormones, as well as the amount of aromatase, which plays an important role in hormone synthesis. Those results strongly suggested that the treatment might prove useful for some dogs with atypical hyperadrenocorticism, although it’s probably not the answer for all. Unfortunately, melatonin and lignan treatment actually increased progesterone and 17-hydroxyprogesterone production by cells, and veterinarians would probably not want to use this treatment for dogs whose condition was caused by problems with those hormones.

This work was funded by AKC Canine Health Foundation grant 844-A.