Endocrinology
TREATMENT CONSIDERATIONS
Steroid Profiles in the Diagnosis of Canine Adrenal Disorders.
Jack W. Oliver, Proceedings 25th ACVIM Forum, Pp. 471-473, Seattle, WA. 2007.
See the Treatment Section. Discussed topics include “Primary Adrenal Tumors”, “Mitotane”, “Trilostane”, “Aromatase Enzyme Inhibitors”, “Anti-Gonadotropin Drugs”, “Melatonin” and Phytoestrogens (“Lignans”).
Treatment Option Considerations
Atypical Cushing's revised October 2009Estradiol Increase (Hyperestrinism)
Estradiol typically causes increased liver involvement (hepatomegaly, steroid hepatopathy, increased ALP and ALT) and PU/PD. Other signs that are seen with true Cushing’s disease can also be present, such as haircoat problems, dilute urine, muscle weakness, hypertension and pot-bellied appearance. Melatonin and lignans may be the best treatment approach at this time. Give them together, and allow 4 months for a good treatment response to occur. Monitor improvement in clinical signs, reduction in ALP and ALT levels or re-run a baseline estradiol level, or our adrenal steroid profile, to see what effects the treatment is having on hormone levels.
See also the “Treatment Section” of Steroid Profiles in the Diagnosis of Canine Adrenal Disorders. Jack W. Oliver, Proceedings 25th ACVIM Forum, Pp. 471-473, Seattle, WA. 2007.Aldosterone
Elevated aldosterone levels should be accompanied by hypernatremia and hypertension, and hypokalemia and muscle weakness. Aldosterone levels can be increased in cases of adrenal hyperplasia or primary adrenal tumor, but aldosterone can also be increased in cases where the renin-angiotensin system is increased (e.g., renal and cardiac problems). Also, low aldosterone level frequently indicates the presence of a primary adrenal tumor, so that ultrasound exam of the adrenals is indicated in this situation.Primary Adrenal Tumors
Primary adrenal tumors have a variety of hormonal secretory patterns, including many that have normal cortisol levels. Steroid hormone panels are the best way to establish whether or not a primary adrenal tumor is functional.Ketoconazole and Lignan
In cases of Atypical Cushing’s disease, with increased intermediate adrenal steroid levels, and elevated estradiol levels, consider using ketoconazole at a conservative dose (see article by Lien and Huang, "Use of ketoconazole to treat dogs with pituitary - dependent hyperadrenocorticism: 48 cases (1994-2007)", JAVMA, 233:1896-1901, 2008) plus lignan. KETOCONAZOLE inhibits the 17-alpha-hydroxylase enzyme early in the adrenal pathway (steroid intermediate levels decrease), and the 11-beta-hydroxylase enzyme late in the adrenal pathway (serum cortisol level decreases). LIGNAN inhibits the 3-beta hydroxysteroid dehyrogenase enzyme early in the adrenal pathway (cortisol and intermediate adrenal steroid levels decrease), along with the aromatase enzyme (estradiol level decreases). Because of these multiple sites of enzyme inhibition with KETOCONAZOLE and LIGNAN, the dose of ketoconazole needed can be reduced, with less chance of liver toxicity occurring. Consider using the protocol of Lien and Haung listed above, plus lignan at 1 mg per pound of body weight once each day.Melatonin Implant
A melatonin implant eliminates the need to give a melatonin pill twice each day. To monitor clinical effectiveness, look for improvement in clinical signs, or run our steroid hormone profile at some point. If the melatonin implant is used, it produces melatonin blood levels for 4 months, so a repeat adrenal profile at that point would be good. Veterinarians have observed very good haircoat re-growth in many instances, in dogs with alopecia.Lysodren; Combination of Melatonin, Lignan and Maintenance Lysodren
Traditional treatment for Cushing’s disease. Predictable effects on hormone levels occur, and as noted on our Treatment Option Sheet, Lysodren effectively reduces cortisol levels, but also those of androstenedione, progesterone and 17-hydroxyprogesterone. In Atypical Cushing’s disease, where cortisol levels are normal but intermediate and/or sex steroids are increased, treatment is often begun with melatonin and lignan. But, if clinical response over time is less than desired, some then add a maintenance dose of Lysodren to the melatonin/lignan treatment. If additional response seems needed, then adjustment can be made in the dose of Lysodren, or in Lysodren treatment frequency.