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 Information
Steroid Profiles for Diagnosis of Atypical Cushing’s Disease: Treatment Option Sheet.Estradiol 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).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. Also, low aldosterone level sometimes indicates the presence of a primary adrenal tumor, so that ultrasound exam of the adrenals is indicated in this situation, and also when aldosterone level is increased.Ketoconazole, Melatonin and Lignans
In cases of Atypical Cushing’s disease with elevated estradiol levels, consider using ketoconazole at a conservative dose (e.g., SID treatment) plus melatonin and lignans. KETOCONAZOLE inhibits the 17-alpha-hydroxylase enzyme early in the adrenal pathway, and the 11-beta-hydroxylase enzyme late in the adrenal pathway; thus, the serum cortisol level decreases. MELATONIN inhibits the 21-hydroxylase enzyme midway in the adrenal steroidogenesis pathway (cortisol level decreases), along with the aromatase enzyme (which converts androstenedione into estradiol, and thus estradiol level declines). LIGNANS inhibit the 3-beta hydroxysteroid dehyrogenase enzyme early in the adrenal pathway (cortisol level decreases), along with the aromatase enzyme (estradiol level decreases). Because of these multiple sites of enzyme inhibition with KETOCONAZOLE and MELATONIN; or KETOCONAZOLE and LIGNANS; or with KETOCONAZOLE and both MELATONIN and LIGNANS, you should be able to lower the dose of ketoconazole needed, with less chance of liver toxicity occurring. Maybe use 5 mg/kg of ketoconazole once daily (SID), plus either melatonin or lignans or both according to our TREATMENT OPTION SHEET (see items 2 or 3 and 5).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.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 lignans. But, if clinical response over time is less than desired, some then add a maintenance dose of Lysodren to the melatonin/lignan treatment.