What drug should you pick for managing hyperadrenocortisism?(Proceedings)

1. Hyperadrenocorticism

     a. Middle-older aged dogs

     b. Clinical Signs

          i. Polyphagia

          ii. Polyuria/polydipsia

          iii. Pyoderma

          iv. Pot bellied appearance

          v. Urinary tract infection

     c. Physical examination

          i. Hepatomegaly

          ii. truncal obesity

          iii. muscle wasting

          iv. panting

          v. bilaterally symmetrical alopecia

          vi. thin, hyperpigmented skin

          vii. Calcinosis cutis

          viii. Lipid deposits

     d. Hyperadrenocorticism-CBC changes

          i. Erythrocytosis

          ii. neutrophilia with a left shift

          iii. stress leukogram

          iv. mature neutrophilia

          v. monocytosis

          vi. eosinopenia

          vii. lymphopenia

     e. Hyperadrenocorticism-Chemistry changes

          i. hyperglycemia (mild)

          ii. elevated Les

          iii. elevated cholesterol

          iv. lipemia

     f. Urinalysis

          i. low specific gravity

          ii. sediment: rbc's, wbc's, bacteria - UTI

     g. Hyperadrenocorticism – etiology

          i. Adrenal tumors (15%)

          ii. Pituitary tumors (85%)

          iii. Both produce an excess of cortisol that causes disease

     h. Hyperadrenocorticism – diagnosis

          i. Low Dose Dexamethasone Suppression Test

               1. Sensitivity (89-92%)

               2. Specificity (75%)

               3. Least specific in animals with concurrent disease

               4. Measure cortisol

          ii. ACTH Stimulation Test

               1. Less sensitive (75-83%)

               2. Specificity (85%)

               3. More specific in animals with concurrent disease

               4. Differentiating Pituitary and Adrenal Disease

               5. Measure cortisol and aldosterone

          iii. Urine Cortisol:Creatinine

               1. Very sensitive (100%)

               2. Not specific

               3. First morning urine

               4. 3 days in a row

               5. All normal

               6. Rule out HAC

     i. Treatment

          i. Trilostane versus lydosren

          ii. Surgery

          iii. Ketoconazole

          iv. Deprenyl (Anipryl)

     j. Treatment considerations

          i. Cost of treatment

          ii. Neurologic disease

          iii. Time of resolution of signs

          iv. Owner frustration

     k. Treatment Pituitary vs Adrenal

          i. Endogenous ACTH concentration

               1. adrenal tumors <10 pg/ml

               2. PDH: high

               3. PDH: overlap with normal

          ii. Abdominal ultrasound

               1. adrenal tumor

               2. bilateral adrenal hyperplasia

     l. Treatment-PDH

          i. o,p'-DDD (Lysodren)

          ii. Trilostane (vetoryl)

          iii. Deprenyl (anipryl)

          iv. Ketoconazole

     m. Treatment – adrenal tumors

          i. Surgery

          ii. Trilostane

          iii. Lysodren

          iv. Trilostane + Lysodren

          v. ketoconazole

     n. Lysodren

          i. DDT derivative

          ii. Kills adrenocortical cells

          iii. Preference for the cortisol producing ones (Fasciculata and reticularis)

          iv. Induction phase-35-50 mg/kg PO q.d. x 5-7 d

          v. Maintenance phase-35-50 mg/kg PO divided twice per week

          vi. 500 mg tablet size

          vii. Compounded

          viii. Include prednisone at 0.5 mg/kg – at least 2 doses

          ix. "Danger signs"

               1. Loss of appetite

               2. Lethargy

               3. Vomiting

               4. Diarrhea

               5. Just ain't right

          x. Side Effects

               1. Adrenal cortical destruction

                    a. Glucocorticoid-deficient addisonian

                    b. Full-blown addisonian

                    c. Often reversible

               2. Liver toxicity

                    a. Often resolves once off Lysodren

                    b. Can't use Lysodren again

          xi. Monitoring

               1. After induction phase

               2. ACTH-stimulation test

               3. Cortisol within normal range

               4. No stimulation with ACTH

               5. Liver panel

               6. Clinical signs

               7. ACTH-stimulation

                    a. Cortrosyn 5 mcg/kg IV/IM

                    b. Cortisol before and 60-90 min after ACTH

                    c. Cortrosyn

                         i. 250 mcg vial

                         ii. Reconstitute and freeze for 6 months

                    d. Normal cortisol range: 1-4 mcg/dl

                         i. Pre 1-4 mcg/dl

                         ii. Post 1-4 mcg/dl

                    e. 4-6 months for ACTH-stim once stabilized

     o. Trilostane: Adrenal Hormones

          i. Compounded

          ii. Vetoryl: Dechra

          iii. 1.5-3 mg/kg bid

          iv. Lower dose bid – more efficacious and safer

          v. Send home prednisone at 0.5 mg/kg – at least 2 doses

          vi. "Danger signs"

               1. Loss of appetite

               2. Lethargy

               3. Vomiting

               4. Diarrhea

               5. Just ain't right

          vii. Side Effects of Trilostane

               1. Addisonian –Glucocorticoid or Glucocorticoids + mineralocorticoids

               2. Adrenal necrosis

               3. Adrenal glands enlarged and bumpy over time

          viii. Elevations of 17 OH Progesterone

          ix. Cortisone decreased

          x. Monitoring-7-10 days after beginning

               1. ACTH-stimulation test

               2. 2-6 hours after trilostane given

               3. Cortisol within normal range

               4. No stimulation with ACTH

               5. Na/K level

     p. Trilostane Versus Lysodren in PDH

          i. Both as efficacious

               1. Control clinical signs

               2. Longevity

          ii. Cost; Both sold commercially

          iii. Trilostane must be given every day

          iv. No lysodren with liver disease

          v. Trilostane: can become Addisonian even after stable longterm treatment

          vi. Adrenal gland hyperplasia/metaplasia

     q. Trilostane Versus Lysodren in Adrenal Tumors

          i. No studies

          ii. Operable-Lysodren to kill metastatic cells (?)

          iii. Inoperable-Trilostane to control excess hormone levels

          iv. Trilostane + Lysodren (?)

     r. Trilostane Versus Lysodren Follow Up

          i. Lysodren – usually fairly stable after induction phase

          ii. Trilostane

               1. Addison's months after treatment starts

               2. Most animals need dose adjustments

     s. Feline Hyperadrenocorticism - Trilostane at 5 mg bid; NO LYSODREN

     t. Deprenyl (anipryl) and ketoconazole