Endocrinopathies of Dogs and Cats Diseases of the Adrenal Gland

dr. Ákos Máthé Department of Internal Medicine Hormones of the Adrenal Gland

• Adrenal medulla (malfunction is very rare!) –Adrenaline, noradrenaline • Adrenal cortex (AC) ~ Zona reticularis / zona fasciculata –glucocorticoids, androgens ~ Zona glomerulosa –Mineralocorticoids Regulation of Adrenocortical Hormones

Part of day K+  Hypovolemia Feeding

Stress Renin

AVP Angiotensin I.  II. CRH

ACTH Aldosterone Cortisol (Corticosterone) Na+ , K+  Hypoadrenocorticism I. ~ Addison’s disease ~ AC hormones  • Pathogenesis ~ Primary (if 90% of AC tissue is lost) – Cortisol  and aldosterone , ACTH – Autoimmune destruction of AC ( atrophy) – (bilateral adrenal tumor, amyloidosis, infection) – „Atypical”: only cortisol  (yet) ~ Secondary – ACTH , cortisol , aldosterone  – Unprofessional glucocorticoid therapy – (Hypophysis tumor, trauma, inflammation) Atrophy of AC and lymphocytic adrenalitis Source: Rijnberk: Clinical Endocrinology of Dogs and Cats Hypoadrenocorticism II.

• Signalment ~ Rare, but life threatening disease of dogs ~ Young and middle-aged animals ~ More frequent in bitches ~ Great Dane, Rottweiler, Poodle, Schnauzer, Westie, Bearded collie, English cocker spaniel ~ (Very rare in cats) Hypoadrenocorticism III.

• Clinical manifestations ~ Aldosterone   dehydration, K+   Addisonian-crisis Cortisol   lethargy, stress response  ~ Periodic improvement and relapse ~ Stress might cause a crisis ~ Depression, weakness, tremor, weight loss, hypothermia, anorexia ~ Vomiting/diarrhea (+/- bloody), abdominal pain, PD/PU ~ Shock, CRT , bradycardia, weak pulse ~ When these signs are present, include Addison’s disease in differential diagnosis ! Hypoadrenocorticism IV. • Laboratory and instrumental findings ~ Normocytic normochromic anemia (dehydration can mask the anemia!) ~ Lack of „stress leukogram”: Neu/Ly <2,3 eosinophilia, lymphocytosis ~ Hyponatremia, hyperkalemia, hypochloremia Na+/K+ <27(<22) ~ (Hypoglycemia), albumin  prerenal azotemia: 1000X(BUN/creatinine)>150 ~ ECG: spiked T wave, Q-T distance , QRS complex wide, P wave low, P-R distance , bradycardia ~ X-ray: microcardia, v. cava caudalis  ~ Abdominal US: „thinner” adrenals ECG Recording of an Addisonian Dog Source: Rijnberk: Clinical Endocrinology of Dogs and Cats Hypoadrenocorticism V. • Diagnosis ~ Differential diagnosis – Renal failure Na/K may be low!! – Gastroenteritis – Acute pancreatitis, (Ileus) ~ ACTH-stimulation test – 5 μg/kg tetracosactide IV (Synacthen inj.)

– Blood sampling: t0, t1 – Positive: t0 cortisol <28nmol/l, t1 cortisol <100 nmol/l – On the morning of the test the hydrocortisone injection should be postponed ~ Single cortisol >55 nmol/l: Addison’s unlikely Hypoadrenocorticism VI. • Treatment ~ Addisonian-crisis – 20-50 ml/kg/h normal saline for 2 hours – Thereafter: 100 ml/kg/24h normal saline – 5 mg/kg hydrocortisone with the first infusion (Solu-Cortef inj.) – Thereafter: 1 mg/kg/6h hydrocortisone SC ~ Maintenance therapy – Fludrocortisone 0,005-0,010 mg/kg/12h (Astonin-H tabl. 0,1 mg) or DOCP 2 mg/kg/25(28) days IM/SC (Desoxycorticosterone-pivalate; Zycortal inj. A.U.V.) – Prednisolone 0,05-0,1 mg/kg/12h (Prednisolon 5 mg tabl.; in stress 2-4x dose !) – Sodium chloride 0,05 g/kg/12h mixed with food Hypoadrenocorticism VII.

• Patient follow-up ~ Controls: 2-3 weeks later, then every 6 months ~ If K+  and Na+ : sodium chloride dose  ~ If K+  and Na+ , or K+  and Na+ : fludrocortisone dose  ~ If Na+  and K+ : fludrocortisone dose  • Prognosis ~ Generally good, if the patient survives the crisis ~ In the secondary form due to hypophyseal disease it is determined by the primary lesion Hypercortisolism of Dogs I.

~ Cushing’s syndrome ~ Cortisol  ~ (Hyperaldosteronism is rare) • Pathogenesis ~ Pituitary-dependent (PDH; 85%) – ACTH , cortisol  – Hypophysis (A.L.) hyperplasia, adenoma ~ Adrenocortical tumors (ADH; 15%) – Cortisol , ACTH  – AC adenoma or carcinoma (usually unilateral) ~ Iatrogenic form: long-lasting glucocorticoid therapy – ACTH , cortisol  !!! (AC atrophy) Pituitary Tumor in a Boxer Dog Source: Rijnberk: Clinical Endocrinology of Dogs and Cats Hormone producing AC tumor Source: Rijnberk: Clinical Endocrinology of Dogs and Cats Hypercortisolism of Dogs II.

• Signalment ~ Common endocrinopathy ~ Middle-aged and old dogs ~ Poodle, Dachshund, Yorkshire terrier, Hungarian vizsla, Boxer ~ PDH: small dogs AC tumors: large dogs Hypercortisolism of Dogs III. • Clinical manifestations ~ Glucocorticoids   proteolysis   GNG , lipogenesis  ~ PD/PU ~ PP, centripetal obesity, abdominal enlargement, muscle wasting ~ Thin, atrophic skin, keratin plugs, alopecia, hyperpigmentation, calcinosis cutis ~ Hepatomegaly ~ Testicular atrophy, anestrus ~ Secondary infections (skin, urinary tract) ~ (Cerebral signs) Body constitution in Cushing’s syndrome Dermatologic signs in Cushing’s syndrome Iatrogenic Cushing’s Syndrome Source: Rijnberk: Clinical Endocrinology of Dogs and Cats Hypercortisolism of Dogs IV. • Laboratory and instrumental findings ~ Leukocytosis, neutrophilia ~ AP  (SIAP ) ~ Cholesterol , lipemia, blood glucose  ~ Low specific gravity of urine ~ Ultrasound: enlargement of adrenal gland(s), metastases (liver, vessels) ~ X-ray: hepatomegaly, osteoporosis, calcinosis cutis, lung metastasis ~ CT: pituitary tumor ~ Blood pressure measurement: hypertension +/- CT image of Pituitary Tumor Source: Rijnberk: Clinical Endocrinology of Dogs and Cats Hypercortisolism of Dogs V. • Diagnosis ~ Measurement of urinary corticoid/creatinine ratios – Not specific; screening test <26*10-6: - >161*10-6: + ~ LDDS test – In the morning: 0,01 mg/kg dexamethasone IV (Dexadreson inj.)

– Blood sampling: t0, t4, t8

– Positive: t8 cortisol >40 nmol/l

– If t4 cortisol <0,5 X t0: PDH ~ ACTH-stimulation test: if iatrogenic ~ is suspected Hypercortisolism of Dogs VI. • Diagnosis - distinguishing PDH and AC tumor

~ Abdominal US PDH ADH ~ HDDS test – In the morning: 0,1 mg/kg dexamethasone IV

– Blood sampling: t0, t4, t8 – If t4 or t8 cortisol <0,5 X t0: PDH If t4 or t8 cortisol <40 nmol/l: PDH ~ Measurement of endogenous ACTH – Frozen sample!! Hypercortisolism of Dogs VII.

• Treatment ~ Mitotane (o,p’-DDD, Lysodren tabl.) – Selective destruction of AC „DUTCH PROTOCOL” – 50-75 mg/kg/24h for 25 days (iatrogenic Addison’s disease is induced) – From the 3rd day replacement therapy is started (prednisolone, fludrocortisone, sodium chloride) – About 25% of patients relapse within one year „AMERICAN PROTOCOL” – 25 mg/kg/12h on first 3-4 days – Maintenance: 12,5 mg/kg/12h on Wednesday and Sunday – Control: ACTH-stimulation test Hypercortisolism of Dogs VIII.

• Treatment ~ Trilostane (Vetoryl caps. A.U.V., Modrenal caps.) – Competitive inhibitor of 3-β-hydroxisteroid- dehydrogenase enzyme; effectively reduces cortisol synthesis – Reversible action – Must be given continuously – (1)2…10 mg/kg/day once or divided twice, with food – Control: ACTH-stimulation test – Rarely: adrenocortical necrosis Hypercortisolism of Dogs IX.

• Treatment ~ Hypophysectomy – Therapy for PDH – Good results – The patient recquires replacement therapy for life: thyroxine + cortisone or prednisolone ~ Adrenalectomy – Unilateral AC tumor: intra- and postoperative hydrocortisone/cortisone/prednisolone for 6-8 weeks – Left: laparoscopic technique – (Bilateral adrenalectomy: in PDH) Hypercortisolism of Dogs X.

• Prognosis Good Iatrogenic Cushing’s syndrome Unilateral AC tumor without metastasis PDH without cerebral signs PDH or AC tumor + diabetes mellitus PDH with cerebral signs Unilateral AC tumor + liver / lung metastasis Poor Hypercortisolism of Cats • Signalment ~ Rare disease ~ Middle-aged and old animals • Clinical manifestations (like the dog, but) ~ Alopecia, hyperpigmentation, keratin plugs are less pronounced ~ The skin is very fragile (full thickness skin defect), unkempt hair coat ~ (Insulin resistant) diabetes mellitus is common • Treatment ~ Trilostane (Vetoryl A.U.V.): 10-30 mg/cat/12-24h PO ~ Hypophysectomy is promising ~ Bilateral adrenalectomy (mitotane is not useful) • Prognosis guarded – poor Cushing’s Syndrome in the Cat Rijnberk: Clinical Endocrinology of Dogs and Cats

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