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Diseases

Endocrine Diseases

Diagnosis and Treatment of Common Endocrine Diseases

Diabetes Mellitus***

Cause:

Loss/dysfunction of beta cells (Type I) - common in dogs

Impaired insulin sensitivity (Type II) - common in cats

Signalment and Clinical Signs:

Risk factors: obesity, indoor, increasing age, other endocrine diseases, genetics, certain drugs

Concurrent diseases: pancreatitis

Causes of insulin resistance: diestrus in intact female, renal disease, hyperthyroidism (cat), hyperadrenocorticism or hypothyroidism (dog)

PU/PD, PP, weight loss, neuropathy (plantigrade stance in cats), cataracts (75-80% dogs within first year of diagnosis), UTI

Diagnosis:

Minimum Database:

CBC: stress leukogram (dog > cat)

Biochemistry: ↑ glucose, cholesterol, triglycerides (dog > cat), ALP > ALT (mild-mod; dog > cat)

Urinalysis: +/- glucosuria, USG often <1.020, UTI

Diabetic Ketoacidosis

Cause:

85%

Hyperadrenocorticism (Cushing’s) in Dogs

Cause:

85% pituitary-dependent (PDH) - Poodles, Dachshunds, Beagles, Boxers, Terriers

15% functional adrenal tumour (AT) - Poodles, Dachshunds, Labs, GSD, Terriers

Signalment and Clinical Signs:

Average age 9-11 years, 75% of PDH cases <20kg

Very Common

Less Common

Uncommon

PU/PD/PG Excessive panting Thin coat Abdominal distension Hepatomegaly Muscle weakness Systemic hypertension

Hyperpigmentation Thin skin Comedones Poor hair growth Urine leakage Lethargy

Neuropathy Myopathy Thromboembolism

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Diagnosis:

Minimum Database:

CBC: stress leukogram, thrombocytosis, mild erythrocytosis

Biochemistry: ↑ ALP (mod-marked), ALT (mild), cholesterol, triglycerides, glucose (mild)

Urinalysis: USG <1.020, proteinuria, +/- UTI (immunosuppression)

Screening Tests:

Urine Cortisol:Creatinine Ratio (>92% Sn, poor Sp)

To rule out HAC (collect urine at home)

ACTH Stimulation Test (90% Sn/Sp)

Dose: 0.005mg/kg cosyntropin IV

HAC if exaggerated response to ACTH

LDDST (lower Sp than ACTH stim)

Dose: 0.01mg/kg dexamethasone IV

HAC if 8h cortisol >40nmol/L (normal <28nmol/L)

Differentiating Tests:

LDDST

PDH if...

4h cortisol <40 nmol/L or <50% of baseline cortisol (0h)

8h cortisol <50% of baseline (but still >40 nmol/L)

20-30% of dogs with severe PDH will not suppress

HDDST

Dose: 0.1mg/kg dexamethasone IV

AT - persistently elevated cortisol

PDH - suppression of cortisol (<40nmol/L) at 4h or 8h

Abdominal Ultrasound

PDH - symmetrical adrenal glands

AT - usually 1 enlarged gland, 1 atrophied gland

Endogenous ACTH Level

PDH (most) - high ACTH

AT - low ACTH

Rule out concurrent disease:

Urine culture, UPCR, abdominal ultrasound, blood pressure, lipase testing

Treatment:

Trilostane (Vetoryl) 1mg/kg BID or 2mg/kg SID in the morning with food (maximum 30mg BID)

Adverse effects: mild GI upset or lethargy (initially), hypoadrenocorticism (reversible)

Monitoring:

Test 4-6 hours after administration and consistently between measurements

@ 10-14 days: ACTH stim - to ensure cortisol not too low (NO dose change)

Post-ACTH cortisol <55nmol/L: Stop treatment. Wait 1 week then measure resting cortisol. If >55nmol/L, restart at decreased dose.

Post-ACTH cortisol 55-193nmol/L: Consider decreasing dose (anticipating overdose in ensuing 2-4 weeks) or continue at same dose

Post-ACTH cortisol >193nmol/L: Continue current dose.

@ 4-6 weeks: ACTH stim

Post-ACTH cortisol <55nmol/L: Stop treatment. Wait 1 week then measure resting cortisol. If >55nmol/L, restart at decreased dose by ~25%. Note: some dogs rebound later in the day*

Post-ACTH cortisol 55-193nmol/L: Continue current dose (good control).

What if patient is still clinical? Consider increasing dose and/or dividing dose from SID → BID

If pre- and post-ACTH cortisol are in lower end of target range, decrease total daily dose by 10-25% + switch to BID dosing

If pre- and post-ACTH cortisol are in upper end of target range, increase total daily dose by 10-25% + switch to BID dosing

Post-ACTH cortisol >193nmol/L:

Check compliance (given with food, pill being swallowed, etc.)

Increase dose by ~25%. Repeat ACTH stim in 2-4 weeks + evaluate clinical signs

Once optimal dose, recheck @ 3 months then q3-6 months

Prognosis:

Mean survival time: 2-2.5 years (if sooner, die from other diseases), younger dogs live longer

Resolution of PU/PD/PP within 1 month, skin and haircoat >3 months

Proteinuria, hypertension and hypercoagulability may not resolve

Potential Complications of HAC:

Proteinuria (>50% at diagnosis, 20-40% of treated dogs have persistent proteinuria)

ACE inhibitor (caution - hyperkalemia with Trilostane)

Fish oil

Anti-platelet drug

Low protein diet

Hypertension (30-86% at diagnosis)

If mild (<180mmHg): treat HAC + monitor BP

If moderate-high (>180mmHg): consider anti-hypertensives + recheck once HAC controlled

Hypercoagulability - pulmonary thromboembolism

Other endocrinopathies (uncommon) - hypothyroidism, diabetes mellitus

Gall bladder mucocele (20-25% of dogs with GBM had HAC)

Macroadenoma - dull mentation, neurological abnormalities

Calcinosis cutis - may not resolve with treatment of HAC

Adrenal Tumour

HAC secondary to AT or incidental on ultrasound

Types:

Cortisol-secreting AT - adenomas + carcinomas

Pheochromocytoma (excess catecholamines) - episodic hypertension, tachycardia

Non-functional AT - adenomas (”incidentaloma”)

Diagnosis:

First investigate if cortisol-secreting

Then investigate for pheochromocytoma (high BP, high HR, catecholamine testing)

If no signs, consider surgical removal vs. monitoring

Non-metastasized:

Surgical removal: survival up to 36 months

Medical treatment: survival >1 year (may need higher dose)

Metastasized adrenal carcinoma:

Poorer prognosis: <1 year

Control clinical signs with Trilostane/Mitotane

Hypoadrenocorticism (Addison’s)

Cause:

85%

Hyperthyroidism in Cats

Cause: Adenomatous hyperplasia of one or both lobes of thyroid gland

Signalment and Clinical Signs:

Average age 12-13 years (<5% are <8 years at diagnosis)

Clinical Signs (Common)

Clinical Signs (Less Common)

PE (Common)

PE (Less Common)

Weight loss Polyphagia Unkempt haircoat PU/PD Increased activity, “nervous’ Intermittent vomiting/diarrhea

Lethargy Decreased appetite

Palpable thyroid Decreased BCS Hyperactive Impaired tolerance to stress Tachycardia Heart murmur Hair coat (dry, dander, alopecia)

Arrhythmia Hypertension Lethargy, weakness Small kidneys

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Apathethic hyperthyroidism: 10% of hyperthyroid cats are “apathetic”

Depressed, anorexia, weight loss, +/- concurrent illness (eg. renal, heart disease)

Diagnosis:

Minimum Database:

CBC: usually normal (+/- ↑ PCV/RBC and MCV)

Biochemistry: ↑ liver enzymes (90%; mild-mod), signs of concurrent kidney disease

Urinalysis: usually normal (unless other diseases present)

Thyroid Tests:

TT4 (high Sp, 10% have normal T4)

Concurrent Diseases:

Thyrotoxic cardiomyopathy (HCM > DCM): tachycardia, arrhythmia +/- CHF (uncommon)

Systemic hypertension: retinal hemorrhage or detachment (uncommon)

May require temporary treatment if BP >180mmHg

Chronic kidney disease: true status masked by hyperthyroidism

10% azotemic at diagnosis → 20-25% azotemic after treatment of hyperthyroidism

Treatment:

Methimazole (Tapazole, Felimazole) 1.25-2.5mg per cat PO q12h

Monitoring:

Increase by 2.5mg/day q2-4 weeks until TT4 in mid-to-lower half of reference range

Decrease dose if TT4 <13 nmol/L

Monitor CBC, biochemistry, U/A ideally (unmasking of CKD)

Recheck q4-6 months once stable

Adverse effects (usually first 4-8 weeks):

GI signs (10%): vomiting, diarrhea

Blood cell abnormalities (<10%): neutropenia, thrombocytopenia, leukopenia (consider other drug options)

Facial excoriation (<5%): scabs on head, pinnae, neck (discontinue medication)

Hepatotoxicity (2%): ↑ liver enzymes, signs of illness

Radioactive iodine (131I): degrades hyperplastic tissue while retaining normal thyroid tissue

After stabilized medically, 7-10 day protocol, approximately $1500, variable protocol

Thyroidectomy: minimal complications but recurrence possible if there is ectopic hyperplastic tissue

Nutritional: y/d only

Compliance critical, cannot go outdoors, Hill’s list of compatible medication

T4 slower to return to normal (~8 weeks)

Prognosis:

Median survival time: 2-5+ years (hyperthyroidism usually does not cause death)

Pre-existing renal disease: reduces prognosis

Hypothyroidism in Dogs

Cause:

Primary (most): lymphocytic thyroiditis, thyroid atrophy - decreased T3 and T4

Secondary (rare) - lack of TSH (pituitary)

Thyroid neoplasia (carcinoma)

Congenital hypothyroidism

Signalment and Clinical Signs:

Average age 7 years (uncommon in <2 years)

Boxer, Golden Retriever, Cocker Spaniel, Ridgeback, English Setter

Metabolic Signs

Skin and Haircoat Signs

Other (Less Common)

Lethargy Weight gain/obesity Exercise intolerance Cold intolerance (“heat seeker”)

Alopecia/thin hair coat/”rat tail” Dry hair coat/excess dander Otitis externa Pyoderma Seborrhea Hyperpigmentation (skin) Bilaterally symmetrical changes

Neuropathy Myopathy Bradycardia Reproductive abnormalities

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Diagnosis:

Minimum Database:

CBC: mild, normocytic, normochromic anemia (↓ EPO stimulation)

Biochemistry: ↑ cholesterol (75%), triglycerides, liver enzymes (30%; mild)

Urinalysis: no specific changes

Thyroid Tests:

Total T4 (high Sn): normal TT4 rules out hypothyroidism, low to low-normal TT4 is non-specific

Free T4 (by equilibrium dialysis): measure if TT4 non-diagnostic or in cases with concurrent illness instead of TT4

TSH: elevated in hypothyroidism (note: <1/3 have normal TSH)

Strongest evidence: ↓TT4 and/or fT4 +/- ↑ TSH

Euthyroid Sick Syndrome:

Any non-thyroidal illness or drugs (steroids, phenobarbital, sulfonamides) can lower TT4, fT4 (to lesser effect), variable effect on TSH

Treatment:

Synthetic sodium levothyroxine (Thyro-Tabs): initial 0.01-0.02mg/kg PO q12h (liquid is q24h)

Monitoring:

@ 3-4 weeks: T4

If too low: Increase dose. Recheck T4 in 4 weeks

If too high: Decrease dose or go to q24h. Recheck T4 in 4 weeks

Once stable, recheck q6-12 months

Prognosis:

Excellent in adults with primary hypothyroidism

Improved activity in 1-2 weeks, weight loss in >8 weeks, hair coat in several months

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