Hypercortisolism in Dogs

• Pituitary-Dependent Hypercortisolism (PDH) is caused by a pituitary adenoma secreting excessive ACTH, which stimulates cortisol production and adrenal enlargement.
• Adrenal-Dependent Hypercortisolism (ADH) results from a functional adrenal tumor autonomously secreting cortisol, leading to contralateral adrenal atrophy.
• PDH accounts for 80-85% of hypercortisolism cases.
• Common clinical signs of hyperadrenocorticism include polyuria, polydipsia, panting, polyphagia, and pot-bellied appearance, also truncal alopecia, muscle wasting and skin changes.
• Common biochemical changes include elevated ALP (most common in dogs), hypercholesterolemia, and low urine specific gravity (<1.020), also thrombocytosis, hypertriglyceridemia, mild ALT elevation, and mature neutrophilia.
• Pursue testing for hypercortisolism only when ≥2 clinical signs or abnormalities are present.
• A highly sensitive test minimizes false negatives, is useful for ruling out disease.
• UCCR is useful when there is low clinical suspicion, such as persistent ALP elevation without other signs, but not when clinical signs strongly suggest HAC.
• UCCRs must be collected at home, ideally pooled from multiple voids in a stress-free environment.
• For UCCR, collect urine at home over multiple voids, submit the pooled refrigerated sample to a lab.
• LDDST requires overnight hospitalization to minimize stress.
• LDDST involves collecting baseline cortisol, injecting dexamethasone, and collecting samples at 4h and 8h, stress/handling can cause false positives.
• ACTH Stimulation test for diagnosis involves baseline cortisol, injecting synthetic ACTH, and a post-sample at 1h.
• ACTH Stimulation test for trilostane monitoring uses the same protocol but with a lower ACTH dose (1 µg/kg) and tests 4-6 hrs post-pill.

Interpretation of Results

• In LDDST, 8h cortisol ≥1.4 µg/dL indicates Cushing's.
• Suppression criteria to diagnose PDH in LDDST: 4h cortisol <1.4 or 4h/8h cortisol <50% of baseline, if suppression seen → PDH, if no suppression → could be ADH or non-diagnostic.
• Normal ACTH Stimulation test: 6-17 µg/dL, Grey zone: 17-22 µg/dL, Cushing's: >22 µg/dL
• Goal for monitoring ACTH Stim: 1-hour post-stim cortisol ~5 µg/dL.
• Ultrasound findings for PDH: Bilaterally normal/enlarged adrenal glands (>0.8-1cm)
• Ultrasound findings for ADH: Unilateral mass, contralateral atrophy; mass >2cm is suspicious for malignancy.
• In Endogenous ACTH: PDH = High ACTH (>20 pg/mL), ADH = Low ACTH (<5 pg/mL)
• Pre-pill cortisol >1.45 µg/dL rules out hypocortisolemia but is not reliable. If signs conflict, perform an ACTH stim.

Trilostane Info

• Trilostane inhibits 3-beta-hydroxysteroid dehydrogenase, blocking cortisol synthesis.
• Trilostane: First recheck at 10–14 days (assess for over-suppression, do not increase dose yet), next recheck at 30 days, can begin increasing dose if needed.
• Trilostane dose increase: after 30 days, if clinical signs persist and cortisol is not over-suppressed
• Goals of Hyperadrenocorticism treatment and surgery: resolve clinical signs, ACTH stim post-pill cortisol ~5 µg/dL, prevent hypo- or hypercortisolemia.
• Surgical options: PDH-Hypophysectomy (limited availability), ADH-Adrenalectomy (requires trilostane pre-treatment ~4w)

Iatrogenic Hypocortisolemia

• Stop trilostane, if GI signs present directly consider GI toxicity vs. hypocortisolemia.
• If hypo suspected, stop trilostane for 5-14 days and start steroids like Prednisone 0.1-0.2 mg/kg/day or Dexamethasone 0.01-0.02 mg/kg/day, signs should resolve quickly after starting steroids

Hypoadrenocorticism

• Typical Addison's is defined as a deficiency of both cortisol and aldosterone (most common).
• Atypical Addison's defined as isolated glucocorticoid deficiency
• Atypical Addison's may still have aldosterone deficiency that is subclinical or develops later.
• Addison's is more common in females, with an average age of ~4 years (range 4 months – 14 years).
• Addison's is genetically predisposed in Standard Poodles, Portuguese Water Dogs, Nova Scotia Duck Tolling Retrievers, and Bearded Collies.
• Clinical signs are episodic GI signs (vomiting, diarrhea, anorexia), lethargy, weakness, and trembling.
• Biochemical changes include Hyponatremia and Hyperkalemia.
• Addison's is called “The Great Imitator" because it mimics many other conditions, leading to frequent misdiagnosis or delayed recognition.
• Pseudo-Addisonian Na:K changes (<27) are associated with Whipworms, Renal disease, and GI protein-losing enteropathy (PLE).
• Also consider Hepatic disease, effusions, and cardiac disease.

Diagnosing Addison's

• If basal Cortisol is >2.0 µg/dL, Addison's is very unlikely, if <2.0 µg/dL, must do ACTH stim test
• Definitive diagnosis of Addison's: ACTH Stimulation Test (same protocol as Cushing's)
• Addisonian result in ACTH Stimulation Test = pre- and post-ACTH cortisol <2.0 µg/dL
• Atypical Addison's means still low cortisol, may need to monitor aldosterone over time.
• Submit aldosterone levels to confirm mineralocorticoid deficiency
• Typical Addison's Treatment includes: Glucocorticoid-Prednisone 0.1-0.4 mg/kg/day PO, taper to lowest effective dose, double dose during stress (travel, visitors)
• Mineralocorticoid options for Typical Addison's Treatment includes: DOCP, start at 1.0-1.5 mg/kg q25-30d, monitor electrolytes at 10–14d and again at 25d, if stable, reduce dose by 10% or extend interval, but not both at once.
• With Typical Addison's treatment: Electrolytes post-injection and periodically, clinical signs and appetite should be monitored.
• Weaning to treat Typical Addison's is done via gradual dose reductions (DOCP) or extended intervals if electrolytes remain normal.
• Taper prednisone to minimum effective dose.
• Atypical Addison's treatment involves only glucocorticoid, prednisone 0.1-0.4 mg/kg/day PO and taper to lowest dose, monitoring clinical signs, periodic electrolytes or aldosterone levels every 3 months in the first 1-2 years.
• Prednisone dose can be tapered over time and if mineralocorticoid deficiency develops, begin DOCP or switch to fludrocortisone for Atypical Addison's.

Adjusting Addison's Treatments

• Adjust medication if Pu/Pd likely if prednisone dose is too high, so taper down.
• Adjust medication if Intermittent lethargy, diarrhea, reduced appetite if may be under-dosed with prednisone or mineralocorticoid, recheck electrolytes and clinical signs.
• Severe hypokalemia indicates Mineralocorticoid dose is too high (esp. DOCP), reduce dose or increase interval between injections.

Steroid Dosage

• Physiologic replacement: Prednisone: 0.1-0.4 mg/kg/day
• Anti-inflammatory: Prednisone: ~0.5-1 mg/kg/day
• Immunosuppression: Prednisone: 2-4 mg/kg/day
• Most Important Acute Therapy involves aggressive IV fluids (0.9% NaCl), replaces Na/Cl, dilutes K, reverses metabolic acidosis.
• Glucocorticoid impact on ACTH test: do not give prednisone, prednisolone, or hydrocortisone before ACTH stim, they interfere with the cortisol assay.
• Dexamethasone can be given because it does not affect cortisol results, making it safe for emergencies before ACTH testing

Diabetes Mellitus Insulin Info

• Basal insulin is a constant low-level insulin secretion between meals and overnight.
• Bolus insulin is a large, rapid insulin release in response to food intake (post-prandial).
• Insulin therapy mimics both (basal and bolus), but most veterinary protocols rely on long/intermediate-acting insulin to provide combined basal and post-prandial control.
• Dogs develop absolute insulin deficiency and will always need insulin
• Cats start with insulin resistance, obesity, diet, or steroids and may progress to insulin dependence.
• Diabetic remission is defined as sustained euglycemia without insulin therapy.
• Diabetic remission is relevant to cats, especially when treated early with insulin + diet or SGLT2 inhibitors.
• Common clinical signs include polyuria, polydipsia, polyphagia, weight loss.
• Unique signs of diabetes includes cataracts (often bilateral, 80% within 2 years) in dogs.
• Unique signs of diabetes includes plantigrade stance from peripheral neuropathy (10%) in cats
• Common biochemical abnormalities include hyperglycemia, glucosuria, low urine specific gravity, hypercholesterolemia, hypertriglyceridemia, and elevated ALP > ALT.
• Stress hyperglycemia is transient hyperglycemia due to stress hormones, can mimic diabetes on labwork. Must confirm with further testing
• Differentiate between stress and true diabetes by using fructosamine or home blood glucose monitoring.

Diabetic Treatment Goals

• Improve/resolution of clinical signs, maintain/achieve ideal body weight and achieve relative glycemic control (BG ~80-250 mg/dL)
• Avoid complications like hypoglycemia or DKA
• Best starting insulins for Dogs: Vetsulin® or NPH
• Best starting insulins for Cats: ProZinc® (PZI) or Glargine
• Dose for dogs: 0.25-0.5 U/kg SQ q12h (round down), dose for cats: 1-2 U/cat SQ q12h.
• Handling: keep refrigerated, discard if clumped/crystallized or after ~3 months (refrigerated)
• Shake Vetsulin® and gently roll others to mix.
• Administration: feed dogs before insulin; if <50% of meal eaten, give half dose, give insulin after eating with Cats, can graze-feed, ensure they're eating.
• Not essential, but helps-low-carb, high-fiber diets reduce post-prandial spikes in dogs
• High-protein (≥40%), low-carb (≤12%) diets support remission and weight loss (if obese) improves insulin sensitivity.
• SGLT2 inhibitors are used only in cats (FDA-approved: Bexacat®, Senvelgo®)
• Simplify monitoring on cats with oral administration, no BG curves needed, may increase remission rates, no refrigeration required.
• Monitoring involves: Blood ketones (esp. BHB) at days 2-3, 7, 14, 30, then q3mo. If BHB rises, switch to insulin (risk of euglycemic DKA)

Monitoring Plans for Diabetes

• Well-behaved dog: in-clinic glucose curves + physical exams 2x/year, fractious dog/cat: continuous glucose monitoring (FreeStyle Libre)
• Continuous glucose monitoring (FreeStyle Libre) is the most helpful tool for glucose curve and insulin adjustments but also fructosamine for overall control

Performing Glucose Curves

• Measure BG before insulin, then every 1–2 hrs for 10–12 hrs, pre-insulin BG, onset of insulin action, nadir (lowest BG), duration of insulin action, overall BG range
• Goal range: 80–300 mg/dL, with nadir ~100-120 mg/dL
• Controlled glucose curve pattern: BG 100–250 all day, nadir ~100-120 → no changes needed.
• Underdosing glucose curve: High BG all day → consider increasing dose.
• Overdosing glucose curve: Very low nadir followed by rebound hyperglycemia (Somogyi effect) → reduce insulin dose.
• Insufficient duration glucose curve: BG initially drops, then rises before next dose → consider switching insulin or adjusting frequency

Hypoglycemia

• Counter-regulatory response is triggered by blood glucose <60 mg/dL or a rapid drop in blood glucose
• Purpose of counter-regulatory response: To raise blood glucose levels via hepatic glycogenolysis, Peripheral insulin resistance
• Hormones involved Acute (within minutes): Glucagon, catecholamines (epinephrine, norepinephrine), Delayed (hours): Cortisol, Growth hormone Client Instructions for Specific Situations:
• Diabetic dog acting normally, but Libre reads 40 mg/dL: DO NOT panic or rush to give sugar, offer a small amount of regular food or a few treats, call the vet ASAP, avoid Karo syrup or honey unless clinical signs are present. If possible, check BG with a glucometer to confirm
• Diabetic cat ataxic post-insulin and collapses: This is a clinical emergency=signs of hypoglycemia. Offer food immediately, administer sugary solution (Karo syrup or honey), ~0.1 mL/kg, apply to buccal mucosa (inside cheek)
• Use a syringe or soaked Q-tip (never stick fingers in cat's mouth), bring to ER or vet immediately
• Non-diabetic dog having a seizure with BG = 20 mg/dL: Emergent case – stabilize urgently, serum insulin-to-glucose ratio helps differentiate insulinoma or paraneoplastic causes
• Must collect blood BEFORE giving dextrose
• Dose: 0.25-1.0 mL/kg, for 5 kg dog → 1.25-5 mL of 50% dextrose. Dilute at least 1:4 with saline before administering, give slowly IV to avoid insulin surge or irritation
• Example: mix 1 mL 50% dextrose with 4 mL saline → administer IV slowly
• To make 1L (1000 mL) IV fluid with 2.5% dextrose add 50 mL of 50% dextrose to 950 mL of fluids → 50 g/L = 2.5%
• To make 1L (1000 mL) IV fluid with 5% dextrose add 100 mL of 50% dextrose to 900 mL of fluids →100 g/L = 5%

Hyper/Hypocalcemia

• Hypercalcemia Differentials: Malignancy (lymphoma, anal sac adenocarcinoma, SCC), Primary hyperparathyroidism, Vitamin D toxicity, Hypoadrenocorticism, Chronic renal disease, Granulomatous disease
• Osteolysis, Spurious/lab error, Multiple endocrine neoplasia (MEN types I & II), Hyperthyroidism (rarely in cats)
• Hypocalcemia Differentials: Primary hypoparathyroidism, Post-thyroidectomy (iatrogenic), Chronic or acute renal failure, Pancreatitis, Puerperal tetany (eclampsia)
• Hypoalbuminemia, Ethylene glycol toxicity, Intestinal malabsorption, Phosphate-containing enemas, Hyper- or hypoadrenocorticism, Nutritional secondary hyperparathyroidism
• Bone promotes calcium release from labile bone pool by increasing osteoclast activity and decreasing osteoblast activity
• Kidney: Increases renal calcium reabsorption (distal tubule), decreases phosphate reabsorption (proximal tubule), stimulates activation of vitamin D
• GI Tract (indirect): Increases calcium absorption via 1,25-(OH)2-vitamin D activation
• PTHrp is a protein produced by non-parathyroid tumors that mimics PTH actions increases calcium.
• Tumors associated with PTHrp: Lymphoma, Anal sac apocrine gland adenocarcinoma (AGASACA)

Interpreting Chem Test Data and PTH level

• Normal patient: Normal ionized calcium, PTH = normal, PTHrp = negative
• Hyperparathyroidism: High ionized calcium, Normal or high PTH (inappropriate), PTHrp = negative
• Hypoparathyroidism: Low ionized calcium, Low or inappropriately normal PTH, PTHrp = negative
• Renal Secondary Hyperparathyroidism: Low or low-normal iCa, High PTH, PTHrp = negative, common in chronic renal disease
• Vitamin D toxicity: High iCa AND high phosphorus, Low or suppressed PTH, PTHrp = negative

Treatment for Hyperparathyroidism

• Surgical: Parathyroidectomy (removal of adenoma), can cause post-op hypocalcemia, start calcitriol pre-op
• Minimally invasive: Ultrasound-guided ethanol ablation or Radiofrequency ablation, medical management, fluid therapy (0.9% NaCl), furosemide (5 mg/kg IV bolus, then CRI)
• Avoid thiazide diuretics, calcitonin (expensive), bisphosphonates (limited use in dogs), corticosteroids only after diagnosis (to avoid masking neoplasia)
• Acute Treatment for Medical Management of Hypoparathyroidism includes: IV calcium gluconate (5–15 mg/kg over 10-30 min), monitor ECG (watch for bradycardia, arrhythmias)
• SQ calcium gluconate q4-6h if IV unavailable, dilute 1:1 with saline
• Long-term Management for Medical Management of Hypoparathyroidism Calcitriol (vitamin D3): 0.03-0.06 µg/kg/day, oral calcium (carbonate preferred)
• Doges: 1-4 g/day, Cats: 0.5-1 g/day, Calcium carbonate ~40% elemental calcium. The goal is to maintain stable calcium >8 mg/dL and eliminate clinical signs

Thyroid Axis and Negative Feedback

• The Hypothalamus releases TRH to stimulate the pituitary to release TSH; stimulating the thyroid gland to produce T4 and T3.
• T4/T3 inhibits further release of TRH and TSH via negative feedback loop Common Etiologies
• Hypothyroidism in dogs is caused by primary gland failure (~95%), causes lymphocytic thyroiditis (immune-mediated) or idiopathic atrophy