Canine Hyperparathyroidism Study Guide

Overview and Clinical Importance

Hyperparathyroidism is an endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH), leading to disruption of calcium homeostasis. This condition can be classified as primary, secondary renal, or secondary nutritional, each with distinct pathophysiology and clinical manifestations. Understanding hyperparathyroidism is essential for the NAVLE as it represents a significant differential diagnosis for hypercalcemia in dogs and requires careful diagnostic workup and appropriate therapeutic intervention.

Classification and Pathophysiology

Types of Hyperparathyroidism

Primary Hyperparathyroidism (PHPT)

Primary hyperparathyroidism results from autonomous, inappropriate secretion of PTH by one or more parathyroid glands, leading to hypercalcemia despite elevated calcium levels. This represents a failure of the normal negative feedback mechanism.

Etiology:

• Parathyroid adenoma: 80-85% of cases (most common cause)
• Parathyroid hyperplasia: 10-15% of cases
• Parathyroid carcinoma: Less than 5% of cases (rare, malignant)

Epidemiology:

• Mean age: 10.5 years (range 5-15 years)
• Breed predisposition: Keeshond (very high prevalence suggesting genetic component)
• No sex predilection
• Accounts for approximately 14% of ionized hypercalcemia cases in dogs

Secondary Renal Hyperparathyroidism

Renal secondary hyperparathyroidism develops as a compensatory response to chronic kidney disease. Unlike primary hyperparathyroidism, PTH secretion is appropriately responding to abnormal calcium and phosphorus homeostasis caused by renal insufficiency.

Pathophysiology:

• Decreased glomerular filtration rate leads to phosphorus retention (hyperphosphatemia)
• Hyperphosphatemia causes decreased ionized calcium via formation of calcium-phosphate complexes
• Reduced synthesis of calcitriol (active vitamin D3) by diseased kidneys
• Hypocalcemia and low calcitriol stimulate compensatory PTH secretion
• Chronic PTH elevation leads to parathyroid gland hyperplasia and excessive bone resorption

Secondary Nutritional Hyperparathyroidism

Nutritional secondary hyperparathyroidism results from dietary imbalances that decrease serum ionized calcium, triggering compensatory PTH secretion. This is most common in young, growing animals fed improper diets.

Dietary Causes:

• All-meat or organ-based diets (low calcium, high phosphorus)
• Calcium deficiency
• Vitamin D deficiency
• Excessive phosphorus intake

Clinical Signs and Presentations

Primary Hyperparathyroidism Clinical Signs

Clinical signs of PHPT are primarily related to the effects of hypercalcemia on multiple organ systems. Importantly, up to one-third of dogs with PHPT may be asymptomatic, with hypercalcemia discovered incidentally on routine bloodwork.

Most Common Signs (Renal/Urinary - seen in up to 50% of cases):

• Polyuria and polydipsia (PU/PD) - hypercalcemia impairs ADH function at collecting ducts
• Urinary tract infections
• Calcium oxalate urolithiasis (bladder stones)
• Hematuria and dysuria

Gastrointestinal Signs:

• Decreased appetite and anorexia
• Vomiting
• Weight loss

Neuromuscular Signs:

• Weakness and lethargy
• Decreased activity level
• Muscle tremors (rare)
• Seizures (uncommon, severe cases)

Skeletal Signs (RARE in PHPT, more common in secondary forms):

• Lameness
• Stiff gait
• Pathologic fractures (minimal trauma)
• Loose teeth

Secondary Hyperparathyroidism Clinical Signs

Secondary hyperparathyroidism (especially renal) typically presents with signs of the underlying condition (chronic kidney disease) PLUS skeletal manifestations from fibrous osteodystrophy. This is more common in young, growing animals.

Renal Signs:

• Polyuria and polydipsia
• Vomiting and dehydration
• Depression and lethargy
• Poor body condition

Skeletal/Fibrous Osteodystrophy Signs:

• Bilateral facial swelling (maxillary and mandibular bone proliferation)
• Rubber jaw syndrome - softening and pliability of mandible and maxilla
• Loose teeth that may be easily displaced
• Difficulty chewing and jaw closure
• Drooling and tongue protrusion
• Pathologic fractures (especially mandible)
• Lameness and reluctance to move

Diagnosis and Laboratory Evaluation

Diagnostic Approach to Hypercalcemia

A systematic diagnostic approach is essential when evaluating hypercalcemia. The key is to differentiate between parathyroid-dependent and parathyroid-independent causes of hypercalcemia.

Laboratory Findings by Type

Key Diagnostic Tests:

• Ionized calcium: Most accurate measure of calcium status; definitive test for hypercalcemia
• Total calcium: Initial screening test; may be falsely elevated with dehydration
• PTH concentration: Must be measured on same sample as calcium for accurate interpretation
• PTHrP: Helps identify humoral hypercalcemia of malignancy
• Urinalysis: Evaluate for UTI, assess urine specific gravity and calcium oxalate crystals
• Renal parameters: BUN, creatinine to assess kidney function

Imaging Diagnostics

Cervical Ultrasonography:

• Normal parathyroid glands: less than 3 mm in diameter
• Parathyroid adenoma: typically appears as a single enlarged, hypoechoic, round mass
• Operator-dependent; may not visualize small glands
• Useful for surgical planning to identify affected gland preoperatively

Radiographic Findings (Fibrous Osteodystrophy):

• Generalized decreased bone opacity (osteopenia)
• Moth-eaten appearance of skull bones (accelerated bone resorption)
• Loss of lamina dura around teeth
• Floating teeth sign - complete loss of alveolar bone support
• Thinning of mandibular and maxillary cortices
• Pathologic fractures (especially in long bones and vertebrae)
• Abdominal radiographs: bladder stones (calcium oxalate uroliths)

Differential Diagnoses for Hypercalcemia

When evaluating hypercalcemia, consider these differentials (mnemonic: HARDIONS):

HARDIONS Mnemonic:

• H - Hyperparathyroidism (primary)
• A - Addison's disease (hypoadrenocorticism)
• R - Renal disease (chronic kidney disease)
• D - Vitamin D toxicosis
• I - Idiopathic (up to 30% of cases)
• O - Osteolytic lesions
• N - Neoplasia (lymphoma, anal sac adenocarcinoma, multiple myeloma)
• S - Spurious (laboratory error, hemolysis, lipemia)

Treatment and Management

Primary Hyperparathyroidism Treatment

Surgical Parathyroidectomy (Treatment of Choice)

Surgical removal of the affected parathyroid gland(s) is the definitive treatment for PHPT, with excellent prognosis if performed before advanced renal damage develops. The success rate approaches 100% when performed by an experienced surgeon.

Preoperative Considerations:

• Attempt ultrasound localization of affected gland (though intraoperative identification often necessary)
• Evaluate renal function thoroughly
• Consider preoperative calcium-lowering medication if severely hypercalcemic (greater than 16 mg/dL)
• Inform owner of post-operative hypocalcemia risk and hospitalization requirements

Surgical Technique:

• Careful visualization of all four parathyroid glands
• Removal of adenomatous gland while preserving vascular supply to remaining glands
• Submit removed tissue for histopathology (adenoma vs hyperplasia vs carcinoma)
• If hyperplasia involves multiple glands: remove 3.5 glands, leaving adequate tissue to prevent permanent hypoparathyroidism

CRITICAL Post-operative Management:

Post-operative hypocalcemia is the most common and serious complication, occurring in 21-71% of dogs. This results from suppression of remaining parathyroid glands and hungry bone syndrome (rapid calcium uptake by previously demineralized bones).

Monitoring Protocol:

• Hospitalization for 5-10 days post-operatively
• Measure ionized or total calcium every 6-12 hours initially
• Monitor for clinical signs of hypocalcemia: muscle tremors, tetany, seizures
• Hypocalcemia typically develops 24-72 hours post-surgery

Treatment of Post-operative Hypocalcemia:

• Acute severe hypocalcemia with clinical signs: IV 10% calcium gluconate (0.5-1.5 mL/kg slowly IV over 10-30 minutes with ECG monitoring)
• Chronic supplementation: Oral calcium carbonate or calcium gluconate (25-50 mg/kg PO every 8-12 hours)
• Calcitriol (active vitamin D): 0.02-0.03 mcg/kg PO every 12-24 hours
• Gradually wean supplements as remaining parathyroid glands resume function (may take weeks to months)

Prognosis:

• Excellent if surgery performed before severe renal damage
• Recurrence: 5-10% in most breeds, up to 50% in Keeshonds
• Permanent hypoparathyroidism: rare if adequate tissue preserved

Alternative Treatment Options

Secondary Hyperparathyroidism Treatment

Renal Secondary Hyperparathyroidism

Treatment focuses on managing the underlying chronic kidney disease and controlling phosphorus levels to reduce PTH stimulation.

Therapeutic Approach:

• Prescription renal diet (restricted phosphorus, moderate protein restriction)
• Intestinal phosphate binders: aluminum hydroxide, calcium carbonate, or sevelamer (administered with meals)
• Calcitriol supplementation (1.5-3.5 ng/kg/day PO) - ONLY after phosphorus controlled to normal range
• Manage concurrent CKD complications (hypertension, proteinuria, azotemia)
• Monitor serum phosphorus, calcium, and PTH every 2-4 weeks initially, then every 3-6 months

Prognosis:

Depends on severity of underlying CKD. Skeletal changes may improve with treatment, but prognosis is guarded to poor in advanced renal failure. Young dogs with congenital nephropathies have poor long-term prognosis.

Nutritional Secondary Hyperparathyroidism

Treatment:

• Dietary correction: switch to balanced commercial diet appropriate for life stage
• Calcium supplementation: 25-50 mg/kg PO every 12 hours initially
• Vitamin D supplementation if deficient
• Cage rest for pathologic fractures
• Supportive care for skeletal pain

Prognosis:

Excellent with proper nutrition. Skeletal changes gradually improve over 3-6 months. Prevention through balanced diet is key.