Primary Hyperparathyroidism

PROFILE

• Primary hyperparathyroidism (PHPT) and primary hypoparathyroidism are the most common primary parathyroid gland diseases.

• Two external parathyroid glands lie outside the thyroid capsule, and two internal parathyroid glands are embedded within the thyroid parenchyma.¹

• Parathyroid glands synthesize and secrete parathyroid hormone (PTH) from chief cells.²

• PTH increases plasma calcium concentration by mobilizing calcium from bone, increasing renal calcium reabsorption, and promoting formation of calcitriol, which increases intestinal calcium absorption.

• PTH promotes phosphaturia by decreasing renal phosphorus reabsorption.

• Parathyroid gland diseases are characterized by abnormalities in serum calcium and phosphorus concentrations.

• Clinical signs are frequently secondary to serum calcium abnormalities.

• Parathyroid glands may also be affected secondary to other disease states (eg, renal secondary hyperparathyroidism).

Related Article: Anesthesia for Parathyroid Disease 

Definition & Pathophysiology^3,4

• Excessive PTH production from autonomously functioning chief cells, usually in a single parathyroid adenoma

• Parathyroid carcinoma, hyperplasia, or multiple parathyroid adenomas are possible but rare.

Systems

• Urinary, neuromuscular, and GI signs are possible.

Incidence & Prevalence

• Accounts for ~13% of dogs with ionized hypercalcemia⁵

• PHPT is caused by adenoma of the parathyroid gland (75%–85% of cases), hyperplasia (5%–15% of cases), and carcinoma (5%–10% of cases).^4,6,7

• Rarer in cats⁸

• More common causes of hypercalcemia in cats include renal failure and idiopathic hypercalcemia (see Table)

Related Article: Polyuria, Polydipsia, & Hypercalcemia

Signalment

Breed Predilection

• Autosomal dominant inheritance causes increased prevalence in keeshonds,9 but PHPT should be considered as a differential for any dog or cat with hypercalcemia.

Age & Range

• Middle-aged to geriatric dogs

Sex Predilection

• No known predilection

Related Article: Hypercalcemia in Dogs and Cats

Clinical Signs<sup3,6 sup>   

• Mainly attributable to hypercalcemia, which may be found incidentally:

• Up to 35% of patients show no clinical signs.

• Affected patients often appear healthier than those with other causes of hypercalcemia (eg, lymphoma).

• Causes(s) and approximate frequency of clinical signs:

• Polyuria/polydipsia from decreased renal tubular response to antidiuretic hormone (50%–60%)

• Hematuria, stranguria, pollakiuria, urinary tract infection, and urinary tract obstruction (50%)

• Calcium phosphate or oxalate urolithiasis may result from calciuria and phosphaturia.

• Dilute urine-specific gravity predisposes patients to infection.

• Lethargy, muscle wasting, and stiffness from decreased neuromuscular tissue excitability (40%–45%)

• Inappetence (37%), vomiting (13%), and constipation (6%) caused by decreased excitability and motility of GI smooth muscle

Physical Examination

• Patients may appear lethargic or weak.

• A cervical mass may be palpated in cats.

• A palpable parathyroid mass is rare in dogs.

• A palpated mass could represent an alternative cause of hypercalcemia (eg, thyroid carcinoma).

• Examination should not identify any finding consistent with other causes of hypercalcemia (eg, lymphadenopathy).

DIAGNOSIS

Definitive

• Histologic examination of parathyroid gland mass(es) following successful surgical removal/ablation and resolution of hypercalcemia

• Plasma PTH can be measured to support diagnosis.

Differentials

• Differential diagnoses for hypercalcemia can vary (see Table)

Laboratory Findings

• Chemistry panel: total hypercalcemia, decreased or borderline-low serum phosphorus concentration, possible azotemia

• Ionized hypercalcemia in >90% of cases³

• Urinalysis: frequent hyposthenuria or isosthenuria

• Crystalluria, bacteriuria, hematuria, and pyuria are possible.

Imaging

• Ventral neck ultrasonography may identify parathyroid masses (see Figure 1, Cervical ultrasound of parathyroid mass (yellow arrow) within the parenchyma of a thyroid gland lobe (white arrow).

• Most masses are small (4–9 mm in diameter).

• Ultrasonography can be highly sensitive and is operator-dependent. 

• Parathyroid scintigraphy with Technetium (99mTc) sestamibi, nuclear medicine imaging, can identify hyperfunctional parathyroid tissue in patients with negative ultrasound findings but may show poor sensitivity and specificity in dogs.¹¹

• Abdominal ultrasonography may reveal urinary tract calculi or other lesions causing hypercalcemia (eg, lymphoma).

• Plain radiography may reveal radio­paque urinary calculi or intrathoracic lesions causing hypercalcemia (eg, anterior mediastinal mass).

Other Diagnostics

•  Plasma PTH concentration

• Values that are increased or in the upper half of reference range are consistent with PHPT in hypercalcemic patients, which should have low PTH values. 

• Serum PTH-related peptide concentration

• Identifies most cases of hypercalcemia of malignancy

TREATMENT

• Definitive treatment requires removal or ablation of parathyroid mass(es).

Medical

• No definitive medical cure

• Medical therapy can ameliorate severe hypercalcemia signs before definitive treatment or can be used to treat or prevent postoperative hypocalcemia following parathyroid nodule removal or ablation (see Hypercalcemia: Treatment Basics and Prevention & Treatment of Hypocalcemia below).

Surgical & Interventional

• Three definitive treatments are described:

• Surgical parathyroidectomy 

• Mass(es) should be located preoperatively using imaging.

• Success rate, 89%–96%6,12 

• Percutaneous ultrasound-guided radiofrequency heat ablation 

• Nodule is destroyed by thermal necrosis from radiofrequency waves applied through IV catheter under ultrasound guidance.

• Equipment is expensive.

• Success rate, 81%–92%12,13

• Percutaneous ultrasound-guided ethanol ablation 

• Ethanol is injected into the nodule with ultrasound guidance, causing coagulation necrosis. 

• Used less frequently because of lower success rates (~72%)¹²

• Parathyroidectomy is most commonly used by the authors, but preferred treatment method depends on local expertise and experience.

FOLLOW-UP

Patient Monitoring

• Patients should be hospitalized with limited exercise for ≥5 days postoperatively to minimize risk and monitor for hypocalcemia.

• Total and ionized serum calcium concentrations should be measured q12–24h for ≥5 days postoperatively.

• Slightly low serum calcium concentration (8–10 mg/dL) should be maintained to prevent iatrogenic hy­­­percal­cemia and promote return of parathyroid function.⁴

• If given, vitamin D and calcium therapy should be tapered and discontinued over 3–5 months, starting 14 days after treatment is initiated.

• Serum calcium should be measured before each reduction.

Complications^4,7

• Postoperative hypocalcemia can occur 4–7 days posttreatment in up to 30% of patients.

• May develop after any treatment method

• Causes signs in up to 10% of patients

• Hypocalcemia risk may correlate with duration and magnitude of preoperative hypercalcemia, but currently there is no method for identifying which patients will be affected.14

• Horner syndrome and transient laryngeal paralysis have been reported following ultrasound-guided treatment.

IN GENERAL

Relative Cost

• Definitive treatment can be expensive, especially if patient requires cystotomy or has clinical hypocalcemia after treatment: $$$$$

• Surgical parathyroidectomy: $$$$$

• Percutaneous ultrasound-guided radiofrequency heat ablation: $$$$

• Percutaneous ultrasound-guided ethanol ablation: $$$$

Prognosis

• Excellent with appropriate management

• Definitive treatment is curative in most cases.

• Approximately 10% of patients have recurrence.⁴

Hypercalcemia: Treatment BasicsThe following can be used to treat patients with PHPT and preoperative clinical hypercalcemia²:

Prevention & Treatment of Hypocalcemia⁴

PHPT = primary hyperparathyroidism, PTH = parathyroid hormone

RUTH GOSTELOW, BVetMed (Hons), DACVIM, MRCVS, is interested in small animal endocrine diseases. Dr. Gostelow graduated from University of London, where she completed a small animal rotating internship. After two years in small animal practice, she returned to University of London to complete a residency in small animal internal medicine to pursue a PhD with a focus in feline diabetic remission.