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Primary Hyperparathyroidism

Ruth Gostelow, BVetMed (Hons), DACVIM, MRCVS Harriet Syme, BSc, BVetMed, PhD, FHEA, DACVIM, DECVIM-CA, MRCVS University of London

Endocrinology & Metabolic Diseases

|November 2013|Peer Reviewed

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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 & Pathophysiology3,4

  • 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 Signs3,6   

  • 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.

Complications4,7

  • 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: $$$$$
  • Surgical parathyroidectomy: $$$$$
  • Percutaneous ultrasound-guided radiofrequency heat ablation: $$$$
  • Percutaneous ultrasound-guided ethanol ablation: $$$$
Cost Key
$ = up to $100
$$ = $101–$250
$$$ = $251–$500
$$$$ = $501–$1000
$$$$$ = more than $1000

Prognosis

  • Excellent with appropriate management
  • Definitive treatment is curative in most cases.
  • Approximately 10% of patients have recurrence.4

Hypercalcemia: Treatment Basics The 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.


References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

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