Parathyroidectomy for Primary Hyperparathyroidism and Nonlocalizing Hyperparathyroidism

Introduction

The parathyroid glands are usually found adjacent to the thyroid gland and produce parathyroid hormone (PTH), which increases serum calcium levels by enhancing bone resorption, increasing calcium reabsorption in the distal tubules of the kidneys, and converting calcidiol to the active calcitriol form of vitamin D, which stimulates intestinal calcium absorption. About 85% of the population have two superior (4th pouch) and two inferior (3rd pouch) parathyroid glands, embryologically originating from the dorsal portion of the respective pharyngeal pouches. Supernumerary (more than four) parathyroid glands may occur in up to 15% of the population, and 1% to 3% of parathyroid glands are ectopic.

Primary hyperparathyroidism (PHPT) affects up to 0.5% of the US population and is 4 times more common in females. When sporadic, PHPT is most commonly associated with parathyroid adenoma (80% to 90% of cases) ( Fig. 84.1 ), glandular hyperplasia (6% to 15%) ( Fig. 84.2 ), double adenomas (2% to 5%), and carcinoma (<5%). Familial conditions such as multiple endocrine neoplasia (MEN) type 1, MEN type 2A, and familial isolated hyperparathyroidism are also associated with PHPT. Radiation exposure and genetic defects in cyclin D1 (PRAD) oncogene, MEN1, and Cyclin dependent kinase inhibitory B (CDKN1B) have been identified as risk factors for the development of adenomas and hyperplasia, but there are many yet unknown factors that cause PHPT. Parathyroidectomy is the only curative treatment for patients with PHPT.

Fig. 84.2, Parathyroid hyperplasia. Surgical clips have been placed on the parathyroid glands.

Key Operative Learning Points

Superior parathyroid glands are most commonly located on the posterolateral aspect of the upper two-thirds of the thyroid lobes. Their location can be estimated 1 cm above and below the intersection between the recurrent laryngeal nerve (RLN) and the inferior thyroid artery.
Inferior parathyroid glands are most commonly found in the thyrothymic tract at the level of the inferior aspect of the thyroid lobes.
The RLN is almost always anterior to the superior parathyroid glands and usually posterior to the inferior parathyroid glands.
Focused approaches to parathyroidectomy are made possible by preoperative localization of the hyperfunctioning parathyroid gland and intraoperative PTH monitoring.

Preoperative Period

History

1.
History of present illness
- a.
  Most patients with PHPT are asymptomatic, but many have nonspecific symptoms such as fatigue, weakness of the proximal extremities, diffuse bone pain, anorexia, and constipation.
- b.
  Symptoms of hypercalcemia
  - 1)
    Urinary system: Polydipsia, polyuria, nephrolithiasis
  - 2)
    Skeletal system: Osteopenia, osteoporosis, or osteitis fibrosa cystic, which presents with bone pain, pathologic fractures, and/or “brown tumors”
  - 3)
    Gastrointestinal system: Peptic ulcer disease (PUD), pancreatitis, cholelithiasis
  - 4)
    Cardiovascular system: Hypertension, arrhythmias, embolic events
  - 5)
    Neurologic system: Depression, anxiety, cognitive dysfunction, psychosis
- c.
  Symptoms of coexistent thyroid disease
  - 1)
    Compressive symptoms such as dysphagia, hoarseness, cervical pressure, globus sensation
2.
Past medical history
- a.
  Previous treatment of PHPT
- b.
  History of radiation therapy to the neck
- c.
  Medical illnesses, to determine candidacy for surgery
- d.
  Past surgical history, especially operations on the neck
3.
Family history: Thyroid or parathyroid disease, familial isolated hyperparathyroidism, MEN type 1 or 2A, or familial hypocalciuric hypercalcemia
4.
Medications
- a.
  Anticoagulants and antiplatelet medications
- b.
  Lithium or thiazide diuretics
  - 1)
    May cause mild hypercalcemia and hyperparathyroidism, so discontinue for at least 1 month before confirming PHPT.
- c.
  Allergies to antibiotics

Physical Examination

1.
Neck
- a.
  Examination findings are nonspecific
- b.
  Assess for thyroid nodules and cervical adenopathy.
- c.
  A palpable mass in the neck in the patient with hypercalcemia may indicate parathyroid carcinoma.
2.
Laryngoscopy
- a.
  Assess preoperative RLN function.
- b.
  Essential prior to reoperation

Laboratory

1.
Most cases of PHPT are diagnosed following an incidental finding of elevated serum calcium.
2.
Calcium, total vitamin D, and PTH should be measured together.
3.
Measure 24-hour urine calcium excretion in order to distinguish PHPT from familial hypocalciuric hypercalcemia.
4.
Other laboratory abnormalities in PHPT include hypophosphatemia and mild hyperchloremic acidosis secondary to renal involvement.
5.
Use creatinine and blood urea nitrogen (BUN) to rule out renal insufficiency.
6.
Patients who have had gastric bypass surgery should have calcium challenge to assure absorptive ability.

Imaging

1.
Preoperative imaging/localization results in
- a.
  Increased operative success
- b.
  Decreased surgical risk/extent of dissection
- c.
  Decreased operative time
2.
Imaging is particularly important prior to reoperation.
3.
Imaging guides the operative approach.
4.
Imaging has no role in the diagnosis of PHPT.
5.
Imaging options:
- a.
  Ultrasound
  - 1)
    Parathyroid adenomas have a homogeneous hypoechoic appearance on ultrasound.
  - 2)
    Ultrasound has emerged as the preferred initial preoperative localization method for many surgeons and endocrinologists.
  - 3)
    Ultrasound can screen for concomitant thyroid lesions that require surgical intervention, though the sensitivity of ultrasound is diminished in those with concurrent thyroid disease.
  - 4)
    As in other applications, the major limitation of sonography is that accuracy is operator-dependent.
- b.
  Technetium-99m sestamibi scintigraphy ( Fig. 84.3 )
  - 1)
    Sestamibi scintigraphy has been the traditional standard for preoperative localization.
  - 2)
    Planar images are captured after the injection of the radiotracer technetium-99m-methoxyisobutylisonitrile (MIBI), which is taken up preferentially by the mitochondria of the cells of the hyperfunctioning parathyroid gland(s).
6.
Patients with familial hyperparathyroidism, MEN type 1, and MEN type 2A only need ultrasound to screen for coexistent thyroid disease because they will undergo four-gland exploration.

Invasive Localization

1.
Invasive localization techniques may be employed if previous imaging is nonlocalizing or conflicting.
2.
Selective venous sampling and arteriography effectively localize pathologic parathyroid glands.
- a.
  Associated with risks such as hematoma of the groin, possible embolic events, and contrast-induced anaphylaxis or acute kidney injury
3.
Fine-needle aspiration of a parathyroid mass under ultrasound guidance can confirm location by measuring PTH in aspirate.

Indications

1.
Symptomatic PHPT, including parathyroid crisis
2.
Familial PHPT
3.
Suspicion for parathyroid cancer
4.
Presence of thyroid disease that can be surgically treated at the same time as PHPT
5.
Asymptomatic PHPT patients in whom at least one of the following is true :
- a.
  Age less than 50 years
- b.
  Serum calcium greater than 1 mg/dL above the upper limit of normal
- c.
  Bone mineral density T score less than –2.5
- d.
  Vertebral fracture
- e.
  Creatinine clearance less than 60 mL/minute or reduced more than 30% for age
- f.
  Twenty-four-hour urine calcium greater than 400 mg/dL
- g.
  Nephrolithiasis or nephrocalcinosis on imaging

Contraindications

1.
Contralateral RLN injury
2.
Symptomatic cervical disc disease
3.
Other comorbidities that preclude surgery

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