Continuing Education Activity

Parathyroidectomy is the surgery to remove one or more of the parathyroid glands in the patient who has hyperparathyroidism. This activity reviews the technique and complications of parathyroidectomy and highlights the role of the interprofessional team in evaluating and managing the patients undergoing parathyroidectomy perioperatively.

Objectives:

• Identify the indications for parathyroidectomy.
• Describe the technique of parathyroidectomy.
• Review the clinical significance of parathyroidectomy.
• Summarize the potential complications of parathyroidectomy.

Introduction

Parathyroidectomy is the surgery to remove one or more of the parathyroid glands in the patient who has hyperparathyroidism. Parathyroidectomy is the only definitive treatment for primary hyperparathyroidism. Most patients with primary hyperparathyroidism have a single parathyroid adenoma, though a significant minority (up to 10%) may have double adenomas, and a small minority will have hyperplasia of all four glands.[1] The traditional parathyroidectomy technique explores all four glands and removes the adenoma(s) based on clinical observation of gland size.

With the development of the preoperative localization technique, the minimally invasive surgery using the radio-guided technique, ultrasound imaging, high-resolution endoscopic technique, rapid intraoperative parathyroid hormone (IOPTH) monitoring has been used by many surgeons to avoid exploration of all glands. The traditional parathyroidectomy still has its advantages and is still routine practice for some surgeons. For completeness' sake, this standard surgery is the operation reviewed in this article.[2][3][4][5]

Anatomy and Physiology

The parathyroid glands are four glands located posterior to the thyroid, with a normal weight ranging from 30 to 50 mg. The two superior parathyroid glands are derived from the fourth pharyngeal pouch and are classically located posterior to the plane of the recurrent laryngeal nerve. Their location is more consistent than the inferior parathyroid glands. The two inferior parathyroid glands are derived from the third pharyngeal pouch as well as thymus; they are classically located inferior to the thyroid and anterior to the plane of the recurrent laryngeal nerve, but sometimes can be located in very aberrant locations in the lower neck, in the parenchyma of the thyroid gland or thymus remnant, in the carotid sheath, the retro-esophageal space, or the mediastinum. There can also exist true ectopic glands, including supra-numerary glands. These may also be located in the carotid sheath, paraesophageal or retro-esophageal space, or intrathyroidal or mediastinal positions.

The four parathyroid glands are supplied by the inferior thyroid artery from the thyrocervical trunk. The superior parathyroid glands may be supplied by the superior thyroid artery in 20% of cases, or more commonly by an anastomotic branch between the inferior thyroid and the superior thyroid artery.

Parathyroid glands regulate calcium by secreting parathyroid hormone (PTH). When the serum calcium level decreases, the chief cells in the parathyroid release PTH. In the kidney, PTH increases calcium reabsorption in the loop of Henle (as well as in the distal tubule and collecting duct), excretion of phosphate, and promotes 25-hydroxy vitamin D converting to active 1,25-dihydroxy vitamin D3. PTH stimulates osteoclast activity in the bone, releases calcium into the blood, and elevates serum calcium levels. In the intestine, activated Vitamin D increases the absorption of calcium.  

Hyperparathyroidism is a disorder with excessive production of PTH due to the overactivity of the parathyroid gland(s). Primary hyperparathyroidism results from autonomous hypersecretion of PTH from the abnormal parathyroid gland. The majority of patients with primary hyperparathyroidism have a single enlarged parathyroid gland, usually an adenoma, though hypercellular parathyroid is also possible. In up to 10% of patients with primary hyperparathyroidism, there will be two abnormal glands. Multiple endocrine neoplasia (MEN) type 1, type 2A, or parathyroid carcinoma can cause primary hyperparathyroidism in rare cases. The high calcium level due to hypersecretion of PTH can lead to neuromuscular symptoms, osteoporosis and bone loss, and kidney stones.

Secondary hyperparathyroidism is due to high PTH levels from the physiological response to hypocalcemia. Vitamin D deficiency and chronic renal failure are the most common causes of secondary hyperparathyroidism.

Tertiary hyperparathyroidism occurs in patients with secondary hyperparathyroidism from chronic renal failure and persistent secretion of PTH after renal transplant.

Indications

Primary Hyperparathyroidism

Parathyroidectomy is indicated for all patients with symptomatic primary hyperparathyroidism.[6] The symptoms include polydipsia and polyuria, nephrolithiasis or nephrocalcinosis, hypercalciuria (24-hour urine calcium level >400 mg/dL), impaired renal function (glomerular filtration rate [GFR] <60 mL/minute), osteoporosis (bone density score <-2.5), fragility fracture or vertebral compression fracture, pancreatitis, peptic ulcer disease or gastroesophageal reflux and neurocognitive dysfunction or neuropsychiatric symptoms attributable to PHPT.

Indications of Parathyroidectomy in Asymptomatic Hyperparathyroidism[7]

• Age younger than 50 years, serum calcium level >1 mg/dL above the normal limit
• Urinary calcium excretion > 400 mg per 24 hours (10 mmol per day)
• Creatinine clearance was reduced by more than 30 percent compared with age-matched persons
• Bone density (lumbar spine, hip, or forearm) that is > 2.5 standard deviations below peak bone mass (T score -2.5)
• Medical surveillance is not desirable or possible
• Surgery requested by the patient

A recent study revealed normocalcemic and hypercalcemic primary hyperparathyroidism had similarly increased cardiovascular risk factors. Parathyroidectomy ameliorated the increased cardiovascular risk factors in both normocalcemic and hypercalcemic PHPT.[8]

Secondary Hyperparathyroidism

Patients with secondary hyperparathyroidism are usually managed medically. Parathyroidectomy is indicated in refractory hyperparathyroidism with hypercalcemia or hyperphosphatemia, or severe symptoms. About 15% of patients will need parathyroidectomy for medically refractory secondary hyperparathyroidism after 5 to 10 years on dialysis.[9]

Tertiary Hyperparathyroidism

Tertiary hyperparathyroidism with symptomatic hypercalcemia is the main indication for parathyroidectomy. Surgical treatment for tertiary HPT has higher cure rates than medical therapy.[10] Limited or subtotal parathyroidectomy is recommended. The goal is a normal calcium level at least six months postoperatively.[11]

Parathyroidectomy is indicated if the hyperparathyroidism is a suspicion of parathyroid carcinoma, especially with significantly elevated calcium or PTH levels (which can be in the thousands of ng/mL), painful large neck mass, or inhomogeneous mass on imaging.[6]

Other indications of parathyroidectomy include parathyroid cyst and parathyroid hypercalcemic crisis (severe hypercalcemia and central nervous system dysfunction).[12][13]

Contraindications

Absolute Contraindication

• Parathyroidectomy is contraindicated in patients with familial hypocalciuric hypercalcemia (FHH) presenting with elevated calcium and PTH levels but low 24-hour urine calcium excretion and a low ratio of 24-hour urinary calcium to creatinine clearance.  Parathyroidectomy does not cure FHH-associated hypercalcemia.[14]

Relative Contraindication

• Contralateral recurrent laryngeal nerve (RLN) injury or vocal cord dysfunction

Equipment

The following equipment is needed:

• Bovie or bipolar cautery, harmonic scalpel, electronic tissue fusion devices, or surgical ties, according to the surgeon's preference.
• Frozen pathology analysis to confirm parathyroid tissue.
• Intraoperative nerve monitoring (IONM): RLN monitoring is an attempt to reduce the risk of nerve injury during parathyroid surgery, especially in re-operative parathyroid surgery.[15][16]
• In focused parathyroidectomy, ultrasound or Gamma probe can be used to localize abnormal gland intraoperatively, and intraoperative parathyroid hormone (IOPTH) assay to confirm the removal of the hyperfunctioning gland should be coordinated with the pathology department if it is planned.

Personnel

• Standard operating room staff, one or two surgeons, and the anesthesiologist.
• The pathologist or clinical chemist should also be involved if IOPTH is planned.

Preparation

Surgery

Parathyroidectomy is the standard treatment for hyperparathyroidism. The goal is to remove the parathyroid gland or glands producing excess PTH. The standard procedure for patients with multi-gland disease, unsuccessful preoperative localization, is the traditional surgical approach of bilateral parathyroid exploration of 4 glands. Focused parathyroidectomy with a smaller incision and less dissection is used in patients with a well-localized solitary adenoma. Compared to bilateral parathyroid exploration, focused parathyroidectomy has similar clinical outcomes: including recurrence, persistence, and reoperation rates but significantly lower overall complication rates and shorter operative time.[17] 

Total parathyroidectomy and subtotal parathyroidectomy (a small remnant of gland left or auto-transplanted) are indicated in secondary or tertiary hyperparathyroidism with parathyroid hyperplasia. Total parathyroidectomy with auto-transplantation carries a higher risk of permanent hypocalcemia and cardiovascular events, whereas the risk of hyperparathyroidism recurrence is higher with subtotal parathyroidectomy.[9][18] Several new technologies, including ultrasound localization of hyperplastic parathyroid glands, radio-guided surgery, endoscopic-assisted parathyroidectomy, and intraoperative assessment of serum PTH levels, can be appropriately used in the practice of parathyroid surgery.[19]

Preoperative Localization

Preoperative localization is critical for focused, minimally invasive parathyroid surgery. The localization imaging studies include Sestamibi scintigraphy (technetium-99-sestamibi scanning), SPECT — sestamibi-single photon emission computed tomography (SPECT or MIBI-SPECT), SPECT and CT fusion, neck ultrasound, 4D-CT, MRI, and PET-CT.[20][21] In the cases with a history of neck surgery, unsuccessful radio-image localization, invasive localization such as selective venous sampling.[22][23]

Pre-op Preparation

Anesthesia

General anesthesia is preferred for parathyroidectomy, especially for patients who need sternotomy, neck dissection. Most surgeons prefer to use general anesthesia with intubation for single gland, focused parathyroidectomy.[24] Recent studies showed local anesthesia with the cervical block is feasible and significantly reduces the cost.[25] Local anesthesia in minimally invasive parathyroidectomy was associated with significantly lower postoperative pain, nausea, and vomiting.[26] General anesthesia is preferred for parathyroidectomy, especially for patients who need sternotomy, neck dissection.

Positioning

The patient is placed on the operating table supine with the neck extended and both arms tucked at the sides. A shoulder roll can be placed to improve the exposure of the neck. The operating table is slightly in reverse Trendelenburg position. Patients with cervical spine disease should be assessed for the safety of neck extension.

Technique or Treatment

Procedure

1. In bilateral exploration, a transverse low collar incision is made about one finger wide above the clavicular head in an existing skin crease. The dissection is carried down through the subcutaneous tissue and the platysma muscle. Hemostasis is obtained by electrocautery or ligation using ties.
2. Dissection continues to elevate the upper subplatysmal flap to the thyroid notch and the lower flap to the sternal notch. Self-retaining retractors are used to retract the skin flaps.
3. The deep fascia is opened by a midline incision along the median raphe of the strap muscles. Dissect the fascia along the anterior margins of the sternocleidomastoid muscle and either retract the strap muscles or divide the sternohyoid muscles and sternothyroid muscles vertically. Blunt dissect to the plane of cleavage between the sternocleidomastoid muscle and the outer boundaries of the sternothyroid muscle.
4. A midline vertical incision is made between the sternohyoid muscles, extending from the thyroid notch to the level of the sternal notch. The sternohyoid muscles are then elevated to develop a plane between the thyroid gland and the sternohyoid muscles. Blunt dissection with the index finger or other blunt instrument such as a Kittner is performed in this plane to the lateral edge of the thyroid to mobilize the entire lateral surface of the thyroid and expose the paratracheal space between the trachea and carotid sheath.
5. Ligate the middle thyroid vein, then retract the thyroid lobe medially and anteriorly; the recurrent laryngeal nerve and the parathyroid glands can be identified at the upper and lower poles of the thyroid lobe. A similar exploration is made on the other side.  The serum sample of PTH is collected for the baseline level.    
6. The solitary adenoma often appears to be enlarged in size and discolored. The enlarged gland is dissected and divided from the surrounding tissue without injuring the recurrent laryngeal nerve especially isolating the inferior parathyroid glands. It is important not to rupture the gland capsule in cases of malignancy but also in benign diseases to prevent parathyromatosis.
7. The tissue specimen is sent for frozen section pathology to confirm it is the parathyroid gland. The PTH serum level is repeated, the removal of the overactive parathyroid gland is confirmed if the level drops >50% AND to within the normal PTH range. Continue to explore additional adenoma if the PTH level doesn’t fall to the expected level.
8. Irrigate the wound, approximate the strap muscles with interrupted absorbable sutures, close the platysma with interrupted absorbable suture, close the skin with a running subcuticular absorbable suture.
9. With preoperative localization of abnormal parathyroid gland, focused parathyroidectomy can be performed only in the imaging identified area. The incision size, the extent of dissection, and the duration of surgery are limited.

Intraoperative Decision Making

1. It is important to fully mobilize the thyroid to search for a missing parathyroid gland. If the upper gland is missing, explore the tracheoesophageal groove, the retropharyngeal space, and above the thyroid cartilage.  The search for a missing lower gland should begin with a thorough exploration of the inferior pole of the thyroid and the surrounding soft tissue. If the gland is not found, performing a formal cervical thymectomy (or at least pulling up the thymus for examination is reasonable).[27]
2. In the patient with four gland hyperplasia, remove three and a half glands. The remnant half gland can be left in situ or implanted into the sternocleidomastoid muscle. In some patients with secondary or tertiary hyperparathyroidism, total parathyroidectomy with subcutaneous forearm autotransplantation is recommended.[28] 
3. For patients with multiple endocrine neoplasia (MEN) type 1-associated PHPT, the initial surgical procedure usually includes resection of three-and-one-half hyperplastic parathyroid glands (subtotal resection) with strong consideration for concomitant cervical thymectomy. For patients with MEN type 2A-associated PHPT, parathyroid hyperplasia is heterogeneous; bilateral exploration is usually performed as the initial procedure, only the visibly enlarged glands are resected. For patients with MEN type 2A-associated recurrent hyperparathyroidism, a complete parathyroidectomy with forearm autotransplantation is typically performed.[6]
4. Parathyroid carcinoma should be completely resected, requiring en bloc resection of the parathyroid mass, and any adjacent tissues have been invaded. Complete surgical resection with microscopically negative margins is the recommended treatment and offers the best chance of cure.[29]

Complications

Postoperative Bleeding and Hematoma

Postoperatively life-threatening hematoma is rare but is a serious complication; the incidence reported was 0.6%.[30] The hematoma compresses the trachea, causes venous congestion of airway structures and subsequent airway compromise.  Immediate wound opening and surgical hematoma evacuation or re-exploration are indicated to alleviate airway compression. Intubation should not be delayed.

Recurrent Laryngeal Nerve Injury

Recurrent laryngeal nerve injury is one of the most feared complications of parathyroid surgery. Injury to the recurrent laryngeal nerve results in paresis or palsy of the vocal cord, causing hoarseness (unilateral damage) or stridor, airway occlusion (bilateral damage), and an increased risk of aspiration, may need immediate reintubation or occasionally tracheostomy. Most recurrent laryngeal nerve injuries are transient. 1.1% of the patient presented a permanent postoperative vocal cord paresis after thyroid and parathyroid surgery due to recurrent laryngeal nerve injury. Injuries after parathyroidectomy are less frequent compared to thyroid surgery. Most patients with transient postoperative recurrent laryngeal nerve injury recovered normal vocal cord mobility within six months.[31] Identifying the recurrent laryngeal nerve during thyroid dissection is the gold standard to avoid nerve injury.[32] 

Intraoperative nerve monitoring during parathyroidectomy is a promising adjunct to visualization alone in detecting nerve structures during neck dissection, which may decrease the likelihood of recurrent laryngeal nerve injury.[33] A reinnervation procedure should be attempted When recurrent laryngeal nerve transection is recognized during parathyroidectomy.[6]

Hypoparathyroidism and Hypocalcemia

The symptoms of postoperative hypocalcemia include perioral numbness, fingertip paresthesia, Chvostek’s sign, Trousseau’s sign, and severe symptoms including tetany, cardiac dysrhythmia, seizures. Most hypocalcemia is transient, and permanent hypocalcemia is reported in only 0.5% to 3.8% of cases.[34] One of the most common causes of postsurgical hypoparathyroidism and hypocalcemia is inadvertent removal of, damage to, or inadvertent devascularization of the parathyroid glands.  Postoperative hypocalcemia may be due to “Hungry bone syndrome” with low serum calcium levels resulting from remineralization of the bone as the stimulus of PTH for high bone turnover is removed after parathyroid surgery.[35] As the American Association of Endocrine Surgeons Guidelines recommends, patients with transient postoperative hypoparathyroidism should be treated with calcium and, if necessary, calcitriol supplements, which should be weaned as tolerated. Patients with prolonged hypoparathyroidism may be considered for recombinant PTH therapy.[6]

Persistent or Recurrent Hyperparathyroidism

Persistent/recurrent hyperparathyroidism occurs in 2% to 5% of patients with sporadic primary hyperparathyroidism.[36] Persistent hyperparathyroidism should be defined as a failure to achieve normocalcemia within6months of parathyroidectomy. Recurrent hyperparathyroidism is defined by the recurrence of hypercalcemia after a normocalcemic interval at more than six months after parathyroidectomy.[6] 

The most common causes of persistent/recurrent hyperparathyroidism include unrecognized four gland hyperplasia, ectopic location of the hyperfunctioning parathyroid gland(s), or operations performed by inexperienced or low-volume parathyroid surgeons.[37][38] A final intraoperative PTH level greater than 40 pg/mL was associated with an increased risk of persistent and recurrent disease irrespective of the number of glands resected.[36] 

The subsequent operation for persistent or recurrent hyperparathyroidism is often recommended to achieve a biochemical cure. But the indication is stricter than initial surgery due to lower cure rates and higher risks in the subsequent operation. Preop evaluation should be made by an experienced parathyroid surgeon, including confirmation of biochemical diagnosis, assessment of indications for surgery, review of prior records if available, and evaluation of RLN function.[6]

Clinical Significance

Parathyroidectomy is the definitive therapy for primary hyperparathyroidism but may also be necessary in secondary or tertiary hyperparathyroidism. Bilateral neck exploration is the standard operation, especially optimal for patients who have multiple gland disease or non-localizing preoperative imaging studies. With improved preoperative localization techniques and intraoperative PTH monitoring, minimally invasive parathyroidectomy is widely used in unilateral exploration. Even a four-gland exploration can be performed in a minimally invasive fashion.[39]

Enhancing Healthcare Team Outcomes

Parathyroidectomy involves a multidisciplinary team to achieve the best clinical outcome. The team includes surgeons, radiologists, pathologists, anesthesiologists, operating room nursing staff. This joint patient management minimizes the delay from diagnosing to operation decision, leading to efficient pre-operative imaging localization, ensuring patient suitability for surgery, managing intraoperative nerve monitoring and PTH level monitor, and optimizing postoperative care.

Nursing, Allied Health, and Interprofessional Team Interventions

Nurses have an important role in the support, education, and care of patients undergoing parathyroidectomy. Preoperative nursing interventions involve routing nursing physiological observations, offering patients psychological support, and education about disease and surgery.

Nursing, Allied Health, and Interprofessional Team Monitoring

Nurses are especially crucial in postoperative patient safety involving hemodynamical monitoring, fluid balance, and electrolyte measurement. In particular, nurses must be aware of potential postoperative complications, including signs of recurrent laryngeal nerve injury, signs of hypocalcemia, neck hematoma. If the patient is discharged with medication, especially opioids, the nurse needs to review these medications with the patient for safety purposes.