Surgery is the only definitive treatment available for primary hyperparathyroidism. Surgical management is clearly indicated in symptomatic patients. In addition, the consensus guidelines of the 4th international workshop provide indications for surgery in “asymptomatic“ patients. These include: 1) significant elevation in serum calcium (>1.0 mg/dL above the upper limit of normal); 2) significant skeletal manifestations demonstrated by reduced bone mineral density (T-score <-2.5 at spine, hip or distal radius), or imaging detected vertebral fractures); 3) significant renal manifestations, including kidney stones (clinically apparent or imaging detected), reduced creatinine clearance (<60cc/min), elevated 24hr urine calcium (>400 mg/d) in conjunction with an adverse biochemical stone risk analysis or nephrocalcinosis on imaging; or 4) age <50 yrs. Treatment of patients that do not meet these criteria is less clear. Patients with neurocognitive symptoms may experience improvement in these symptoms following surgery, but this is less predictable. Medical management may be preferred in carefully selected patients with mild, asymptomatic disease.
The surgical approach to primary hyperparathyroidism has evolved with the understanding of disease etiology and the advent of new techniques and surgical adjuncts. In general, surgical techniques can be divided into: 1) bilateral/4-gland exploration; and 2) focused approaches. More important than the technique or surgical adjuncts used is the experience and volume of the surgeon and team. Higher volume, specialized parathyroid practices have been associated with improved outcomes/lower morbidity.
Four Gland Parathyroid Exploration (Bilateral Exploration)
The traditional approach to parathyroid surgery is the bilateral neck exploration. The surgeon explores both sides of the neck, attempts to locate all glands and remove all or most (in the case of multi-gland hyperplasia) of the abnormal parathyroid tissue. Abnormal parathyroids are determined via the surgeon’s assessment of the size and appearance of each gland. Biopsies may be performed depending on surgeon preference, experience, and the clarity of surgical findings. Routine biopsy of all four glands is not required and may result in higher post-operative rates of hypocalcemia. In experienced hands, this approach leads to excellent cure rates in the range of 95-98%. This is typically done though a cervical incision located low or mid neck and slightly curved to match the natural lines of the skin (for best cosmetic results). The size of incision is largely determined by the need for safe exposure of the anatomy, but most experienced surgeons can perform this operation through a relatively small (<2 inch) incision. The duration of the surgery is largely dictated by the complexity of the surgical findings and can range from 20 minutes to several hours. When a bilateral exploration is planned, pre-operative localization studies and operative adjuncts are not mandatory but may be used by some surgeons to guide the operation.
Directed Parathyroidectomy (Focused or minimally invasive exploration)
The traditional bilateral exploration is a safe surgical procedure with excellent outcomes in experienced hands. However 80-85% of patients with primary hyperparathyroidism have a single adenoma as the cause. Thus, more focused operations have been developed with the goal of reducing operative time and extent of dissection, potentially leading to reduced postoperative pain, shorter length of stay, improved cosmesis, and less post-operative hypocalcemia. Pre-operative localization is mandatory if a focal approach is used. Most commonly, a focused approach refers to the image-guided identification and removal of a single abnormal gland. Some surgeons may perform a unilateral exploration in which both glands on the side of the localized gland are identified. The observation of a normal gland on the side of the localized gland further reduces the likelihood of multi-gland disease. Of note, the term minimally invasive parathyroidectomy (MIP) has not been used exclusively to refer to focal explorations, with some centers describing a bilateral exploration through a small incision under this heading. A focused exploration may be performed through a small central incision or a lateral incision over the site of the localized gland. In appropriately selected patients, the immediate outcomes of a focused approach are similar to a bilateral exploration. These finding have led to a rapid increase in the utilization of this technique. More recently, a few reports of a potentially increased late recurrence rate following focal exploration has led some centers to re-examine their indications for focused surgery to ensure appropriate patient selection. Some centers continue to offer, or have returned to, routine bilateral exploration for all patients. Appropriate patient selection is key, with bilateral exploration preferred or required in patients with non-localizing or discordant imaging, suspicion of a hereditary cause of hyperparathyroidism, and in patients with a history of lithium use.
Several surgical adjuncts have been developed to guide or inform decision making during parathyroidectomy. While many of these were developed to facilitate a more focused approach, they may also be used during bilateral explorations to inform intraoperative decision making.
Intraoperative Parathyroid Hormone Monitoring
Intraoperative PTH monitoring (IOPTH) is perhaps the most widely used surgical adjunct in parathyroid surgery. Given the short half-life of PTH in the circulation (3-4 minutes), a rapid assay for PTH samples providing real-time intraoperative information may support the appropriateness of single gland resection via a focused approach. The Miami criteria, a >50% drop from the highest pre-resection level by 10 minutes is commonly used to indicate a successful single gland resection. In addition, a return of the PTH level to within the normal range provides further reassurance. However, IOPTH is not perfect, and both false positive and false negative results have been encountered. As well, the IOPTH results take time (10-40 minutes) to be reported and can thus extend operative time. When a bilateral exploration is utilized, IOPTH is not required but may be used to guide the operation. When multi-gland disease is found, IOPTH has been shown to accurately indicate an appropriate extent of resection.
Radioguided Parathyroid Surgery
A small-dose injection of Tc99-Sestamibi on the morning of surgery may allow the use of a handheld gamma probe to guide various aspects of parathyroidectomy. This information may then guide: 1) positioning of the incision in a focused, single gland operation; 2) identification of hyperactive parathyroid glands intraoperatively (including ectopic glands and in re-operative cases); 3) confirmation that tissue removed is hyperactive parathyroid; and 4) clarification of misleading pre-operative localization (e.g., sestamibi-avid thyroid nodules). The benefits of this technique have been debated, and its use is largely based on surgeon preference. As with all adjuncts, these tools are not a replacement for surgeon knowledge and experience.
This adjunct refers to the use of an endoscopic camera to facilitate a minimally invasive approach. Essentially, the camera provides exposure, lighting, and magnification which may facilitate the use of a smaller incision. In experienced hands, this approach is safe and effective. It may facilitate a less invasive approach but requires more equipment (with associated cost) and may lengthen OR time.
In 80-85% of patients, a single gland adenoma will be found. Thus 15-20% of patients will have multiple abnormal parathyroid glands. 10% will have hyperplasia of all four glands. While single or double adenomas can be treated by resection of the abnormal glands, multi-gland hyperplasia presents an additional challenge. Most commonly, a subtotal parathyroidectomy (removal of three and a half glands, leaving a vascularized remnant of appropriate size) is performed. Additionally all glands can be removed and a small portion can be auto-transplanted to provide adequate parathyroid function. In these cases, given the greater extent of glands removed and the need to leave abnormal parathyroid tissue behind, the chance of post-operative hypoparathyroidism and recurrence are both increased. In some hereditary syndromes, additional glands may be more common, and cervical thymectomies may be required to ensure these are not left behind.
Parathyroid autotransplantation involves the reimplantation of parathyroid tissue into the body. This may be required in patients with multi-gland hyperplasia requiring resection of all four parathyroids. The tissue is “minced” into small pieces and placed in a muscle. Most commonly, auto-transplantation following parathyroidectomy will be due to multi-gland disease and resection of all glands. As such, the tissue is by definition abnormal and as such would typically be placed in a forearm muscle. This site, remote from the neck is used due to ease of access should recurrence occur secondary to the graft. Breaking down the parathyroid tissue into smaller pieces facilitates diffusion required to nourish the parathyroid tissue until a blood supply is established. These transplanted parathyroid glands often take 4-6 weeks to function. In the interim, the patients will require oral calcium and cacitriol supplementation. Some patients will require IV calcium.
Cryopreservation of Parathyroid Tissue
In instances of uncertainty regarding the volume or function of remaining parathyroid tissue (typically multi-gland disease and re-operative cases), some of the removed parathyroid tissue can be cryopreserved to provide a margin of safety against permanent hypoparathyroidism. This involves freezing the resected tissue. If the patient develops ongoing hypoparathyroidism following surgery, the tissue can be thawed, minced, and re-implanted. Interestingly, the rate of implantation of cryopreserved tissue is low. In addition, there are costs associated with this procedure, and the success rate is variable; few centers offer this option. As a result, it should be used selectively as determined by an experienced parathyroid surgeon.
Parathyroidectomy can be performed under general or local anesthesia. The choice may depend on the practice pattern of the center/surgeon, comorbidities, patient preference, and the operative plan. Most patients tolerate general anesthetic quite well. An endotracheal tube or LMA airway may be used. There may be an increased incidence of post-operative sore throat and nausea associated with general anesthesia. Local anesthetic involves the use of a regional nerve block and local infiltration typically with a combination of long and short acting anesthetic. Additional sedation may be used for patient comfort. Similar to endoscopy, the patient under sedation may not remember the operation. A small portion of patients will be transitioned to a general anesthetic due to discomfort, anxiety, or excessive movement during the operation. Local anesthetic may reduce post-operative nausea and avoids the use of an endotracheal tube with its potential to cause sore throat and irritation of the vocal cords.
Risks and Potential Complications of Parathyroid Surgery
Like all surgical procedures, parathyroidectomy has some associated risks. Aside from the general risks associated with surgery and anesthesia, specifics risks discussed with the patient prior to parathyroidectomy would include: 1) recurrent laryngeal nerve injury; 2) hypoparathyroidism/hypocalcemia; 3) neck hematoma; and 4) wound infection. Surgical risks vary with the experience and volume of the surgical practice. That is to say, high volume surgeons typically have lower complication rates. Complication rates may also be higher in the setting of re-operative neck surgery. General surgical complications including cardiopulmonary problems and venous thromboembolism are fortunately very rare following parathyroid surgery.
Recurrent Laryngeal Nerve Injury
The recurrent laryngeal nerves, branching from the vagus nerves, travel in proximity to the tracheoesophageal grooves bilaterally. They are in close proximity to the parathyroid glands. Damage to one of these structures results in hoarseness of the voice. Permanent damage is rare, occurring in less than 1% of procedures (in experienced hands). Temporary injury secondary to stretch or local irritation may occur (3-5%). In temporary injury, the voice will return to normal, but this may take days, weeks or even months to occur. A patient with post-operative hoarseness without documentation of an observed injury to the nerve intraoperatively should be followed. If the voice does not return to normal by 6 months, the vocal cords should be assessed. In the unfortunate case of permanent nerve injury, a number of procedures and speech therapy are available to improve the strength and quality of the voice.
Post-operative hypocalcemia may occur following parathyroid surgery. This may be due to hypoparathyroidism resulting from removal of a significant mass of parathyroid tissue. Post-operative hypoparathyroidism may be temporary, resolving when residual supressed glands or those “stunned” by adjacent dissection return to normal function or when an auto transplant starts functioning. In rare cases, hypoparathyroidism may be permanent. Post-operative hypoparathyroidism that persists beyond six months is likely to be permanent. Fortunately, this is a rare phenomenon (<1%). Another potential cause of hypocalcemia post parathyroidectomy is “hungry bones.” In primary hyperparathyroidism, this is a rare occurrence usually seen in those with longstanding hyperparathyroidism and significant bone disease. The experienced parathyroid surgeon should be able to distinguish the potential causes of hypocalcemia based on the clinical context and the pattern of calcium, phosphate, and PTH values post-operatively.
Symptoms of hypocalcemia include numbness and tingling in fingers, toes, or around the mouth. In addition, with more significant drops in calcium, patients may experience muscle cramping. Clinical signs of hypocalcemia include Chvostek’s sign (tapping over the facial nerve root eliciting twitching at the ipsilateral corner of the mouth) and Trousseau’s sign (carpal-pedal spasm elicited by inflation of a blood pressure cuff above systolic for 2-3 minutes). The latter is seldom performed, as it can be quite painful for the patient. Routines for post-operative measurement of serum calcium (albumin corrected), phosphate, and PTH will be center dependent. Symptoms can be treated with oral calcium and vitamin D supplementation. If they do not resolve promptly or are more severe, serum measurement of calcium (+/- phosphate and/or PTH) should be performed to guide further management. Post-operative calcium and vitamin D supplementation may be utilized selectively (based on post-operative labs) or routinely to prevent hypocalcemia in discharged patients and to promote bone remineralization. If cryopreservation was performed, autotransplantation can be attempted in patients with permanent hypoparathyroidism
Significant post-operative bleeding is a rare complication following parathyroid surgery (<1%). However, a neck hematoma is potentially quite serious given the possibility of airway compromise from direct compression and swelling. To minimize the risk, “blood thinner” medications including antiplatelet agents, coumadin, heparin, and others should be held for an appropriate period of time prior to surgery if safe to do so. In some patients, continuing anti-platelet therapy through the surgical period may be required for cardiac risk mitigation. In addition, some supplements may contain ingredients that can increase bleeding risk. As such, it is prudent to discontinue potentially risky vitamins and herbal supplements for a period of time prior to surgery. Most hematomas tend to occur early after surgery (<6hrs). However, delayed bleeding has been observed even a week after surgery. An expanding neck hematoma requires prompt assessment by the surgical team.
Fortunately, wound infections are extremely rare following parathyroid surgery (<0.5%). No evidence exists to support the use of pre-operative antibiotics for surgical site prophylaxis in these patients. In the rare instance that a wound infection is suspected due to fever, redness, and swelling, prompt evaluation by the surgical team should occur.
Length of Stay
Parathyroidectomy may be performed as a day procedure or involve an overnight stay in hospital. The choice is often practice dependent and should take into account the patient’s comorbidities and early post-operative course. On rare occasions, patient factors or post-operative complications may require a more prolonged stay. Patients with a planned same-day discharge will be observed for an appropriate period of time to ensure they meet discharge criteria and do not develop significant complications. Early post-operative labs may be performed to inform the need for calcium supplementation. Patients admitted for an overnight stay will be monitored for complications and likely have blood work performed the following morning to assess for hypocalcemia.
Patients may experience incisional pain as well as a sore throat following parathyroid surgery. Both are typically mild. Surgeons may infiltrate long acting local anesthetic to facilitate early post-operative pain control. Most patient will be discharged with a prescription for a small quantity of narcotic-containing pain killer. These are typically needed for just 2-3 days. Some patients experience adequate pain control with non-narcotic analgesics such as Tylenol and NSAIDS. There are no specific restrictions on eating following parathyroid surgery; however, some patients will prefer softer foods for a few days due to a sore throat. Throat lozenges, cold drinks, and ice chips may also improve sore throat symptoms.
In addition to pain medications, some patients may be discharged on calcium and vitamin D supplements. Depending on the practice, these supplements may be routinely prescribed with the goal of avoiding post-operative hypocalcemia and enhancing bone remineralization. In other centers, calcium and vitamin D supplementation may be used selectively based on post-operative blood work. Calcium and vitamin D supplements can then be reassessed at a post-operative follow-up visit. Patients should be able to resume all of their previous home medications shortly after surgery.
Care of the Incision and Wound Healing
All surgical incisions result in a scar of some description. Neck incisions used in parathyroid surgery typically heal with excellent cosmetic results, particularly if they can be placed in a pre-existing skin crease. During the initial inflammatory and proliferative phases, the incision may be somewhat raised, irregular, and pink. The remodelling phase typically begins at around 21 days following surgery and may last for a full year. During this time, collagen remodelling results in an incision that flattens, softens, and more closely approximates the colour of the surrounding skin. Many patients will inquire about or wish to use vitamin E or other commercially available scar treatments. While clear evidence to support the efficacy of these treatments is lacking, they are unlikely to cause any harm. Patients should be instructed to use sunscreen, as excess exposure during the remodelling phase may result in a more noticeable scar.
Return to Work
Patients will be counselled about return to work by their surgeons. Time off work will depend on the surgical practice, the nature of the work, and the patient’s recovery. Recovery periods are commonly less than two weeks. Driving should be avoided until the patient is off narcotic medications and has full neck motion. Instructions to resume showering/bathing will be provided by the surgeon and vary according to practice and the type of closure used. Patients should ask their surgeon about any recommended travel restriction.
Follow-up Appointments After Surgery
Patients should schedule follow-up appointments with their surgeon as per the protocol of the particular practice. Post-operative calcium, PTH and other labs will likely be drawn at or prior to this visit. The incision will be inspected, pathology reviewed, and any additional patient questions can be addressed. Calcium, PTH, and other related labs will likely be done at 6 months following surgery, and the calcium level will then be monitored yearly. Bone mineral density scans may also be followed in patients with reduced bone density prior to surgery.