Hyperparathyroidism in Otolaryngology and Facial Plastic Surgery Treatment & Management

Controversy exists regarding the need and timing of surgery in asymptomatic patients who have slow progressive parathyroid disease. If patients are to be medically observed, the potential renal and bone disease should be periodically assessed.

In patients who are not candidates for surgery, ultrasound-guided alcohol ablation and angiographic embolization are considerations.

Medical management of hyperparathyroidism is generally reserved for patients with poor medical conditions, advanced age with mild hypercalcemia, no evidence of dementia, and no significant bone demineralization. Serum calcium levels should be only mildly elevated, and renal status, bone density, and bone mass should be normal. Severe hypercalcemia (> 14mg/dL) may be a medical emergency, and the initial treatment requires intravenous saline infusions, diuresis, calcium binders and bisphosphonates.) Medical follow-up care may also be indicated when neck exploration has not been successful.

Medical follow-up care should include biannual measurements of serum calcium levels, parathyroid hormone (PTH) levels, and bone mass, as well as assessment of renal status. Ask patients specifically about symptoms of weakness, fatigue, and depression.

The surgical procedure selected to remove the pathologic gland or glands depends on the philosophy and experience of the surgeon and the nature of the disease in each patient. A focused parathyroidectomy is effective in most cases; however, some controversy exists regarding the following procedures:

• Unilateral versus bilateral explorations in patients with primary hyperparathyroidism
• Total parathyroidectomy versus seven-eighth parathyroidectomy in patients with chronic renal failure or diffuse, nonrenal hyperplasia.

Adenoma and hyperplasia

Parathyroid adenomas vary in size and shape and are often bilobed. A halo of fat, at least at one pole, usually surrounds parathyroid adenomas and aids in identification. The gland often turns red-brown when manipulated, probably because of vasospasm of its feeding artery.

Classical surgical approach

This technique was most often performed between 1930 and 1960. The standard, time-honored (but dated) approach uses a typical thyroidectomy collar incision with wide exposure. The upper and lower subplatysmal flaps are raised, and the anterior cervical veins are not ligated and are left on the anterior surface of the strap muscles. The strap muscles are separated in the midline, exposing the thyroid isthmus. On the side to be dissected, the area lateral to the inferior thyroid veins is explored first, and an inferior adenoma is often visible with minimal dissection. If an inferior adenoma is not visible, the lateral aspect of the thyroid lobe is rotated anteromedially and the superior gland is usually seen on the posterior superior surface of the lobe. When present, the middle thyroid vein may require ligation.

The inferior thyroid artery (ITA) is identified just medial to the carotid artery, and a vessel loop is placed on the ITA. The artery is followed medially, and the recurrent laryngeal nerve (RLN) is always identified passing either over or under the artery. With careful dissection, the distal branches of the artery can be seen feeding each normal or pathologic parathyroid gland. Before the gland is removed, the RLN is followed to its point of entry into the cricothyroid membrane. Bleeding is usually minimal with this technique; minimal bleeding is controlled with bipolar cautery. The distal arterial branches are tied, when necessary.

Once the adenoma has been removed and sent for frozen section diagnosis of parathyroid tissue, the ipsilateral gland is identified. If the gland appears normal, it is not disturbed. If the gland is enlarged, biopsy is performed, and the specimen sent to confirm the presence of hyperplasia. If both glands are found to be hyperplastic, the opposite side of the neck is explored. If the 2 contralateral glands are confirmed as hyperplastic, most surgeons perform either a seven-eighth parathyroidectomy or a total parathyroidectomy with autotransplantation of a small fragment into forearm musculature for easy access in the future.

General endotracheal anesthesia was standard. Operative time was longer since a bilateral exploration was done. A postoperative drain was routinely used and an overnight stay was typical.

Minimally invasive approach (targeted parathyroidectomy, focused parathyroidectomy, selective parathyroidectomy)

This technique became popular in the 1990s and is most often used today. This approach was pioneered by the noted Norman Parathyroid Center in Tampa, Florida. A small transverse incision is placed in the lower neck, in the midline, or off the midline on the side of the adenoma. Both ipsilateral parathyroid glands can be reached through a small incision off the midline incision with aggressive retraction. A bilateral exploration can be performed through the small midline incision. The dissection is minimal and exposure may be limited. The amount of dissection may be further reduced if intraoperative PTH monitoring or intraoperative radioguidance is used. In the off-midline approach, instead of separating the strap muscles in the midline, the lateral aspect of the sternothyroid and sternohyoid muscles are separated from the medial border of the sternocleidomastoid muscle. The carotid sheath is exposed and the adenoma removed.

This approach can easily be performed with laryngeal mask anesthesia or under local anesthesia with intravenous sedation in carefully selected patients. This approach has been proven to be safe in adult patients of all ages, including elderly persons.^[8] Morbidity is reduced. A drain is not required. Operative time is further reduced, and often the patient can be discharged from the same-day unit or postoperative care unit within an hour or 2 after surgery, even in morbidly obese patients. Preoperative loading and postoperative administration of oral calcium citrate makes postoperative hypocalcemia extremely unlikely.^[9]

There is no learning curve for this technique in the hands of an experienced parathyroid surgeon.

In 2009, the Norman Parathyroid Center presented their findings and recommendations regarding unilateral and bilateral exploration in primary hyperparathyroidism.^[10] That center is devoted to parathyroid surgery and performs 1800 parathyroidectomies per year (13/day, 3 days/wk). They have a first-operation cure rate of 99.5%. They reviewed 3000 consecutive primary parathyroid operations over a 20-month period and listed 18 objective factors that influence the decision for unilateral versus bilateral surgery. Their surgical approach is worth noting and includes the following:

• Laryngeal mask anesthesia (no endotracheal intubation)
• No use of local anesthesia
• Propofol and midazolam as priming agents
• No recurrent laryngeal monitoring
• Two- to 2.5-cm midline horizontal incision in the lower neck
• All operations take place within 2 hours of sestamibi scanning on the morning of surgery (no preoperative scanning).
• Ultrasound is not performed (but may have been performed by the referring endocrinologist).
• No intraoperative PTH monitoring is performed.
• The gamma probe is used ex vivo and is not used in the wound; any gland that is physiologically overactive is marked for removal. Abnormal activity by the probe is the only criterion used for gland removal.
• No frozen sections are performed.
• At least 2 glands are always assessed and a biopsy specimen it taken from the ipsilateral gland for permanent section.
• Ipsilateral thyroid abnormalities are always examined and pathology is removed.
• If a unilateral exploration becomes a bilateral exploration, the operative time increases by only 5 minutes.
• All patients are discharged from the recovery room.

Using these techniques, 21% of patients had more than 1 gland removed, most commonly a second adenoma (9.8%), followed by a clinically enlarged, nondormant gland (9.3%), followed by 4-gland hyperplasia (2.1%), followed by 3 adenomas (0.6%). They achieved a 99.9% cure rate, which could never be obtained with a focused, single-gland exploration. There were certain preoperative criteria that always indicated a bilateral exploration. The most common were the following:

• Multiple endocrine neoplasia syndromes
• Teenagers (high risk of multiple adenomas)
• Familial hereditary hyperparathyroidism

Renal (secondary) hyperparathyroidism

Generally, but not always, diffuse hyperplasia of all 4 glands is present. The glands may be voluminous and weigh in excess of 100 grams. The classic surgical approach is used. Each RLN is identified. All abnormal parathyroid tissue is removed. When fewer than 4 glands are hyperplastic, the normal sized glands may be left intact. When 4 large hyperplastic glands are removed, a small fragment of one gland may be reimplanted into a forearm muscle or strap muscle. The treating nephrologist often prefers reimplantation in order to preserve some parathyroid function. Total postoperative hypoparathyroidism is more debilitating and more difficult to medically manage than an autotransplanted patient with a small fragment of revitalized parathyroid tissue.

Tertiary hyperparathyroidism

In patients with tertiary hyperparathyroidism, the residual tissue or adenoma is usually identified preoperatively with ultrasonography and sestamibi scan, allowing rapid access to the involved area. Scarring from prior surgery can be problematic and may place the RLN at risk of iatrogenic injury. The surgical approach in this situation is to proceed to the localized site immediately and to remove the lesion with as little dissection as possible. The RLN may not be routinely exposed, especially if severe scarring is present from prior surgery. This surgery usually removes all remaining parathyroid tissue and results in permanent hypoparathyroidism.

Parathyroid carcinoma

When the rare parathyroid carcinoma is encountered, the goal is wide local excision with selective neck dissection, which allows removal of metastatic nodal disease and all involved soft tissues. The mass is usually large, gray-white, and locally invasive. Aggressively removing the mass, along with the ipsilateral thyroid gland and adjacent soft tissue, is required. Postoperative radiotherapy may be necessary in cases with residual tumor. Patients with recurrent parathyroid carcinoma can be identified based on rising PTH levels.

Familial parathyroid disorders

As mentioned above, the hereditary parathyroid disorders require an advanced knowledge of the genetics of transmission, associated conditions, and special treatment considerations (see Table 2).

Table 2. Surgical Therapy in Patients With Hereditary Parathyroid Disorders (Open Table in a new window)

Ancillary intraoperative tools

• Intraoperative rapid PTH monitoring (i-PTH): Although intraoperative rapid PTH monitoring is not necessary for routine cases in which the location of the adenoma is preoperatively known, it may have special value in reexplorations and when a second adenoma is suspected. The chemoluminescent immunoreactive technique has demonstrated PTH to have a half life of 3-5 minutes. The circulating PTH level has been shown to be reduced by 50% within 10 minutes following successful removal of an adenoma. Additional equipment, time, and expense are necessary. A venous baseline sample is taken prior to the skin incision and then at 5 and 10 minutes after specimen removal. The turnaround time for results, in the best of hands, is 10-15 minutes.
• Intraoperative total serum calcium monitoring: In all cases, the serum calcium level has been shown to drop within 5 minutes of successful removal of a parathyroid adenoma. Calcium monitoring is less expensive than i-PTH monitoring and is readily available in all hospitals.
• Intraoperative sestamibi radiomonitoring (gamma probe):^[11] Minimally invasive radioguided parathyroidectomy requires that surgery be performed within 1.5-3 hours after the injection of sestamibi so that the adenoma still has a high gamma emission. The hand-held probe guides the surgeon to the area of increased activity. The excised specimen still emits radioactivity greater than 20% of the background check.
• Endoscopic parathyroidectomy

  • The pure endoscopic approach requires preoperative localization of a single adenoma. The technique is contraindicated in patients with a history of prior neck surgery, prior neck radiation, abnormal anatomy, and multigland disease. Reported complications include dramatic subcutaneous emphysema from chin to scrotum. Hypercapnia and tachycardia have also been reported. Exposure is limited and the working space is small.
  • A video-assisted technique uses carbon dioxide insufflation for only 3 minutes at the start of the procedure and begins the dissection under the strap muscles. A small skin incision (1.5 cm) in the midline is made and used to perform the parathyroidectomy on the video monitor.
  • Gasless video-assisted robotic parathyroidectomy is being performed, but reference is made to a substantial learning curve and mean exposure and docking times ranging from 31-51 minutes, which exceeds the normal time for other approaches by experienced parathyroid surgeons. This technique avoids the problems of carbon dioxide insufflation of the neck and complications related to insufflation. Robotic console times ranged from 25-105 minutes for single adenoma removal.^[12]
• Transaxillary and submammary endoscopic approaches: More reports now describe transaxillary and submammary endoscopic approaches to parathyroid disease that use laparoscopic techniques.

Monitoring of serum calcium levels and management of hypocalcemia were the traditional tasks of postoperative care. This is minimized by preoperative calcium and vitamin D loading. This author also adds calcium carbonate to the intravenous solution being administered in the operating room. In addition, modern minimally invasive techniques, even with bilateral explorations, now allow all but the most complicated patients to be discharged within hours of surgery. Prevention of a wound seroma with an appropriate closed suction drain may be necessary if bleeding has been encountered, but this is usually not necessary. The skin is approximated with a skin adhesive (Dermabond). Wound healing is delayed in patients with renal disease.

Transient hypocalcemia in patients with primary hyperparathyroidism is generally mild, and the serum calcium level slowly drops and gradually returns to normal without tetany. Oral calcium supplements may be given for a period of weeks with calcitriol (Rocaltrol) 0.25 mg 2 or 3 times per day to enhance GI absorption.

Dramatic hypocalcemia due to severe bone hunger is observed in patients with secondary and tertiary parathyroidectomy due to marked calcium depletion from bone, which is often rapidly and acutely reversed in the first few hours postoperatively in patients with chronic renal disease. Hungry bone uptake of ionized serum calcium is so swift that a continuous calcium infusion is often needed to avoid tetany. Continuous calcium infusion is required until oral calcium and vitamin D supplements begin to maintain the serum calcium levels near the reference range. Calcitriol (Calcijex) injection during dialysis is often required.

Calcitriol (the active form of vitamin D-3) injection in patients with renal disease, a population in whom treatment proves difficult, stimulates intestinal calcium absorption and aids in the treatment of chronic hypocalcemia.

A primary care physician or surgeon observes patients with primary hyperparathyroidism annually to monitor serum calcium levels; patients with genetic parathyroid disorders may develop a second adenoma or recurrent hyperparathyroidism.

Patients with chronic renal disease are monitored indefinitely because of the nature of their disease and its intimate relationship to kidney disease and phosphorus retention.

Transient hypocalcemia is anticipated but may be mild and without clinical signs. This is especially true if the patient is preloaded with calcium citrate and vitamin D for 1-2 weeks prior to surgery. Difficult-to-manage severe hypocalcemia can lead to tetany if not treated. Permanent hypoparathyroidism and recurrent laryngeal nerve injury are also potential complications. If the adenoma is not found or if a second adenoma is not identified, hypercalcemia will persist.

Successful exploration and removal of an adenoma is curative, and the abnormal calcium metabolism is quickly reversed. However, soft tissue calcifications may resorb very slowly. Nephrolithiasis requires continued urologic management. Somatic symptoms such as fatigue, joint pain, and mental changes are often quickly eliminated. Some patients report an excellent and dramatic sense of well-being shortly after surgery.

Successful treatment of secondary and tertiary hyperparathyroidism is equally rewarding for both surgeon and patient. These patients generally feel much stronger and less depressed and are pleased with the elimination of pain from bones, joints, and soft tissue calcifications. Relief from disabling pruritus is an additional benefit.

As with all surgical modalities, improvements and refinements are always on the horizon. Although innovations may have value in specific cases, most patients with hyperparathyroidism can be successfully managed with the standard methods described above (see Treatment).

CT scan or ultrasound-guided needle localization and ablation of adenomas with alcohol may have value in elderly patients with severe hypercalcemia who are very ill and who cannot endure parathyroidectomy under local or general anesthesia.