Minimally Invasive Surgery of the Parathyroid
In the past, parathyroidectomy involved an open procedure with a neck incision not unlike that used for a thyroidectomy, and it required the inspection of all 4 parathyroid glands, with removal of the offending gland or glands. Its major indication is for primary hyperparathyroidism, and usually the largest parathyroid was suspected and removed. Eventually, the use intraoperative physiologic studies improved the likelihood that the offending gland or glands were removed. Concurrently, there has been a push from the public as well as within the surgical community for less and less invasive procedures, with a goal of decreased recovery time, increased cosmesis, and decreased operative time and complications.
This article discusses minimally invasive techniques for parathyroidectomy (MIP) with a focus on minimally invasive radioguided parathyroidectomy (MIRP).
A detailed description of the relevant embryology and anatomy can be found in Parathyroid Gland Anatomy. The parathyroids are derived from the third and fourth pharyngeal pouches. The inferior parathyroids come from the third pharyngeal pouch and follow the descent of the thymus until they rest on the dorsal surface of the thyroid, usually in a plane anterior to the superior parathyroids. In contrast, the superior parathyroids develop from the fourth branchial arch and descend into the neck with the thyroid gland.
There are usually 2 glands on each side of the thyroid, although 3-7% of the population may have an accessory (or supernumerary) parathyroid, and 3-6% may have fewer than 4 glands. The glands may occasionally descend incompletely, or too far, and lie in aberrant locations, including the anterior or posterior mediastinum, the bifurcation of the carotids, or in the retroesophageal, retropharyngeal, or retrolaryngeal regions. The inferior thyroid artery usually provides the vascular supply for both the superior and inferior parathyroid glands, although 20% of superior parathyroids may be supplied solely by the superior thyroid artery. 
Intrathyroidal parathyroid glands are described, although there is some controversy surrounding their existence. Some state that these parathyroids are not truly within the thyroid but instead are extracapsular, with the thyroid surrounding it. Others describe true intrathyroidal parathyroids with an incidence of 0.5-3%. 
The primary indication for a parathyroidectomy is primary hyperparathyroidism. Classically, these patients are referred to an otolaryngologist’s practice from either the primary care physician or endocrinologist.
These patients are described as having signs and symptoms following the mnemonic “bones, stones, groans, and psychiatric overtones”—including skeletal complications (pathologic fractures, osteitis fibrosa cystic, osteoporosis), renal disease (nephrolithiasis, nephrocalcinosis, diabetes insipidus, renal failure), gastrointestinal symptoms (constipation, nausea, vomiting), and psychiatric (mood swings, depression, psychosis) and central nervous system (lethargy, ataxia, delirium) manifestations. 
Many patients, however, present only with signs of elevated serum calcium and parathyroid hormone (PTH) levels and subtle symptoms of fatigue, depression, emotional lability, joint pain, or abdominal pain. 
Previous radiation exposure to the head and neck has been a listed contraindication to minimally invasive procedures, secondary to the increased risk of multiglandular disease and the possibility of coexisting thyroid cancer.  However, Rahbari et al performed a prospective cohort study to determine the effectiveness of MIP, and they show no significant differences between the presence of concurrent thyroid diseases, multigland parathyroid disease, or eventual operation chosen between the cohort that had a history of head and neck radiation and the cohort that had no exposure to radiation. 
For patients with multiglandular disease, a minimally invasive approach may not be practical or indicated. Additionally, it is important to distinguish patients with familial hypocalciuric hypercalcemia from patients with true primary hyperparathyroidism, as the first group would not benefit from a parathyroidectomy.
As part of the preoperative planning for MIP, it is important to localize the offending parathyroid gland. At the authors’ institution, patients undergo a double-phase technetium Tc-99m (99m Tc)  sestamibi scan, either alone or as 3-dimensional nuclear imaging fused with CT of the neck (single-photon emission computed tomography [SPECT]) preoperatively.99m Tc sestamibi is a radiotracer that is localized by the mitochondria of the parathyroids, and, by performing a delayed scan, those parathyroids with retained tracer are concerning for adenoma.
A recent meta-analysis by Cheung et al compared a variety of imaging studies to aid with localization and determined that SPECT had a pooled sensitivity and positive predictive value of 78.9% and 90.7% based on 9 studies, with a range of sensitivities between 61.4% and 100% in the studies analyzed. For patients who localize to one gland, MIP is offered, with the caution that a parathyroid exploration may still be necessary based on intraoperative findings. 
Miyabe described the use of 3-dimensional ultrasonography, which provides coronal images similar to a surgeon’s view, and determined a lower operative time when compared with traditional 2-dimensional ultrasonography. 
Aside from the use of a radioactive tracer, ultrasound is commonly used to identify parathyroid adenomas, although its use is subject to operator technique and interpretation. Sensitivities ranged from 48.3-96.2% in the studies analyzed in the meta-analysis by Cheung et al. The pooled sensitivity for ultrasound based on 19 studies was 76.1% and 93.2%, respectively. 
Another novel approach described by D’Agostino et al was recently published and used a 3-dimensional rendering of a CT scan that is then used intraoperatively to help with localization. The patient has a CT scan performed with neck extension and the rendered scan is overlaid over a visual image of the patient’s neck in the operating room. A separate technician is used to aid with manipulation of the rendered scan as it pertains to the operation. The authors describe a 77.2% and 64.9% accuracy of the CT scan with regard to correct identification of laterality and location, respectively. 
The reported outcomes from parathyroidectomy for primary hyperparathyroidism are very positive, with success rates nearing 100%. Adil et al reported 100% of patients who underwent MIP had a hyperfunctional parathyroid identified and excised, with appropriate drops in intraoperative PTH levels.  Beyer et al reported 100% rates of eucalcemia (cure) at 3 months amongst bilateral neck exploration and 99% amongst MIP surgery, with 1 failure. Additionally, they found lower costs, operating time, and length of stay in the hospital to be associated with the minimally invasive approaches.  A more recent review by Schneider et al found no difference in outcomes between minimally invasive and open approaches, with the exception of increased transient hypocalcemia in the open approach group (1.9% vs 0.1%).  Leder et al reviewed the laryngeal physiology and acoustics of patients before and after MIP surgery and found not differences amongst a variety of parameters. 
At the authors’ institution, patients are asked to stop anticoagulating agents 3-5 days prior to surgery as long as it is not medically contraindicated.
Postoperatively, patients are usually discharged the same day. Patients are asked to perform routine skin care for their incision, including the use of hydrogen peroxide and an antibiotic ointment. Sutures are usually removed at the first postoperative visit within the first week. Shin et al compared outpatient parathyroidectomy in patients older and younger than 70 years and found no differences in complications, despite higher levels of creatinine and PTH levels in the elderly patients. 
Elements of informed consent
A key component of the consent process includes discussing the risk of recurrent laryngeal nerve (RLN) injury. Additionally, the authors obtain consent from the patient for a possible parathyroid gland exploration if there is a failure to localize the parathyroid adenoma or if evidence is found to suggest multiglandular disease intraoperatively. Other risks include persistent hyperparathyroidism, bleeding, infection, risk of hypocalcemia, scarring, and the risks of anesthesia.
When performing MIRP, the authors have the patient undergo a second [2, 13, 14] technetium sestamibi scan, using 20 mCi of radiotracer and image acquisition 15 minutes and 2 hours after injection. The skin overlying the suspected hyperactive gland is marked with a felt pen.
The authors use the following tools during surgery:
Basic head-and-neck set – No. 3 knife handle, No. 15 blade, Adson tissue forceps with and without teeth, DeBakey Forceps, Halsted mosquito forceps, Rienhoff swan neck clamp (or burlisher clamp), Allis tissue forceps, Richardson retractor, peanut/Kittner sponges, double–pronged skin hooks
Weitlaner retractor (alternatively, other self-retaining retractors may be used)
Bovie electrocautery, harmonic scalpel, and/or Shaw scalpel
Bipolar electrocautery forceps
If intraoperative neural monitoring is to be performed – Nerve monitoring leads and surface electrode–primed endotracheal tube; nerve stimulator
The authors perform MIRPs with the patient under general endotracheal anesthesia, unless contraindicated.
Shindo et al reviewed MIP procedures performed using local anesthesia and intravenous sedation at their institution. The study found MIP could be performed safely using method of anesthesia, and they noted low complication rates as well as shorter operating times compared with when MIP is performed using general anesthesia.
The use of regional anesthesia via a cervical block has also been described in the literature. Miccoli et al compared bilateral deep cervical blocks with intravenous sedation to general anesthesia and found no significant difference in complications but also found shorter operating time and decreased postoperative pain with the use of regional anesthesia. 
Carling et al studied those cases requiring conversion to general anesthesia and found the conversions occurred secondary to concurrent thyroid lesions, evidence of multiglandular disease, or patient discomfort. In all cases (47 of 441), the conversion was performed in a safe, controlled manner. 
A previous report by Inabnet et al describes the use of local anesthesia without routine sedation during parathyroidectomy. The technique used local anesthetic injection to the skin, strap muscles, and thyroid capsule. 
The authors position the patient in the supine position with a rolled blanket or a gel pad under the shoulders to allow for extension of the neck.
If during surgery, intraoperative PTH values are being used, vials of blood for PTH levels should be sent immediately after removal of the specimen and 10 minutes after removal. As described in the literature, a drop in the PTH level of 50% is consistent with removal of the parathyroid adenoma. [18, 19, 20] Leiker et al reviewed PTH half-life and determined the median half-life to be approximately 4 minutes, and, although the half-life was affected by body mass index and age, this was not clinically significant. 
Intraoperative nerve monitoring (IONM) of the RLN can serve as an aid and adjunct to a minimally invasive procedure. While the RLN is not routinely identified during MIP, using IONM may help prevent a transient injury to the RLN. 
Harrison and Triponez reviewed common intraoperative techniques for primary hyperparathyroidism, including the use of intraoperative parathyroidectomy, gamma probe, frozen section, methylene blue, and IONM. The review notes level II evidence supporting intraoperative PTH monitoring for MIP and level IV evidence supporting the gamma probe or IONM. 
Depending on the surgical technique, lengths varying from 15-40 mm are described for the incision. Additionally, authors describe placing the incision 20-40 mm above the sternal notch within a skin crease, while others describe placing the incision in a skin crease overlying the suspected adenoma. [15, 16, 24, 25] The authors use a 15- to 25-mm incision placed midline at a level overlying the suspected adenoma (as marked during preoperative localization).
Two approaches to the parathyroid are described: an anterior approach and a lateral approach. Depending on the location of the parathyroid adenoma, as well as a history of prior neck operation, one approach may be preferred over the other. Shindo et al describe using a lateral approach when the parathyroid adenoma is located posterior to the thyroid lobe, inferior to the thyroid in a plane posterior to the thyroid lobe, or deep to the carotid. 
Prior to beginning the operation, the gamma probe is calibrated, and 3 readings are recorded with the patient’s background radiation values (usually by pointing the probe to the patient’s leg).
The anterior approach involves approaching the thyroid and parathyroids from the midline. After the incision is made, subplatysmal planes should be elevated circumferentially from the thyroid cartilage to the sterna notch. Self-retaining retractors can be used to maximize exposure, and then the sternothyroid muscles should be separated in the midline (electrocautery or the harmonic scalpel can be used). This allows for adequate exposure of the thyroid gland and its overlying fascia.
Once the suspicious parathyroid has been identified, careful dissection with blunt instruments is used to free the gland from the surrounding fascia. A harmonic scalpel can be used to simultaneously ligate the vascular supply to the gland and remove the specimen.
The gamma probe is used for confirmation, by measuring the gamma radiation (3 readings) from the specimen. Lastly, 3 readings are taken from the intraoperative bed. Murphy and Norman describe a “20% rule” whereby tissue containing more than 20% of background radioactivity in a patient with localization is consistent with a parathyroid adenoma.  Quillo et al independently evaluated this rule at their institution, finding it to be accurate in 99% of their studied population.  At the authors’ institution, anecdotal findings suggest this may occasionally be misleading, and the authors also send a PTH level immediately after removal of the gland, and at 10 minutes after removal, expecting to see a 50% decline between the 2 measurements. 
It is imperative to obtain hemostasis after parathyroidectomy. This is best performed with selective bipolar cautery. A thin layer of thrombin mesh may be applied if deemed necessary. The neck is then closed in a layered fashion with special attention to a meticulous skin closure.
Instead of separating the strap muscles at the cervical linea alba, the parathyroid gland is approached by dissecting between the anterior border of the sternocleidomastoid muscle and the lateral aspect of the straps (sternohyoid muscle). Once the anterior border of the SCM is identified, the SCM is retracted laterally to expose the strap muscles. The fascia overlying the strap muscles is incised, and dissection is carried posteriorly to expose the thyroid lobule. Dissection is carried out medial to the carotid sheath and lateral to the thyroid lobule down to the prevertebral fascia. Dissection can then be carried medially (posterior to the thyroid lobule) to expose the region where the parathyroid adenoma can be found.
Once the parathyroid has been identified, a similar procedure as described for the anterior approach can be carried out. The gamma probe can be used in a similar fashion to that described for the anterior approach.
Despite preoperative localization studies, occasionally individuals fail to have a single localizing gland. Initial scans may have shown ambiguous results or mildly positive localization. Additionally, if multiple localization studies were performed (ultrasound and sestamibi), they may reveal conflicting results. In the event intraoperative evidence of multiglandular disease is found (failure of background radiation or intraoperative PTH to appropriately decline), it may be necessary to evaluate the other 3 parathyroid glands. Some suggest performing a three-and–a-half gland parathyroidectomy with reimplantation of half of the parathyroid either into the SCM or into forearm musculature. 
Instead of requiring the use of a radiotracer the day of surgery, other surgeons describe the use of intraoperative ultrasound to confirm localization and removal.  Davis et al and Livingston et al used ultrasound in those patients who were sestamibi negative and described a 56% and 94% localization rate, respectively, using ultrasound. [32, 33] Prasannan et al used surgeon-performed ultrasonography in the preoperative evaluation and again intraoperatively, determining it to have a sensitivity of 82% with a 96.3% positive predictive value, and an 85% correlation with sestamibi. 
Casserly and Timon describe the gasless MIVAP procedure in detail, initially described by Miccoli et al in 1998.  The patient is positioned without a shoulder roll in extension, and a 1.5- to 2-cm midline incision is made 3 cm above the sterna notch. Dissection is carried down to the thyroid gland, and the strap muscles are dissected off the gland on the side with the parathyroid adenoma, carrying dissection into the space between the thyroid capsule and the carotid sheath. After opening this space, a 30° endoscope is introduced, pointing towards the head. Using the view from the endoscope, dissection and removal of the parathyroid gland is carried out. [36, 37]
In 2010, a follow-up report by Casserly et al described the average incision length from this procedure to be 1.7 cm and significantly improved scar outcomes compared with a traditional open parathyroidectomy approach.  Lombardi et al performed a thorough review of the literature regarding video-assisted approaches, including fully endoscopic approaches using carbon dioxide insufflation. The review found level II evidence supporting the use of MIVAP over the insufflation-based techniques, and they also found evidence indicating lower pain, shorter operating times, and better scar outcomes compared with “open minimally invasive parathyroidectomy” based on a prospective randomized trial from Poland. [38, 39]
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David Goldenberg, MD, FACS Chief of Otolaryngology-Head and Neck Surgery, Professor of Surgery and Oncology, Pennsylvania State University College of Medicine; Director of Head and Neck Surgery, Department of Surgery, Division of Otolaryngology-Head and Neck Oncology, Milton S Hershey Medical Center
David Goldenberg, MD, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Head and Neck Society, American Thyroid Association, Israeli Medical Association
Disclosure: Nothing to disclose.
Neerav Goyal, MD, MPH Assistant Professor of Surgery, Director of Head and Neck Surgery, Division of Otolaryngology-Head and Neck Surgery, Penn State Hershey Medical Center
Neerav Goyal, MD, MPH is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society
Disclosure: Nothing to disclose.
James G Norman, MD, FACE, FACS Director of Parathyroid Surgery, Norman Parathyroid Clinic
James G Norman, MD, FACE, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association of Clinical Endocrinologists, American College of Surgeons, American Gastroenterological Association, American Head and Neck Society, American Pancreatic Association, Association for Academic Surgery, Association of VA Surgeons, Endocrine Society, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Laparoendoscopic Surgeons, Society of University Surgeons, Southeastern Surgical Congress, American College of Endocrinology, American Association of Endocrine Surgeons, Pancreas Club
Disclosure: Nothing to disclose.
Douglas E Politz, MD, FACS, FACE Norman Parathyroid Center
Douglas E Politz, MD, FACS, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Surgeons, American Medical Association, Society for Surgery of the Alimentary Tract, American College of Endocrinology, American Association of Endocrine Surgeons, American Society of Breast Surgeons
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine
Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;Cliexa;Preacute Population Health Management;The Physicians Edge<br/>Received income in an amount equal to or greater than $250 from: The Physicians Edge, Cliexa<br/> Received stock from RxRevu; Received ownership interest from Cerescan for consulting; for: Rxblockchain;Bridge Health.
Benoit J Gosselin, MD, FRCSC Associate Professor of Surgery, Dartmouth Medical School; Director, Comprehensive Head and Neck Oncology Program, Norris Cotton Cancer Center; Staff Otolaryngologist, Division of Otolaryngology-Head and Neck Surgery, Dartmouth-Hitchcock Medical Center
Benoit J Gosselin, MD, FRCSC is a member of the following medical societies: American Head and Neck Society, American Academy of Facial Plastic and Reconstructive Surgery, North American Skull Base Society, American Academy of Otolaryngology-Head and Neck Surgery, American Medical Association, American Rhinologic Society, Canadian Medical Association, Canadian Society of Otolaryngology-Head & Neck Surgery, College of Physicians and Surgeons of Ontario, New Hampshire Medical Society, Ontario Medical Association
Disclosure: Nothing to disclose.
Minimally Invasive Surgery of the Parathyroid
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