Thyroid and Parathyroid Diseases: Medical and Surgical Management

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There is clear evidence showing progression to symptomatic PHPT in up to a third of patients who do not undergo surgery [ 10 ].

Calcium intake should follow guidelines for all individuals established by the Institute of Medicine and should not be limited in patients with PHPT who do not qualify for surgery [ 6 , 10 , 40 ]. Vitamin D repletion should be performed cautiously because there is a risk of exacerbating hypercalcemia and hypercalciuria. Pharmacologic agents such as calcimimetics and bisphosphonates have been used to decrease serum calcium and improve BMD, respectively. There is minimal data on fracture rates associated with bisphosphonate therapy in PHPT [ 40 ].

Combination therapy using calcimimetics and bisphosphonates appears to achieve both goals of lowering serum levels of calcium and stabilizing BMD [ 40 ]. However surgical management is more successful and cost effective than pharmacologic therapy [ 6 ] and it remains the treatment of choice, as it is the only means for cure. There are important aspects of the preoperative evaluation specifically pertinent to patients with PHPT.

A history of prior neck irradiation, whether used to treat breast cancer [ 41 ], lymphoma, head and neck malignancies or benign conditions such as acne has been associated with increased risk for parathyroid disease [ 42 , 43 ]. Prior neck surgery or radiation will cause more cervical scarring, making the operation more difficult. Evaluation of vocal cord function is mandatory in these patients as well as in those already with signs of vocal cord dysfunction. Indirect mirror examination, flexible fiber optic laryngoscopy or recently developed techniques such as laryngeal ultrasonography [ 44 , 45 ] are all acceptable methods for evaluation.

All medications should be reviewed, especially those that affect calcium or PTH including lithium, anticonvulsants, calcium-containing products, anticoagulants, thiazide diuretics and vitamin D. It is important that thyroid goiters and nodular disease be assessed preoperatively, with potential biopsies when indicated for the purpose of addressing both problems at the initial operation.


When reviewing DEXA imaging, decreases in BMD are usually most pronounced at cortical bone sites such as the distal radius and it is therefore imperative to include this site during the evaluation [ 6 ]. Newer imaging modalities may be more sensitive than DEXA in detecting decreases in trabecular BMDs, however recommendations based on these modalities have not been validated.

When patients present in hypercalcemic crisis, the surgeon must facilitate stabilizing the patient prior to proceeding to expeditious parathyroidectomy. The goal of initial treatment in these instances focuses on bringing down serum calcium levels, ideally into a eucalcemic state. This requires fluid resuscitation with normal saline, management with bisphosphonates to shift serum calcium toward the bones and furosemide to excrete calcium into the urine. Imaging is an important localizing method that should be ideally ordered by the surgeon due to the high variability between different studies and institutions.

It is not a diagnostic study and has no utility in excluding or confirming the diagnosis of PHPT [ 6 ]. There is no reason to obtain an imaging study if surgery is not planned and negative or nonlocalizing imaging should not inhibit referral to an experienced parathyroid surgeon [ 2 , 48 ].

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These results would simply necessitate a four-gland exploration as opposed to a directed parathyroidectomy. The surgeon should work in concert with the nuclear medicine physician and radiologist to evaluate the quality of results for optimal operative planning. Imaging options include: cervical ultrasound, nuclear scintigraphy, a sestamibi scan, for example, 4-dimension computed tomography 4D CT , MRI and venous sampling.

The most cost effective strategy is cervical ultrasound by an experienced sonographer, combined with sestamibi imaging or 4D CT [ 6 , 49—51 ]. Cervical ultrasound is advantageous due to its low expense, lack of ionizing radiation and ability to evaluate the thyroid for concomitant pathology. It can be performed by the operating surgeon and repeated in the operating room on the day of surgery. Limitations include difficulty in evaluating retroesophageal or mediastinal lesions and it is highly operator dependent.

Thyroid and Parathyroid Diseases: Medical and Surgical Management

Localization accuracy and sensitivity increases when ultrasonography is combined with sestamibi imaging [ 6 ]. Technetium Tc 99m sestamibi is the most common radioisotope in parathyroid scintigraphy and can be combined with single-photon emission computed tomography which can identify ectopic parathyroid glands, including mediastinal or retroesophageal glands. The radiation dose is minimal and it is relatively inexpensive, however the sensitivity in multigland disease is poor [ 6 ].

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Although traditional CT has little utility, 4D CT protocol has increased sensitivity with excellent anatomic detail. It is unlikely for any imaging study to demonstrate enlargement of all four parathyroid glands, instead four-gland hyperplasia should be considered when there is enlargement of more than one gland [ 40 ].


Venous sampling and MRI can be considered in cases of re-operation, contraindications to radiation or difficult localization [ 6 ]. Preoperative fine-needle aspiration FNA of parathyroid lesions is not recommended and rarely necessary [ 6 ]. FNA biopsy can cause trabecular scarring that mimics the appearance of cancer, which would necessitate a more extensive resection and confound the surgical decisions.

Since the surgical management of PHPT has evolved to a focused, unilateral approach, thyroid nodules and cancer can be missed during the index operation. For this reason, preoperative ultrasonography should be performed on all PHPT patients for the purposes of localizing parathyroid adenomas as well as detecting concomitant thyroid nodules. If thyroid nodules meet criteria, FNA should be performed followed by the appropriate thyroid resection during the same initial parathyroidectomy operation.

Alternatively, it is recommended that serum PTH and calcium concentrations be evaluated preoperatively in patients presenting with thyroid disease to also address both diseases simultaneously [ 52 ].

Minimally invasive parathyroid surgery

Two main surgical approaches have evolved among parathyroid surgeons involving the use of four-gland exploration versus directed parathyroidectomy. Both techniques have yielded excellent results with minimal complication rates when performed by an experienced parathyroid surgeon [ 2 , 53 , 54 ]. The surgical volume that defines an experienced surgeon is variable among the literature but ranges between 20 and 50 parathyroidectomies annually, which has shown to result in lower costs, lower complication rates and decreased rates of persistent or recurrent PHPT [ 55—57 ].

Bilateral cervical exploration under general anesthesia has historically been the standard of care for definitive treatment of PHPT, regardless of preoperative imaging. This is still preferred at some institutions due to the inability of preoperative imaging to consistently identify local disease [ 2 ]. It mandates that all four parathyroid glands be identified and assessed, to determine whether multigland disease versus a single adenoma exists. Four-gland exploration can be performed through a small cosmetically appearing neck incision in the outpatient setting.

This is due to the primary concern that residual enlarged parathyroid glands remaining in situ can cause recurrent or persistent disease [ 2 , 61 ]. In comparison, directed parathyroidectomy is a focused, imaged-guided technique that targets the presumed hyperfunctioning parathyroid adenoma without necessarily identifying additional parathyroid glands.

Thyroid and Parathyroid Diseases: Medical and Surgical Management

Intraoperative adjuncts are used to determine whether further pathologic gland s remain in situ. It has become an acceptable and effective surgical approach over the last two decades and avoids the need to perform an extensive bilateral neck dissection [ 2—4 ]. This approach is used primarily in patients who clinically and radiographically appear to have a single hyperfunctioning gland [ 6 ]. It is not generally recommended in patients with suspected multigland disease [ 6 ].

Directed parathyroidectomy has the advantages of shorter operative times, decreased surgical dissection, lower costs, shorter hospital stays and a decreased risk of transient postoperative hypocalcemia [ 2—3 , 62 , 63 ] compared with bilateral neck explorations [ 63 ].

Thyroid and Parathyroid Diseases—Medical and Surgical Management - Suren Krishnan,

This approach can be accomplished through a small midline or lateral cervical incision. During the procedure, it is recommended to use intraoperative adjuncts to avoid failure rates [ 6 ]. In these cases, the surgeon can then proceed with a directed parathyroidectomy and afford the patient a bilateral exploration. This can be useful in cases of intrathyroidal or ectopic glands poorly visualized at the time of resection [ 67 ].

Although success rates vary, there is overall accuracy in localization with this adjunct [ 67—70 ]. Frozen section analysis is not generally recommended, as it does not provide any information regarding residual hyperfunctioning parathyroid tissue in situ. If the surgeon is in doubt of the tissue of origin of a specimen, frozen section can be helpful to distinguish thyroid nodule from parathyroid from lymph node or thymic tissue. However given the added time and cost, routine use of frozen section is not advised.

For these patients, PTH levels from jugular vein sampling prior to skin incision were drawn and often pointed to the correct side harboring the abnormal gland.

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  7. This allowed for a successful unilateral neck exploration. Although bilateral neck exploration has been shown to discover multigland disease at a higher rate, there is no statistical difference in success rates between the two approaches when reviewing multiple series [ 2 , 59 , 71 ]. Intraoperative neuromonitoring for recurrent laryngeal nerve function is advocated by some surgeons but requires general anesthesia with endotracheal intubation.

    This is usually considered when a concomitant thyroid procedure is needed or in cases of reoperation. It is not usually indicated for routine parathyroid procedures. Transcervical-mediastinal and thorascopic approaches are often indicated for ectopic and mediastinal glands.

    If normal parathyroid glands appear devascularized during the procedure, immediate autotransplantation is recommended. When parathyroid cancer is suspected, an en bloc resection without violating the parathyroid capsule is the standard of care [ 6 ], often necessitating a thyroid lobectomy when the gland is abutting the thyroid gland. There is insufficient evidence to recommend a prophylactic central neck dissection during this resection.

    Adjuvant radiation therapy is not routinely recommended for parathyroid cancer but is instead reserved for palliative care options [ 6 ]. When performing parathyroid surgery on patients with a known hereditary condition, bilateral exploration is usually the recommended approach, with some exceptions. The operation is often more challenging due to the nature of a more extensive surgery while balancing the goals of achieving normocalcemia and avoiding permanent hypoparathyroidism [ 2 , 6 , 72 ]. These patients are at a higher risk for recurrent disease making re-operations more difficult [ 2 , 72 ].

    The surgeon must take into consideration each hereditary condition and appropriately adjust the therapeutic approach. Patients with MEN 1 syndrome are likely to have other endocrinopathies such as pituitary, pancreaticoduodenal, thymic and bronchial carcinoid tumors that can be addressed at the time of parathyroidectomy [ 2 ]. A subtotal parathyroidectomy is the treatment of choice, excising 3.

    An acceptable alternative is to perform a total parathyroidectomy with upper extremity autotransplantation, however this is associated with higher rates of permanent hypoparathyroidism [ 2 , 77 ]. While this approach potentially avoids recurrent disease in the neck, forearm autografts are also at risk for hyperplasia which can be difficult to distinguish in the setting of simultaneous cervical recurrence [ 2 ]. Directed parathyroidectomy with intraoperative PTH monitoring can be considered only if preoperative localization studies clearly demonstrate a single enlarged gland [ 78 ].

    However this places the patient at higher risk for persistent or recurrent disease [ 2 , 77 ]. Another described approach involves removing both glands from the ipsilateral neck along with the cervical thymus. If recurrence occurs, reoperation is focused in the contralateral neck with less scarring, however this risks removing the most normal parathyroid gland that may have been the ideal remnant [ 2 ].