The increasing role of minimal invasive radioguided parathyroidectomy for treating single parathyroid adenomaG Grassetto, D Rubello
Department of Nuclear Medicine, Santa Maria della Misericordia Hospital, Rovigo, Italy
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.109477
Source of Support: None, Conflict of Interest: None
As Karahan, et al.,  have shown in their study published in the present issue of the journal entitled: "Minimally invasive parathyroidectomy under local anesthesia", the treatment of choice in case of primary hyperparathyroidism is surgery. The success of the surgical treatment (patient's calcium level returns to normal) depends on the success of localization, identification and removal of abnormal glands.
The first parathyroidectomy dates back to 1925, probably for parathyroid carcinoma that relapsed early, and the first successful treatment of primary hyperparathyroidism by conventional cervicotomy and bilateral neck exploration dates back to 1928. ,,,, From that day on, when the correlation between hyperparathyroidism symptoms and increased production of parathyroid hormone by an overactive parathyroid gland became clear, parathyroid surgery received a large development and radical changes.
Bilateral neck exploration remained the pivotal strategy of hyperparathyroidism treatment for a long time, until 1982 when Tibblin proposed unilateral neck exploration. ,, This approach seemed enough to study at least two parathyroid glands obtaining information sufficient for suspecting a multigland disease (hyperplasia).  Nevertheless, this selective approach, even though curative in many cases thanks to the large prevalence of hyperparathyroidism caused by single adenoma (85%), remained a hazard and unavoidable failures eclipsed it. ,,,,,
Conventional cervicotomy with bilateral neck exploration was considered imperative in the pre-imaging era because the discrimination between single (adenoma) and multigland (hyperplasia) disease was based only on the macroscopic appearance of the glands. So, in the absence of a reliable pre-operative or intra-operative imaging study to identify or localize abnormal parathyroid glands, conventional four-gland exploration is mandatory. So much as, in 1990, the National Institutes of Health (NIH) concluded that pre-operative localization in primary hyperparthyroidism patients without prior neck surgery was rarely indicated and not proven to be cost-effective. So NIH indicated the four-gland exploration as the operation of choice in hyperparathyroidism. ,
From the last decade of the 20 th century, the diffusion of imaging modalities enables to visualize and localize the parathyroid tissue, have allowed the surgeons to plan a more selective approach called minimally invasive parathyroidectomy (MIP). Also, the introduction of intraoperative quick PTH (parathyroid hormone) assay, that gives the opportunity to measure PTH blood levels during surgery, has permitted the wide spread of this surgery. In fact, the fast decrease of PTH level after gland removal greater than 50% respect on pre-operative value, allows to early evaluate the success of surgery during operation. ,,,
The introduction and successful implementation of MIP has revolutionized the surgical approach to hyperparathyroidism.  The cervicotomy access can be very short, especially for inferior parathyroid disease, and local anesthesia with or without sedation can be adopted.  MIP provides smaller neck incision and less tissue dissection with better cosmetic, lower morbidity, shorter operating time and earlier discharge. ,,
It is worth noting that not all the patients with primary hyperparathyroidism are good candidates for MIP. Accurate initial diagnosis and careful patient selection criteria must be considered: a successful surgery cannot rescind these steps. ,
As is well known, the diagnosis of primary hyperparathyroidism is biochemical: increment of PTH blood level, increase blood and urine calcium level, decrease in blood phosphate level and increase in urine phosphate level.  Only after the diagnosis can the imaging modalities be applied with the purpose to localize the parathyroid tissue and to discriminate between single and multigland disease. Parathyroid pathologic glands can be visualized by many imaging techniques: scintigraphy, high-resolution ultrasound, computed tomography and magnetic resonance. , By now it appears to be clear that 99m Tc-Sestamibi parathyroid scintigraphy, together with neck ultrasonography, is the most sensitive and specific imaging technique to localize parathyroid glands. , 99m Tc-Sestamibi parathyroid scintigraphy specificity and sensibility show further increase when the dual tracer-subtraction protocol is used and when SPECT (single photon emission computed tomography) acquisition of neck and thorax are gained other than planar imaging. ,,,, Tomographic sections allow to better localize deeper, posterior parathyroid glands and the ectopic ones, especially if an hibrid instrumentation is used: SPECT/CT technique permits to better localize foci of Sestamibi uptake by software fusion between coregistration of morphological CT imagines and functional sections. , Dual-phase 99m Tc-Sestamibi protocol, that is a simplification of double tracer-subtraction scintigraphy, must be considered when dual-tracer subtraction protocol cannot be used, especially in the presence of iodine saturation of the thyroid or during thyroid drugs' assumption. 
Only when a single parathyroid disease (adenoma) diagnosis and localization are clear the MIP approach should be considered. In particular, MIP can be suggested if: a) there is high likelihood of solitary parathyroid adenoma at pre-operative 99m Tc-Sestamibi/US imaging; b) there is an unambiguous 99m Tc-Sestamibi uptake in the adenoma; c) 99m Tc-Sestamibi avid thyroid nodules are absent.  Many works reported in the literature state that, using these criteria, about two-thirds of all primary hyperparathyroidism patients can benefit from MIP. ,,,,,,,,, In cases of big adenomas, thyroid goiter or multiple glands' disease, bilateral neck exploration remains the recommended approach. In particular, when thyroid goiter is associated with parathyroid disease, the MIP can fail both due to the encumbrance caused by thyroid gland and for the low reliability of localizing imaging procedures.  Moreover, if during minimally invasive surgery the suspicion of malignant parathyroid disease arises, it is mandatory to convert the surgical approach from mini to open.  Also, when the location of the parathyroid adenoma is uncertain and intraoperative quick PTH assay is not available, bilateral neck exploration surgery is preferred. 
The minimally invasive approach, proposed in case of primary hyperparathyroidism supported by single parathyroid adenoma, is usually performed by video, endoscopic or radioactive assistance. The radio-guided procedure takes advantage of the detectability of 99m Tc-Sestamibi during surgical intervention by a gamma detecting intraoperative probe and of the different kinetics of this radioactive compound between thyroid and parathyroid tissue. , The first protocol for radio-guided MIP was proposed by Norman in 1997 and consists of a single-day procedure: in the same day the patient is submitted to a dual-phase scintigraphy with 740-925 MBq of 99m Tc-Sestamibi and, 2-3 h p.i. (post injection), he undergoes radio-guided surgery. ,, This protocol has the advantages of being cost-effective and rapid because it takes only one day to perform both, imaging localization and surgical treatment. Nevertheless, it has the limitation of using dual-phase 99m Tc-Sestamibi scintigraphy, which, is characterized by a sub-optimal sensititivity and specificity in comparison to double-tracer scan, especially in the presence of thyroid nodules. Moreover, performing diagnostic imaging and surgery in the same day does not allow to correctly organize the operating schedule and approaches (MIP versus open surgery). 
A few years later, in 2000, Casara and Rubello proposed the low-dose multiple-day 99m Tc-Sestamibi protocol: the first day a double-tracer subtraction protocol 99m Tc-Sestamibi scintigraphy is performed in association with neck ultrasound; then, within one week of the scintigraphy, the radio-guided MIP is carried out upon 37 MBq 99m Tc-Sestamibi injection in the operating room 10 min before surgery. , The low-dose protocol provides two advantages: a) less radiation exposure to the patient and operating personnel (approximately 20 times lower than Norman's protocol) b) more accurate scheduling and planning of surgical approach. ,
Both described protocols are safe and effective with reported intraoperative parathyroid adenoma detection close to 95%, without major intraoperative surgical complications. 
In conclusion, minimally invasive radio-guided parathyroidectomy has an important role in primary hyperparathyroidism treatment but it cannot be separate from an accurate diagnosis and localization of parathyroid glands, especially if a thyroid disease is associated. With this purpose double-tracer 99mTc-Sestamibi with subtraction protocol and neck/thorax SPECT/CT, together with neck ultrasound, constitute a better diagnostic imaging approach to primary hyperparathyroidism and allow to choose the most accurate surgical procedure.