Minimally invasive parathyroidectomy under local anesthesia÷ Karahan1, A Okus1, B SevinÁ1, MA Eryilmaz1, S Ay1, M «ayci2, C Duran3
1 Department of General Surgery, Internal Medicine Clinic, Konya Training and Research Hospital, Konya, Turkey
2 Department of Nuclear Medicine, Internal Medicine Clinic, Konya Training and Research Hospital, Konya, Turkey
3 Department of Endocrinology, Internal Medicine Clinic, Konya Training and Research Hospital, Konya, Turkey
Background: More than 85% of primary hyperparathyroidism (PHPT) cases are due to solitary, benign parathyroid adenomas. Recently, the success rate of Tc99m sestamibi scintigraphy in localization has made minimally invasive parathyroidectomy (MIP) more prominent. MIP is as effective as conventional bilateral neck exploration. Moreover, it offers lower morbidity, cost effectiveness, and better cosmetics effects. Aim: We aimed to evaluate the success of MIP, which happens only under local anesthesia, in this study. Materials and Methods: Total of 63 patients were operated for PHPT, of which 54 had solitary adenoma. Five patients underwent bilateral neck exploration under general anesthesia for thyroid nodules or unlocalizated adenomas. A total of 49 patients underwent MIP under local anesthesia without any sedation. During MIP, gamma probe was used for all patients. The patients were followed for parathyroid functions. Results: The mean age of 49 patients with MIP (5 male, 44 female) was 59 years. The mean follow-up time was 16.4 (±10.1) months (range: 2-36 months). Of the 49 patients, 47 (96%) were totally cured. In 2 patients, the procedure was switched to conventional bilateral neck exploration. Temporary hypocalcaemia was noted in 4 patients. Conclusions: If the adenoma is localizated, MIP under only local anesthesia can be performed with a high success rate. Gamma probe-guided MIP under local anesthesia is an effective and safe method. It has the advantage of being minimally invasive and, therefore, it should be preferred over the conventional method.
Keywords: Gamma probe, local anesthesia, minimally invasive parathyroidectomy, primary hyperparathyroidism, parathyroid adenoma
Primary hyperparathyroidism (PHPT) is caused by autonomous excess parathormone (PTH) secretion from one or more parathyroid glands. The incidence of PHPT increases after the age of 50 years, and is 2-4 times more common in females. PHPT may be caused by single adenoma (80-85%), parathyroid hyperplasia (10-15%), multiple adenomas (2-3%), and parathyroid carcinoma (1%). ,,, PHPT is the most common cause of hypercalcemia in outpatient clinics with an incidence of 25 in 100000, and it increases with age. 
Symptomatic PHPT can be accompanied by urinary stones, osteopenia, hypertension, peptic ulcer disease, fatigue, or mental status changes like somatic complaints. When calcium assays were not routinely followed, urinary system stones and osteodystrophic bone disease were common. However, with the introduction of easy and safe calcium and PTH assays, renal and osteodystrophic disease incidence has decreased to < 20%. Therefore, the diagnosis rate has increased 4-5 folds in recent years and most of the PHPT patients are diagnosed in asymptomatic state. ,
Conventional surgical approach to PHPT included exploration of bilateral neck areas and resection of the abnormal gland. However, minimally invasive procedure has become more used with the improvement of imaging technology, and with 80-85% of PHPT being single adenomas. After the first introduction of minimally invasive parathyroidectomy (MIP) by Norman and Chheda  in 1997, it became more common. MIP can be performed under general anesthesia, cervical blockage, or local anesthesia with sedation. In this study, we present our results of MIP in PHPT under local anesthesia without sedation.
Study period, case definition and pre-op work up
Data of 63 patients who underwent surgery due to PHPT between November 2009 and March 2012 at Konya Training and Research Hospital was evaluated. PHPT was diagnosed by both an increase in serum calcium and PTH levels. Symptomatic and asymptomatic patients who met the criteria of 2002 National Institutes of Health (NIH) guidelines were selected for the surgery.  A surgeon, endocrinologist, and a nuclear medicine specialist were involved in assessment and evaluation of all the patients. Pre surgery, the patients were evaluated by ultrasonography (Siemens, Acuson Antares, Siemens Medical Solutions, USA) and Technetium (Tc) 99 m sestamibi dual-phase parathyroid scintigraphy (MIBI; Siemens E-cam Signature Dual Head, Siemens Medical Solutions Hoffman Estates, IL USA). Localization, extent of the adenoma, and the findings of nodular goiter were all recorded.
The patients with parathyroid hyperplasia underwent bilateral neck exploration and subtotal parathyroidectomy. The patients with surgical indications for nodular goiter, unlocalized adenomas despite the imaging studies and before neck surgery were candidates for exploration under general anesthesia. After preoperative detection of the adenoma, adenoma localization was assigned by 1 mCi Tc 99 sestamibi given through the antecubital vein, 1 hour before the surgery. Infiltration anesthesia with 5-8 ml of 2% prilocaine (Citanest®, AstraZeneca Türkiye Ýlaç Sanayi ve Ticaret), diluted with 0.9% isotonic sodium chloride solution, was performed. A skin incision of 2-3 cm was made on the area of the highest radioactivity count. Further anesthetic was administered with the cooperation of the patient. Adenoma was located with the guidance of a gamma probe (Crystal Gamma Probe, CXS-SG03, Germany), and it was totally excised after ligating the parathyroid vessels. Radioactivity count was measured at the rest tissue and the excised tissue. More than 50% decrease at the parathyroid bed was accepted as a successful procedure.
In case of any doubt in localization of the adenoma, MIP was planned similarly. When the adenoma could not be found, or the radioactivity count did not decrease to >50% (suspicion for a second adenoma), bilateral neck exploration under general anesthesia was done. No drainage tube was used for the MIP patients.
Post-op follow up
All MIP patents were discharged on the first day after the exclusion of hypercalcemia and the documentation of the decrease in PTH. Both intravenous or oral calcium and vitamin D were administered to the patients with hypercalcemia. The patients were discharged when the serum calcium levels were in the normal range. Follow up was done on days 30, 60 and 360. when the calcium and PTH levels were recorded.
There were 8 male and 55 female patients. The mean age was 51.8±1.4 years, mean calcium and PTH levels 10.9±0.15 mg/dl (reference: 8.4-10.2 mg/dl) and 473±86.6 pg/ml respectively (reference: 11-67 pg/ml) preoperatively, and 8.6±0.12 mg/dl and 113.8±31.8 pg/ml respectively at the postoperative first day. The mean follow-up time was 16.4±10.1 (2-36) months.
In 54/63 (84.1%) patients, PHPT was due to parathyroid adenoma [Table 1]. In 50/54 patients with adenoma, the localization was detected by MIBI. The ability of the MIBI to detect adenomas was 93%; however, it was 47% for ultrasonography. In 54% of adenomas ( n=29), there was an accompanying nodular goiter. Among the patients with adenoma, 2 patients with accompanying nodular goiter, 2 patients with unlocalized adenomas, and 1 patient with double adenoma underwent bilateral neck exploration under general anesthesia. The 49 patients underwent MIP under local anesthesia [Table 2]. In 1 patient, the adenoma could not be found at the time of operation and in another with atypical localization (retroeosefageal), the procedure was switched to exploration under general anesthesia. The success rate of MIP was thus 96%. The localizations of the adenomas are given in [Table 3], and the most common localization was in the lower right (50%).
Safety and complications
Either temporary or persistent, there was no vocal cord paralysis after MIP. Temporary hypercalcemia was observed in 4 patients (6.3%). Recurrent hypercalcemia was observed in 2 patients at the follow-up visits. In one of those patients, a second adenoma was detected, and the patient was reoperated. In the other patient, there was no other adenoma detected by imaging studies and the patient is still being followed up.
The aim of the surgical treatment of PHPT is to remove the gland that causes abnormal calcium levels and to maintain normocalcemia. Moreover, in long term, it is to prevent bone mineral loss (or osteopenia) and systemic effects of hypercalcemia. 
Classical symptoms of PHPT such as bone pain, pathological fractures, urinary system stones, fatigue, and muscle weakness are related to hypercalcemia. The preferred treatment should be surgery in these symptomatic patients. However, because of the developments in diagnostic processes, PHPT cases are diagnosed earlier. When asymptomatic cases are evaluated, they have behavioral and mental disorders (e.g., fatigue, lethargy, depression, concentration disorders), which impair the quality of life. ,,, Moreover, hypercalcemia is related to increased mortality rate due to cardiovascular disorders such as left ventricular hypertrophy and arrhythmias. Several studies show the improvement of quality of life and decrease in the mortality rate by surgical treatment. ,
The standard surgical treatment was bilateral (four-glands) neck exploration under general anesthesia until 1990s. The success rate of this procedure is 95-97%, and hypercalcemia rate is 15%.  Tc 99 sestamibi scintigraphy has been used for parathyroid localization since 1989, and its sensitivity is reported as >85%. In this study, MIBI was found to be effective in localization of adenoma with a success rate of 93%. The radioactive sestamibi, used in MIBI, is kept by the mitochondria of oxiphilic cells of the parathyroid gland. Thyroid nodules can also keep sestamibi, and that may cause false positive results in patients with nodular goiter. On the other hand, small adenomas (less radioactivity is kept) and cystic adenomas (cannot be imaged) may cause false negative results.  Besides, multiple adenomas (multiglandular disease) may cause false negativity. , Sensitivity of MIBI is higher, especially in adenomas >1 gr.  Ultrasonography has a lower sensitivity for adenoma localization; however, the combination of the two techniques has a sensitivity rate >95%.  In our study, the success rate of ultrasonography was found to be 47%, which may have been caused by the user experience. Ultrasonography is especially helpful in detection of nodular goiter and anatomical relations of the adenoma. ,,,
Parallel with the improvements of localization methods, minimally invasive parathyroidectomy that offers the chance of unilateral intervention, became more prominent. Preoperative imaging (mainly scintigraphic) techniques have changed the surgical strategy from wide traditional bilateral neck exploration to limited neck exploration. Developments during the past 10-15 years with regard to both the accuracy of preoperative localizing imaging techniques and intraoperative minimally invasive procedures in order to provide endocrinologists and endocrine surgeons with further information about the newly available diagnostic and therapeutic tools for use in PHPT patients with a solitary adenoma.  MIP has similar success rates with bilateral neck exploration. , In adenoma-caused PHPT, MIP has a success rate >90%. ,,,,, However, MIP is required for preoperative localization studies. After localization of the adenoma, MIP can provide us smaller incision, better cosmetics, less tissue dissection, lower morbidity (hipoparathyroidism and recurrent laryngeal nerve injury), and shorter operation time and hospital stay. MIP can be applied as an outpatient surgery. ,,,,,,
Success of MIP can be enhanced with the guidance of gamma probe or the measurement of intact PTH levels. If the intact PTH levels decrease to >50%, the procedure is accepted as sufficient. If the decrease is <50%, another adenoma should be searched. Especially in multiple adenomas, intact PTH measurement is an important guide.  Several studies show the improvement of MIP by intact PTH measurement and the use of Gamma probe. ,,, Radio-guided MIP consists of low dose (1 mCi)) of Tc-sestamibi, given by intravenous injection, in the operating theatre a few minutes before surgery, thus allowing the radiation exposure dose to the patient and operating theatre personnel to be minimized. MIP using the Tc-sestamibi is a safe and effective treatment in PHPT patients with a high likelihood of a solitary parathyroid adenoma at preoperative imaging.  However, in specialized centers and with experience, the same results can be achieved without the use of those guidance. ,,,, In this study, compatible with the literature, we had a 96% success rate with gamma probe-assisted MIP. The use of gamma probe increases the experience in parathyroid surgery.  We did not measure intact PTH levels as it is an expensive method.
MIP is used for the excision of abnormal parathyroid gland with a smaller incision. MIP can be applied under general anesthesia, , cervical blockage,  and sedation with local anesthesia. ,, However, there is only little information that it can be performed under local anesthesia without sedation. In this study, we have shown that MIP can be applied under only local anesthesia with the same success rate. Furthermore, this procedure does not have the risks and expense of general anesthesia. Especially for co-morbid patients who are risky for general anesthesia,  MIP can be easily performed under local anesthesia.
To conclude, MIP is a safe and effective method with a success rate of >95% for patients with single adenoma. A good preoperative evaluation and peroperative use of gamma probe improve the surgical success.
The authors are grateful to Osman Doðru, Cemil Er, Bekir Gürocak, and Canan Sevinç for their contributions to the study.
[Table 1], [Table 2], [Table 3]