A novel, noninvasive imaging technique for intraoperative assessment of parathyroid glands: confocal reflectance microscopy

BACKGROUND: Successful surgical management of primary hyperparathyroidism requires the ability to identify and distinguish normal from abnormal parathyroid tissue. Microscopic pathologic confirmation often helps with the diagnoses and decisions regarding the extent of parathyroid resection. Confocal reflectance microscopy (CRM) is an optical method of noninvasively imaging tissue without fixation, sectioning, and staining as in standard histopathology. The goal of this study was to determine if CRM imaging could be used to distinguish normal from diseased parathyroid tissue intraoperatively. METHODS: In this study, 44 parathyroid glands from 21 patients undergoing operations for primary hyperparathyroidism were imaged immediately after excision. CRM images were compared with conventional hematoxylin-and-eosin stained sections obtained from the same gland. The percentage area occupied by fat cells was calculated in images of both normal and diseased glands. RESULTS: Characteristic microscopic features of parathyroid glands were distinguishable by CRM and correlated well with histopathology. The stromal fat content of normal and diseased glands could easily be determined. The percentage area occupied by fat cells differed significantly (P <.00001) in normal glands (average, 23.0% +/- 10.9%) and adenomatous glands (average, 0.4% +/- 0.7%). CONCLUSIONS: CRM imaging rapidly revealed microscopic features that reliably differentiated normal and diseased parathyroid glands. The success of this preliminary ex vivo study promotes interest in further development of an in situ probe for in vivo clinical diagnostic use.     

Transplantation of the parathyroid glands in man: clinical indications and results.

The physiologic function of human parathyroid autografts and allografts has not been demonstrated conclusively. During the past 30 months, we have transplanted parathyroid glands in 29 patients and tested their functional status. One immunosuppressed aparathyroid patient received a parathyroid allograft from a parent who previously had been his renal transplant donor. Twenty-seven patients with renal failure and secondary hyperparathyroidism received parathyroid autografts immediately after total parathyroidectomy, and one patient received a parathyroid autograft at the time of total parathyroidectomy for primary chief cell hyperplasia. At transplantation 1 times 1 mm. parathyroid pieces were grafted into the forearm musculature. Of 11 transplanted patients (one allograft and ten autografts) followed for 1 year, ten are normocalcemic; only two (autografted patients) are on supplemental calcium. Ten of the 29 patients have had biopsies performed, and all have had intact parathyroid architecture and intracellular secretory granules demonstrated by light and electron microscopy. Parathyroid hormone content in the grafted tissue of five patients was 179 plus or minus 118.8 ng. per milligram. In 11 random patients in whom bilateral measurements have been made, the parathyroid hormone content in the antecubital vein blood draining the grafted tissue has been markedly higher than that in the simultaneously sampled antecubital vein blood of the nongrafted arm. These data demonstrate that parathyroid autografts or allografts secret hormone and maintain a normal serum calcium in the host.     

Near infrared fluorescence imaging of rabbit thyroid and parathyroid glands

Background

Near infrared fluorescence imaging using intravenous methylene blue (MB) is a novel technique that has potential to aid the parathyroid gland (PG) localization during thyroid and parathyroid surgery. The aim of this study was to examine MB fluorescence in the rabbit neck and determine the influence of MB dose and time following administration on fluorescence from thyroid and PGs.

Methods

Thyroid and external PGs were exposed in six New Zealand white rabbits under anesthesia. Varying doses of MB (0.025–3 mg/kg) were injected through the marginal ear vein. Near infrared fluorescence from exposed tissues was recorded at different time intervals (10–74 min) using Fluobeam 700. Specimens of identified glands were then resected for histologic assessment.

Results

Histology confirmed accurate identification of all excised thyroid and PGs; these were the only neck structures to demonstrate significant fluorescence. The parathyroid demonstrated lower fluorescence intensities and reduced washout times at all MB doses compared with the thyroid gland. A dose of 0.1 mg/kg MB was adequate to identify fluorescence; this also delineated the blood supply of the external PGs.

Conclusions

The study demonstrates that near infrared fluorescence with intravenous MB helps differentiate between thyroid and PGs in the rabbit. This has potential to improve outcomes in thyroid and parathyroid surgery by increasing the accuracy of parathyroid identification; however, the findings require replication in human surgery. The use of low doses of MB may also avoid the side effects associated with currently used doses in humans (3–7 mg/kg).     

A multicenter evaluation of near-infrared autofluorescence imaging of parathyroid glands in thyroid and parathyroid surgery

BackgroundThe usefulness of incorporating near-infrared autofluorescence into the surgical workflow of endocrine surgeons is unclear. Our aim was to develop a prospective registry and gather expert opinion on appropriate use of this technology.MethodsThis was a prospective multicenter collaborative study of patients undergoing thyroidectomy and parathyroidectomy at 7 academic centers. A questionnaire was disseminated among 24 participating surgeons.ResultsOverall, 827 thyroidectomy and parathyroidectomy procedures were entered into registry: 42% of surgeons found near-infrared autofluorescence useful in identifying parathyroid glands before they became apparent; 67% correlated near-infrared autofluorescence pattern to normal and abnormal glands; 38% of surgeons used near-infrared autofluorescence, rather than frozen section, to confirm parathyroid tissue; and 87% and 78% of surgeons reported near-infrared autofluorescence did not improve the success rate after parathyroidectomy or the ability to find ectopic glands, respectively. During thyroidectomy, 66% of surgeons routinely used near-infrared autofluorescence to rule out inadvertent parathyroidectomy. However, only 36% and 45% felt near-infrared autofluorescence decreased inadvertent parathyroidectomy rates and improved ability to preserve parathyroid glands during central neck dissections, respectively.ConclusionThis survey study identified areas of greatest potential use for near-infrared autofluorescence, which can form the basis of future objective trials to document the usefulness of this technology.     

Laparoscopic simultaneous bilateral adrenalectomy: assessment of feasibility and potential indications

Objective: To report a single‐center experience with laparoscopic simultaneous bilateral adrenalectomy (LSBA) and to evaluate its safety, surgical outcomes, and potential indications of the procedure. Methods: A total of 21 patients underwent LSBA between 2000 and 2010 at our institution. Four patients had bilateral Cushing's syndrome (CS), two had bilateral pheochromocytoma, and one had a bilateral metastatic tumor. Eleven patients had unilateral or bilateral aldosterone‐producing adenoma (APA), associated with CS or subclinical CS. Three patients had unilateral APA with contralateral non‐functioning adenoma. Partial adrenalectomy was performed first by using with four ports. After the excision of one gland, the contralateral gland was removed after repositioning of the patient. Results: LSBA was completed in all 21 patients without major complications. Mean operative time was 329.7 min and the estimated blood loss was 94.1 mL. Mean tumor size was 21.8 mm. Of the 16 patients receiving an adrenal‐sparing procedure, nine of 11 discontinued glucocorticoid replacement after 2 years. The remaining five patients receiving bilateral total adrenalectomy required 0.5–0.75 mg of dexamethasone permanently. No open conversions, no deaths or no adrenal insufficiencies were encountered. Conclusions: LSBA represents a safe and viable treatment option for selected patients with bilateral adrenal disease.     

Hyperparathyroidism: ectopic parathyroid glands.

A patient with a parathyroid adenoma located beneath the throid capsule and within a benign thyroid adenoma is reported on. To the best of our knowledge, this lesion has not previously been reported. This case points out the difficulties that may be encountered when it is necessary to locate a missing parathyroid gland in a patient with multinocular goiter. In this clinical setting there may be a role for use of the various technics recommended for preoperative localization of a parathyroid adenoma.     

Magnetic resonance imaging of the thyroid, thymus, and parathyroid glands

Magnetic resonance (MR) images of the neck were obtained in 16 patients with use of a variety of spin echo and inversion recovery pulse sequences. Anatomic resolution was best with high-resolution spin echo images obtained with the pulse sequence repetition rate equal to 2.0 seconds and the echo delay equal to 28 msec because this imaging technique offered excellent contrast between normal tissues and had the highest signal noise ratio. The spatial resolution of MR was nearly as good as state of the art computerized tomography (CT). However, streak artifacts caused by motion and x-ray beam hardening often limited CT but did not affect MR. Tumors and lymph nodes were more easily differentiated from muscle and blood vessels with MR than with CT because of the superior soft-tissue contrast of MR. Tissue characterization allowed MR differentiation of thyroid nodules, thyroid cysts, and parathyroid tumors from normal thyroid tissue. Thyroid cyst fluid had the greatest water content and longest T1 and T2 relaxation times of all tissues studied. However, nonspecifically increased T1 and T2 relaxation times overlapped for a variety of neoplastic and inflammatory conditions. With further experience, MR imaging is likely to become a useful technique for the evaluation of neck masses.     

Applied embryology of parathyroid glands

The article describes the normal structure of the parathyroid glands (PTG) and their development, anomalies of migration in the process of embryogenesis and congenital ectopias of PTG as well as possible supplementary PTG and their congenital ectopias.     

Cysts of the parathyroid glands

Cysts of epithelial bodies are rare causes of hyperparathyroidism. Reported in this paper are 2 patients with clinical symptoms of hyperparathyroidism, high blood calcium levels and established hormones in their epithelial bodies. Cysts of epithelial bodies were diagnosed by means of angiography, computed tomography, and sonography. Various aetiological factors behind cyst formation in epithelial bodies are discussed.     

Thoracoscopic resection of ectopic parathyroid glands

BACKGROUND: The vast majority of parathyroid glands in hyperparathyroidism can be resected through a cervical approach. In approximately 2% of the cases, the ectopic gland is in the mediastinum in a location that requires a thoracic approach. METHODS: We report 7 such cases that were resected using video-assisted thoracic surgery to avoid the need for an open surgical procedure. RESULTS: All glands were successfully identified preoperatively and subsequently resected. Hospital stay averaged less than 3 days with only one minor complication. CONCLUSIONS: Ectopic mediastinal parathyroid glands may be safely and accurately resected using video-assisted thoracic surgery to avoid open approaches.     

Cancer of the parathyroid glands.

Hyperfunctioning parathyroid carcinoma is a relatively rare endocrine tumor, accounting for approximately 1% of all cases of primary hyperparathyroidism. The diagnosis is suspected when the tumor is large, parathyroid hormone (iPTH) levels are high, and a palpable tumor is present in the neck. Patients who have recurrence of hyperparathyroidism several months after surgical treatment should be suspected of having a recurrent or persistent parathyroid carcinoma. At operation, a large invasive tumor is usually found. The fibrous, inflammatory-like reaction is the most characteristic indication of malignancy. Even in tumors with minimal invasiveness, the possibility of a carcinoma should be considered if the tumor has mitotic activity and a monotonous instead of a pleomorphic cellular population. If the surgeon can recognize the possibility of parathyroid malignancy and adequately treat the patient during the initial operation, more gratifying results should be obtained.     

Surgical anatomy of human parathyroid glands

In an autopsy study of 503 cases the parathyroid glands were dissected, and the number of glands in each case and the anatomic distribution of the glands were recorded. In 18 cases (3%) only three glands were found. In these cases the lower combined weight suggested that a fourth gland had been missed. In 421 cases (84%) there were four glands and in 64 cases (13%) there were supernumerary glands. Most often the supernumerary gland was a fifth gland, usually in the thymus. The anatomic distribution of the glands showed considerable constancy. The positions of the glands on the one side were symmetrical with those on the other side in approximately 80% of cases. The superior parathyroids were frequently found just above the intersection between the recurrent laryngeal nerve and the inferior thyroid artery. The inferior parathyroids most often lay somewhat more ventrally, close to the lower thyroid pole or in the upper thymus or thyrothymic ligament. In a few cases the lower parathyroids were situated higher up in the neck, obviously because of a failure of descent during the embryologic development. In view of the number of supernumerary glands and their location, it is concluded that wide excision of fat tissue surrounding the parathyroids and thymectomy should be performed during operation in patients with hyperparathyroidism secondary to uremia or those with multiple endocrine neoplasia syndromes.     

Autotransplantation of human parathyroid glands.

Six patients with primary hyperparathyroidism have had glands autotransplanted into their forearm or deltoid region immediately after presumed total parathyroidectomy. Five hyperplastic glands were transplanted; two patients are normocalcaemic, two are hypercalcaemic and one is hypocalcaemic. The one normal transplanted gland did not show any evidence of function. We conclude that immediate transplantation of parathyroid tissue following total parathyroidectomy may not be the procedure of choice.