Parathyroid Tissue In Patients Research Articles

Subcutaneous forearm transplantation of autologous parathyroid tissue in patients with renal hyperparathyroidism

Parathyroidectomy is required in up to 5% of patients with chronic renal failure. Intramuscular transplantation of autologous parathyroid tissue in the forearm has been the traditional method of transplantation at the time of total parathyroidectomy. The removal of an intramuscular transplantation can be technically difficult should graft-dependent hyperparathyroidism (GRH) occur. This problem resulted in our initiating a study of subcutaneous transplantation with total parathyroidectomy in patients with renal failure. Twenty-six patients who were receiving dialysis therapy underwent total parathyroidectomy and subcutaneous transplantation. Parathyroid tissue was diced into 1- to 2-mm pieces, and 6 pieces were grafted into 6 subcutaneous pockets of the forearm. Intact parathyroid hormone was measured within 48 hours of operation and in the bilateral antecubital veins 1 to 24 months after the operation to assess completeness of resection and graft function, respectively. No major surgical complications occurred. Symptoms improved in 24 patients (85%). Graft failure rate was 4.3%. No GRH was observed. Follow-up was 4 to 55 months (mean, 27 months). This study indicates that the subcutaneous transplantation function is comparable to intramuscular transplantation and suggests a decreased incidence of GRH. Subcutaneous transplantation is technically easier than intramuscular transplantation and has the additional advantage of easy removal should GRH occur.

Localization of Abnormal Parathyroid Tissue With Use of Technetium-99m-Sestamibi

To evaluate the efficacy of "double-phase" technetium-99m-sestamibi scanning in the localization of abnormal parathyroid tissue in patients with hyperparathyroidism. We present a prospective review of patients with hyperparathyroidism seen at a university teaching hospital between June 1994 and May 1997. Twenty-four patients entered into the study underwent preoperative localization with double-phase technetium-99m-sestamibi. The nuclear medicine results were compared with the operative findings. The Tc-99m-sestamibi scan correctly identified the location of single parathyroid adenomas in 22 patients (100%). Of the other two patients, both with diffuse parathyroid hyperplasia, one had a negative sestamibi scan and one had only the two inferior parathyroid glands localized on the sestamibi scan. One patient with recurrent hypercalcemia, who previously underwent total parathyroidectomy and parathyroid autotransplantation into the left forearm, had activity localized to that forearm but not to the neck. Subsequently, hyperplastic parathyroid tissue was successfully removed from the transplantation site. Another patient, who had previously undergone two unsuccessful surgical explorations prompted by hyperparathyroidism, had sestamibi localization of an adenoma inferior and medial to the right submandibular gland. The third surgical exploration disclosed a large adenoma medial to the carotid artery, just below the angle of the jaw. In two elderly, debilitated women with positive scans, adenomas were removed with use of local anesthesia. Of 22 patients in whom long-term follow-up was available, 21 remained normocalcemic for a mean period of 11.4 +/- 1.7 months postoperatively. One patient in whom hyperplastic parathyroid tissue had been removed from the left forearm had recurrence of hypercalcemia 1 year after operation. Technetium-99m-sestamibi scanning is a reliable method for identifying parathyroid adenomas but not as helpful in localizing hyperplastic parathyroid glands. The precise localization of an adenoma simplifies surgical exploration and in selected patients may allow excision of the adenoma under local anesthesia. Tc-99msestamibi scanning has become the preferred method for noninvasive localization of abnormal parathyroid glands.

Use of a rapid intraoperative parathyroid hormone assay in the surgical management of parathyroid disease.

To evaluate the utility of a rapid intraoperative parathyroid hormone (PTH) immunoradiometric assay in the surgical management of parathyroid disease, particularly with reference to limiting extent of cervical exploration. Nonrandomized prospective study. Academic tertiary care center. Forty-three consecutive patients undergoing parathyroid exploration for adenoma or hyperplasia had rapid PTH assays performed from blood drawn at induction and 7 minutes after resection of all hyperfunctioning parathyroid tissue. Excision of all hyperfunctioning parathyroid tissue as assessed by bilateral neck exploration, postoperative normalization of serum calcium and PTH levels, and resolution of clinical symptoms. The intraoperative rapid PTH assay accurately reflected whether all hyperfunctioning parathyroid tissue was excised in every patient. In 41 patients, all hyperfunctioning parathyroid tissue was resected at the time of surgery and confirmed by a corresponding decrease in the intraoperative postexcision rapid PTH determination as well as by subsequent normalization of postoperative serum calcium and PTH levels and resolution of clinical symptoms. In 2 patients, the postexcision rapid PTH assay determination was not consistent with removal of all hyperfunctioning parathyroid disease and both patients demonstrated persistent hyperparathyroidism postoperatively. The intraoperative rapid PTH assay may be of significant benefit in permitting directed unilateral parathyroid explorations for adenoma when combined with preoperative localization with a technetium-99m sestamibi scan. Additionally, the rapid PTH assay has proved to be of benefit in confirming excision of all hyperfunctioning parathyroid tissue in patients with multiple gland hyperplasia, particularly those who may harbor ectopic parathyroid tissue.

Combined Tc-99m MIBI and Tc-99m RBC for anatomic localization of ectopic mediastinal parathyroid adenomas.

Preoperative localization of abnormal parathyroid tissue in patients with persistent or recurrent hyperparathyroidism is recommended as a standard of care. A high percentage of these patients have ectopic tissue in the mediastinum. Tc-99m MIBI imaging alone for detection of ectopic parathyroid tissue in the mediastinum does not provide a sufficient number of anatomic landmarks, which makes communication regarding the exact location of any area of abnormal uptake difficult. We report the use of concomitant Tc-99m RBC and Tc-99m MIBI imaging for precise anatomic localization of ectopic mediastinal parathyroid tissue in 4 patients. It is thought that this combination of studies allows improved communication with referring physicians, surgeons, and radiologists for planning both surgical approach and correlative imaging studies. It is hoped that in the future this combination of studies may obviate the need for other imaging studies.

Five to 10 years follow-up after total parathyroidectomy and autotransplantation of parathyroid tissue: evaluation of parathyroid function by use of ischaemic blockade manoeuvre.

The aim of the present study was to assess the long-term function of autotransplanted parathyroid tissue in patients with chronic renal disease. We examined the medical records of a consecutive series of 21 patients with chronic renal failure, who had undergone total parathyroidectomy with autotransplantation. During the time of follow-up, on average 79 months, one patient developed graft-dependent recurrent hyperparathyroidism and one patient suffered from persistent hypoparathyroidism. Nine of the patients were available for a clinical study. In these patients we measured the plasma concentration of intact PTH in blood from the arm contralateral to the graft-bearing arm at rest and during a short-lasting ischaemic blockade of the graft site from the circulating blood. At rest all nine patients had parathyroid hormone (PTH) values within the normal range. The ischaemic blockade produced a marked reduction in the plasma concentration of intact PTH in eight of the patients indicating well functioning autografts. Prior to the examination the patient with recurrent hyperparathyroidism had undergone resection of the autograft. In this patient, ischaemia of the former graft site did not cause any change in the concentration of PTH indicating normally functioning residual parathyroid tissue in the neck. Thus, the ischaemic blockade manoeuvre seems suitable for the assessment of autografted parathyroid tissue. Our results indicate that total parathyroidectomy with autotransplantation provides a rational alternative to the surgical treatment of secondary hyperparathyroidism.

Hyperparathyroidism in high-risk surgical patients: evaluation with double-phase technetium-99m sestamibi imaging.

To evaluate the accuracy of technetium-99m sestamibi as a single agent in the detection and localization of hyperfunctioning parathyroid tissue in patients who underwent prior neck exploration or who otherwise are high surgical risks. Thirty-nine patients with hyperparathyroidism underwent 40 double-phase Tc-99m sestamibi studies. Histopathologic correlation was obtained for all studies. Thirty patients had solitary adenomas, and nine had hyperplastic glands. One developed recurrent hypercalcemia after five-gland resection and underwent repeat imaging and operation. Double-phase sestamibi imaging prospectively enabled localization of 46 (77%) of 60 abnormal glands. Twenty-eight (93%) of 30 adenomas were correctly localized, whereas 18 (60%) of 30 hyperplastic glands were localized. The overall specificity of the study was 98% with one false-positive study. Gland weight and vascularity were statistically significant predictors of uptake of sestamibi. Double-phase Tc-99m sestamibi imaging is a promising technique for localization of parathyroid adenomas in high-risk surgical patients. Localization of multiple hyperplastic glands remains a challenge.

Localization of Mediastinal Parathyroid Adenoma in Recurrent Postoperative Hyperparathyroidism With Tc-99m Sestamibi SPECT

The preoperative localization of abnormal parathyroid tissue in patients with persistent or recurrent hyperpara-thyroidlsm after previous surgical neck exploration has been a difficult diagnostic problem. As a complicating factor, approximately 20% of parathyroid glands are found in ectopic locations, the mediastinum being the most frequent of these sites. Recently, Tc-99m sestamibi has been reported to successfully detect and localize parathyroid adenomas preoperativeiy. In this patient with postoperative, recurrent hyperparathyroidism, Tc-99m sestamibi SPECT demonstrated abnormal focal accumulation in a mediastinal location, which correlated with a surgically proven parathyroid adenoma.

Primary hyperparathyroidism: preoperative parathyroid imaging with regional body FDG PET.

To explore the feasibility of use of positron emission tomography (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) to localize abnormal parathyroid tissue. Regional body FDG PET with attenuation correction was performed in 17 adult patients with primary hyperparathyroidism (HPT) prior to surgical neck exploration. The regional body FDG PET results were correlated with surgical and histopathologic findings. Surgical neck exploration revealed 18 parathyroid adenomas in 16 patients and four hyperplastic parathyroid glands in one patient. Regional body FDG PET allowed correct localization of 17 of the 18 parathyroid adenomas (94% sensitivity) and two of the four hyperplastic parathyroid glands (50% sensitivity). Three false-positive FDG PET findings were encountered, including two follicular thyroid adenomas. Regional body FDG PET is a promising procedure for preoperative localization of pathologic parathyroid tissue in patients with primary HPT.

Thyroid and parathyroid imaging

With the advent of better thyroid function tests, a tumor marker, and fine-needle aspiration, the role of thyroid imaging studies in the evaluation of the patients with thyroid disease has diminished. Although multimodality thyroid imaging had improved our understanding of thyroid disease, current indications for thyroid imaging are the solitary or dominant thyroid nodule, an upper mediastinal mass, differentiation of hyperthyroidism, detection and staging of postoperative thyroid cancer, neonatal hypothyroidism, thyroid developmental anomalies, and the thyroid mass post-thyroidectomy for benign disease. To provide optimal, cost-effective, care for the thyroid patient, the physician must understand the advantages and disadvantages of each imaging modality--scintigraphy, real-time sonography (RTS), computed tomography, and magnetic resonance--in specific clinical settings. Similarly, preoperative noninvasive localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism undergoing their initial neck exploration usually is not warranted. In this situation, the best localization procedure is to enlist the services of an experienced parathyroid surgeon. However, if this is not feasible because of local constraints, both sestamibi methoxy isobutyl isonitrile (MIBI) scintigraphy and magnetic resonance imaging (MRI) provide excellent localization (< 90%) of juxta-thyroidal and ectopic parathyroid adenomas. Hyperplastic glands are more difficult to detect because of their smaller size, and tandem studies (MIBI and MRI) should provide higher sensitivity before initial exploration, especially in patients with ectopic glands. In patients with persistent or recurrent disease, multimodality imaging with MIBI, MR, computed tomography and RTS in a sequential fashion is warranted to optimize two-test, site-specific localization.

Serum vitamin D metabolites and calcitriol receptor concentration in parathyroid tissue in primary hyperparathyroidism.

Vitamin D metabolites in serum and calcitriol receptor concentration in parathyroid tissue were examined in 52 patients operated on for primary hyperparathyroidism. The calcitriol receptor levels were not different in parathyroid adenomas (mean 224 fmol/mg of protein, range 29-509, N = 43), normal parathyroid tissue (mean 245, range 31-690, N = 20), and primary parathyroid hyperplasia (mean 172, range 46-477, N = 9). Preoperative serum levels of calcitriol concentration correlated inversely to the calcitriol receptor in normal parathyroid tissue in patients with adenoma (r = -0.57, N = 17, p = 0.017), but no such correlation was found in the corresponding adenomas (r = 0.14, p = 0.59). In 31 patients in whom both pre- and postoperative vitamin D metabolite analyses were carried out, 23 had lower calcitriol postoperative concentrations compared to preoperative values (p = 0.012, sign test). No change was found in the other vitamin D metabolites postoperatively. By multiple regression analysis calcitriol concentration in serum was inversely correlated to the serum concentration of urea and phosphate (p = 0.003). We conclude that calcitriol may influence calcitriol receptor expression in normal parathyroid tissue, but not in adenomatous parathyroid gland. Furthermore, serum calcitriol was correlated to the renal function, and phosphate level, and in most patients the calcitriol concentration was lower after the operation.

Primary Hyperparathyroidism: A Surgical Perspective

Primary hyperparathyroidism is a common disorder and one that can usually (approximately 95%) be successfully treated by parathyroidectomy. PTH assays have become quite accurate for confirming the diagnosis. In patients with malignancy-associated hypercalcemia, parathyroid-like protein levels are usually increased, and radioimmunoassays being developed to quantitate serum levels of this protein will make the diagnosis easier. Treatment for a parathyroid adenoma is removal of the tumor and identification of the normal parathyroid glands. Treatment for primary or secondary hyperplasia is usually subtotal parathyroidectomy. Recurrent hyperparathyroidism is uncommon, except in patients with familial hyperparathyroidism, MEN-1 parathyroid carcinoma, or renal failure and secondary hyperparathyroidism. Persistent hyperparathyroidism is more common and is usually due to surgeon inexperience, but it is also caused by ectopically situated parathyroid glands, multiple abnormal parathyroid glands, or supranumerary parathyroid glands. Preoperative localization studies using ultrasound, thallium-technetium scanning, MRI, or CT scanning are reliable in patients with solitary parathyroid adenomas, but often fail to detect all of the abnormal parathyroid tissue in patients with multiple abnormal parathyroid glands. Intraoperative use of urinary cyclic AMP assays and rapid PTH assays have recently been used experimentally during parathyroid explorations to determine whether all hyperfunctioning parathyroid tissue has been removed, but these methods are not yet reliable or fast enough to be generally accepted. Most patients with primary hyperparathyroidism who are successfully treated by parathyroidectomy experience psychological, clinical, and metabolic benefits.

Use of thallium-technetium parathyroid scans.

Localization of parathyroid pathology prior to reoperative neck exploration for hyperparathyroidism decreases operating time and potential morbidity. A color-graded nuclear scan using computer subtraction of technetium 99m from thallium-201 images is an accurate means of locating the parathyroid tissue in patients who have previously had one or more neck explorations.

Role of selective venous catheterization of the small thyroid veins as a diagnostic study in hypercalcemic states

Previous studies of selective venous catheterization stress its value in localizing hyperfunctioning parathyroid tissue in patients with an established diagnosis of hyperparathyroidism. Our study presents our experience with selective venous catheterization as a diagnostic aid in the differential diagnosis of hypercalcemia. In our four patients, an extensive metabolic work-up did not resolve the differential diagnosis of hypercalcemia, and selective venous catheterization provided the ultimate data that led to the correct diagnosis of hypercalcemia in each patient. Selective venous catheterization can be an important diagnostic study in carefully selected patients with hypercalcemia.