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Background: Primary hyperparathyroidism historically necessitated bilateral neck exploration to remove abnormal parathyroid tissue. Improved localization allows for focused parathyroidectomy with lower complication risks. Recently, positron emission tomography using radiolabeled 18F-fluorocholine demonstrated high accuracy in detecting these lesions, but its cost-effectiveness has not been studied in the United States., Methods: A decision tree modeled patients who underwent parathyroidectomy for primary hyperparathyroidism using single preoperative localization modalities: (1) positron emission tomography using radiolabeled 18F-fluorocholine, (2) 4-dimensional computed tomography, (3) ultrasound, and (4) sestamibi single photon emission computed tomography (SPECT). All patients underwent either focused parathyroidectomy versus bilateral neck exploration, with associated cost ($) and clinical outcomes measured in quality-adjusted life-years gained. Model parameters were informed by literature review and Medicare costs. Incremental cost-utility ratios were calculated in US dollars/quality-adjusted life-years gained, with a willingness-to-pay threshold set at $100,000/quality-adjusted life-year. One-way, 2-way, and threshold sensitivity analyses were performed., Results: Positron emission tomography using radiolabeled 18F-fluorocholine gained the most quality-adjusted life-years (23.9) and was the costliest ($2,096), with a total treatment cost of $11,245 or $470/quality-adjusted life-year gained. Sestamibi single photon emission computed tomography and ultrasound were dominated strategies. Compared with 4-dimentional computed tomography, the incremental cost-utility ratio for positron emission tomography using radiolabeled 18F-fluorocholine was $91,066/quality-adjusted life-year gained in our base case analysis, which was below the willingness-to-pay threshold. In 1-way sensitivity analysis, the incremental cost-utility ratio was sensitive to test accuracy, positron emission tomography using radiolabeled 18F-fluorocholine price, postoperative complication probabilities, proportion of bilateral neck exploration patients needing overnight hospitalization, and life expectancy., Conclusion: Our model elucidates scenarios in which positron emission tomography using radiolabeled 18F-fluorocholine can potentially be a cost-effective imaging option for primary hyperparathyroidism in the United States. Further investigation is needed to determine the maximal cost-effectiveness for positron emission tomography using radiolabeled 18F-fluorocholine in selected populations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Preoperative parathyroid imaging guides surgeons during parathyroidectomy. This study evaluates the clinical impact of 18 F-fluorocholine positron emission tomography for preoperative parathyroid localization on patients with primary hyperparathyroidism., Methods: Patients with primary hyperparathyroidism and indications for parathyroidectomy had simultaneous 18 F-fluorocholine positron emission tomography imaging/magnetic resonance imaging. In patients who underwent subsequent parathyroidectomy, cure was based on lab values at least 6 months after surgery. Location-based sensitivity and specificity of 18 F-fluorocholine positron emission tomography imaging was assessed using 3 anatomic locations (left neck, right neck, and mediastinum), with surgery as the gold standard., Results: In 101 patients, 18 F-fluorocholine positron emission tomography localized at least 1 candidate lesion in 93% of patients overall and in 91% of patients with previously negative imaging, leading to a change in preoperative strategy in 60% of patients. Of 76 patients who underwent parathyroidectomy, 58 (77%) had laboratory data at least 6 months postoperatively, with 55/58 patients (95%) demonstrating cure. 18 F-fluorocholine positron emission tomography successfully guided curative surgery in 48/58 (83%) patients, compared with 20/57 (35%) based on ultrasound and 13/55 (24%) based on sestamibi. In a location-based analysis, sensitivity of 18 F-fluorocholine positron emission tomography (88.9%) outperformed both ultrasound (37.1%) and sestamibi (27.5%), as well as ultrasound and sestamibi combined (47.8%)., Conclusion: Long-term results in the first cohort in the United States to use 18 F-fluorocholine positron emission tomography for parathyroid localization confirm its utility in a challenging cohort, with better sensitivity than ultrasound or sestamibi., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Identification of diseased and normal parathyroid glands during parathyroid surgery can be challenging. The aim of this study was to assess whether near-infrared (NIR) fluorescence imaging using administration of a low-dose Methylene Blue (MB) at the start of the operation could provide optical guidance during parathyroid surgery and assist in the detection of parathyroid adenomas., Methods: Patients diagnosed with primary hyperparathyroidism planned for parathyroidectomy were included. Patients received 0.5 mg/kg MB intravenously directly after start of anesthesia. During the operation, NIR fluorescence imaging was performed to identify parathyroid adenomas. Imaging results were compared with a previous published feasibility study in which 12 patients received MB after intraoperative identification of the adenoma., Results: A total of 13 patients were included in the current study. In 10 of 12 patients with a histologically proven adenoma, the adenoma was fluorescent. Mean signal to background ratio was 3.1 ± 2.8. Mean diameter of the resected lesions was 17 ± 9 mm (range 5-28 mm). Adenomas could be identified up to 145 minutes after administration, which was the longest timespan until resection. Interestingly, in 3 patients, a total of 6 normal parathyroid glands (median diameter 2.5 mm) with a signal to background ratio of 1.8 ± 0.4 were identified using NIR fluorescence imaging., Conclusion: Early administration of low-dose MB provided guidance during parathyroidectomy by identifying both parathyroid adenomas and normal parathyroid glands. In patients in whom difficult identification of the parathyroid adenoma is expected or when normal glands have to be identified, the administration of MB may improve surgical outcome., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Intrathyroidal parathyroid adenomas (ITPAs) are a rare entity. The aim of this study is to describe the experience of 2 endocrine surgery centers and to distinguish characteristics of intrathyroidal parathyroid adenoma and nonintrathyroidal parathyroid adenomas., Methods: We included patients who had undergone operations for primary hyperparathyroidism who had intrathyroidal parathyroid adenomas. Patients with single intrathyroidal parathyroid adenomas were also compared to age- and sex-matched controls with nonintrathyroidal parathyroid adenomas., Results: Of 4,868 patients who underwent parathyroidectomy between January 2002 and June 2011, we identified 53 (1%) patients with intrathyroidal parathyroid adenoma. Sestamibi and ultrasound scans correctly identified the adenoma in 35 (70%) and 11 (61%) cases, respectively. Single adenomas were identified in 44 (83%) patients, double adenomas in 4 (8%) patients, and hyperplasia in 5 (9%) patients. Lobectomy was performed in 17 (32%) patients; enucleation was used in 36 (68%) patients. Cure was achieved in all patients and no patients experienced a recurrence. Patients with single intrathyroidal parathyroid adenomas had significantly smaller glands than patients with nonintrathyroidal parathyroid adenomas (325 ± 47 vs 772 ± 61 mg; P < .0001); however, no significant difference was identified between the groups with regard to demographics, symptoms, preoperative laboratory values, or outcomes., Conclusion: Single intrathyroidal parathyroid adenomas are smaller than nonintrathyroidal parathyroid adenomas, but patients with intrathyroidal parathyroid adenomas present with similar laboratory values and symptoms. Recognition of this rare entity can lead to a successful surgical outcome., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Purpose: We hypothesized that patients referred for the evaluation and management of primary hyperparathyroidism (pHPT) often do not have pHPT and that they may be harmed by unwarranted parathyroidectomy (PTX)., Methods: We reviewed all patients who were referred to our endocrine surgery practice between 2008 and 2011 with International Classification of Diseases, Ninth Revision codes for HPT (252.00), benign or malignant parathyroid tumors (227.1, 194.1, respectively), or hypercalcemia (275.42). Patients with renal failure were excluded. Clinical parameters for investigation included age, sex, presentation, laboratories, imaging studies, and referring physician., Results: Three hundred twenty-four patients were referred for pHPT. The diagnosis was confirmed in 265 (82%), of whom 211 (80%) underwent PTX. Misdiagnoses occurred in 60 of 324 patients (19%). Of these, 54 (90%) had secondary HPT and 6 (10%) had hypercalcemia but no pHPT. Before referral, 70% of misdiagnosed patients underwent localizing studies, 57% of which suggested a positive finding., Conclusion: Considerable confusion exists regarding the differentiation of primary and secondary HPT. Surgeons should be cautioned that patients who are referred for parathyroidectomy, even those with complete laboratory and radiographic evaluations, might not have pHPT at all., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: We reviewed reoperations for persistent or recurrent sporadic parathyroid adenoma to evaluate and compare our current results and outcomes to our previous experience., Methods: From 1996 to 2008, 237 patients with persistent or recurrent hyperparathyroidism after failed operation underwent reoperation. Patients were re-explored with the assistance of non-invasive and sometimes invasive imaging., Results: A missed adenoma was suspected pre-operatively in 163 patients. Reoperation resulted in long-term resolution of hypercalcemia in 92%. Adenomas were in entopic locations in 32%; the most frequent ectopic location was the thymus (20%). Sestamibi scanning and ultrasonography were the most successful non-invasive imaging studies (96% positive predictive value (PPV) and 84% PPV respectively). Forty-four percent of patients had a reoperation based solely on non-invasive imaging. Of the invasive procedures performed, arteriography resulted in the best localization (92% PPV). Permanent recurrent laryngeal nerve injury occurred in 1.8%., Conclusion: Compared to our prior experience (1982-1995), outcomes remained similar (92% resolution of hypercalcemia and 1.8% recurrent nerve injury currently versus 96% and 1.3% previously). Fewer patients received invasive studies for pre-operative localization (56% vs 73%, respectively). The decreased use of invasive imaging is due to technical improvements and greater confidence in the combination of ultrasonography and sestamibi scanning.

Background: The aim of this study was to determine the ability of localizing studies and rapid intraoperative parathyroid hormone (PTH) to predict the success of a limited approach in patients who then underwent bilateral exploration., Methods: Preoperative sestamibi-iodine subtraction scan and neck ultrasonography (US) were used to direct a focal (1-gland) and unilateral (1-sided) parathyroid exploration by using rapid intraoperative PTH determinations in 350 patients with sporadic primary hyperparathyroidism. Regardless of the findings, the contralateral side was then explored., Results: A single gland was predicted by sestamibi in 290 patients (83%), US in 298 patients (85%), and concordance of both in 205 patients (59%). Unilateral parathyroid exploration, directed by these studies, would correctly identify single-gland disease in only 68%, 74%, and 79%, respectively. The addition of intraoperative PTH would increase the success rate to 73%, 77%, and 82%, respectively. The finding of 2 normal or 2 abnormal glands on 1 side would force bilateral exploration, and additional unsuspected pathology was found in 13%, 13%, and 9%, respectively. This failure rate would increase to 21%, 18%, and 15%, respectively, if the analysis assumed a focal rather than unilateral approach to the initial exploration., Conclusions: Even in patients with concordant sestamibi and US scans, and an appropriate PTH drop, additional abnormal parathyroid glands were found on complete exploration in 15%. A bilateral approach offers the best opportunity for the long-term cure of primary hyperparathyroidism.

Background: We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas., Methods: This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease., Results: All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%., Conclusions: We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

Background: In an effort to determine an efficient algorithm for the evaluation of patients with parathyroid adenomas in the reoperative setting, we explored the combination of using ultrasound scans (US) and sestamibi scintigraphy as the only preoperative imaging tests., Methods: We analyzed the outcomes of 62 consecutive patients who were treated between January 1995 and May 1999 and who were referred for persistent primary hyperparathyroidism after initial surgical exploration, at which time no abnormal parathyroid glands had been found. Although all patients underwent US, computed tomography scan, magnetic resonance imaging, and sestamibi scan, we analyzed the success of localization and reoperation using only the results of US and sestamibi scan., Results: Sixty-one patients (98%) underwent curative reoperations. The sensitivity, positive predictive value, and accuracy for US were 90%, 86%, and 84%, respectively; the corresponding values for sestamibi imaging were 78%, 94%, and 74%, respectively. In 58 of 62 cases (94%) preoperative US and/or sestamibi scan accurately identified the adenoma. In 3 patients for whom combined US and sestamibi scan were inaccurate, 1 adenoma was found by intraoperative US in the strap muscle; 1 adenoma was found by blind cervical thymectomy, and 1 adenoma was found by planned sternotomy that was based on computed tomography findings., Conclusions: This study supports an algorithm of obtaining US and sestamibi scan as the initial and perhaps only preoperative localization tests for patients with primary hyperparathyroidism after failed operation, at which time no abnormal glands had been found.

Background: The goal of this study was to identify factors that might aid in diagnosis and intraoperative management of hyperparathyroidism., Methods: We analyzed biopsy specimens of 242 parathyroids from 159 patients by use of flow cytometry and image cytometry (ICM) for DNA index (DI), defined as the content of nuclear DNA compared with that expected for a DNA diploid standard, for proliferative index (PI), and for ploidy (diploid versus aneuploid or tetraploid)., Results: True normal and normal parathyroids from patients with solitary adenomas were uniformly diploid. Abnormal ploidy (aneuploidy or tetraploidy) was identified frequently in adenomas and occasionally in hyperplasias with the exception that multiple endocrine neoplasia (MEN) biopsy specimens were uniformly diploid. DI for adenomas was similar to that for hyperplasias, and DI of both was higher than for normal glands. ICM-DI correlated positively with flow cytometry-DI and patient age and inversely with serum parathyroid hormone. PI was relatively low in all groups but was higher for hyperplasias versus normal parathyroids from patients with solitary adenomas and MEN versus non-MEN. PI correlated inversely with patient age., Conclusions: DI by ICM differentiates normal from abnormal parathyroids. DI might influence extent of resection in two- and three-gland hyperplasia and selection of the most appropriate gland for autografting and cryopreservation in patients with four-gland hyperplasia.

Cowden's disease is a well-described clinical syndrome, the primary symptoms of which are orocutaneous hamartomas and disseminated gastrointestinal polyposis. In general, the gastrointestinal polyps are benign, and the incidence of malignant transformation is believed to be low. Other associated manifestations of Cowden's disease include breast cancer and thyroid disease (benign and malignant). A patient with previously unrecognized Cowden's disease underwent upper gastrointestinal endoscopy for surveillance of hyperplastic gastric polyps, and a gastric carcinoma in situ was detected. During the course of follow-up the patient was found to have primary hyperparathyroidism resulting from a parathyroid adenoma. Although several benign proliferative and malignant conditions are associated with Cowden's disease, neither parathyroid adenoma nor gastric carcinoma has been reported previously.

Background: Between 5% and 10% of patients who undergo cervical exploration for primary hyperparathyroidism will have persistent or recurrent hyperparathyroidism. Many of these patients have parathyroid tumors in unusual locations. One such site of ectopic parathyroid tissue is an undescended parathyroid adenoma at or superior to the carotid bifurcation. We describe our experience with the preoperative localization and surgical management of undescended parathyroid adenomas., Methods: From 1982 to 1993 a consecutive series of 255 patients have undergone localization studies and surgical exploration for persistent or recurrent hyperparathyroidism at the Clinical Center of the National Institutes of Health. Operative strategy was determined by review of the patient's surgical history, disease reports, and data from localizing studies. Patients with an undescended parathyroid adenoma identified before the operation were examined with a direct approach high in the neck. Patients who did not have definitive preoperative localization were explored with the previous transverse cervical incision., Results: Seventeen undescended parathyroid adenomas were identified in 255 patients. Thirteen (76%) of 17 patients had an undescended parathyroid adenoma precisely localized before the operation and were examined via a limited, oblique incision high in the neck anterior to the sternocleidomastoid muscle. In the 13 patients who had undergone accurate localization before the operation, the median operative time was 75 minutes compared with 235 minutes for four patients who did not have an undescended parathyroid adenoma identified before the operation and were examined via a previous transverse cervical incision. All patients were cured of their hyperparathyroidism., Conclusions: Undescended parathyroid adenomas were the cause of failed cervical exploration in 17 (7%) of 255 patients. Accurate preoperative localization of these lesions is possible in most cases with a combination of noninvasive and invasive modalities. Successful preoperative localization can convert a prolonged exploration of the neck and mediastinum into a brief, curative procedure with minimal morbidity.

Background: The purpose of this study was to assess the contribution of technetium 99m sestamibi iodine 123 (T/S) imaging to preoperative and intraoperative management of patients with persistent hyperparathyroidism., Methods: During a period of 10 months, all patients being prepared for reoperative parathyroid surgery (n = 10), two patients deemed significant operative risks (one patient with severe chronic obstructive pulmonary disease and one patient with severe cervical spine ankylosing spondylitis), and two patients who had undergone prior thyroid operation were studied with T/S imaging. Six patients undergoing reoperative surgery had undergone one, three had undergone two, and one had undergone three prior procedures., Results: T/S imaging correctly localized 14 of 16 parathyroid tumors. By comparison, only 1 of 6 thallium technetium and 3 of 12 computed tomography (CT) scans (in seven patients) were positive. T/S imaging guided the reoperative surgical approach accurately in 12 of 14 patients, including one case of an undescended left lower gland at the level of the mandible and identification of a third gland on the left in another case. Sternal split was required to remove three lesions localized by T/S imaging, two beneath the aortic arch and one nestled in the aortopulmonary window in a patient who had undergone two prior procedures including a sternal split. In these three cases T/S imaging was particularly useful, because CT scans, thallium technetium scans, magnetic resonance imaging, and arteriography were not diagnostic. The outcome after operation was favorable in all 14 cases, with correction of hypercalcemia and no permanent laryngeal nerve injuries or hypocalcemia., Conclusions: We concluded that T/S imaging is more accurate than thallium technetium and CT scans in evaluation of patients with persistent hyperparathyroidism.

Background: Parathyroid carcinoma is often over-diagnosed based on histologic appearance alone. We limited the definition of the disease to patients with recurrence, metastases, or frank capsular invasion on histologic examination., Methods: With these criteria, fourteen cases of parathyroid carcinoma seen at our institution from 1955 to the present were identified., Results: All patients presented with hypercalcemia, and all deaths were due to hypercalcemia. Two patients have been free of disease after initial operation for 31 and 180 months. Six other patients had a prolonged course with a median survival more than 80 months. Two of these patients have undergone one reexcision each for local recurrence, and four have undergone multiple resections for local recurrence or metastases. These reoperations usually resulted in satisfactory, albeit temporary, control of hypercalcemia. Finally, six patients died of disease after an aggressive course, with a short median survival (47 months). Four of these patients were seen in the 1950s before an aggressive approach to metastatic disease was adopted., Conclusions: The types of clinical courses observed in this study may be more reflective of the varied biologic features of parathyroid carcinoma and the approach to recurrence than of the initial operations. For patients with recurrent or distant disease, an operation appears to prolong survival and palliate the symptoms of hypercalcemia.

The incidence of parathyroid carcinoma in patients surgically treated for primary hyperparathyroidism at the University of Michigan Hospital was 0.4% during an 18-year period. The courses of the five patients with metastatic disease are described. Histologic reevaluation and assessment of the DNA ploidy pattern were performed in each case. Localization studies preceded all reexplorations. The number of operative procedures in each patient ranged from two to 10. Two patients are living with recurrent disease and one has been disease free for 42 months. Two patients died after 2 and 12 years, respectively. Three patients had aneuploid tumors; one had a diploid tumor. One patient had both aneuploid and diploid cell populations. Dilemmas in diagnosis, localization, and medical and surgical management were encountered in patients with metastatic carcinoma. The chosen treatment should be evaluated individually in each case because of the variability in aggressiveness of this malignancy. Surgical resection proved most effective in some of these patients for both local and distant recurrences. Bisphosphonates and gallium nitrate have been reported to be effective in controlling hypercalcemia. Only the former had some effect in one of our patients.

Congenital hypothyroidism may result in severe mental retardation if this condition is not diagnosed in the neonatal period. Primary hyperparathyroidism in children is even more uncommon, and by 1977 had been reported in only 60 children under the age of 16 years. To our knowledge, we are reporting the first child with both congenital hypothyroidism and primary hyperparathyroidism. Because the normal anatomic relationship of the parathyroid glands to the thyroid gland was absent, preoperative localization studies were necessary. Ultrasonography, radionuclide scanning, and magnetic resonance imaging all indicated a right paratracheal mass in the region where the right lobe of the thyroid gland should be located. At operation, a single, enlarged parathyroid gland that measured 1.5 X 1.2 X 0.5 cm and weighed 500 mg was removed. The discharge serum calcium level was 9.3 mg/dl and has remained normal 2 years later.

Adenolipoma--or parathyroid hamartoma--has been described s a very rare lesion of the parathyroid gland, often unassociated with clinical hyperparathyroidism. A few reported cases in which the diagnosis was discovered pathologically following parathyroid resection for hyperparathyroidism have been called unique. In a 2-year period the diagnosis of parathyroid adenolipoma was made in three instances, with each clinical presentation consistent with primary hyperparathyroidism. In the first patient, a 64-year old man reporting to an emergency department for treatment of migraine headache, a prolonged history of unrecognized hypercalcemia was discovered, and he underwent cervical exploration. At operation, a 105 by 2.0 cm tumor weighing 17.5 gm was encountered. The other two patients were middle-aged women who had hypercalcemia (one requiring preoperative calcitonin treatment). The diagnosis of adenolipoma was made morphologically, although the clinical course was otherwise indistinguishable from other forms of primary hyperparathyroidism. Each of the three patients were cured following adenolipoma resection. This small series of patients in the experience of a single surgeon in a brief period might indicate that this diagnosis is by no means rare, and the functional nature of these tumors was the characteristic that brought them to diagnosis. The hypercalcemia was somewhat more severe in these cases--but the hyperparathyroidism was otherwise unremarkable. The morphologic features of these tumors include unusual size, proliferating fat content, and a fibrillar stroma. Adenolipoma of the parathyroid can cause primary hyperparathyroidism and should be considered in the differential diagnosis of the morphologic lesions of the parathyroid glands that can produce a hypercalcemic syndrome.

The surgeon's gross evaluation, the hematoxylin and eosin stain, which assesses extracellular fat, and a new intracellular fat stain, osmium carmine, were comparatively evaluated in 30 consecutive patients who underwent surgery for primary hyperparathyroidism. The surgeon's gross judgment of enlarged and normal parathyroid tissue resulted in the correct functional assessment in 98% and 97% of the glands, respectively. The surgeon's functional assessment was correct in seven of 10 parathyroid glands that were considered by gross examination to be slightly enlarged (50 to 80 mg). The osmium carmine intracellular fat stain provided a correct functional assessment in all 10 of these glands. The osmium carmine stain also appears to have a role in providing scientific quantitative data to limit operations in patients who have a parathyroid adenoma to removal of the adenoma and biopsy of a grossly normal gland that demonstrates normal intracellular fat. Only one side of the neck was explored in 11 patients who fulfilled these criteria. There has been no persistent or recurrent hypercalcemia in these patients.

Extracapsular hemorrhage from spontaneous rupture of a hyperplastic parathyroid gland is exceedingly rare. Rupture of an intrathoracic parathyroid adenoma mimicking a dissecting thoracic aortic aneurysm has been reported in two cases. Hypercalcemic crisis associated with contained hemorrhage within a parathyroid adenoma has been well documented. We present the first reported case of spontaneous rupture and extracapsular hemorrhage of a cervical parathyroid adenoma. Serum calcium levels should be obtained when spontaneous cervical or mediastinal hemorrhage develops without obvious cause.

Lipoadenoma is the accepted diagnosis of a single enlarged parathyroid gland that contains large quantities of mature fat cells and focal myxoid stroma, all widely separating small parenchymal cell nests in patients with hyperparathyroidism. Here we are reporting, for the first time, on five cases of hyperparathyroidism in which all four parathyroid glands are enlarged and each gland is noted to have an admixture of fat and parenchymal cells. We will introduce the descriptive diagnosis of lipohyperplasia to name this condition and keep it in perspective with other forms of parathyroid disease. All five patients were women between the ages of 36 and 62 years who underwent neck exploration, at which time four enlarged light-tan parathyroid glands were observed. Three and one half gland resections were performed, and all patients returned to a normocalcemic state except one who had borderline serum hypercalcemia after operation. Most of the resected parathyroid glands weighed in the range of 100 to 200 mg. The largest measured gland weighed 820 mg. Parathyroid histology showed an admixture of mature fat cells with parathyroid parenchymal cells often in a 1:1 ratio. One patient who had renal failure exhibited a lower ratio of fat cells. Two patients had chronic lymphocytic thyroiditis that was severe enough to require synthetic thyroid hormone therapy. Two patients had a history of urinary tract infections. Three patients had hypertensive cardiovascular disease, and several patients had arteriosclerotic cardiovascular disease. One patient had diabetes mellitus, one had a history of pituitary adenoma, and one had polydipsia. All of these patients were first seen with parathyroid glands measuring an average of five times normal size, yet they showed the usual 50% fat/50% parenchyma pattern of normal mature parathyroid glands. This means that the enlarged glands contain a 500% increase in parathyroid tissue, justifying the diagnostic term "lipohyperplasia." This easily represents enough parathyroid tissue to generate excessive parathyroid hormone production. At this time, there is no explanation of the pathogenesis of lipohyperplasia or how it varies from other previously described forms of parathyroid hyperplasia.

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.

Hyperparathyroid crisis is a rare disease manifested by elevated serum calcium, weakness, nausea and vomiting, altered states of consciousness, and elevated circulating parathormone. This hypercalcemic state is noted for a frequently acute presentation and associated high mortality rate, approaching 60% in some series. Ten patients in parathyroid crisis were observed in a consecutive personal series of 325 cases of operatively proved hyperparthyroidism. All 10 patients were successfully treated. Each patient remained or lapsed into persistent coma despite extensive medical management and normalization of serum calcium in some instances. An emergency parathyroidectomy was performed in all cases. Reversal of the comatose state was noted in all patients within 24 hours, followed by gradual normalization of serum calcium. Serum calcium ranged from 15 to 19.6 mg/dl. The blood urea nitrogen level was elevated in six patients. A single adenoma was found in nine patients and multiglandular disease involving the neck and the mediastinum in one. All patients survived. The successful treatment of this disease demands prompt and accurate diagnosis coupled with vigorous medical therapy and emergency parathyroidectomy if the patient's status continues to deteriorate.

During the past 3 years (June, 1974, to July, 1977), 51 patients underwent reoperation for persistent or recurrent hyperparathyroidism at the Mayo Clinica. The overall success rate for cervical reoperation was 72% and for mediastinal reoperation, was 64%. Arteriography alone provided accurate preoperative localization of missing parathyroid tumors in 11 of 17 patients at a cost per patient benefited of approximately $1,700. Selective thyroid venous sampling with parathormone assay alone correctly lateralized hyperfunctioning glands in only four of nine patients at a cost per patient benefited of approximately $1,900. When used in combination, these studies provided correct localization or lateralization of parathyroid tumors in five of seven patients at a cost per patient benefited of approximately $2,000. Three patients experienced significant neurological complications as a result of thyrocervical arteriography. There were no complications due to venous sampling. In patients who has undergone a less than thorough initial explorations due to venous sampling. In patients who had undergone a less than thorough initial exploration of the neck, the success rate for reoperation was not enhanced by obtaining preoperative tumor localization studies. However, in those patients who had had a thorough and systematic exploration of the neck at their first operations, the success rate for reoperation was almost doubled when preoperative arteriography or venous sampling (or both) was employed.

Forty-three cases of primary hyperparathyroidism were studied with the specific red cell adherence test (SRCA) to determine the presence or absence of ABO(H) cell surface antigens on abnormal parathyroid tissue. Of the 27 patients with the clinicopathologic diagnosis (CPD) of adenoma, 24 (89%) had lost the ABO(H) cell surface antigen of the abnormal gland. Among the 15 patients with the CPD of hyperplasia, the parathyroid tissue from three (20%) had lost its red cell antigen. In one patient, a metastasis from a parathyroid carcinoma had lost the ABO surface antigen. Several patients in whom conflicting SRCA and CPD were obtained had factors that raised doubts as to the validity of their CPD. The SRCA is a simple test that may aid in the difficult differentiation between parathyroid adenoma and hyperplasia.

The appropriate choice of imaging techniques to localize parathyroid tumors preoperatively remains controversial. We report the first prospective, blinded study to compare the efficacy of four imaging modalities in 100 patients with primary hyperparathyroidism (pHPT). Patients were examined by computer-assisted thallium 201/technetium 99m subtraction scintigraphy (TTS), computed tomography (CT), ultrasonography (US), and magnetic resonance (MR). Each study was performed and interpreted independently. Subsequent neck exploration and "curative" parathyroidectomy allowed correlation of surgical findings with imaging reports to score their accuracy. Overall sensitivities of the four imaging modalities were TTS, 73%, CT, 68%, US, 55%; and MR, 57%; with respective specificities of 94%, 92%, 95%, and 87%. Sensitivities for lesions located below the thyroid gland (thymic tongue and mediastinum) were TTS, 90%; CT, 46%; US, 44%; and MR, 50%; with respective specificities of 100%, 99%, 100%, and 94%. There was a significant increase in overall sensitivity when TTS and CT (90%, p less than 0.01) or TTS and US (85%, p less than 0.05) were used together; however, the combination of any three or even four imaging modalities did not increase sensitivity further. For small parathyroid tumors (less than or equal to 250 mg), no imaging technique had a sensitivity of more than 50%. None of the imaging studies accurately localized small hyperplastic parathyroid glands found in patients with multiple gland disease. Preoperative parathyroid imaging may not be indicated in pHPT patients undergoing first-time neck exploration because surgeons experienced in parathyroid surgery have a 93% to 96% cure rate.

Selective venous catheterization with parathyroid hormone radioimmunoassay has been used effectively to localize parathyroid tumors in patients who have previously had failed parathyroid operations. We have analyzed our experience comparing radioimmunoassay and bioassay of parathyroid hormone for localization of parathyroid tumors by selective venous sampling. The bioassay, which uses a guanyl nucleotide-amplified adenylate cyclase assay with canine renal plasma membranes, localized the tumors in six of nine patients who had previously undergone neck operations. The radioimmunoassay localized the tumors in eight of the nine patients. The advantage of the bioassay is that it requires only 50 microliter serum per per sample and 1 day of assay time compared with the radioimmunoassay, which requires 700 microliter serum per sample and 7 days of assay time. The bioassay may be important in patients with severe hyperparathyroidism who require an urgent operation.

The objective of this review was to study the clinical course and the applicable diagnostic criteria in 12 patients with functioning parathyroid carcinoma, two patients with nonfunctioning parathyroid carcinoma, and a fifteenth patient who had an atypical intrathyroid tumor. The biologic patterns fell into four groups. The patients with functioning parathyroid carcinoma had either a prolonged tumor existence punctuated by hypercalcemic episodes ameliorated by operation to remove the tumor or an aggressive course with widespread metastases. The nonfunctioning cancers were aggressive cancers. The fourth group had one patient (others could have been considered) in whom a definitive diagnosis could not be made. The initial recognition of this cancer is sometimes difficult because consistent diagnostic features, either clinically or pathologically, are lacking. Enbloc resection at the first operation remains the best chance for cure. Surgical resection of recurrent disease appears to be the most effective palliative approach. Death results from hypercalcemia rather than from organ replacement by tumor.