Parathyroid cysts

Cystic neck masses may be accurately diagnosed by sonography, and some nonfunctioning parathyroid cysts can be cured by percutaneous aspiration. Primary hyperparathyroidism should be considered in all patients with cystic neck masses. Parathyroid cysts can often be recognized from the characteristics of the cyst fluid which is usually clear and colorless, contains elevated parathyroid hormone levels and normal or low thyroid hormone levels, and may contain parathyroid cells. Parathyroid cysts may be multiple; all four parathyroid glands should therefore be identified and appropriately removed or hyperparathyroidism may persist.     

Recurrent hyperparathyroidism due to implantation of parathyroid tissue

Recurrence of hyperparathyroidism after initially successful primary operation is usually caused by inadequate resection of diseased tissue or recurrent carcinoma. Since it is known that normal parathyroid tissue may be autotransplanted into a muscle bed, it is plausible that inadvertent implantation of parathyroid tissue spilled at operation may occur. In four of 23 reoperations for hyperparathyroidism in an 11 year period, we found evidence that iatrogenic parathyroid implantation had occurred. Two of the four patients had multiple parathyroid implants in the previous operative field, and one of these patients had documented spillage of a cystic adenoma during the original operation. Another two of the four patients were found to have recurrent adenomas containing suture material at sites of previous excision of the adenomas. No patient had gross or histologic evidence of parathyroid carcinoma. We conclude that inadvertently spilled parathyroid tissue may implant in the neck or mediastinum and cause persistent or recurrent hypercalcemia. Therefore, all efforts should be made to handle the parathyroid glands only by their pedicles and not to crush, suture, or violate the capsule. Needle aspiration of parathyroid cysts could lead to implantation along the needle tract.     

Cysts of the parathyroid glands. Apropos of 6 cases

Parathyroid cysts are rare lesions. Pathological examination distinguishes the "true" parathyroid cysts (non functional) most often present and cystic degeneration of a parathyroid adenoma (rare) with clinical or biochemical evidence of hyperparathyroidism. With the increased use of ultrasound and fine needle aspiration biopsies, the diagnosis of these cysts can be confirmed by an elevated parathyroid hormone (PTH) assay. The non-functioning parathyroid cysts can be successfully treated by total aspiration of the cyst fluid. Surgical exploration of all parathyroid glands is the treatment of choice for hyperparathyroidism. The different proposed etiologies for parathyroid cysts are discussed.     

Salivary heterotopia, cysts, and the parathyroid gland: branchial pouch derivatives and remnants

Five cases of periparathyroid salivary heterotopia associated with cysts were studied. The specimens were obtained from three men and two women age 36 to 62 years who underwent surgery for primary hyperparathyroidism (four patients) and thyroid nodule (one patient). The heterotopia-cyst combination occurred with normal and abnormal parathyroid glands (four inferior and one of unknown location). Review of histologic slides of all parathyroid glands excised from 258 patients during a 1-year period at the Mayo Clinic revealed two similar salivary gland-cyst units. Seven more cases featured one or more periparathyroid cysts, five with other nonsalivary-type epithelial accompaniments. One of the latter additionally had a focus of parathyroid cells in the cyst wall, and associated thyroid parenchyma with C cells, and cartilage.     

Surgical significance of undescended parathyroid gland in renal hyperparathyroidism

BACKGROUND: In renal hyperparathyroidism, in which basically all parathyroid glands are hyperplastic, overlooking one undescended parathyroid gland becomes important. METHODS: Between July 1973 and December 2004, 1750 patients in our department underwent parathyroidectomy for severely advanced renal hyperparathyroidism. We evaluated the frequency and location of undescended parathyroid glands and the clinical findings and the prognosis of patients with such glands. RESULTS: Undescended parathyroid glands in our series of renal hyperparathyroidism numbered 16 of 1750 cases (0.91%). In 9 patients, the glands were removed at the initial parathyroidectomy in our hospital. Two of these glands were detected by preoperative imaging; 6 glands were removed with an undescended thymus. The mean weight of the undescended parathyroid glands that were removed at initial operations was 470 mg (30 to 1392 mg). In 7 other patients, unrecognized undescended glands were responsible for persistent hyperparathyroidism in 6 patients and recurrent disease in 1 patient. In 4 of these 7 patients, the initial parathyroidectomy was performed at our hospital; in the other 3 patients, the initial parathyroidectomy had been done at another hospital, and the glands were removed on reoperation. The mean weight of these glands was 1295 mg (range, 444-2396 mg). In 12 of a total of 16 patients with undescended glands, there appeared to be an inferior parathyroid gland, and the other 4 glands appeared to be a superior gland. No glands were detected by sestamibi scans. CONCLUSION: In operations for renal hyperparathyroidism, an undescended parathyroid gland can be readily overlooked, which leads to persistent or recurrent hyperparathyroidism. Because an undescended parathyroid gland is not always an inferior gland, in surgery for persistent and/or recurrent renal hyperparathyroidism, it is very important to examine carefully the submandibular portion to detect such an undescended gland.     

Ectopic and supernumerary parathyroid glands in patients with refractory renal hyperparathyroidism

BackgroundThe aims of this study were to determine the rate of ectopic and supernumerary parathyroid glands and the outcome of surgical therapy in patients with refractory renal hyperparathyroidism.Materials and MethodsA retrospective review of all patients who underwent parathyroidectomy for refractory renal hyperparathyroidism was completed. Operative and pathology reports were reviewed, and the number and location of resected parathyroid glands, patient outcomes, and follow-up were determined.ResultsDuring the period 1993–2019, a total of 68 patients underwent subtotal or total parathyroidectomy for renal hyperparathyroidism. Of those, 59 patients (87%) were on dialysis for an average of 6.7 years. We determined that 18 patients (26%) had 24 ectopic parathyroid glands, including 9 (13%) patients with 11 supernumerary glands. A total of 2 patients had a supernumerary gland in a normal anatomic location. Of the 24 ectopic glands, 14 (58%) were in the thymus. After parathyroidectomy, 4 patients (5.9%) had persistent hyperparathyroidism, 6 patients (8.8%) developed recurrent hyperparathyroidism, and 2 patients (3%) had permanent hypoparathyroidism.ConclusionEctopic and supernumerary parathyroid glands occurred in 26% and 16% of patients with renal hyperparathyroidism, respectively, and the thymus was the most common location. Thorough neck exploration and transcervical thymectomy are important to help reduce persistent and recurrent hyperparathyroidism after parathyroidectomy for renal hyperparathyroidism.     

Initial failure of surgical exploration in patients with primary hyperparathyroidism

To determine the causes of failures of cervical exploration for primary hyperparathyroidism, we reviewed 892 patients operated on by one surgeon from 1953 to 1990. Twenty-seven patients (3%) remained hypercalcemic or developed hypercalcemia within 6 months of surgery. Of these, five patients had one adenoma removed initially; at reoperation, three patients had a second adenoma that was successfully removed, whereas the other two patients had hyperplasia and required subtotal parathyroidectomies. No enlarged parathyroid glands were identified in 22 patients. Eventually, six patients became normocalcemic spontaneously, seven patients underwent re-exploration with a successful outcome in all but one case, two patients had ectopic hyperparathyroidism associated with carcinoma elsewhere, and seven patients refused reoperation and remain hypercalcemic. The failure rate of surgical exploration for primary hyperparathyroidism can be reduced by systematically exploring all four parathyroid glands. All abnormal parathyroids should be removed with histologic verification. When no abnormal glands are found, localization studies should be performed before re-exploration.     

Different pathological findings in each of four parathyroid glands in a long-standing hemodialysis patient

A 51-year-old male patient with chronic renal failure, who had required dialysis for 22 years, presented with a cervical mass. Laboratory data were consistent with secondary hyperparathyroidism due to chronic renal failure. Cervical exploration was performed with excision of four parathyroid glands and autotransplantation of the normal gland into the forearm. The cervical tumor of the right inferior gland demonstrated parathyroid carcinoma histologically. Adenoma of the right superior gland and hyperplasia of the left superior gland were also recognized. The left inferior gland was normal. A few cases of parathyroid carcinoma in patients on maintenance hemodialysis have been previously reported. However, this is the first report in which all four parathyroid glands revealed different pathological findings: carcinoma, adenoma, hyperplasia and normal gland. Chronic stimulation of the parathyroid glands to release parathyroid hormone might have caused the variety of findings in the four parathyroid glands.     

Multiple parathyroid adenomas: report of thirty-three cases

An increasing number of patients with primary hyperparathyroidism are found to have two or three enlarged parathyroid glands. Of 865 patients successfully operated on by one surgeon (J.N.A.), multiple enlarged parathyroid glands (adenomas) were found and resected in 33 cases (3.8%), with resulting normocalcemia lasting from 1 to 22 years (mean 5.8). Twenty-nine patients had two adenomas and four had three adenomas. In 28 patients the multiple adenomas were synchronous. Twenty-five patients underwent removal of all of the enlarged parathyroid glands in one operation; in three patients one adenoma was removed, reoperation for persistent hypercalcemia was performed, and a second adenoma was resected with cure. In five patients one adenoma was removed, normocalcemia ensued for 3 to 18 years, and a second (metachronous) adenoma occurred and was resected successfully. Although 10 of 70 enlarged parathyroid glands removed were labeled hyperplasia, cure in all but one of our patients by selective resection of only enlarged parathyroid glands emphasizes the unreliability of histologic criteria in differentiating between parathyroid adenoma and hyperplasia. Based on this study, we support the existence of multiple adenomas and advocate removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism.     

Anatomical heterogeneity of parathyroid glands in posttransplant hyperparathyroidism

Successful renal transplantation may be complicated by persistent hyperparathyroidism due to diffuse parathyroid hyperplasia remaining from a prolonged period of pretransplant chronic renal failure treatment. Posttransplant hyperparathyroidism is distinct from primary hyperparathyroidism, being characterized by multiple gland involvement and diffuse hyperplasia rather than a single adenoma. The gross pathologic anatomy of the parathyroid glands was assessed in 17 successful renal transplant recipients. Individual and total gland volumes were measured at the time of total parathyroidectomy and forearm reimplantation. Parathyroid hyperplasia was heterogenous in both location and gland size. Right-sided glands were enlarged more than left-sided ones. Subjects with primary tubulointerstitial disease exhibited greater hyperplasia than patients with glomerular disorders. Clinicians should be aware of the heterogeneity of the gland enlargement in patients with diffuse parathyroid hyperplasia, so that these patients are not misdiagnosed as suffering from adenomatous parathyroid disease.     

The rationale against routine subtotal parathyroidectomy for primary hyperparathyroidism

Our therapeutic approach to the treatment of primary hyperparathyroidism has been the resection of only the abnormally enlarged parathyroid gland, the normal-appearing parathyroids being left intact. During the past twenty-five years we have operated on 292 patients with primary hyperparathyroidism. In all cases the serum calcium levels returned to within normal limits during the immediate postoperative period, and there were no instances of permanent hypoparathyroidism. To determine the long-term efficacy of this therapeutic approach, a retrospective study of 101 patients operated on for primary hyperparathyroidism during a nine year period from July 15, 1965 through June 30, 1974 was made. Of the 101 patients, eight were dead and nine could not be located. Of the remaining eighty-four patients, only two required reoperation because of recurrent hypercalcemia; one had MEA-I and eventually three and a half glands were removed, and the other had recurrent hypercalcemia after a three year normocalcemic interval, and after a second operation with resection of an enlarged parathyroid gland, he has remained normocalcemic. The other eighty-two patients (97 per cent of those reevaluated and 82 per cent of the total operated on) have remained symptom-free and normocalcemic for periods ranging from three to twelve years. Only one patient (if we exclude the patient with MEA-I) has elevated serum parathormone levels with borderline levels of serum calcium. Our results suggest that the optimal surgical treatment of primary hyperparathyroidism, except for cases of MEA, is resection of only the abnormally enlarged parathyroid glands after exploration and identification of all four glands in every case. If all four glands are enlarged, three and a half should be resected.     

Hypercalcemic hyperparathyroidism and hypophosphatemic osteomalacia complicating neurofibromatosis

Summary Neurofibromatosis is sometimes complicated by impaired renal tubular reabsorption of phosphate, hypophosphatemia, and osteomalacia. Hyperparathyroidism has also been reported in patients with neurofibromatosis. When hypercalcemia and elevated levels of parathyroid hormone are found in osteomalacia, however, it may be difficult to determine if the hyperparathyroidism was primary or tertiary. We describe a patient with neurofibromatosis, hypercalcemic hyperparathyroidism, hypophosphatemic osteomalacia, vitamin D deficiency, and clear-cell hyperplasia of all four parathyroid glands. Serial biomechanical, bone biopsy, and densitometric studies confirmed that treatment with ergocalciferol, calcium, and phosphate supplements significantly improved the osteomalacia but caused increased parathyroid overactivity. After subtotal parathyroidectomy, the parathyroid hormone concentration became normal and the bone mineral content increased at the spine and hip, but inappropriate phosphaturia persisted. The findings indicate that hyperparathyroidism, osteomalacia, and vitamin D deficiency adversely affect each other.     

Thallium-technetium subtraction scintigraphy as an aid to parathyroid surgery

We describe the application of thallium-technetium subtraction scintigraphy in nine patients with failed previous parathyroid surgery or with tertiary hyperparathyroidism due to chronic renal failure. The technique successfully located all adenomas, but only 45% of hyperplastic glands. The series included three abnormal glands located retrosternally. The technique appeared to be more useful in patients with primary hyperparathyroidism than in tertiary hyperparathyroidism, possibly related to differences in gland mass. We conclude that this method of scintigraphy is a valuable adjunct to the management of patients with parathyroid disorders, particularly those requiring revision surgery.     

Prospective evaluation of the efficacy of technetium 99m sestamibi and iodine 123 radionuclide imaging of abnormal parathyroid glands.

BACKGROUND. Technetium 99m sestamibi is an isonitrile radionuclide imaging agent that, when used with subtraction iodine 123 thyroid scans, has the potential for imaging abnormal parathyroid glands. METHODS. We prospectively evaluated 20 patients with hyperparathyroidism to study the efficacy of Tc 99m sestamibi and 123I subtraction radionuclide scanning for the imaging of abnormal parathyroid glands. All patients underwent neck exploration and histologic confirmation of all parathyroid glands identified. RESULTS. The solitary adenomas in 11 of 16 patients with primary hyperparathyroidism were localized with sestamibi scans. The scans in four of five patients with diffuse parathyroid hyperplasia showed bilateral localization consistent with enlarged glands. The fifth patient previously underwent a subtotal parathyroidectomy, and a fifth supernumerary gland was localized with the sestamibi scan. Four patients had hyperparathyroidism related to kidney disease. Three of these had bilateral localization of enlarged glands. The fourth patient had undergone two previous operations, and a fifth supernumerary gland was localized with the sestamibi scan. CONCLUSIONS. The preliminary data indicate that Tc 99m sestamibi in combination with 123I radionuclide scanning may be useful in the preoperative localization of abnormal parathyroid glands. This technique localized all of the solitary adenomas that were subsequently resected, and in two reoperative cases it identified the remaining solitary gland causing persistent hypercalcemia.     

Primary hyperparathyroidism associated with two enlarged parathyroid glands

An increasingly recognized although small percentage of patients with primary hyperparathyroidism have enlargement of two parathyroid glands. We have treated nine patients with primary hyperparathyroidism associated with such double parathyroid gland enlargement. In four of these patients, marked asymmetry of the two enlarged glands was noted and the failure to recognize and excise a second enlarged parathyroid gland resulted in persistent or recurrent hyperparathyroidism. In one of these patients, the second enlargement was present in a super-numerary mediastinal gland. The subsequent excision of the second enlarged parathyroid gland resulted in normocalcemia in each instance. This contrasts with five patients in whom initial excision of two enlarged glands resulted in normocalcemia with no recurrence of hypercalcemia. Only three patients fulfilled the histologic criteria of true double adenomas. The remainder showed multiglandular hypercellularity. This experience supports identifying all parathyroid glands and recognizing that even minimal enlargement of a gland may be important pathophysiologically, regardless of its histopathologic classification. Excision of both enlarged glands, even if asymmetric, is appropriate.     

Ultrasound scanning for preoperative location of parathyroid tumours

Ultrasonic examination of the parathyroid glands has been used in 50 consecutive patients with surgically verified hyperparathyroidism. It revealed 21 of 32 parathyroid adenomas located in the neck. In 16 patients with primary or secondary (uraemic) hyperplasia, 11 out of 48 hyperplastic glands in the neck were identified by ultrasound. A parathyroid adenoma was revealed in all (3) patients with hypercalcaemic crisis. Enlarged parathyroid glands were correctly located in all (5) patients with adenomas and previous explorations of the neck, whereas two out of three glands were visualized by ultrasound prior to secondary explorations in 3 patients with hyperplasia associated with the multiple endocrine neoplasia syndrome type 1. Undetected parathyroid glands were generally smaller than those visualized by ultrasonic examination. It was often difficult to unequivocally establish that identified lesions represented parathyroid glands. Irregular noduli and cysts of the thyroid as well as lymph nodes could be misinterpreted as parathyroid lesions. A nodular thyroid goitre was present in almost half of the patients with a negative ultrasonic examination of the parathyroid glands.     

Histopathological study of the parathyroid gland in renal hyperparathyroidism

From July 1973 to July 1984, 50 patients underwent parathyroidectomy because of secondary hyperparathyroidism due to chronic renal failure. One hundred fifty-eight excised parathyroid glands in 41 of these patients were submitted to the histopathological examinations in the relations to their clinical features which revealed the following findings. Inspite of secondary hyperparathyroidism, eleven of 41 patients showed four unevenly enlarged parathyroid glands with one or two glands weighing less than 100mg. The glands were divided into three adenomas, 101 diffusely and 54 nodulary hyperplastic glands. The nodular type hyperplasia, which had a greater proportion of clear chief cells, vacuolated chief cells, transitional oxyphil cells and oxyphil cells, was more hyperplastic than the diffuse type. The patients with the nodular type showed more advanced clinical features in the secondary hyperparathyroidism.     

Sestamibi/iodine subtraction single photon emission computed tomography in reoperative secondary hyperparathyroidism

BACKGROUND: Sestamibi/iodine subtraction single photon emission computed tomography (SPECT) has been used successfully for the preoperative localization of adenomatous and hyperplastic parathyroid tissue in primary hyperparathyroidism, but the clinical usefulness of this technique in secondary hyperparathyroidism remains uncertain. The purpose of this study was to evaluate parathyroid localization that uses sestamibi/iodine subtraction SPECT in patients with secondary hyperparathyroidism before reoperative parathyroid surgery. METHODS: Fourteen consecutive patients with chronic renal failure and secondary hyperparathyroidism who had previously undergone total parathyroidectomy combined with parathyroid autotransplantation in a sternocleidomastoid muscle were studied. Before reoperation, each patient received 400 microCi of sodium iodide I 123 orally and 20 to 25 mCi of technetium Tc 99m ((99m)Tc)-sestamibi intravenously, followed by sestamibi/iodine subtraction SPECT of the neck and chest. At surgery, the location, weight, and histopathologic results of all identified parathyroid tissue were recorded. RESULTS: At surgery, 1 hyperplastic parathyroid gland was resected from each of 13 patients; including 1 undescended gland, 6 parathyroid autotransplants, and 5 mediastinal glands. The mean weight of the resected parathyroid glands was 1707 mg (range, 85-5300 mg). Sestamibi/iodine subtraction SPECT correctly identified and localized all 13 parathyroid glands (100% sensitivity) and was negative in the 1 patient whose surgery was unsuccessful. CONCLUSIONS: The (99m)Tc-sestamibi/(123)I subtraction SPECT is able to correctly localize hyperplastic parathyroid tissue in patients with secondary hyperparathyroidism who have previously undergone parathyroid surgery and is a clinically useful study before reoperation.     

Surgical management of parathyroid disease

Primary hyperparathyroidism is a common endocrine disorder caused by excessive PTH production by one or more parathyroid glands. The diagnosis is via biochemistry and surgery is the definitive treatment. All patients with symptomatic disease or evidence of end-organ damage should be offered surgery if possible. Imaging studies are used to plan surgical strategy. The majority of patients with primary hyperparathyroidism have a single parathyroid adenoma. Positive imaging studies allow patients to undergo minimally invasive surgery. Negative imaging does not rule out surgery and patients should be offered a traditional bilateral neck exploration. Secondary hyperparathyroidism is most commonly caused by renal failure. Medical management is the first line treatment, followed by parathyroidectomy in selected cases. Tertiary hyperparathyroidism is seen in patients with continued autonomous function of the parathyroid glands after removal of the underlying stimulus. It is commonly seen in renal transplant patients and parathyroidectomy has a role.     

Total parathyroidectomy and autotransplantation of parathyroid tissue for renal hyperparathyroidism. A one- to six-year follow-up.

From 1975 to 1981 total parathyroidectomy and parathyroid autotransplantation were carried out in 62 patients for renal (secondary) hyperparathyroidism. The paper reports on 46 patients followed for one to six years (mean 2.2 +/- 1.2 years). Forty-one were on chronic hemodialysis, three were predialytic, two had a functioning renal graft. There have been two different groups of indications: one in which hypercalcemia was the main reason for surgery (59%), the other in which severe renal osteopathy (bone pain, radiologic and histologic signs, elevation of alkaline phosphatase, and parathyroid hormone) was observed. Among 45 patients not previously operated on for hyperparathyroidism, five parathyroid glands were removed in three patients, four glands were removed in 36 patients, and three glands were removed in five patients. In one patient previously operated (thyroid surgery), two glands were removed. Tissue was immediately autografted into a forearm muscle. One patient (two glands removed) received a cryopreserved tissue six months after neck exploration. An improvement of bone pain, pruritus, and radiologic signs of renal osteopathy was noted in about 80% of patients. At one to six years no patient was hypercalcemic, in 44 patients the grafted tissue was functioning normally after an average time of 5.8 +/- 1.4 months. One patient is still on low-dose, supplemental therapy for slight hypocalcemia 14 months after autotransplantation. In another patient a part of the grafted tissue was removed for increasing parathyroid hormone levels. Serum concentration of alkaline phosphatase and serum parathyroid hormone decreased after surgery. One- to six-year results after total parathyroidectomy and autotransplantation for renal hyperparathyroidism are considered to be extremely satisfactory.