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PubMed1993

Reoperation for suspected primary hyperparathyroidism.

A retrospective analysis of 93 patients undergoing 128 re-explorations for persistent or recurrent hypercalcaemia is presented. Seventy-six patients (82 per cent) became normocalcaemic after between one and five reoperations. Nine patients had hypercalcaemia caused by sarcoidosis, familial hypocalciuric hypercalcaemia or metastatic disease, and two had parathyroid carcinoma. Fifteen patients (16 per cent) developed permanent hypoparathyroidism requiring vitamin D and/or calcium therapy and nine had permanent recurrent laryngeal nerve paralysis. Undetected adenomas (41 cases) and inadequate resection in hyperplastic disease (28) were the predominant causes of initial failure. Reoperation for persistent or recurrent hyperparathyroidism restored normocalcaemia in the majority of patients. This 'cure' was achieved at the cost of considerable morbidity and a careful risk-benefit analysis of each patient is recommended before performing reoperative parathyroid surgery.

Adenoma↗

PubMed2006

Drug Insight: renal indications of calcimimetics.

Calcimimetics suppress the secretion of parathyroid hormone by sensitizing the parathyroid calcium receptor to serum calcium. Cinacalcet (Sensipar/Mimpara), Amgen Inc., Thousand Oaks, CA), the first-in-class calcimimetic agent approved for treatment of secondary hyperparathyroidism in dialysis patients, is, in association with higher dose of a calcium-based oral phosphate binder, a well-tolerated and effective alternative to standard treatments such as vitamin D derivatives in association with a non-calcium-based oral phosphate binder. Here, we present an overview of evidence in support of this assertion. We extend our discussion to encompass other indications for calcimimetics -- secondary hyperparathyroidism in predialysis chronic kidney disease patients, hypercalcemic hyperparathyroidism in renal transplant recipients, primary hyperparathyroidism, and hypercalcemia associated with parathyroid carcinoma -- as well as providing guidance on optimal usage of this drug.

Calcium↗

PubMed1995

Carcinoma of the thymus with clear-cell features. Report of eight cases and review of the literature.

We report eight cases of thymic carcinoma with clear-cell features and review the five previously reported cases. The tumor was composed of cells with clear cytoplasm and rather bland nuclear features, and showed a lobular or occasionally sheet-like growth pattern. Cytoplasmic glycogen was demonstrable in 92% of cases, whereas mucin was absent in all cases tested. The tumor cells were uniformly immunoreactive for low- and high-molecular-weight keratins and were reactive for epithelial membrane antigen in 22% of cases. The differential diagnosis includes mediastinal seminoma, parathyroid carcinoma, and metastatic clear-cell carcinoma. The diagnosis of primary thymic carcinoma depends on the exclusion of other primary sites clinically, particularly lung and kidney, and the demonstration of postivity for keratins and negativity for placental alkaline phosphatase. Thymic carcinoma with clear-cell features behaves as a high-grade thymic carcinoma: including our cases and the previously reported cases, nine of 13 patients (69%) are either dead of disease or have persistent disease at the latest follow-up. The importance of this entity is recognition of its aggressive clinical behavior and its distinction from other primary and metastatic clear-cell neoplasms of the mediastinum.

Adult↗

PubMed1989

Expression of transcripts encoding a parathyroid hormone-related peptide in abnormal human parathyroid tissues.

A PTH-related peptide (PTHRP) has been identified and its cDNA cloned from human tumors associated with the syndrome of humoral hypercalcemia of malignancy. The human PTHRP gene has been recently isolated and found to be a complex transcriptional unit using multiple promoters and containing alternatively spliced 3' exons which result in three mRNA classes, each class encoding a PTHRP with a unique carboxy-terminus. The PTHRP gene appears to be expressed in a number of normal tissues, and PTHRP transcripts have been previously reported to be overexpressed in a small sample of human parathyroid adenomas. In the present study we surveyed RNA prepared from a total of 60 abnormal human parathyroid glands for PTHRP gene expression using a combination of Northern blotting and RNase protection techniques. Apparent overexpression of PTHRP mRNA was observed in two thirds of parathyroid adenomas, whereas no overexpression was found in 7 examples of sporadic primary hyperplasia, 5 examples of secondary hyperplasia, and 3 examples of parathyroid carcinoma. Apparent overexpression was also observed in 1 of 4 cases of multiple endocrine neoplasia type 1, 1 of 2 examples of multiple endocrine neoplasia type 2, and 1 gland considered to represent tertiary hyperparathyroidism. Northern analysis of poly(A)+ RNA prepared from three representative adenomas using region-specific probes indicated that two putative promoters are used and revealed a pattern of preferential splicing of transcripts to include the most distal 3' exon. These findings suggest that the PTHRP gene is commonly overexpressed in adenomatous parathyroid glands, but not in sporadic primary hyperplasia, that this overexpression does not seem to be dependent on the use of a single specific promoter, and that adenomatous parathyroid cells appear to preferentially use one of several alternative splicing pathways. It is presently not known whether PTHRP is secreted by abnormal parathyroid tissues and, if so, in what form.

Adenoma↗

PubMed1988

[Treatment strategies for parathyroid neoplasms].

Parathyroid carcinoma, as a malignant tumour of an endocrine gland, is a rare entity. This causes difficulties in the diagnosis as well in the therapeutic approach. Some clinical courses of this malignant disease are demonstrated. The therapeutic options--surgically and medically--are reported and analysed.

Calcium↗

PubMed1996

The accuracy of parathyroid gland localization in primary hyperparathyroidism using sestamibi radionuclide imaging.

Primary hyperparathyroidism is a common condition due to either a parathyroid adenoma or, less commonly, parathyroid hyperplasia, whose treatment is essentially surgical. We have, therefore, assessed the accuracy of Tc-99m pertechnetate/Tc-99m sestamibi (methoxy-isobutyl isonitrile) imaging in the localization of adenomas and hyperplastic parathyroids. The clinical records of all patients who had Tc-99m pertechnetate/Tc-99m sestamibi imaging and parathyroid surgery at this hospital were reviewed. The technique used involves standard subtraction methodology with the addition of a novel change detection algorithm to optimize localization. Of 46 patients scanned in 48 patient episodes, 36 patients had adenomas; 28 (78%) were accurately localized to the correct quadrant, and 4 were correctly lateralized. Two patients with parathyroid carcinomas had their metastases correctly localized. Thus, in 34 of 38 (89.5%) of the scans, adenomas or carcinomas were able to be anatomically localized. Six patients presented with hyperplasia; 5 were diagnosed by sestamibi scans, and 3 of these accurately localized all hyperplastic glands. Four additional patients had known hyperplasia, of which 2 were rendered normocalcemic after removal of their sestamibi-positive glands; the other 2 had small second glands detected only at surgery. In patients with unknown pathology, imaging suggested that 6 patients had hyperplasia; this was correct in 5 cases (83%). Nine of the 12 scans in patients who had had previous parathyroid surgery accurately localized the tumors, 7 in the neck and 2 outside. We suggest that sestamibi imaging can help to distinguish hyperplasia from adenomatous disease; when imaging is required, we recommend it as the imaging modality of choice in all patients with primary hyperparathyroidism, especially in reoperated patients.

Adenoma↗

PubMed2006

Role of SPECT/CT in the preoperative assessment of hyperparathyroid patients.

PURPOSE: Our purpose was to assess the clinical value and additional benefit of fusion single-photon computed tomography (SPECT) and computed tomography (CT) images in locating the parathyroids in a selected group of patients affected by primary (PHP) and secondary hyperparathyroidism (SHP). MATERIALS AND METHODS: Sixteen patients (11 women and five men; age range 35-80 years) with severe hyperparathyroidism (HP) (ten PHP, six SHP) were studied by ultrasound (US), and, after i.v. injection of 370 MBq of 99mTc-sestamibi, by planar parathyroid scintigraphy, SPECT and SPECT/CT using a dual-detector scintillation camera GE Infinia Hawkeye. All patients underwent parathyroidectomy. RESULTS: US findings were inconclusive in 12/16 patients affected by multinodular goitre, and two probable eutopic parathyroid glands were identified. "Double phase" parathyroid scintigraphy identified 14 probable parathyroid glands, SPECT 23 (14 ectopic and nine eutopic) and SPECT/CT confirmed all 23 probable parathyroid lesions, offering more precise localisation and an evident improvement in diagnostic accuracy. Sixteen of these foci of increased uptake were hyperplastic parathyroid glands, six were adenomas, one was a parathyroid carcinoma and one was a thyroid follicular carcinoma. Surgical detection of the 23 sestamibi-positive lesions was correctly matched with 100% of SPECT/CT images and 61% of SPECT data alone. Hybrid imaging thus provided additional data in 39% of lesions, and in three patients with retrotracheal glands, it modified the surgical approach. CONCLUSIONS: We believe 99mTc-sestamibi SPECT/CT to be a more reliable presurgical method to study a patient subgroup affected by PHP or SHP in whom conventional US and other scintigraphic methods have failed for intrinsic reasons due to the concomitant presence of multinodular goitre or ectopic parathyroid gland. The additional practical benefit derived from this methodology was evident. In fact, anatomical information provided by CT enables precise localisation of the functional abnormalities highlighted by SPECT, and both are essential to a correct surgical approach.

Adult↗

PubMed1984

[Reoperation for primary hyperparathyroidism].

Twenty-one patients in a series of 283 treated surgically for primary hyperparathyroidism between 1960 and 1982, underwent reoperation. Eleven had been previously treated elsewhere. The initial cervicotomy was negative in fourteen cases, but had led to the ablation of one or more adenomas in seven. The reason for reoperation was recurrence or persistence of hyperparathyroidism (HPT). It was commenced by cervicotomy in the eleven patients initially treated elsewhere, and by cervicotomy and/or sternotomy for the others. Reoperation involved ablation of adenomas in thirteen cases, but was negative in the remaining eight. Three of the eight underwent a second reoperation, with success in two cases. Overall, reoperations led to ablation of sixteen adenomas in fifteen patients. Ten adenomas were ectopic, including eight located mediastinally . Ten sternotomies were performed, leading to ablation of four mediastinal adenomas. Postoperative complications included five recurrent paralyses and two severe cases of hypocalcemia. One patient with parathyroidal carcinoma died of malignant hypercalcemia. Fifteen of the twenty one patients (71%) were cured of their HPT. Basing themselves on these cases, and a review of the literature, the authors describe the indications and practical management of reoperative surgery for primary HPT.

Adenoma↗

PubMedDate not supplied

Fine needle aspiration of osteitis fibrosa cystica.

The cytology findings of a fine needle aspiration biopsy from osteitis fibrosa cystica (brown tumor) of the rib in a patient with primary hyperparathyroidism due to parathyroid carcinoma are discussed. Many multinucleated osteoclast-type giant cells, characteristic of either osteitis fibrosa cystica or benign giant cell tumor of bone, were noted. There were also spindly or fibrillary cells with single, ovoid nuclei, probably of stromal origin.

Aged↗

PubMed1975

[Familial cancer of the parathyroid glands. Importance of angiography in the diagnosis of regional recurrences. Considerations on 2 cases].

The authors report two new cases of functional parathyroid carcinoma, the course of which varied between 5 and 7 years. The main fact was their familial character, as the disease affected two siblings. No similar case was found in the world literature. These two cases were characterised by symptoms in the bones or pancreatic symptoms which dominated the whole clinical course. Finally, the second case was studied by angiography which permitted the authors to localise a lymphnode metastasis on the opposite side. As far as treatment was concerned, the frequency and severity of local and regional spread justifies wide removal at an early stage. This attitude is necessary in any case of parathyroid tumor with an infiltrating character.

Adult↗

PubMed2005

One stage treatment of parathyroid cancer.

AIM: To review the methods of treating parathyroid cancer in our series and report successful use of intraoperative frozen section to enable one stage surgical management. METHOD: Seven cases of parathyroid cancer presented from 1991-2002. The presenting features, diagnosis and treatment are presented. They are separated into two groups based on method of referral and treatment. RESULTS: Patients presented with symptoms of hypercalcaemia. Median corrected calcium was 3.49 mmol/l. Parathyroid hormone levels were raised in seven of eight cases, range 14.5-495 pmol/l. A high index of pre-operative suspicion and use of frozen section enabled a one step surgical procedure. Recurrence was impossible to treat successfully. Radiotherapy appeared successful for residual disease. CONCLUSION: A high pre-operative index of suspicion for parathyroid carcinoma with use of frozen section at time of operation permits an optimal one step surgical procedure by en bloc resection followed by central lymph node excision. In cases where diagnosis has been made post-operatively radiotherapy may be beneficial.

Adult↗

PubMed1986

Improved diagnosis of primary hyperparathyroidism by defining the inverse relationship between serum immunoreactive parathyroid hormone and calcium.

Serum concentrations of immunoreactive parathyroid hormone (iPTH) measured with a mid-region specific radioimmunoassay and total calcium were correlated in 300 healthy subjects and 158 patients with surgically verified primary hyperparathyroidism (HPT). All the healthy individuals could be separated from the patients by a monoexponential declining curve in which iPTH at concentrations of 0.60 micrograms/l and 0.33 micrograms/l corresponded to calcium concentrations of 2.20 mmol/l and 2.60 mmol/l, respectively. In 22 patients more than one sample was analysed and serum iPTH and calcium were inversely correlated. In contrast, three patients with parathyroid carcinoma showed no reciprocal fluctuations between serum iPTH and calcium. Of 75 patients with hypercalcaemia due to malignant diseases (metastatic mammary carcinoma, bronchial carcinoma, renal carcinoma, myelomatosis), 62 had a normal iPTH/calcium relationship. Two patients with myelomatosis had a temporary elevation of serum iPTH and calcium due to renal impairment. One patient with bronchial carcinoma probably had ectopic production of iPTH. The remaining 10 patients (six mammary carcinomas and four bronchial carcinomas) were found in the pathological iPTH/calcium range. In conclusion, we have demonstrated that an inverse relationship exists between serum iPTH and calcium in patients with non-malignant, primary HPT. Evaluation of iPTH and calcium in the same serum sample gave a correct diagnosis in more than 90% of patients with primary HPT.

Adult↗

PubMed1991

Disodium pamidronate in the preoperative treatment of hypercalcemia in patients with primary hyperparathyroidism.

Nine patients (median age, 81 years) with primary hyperparathyroidism were treated with intravenous infusions of disodium pamidronate (APD), which is a bisphosphonate drug. Six patients had severe hypercalcemia (serum calcium concentration, greater than 3 mmol/L) persisting after rehydration with saline and treatment with furosemide; three patients had moderate hypercalcemia with pronounced symptoms (serum calcium concentration 2.8 to 2.9 mmol/L). Three of the patients were considered to have hypercalcemic crises. In all patients, the raised serum calcium levels were lowered by the disodium pamidronate infusions. One week after a single infusion of 15 to 60 mg disodium pamidronate, six of the nine patients had serum calcium concentrations within the normal reference interval and two patients had slightly raised values. Transient asymptomatic hypocalcemia was noted in one patient. All patients tolerated the infusions well, and no side effects were noted. In the patients with verified parathyroid adenomas, a temporary increase in parathyroid hormone levels were observed concomitant with the drop in serum calcium level. The patient with parathyroid cancer displayed no such effect indicating an autonomous parathyroid hormone secretion from the parathyroid carcinoma tumor. The good effect of treatment with the osteoclast inhibitor disodium pamidronate on hypercalcemia caused by primary hyperparathyroidism suggests that this hypercalcemia is mainly due to an increased osteoclast activity. The number of patients in this series is yet too small to allow general conclusions. But the case histories in this series show that disodium pamidronate promises to be of value in different clinical situations for the treatment of severe hypercalcemia in patients with hyperparathyroidism. It can be used (1) preoperatively to investigate whether the patient's symptoms are related to the hypercalcemia, (2) in the treatment of hypercalcemic crises when "forced diuresis" has failed to normalize the serum calcium, (3) after unsuccessful parathyroid surgery when it can be used as a long-term treatment before reoperation, giving time for localization studies and healing of the scar reaction, and (4) in aged and fragile patients where it can be tried as an alternative to surgery.

Adolescent↗

PubMed1991

Neuroendocrine neoplasms of the mediastinum.

Neuroendocrine neoplasma of the mediastinum include thymic carcinoid and small cell carcinoma, parathyroid tumors, and aorticopulmonary or paravertebral paragangliomas. All of these lesions are composed of cells with similar morphological, functional, and biochemical attributes, and may be the sources of eutopic or ectopic hormonogenesis. However, their clinical, immunohistochemical, and ultrastructural features are dissimilar in part, and allow for the effective application of special studies in differential diagnosis. This report presents a review of the above-cited neoplasms, and provides recommendations regarding their pathologic evaluation and treatment.

Adenocarcinoma↗

PubMed1998

Effect of surgeon expertise on the outcome in primary hyperparathyroidism.

BACKGROUND: Success in surgery for primary hyperparathyroidism (PHPT) is thought to be closely linked to surgical expertise. We investigated the effect of the surgeon's experience on the postoperative outcome in patients with PHPT. DESIGN: Cohort study with retrospective analysis. SETTING: University tertiary care center. PATIENTS: Two hundred thirty consecutive patients with PHPT. We excluded patients with prior cervical surgery, parathyroid carcinoma, multiple endocrine neoplasia types 1 and 2, and renal hyperparathyroidism. INTERVENTIONS: All 230 patients underwent bilateral neck exploration for PHPT. MAIN OUTCOME MEASURES: We registered complication rates, fulfillment of predefined operative concepts, and operative time in 230 cervical revisions for PHPT and compared the results of experienced surgeons (40 or more cervical revisions for PHPT performed before 1988) with those of surgeons still in training. RESULTS: Two surgeons classified as experienced operated on 75 patients. Under supervision of these surgeons, most operative procedures (n=155) were performed by 12 different surgeons classified as less experienced. Complications were observed in 31 patients (13.5%) with no statistical difference between the specialists and the less-experienced surgeons (P=.85). The ability to demonstrate 4 or more parathyroid glands was significantly increased for the specialists (74.7% vs 51.6%; P<.001), who also terminated the operation earlier (average, 15 minutes; P<.001). CONCLUSION: In an analysis of 230 operations for PHPT in patients without prior neck surgery, no effect of the surgeon's experience on postoperative outcome was demonstrated. Under the supervision of experienced endocrine surgeons, less-experienced surgeons perform cervical revisions for PHPT with comparable results, although with longer operating time.

Adolescent↗

PubMed1995

Hereditary hyperparathyroidism-jaw tumor syndrome: the endocrine tumor gene HRPT2 maps to chromosome 1q21-q31.

The syndrome of hereditary hyperparathyroidism and jaw tumors (HPT-JT) is characterized by inheritance, in an autosomal dominant pattern, of recurrent parathyroid adenomas, fibro-osseous tumors of the mandible and/or maxilla, Wilms tumor, and parathyroid carcinoma. This syndrome is clinically and genetically distinct from other endocrine neoplasia syndromes and appears to result from mutation of an endocrine tumor gene designated "HRPT2." We studied five HPT-JT families (59 persons, 20 affected); using PCR-based markers, we instituted a genomewide linkage search after excluding several candidate genes. Lod scores were calculated at various recombination fractions (theta), penetrance 90%. We mapped HRPT2 to the long arm of chromosome 1 (1q21-q31). The maximal lod score was 6.10 at theta = .0 with marker D1S212, or > 10(6) odds in favor of linkage. In six hereditary Wilms tumor families (96 persons, 29 affected), we found no linkage to 1q markers closely linked with HRPT2 (lod scores -15.6 [D1S191] and -17.8 [D1S196], theta = .001). Nine parathyroid adenomas and one Wilms tumor from nine members of three HPT-JT families were examined for loss of heterozygosity at linked loci. The parathyroid adenomas and Wilms tumor showed no loss of heterozygosity for these DNA markers. Our data establish that HRPT2, an endocrine tumor gene on the long arm of chromosome 1, is responsible for the HPT-JT syndrome but not for the classical hereditary Wilms tumor syndrome.

Child↗

PubMed2005

A systematic review of the diagnosis and treatment of primary hyperparathyroidism from 1995 to 2003.

OBJECTIVE: To systematically review the current preoperative diagnostic modalities, surgical treatments, and glandular pathologies associated with primary hyperparathyroidism. STUDY DESIGN: A systematic literature review. RESULTS: Of the 20,225 cases of primary hyperparathyroidism reported, solitary adenomas (SA), multiple gland hyperplasia disease (MGHD), double adenomas (DA), and parathyroid carcinomas (CAR) occurred in 88.90%, 5.74%, 4.14%, and 0.74% of cases respectively. Tc 99m -sestamibi and ultrasound were 88.44% and 78.55% sensitive, respectively, for SA, 44.46% and 34.86% for MGHD, and 29.95% and 16.20% for DA, respectively. Postoperative normocalcemia was achieved in 96.66%, 95.25%, and 97.69% of patients offered minimally invasive radio-guided parathyroidectomy (MIRP), unilateral, and bilateral neck exploration (BNE). Intraoperative PTH assays (IOPTH) were helpful in approximately 60% of bilateral neck exploration conversion (BNEC) surgeries. CONCLUSION: The overall prevalence of multiple gland disease (MGD and DA) was lower than often suggested by conventional wisdom. Furthermore, preoperative imaging was less accurate than it is often perceived for accurately imaging MGD. MIRP and UNE were more successful in achieving normocalcemia than is typically quoted. IOPTH was a helpful but not "fool-proof" adjunct in parathyroid exploration surgery. SIGNIFICANCE: These results support a greater role for the treatment of primary hyperparathyroidism using less invasive approaches. EMB rating: B-3.

Humans↗

PubMed2002

[Primary juvenile hyperparathyroidism. Report of 24 cases].

AIM OF THE STUDY: Primary hyperparathyroidism usually affects elderly patients. Juvenile primary hyperparathyroidism is rare, and raises diagnostic and prognostic problems. The aim of this retrospective study on 24 patients is to establish clinical, histological, and therapeutic features of juvenile primary hyperparathyroidism. PATIENTS AND METHODS: From 1986 to 2001, 673 patients were treated for primary hyperparathyroidism in our department. Twenty four patients were younger than 30 years old (3.5%). There were 14 women and 10 men. Mean age was 23 year (14-30). Clinical manifestations, pathologics findings and postoperative results were studied. RESULTS: Sixteen patients presented a sporadic form of primary hyperparathyroidism with a single adenoma. Clinical manifestations were renal symptoms in 11 cases and acute hypercalcemia syndrome in 2 cases. Seven patients had a NEM I syndrome: parathyroid lesions were 6 hyperplasia and one adenoma. A 27 years old woman presented a recurrent familial isolated hyperparathyroidism. She was operated on 10 years before and at reoperation parathyroid carcinoma was found. Nineteen patients were cured after a post operative follow up ranging from 3 to 168 months. One patient had an asymptomatic hypercalcemia recurrence. Two patients presented permanent hypoparathyroidism treated with calcitriol and calcium. CONCLUSION: Sporadic forms represent majority of cases of juvenile hyperparathyroidism. Renal manifestations are usual. Nevertheless, multiple endocrine neoplasia type 1 has to be evocated.

Adenoma↗