Last Modified: November 1, 2001
Table of Contents
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UI - 21347504
AU - Miedlich S; Lohmann T; Schneyer U; Lamesch P; Paschke R
TI - Familial isolated primary hyperparathyroidism--a multiple endocrine neoplasia type 1 variant?
SO - Eur J Endocrinol 2001 Aug;145(2):155-60
AD - Medical Department III, University of Leipzig, Germany.
OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is defined as hereditary primary hyperparathyroidism without the association of other diseases or tumors. Linkage analyses suggest that different genotypes can lead to the same phenotype of primary hyperparathyroidism. Hereditary syndromes associated with primary hyperparathyroidism are multiple endocrine neoplasia type 1 and type 2 (MEN 1 and MEN 2). In MEN 1, multiple parathyroid adenomas occur in more than 90% of the patients. Therefore, it has been suggested that FIHP could represent a variant or partial expression of MEN 1. DESIGN: We report on a large FIHP kindred with a MEN1 gene mutation. Nineteen family members (aged 10 to 87 years) were screened. Furthermore, statistical comparison by Fisher's exact tests of FIHP families with MEN1 gene mutations and MEN 1 families with two or more endocrinopathies was carried out to investigate genotype-phenotype correlations. METHODS: Mutational analysis of leucocyte DNA was carried out by direct sequencing of the complete coding region of the MEN1 gene. Screening of MEN 1 manifestations was carried out by determination of serum calcium, phosphate, parathyroid hormone, prolactin, ACTH, cortisol, IGF-I, gastrin, glucose, insulin, glucagon, serum potassium, aldosterone, plasma renin and urinary hydroxyindoleacetic acid. RESULTS: We detected an in-frame deletion mutation in exon 8 of the MEN1 gene resulting in the deletion of one glutamine acid residue at position 363. It was found in eight individuals. Two of these family members (aged 42 and 60 years) were operated for primary hyperparathyroidism, and three (aged 13 to 40 years) showed mild hypercalcemia and parathyroid hormone levels within the upper normal range or slightly elevated, without any clinical symptoms. Two individuals (aged 12 and 19 years) were normocalcemic. One could not be tested. None of them had clinical evidence of other MEN 1 manifestations. Statistical comparison of the mutation types in families with FIHP and families with two or more MEN 1-associated endocrinopathies reported in other studies reveals a significant difference. In families with FIHP, missense/in-frame mutations have been found in 87.5% of cases whereas in families with tumors in various endocrine glands these mutation types occur much less frequently (21-34%, P<0.05). CONCLUSIONS: These studies indicate that FIHP can represent a partial MEN 1 variant and is often caused by missense/in-frame mutations.
UI - 21347505
AU - Velin AK; Herder A; Johansson KJ; Trulsson LM; Smeds S
TI - Telomerase is not activated in human hyperplastic and adenomatous parathyroid tissue.
SO - Eur J Endocrinol 2001 Aug;145(2):161-4
AD - Department of Biomedicine and Surgery, University Hospital, Linkoping, Sweden.
BACKGROUND: Telomerase is a specific enzyme that appears to have a key role in cellular senescence and the progression of neoplastic tissue. High telomerase activity has been found in several cancers, but not in most normal and benign tissue. Little is known about the influence of telomerase on the abnormal growth associated with hyperparathyroidism. OBJECTIVE: To analyse telomerase activity in parathyroid tissue obtained from 29 patients undergoing surgery for primary hyperparathyroidism. DESIGN: Tissue for telomerase activity measurements was collected from six hyperplastic, 20 adenomatous and 22 normal parathyroid glands. METHODS: The highly sensitive PCR-based telomeric repeat amplification protocol, TRAP, combined with ELISA, was used to detect telomerase activity in tissue extracts containing 3.0 microg protein. RESULT: Telomerase was not activated in any of the analysed tissue by 3 microg protein. Reassay of 12 samples containing 6.0 microg protein verified these negative TRAP results. CONCLUSION: Our findings indicate that telomerase is not a part of the mechanism promoting parathyroid proliferation and the underlying conditions remain to be determined.
UI - 21392396
AU - Pahlavan PS
TI - Hypercalcemia due to parathyroid adenoma.
SO - Saudi Med J 2000 Jun;21(6):596-7
UI - 21365244
AU - Mihai R
TI - Molecular influences in thyroid and parathyroid surgery.
SO - Best Pract Res Clin Endocrinol Metab 2001 Jun;15(2):177-88
AD - University Department of Surgery, Bristol Royal Infirmary, Bristol, UK.
Recent progress in molecular biology and genetics has made a major impact on the management of patients with multiple endocrine neoplasia syndromes MEN-1 and MEN-2. The understanding of the mechanisms involved in inherited thyroid and parathyroid tumours also offered valuable answers for other models of neoplasia. In addition, parathyroid surgery has witnessed rapid progress, from the cloning of the calcium receptor to the development of calcimimetics, a new class of drugs that could shift the management of hyperparathyroidism from surgical intervention to medical treatment. Laboratory techniques initially designed for research are more and more being used for clinical diagnosis. For example, the use of the polymerase chain reaction is currently being evaluated in the early diagnosis of metastatic thyroid carcinoma by identifying specific gene products in the local lymph nodes. This chapter attempts to convince the reader that molecular biology is no longer restricted to the laboratory but has an increasing impact on clinical decisions to which an endocrine surgeon is exposed. Copyright 2001 Harcourt Publishers Ltd.
UI - 21223267
AU - Rubello D; Saladini G; Casara D
TI - [The role of scintigraphy with dual tracer and potassium perchlorate (99mTcO4 & KClO4/ MIBI) in primary hyperparathyroidism]
SO - Minerva Endocrinol 2001 Mar;26(1):13-21
AD - Servizio di Medicina Nucleare II, Unita Operativa di Radioterapia e Medicina Nucleare, Azienda Ospedaliera, Padua, Italy.
BACKGROUND: The diagnostic value of scintigraphy using a dual tracer and high-resolution neck ecotomography in the preoperative localisation of parathyroid enlargements was evaluated in a group of consecutive patients suffering from primary hyperparathyroidism (HPT) who were uniformly studied and subsequently operated by the same surgical team. METHODS: Scintigraphic imaging and high-resolution neck ecotomography were carried out in a single session on 143 patients. Scintigraphic imaging was performed using a dual tracer, 99mTc-pertechnetate/99mTc-MIBI), modified by the addition of potassium perchlorate (KCL04) to achieve a rapid washout of 99mTc04 from the thyroid and, consequently, to achieve good quality and rapid MIBI images. In a limited number of patients (21 cases) SPECT was also performed. Limited surgery was planned in patients with evidence of single parathyroid lesions and with normal thyroid parameters, in the form of either unilateral or with mini-invasive surgery (91 cases). Patients with eco-scintigraphic evidence of multiglandular parathyroid pathology or the coexistence of a nodular thyroid goitre, or in patients suffering from MEN or familial HPT, or lastly those with negative eco-scintigraphic results under-went more extensive surgery with bilateral exploration of the neck (52 cases). A single parathyroid lesion was diagnosed during surgery in 90 out of 91 patients undergoing planned unilateral or mini-invasive exploration of the neck. Therefore, in our experience, the predictive value of preoperative imaging as a mean of identifying single parathyroid lesions was 98.9% with a clear impact on the choice of conservative surgery. After the removal of the parathyroid to which preoperative imaging referred, it was only necessary in one patient to extend surgical exploration to the other side of the neck to remove another enlarged parathyroid owing to persistent high PTH. RESULTS: The sensitivity of scintigraphy and high-resolution neck ecotomography in pa-tients with a single adenoma was 94% and 83.7% respectively, whereas it was 76.9% and 64.5% respectively in the group of patients with multiglandular pathology. It is worth underlining that in all 31 patients with associated nodular thyroid pathology, the evaluation of thyroid scintigraphic imaging using 99mTc04 and high-resolution neck ecotomography enabled the preoperative diagnosis of thyroid pathology, therefore guiding the surgeon towards more extensive surgery. SPECT enabled the parathyroid adenoma to be correctly localised in a deep site in 5 patients, in the neck in 3 cases and at the mediastinum in 2 patients, providing additional data that helped the surgeon to plan surgery. CONCLUSIONS: In conclusion, in our experience: a) an integrated diagnostic approach based on scintigraphy 99mTc04 & KCLO4/MIBI and high-resolution neck ecotomography was an extremely accurate mean of identifying patients with single parathyroid lesions before surgery, enabling them to undergo limited surgery, b) scintigraphy with a dual tracer might be the elective methods for studying patients with HPT because it allows the contemporary diagnosis of possible thyroid diseases. This aspect is extremely important in geographical areas with a high predominance of nodular thyroid pathology, c) SPECT scintigraphic analysis may be useful in some patients with suspected parathyroid adenoma localised in a deep seat, allowing a more precise identification of the latter and better surgical planning.
UI - 21223268
AU - Pelizzo MR; Piotto A; Bergamasco A; Rubello D; Casara D
TI - [Parathyroid carcinoma. Therapeutic strategies derived from 20 years of experience]
SO - Minerva Endocrinol 2001 Mar;26(1):23-9
AD - Azienda Ospedaliera, Istituto di Clinica Chirurgica III, Universita degli Studi, Padua, Italy.
BACKGROUND: Carcinoma of the parathyroid is a rare endocrine tumour which can be difficult to diagnose even for expert anatomopathologists. METHODS: A retrospective study was carried out on all the cases of parathyroid pathology observed between January 1980 and October 2000: parathyroid carcinoma was diagnosed in 17 (3.59%) out of 478 patients treated for hyperparathyroidism. We describe their clinical presentation, treatment and results obtained. The patients included 9 women and 8 men, with a male/female ratio of 1.14 and a mean age at diagnosis of 56.9 years (range 30-83). All the patients, except one, the only non-secreting case, presented hypercalcemia, and 10 patients presented serum calcium levels above 3 mmol/L. The symptoms at onset included: nephrolithiasis in 10 cases, osteoporosis in 4 (3 of which presented uremic syndromes), gastrointestinal symptoms (gastritis) in 1 case, a palpable cervical mass in 1 patient and recurrent nerve palsy in one case suffering from familial IPT. A variety of imaging techniques were used for the preoperative localisation: high-resolution ultrasonography of the neck was carried out in all 17 patients and was positive in 15 cases; scintigraphy (99mTcO4/201Tl or 99mO4/MIBI) was carried out in 16 patients and was positive in 14; CAT was positive in 6 out of 17 patients. Three patients underwent the first operation in another hospital and were referred to our department for resistance or recidive. Initial surgery was restricted to simple parathyroidectomy in 4 cases; parathyroidectomy was extended to the entire gland in 3 patients with uremic syndrome and to the ipsilateral thyroid lobe in 7 cases. Three patients underwent parathyroidectomy extended en bloc to the adjacent structures, and recurrent lymph node dissection was also performed in 2 of these patients. Lymph node involvement was never demonstrated during the first operation. The dimensions of the tumour varied from 1 to 6.7 cm; we found signs of invasion of the neighbouring structures in 3 patients. RESULTS: Parathyroid carcinoma was correctly diagnosed during the first operation in 14 cases (this diagnosis was suspected in 10 cases following intraoperative frozen session), whereas the first diagnosis was of benign disease in 3 patients. Blood levels of calcium, phosphorus and PTH returned to normal after the first operation in 13 patients. These values diminished, but did not return to normal in 2 cases. Two patients relapsed, respectively 5 and 175 months after the first operation. A total of 10 reoperations were performed in 4 patients with persistent/recurrent symptoms (from a minimum of 1 to a maximum of 4). Recidive presented characteristics of local invasiveness in one case and the persistence was supported by micro-insemination of the pre-thyroid compartment and muscles in another two cases. At reoperation, lymph node metastasis was associated with local recidive only in one case. Two patients underwent radiotherapy after surgery and one received chemotherapy. At the last check-up (October 2000), 14 patients were alive and disease-free (82.25%). Two presented slight persistent hypercalcemia (with values ranging between 2.65 and 2.80 mmol/L), but without any macroscopic localisation of disease (11.76%). Only 1 patient died (5.88%) (one year after the first operation and 7 months after the last one). Death was caused by uncontrollable hypercalcemia supported by widespread metastasis to the bones and lungs. The 5 and 10-year survival rates were calculated as 94.12%. CONCLUSIONS: In conclusion, high blood levels of calcium and PTH, a palpable mass at the neck, with recurrent nerve paralysis, aspects of local invasiveness should alert the surgeon and guide him towards surgery that includes resection of the parathyroid en bloc with the adjacent structures, although there is no proof that a more extensive surgery is correlated with a more favourable prognosis. Being the majority of recidive functional, monitoring serum calcium and PTH levels offers a useful market which precedes their macroscopic demonstration.
UI - 21223269
AU - Rubello D; Pagetta C; Pelizzo MR; Casara D
TI - [Primary hyperparathyroidism in patients treated for non-medullary thyroid carcinoma]
SO - Minerva Endocrinol 2001 Mar;26(1):31-4
AD - Servizio di Medicina Nucleare II, Unita Operativa di Radioterapia, Azienda Ospedaliera, Universita degli Studi, Padua, Italy.
The authors report three cases of primary hyperparathyroidism (HPT) in patients with differentiated thyroid carcinoma (DTC) developed a few years after initial surgical and radiometabolic treatment of DTC. The early diagnosis of HPT in these patients was made possible because of laboratory tests performed during follow-up, including the assay of serum calcium and serum phosphorus levels. Scinti-graphy using 99mTc-MIBI enabled the correct preoperative localisation of a single parathyroid adenoma in two of these patients and multiglandular pathology in the third.
UI - 21223270
AU - Pelizzo MR; Piotto A; Rubello D; Piazzolla P; Merante Boschin I; Toniato A; Bernante P; Bergamasco A; Casara D
TI - [Radio-guided parathyroidectomy. A prospective study in 54 patients with primary hyperparathyroidism]
SO - Minerva Endocrinol 2001 Mar;26(1):35-9
AD - Istituto di Clinica Chirurgica III, Azienda Ospedaliera, Universita degli Studi, Padua, Italy.
BACKGROUND: The contribution of nuclear-medical mapping using 99mTc-MIBI (MIBI) and the use of an intraoperative probe in primary hyperparathyroidism (I degrees HPT) surgery was evaluated prospectively in a series of patients undergoing parathyroidectomy. METHODS: Fifty-four patients, who were operated between May 1999 and July 2000, under-went a systematic preoperative evaluation using scintigraphy with a dual tracer 99Tc04/MIBI and image subtraction, and high-resolution neck ecotomography. Surgery was performed using a mini-invasive technique through an incision measuring 2-2.5 cm at the base of the neck in 46 patients; the other 8 patients underwent open surgery with bilateral exploration of the neck. MIBI was injected intravenously in the operating theatre following the induction of anesthesia and after 32 minutes on average, radioactivity was measured using a manual gamma probe. Radioactivity was also counted intraoperatively at the tip of the lung contralateral to the pathological gland, a parameter used as the base activity (B), in the presumed seat of the hyperfunctioning parathyroid (P), in correspondence with healthy thyroid tissue (T) and any associated thyroid nodes (N). Radioactivity was also recorded at the level of the empty parathyroid compartment after removal of the corresponding gland, and on the parathyroid removed ex vivo . RESULTS: The ratio between the three main parameters, T/B, P/B and P/T was respectively 1.6 (range=1.5 - 1.8), 2.7 (range=1.6-4.0) and 1.6 (range=1.1-2.8). In 4 cases (7.4%), the small size of the parathyroids, adjacent to thyroid nodes, meant that the parathyroid measurement of MIBI was smaller than the thyroid measurement. The histological finding was consistent with: single parathyroid adenoma in 49 cases, multiple adenomas in 3 cases, parathyroid carcinoma in 2 cases. Rapid intraoperative PTH normalised in all patients. CONCLUSIONS: The significant difference in radioactivity levels recorded in the patients, showed that the technique is useful to the surgeon as a means of intraoperative assay for hyperfunctioning parathyroids, even if it cannot obviously replace experience or the value of preoperative scientigraphic and ecotomographic imaging.
UI - 21254130
AU - Tewari KS; Steiger RM; Lam ML; Rutgers JK; Berkson RA; DiSaia PJ
TI - Bilateral pheochromocytoma in pregnancy heralding multiple endocrine neoplasia syndrome IIA. A case report.
SO - J Reprod Med 2001 Apr;46(4):385-8
AD - Divisions of Gynecologic Oncology and Maternal-Fetal Medicine and Department of Obstetrics and Gynecology, University of California, Irvine, Medical Center, Orange, 101 The City Drive, Orange, CA 92868, USA.
BACKGROUND: Multiple endocrine neoplasia syndrome type IIA (MEN IIA) has rarely been encountered in pregnancy. CASE: A 22-year-old, nulliparous woman developed bilateral pheochromocytomas during pregnancy. This finding aroused suspicion for MEN IIA, and close endocrinologic follow-up was arranged. Four years later, hyperparathyroidism developed, and the diagnosis was established. The patient underwent prophylactic total thyroidectomy with parathyroid exploration. CONCLUSION: This was the first case of MEN IIA in pregnancy in which the diagnosis was established prior to the development of medullary thyroid cancer, thereby allowing prophylactic thyroidectomy. The presence of bilateral neoplastic disease in young patients may be indicative of a hereditary predisposition to malignancy.
UI - 21417809
AU - van Dalen A; Smit CP; van Vroonhoven TJ; Burger H; de Lange EE
TI - Minimally invasive surgery for solitary parathyroid adenomas in patients with primary hyperparathyroidism: role of US with supplemental CT.
SO - Radiology 2001 Sep;220(3):631-9
AD - Department of Radiology, University Medical Center Utrecht, the Netherlands. firstname.lastname@example.org
PURPOSE: To determine the role of ultrasonography (US) with supplemental computed tomography (CT) in patients with primary hyperparathyroidism who undergo minimally invasive surgery instead of conventional neck exploration. MATERIALS AND METHODS: US and CT were performed in 61 consecutive patients with primary hyperparathyroidism (part 1) to identify and localize solitary adenomas for resection by means of minimally invasive surgery and to provide a surgical road map. In part 2, involving 33 consecutive patients, CT was performed only when no solitary adenoma was identified with US or for road map information. Minimally invasive surgery was considered successful when serum calcium levels normalized and remained stable. RESULTS: In part 1, 46 definite solitary adenomas were found with US and two additional ones with CT. Minimally invasive surgery was successful in 45 patients and failed once. In part 2, US helped identify 23 solitary adenomas, and CT helped to find one. Minimally invasive surgery was successful in 22 patients and failed in two. Combined results in 94 patients demonstrated successful minimally invasive surgery in 67 (71%), with 64 of them selected with US alone (95% CI: 61, 80). The sensitivity of US in the diagnosis of solitary adenoma was 78% (95% CI: 67%, 86%), with a positive predictive value of 96% (95% CI: 88%, 99%). CONCLUSION: US examination of patients with primary hyperparathyroidism allowed successful selection for minimally invasive surgery in more than two-thirds of the cases, with additional CT useful chiefly for surgical road mapping.
UI - 21389303
AU - Saky MT; Hasinski S; Rose LI
TI - Ectopic primary hyperparathyroidism.
SO - Endocr Pract 2001 Jul-Aug;7(4):272-4
AD - Division of Endocrinology and Metabolism, Department of Medicine, MCP Hahnemann University Hospital, Philadelphia, Pennsylvania 19102, USA.
OBJECTIVE: To review an unusual case of ectopic primary hyperparathyroidism. METHODS: We present a case report, including longitudinal results of laboratory studies, and comment on the difficulties with standard imaging techniques, interpretation of parathyroid pathologic findings, and use of invasive localization techniques. RESULTS: A 74-year-old woman underwent repeated assessments because of hypercalcemia. When standard parathyroid 99mTc sestamibi imaging was negative for adenoma and initial surgical exploration of the neck and removal of 3' parathyroid glands were unsuccessful in correcting the hyperparathyroidism, the ectopic adenoma was ultimately localized on an extended-field 99mTc sestamibi scan in the region of the right dome of the diaphragm. The localization was confirmed by selective venous sampling and angiography. The ectopic parathyroid adenoma was embolized, and 1 month later, the serum calcium level was normal. CONCLUSION: Ectopic lesions should be considered when standard imaging techniques are nonrevealing and standard neck exploration fails to disclose a parathyroid adenoma in a patient with persistent hypercalcemia. Selective venous sampling and angiography can assist in localization of ectopic parathyroid adenomas.
UI - 21411848
AU - Dundar E; Grenko RT; Akalin A; Karahuseyinoglu E; Bildirici K
TI - Intrathyroidal water-clear cell parathyroid adenoma: a case report.
SO - Hum Pathol 2001 Aug;32(8):889-92
AD - Department of Pathology, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey.
Adenomas of the parathyroid gland, the majority of which contain mixed cell populations, are the most frequent cause of primary hyperparathyroidism. Parathyroid adenomas composed exclusively of water-clear cells are exceptionally rare. Until now, only 2 cases have been reported in English literature. We report a water-clear cell adenoma of the parathyroid gland in an intrathyroidal position, which has not been described previously according to our knowledge.