• Expression of cellular retinol- and retinoic acid-binding proteins in normal and pathologic human parathyroid glands.

• 99mTc-MIBI scintigraphy of parathyroid adenomas and its relation to tumour size and oxyphil cell abundance.

• Methodological considerations influence the clinical value of parathyroid localisation diagnostics.

• [Value of a structured report for the interpretation of parathyroid scintigraphy in primary essential hyperthyroidism]

• Role of US with supplemental CT for localization of parathyroid adenomas.

• Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe localization in surgery for primary hyperparathyroidism.

• Expression of parathyroid hormone-related protein (PTHrP) in parathyroid tissue under normal and pathological conditions.

• Parathyroid carcinoma.

• Asymptomatic hyperparathyroidism caused by a giant parathyroid adenoma.

• Intraoperative localization of parathyroid glands with gamma counter probe in primary hyperparathyroidism: a prospective study.

1
UI - 11914476
AU - Melhus H; Li Q; Nordlinder H; Farnebo LO; Grimelius L
TI - Expression of cellular retinol- and retinoic acid-binding proteins in normal and pathologic human parathyroid glands.
SO - Endocr Pathol 2001 Winter;12(4):423-7
AD - Department of Medical Sciences, Uppsala University Hospital, S-751 85 Uppsala, Sweden. Hakan.Melhus@medsci.uu.se
We have previously reported data establishing the human parathyroid gland as a target organ for vitamin A. In the present study, we identified Ito-like cells in parathyroid glands, suggesting local stores of vitamin A. Furthermore, we used immunohistochemistry to investigate the expression of the cellular retinol-binding protein type 1 and the cellular retinoic acid-binding protein type 1 (CRABP I) in histologically normal glands, in remnants of "normal" glandular tissue adjacent to adenoma, in adenomas, and in hyperplastic glands of chief cell type. All normal and abnormal glands displayed immunoreactivity to the two antibodies. CRABP I appeared in the cytoplasm, cell membranes, and nuclear membranes in normal glands, but only exceptionally in the nuclear membranes in abnormal glands. Since retinoic acid inhibits the secretion of parathyroid hormone and CRABP I is thought to play a key role in regulating the amount of retinoic acid available to interact with specific nuclear receptors, these data may suggest impaired transport of retinoic acid to cell nuclei, thus contributing to the development of hyperparathyroidism.

2
UI - 11303892
AU - Melloul M; Paz A; Koren R; Cytron S; Feinmesser R; Gal R
TI - 99mTc-MIBI scintigraphy of parathyroid adenomas and its relation to tumour size and oxyphil cell abundance.
SO - Eur J Nucl Med 2001 Feb;28(2):209-13
AD - Department of Nuclear Medicine, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel. adrian-p@inter.net.il
The aim of this study was to assess the correlation between technetium-99m methoxyisobutylisonitrile (MIBI) uptake by parathyroid adenomas, oxyphil cell content and volume of the lesions. Thirty-one patients with parathyroid adenomas were evaluated prospectively. Preoperative double-phase 99mTc-MIBI scintigraphy was performed in all patients and tracer uptake by parathyroid lesions was assessed semi-quantitatively employing region of interest ratios to normal adjacent neck areas. Surgical specimens underwent histological evaluation and oxyphil cell content was determined. The intensity of tracer uptake was compared with oxyphil cell content, volume of the lesions and serum levels of calcium and parathormone. 99mTc-MIBI tracer uptake was correlated with oxyphil cell content, volume of parathyroid lesions and the functional status of the parathyroid adenomas. Tracer accumulation in oxyphil cells might partially explain the preferential 99mTc-MIBI retention in parathyroid lesions.

3
UI - 11504097
AU - Gabriel M; Erler H; Bacher-Stier C; Kendler D; Donnemiller E;
TI - Decristoforo C; Moncayo R Methodological considerations influence the clinical value of parathyroid localisation diagnostics.
SO - Eur J Nucl Med 2001 Jul;28(7):942-3

4
UI - 12050949
AU - Zettinig G; Prager G; Kurtaran A; Kaserer K; Czerny C; Dudczak R;
TI - Niederle B [Value of a structured report for the interpretation of parathyroid scintigraphy in primary essential hyperthyroidism]
SO - Acta Med Austriaca 2002;29(2):68-71
AD - Universitatsklinik fur Nuklearmedizin, Ludwig Boltzmann Institut fur Nuklearmedizin, Universitat Wien. georg.zettinig@akh-wien.ac.at
The aim of the study was to evaluate whether a four-stage report scheme increases the diagnostic accuracy of dual phase Tc-99 m sestamibi scintigraphy (MIBI-scintigraphy) in patients with primary hyperparathyroidism (pHPT). We analysed the scans of 35 patients with primary hyperparathyroidism referred for Tc-99 m sestamibi scintigraphy and compared them with the sonographic and surgical findings. All scans were interpreted following a four-stage report scheme: Group A--typical scintigraphic findings of a single gland disease, group B--scan consistent with single gland disease, group C--multiple gland disease, group D--non diagnostic scan. Twenty-three scans were ranked in group A. In all these patients, scintigraphy diagnosed both the side and the localization of the adenoma correctly. Sonography made the correct diagnosis in 21/23 individuals and showed false-positive results in 2/23 cases. Group B included 10 scans. In 7/10 individuals, both the side and the localization of the adenoma were diagnosed correctly, whereas in 2/10 patients only the side was diagnosed. The scan of a single patient with hyperplasia of all 4 parathyroid glands was falsely interpreted as "consistent with a left caudal single gland disease". Sonography made the correct diagnosis in 8/10 cases, two individuals were diagnosed as false positive and false negative, respectively. No scan was interpreted as multiple gland disease (group C) and two scans were non diagnostic (group D). Both patients of the last group were correctly diagnosed by sonography. These findings suggest that in case of typical scintigraphic findings of single gland disease, scintigraphy but not sonography should be the primary localization technique for minimally invasive parathyroidectomy.

5
UI - 12034964
AU - Spieth ME; Gough J; Kasner DL
TI - Role of US with supplemental CT for localization of parathyroid adenomas.
SO - Radiology 2002 Jun;223(3):878-9; discussion 879

6
UI - 12049536
AU - Jaskowiak NT; Sugg SL; Helke J; Koka MR; Kaplan EL
TI - Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe localization in surgery for primary hyperparathyroidism.
SO - Arch Surg 2002 Jun;137(6):659-68; discussion 668-9
AD - Department of Surgery, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
HYPOTHESIS: Intraoperative quick parathyroid hormone (qPTH) monitoring and gamma probe (GP) localization greatly aid the surgeon. DESIGN: Prospective case series of patients undergoing parathyroidectomy (PTX) with preoperative localization studies, operative data (including intraoperative qPTH values and GP localization), and outcomes. Follow-up was complete (mean, 4.2 months). SETTING: University teaching hospital. PATIENTS: We studied 57 consecutive patients with primary hyperparathyroidism from December 1, 1999, through November 30, 2000. Of these, 51 underwent first-time PTX, and 6, reoperative PTX (rePTX). MAIN OUTCOME MEASURES: Cure rate and morbidity after PTX or rePTX; sensitivity and accuracy of preoperative localization studies; prediction of cure from results of qPTH monitoring (comparing Nichols [>50% fall from the highest baseline level and lower than the lowest baseline] or normal-limit [>50% fall from first baseline level and lower than upper limit of the reference range] criteria); and value of GP localization. RESULTS: Patients were cured in 50 (98%) of 51 PTX and 6 (100%) of 6 rePTX for single adenomas (n = 49), double adenomas (n = 4), and multigland hyperplasia (n = 3). Nichols criteria for qPTH monitoring correctly categorized 45 (92%) of 49 cured single adenomas 10 minutes after excision. Only 35 (71%) of these adenomas were correctly categorized as cured by means of the normal-limit criteria. In double adenomas, both sets of criteria in the 10-minute samples indicated unresected glands in only 2 of 4 cases. Preoperative sestamibi parathyroid scans correctly localized 38 (76%) of 50 single adenomas. The GP was used in 54 of 57 cases. All adenomas measured greater than 20% of background ex vivo, but 6 thyroid nodules also measured greater than 20% ex vivo. In double adenomas, the GP helped locate the second adenoma in only 1 of 4 cases. The GP was graded as crucial in 2 cases with dense scar (both rePTX), helpful in 12 (22%) of 54 cases (particularly in retroesophageal glands), confirmatory in 32 (59%), and not helpful in 8 (15%). The GP helped localize 3 (43%) of 7 glands not seen on sestamibi parathyroid scans. CONCLUSIONS: Intraoperative qPTH monitoring confirmed cure in most cases. For single adenomas, use of the Nichols criteria for qPTH assessment allowed more accurate and faster confirmation than the normal-limit criteria. The GP was less useful but was crucial in 2 rePTX cases; it was not specific for parathyroid tissue. Both techniques have potential pitfalls that could result in surgical failure.

7
UI - 11813867
AU - Kitazawa R; Kitazawa S; Maeda S; Kobayashi A
TI - Expression of parathyroid hormone-related protein (PTHrP) in parathyroid tissue under normal and pathological conditions.
SO - Histol Histopathol 2002 Jan;17(1):179-84
AD - Department of Biomedical Informatics, Kobe University Graduate School of Medicine, Japan. kitazawa@med.kobe-u.ac.jp
Parathyroid hormone-related protein (PTHrP), a factor responsible for malignancy associated hypercalcemia, plays a physiological roles such as bone development and placental calcium transport. The expression of PTHrP in adult human parathyroid tissues under normal and pathological conditions was analyzed. By immunohistochemistry, PTHrP expression was detected in 86% of normal parathyroid (12/14 cases), 74% of adenomas (14/19) and 89% of hyperplasia secondary to chronic renal failure (16/18). PTHrP protein was observed mainly in the cytoplasm of oxyphil cells, consistent with the localization of its mRNA demonstrated by in situ hybridization. The rate of PTHrP-positive cells was higher in areas consisting of oxyphil cells than in those of non-oxyphil cells, regardless of whether the parathyroid was normal or pathological. In the normal parathyroid, an age-related increase in PTHrP expression was observed with a relative increase in oxyphil cells, reflecting aging and deterioration of parathyroid tissue. In adenoma, cases with a predominance of oxyphil cells expressed PTHrP, whereas clear cell adenoma did not. In secondary hyperplasia, the rate of PTHrP-expressing cells was higher than in normal parathyroid or adenoma, with varying levels of expression among nodules. We speculate that PTHrP could act through the paracrine/autocrine mechanism to regulate proliferation and differentiation of normal and neoplastic parathyroid cells.

8
UI - 12057115
AU - Kebebew E
TI - Parathyroid carcinoma.
SO - Curr Treat Options Oncol 2001 Aug;2(4):347-54
AD - Department of Surgery, University of California, San Francisco, 513 Parnassus, S343, San Francisco, CA 94141-9918, USA. tron@itsa.ucsf.edu
Although parathyroid neoplasms are common and cause primary hyperparathyroidism, parathyroid carcinoma is a rare entity. At times it can be difficult to diagnose. Patients with parathyroid carcinoma usually present with profound symptoms of hyperparathyroidism and highly elevated serum calcium and parathyroid hormone (PTH) levels. At the time of neck exploration, a large, gray-white, locally invasive tumor is commonly encountered. The course of patients with parathyroid carcinoma is variable; unfortunately, more than 50% have persistent or recurrent disease due to regional or distant disease. Surgical resection is the principal treatment for patients with parathyroid carcinoma. The optimal surgical treatment is en bloc tumor resection with ipsilateral thyroid lobectomy when the diagnosis is suspected and until it is proven otherwise. Patients who have persistent or recurrent parathyroid carcinoma should have localizing studies to identify loco-regional or distant tumor sites. Reoperation in patients with localized parathyroid carcinoma is recommended because it relieves symptoms of hypercalcemia, and it normalizes serum calcium and PTH levels in most patients. For patients who have unresectable parathyroid carcinoma, a protocol-based treatment with chemotherapy and external radiotherapy should be considered. Additionally, second-generation bisphosphonates and the NPS R-568 calcimimetic agent may be useful in normalizing the serum calcium and improving symptoms of hypercalcemia. However, they do not treat the tumor and are rarely effective in the long term.

9
UI - 12082964
AU - Madiba TE; Rughubar KN; Haffejee AA; Motala AA
TI - Asymptomatic hyperparathyroidism caused by a giant parathyroid adenoma.
SO - S Afr J Surg 2002 Feb;40(1):19-21
AD - Departments of Surgery, Pathology and Medicine, University of Natal and King Edward VIII Hospital, Durban.
On routine investigation a 57-year-old woman was found to have primary hyperparathyroidism caused by a giant parathyroid gland. The gland was removed successfully and histological examination proved it to be a parathyroid adenoma.

10
UI - 12113540
AU - Saaristo RA; Salmi JJ; Koobi T; Turjanmaa V; Sand JA; Nordback IH
TI - Intraoperative localization of parathyroid glands with gamma counter probe in primary hyperparathyroidism: a prospective study.
SO - J Am Coll Surg 2002 Jul;195(1):19-22
AD - Department of Surgery, University Hospital of Tampere, Finland.
BACKGROUND: Technetium 99m-sestamibi imaging might be the best method to localize abnormal parathyroid glands. No studies to date have compared preoperative imaging and intraoperative gamma probe localization in patients with primary hyperparathyroidism. STUDY DESIGN: This prospective study included 20 arbitrarily selected patients with primary hyperparathyroidism, verified by elevated serum ionized calcium and intact parathyroid hormone concentrations and low serum phosphatase level. Each patient underwent both preoperative imaging study of the parathyroid glands with technetium 99m-sestamibi (dose 740MBq) and intraoperative localization with a handheld gamma probe. Full collar exploration served as the gold standard. RESULTS: Hypercalcemia and hypophosphatemia normalized in each patient. A single parathyroid adenoma was confirmed histologically in 16 and hyperplasia (4 abnormal glands) in 4 patients. None of the patients had multiple adenomas. The sensitivity of the preoperative scan was 81% (13 of 16 patients) in adenoma patients and 100% (4 of 4 patients) in hyperplasia. The corresponding specificity was 88% and 100%. Intraoperatively only 8 of 16 adenomas were correctly detected (sensitivity 50%), and none of the hyperplastic glands were correctly detected. CONCLUSIONS: In unselected patients with primary hyperparathyroidism, preoperative technetium 99m-sestamibi imaging is more accurate than intraoperative gamma probe detection in localizing abnormal parathyroid glands.

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