The calcium-sensing receptor and vitamin D receptor expression in tertiary hyperparathyroidism

The parathormone (PTH) production is controlled by calcium and vitamin D, which interact with the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR), respectively. All of these elements control calcium homeostasis, which is crucial for many physiological processes. Thus, impairment of the upstream component of this system, e.g. a decrease of CaSR and/or VDR, could result in hyperparathyroidism (HPTH). Therefore, the aim of this study was to assess the expression of CaSR and VDR in a tertiary form of HPTH (T-HPTH). The study involved 19 T-HPTH patients qualified for parathyroidectomy and 21 control parathyroids harvested from multi-organ cadaver donors. The small fragments of harvested glands were homogenized and used for Western blot analysis, whereas the remaining tissues underwent routine hematoxylin-eosin staining or immunostaining for CaSR and VDR. Among 64 T-HPTH parathyroids, 58 revealed the morphology of benign hyperplasia, 2 were identified as adenoma and 4 were classified as normal; some glands displayed a mixed histological phenotype. Western blot analysis revealed a decrease of CaSR and VDR in hyperplasia and adenoma-derived samples. However, no correlation between the types of hyperplasia and receptor expression was observed. On the other hand, microscopic analysis of CaSR- and VDR-immunostained sections revealed a highly differentiated and significantly decreased mean expression of both receptors, which correlated with parathyroid histology. The reason behind the impaired expression of CaSR and VDR in T-HPTH is unclear. It presumably results from constant parathyroid stimulation at the stage of S-HPTH, followed by further development of polyclonal autonomy. However, the verification of this thesis requires further study.     

Parathyroid hormone immunohistochemistry in dogs with primary and secondary hyperparathyroidism: the question of adenoma and primary hyperplasia

In primary hyperparathyroidism, calcium homeostasis is disrupted by excessive synthesis and secretion of parathyroid hormone (PTH), which is usually caused by a solitary adenoma, or less often by nodular hyperplasia or carcinoma of the parathyroid glands. So far, the distinction between these forms of primary hyperparathyroidism has been made by histological examination. In this report clinical and histological findings, including PTH immunohistochemistry, are described in five dogs with primary hyperparathyroidism, three dogs with secondary hyperparathyroidism due to chronic renal failure, and eight control dogs. In the dogs with primary hyperparathyroidism, nodular adenomatous hyperplasia was found in two animals and parathyroid adenoma in three. The dogs with chronic renal failure had diffuse parathyroid gland hyperplasia. The parathyroid glands of the control dogs and the inactive cells surrounding the hyperplastic nodules showed slight to moderate, localized, paranuclear PTH immunolabelling. In the primary nodular and secondary diffuse hyperplasia, all parathyroid cells had a diffuse cytoplasmic PTH labelling pattern, sometimes in combination with localized paranuclear labelling. In parathyroid adenoma, areas with either paranuclear labelling or diffuse cytoplasmic labelling were observed. As both parathyroid adenoma and primary nodular parathyroid gland hyperplasia have characteristics of intrinsic autonomy (i.e., suppression of the remaining endocrine tissue), there would seem to be no functional difference between the two abnormalities. It is argued that primary (multi)nodular hyperplasia is a multiple form of parathyroid adenoma.     

Parathyroid nodules in a patient with chronic renal failure: Hyperplasia or neoplasia?

Enlarged parathyroid glands found at autopsy in a 69-year-old-old man with chronic renal failure and hyperparathyroidism were examined and compared with his parathyroidectomy specimens from 5 years previously. Histology, immunohistochemistry, and DNA analysis did not discriminate conclusively between nodular hyperplasia and adenoma. Although transformation of parathyroid hyperplasia to adenoma remains an attractive hypothesis, conclusive distinction between dependent secondary hyperparathyroidism and autonomous tertiary hyperparathyroidism cannot be made at present on the basis of morphology.     

Pathologic study of parathyroid glands in tertiary hyperparathyroidism

Tertiary hyperparathyroidism is defined as persistent parathyroid hyperfunction developing from the secondary hyperplasia that occurs after restoration of renal function by dialysis or kidney transplantation. Controversy continues as to whether parathyroid adenoma or hyperplasia accounts for the autonomous hyperfunction. A review of 128 parathyroids from 41 patients with tertiary hyperparathyroidism revealed marked hyperplasia in 39 patients (95 per cent), with a predominance of chief cells, an abundance of oxyphil cells, and 10- to 40-fold increases in parathyroid mass. This hyperplasia was considered to be the predominant morphologic feature of tertiary hyperparathyroidism. Adenomas, found only in two patients (5 per cent), seem to be rare. Diffuse, moderately enlarged hyperplastic glands were found predominantly in patients with transplants, whereas nodular, markedly enlarged hyperplastic parathyroids were observed more frequently in patients treated by dialysis. In spite of the different patterns of hyperplasia and the different gland sizes in these two groups of patients, the grades of hypercalcemia were similar. The results of ultrastructural studies indicate that the majority of parenchymal cells in diffuse, and some cellular areas in nodular, hyperplasia may consist of cells with high secretory activity that do not respond normally to hypercalcemia. It is concluded that both increased parenchymal mass and cellular differentiation, leading to hyperactivity, account for tertiary hyperparathyroidism.     

Parathyroid hyperplasia in tertiary hyperparathyroidism: a pathological and immunohistochemical reappraisal

Thirty-one parathyroid glands from 11 patients with tertiary hyperparathyroidism were examined histologically and immunohistochemically to characterize better the nature of the accompanying parathyroid hyperplasia. The parathyroids showed varying degrees of nodular and diffuse hyperplastic involvement as well as apparently normal background tissue. The nodules were usually multiple within any one gland and, together with diffuse hyperplastic tissue, showed a varied cyto-architectural pattern. All glands studied showed both cellular argyrophilia and parathyroid hormone immunoreactivity. The staining pattern for parathyroid hormone ranged from negative or weak to strong, and from patchy to diffuse in hyperplastic tissue from different glands and within the same gland, regardless of the cell type. Apparently normal areas usually showed only patchy weak to moderately strong parathyroid hormone positivity. From the data obtained the most striking feature of the parathyroid glands in tertiary hyperparathyroidism is their extreme variability, both morphological and functional, as indicated by parathyroid hormone immunoreactivity. Furthermore, the generally lesser degree of parathyroid hormone immunoreaction observed in apparently normal parathyroid tissue may reflect suppression of hormone synthesis, with accompanying morphological regression to normal of pre-existent diffuse hyperplasia by autonomous hyperfunctioning nodules associated with tertiary hyperparathyroidism.     

Decreased expression of calcium receptor in parathyroid tissue in patients with hyperparathyroidism secondary to chronic renal failure

The response of parathyroid cells to serum calcium is regulated by a calcium-sensing receptor protein (CaR). In patients with chronic renal failure, hypocalcemia contributes to the parathyroid hyperplasia and increased parathyroid hormone secretion characteristic of secondary hyperparathyroidism (sHPT). However, patients with uremia also display reduced sensitivity to extracellular calcium; this seems to be owing to an alteration of the receptor mechanism. This study examined calcium receptor expression in the parathyroid tissue of patients with sHPT, using immunohistochemical technicques and comparison with normal tissue and parathyroid glands of patients with primary hyperparathyroidism. In all the glands studied, immunostaining was more intense in chief cells than in oxyphilic, transitional, and clear cells. The parathyroid glands of patients with sHPT displayed significantly reduced expression of CaR with respect to morphologically normal ones; a very similar reduction is reported in adenomas. Furthermore, in glands displaying multinodular hyperplasia, expression was less marked in nodule-forming cells than in internodular areas. The decreased expression of calcium receptors in the parathyroid tissue of uremic patients was thought to be owing to the different cell populations present; these parathyroid glands contained predominantly transitional, oxyphilic, and clear cells, which normally express fewer receptors than chief cells, which are more abundant in normal glands.     

Random cytochrome-C-oxidase deficiency of oxyphil cell nodules in the parathyroid gland. A mitochondrial cytopathy related to cell ageing?

Cytochrome-c-oxidase (complex IV) was histochemically studied in oncocytic adenoma (n = 10) and carcinoma of the thyroid gland (n = 3), cystadenolymphomas and oncocytic adenomas of the major salivary glands (n = 9), oncocytic neoplasia of the kidney (n = 1) and in 21 parathyroid glands with primary hyperparathyroidism and adenomatous proliferation (n = 17) and secondary hyperparathyroidism with hyperplasia (n = 4). Only in the parathyroids defects of cytochrome-c-oxidase were found being expressed in all 4 glands with hyperplasia (14 defects) and in 5 of the 17 adenomas (11 defects). All defects were confined to foci with oxyphil cell differentiation, the defect areas varying from 0.09 to 21.10 sq mm in hyperplastic glands and from 0.11 to 13.88 sq mm in adenomas, the size of the oxyphil foci varying from 0.12 sq mm-105.38 sq mm. However, not every oxyphil nodule of a gland was devoid of cytochrome-c-oxidase activity. Of 6 predominantly oxyphil adenomas, 4 showed no defects. No defects were observed either in 2 adenomas without oxyphil cells. Further enzymes of the respiratory chain, succinate dehydrogenase (complex II) and ATP synthetase, (complex V) were devoid of defects. In parathyroids with hyperplasia and oxyphil areas, defects of cytochrome-c-oxidase occurred significantly more often and tended to be larger than in adenomas, statistical analysis revealing a significant correlation between the occurrence of defects and the number of oxyphil foci but not with the total oxyphil area.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypothesis: the case for quaternary hyperparathyroidism

We report the case of a young woman with hyperparathyroidism due to a large parathyroid adenoma associated with severe vitamin D deficiency. The case is noteworthy for the size of the parathyroid adenoma and for the young age at presentation, and is more typical of the presentation of hyperparathyroidism seen in developing countries where the prevalence of vitamin D deficiency is high. Vitamin D is known to have a suppressive effect on parathyroid cell proliferation and parathyroid hormone synthesis. Vitamin D deficiency may result in a compensatory increase in the secretion of parathyroid hormone (secondary hyperparathyroidism) which involves hyperplasia of all four parathyroid glands. Secondary hyperparathyroidism can become autonomous and this has been termed tertiary hyperparathyroidism, the underlying pathology of which has been variably described in the literature as adenoma formation or four gland hyperplasia. The pathogenesis of parathyroid adenoma formation in vitamin D deficiency remains unclear. It is possible that a proportion of cases represent the coincidence of primary hyperparathyroidism in patients with vitamin D deficiency. Alternatively, we hypothesise that autonomous four gland hyperplasia or tertiary hyperparathyroidism may progress to adenoma formation and that this should be termed 'quaternary hyperparathyroidism'.     

Brown tumors mimicking bone metastases

Brown tumors are rare skeletal manifestations of hyperparathyroidism (HPT) that may mimic cancer metastasis. Here, we present a 52-year-old woman with HPT and multiple foci of technetium uptake due to brown tumors on bone scintigraphy. Screening tests were negative for cancer and serum parathormon (PTH) measurement; parathyroid ultrasonography and scintigraphy suggested HPT. A chief cell adenoma in right and hyperplasia in the left parathyroid glands were surgically removed after which hungry bone syndrome emerged. Biopsy of the femur lesion during an open reduction with fixation operation due to a fracture established the diagnosis of a brown tumor. Brown tumors are important to consider in the evaluation of patients presenting with multiple foci of uptake on bone scanning and without an established primary neoplasm.     

Bromocriptine enhances the uptake of99mTc-MIBI in patients with hepatocellular carcinoma

99m Tc-methoxyisobutyl isonitrile(MIBI) is a suitable transport substrate for the multidrug resistance gene product P-glycoprotein(P-gp) and widely used for tumor imaging.Bromocriptine has been shown to inhibit the ATPase activity and the function of P-gp.We hypothesized that bromocriptine could promote the accumulation of MIBI by inhibiting P-gp activities,a feature that can be taken advantage of for enhancing 99mTc-MIBI imaging.In the current study,we sought to investigate whether bromocriptine enhanced the uptake of 99mTc-MIBI in hepatocellular carcinoma patients.Sixty primary hepatocellular carcinoma patients received 99mTc-MIBI single photon emission computer tomgraphy(SPECT) prior to surgery.99mTc-MIBI SPECT was performed 15 and 120 min after injection of 20 mCi 99mTc-MIBI,and early uptake,delayed uptake(L/Nd),and washout rate(L/Nwr) of 99mTc-MIBI were obtained.In addition,a second 99mTc-MIBI SPECT was performed according to the same method 48 h after bromocriptine administration.We found that,prior to bromocriptine administration,significant MIBI uptake in tumor lesions was noted in only 10(16.7%,10/60) patients with hepatocellular carcinoma.No significant MIBI uptake was observed in the tumor lesions of the remaining 50(83.3%,50/60) hepatocellular carcinoma patients.Following bromocriptine administration,all the patients without apparent MIBI uptake demonstrated significant MIBI uptake on 99mTc-MIBI SPECT(P < 0.05).Our findings indicate that bromocriptine enhances the uptake of 99m Tc-MIBI in patients with hepatocellular carcinoma.     

Parathyroid carcinoma in familial hyperparathyroidism.

Two families with hereditary hyperparathyroidism are described. One member of each family developed a parathyroid carcinoma. In one case this recurred locally and metastasised. This patient showed hyperplasia of one of the three other parathyroid glands. It is possible that the different parathyroid lesions found in familial hyperparathyroidism may be the result of a progression from hyperplasia to formation of benign or malignant tumours. The remainiing hyperplastic glands may be suppressed by hypercalcaemia. There was no evidence of multiple endocrine neoplasia in either family. Three members of a first family had ichthyosis and both affected members of the second had tumours of the jaw, one of which was an ossifying fibroma, suggesting a possible association of these conditions with familial hyperparathyroidism.     

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

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.     

Ultrasonography methods in the diagnosis of renal osteodystrophy

Bone disease, i.e. renal osteodystrophy, is commonly seen in patients with chronic renal failure. It encompasses all the disorders of mineral and bone metabolism associated with chronic renal insufficiency, i.e. secondary hyperparathyroidism, retention and accumulation of beta 2 microglobulin and aluminum. The most frequent cause of renal osteodystrophy is secondary hyperthyroidism, with a consequence of high turnover bone disease. Secondary hyperparathyroidism, i.e. increased parathyroid hormone (PTH) secretion and parathyroid gland hyperplasia, develops early in the course of chronic renal insufficiency. Hypocalcemia, phosphate retention and deficiency of calcitriol stimulate PTH synthesis and secretion and parathyroid cell proliferation, i.e. hyperplasia. Parathyroid cell proliferation is initially polyclonal (diffuse hyperplasia), and later it is monoclonal or multiclonal (nodular hyperplasia). Calcitriol receptors as well as calcium-sensing receptors are significantly reduced in parathyroid glands in nodular hyperplasia. Patients with such parathyroid gland hyperplasia are often resistant to vitamin D therapy. A specific form of bone disease is beta 2 amyloidosis. Destructive arthropathy, cystic changes and carpal tunnel syndrome are clinical manifestations of dialysis-related amyloidosis, which is one of the major complications in patients on longterm hemodialysis. Aluminum intoxication leads to the low turnover bone disease and consequential osteomalacia or aplastic bone lesions, the cause of which has not yet been fully clarified. Ultrasound can be a useful, economical and noninvasive method in the evaluation of renal osteodystrophy. Ultrasound waves are very important for noninvasive imaging of soft tissue, especially parathyroid glands, pathologic changes of the joints, and for detection of metastatic calcifications. They are also useful in the evaluation of skeletal status in dialysis patients. Ultrasound waves of a frequency above the limit of human hearing are used in the morphological diagnosis of parathyroid gland. Today, because of its simplicity and non-invasiveness, it is a generally accepted method for the detection of enlarged parathyroid gland in patients with secondary hyperparathyroidism, for the monitoring of pathologic changes, and for making decisions on the method of treatment based on the size and number of parathyroid glands. Ultrasound can distinguish nodal from diffuse parathyroid hyperplasia. Under ultrasound guidance it is possible to perform fine needle aspiration biopsy, to confirm ultrasound findings, and percutaneous inactivation of parathyroid gland (PEI) with alcohol. Ultrasound is useful in the diagnosis of pathologic changes of the musculoskeletal system in patients with beta 2 amyloidosis, to assess the process of its spread, especially in the shoulder joint where the changes are most pronounced (rotator cuff thickness, amyloid deposits as hyperechogenic pads, and detection of fluid in the joint), but it can also be used to examine other joints as well as soft tissue in which metastatic calcifications may occur. Standard ultrasound equipment (pulse-echo) and linear probe of 5-13 MHz are used, also serving for ultrasound examination of the neck, joints and soft tissue. Quantitative bone ultrasonometry is based on different physical characteristics of the ultrasound including: transmission, Speed Of Sound (SOS) in meters/sec and Broad Band Attenuation (BUA) in dB/MHz, and different concepts of the apparatus. These parameters depend on the strength and architecture of the bones and describe better the changes in bone structure in dialysis patients by calculation of the Stiffness Index (QUI), better than the standard bone densitometry by dual-energy x-ray absorptiometry, which only measures bone density. Combined ultrasound measurement of the bone in several locations may be successful in monitoring dialysis patients.     

Expression of the α- and β-subunits of human chorionic gonadotropin by subsets of parathyroid cells in states of hyperparathyroidism

The α-subunit of human chorionic gonadotropin (hCG-α) has previously been found to be expressed in hyperplasias and tumours of numerous endocrine tissues including all those involved in MEN-I syndrome except the parathyroid glands. In the present immunohistochemical investigation of 86 patients with various states of hyperparathyroidism, expression of hCG-α by subsets of parathyroid cells was shown in 46 cases (54 per cent) including all states of hyperparathyroidism investigated: primary adenoma (n=34, 44 per cent); uraemic secondary hyperplasia (n=34, 53 per cent); MEN-I (n=13, 77 per cent); MEN-II (n=2, 100 per cent); and parathyroid carcinoma (n=3, 100 per cent). Although the number of parathyroid cells expressing hCG-α was in general low, the occurrence of numerous immunoreactive cells appeared to be concentrated in primary adenoma and MEN-I (20 and 33 per cent of positive cases, respectively). No expression was found in ten normal control glands, except for very rare cells in one case. Expression of hCG-α was in part associated with that of hCG-β, which appeared to be more commonly expressed than hCG-α in cases of secondary hyperparathyroidism. In separate experiments, Bouin fixation was found to preserve the immunoreactivity of hCG-α and hCG-β better than the formalin fixation used in this study, suggesting that the figures may be underestimates. These immunohistochemical results are in agreement with a previous biochemical study showing hCG-α and hCG-β in extracts of parathyroid tumours and extend to the parathyroid glands the otherwise ubiquitous finding of hCG-α expression in MEN-I-related neoplasms. © 1998 John Wiley & Sons, Ltd.     

The parathyroid adenoma. A histopathologic definition with a study of 172 cases of primary hyperparathyroidism

There is unanimous agreement that parathyroid adenoma lacks precise histopathologic definition. Likewise, it is generally accepted that hyperplasia may involve the parathyroid glands unequally, causing tumorous enlargement of a single parathyroid gland. On the basis of observations of the histologic features of the normal parathyroid gland and on the accepted definition of an adenoma, and based on the concept of unequal or "focal" hyperplasia, histopathologic criteria for the recognition of adenoma and its differentiation from hyperplasia were formulated. Study of 172 cases of primary hyperparathyroidism with the use of these criteria showed that adenomas accounted for only 5.8% of cases of primary hyperparathyroidism and that hyperplasia with single gland enlargement accounted for 75.1%. The literature and data supporting the view that solitary masses of the parathyroid glands more often represent hyperplasia than adenoma are cited.     

Immunohistochemical study of fatty acid synthase, Ki67, proliferating cell nuclear antigen, and p53 expression in hyperplastic parathyroids.

Patients with secondary hyperparathyroidism following chronic renal disease frequently develop hyperplastic parathyroids. Hyperplastic parathyroids have an increased number of chief cells, a decreased amount of stromal fat, and a nodular or diffuse histologic pattern. Hyperplastic parathyroids may also express higher proliferative activity compared with controls. We evaluated the morphologic features and immunohistochemical expression of fatty acid synthase (FAS), Ki67, proliferating cell nuclear antigen, and p53 protein in 78 hyperplastic parathyroids from 20 patients with secondary hyperparathyroidism. Twenty normal parathyroids incidentally removed during nonneoplastic thyroid surgery were used as controls. Our results showed that hyperplastic glands overexpress FAS (P =.06). Statistical analysis also revealed a significant association between FAS and p53 protein (P =.006) and between FAS and hyperplastic glands with a predominant nodular pattern (P =.02). Hyperplastic parathyroids from patients with chronic renal failure strongly express FAS. Fatty acid synthase may therefore be a potential biological indicator of highly proliferating parathyroid cells.     

Normocalcemic primary hyperparathyroidism in patients with recurrent kidney stones: pathological analysis of parathyroid glands

The lack of overt elevation of serum calcium concentration in some patients suffering from primary hyperparathyroidism is an intriguing clinical phenomenon. Previous studies have substantiated abnormal parathyroid tissue in these patients, but the extent and mode of derangements remained largely undefined. The parathyroid tissues from patients of normocalcemic primary hyperparathyroidism (NCPHPT) and those having normal parathyroid glands, hypercalcemic primary hyperplasia, secondary hyperplasia, and adenoma were compared by undertaking quantitative immunohistochemistry analysis on tissue microarray. The statistic results suggested that the parathyroid tissue of NCPHPT approximates more to normal gland than to its counterpart in other groups of parathyroid proliferative diseases in terms of the lack of significant alterations of calcium-sensing receptor (CaSR), chromogranin A (CGA), parathyroid hormone (PTH), and proliferation index (Ki67). On the other hand, the depressed vitamin D receptor (VitDR) and elevated cyclin D1 (CyD1) of NCPHPT indicated the inherent functional abnormalities in parathyroid cells. Our results imply that inherent functional disengagement may exist between CaSR and CyD1 or between CaSR and VitDR or both in parathyroid cells of symptomatic NCPHPT. Lack of enhanced release of CGA and PTH and discordance between proliferative activity and CyD1 expression in parathyroid cells may further hinder the development of hypercalcemia.     

Fat staining in parathyroid disease—Diagnostic value and impact on surgical strategy: Clinicopathologic analysis of 191 cases

The study comprised 191 cases of surgically treated hyperparathyroidism, with all principal types of parathyroid disease represented. At least two complete glands stained with a modified isopropanol oil red O method for fat, in addition to sections stained with hematoxylin-eosin, were available in each case. On the basis of the morphologic evaluation and the clinical follow-up data, it is concluded that access to two complete glands and the use of fat staining allow highly reliable intraoperative distinction between adenoma and hyperplasia. Of 105 patients followed up for at least one year (mean, 20 months) in whom adenomas were diagnosed, a single possible error was identified. In each of 68 cases classified as hyperplasia on the basis of two abnormal glands, every additional complete gland available (total, 182 glands) was at least partially abnormal, with distinct signs of hyperactivity, irrespective of size. The rate of equivocal findings for cases in which two glands were available (probably adenoma but hyperplasia not excluded) was 8 per cent in 165 cases of primary hyperparathyroidism. These results justify limitation of surgery to one side of the neck in patients in whom adenoma is diagnosed on the basis of a complete, functionally normal (inactive) gland in addition to the presumed adenoma. Thus, the methods described provide a basis for optimal utilization of imaging techniques that allow preoperative localization of parathyroid adenomas.     

Histological and clinical features of non-familial primary parathyroid hyperplasia.

Relations between histopathological characteristics and clinical data were retrospectively investigated in patients with sporadic primary hyperparathyroidism due to hyperplasia. The study comprised 100 patients with chief cell hyperplasia and nine with hyperplasia of the water-clear cell type operated on during the period of 1959-1989. The chief cell hyperplasia was associated with a renal stone disorder as the predominant symptom in 41 patients, psychiatric/neuromuscular manifestations in 26 patients, while 23 patients were apparently asymptomatic. The remaining ten patients had miscellaneous symptoms. Patients with renal stones were more frequently of the male sex and generally had lower serum calcium values and less marked increments in total parathyroid glandular weights than patients with other symptoms or those who were overtly asymptomatic. Two main morphological patterns, diffuse and nodular hyperplasia, were encountered in chief cell hyperplasia. Diffuse hyperplasia was usually found in moderately enlarged glands, with a less variable size and morphology. It was also more prevalent among young patients having moderate hypercalcaemia and either recurrent renal stones or neuromuscular/psychiatric symptoms. The glands affected by nodular hyperplasia were asymmetric in size with a variable cellular arrangement and a high proportion of oxyphil cells. Nodular hyperplasia was irrespective of symptoms more frequent in the elderly patients. Water-clear cell hyperplasia was not encountered during the last decade of the study and until then it was an occasional finding in patients with marked hypercalcaemia. In this histological entity the glands were greatly and asymmetrically enlarged.     

Parathyroid hyperplasia in multiple endocrine neoplasia type 1: a pathological and immunohistochemical reappraisal

Twenty-nine parathyroid glands from nine patients with multiple endocrine neoplasia type 1 (MEN 1) syndrome were examined histopathologically and immunocytochemically to characterize better the nature of the accompanying parathyroid hyperplasia. The parathyroids showed varying degrees of nodular and diffuse (partial and total) hyperplastic involvement as well as apparently normal tissue. The nodules were usually multiple within any one gland and showed a varied cytoarchitectural pattern. All glands studied showed both cellular argyrophilia and parathyroid hormone immunoreactivity. The staining pattern for parathyroid hormone ranged from negative or weak to strong and from patchy to diffuse in hyperplastic tissue from different glands and within the same gland. Apparently normal areas usually showed the strongest positive reaction. Amyloid material was observed within glandular lumens from hyperplastic areas in over half of the studied cases and stained positively for parathyroid hormone. This suggests that the hormone could be the precursor molecule of parathyroid amyloid as occurs with hormone-derived amyloid from other endocrine tumours. The overall findings indicate that the most striking feature of the parathyroid glands in MEN 1 is their variability, both morphological and functional, as indicated by their parathyroid hormone immunoreactivity.