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We developed a novel model for studying hyperparathyroidism by growing ex vivo 3-dimensional human parathyroids as part of a microphysiological system (MPS) that mimics human physiology. The purpose of this study was to validate the parathyroid portion of the MPS. We prospectively collected parathyroid tissue from 46 patients with hyperparathyroidism for growth into pseudoglands. We evaluated pseudogland architecture and calcium responsiveness. Following 2 weeks in culture, dispersed cells successfully coalesced into pseudoglands ∼500-700 µm in diameter that mimicked the appearance of normal parathyroid glands. Functionally, they also appeared similar to intact parathyroids in terms of organization and calcium-sensing receptor expression. Immunohistochemical staining for calcium-sensing receptor revealed 240-450/cell units of mean fluorescence intensity within the pseudoglands. Finally, the pseudoglands showed varying levels of calcium responsiveness, indicated by changes in parathyroid hormone (PTH) levels. In summary, we successfully piloted the development of a novel MPS for studying the effects of hyperparathyroidism on human organ systems. We are currently evaluating the effect of PTH on adverse remodeling of tissue engineered cardiac, skeletal, and bone tissue within the MPS., (© 2018 S. Karger AG, Basel.)

Water clear cell adenoma of the parathyroid gland is a rare neoplasm composed of large clear cells with foamy cytoplasm and mild nuclear pleomorphism, compressing the residual nonneoplastic parathyroid tissue. The differential diagnosis includes a variety of neoplasms with clear cell features. In this article, we provide an overview of the entity with a historical perspective, in order to help pathologists in distinguishing it from other neoplasms in their daily practice.

Reported morphologies of the ultimobranchial body had varied between researchers: a cluster of mitotic cells, a duct-like structure and a rosette-like cell mass. To clarify the true morphology, we studied tilted horizontal sections of 20 human embryos (crown-rump length 5-18 mm; 4-6 weeks). The sections displayed a ladder-like arrangement of the second to fourth endodermal pouches and, in 5 early embryos we found the fifth pouch attached to the fifth ectodermal groove near the fourth pharyngeal arch artery. The bilateral fifth pharyngeal pouches protruded anterolaterally to form a U-shaped lumen surrounding the arytenoid swelling. The third to fifth pouches were each characterized by a pedal-shaped inferior end. We identified several types of cell clusters as candidates for the ultimobranchial body, but morphologically most of them were, to various degrees, likely to correspond to the blind end of the lower pouch when cut tangentially. Because of the topographical relation to the common carotid artery, a cyst-like structure with a cell cluster seemed to be the most likely candidate of the ultimobranchial body (a common anlage of the thymus and parathyroid). However, we were not able to deny a possibility that a certain plane cutting the pouch end incidentally provided such a cyst-like structure in sections. At any stage, the ultimobranchial body might not appear as a definite structure that is discriminated from others with routine staining. A concept of the ultimobranchial body might be biased by comparative anatomy that shows the ultimobranchial gland in adult birds and reptiles.

While performing thyroid surgery, the unintentional lesion of parathyroid glands and laryngeal nerves results in a profound alteration in patient's quality of life. To minimize thyroid surgery morbidity, the surgeon must have an in-depth knowledge of the thyroid gland morphology and its anatomical relations in the anterior compartment of the neck. This work intended to simulate total thyroidectomies using cadaver parts and isolate fragments that may correspond to parathyroid glands. The thyroid glands and "eventual" parathyroid glands were then submitted to histological study. Ninety-two cadaver parts were used for macroscopic dissection. A total of 242 fragments were isolated, 154 of which were confirmed through histological study to be parathyroid glands. In 36 cases, all "eventual" parathyroid glands isolated during dissection were confirmed through histological verification. In 40 cases, some glands were confirmed. In 16 cases, none of the "eventual" parathyroid glands was confirmed. The 92 thyroid glands isolated during dissection were also submitted to histological study. In 21 thyroid glands, 16 parathyroid glands were identified in the histological cuts: 8 sub-capsular, 8 extra-capsular, 6 intra-thyroidal. There was no statistical difference between the dimensions of the parathyroid glands. Parathyroid gland identification and preservation are sometimes a challenge during thyroid surgery, difficulty that has been demonstrated during dissection of cadaver parts.

Introduction: Impact of in utero exposure to nicotine, on the structure of the thyroid-pituitary axis and the parathyroid glands have been examined in 1-month-old rats and compared with that of thiocyanate., Materials and Methods: Three pregnant female groups were used; control, nicotine and thiocyanate. Treatment started from gestation day (4-20) and the specimens were harvested from the male offspring of all groups at the age of 1 month and processed for light, electronmicroscopic and immunohistochemical examination. Total triiodothyronine (tT3), total thyroxine (tT4) and total thyrotropin (TSH) were quantitatively determined in serum., Results: Both nicotine and thiocyanate activated the thyroid follicular cells, with an increase in height (about 30 %) and a negative feedback on the pituitary thyrotrophs which revealed a reduction in the number of cytoplasmic secretory granules, particularly the thiocyanate group. However, in thiocyanate group there was signs of impaired secretory activity of the thyroid gland. The arbitrary area of parathyroid chief cells, increased (about 45 %) particularly in nicotine group, with signs of reduced activity and a positive feedback on the parafollicular cells which revealed hypertrophy, proliferation (25 %) and increased intensity of positive immunohistochemical reaction for calcitonin., Conclusion: Nicotine impaired chief parathyroid cells activity and consequently activated parafollicular cells. Thiocyanate reduced pituitary thyrotrophs activity, whereas both nicotine and thiocyanate increased thyroid follicular cells activity. This impact of in utero exposure persisted for 1-month postnatal.

We qualitatively and quantitatively investigated the parathyroid glands of golden hamsters aged 6, 12, 18, 24 and 30 months. Percent area of rER in the parathyroid gland in golden hamsters at 24 months of age was significantly higher when compared to 6 and 12 months of age, and the percent area at 30 months of age was significantly higher when compared to 12 months of age, but there were no significant differences between 24 and 30 months of age. Percent area of the Golgi apparatus at 24 and 30 months of age was significantly higher when compared to 6, 12 and 18 months of age. Ultrastructurally, we believe that in the parathyroid gland of the golden hamster, synthesis and release of parathyroid hormone increase gradually from 6 to 24months of age and are maintained from 24 to 30 months of age.

This study aimed to examine the effects of genistein on the structural and functional changes in parathyroid glands (PTG) and sodium phosphate cotransporter 2a (NaPi 2a) in orchidectomized rats. Sixteen-month-old Wistar rats were divided into sham-operated (SO), orchidectomized (Orx) and genistein-treated orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered subcutaneously for 3 weeks, while the controls received vehicle alone. PTG was analyzed histomorphometrically, while the expressions of NaPi 2a mRNA/protein levels from kidneys were determined by real time PCR and Western blots. Serum and urine parameters were determined biochemically. The PTG volume in Orx rats was increased by 30% (p<0.05), compared to the SO group. Orx+G treatment increased the PTG volume by 35% and 75% (p<0.05) respectively, comparing to Orx and SO animals. Orchidectomy led to increment of serum PTH by 27% (p<0.05) compared to the SO group, Orx+G decreased it by 18% (p<0.05) comparing to Orx animals. NaPi 2a expression in Orx animals was reduced in regards to its abundance in SO animals, although it was increased in Orx+G group compared to the Orx. Phosphorus urine content of Orx animals was raised by 12% (p<0.05) compared to that for the SO group, while Orx+G induced a 17% reduction (p<0.05) in regards to Orx animals. Our study shows that Orx increases PTG volume and serum PTH level, while protein expression of NaPi 2a is reduced. Application of genistein attenuates the orchidectomy-induced changes in serum PTH level, stimulates the expression of NaPi 2a and reduces urinary Pi excretion, implying potential beneficial effects on andropausal symptoms.

Background: Cryopreservation of parathyroid tissue is used in the surgical treatment of secondary hyperparathyroidism. After surgical resection, the tissue is temporarily maintained in a cell culture solution until it arrives at the specialized laboratory where the cryopreservation process will take place. The present study evaluates the time that the human hyperplastic parathyroid gland tissue can wait before cryopreservation, based on parathyroid cell ultrastructural integrity., Methods: This prospective study included 11 patients who underwent total parathyroidectomy with heterotopic autotransplantation and cryopreservation of parathyroid tissue fragments. Part of the tissue was kept in cell culture solution at 4 °C. Five time periods between 2 and 24 h were defined, and parathyroid fragments were kept in the solution for that length of time. At the end of each period, the fragments were removed from the transport solution, fixed, and prepared for ultrathin sections., Results: Of the 11 cases studied, 10 showed ultrastructural findings consistent with cellular viability in tissue fragments that remained in the transport solution up to 12 h. Electron microscopy revealed that cell adhesion and the integrity of plasma membranes, nuclei, and mitochondria were preserved in one case for up to 24 h. Changes in mitochondrial structure represented the most constant ultrastructural damage seen in the cases studied, in addition to the presence of edema and cell vacuoles., Conclusions: Analysis of the ultrastructure of hyperplastic parathyroid gland tissue showed that ultrastructural integrity was in most cases properly maintained in fragments stored up to 12 h in a cell culture solution at 4 °C.

The detailed ultrastructural changes of uremia-induced hyperplastic parathyroid gland and the effects of current medical treatments for secondary hyperparathyroidism were investigated. Marked enlargement of parathyroid cell with accumulation of mitochondria and lipids and a significant increase in the thickness of the pericapillary area with increased fibrosis and appearance of fibroblast like cells were noted in the hyperplastic gland caused by uremia and phosphate retention. These ultrastructural changes and biochemical findings indicating hyperparathyroidism were significantly suppressed by all of the treatment using phosphate restriction, calcitriol, and cinacalcet. The characteristic ultrastructural changes, including the morphologic evidence of nodule formation, were indicated.

In order to record the effects of heroin on plasma calcium (Ca) and inorganic phosphate (Pi) levels as well as parathyroid gland and C cells, two sub-lethal doses (0.50 LD50 and 0.75 LD50) of the drug were administered intramuscularly in Rattus norvegicus for 30 days. Plasma Ca level of control rats ranged between 9.53 +/- 0.32 - 9.88 +/- 0.22 mg 100 ml(-1) while plasma Pi concentration fluctuated between 4.55 +/- 0.18 - 4.71 +/- 0.24 mg 100 ml(-1). Sub-lethal heroin administration induced progressive increase in plasma Ca level during the first seven days (p < 0.001), thereafter the level declined on day 15 and 30. However plasma Pi level of the heroin-treated rats registered increase with the peak value (p < 0.001) on day 30. The treatment elicited degenerative changes in parathyroid gland as evident by cytoplamic vacuolization, presence of more pycnotic nuclei and occurrence of patchy areas among the chief cells. Degenerative changes were also noticed in cristae of mitochondria, Golgi complex and endoplasmic reticulum. There was decrease in chromatin material in the nucleus and loss of hormone granules in the cytoplasm. Oxyphil cells of the heroin-treated rat depicted dilation of endoplasmic reticulum and damaged cristae. Sub-lethal heroin administration in the rat for 30 days induced dilation in endoplasmic reticulum and loss of secretory granules in C cells.

The pathogenesis of primary hyperparathyroidism (I degrees -HPT) and secondary hyperparathyroidism (II degrees -HPT) remains to be elucidated. To characterize their pathophysiology, we investigated the effects of calcium and phosphate on cell proliferation and PTH release in an organ culture of parathyroid tissues. Dissected parathyroid tissues obtained from patients with I degrees -HPT (adenoma) or II degrees -HPT (nodular hyperplasia) were precultured on a collagen-coated membrane for 1-4 week. After changing the medium for one containing various concentrations of phosphate, PTH release and [(3)H]thymidine incorporation were studied. In contrast to dispersed parathyroid cells cultured in a monolayer, calcium decreased PTH release in a concentration-dependent manner in parathyroid tissues. Furthermore, when parathyroid tissues obtained from II degrees -HPT were precultured for 1-4 weeks, PTH release and parathyroid cell proliferation were significantly increased in high-phosphate medium. These phosphate effects were also observed to a lesser extent in parathyroid tissues obtained from I degrees -HPT, but there was no significant difference between I degrees -HPT and II degrees -HPT. Microarray analyses revealed that mRNA levels of PTH, CaSR, and VDR were well preserved, and several growth factors (e.g. TGF-beta1-induced protein) were abundantly expressed in II degrees -HPT. Using organ cultures of hyperparathyroid tissues, in which PTH release and CaSR are well preserved for a prolonged period, we have demonstrated that phosphate stimulates parathyroid cell proliferation not only in II degrees -HPT but also in I degrees -HPT. Although the mechanism responsible for phosphate-induced cell proliferation remains to be elucidated, our in vitro findings suggest that both parathyroid tissues preserve to some extent a physiological response system to hyperphosphatemia as observed in normal parathyroid cells.

Background: During the pathologic examination of neck dissection specimens, unexpected findings within the lymph nodes may be discovered. Such findings may include benign epithelial inclusions, a second primary tumor, or chronic inflammatory diseases., Methods: We report a case of a 59-year-old man who underwent a laryngectomy and bilateral neck dissection for a right transglottic squamous carcinoma of the larynx. During the procedure, a large lymph node measuring 2.5 x 2.2 x 0.8 cm was found at the right level IV., Results: Histologic examination of the neck dissection specimen revealed benign parathyroid inclusions in the enlarged lymph node. The heterotopic cells expressed parathyroid hormone. This case represents a unique example of heterotopic parathyroid inclusions in a cervical lymph node., Conclusion: Parathyroid tissue should be included in the differential diagnosis of cervical intranodal epithelial inclusions.

Serum calcium (Ca) level of Rattus norvegicus ranged between 13.08 +/- 0.41 - 13.25 +/- 0.39 mg/100 ml whereas serum inorganic phosphate (Pi) concentration varied between 4.21 +/- 0.28 - 4.33 +/- 0.26 mg/100 ml. Sublethal (0.50 LD50 and 0.75 LD50) administration of Mipcin induced a progressive dose-dependent decline in serum Ca level in the rat which was statistically significant at 7 and 14 days. Serum inorganic phosphate level of the treated rats did not exhibit significant fluctuation during the entire course of investigation. Parathyroid chief cells of the experimental rats exhibited degranulation, vacuolation, loss of secretory (hormone) granules and lipid droplets, decreased chromatin in nuclei and damages in the endoplasmic reticulum as well as cristae of mitochondria at 14 days of the treatment. Not much of changes could be seen in the oxyphil cells of parathyroid as well as thyroid C cells of the Mipcin-treated rats.

Although the parathyroid water-clear cell is very rare, it has clinical significance because of its association with parathyroid hyperplasia or adenoma. SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal model for senile osteoporosis. We investigated the morphology of the parathyroid glands in SAMP6 and age-matched normal mouse SAMR1. The parathyroid water-clear cells, which contained numerous vacuoles and the crystalloid inclusions, were found in SAMP6 mice at 5, 8 and 12 months of age. It was noted that the number of water-clear cells increased with aging, which are fairly consistent with the change of the serum parathyroid hormone (PTH) level. We did not find any water-clear cells in the parathyroid glands of SAMR1 mice. The existence of water-clear cells may represent hyperfunction of the parathyroid glands in SAMP6.

Objective: To review one institution's experience with parathyroid lipoadenomas and to report the associated clinical characteristics., Methods: We present a case series of parathyroid lipoadenomas. A parathyroid lipoadenoma was defined as a single adenoma with more than 50% fat on histologic examination in conjunction with primary hyperparathyroidism and resolution of hypercalcemia postoperatively. Patients who fulfilled the diagnostic criteria were identified from the surgical pathology files of the Mayo Clinic., Results: Five cases of parathyroid lipoadenomas, including 1 oxyphil lipoadenoma, were identified during the period from 1971 to 2001. The clinical picture of the study subjects resembled that of a typical patient with primary hyperparathyroidism. Parathyroid lipoadenomas were identified in 3 women (60%) and 2 men (40%), and only 1 patient presented with possible hypercalcemia-related symptoms of nephrolithiasis and hip fracture, leading to diagnosis. The mean serum calcium concentration was 11.1 mg/dL. Preoperatively, all study subjects had elevation of serum parathyroid hormone levels. Two of 3 patients (67%) had the tumor identified preoperatively by neck ultrasonography., Conclusion: A parathyroid lipoadenoma is a rare cause of primary hyperparathyroidism. The clinical features of this pathologic entity are similar to those of the more common pathologic variants of parathyroid disease associated with primary hyperparathyroidism.

Plasma Ca concentration (annual mean) in males Coturnix cotumix coturnix was 10.27 +/- 0.14 mg/100 ml while it was slightly higher (11.85 +/- 0.15 mg/100 ml) among females. Plasma Pi levels (annual mean) in males and females were 5.62 +/- 0.12 mg/100 ml and 6.52 +/- 0.20 mg/100 ml, respectively. While the males did not exhibit marked fluctuation in plasma Ca and Pi levels either in winter or summer, the females did record significant elevation in the levels of both these electrolytes during breeding season. The peak values of plasma Ca (17.66 +/- 0.38 mg/100 ml) and Pi (8.64 +/- 0.22 mg/100 ml) in females were observed during June. Parathyroid gland of the grey quail exhibited hyperactivity (hypertrophy and hyperplasia) during breeding season, however, the activity was more conspicuous among females than in males. The maximum increase in cell and nuclear diameters were observed in females during May-July. The follicles were also filled with AF- and PAS-positive materials during these months. The glands depicted signs of hypoactivity and degeneration during peak winter season (November-December) as evident by decrease in cell and nuclear diameters as well as vacuolation in the chief cells.

Objective: To compare the morphology of different parenchymal cell types in healthy human parathyroid glands (HPGs) in cytologic smears with their structure on histologic sections and to establish criteria for their recognition in smears., Study Design: The HPGs of 47 subjects (27 females and 20 males) were incidentally removed during surgery on the thyroid gland. The tissue of glands with a normal macroscopic and microscopic appearance was analyzed in cytologic smears and on histologic sections., Results: In cytologic smears (as well on histologic sections), dark and light chief cells predominated. Dark chief cells, which were more numerous than light ones, had a smaller nucleus without a visible nucleolus. The nucleus of light chief cells was larger with 1 or 2 nucleoli visible. The cytoplasm of both types of chief cells was poorly defined, grey-blue and often vacuolated. In the smears, the cytoplasm of oxyphilic cells was dense, gray-rose and well defined. In dark oxyphilic cells, the nuclei were smaller and without a visible nucleolus. Light oxyphilic cells had a larger nucleus and visible nucleolus., Conclusion: The identification and distribution of 4 parenchymal cell subtypes in the smears of pathologically altered HPGs may yield insights into the possible role of these cells in a specific disease.

In situ hybridization (ISH) is a morphology-oriented technique for demonstrating the presence of specific nucleic acid sequences at chromosomal, cytological and histological levels. It is, however, sometimes difficult to recognize specific cell identity, early phase mRNA expression and alternative splicing because of the limited resolution of the light microscope. To overcome this limitation, we developed an improved technique for ISH at the electron microscopic level, in which pre-embedding hybridization with a non-radioactively labeled probe was used, followed by post-embedding immunoglobulin gold colloid staining. By applying this technique, early phase bone morphogenetic protein-3 mRNA in the nuclei and cytoplasm was successfully demonstrated in a differentiating chondrocytic cell lineage. Moreover, with oligo-DNA probes specific for alternative spliced forms of parathyroid hormone-related protein mRNA, we demonstrated such forms in a hyperplastic parathyroid gland attributed to renal failure.

Daily intramuscular administration of two doses--0.50 LD550 (150 mg/kg b w) and 0.75 LD50 (225 mg/kg b w) of diazinon for 14 days induced progressive hypocalcemia without altering serum inorganic phosphate value in Rattus norvegicus. Hypocalcemic response of the pesticide was dose- as well as time-dependent. Parathyroid chief cells of the experimental rats exhibited degranulation, vacuolation, loss of secretory granules and lipid droplets, decreased chromatin, and degenerative changes in endoplasmic reticulum, Golgi complex as well as cristae of the mitochondria. Not much of ultrastructural changes could be seen in the C cells of the rats treated with diazinon.

We investigated the morphology and the distribution of the nerve fibres in golden hamster (Mesocricetus auratus) parathyroid glands using antibodies to calcitonin gene-related peptide (CGRP) and substance P, and electron microscopy. CGRP-immunoreactive nerve fibres were densely distributed in the interstitial tissues and the capsules of the hamster parathyroid glands. Some nerve fibres were detected in close proximity of the parathyroid chief cells. The distribution pattern for substance P-immunoreactive nerve fibres was roughly the same as for CGRP-immunoreactive fibres. Ultrastructurally, we found numerous nerve fibres joining the blood vessels. Axon bundles were located adjacent to the smooth muscle cells of the arterioles. The axons formed structurally specialized neuromuscular junctions with the vascular smooth muscle cells. Some axons were in close vicinity to the parathyroid chief cells. These findings indicate that the hamster parathyroid gland contain CGRP and substance P, which may regulate the blood flow and the secretory activity of the gland.

Iron lactate was given to Sprague-Dawley rats intravenously at the dosage of 10 mg/kg/day and the early effects on the parathyroid gland were examined ultrastructurally along with the blood level of parathyroid hormone (PTH) after single, 3-day or 6-day administration. Blood levels of electrolytes and other parameters related to osteoclast dynamics were also measured by blood chemistry and histopathology. The plasma parathyroid hormone (PTH) level was elevated in the single and 3-day dosing group but was reduced in the 6-day dosing group. Histopathologically, an increase of osteoclasts in the primary spongiosa was observed in the 3- and 6-day dosing groups. Image analysis of the parathyroid gland revealed that the average area of the storage granule decreased during a experimental period, with the number of storage granules decreasing in the 3- and 6-day dosing group. The chief cells of the parathyroid gland were moderately atrophied in the 6-day dosing group. These results demonstrate that iron lactate immediately promotes discharge of PTH from the storage granules after the treatment and induces an increase of osteoclasts in the primary spongiosa. The findings collectively suggest a pathophysiological mechanism of iron lactate-induced osteopenia in rats.

SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal model for senile osteoporosis. We investigated the morphology of the parathyroid gland and thyroid C cell, together with the serum parathyroid hormone (PTH) and calcitonin (CT) in SAMP6 and age-matched normal mice SAMR1. We did not find any significant differences between SAMR1 and SAMP6 at 1 month of age with regard to the serum PTH level and the morphology of the parathyroid glands. As compared with SAMR1, the serum PTH level was significantly higher in SAMP6 at 2, 5 and 12 months of age. In the parathyroid chief cells of SAMP6 at 2, 5 and 12 months of age, the Golgi complexes and the cisternae of the granular endoplasmic reticulum were well developed. Numerous secretory granules were located near the plasma membranes and mitoses were sometimes observed. There was no marked difference between SAMR1 and SAMP6 regarding the morphology of the thyroid C cells and the serum CT level. These findings suggest that the secretory activity of the parathyroid gland is stimulated in SAMP6 at 2, 5 and 12 months of age. The parathyroid follicle was sometimes found in SAMP6, and the significance of this structure was also discussed.

We qualitatively and quantitatively investigated parathyroid glands of the UM-X7.1 cardiomyopathic hamster at 1, 2, 6 and 12 months of age to compare them with those of the normal hamster. We found that at 1 month of age in the UM-X7.1 hamster, the Golgi apparatus, lipid droplets and secretory granules decreased. There were no significant differences between the UM-X7.1 hamster and the control hamster at 2 months of age. At 6 months of age, the Golgi apparatus, rER and the secretory granules significantly increased in the UM-X7.1 hamster. At 12 months of age, the Golgi apparatus and lysosomes increased, while the secretory granules decreased. Ultrastructurally, we consider that in the UM-X7.1 hamster, the synthesis and release of the parathyroid at 6 months of age may be activated by an excessive amount of circulating catecholamine, and the functional activity of the parathyroid glands at 12 months of age may be depressed by the increased plasma calcium level. These findings suggest that the activities of the synthesis and release of the parathyroid hormone were the highest at 6 months of age in the UM-X7.1 hamster.

Morphological changes in parathyroid chief cells were investigated in rats with humoral hypercalcaemia of malignancy (HHM), induced by intraperitoneal inoculation with a rat pulmonary adenocarcinoma cell line, IP-B12. Inoculation with IP-B12 cells resulted in the production of parathyroid hormone-related protein (PTHrP); thus, IP-B12-bearing rats developed hypercalcaemia, with elevated plasma PTHrP concentrations and decreased serum PTH, at 5 to 7 weeks after the inoculation. Morphometrical analysis revealed an increase in the cytoplasmic area of chief cells in IP-B12-bearing rats, as compared with controls. Ultrastructurally, although the number of mature storage granules in the chief cells was similar in controls and IP-B12-bearing animals, degraded granules were significantly increased in tumour-bearing rats. In addition, the chief cells of IP-B12-bearing rats showed a trend towards decreased tortuosity of the cytoplasmic membrane, with simple interdigitations between adjacent cells. These findings suggested that under HHM conditions, PTH granules in the chief cells were maintained in the form of storage granules and were hydrolysed, resulting in the suppression of PTH release into the blood circulation. Serum PTH concentrations may be regulated by inhibition of secretion rather than suppression of granular synthesis in hypercalcaemic rats. This is the first description of morphological changes in the parathyroid gland of rats with HHM., (Copyright 2004 Elsevier Ltd.)

The relationship between secretion of parathyroid hormone (PTH) and biologic characteristics, including cell proliferation or monoclonality, is not yet fully understood. To evaluate secretory activity of glands or nodules histopathologically, we focused on the co-expression of chromogranin A (CgA) and parathyroid hormone (PTH) in each gland or nodule. A total of 55 glands from 38 patients with normal parathyroid glands, hyperplastic glands (diffuse and nodular) and primary adenomas were compared. Co-expression of PTH and CgA was decreased to 44.4% in diffuse hyperplastic glands, and to 39.6% in 91 hyperplastic nodules, in contrast to normal glands and primary adenomas that showed constant co-expression of PTH and CgA. Immunohistochemical study of PTH showed a coarse granular pattern predominantly in PTH-positive/CgA-positive nodules, and a dot-like pattern mainly in PTH-positive/CgA-negative nodules. Laser scanning microscopy and immunoelectron microscopy confirmed that a dot-like pattern is based on a positive reaction of PTH at the Golgi apparatus. MIB-1 LI was 12.6 +/- 11.6 in PTH-positive/CgA-positive, and 19.3 +/- 27.3 in PTH-positive/CgA-negative nodules. In conclusion, a combination of PTH and CgA could provide more information about the physiologic state of secretory activity of each nodule than does the simple observation of PTH immunoreactivity.

Cigarette smoking has been identified as one of the risk factors to induce osteoporosis. However, we find no study on the morphology of the parathyroid gland under smoking exposure. We studied the ultrastructure of the parathyroid gland, lung and femur of the golden hamster exposed to cigarette smoke. Four-week-old male hamsters were housed in a plastic case (48x31x30 cm) and were exposed to cigarette smoke for 12 weeks, 5 minutes exposure, 4 times a day, 4 days a week. There were no differences in serum calcium level and the whole bone mineral density between the control and the smoke-exposed groups. In the parathyroid gland of the smoke-exposed animals, the Golgi complexes associated with many prosecretory granules were well developed and many secretory granules were located near the plasma membrane. Large lipid-like inclusion bodies were observed in the alveolar macrophages of the smoke-exposed animals. The femur morphology showed a wider area of resorbing surface in the smoke-exposed group than in the control group. From these findings, it is conceivable that the secretory activity of the parathyroid gland was stimulated with cigarette smoke exposure.

Progressive telomere shortening with aging was studied using normal thyroid tissue specimens from 46 human subjects aged between 0 and 98 yr and normal parathyroid tissue specimens from 21 human subjects aged between 0 and 83 yrs. There has hitherto been no information documented about telomere length in such thyroid and parathyroid tissues. Age-related shortening at rates of 91 and 92 base pairs (bp) per year, respectively, were observed. Telomere lengths of normal thyroid tissues were 16.53 +/- 1.10 (mean +/- SE), 14.31 +/- 0.80, 11.27 +/- 0.68 and 8.73 +/- 1.08 kbp for age groups less than 2, 20-50, 51-80 and more than 80 yr. Telomere lengths of normal parathyroid tissues were 15.80 +/- 1.46 (mean +/- SE), 15.36 +/- 0.86 and 10.93 +/- 0.78 kbp for age groups less than 4, 20-50 and 51-80 yr. Telomere shortening occurred after 50 yr of age in thyroid and parathyroid tissues. Human thyroid and parathyroid tissues do not seem to show the rapid reduction in telomere length early in life that was reported for some human cell types, suggesting that the rate of telomere shortening has tissue-specific characteristics.

Young female rats were fed with normal (1.18%) or low (0.05%) calcium diet for 3, 7, 15 or 30 days. The morphology of the parathyroid glands was studied together with serum calcium, parathyroid hormone (PTH), calcitonin and bone mineral density (BMD). As compared to the animals fed with the normal calcium diet, BMD of whole body of the rats fed with the low calcium diet was significantly decreased, whereas the serum PTH level was increased. The parathyroid glands in the rats fed with the low calcium diet were markedly enlarged. In the parathyroid chief cells of the rats fed with the low calcium diet, the Golgi complexes and the cisternae of the granular endoplasmic reticulum were well developed, while the large granules and large vacuolar bodies decreased. Some secretory granules located near the plasma membrane. A proportionally larger increase of the cytoplasm was estimated in the rats fed with the low calcium diet for three and seven days. Enlargement of the cytoplasm and rather frequent mitoses of the chief cells were observed in the rats fed with the low calcium diet for 15 and 30 days. These findings suggest that the rapid bone loss in young rats induced by the low calcium diet is essentially due to stimulated activity of the parathyroid gland. The stimulated gland may be a result of hypertrophy at the early stage and a combination of hypertrophy and hyperplasia at the later stage of calcium deficiency.

Background: Technetium-99m-sestamibi (sestamibi) is the imaging agent of choice for preoperative parathyroid localization. The subcellular localization of sestamibi uptake in enlarged parathyroid glands in patients with hyperparathyroidism has not been determined. This study investigated the mechanism of retention of sestamibi by human parathyroid tissue., Methods: Twenty-three freshly harvested and 15 cryopreserved parathyroid glands excised from patients with primary or secondary hyperparathyroidism were analyzed for subcellular localization of Tc-99m-sestamibi. Tissues were incubated with 100 microCi of sestamibi and isolated for mitochondria by differential centrifugation, and the integrity of subcellular fractions was quantified with the mitochondrial enzyme marker, succinate dehydrogenase., Results: Ninety-two percent of sestamibi activity was associated with mitochondria. Furthermore, after adding the mitochondrial uncoupler, carbonylcyanide m-chlorophenylhydrazone (CCCP), to fresh parathyroid tissues, 84.96% and 73.86% of sestamibi was released from the mitochondrial and tissue fragment components, respectively. In addition, sestamibi activity in the mitochondrial component of cryopreserved human parathyroid tissue decreased to the same amount as the CCCP-treated group., Conclusions: These data confirm that mitochondrial activity is the major component of sestamibi uptake by human parathyroid tissue in patients with hyperparathyroidism.

Background: Intraoperative parathyroid gland identification and preservation is often a challenge even in the hands of experienced surgeons as they could be indistinguishable from fat or thyroid tissue., Objective: The goal of this study was to demonstrate the use of the Cytoscan Model E-II, which uses orthogonal polarization spectral (OPS) imaging technology, as an intravital microscope in identifying parathyroid glands intraoperatively and differentiating the parathyroid glands from fat and thyroid tissue in a rabbit model., Methods: The necks of 4 New England white rabbits were explored with the animals under a general anesthesia. The Cytoscan was used to obtain images of the vasculature of tissue suspected to be parathyroid, fat, and thyroid tissue. These were confirmed by histologic evaluation., Results: All tissues were correctly identified by the Cytoscan and confirmed by histologic analysis. There was an obvious difference in the images obtained of fatty tissue as compared with parathyroid tissues. There was also an appreciable difference between parathyroid and thyroid tissue based on the difference in vascularity., Conclusions: OPS imaging technology can be used in identifying parathyroid glands based on the difference in vascularity from fat and the pattern and density of vessels when compared with thyroid tissue in a rabbit model., Significance: The Cytoscan may play a future role in real time intraoperative identification of human parathyroid glands. Future investigation is warranted.

We investigated hamster parathyroid glands of different ages using electron microscopy and found a new cell type in young, adult and senile hamsters. Theses special cells were located in interstitial tissues and invariably contained several lipid droplets within the cytoplasm. The cells showed an elongated spindle with some cell processes. The cells contained small Golgi complexes and moderate cisternae of the granular endoplasmic reticulum. The morphological characteristics of these cells were mostly the same as those of lipid-storing cells in other organs (Yamada and Hirosawa, 1976). After vitamin A administration, the lipid droplets in these cells markedly increased in number and also in volume density. The other morphological features of these cells resembled those of the control animals. We called these cells parathyroid lipid-storing cells. They may incorporate and store vitamin A within the lipid droplets. They can be classified as one of the cellular components in hamster parathyroid gland.

Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 microm2; SE 0.171) through PA (3.638 microm2; SE 0.125) to PC (4.701 microm2; SE 0.179); these differences were highly significant (P<0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P<0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 microm2; SE 0.106) than in nonrecurrent PH (2.261 microm2; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions.

This study was conducted to evaluate the acute effects of caffeine on the ultrastructure of the parathyroid glands in golden hamsters. Caffeine was given orally at either 2.5 mg (low dose) or 10 mg (high dose) per 100 g body weight. Caffeine caused a dose dependent decrease of the serum calcium level 2 hours after administration. Transmission electron microscopy of the parathyroid gland revealed that the volume densities occupied by the Golgi complexes and rough endoplasmic reticulum (RER) were found significantly higher 2 hours after receiving high dose of caffeine. Statistical analysis revealed no significant differences regarding to the bone mineral content (BMC) and bone mineral density (BMD). It is considered that the synthesis of parathyroid hormone is stimulated following caffeine administration.

The ultrastructure of the parathyroid gland and the SEM appearances of the tibia were studied in hamsters with and without administration of caffeine. Caffeine was treated orally each day at either 2.5 mg (low dose) or 10 mg (high dose) per 100 g body weight for a period of 17 or 32 days. Statistical analysis showed no significant differences among all groups examined regarding the serum calcium level. Transmission electron microscopy of the parathyroid gland revealed that the volume densities occupied by the mitochondria, Golgi complexes and rough endoplasmic reticulum of caffeine-treated groups were found significantly higher when compared with controls. The number of secretory granules observed close to the cell membrane per total amount of these granules revealed significant increase in all caffeine-treated animals. The bone mineral content (BMC) values were closely related to body weight. In the high dose caffeine-treated hamsters increment of the mean BMC and body weight values was significantly lower than those of the controls after 32 days. In the scanning electron microscopic studies of the tibia, no alteration in the morphometric parameters was demonstrated. It is considered that the synthesis and release of parathyroid hormone is stimulated following caffeine consumption. Our data suggest that although chronic administration of caffeine in the hamster may slightly increase bone turnover as evidenced by the BMC decrease, bone morphometry was not altered. Thus the osteoporotic changes were not proved in this study.

The distribution and morphology of the parathyroid macrophages in golden hamsters from neonatal to senile periods were investigated using the monoclonal antibody to ED2 and electron microscopy. The results showed that definite ED2-positive cells were hardly detectable in the parathyroid gland of 1-day-old hamsters. A few ED2-positive cells could be identified in the parathyroid gland of 10-day-old hamsters. The ED2-positive cells were more densely and became conspicuous in 1-, 3-, and 12-month-old hamsters. The number of the cells seems to be increased with aging. Ultrastructurally, we did not find any macrophages in parathyroid glands of 1-day-old hamsters. In the 10-day-old hamster parathyroid gland, a few macrophages existed only in the interstitial tissues. In the parathyroid gland of 1-, 3-, and 12-month-old hamsters, many macrophages were found in the perivascular regions, some cells located among the parenchymal chief cells with no obvious vascular association. These cells showed some physical contacts with chief cells. These results suggest that the parathyroid macrophages exhibit dramatical changes in their distribution and morphology from neonatal to senile periods.

The ultrastructure of the parathyroid glands of Rattus rattus was investigated. In the chief cells, the nucleus showed deep indentations, and lysosomal inclusions and rod-shaped crystalloids were present. Their ultrastructure is described, and the role of the lysosomal inclusions is discussed.

The ultrastructure of the parathyroid gland in golden hamsters after long-term treatment with ethanol was studied. Male hamsters of experimental groups were given ethanol at the concentration of 7% for 3 and 5 months with food and water freely available. In the ethanol-treated hamsters, the Golgi complexes associated with many prosecretory granules were well developed and many secretory granules were located near the plasma membrane as compared with those of the control animals. Exocytotic events were observed in 5-month-treated animals. These findings suggest that the secretory activity of the parathyroid gland is stimulated after long-term treatment with ethanol.

The ultrastructure of the parathyroid gland (PTG) of the UM-X7.1 cardiomyopathic hamster (the UM-X7.1) was qualitatively and quantitatively compared with that of the normal hamster. In the UM-X7.1, the Golgi apparatus and rER were well developed compared with those of the control hamster. Morphometric analysis revealed that the mean values of the Golgi apparatus, rER and large vacuolar bodies were significantly greater in the UM-X7.1 than in the normal hamster and the mean value of lipid droplets was significantly less in the UM-X7.1 than in the normal hamster. Ultrastructurally, we consider that in the UM-X7.1, the synthesis and release of the parathyroid hormone may be activated by an excessive amount of circulating catecholamine, and the functional activity of the PTG may be higher than that in the normal hamster.

Thyroid vascular casts were made by injecting a resin, Mercox, into 3 types of hypertensive rats (spontaneously hypertensive rats, SHR, stroke-prone SHR, SHRSP, malignant SHRSP, M-SHRSP), and the vascular casts were observed by scanning electron microscopy (SEM). There was no difference in the general morphology of the vascular casts between SHR and the control (Wistar Kyoto rats, WKY). However, the density and the diameter of blood vessels in SHRSP and M-SHRSP were significantly different from those in WKY, and abnormal vasculatures that formed protrusions with free endings were observed in M-SHRSP. It was concluded that thyroid vascular networks in hypertensive rats were transformed into abnormal formations with decreased capillary diameter in parallel with the progress of hypertension.

The objective of this review is to correlate endocrinologic data from mechanistic studies with quantitative histopathology in selected examples of toxic endpoints of the endocrine system in laboratory animals. Mechanistic data can aid in the interpretation of animal toxicology findings and help clarify their significance in risk assessment. Endocrine organs of rodents frequently undergo proliferative changes with advancing age and following chronic exposure to large doses of xenobiotic chemicals, and the sensitivity of rodent endocrine tissues appears to be increasing. Many xenobiotic chemicals in large doses disrupt thyroid function in rodents either by a direct effect on the thyroid influencing synthesis of thyroid hormones or by adversely influencing their peripheral metabolism. A number of chemicals disrupt thyroid function by inhibiting the important enzyme, thyroperoxidase (TPO). A contemporary example of a chemical acting as TPO-inhibitor is sulfamethazine. In short-term mechanistic studies in rats there was a log-dose response relationship in circulating levels of thyroid and pituitary hormones plus a similar non-linear dose-response in morphologic changes in thyroid follicular cells. Endocrinologic data from mechanistic studies and histopathologic/ultrastructural findings will also be presented for the effects of the food color, FDC Red No. 3 (Erythrosine), on the thyroid gland in rats and parathyroid hormone-related protein (a major causative factor in cancer-associated hypercalcemia) on parathyroid chief cells in mice.

We studied the ultrastructure of the parathyroid gland of young golden hamsters after short-term treatment with ethanol (1.5 g/kg bw or 6.0 g/kg bw). We did not find any ultrastructural changes of the parathyroid gland after administration of 1.5 g/kg ethanol. In the hamsters, 3 hours after administration of 6.0 g/kg ethanol, the mean serum calcium concentration was significantly low as compared to that of the control animals. In the parathyroid gland 1 hour after administration of 6.0 g/kg ethanol, the Golgi complexes associated with a few prosecretory granules and the volume density occupied by the Golgi complexes decreased compared with that of the control animals. In the parathyroid glands 3 hours after administration of 6.0 g/kg ethanol, the Golgi complexes decreased as compared with those of the control animals, while the large vacuolar bodies increased. These findings suggest that the cellular activity of the parathyroid gland is suppressed after short-term treatment with ethanol. Intracellular lumen was found in the parathyroid chief cells 3 hours after administration of 6.0 g/kg ethanol, and the significance of this structure is discussed.

The ultrastructure of the parathyroid gland and ultimobranchial gland of the snake, Elaphe quadrivirgata, was studied. The parenchyma of the parathyroid gland was consisted of chief cells arranged in cords. Oxyphil cells and water-clear cells were not recognized. The chief cells contained irregular shaped nucleus, moderately-developed mitochondria, granular endoplasmic reticulum and Golgi complexes. A few secretory granules of 100-300 nm in diameter distributed in the cytoplasm. Small aggregations of glycogen particles and lipid droplets were dispersed widely in the cytoplasm. The ultimobranchial glands consisted of follicles and interfollicular aggregates of C-cells. Follicles were invaginated and composed of C-cells, goblet cells and ciliated cells. C-cells were located in the basal position of the follicle and possessed variety of secretory granules of 100-300 nm in diameter in the basal region of the cell. C-cells presented various secretory cycles. Goblet cells projected microvilli into follicular lumen. At the apical region the goblet cells had large granules of 300-1,200 nm in diameter. Ciliated cells projected cilia intermixed with micovilli from the apical surface of the cell into the follicular lumen.

To investigate the morphological changes of the parathyroid gland of the immobilized hamsters, we studied the ultrastructure of the parathyroid gland of golden hamsters kept in special small cage (Ballman cage II). All hamsters of the control group were kept in one ordinary cage. Each hamster of the isolated group was kept in ordinary cage individually. Each hamster of the immobilized group was kept in Ballman cage II individually. All hamsters were kept for 5 days. On the first and fifth day of the experiment, bone mineral content (BMC) and bone mineral density (BMD) of whole body were measured by dual energy X-ray absorptiometry (DXA). In the control and isolated groups, BMD of the fifth day was significantly increased as compared to that of the first day. In the immobilized group BMC and body weight were significantly decreased. There was no significant difference among 3 groups concerning the mean serum calcium level. Volume density of the cell organelles and inclusions was estimated and compared among 3 groups. Volume density of the lysosomes and large vacuolar bodies of the isolated and immobilized groups was significantly higher than that of the control group. Much more lipid droplets were observed in the immobilized group than the control and isolated groups. No particular differences were observed as to the Golgi complex in the isolated and the immobilized groups compared to the control group. These findings suggest that the cellular activity of the parathyroid gland is suppressed with immobilization.

An original human parathyroid cell culture model from uremic patients with IIo hyperparathyroidism has been developed, with its main feature being long-term functionally active viability up to 5 months, as assessed by persistent responsiveness to changes of extracellular Ca2+ concentrations ([Ca2+]e). In addition to the inhibitory effect of increasing [Ca2+]e, increasing extracellular phosphate exerted a biphasic effect on parathyroid hormone (PTH) secretion. The presence of the Ca2+-sensing receptor (CaR), on which depends the response to [Ca2+]e and its persistence, has been demonstrated in our culture system both by direct detection and by inhibition of its activity. CaR protein was detected by Western blot analysis with a specific anti-CaR antibody. CaR gene transcripts have been identified by reverse transcription-polymerase chain reaction analysis. mRNA (by in situ hybridization) and protein (by immunocytochemistry) expression were detected for both CaR and PTH. Adding a specific anti-CaR antibody to the medium induced a marked reduction of low [Ca2+]e-stimulated PTH release, which decreased to levels equivalent to those obtained in high [Ca2+]e medium. The described long-term functionality could be due to several factors, including the clustered cell type of culture yielded by our preparation procedure, the growth characteristics of hyperplastic uremic tissue, and the use of a phosphate-rich medium. The present model, because of its long-term functionality, is a unique tool for the exploration of PTH synthesis and secretion and for studies of parathyroid cell growth in vitro.

The ultrastructure of the parathyroid glands (PTG) of magnesium (Mg)-treated golden hamsters exposed to centrifugation at 1.2 G for 7 days was compared to that of the control, Mg-treated or centrifuged groups. In the PTG of the Mg-treated group exposed to centrifugation, the Golgi apparatus increased compared with that of the Mg-treated group, but was similar to that of the control and centrifuged groups. The cisternae of the rough endoplasmic reticulum (rER) increased compared with that of the Mg-treated group and decreased compared with that of the centrifuged group, but was the same as that of the control group. There were no significant differences among the 4 groups with regard to lysosomes, large vacuolar bodies, lipid droplets and secretory granules. These observations suggest that the rER is sensitive to centrifugation compared with the Golgi apparatus and more importantly the inhibitive effect of Mg on the synthesis of the hamster parathyroid hormone is enfeebled by centrifugation at 1.2 G.

We examined the effect of magnesium (Mg) on the fine structure of the golden hamster parathyroid gland in vivo and in vitro. In the in vivo study, the principal changes in the parathyroid glands 10 and 30 min, and 1 hr after Mg injection showed a significant decrease in the area of the Golgi apparatus and cisternae of the rough endoplasmic reticulum compared with those of the control animals. The serum calcium level in the experimental animals 30 min and 1 hr after the injection was significantly low compared with that of the control animals. In the vitro study, the area of the Golgi apparatus in the Mg-treated group significantly decreased as compared with that of the control group. These changes suggest that Mg directly suppresses the synthesis of hamster parathyroid hormone in the short term.

The large vacuolar bodies in the parathyroid glands of pregnant golden hamsters after administration of CaCl2 or EDTA were investigated. In the parathyroid glands of the pregnant animals 15 min after administration of CaCl2, the mean serum calcium concentration was significantly high when compared to that of the control animals. In the parathyroid glands of the pregnant animals 15, 30 and 60 min after administration of EDTA, the mean serum calcium concentration was significantly low when compared to that of the control animals. In the parathyroid glands of the pregnant animals 15 min after administration of CaCl2, the percentage area occupied by large vacuolar bodies was significantly increased when compared to that of the control animals. In the parathyroid glands of the pregnant animals 15 min after administration of EDTA, the percentage area occupied by large vacuolar bodies was significantly decreased when compared to that of the control animals.

Fine-needle aspirates and tissue sections from 120 surgically treated parathyroid (PT) lesions and histologic archive material from PT lesions in 1,500 additional cases of hyperparathyroidism were reviewed to assess the importance of various features in distinguishing PT disease from other types of lesions by aspiration cytology. We conclude that the morphologic variation shown by PT lesions is so many-sided that this distinction cannot be based on the presence or absence of a single feature only. Instead the cytologic picture as a whole must be taken into account and evaluated with full knowledge of the anatomical conditions pertaining to the lesion examined. If still in doubt, the diagnosis can be substantiated by supplementary immunocytochemical examinations.

We performed scintigraphy with technetium-99m-methoxyisobutylisonitrile (MIBI) in 10 patients with parathyroid adenoma (7 lesions) or hyperplasia (9 lesions). Correlation between an amount of accumulation of MIBI and histological types of the lesions were evaluated with special reference to an amount of oxyphilic cell in the lesions. Selected lesions were also evaluated for mitochondrial density by electromicroscopy and showed increased mitochondrial density in the oxyphilic cells. All lesions equal to or above 220 mg showed positive scintigraphic results despite differences in cell types. Undetected lesions were all equal to or below 100 mg. The scintigraphic results for 2 lesions with abundant oxyphilic cells were both positive although those for 11 lesions with abundant chief cells only 6 were positive, probably because these lesions were smaller in the hyperplasia group. In conclusion, MIBI uptake in parathyroid lesions was not dependent on the cell type but either on the size or functional state of the lesions.

We report the culture and cloning of human endothelial cells derived from parathyroid tissue surgically removed from a patient affected by Multiple Endocrine Neoplasia Type 1 syndrome. These cells, known as HPE, have been isolated and maintained in culture by serial passages for more than 15 months. The clonal cell line grows in a medium containing serum substitutes which favour endothelial cell growth. HPE cells replicate with a mean doubling time of 120 h, showing typical functional and morphological features of endothelial cells, such as uptake of acetylated low density lipoprotein and positive reaction for Factor VIII-Related Antigen. Basic fibroblast growth factor, vascular endothelial growth factor, insulin-like growth factor type I and ascorbic acid stimulate cell proliferation, whereas transforming growth factor beta and heparin act as inhibitory factors. Prostaglandin E2, secretin and epinephrine increased cAMP production, while human parathyroid hormone, histamine and glucagon were inert. Cells were found to express pro-collagen alpha 1 (type I) mRNA. In HPE cells Restriction Fragments Length Polymorphism and PCR analysis did not show allelic loss at chromosome 11q12-13, known to be a typical feature of MEN 1 parathyroid tumors. These cells are the first example of an established normal human clonal cell line with an endothelial phenotype.