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PubMed1993

Primary parathyroid gland hyperplasia in dogs: six cases (1982-1991).

Persistent hypercalcemia attributable to parathyroid gland hyperplasia was identified in 6 dogs with primary hyperparathyroidism. Clinical signs included polydipsia (n = 4), polyuria (n = 4), and signs caused by cystic calculi (n = 3). Abnormal clinical pathologic findings included hypercalcemia (mean, 13.6 mg/dl; range, 12.6 to 14.7 mg/dl; n = 6), hypophosphatemia (mean, 2.2 mg/dl; range, 1.4 to 2.9 mg/dl; n = 6), high serum alkaline phosphatase activity (mean, 222 IU/L; range, 161 to 286 IU/L; n = 3), and isosthenuria (mean, 1.012; range, 1.006 to 1.017; n = 6). Serum parathyroid hormone concentration was within the reference range or high (mean, 23 pmol/L; range, 7 to 119 pmol/L; reference range, 1.5 to 13 pmol/L) in all dogs. At surgery, the number of large parathyroid glands was variable, being limited to 1 gland in 3 dogs, 2 glands in 2 dogs, and 4 glands in 1 dog. All visibly large parathyroid glands were surgically removed from each dog. Serum calcium concentration decreased into or below the reference range within 72 hours of surgery in all dogs, confirming the diagnosis of primary parathyroid disease. Multiple nodules of adenomatous hyperplasia were identified in each dog. All 6 dogs were treated with vitamin D and calcium carbonate following surgery. The dog from which all 4 parathyroid glands were removed has remained eucalcemic for more than 1 year with vitamin D supplementation. Vitamin D and calcium administration was discontinued within 4 to 12 weeks of surgery in the remaining 5 dogs. These dogs remained eucalcemic without vitamin D supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1984

Parathyroid glands in familial benign hypercalcemia (familial hypocalciuric hypercalcemia).

The histologic characteristics of the parathyroid glands in familial benign hypercalcemia (familial hypocalciuric hypercalcemia) are disputed, some finding parathyroid hyperplasia and others finding no abnormalities. To further investigate this issue, the histologic appearance of 82 parathyroid glands from 47 control patients (surgical and autopsy) were compared with those of 28 glands from 23 patients with familial hypocalciuric hypercalcemia who had undergone surgery for suspected primary hyperparathyroidism. Median and mean weights of 23 parathyroid glands from 12 patients with familial hypocalciuric hypercalcemia were 50 mg and 60 mg, respectively, with a range from 5 to 181 mg. Eighty-three percent of individual glands were within extreme normal limits for weight (less than 75 mg). Percent parenchymal area in familial hypocalciuric hypercalcemia was slightly but significantly less than control values (62 +/- 2 versus 71 +/- 2 percent, respectively; (p = 0.009). Conversely, percent fat was higher in familial hypocalciuric hypercalcemia than control values (30 +/- 3 versus 21 +/- 2 percent, respectively; p = 0.015). Stromal area was 8 +/- 1 percent in each group. Although 15 to 20 percent of parathyroid glands in familial hypocalciuric hypercalcemia exceeded normal size, most were indistinguishable from normal by size, weight, and microscopic appearance. The significantly reduced percent parenchyma in glands from patients with familial hypocalciuric hypercalcemia further suggests that the condition is not uniformly accompanied by typical parathyroid hyperplasia and should not be thought of as merely a variant of the latter.

Adenoma↗
PubMed1989

Primary hyperparathyroidism associated with two enlarged parathyroid glands.

An increasingly recognized although small percentage of patients with primary hyperparathyroidism have enlargement of two parathyroid glands. We have treated nine patients with primary hyperparathyroidism associated with such double parathyroid gland enlargement. In four of these patients, marked asymmetry of the two enlarged glands was noted and the failure to recognize and excise a second enlarged parathyroid gland resulted in persistent or recurrent hyperparathyroidism. In one of these patients, the second enlargement was present in a super-numerary mediastinal gland. The subsequent excision of the second enlarged parathyroid gland resulted in normocalcemia in each instance. This contrasts with five patients in whom initial excision of two enlarged glands resulted in normocalcemia with no recurrence of hypercalcemia. Only three patients fulfilled the histologic criteria of true double adenomas. The remainder showed multiglandular hypercellularity. This experience supports identifying all parathyroid glands and recognizing that even minimal enlargement of a gland may be important pathophysiologically, regardless of its histopathologic classification. Excision of both enlarged glands, even if asymmetric, is appropriate.

Adult↗
PubMedDate not supplied

Calcitriol pulse therapy and histology of parathyroid glands in hemodialysis patients.

BACKGROUND: Calcitriol pulse therapy (CPT) is considered the most appropriate treatment of secondary hyperparathyroidism (sHPTH). This treatment inhibits parathyroid hormone (PTH) synthesis and secretion, suppresses parathyroid cell proliferation and controls parathyroid gland growth. However, not much is known about the effect of such therapy on parathyroid morphology. METHODS: To investigate this, we studied all first parathyroidectomies (PTx, either total or subtotal) effected in 30 hemodialysis (HD) patients referred to our surgery department by five regional dialysis units in 2000-2001. Six patients were excluded from the study because of either the persistence or the precocious relapse (in the 1st 6 months post-operation) of sHPTH. Twenty-four HD patients were considered eligible as four parathyroid glands were ablated in each patient; 96 glands were then examined histologically. The cohort consisted of 16 males and 8 females with a mean age of 54 +/- 13 SD yrs (range 20-73) and a dialysis duration of 142 +/- 71 months (range 14-289). Data concerning calcitriol treatment (doses, administration route and treatment duration) were collected for each patient. The patients were subdivided into two groups according to the treatment effected in the months preceding PTx: group A (n=13), treated by either intravenous (i.v.) (n=12) or per os (n=1) CPT, and group B (n=11), not treated at all with calcitriol or vitamin D sterols. Parathyroid gland morphology and the parenchymal cell distribution of the parathyroid glands were evaluated by a semiquantitative assessment. Serum intact PTH (iPTH), alkaline phosphatase (AP), calcium (Ca) and phosphate (P) levels were studied pre- and post-PTx. RESULTS: Chief cells (CC) were found in all glands, either alone or associated with oxyphil cells (OC). OC were present in 13 of 24 patients (54%); however, it must be underlined that they were present 12 times in group A parathyroid glands (92%), and only once in group B (9%) (p<0.01). Nodular hyperplasia was found in 71% (17/24) of patients: 92% (12/13) in group A, and 45% (5/11) in group B (p<0.05). There were no significant differences in age, gender, dialysis duration, serum levels of iPTH, AP, Ca and P levels between the two groups. CONCLUSIONS: There was a strong association between OC presence in parathyroid glands and CPT. Furthermore, nodular hyperplasia appeared to be associated significantly with CPT. There is still speculation regarding the meaning of these CPT effects on parathyroid gland histology and consequently on sHPTH pathophysiology.

Adult↗
PubMed1991

Ultrastructural studies on the effects of hypergravity environment on the parathyroid glands in golden hamsters of different ages.

The ultrastructure of the parathyroid glands of infantile, young, adult and senile golden hamsters subjected to a hypergravity environment was studied. In the parathyroid glands of 5-, 10- and 20-day-old, and 1- and 3-month-old golden hamsters exposed to a hypergravity environment, the Golgi complexes were significantly increased, and in 5-, 10- and 20-day-old, and 1- and 8-month-old animals exposed to a hypergravity environment, the cisternae of the granular endoplasmic reticulum appeared to be increased as compared to those of each control group. In addition, in centrifuged animals numerous prosecretory granules were observed in the Golgi areas, and many secretory granules were located in the peripheral cytoplasm. The ultrastructure of the parathyroid glands of 14-month-old centrifuged animals resembled that of 14-month-old control animals. These results suggest that the secretory activity of the parathyroid gland may be stimulated in infantile, young and adult golden hamsters subjected to a hypergravity environment and may not be stimulated in senile animals subjected to a hypergravity environment.

Aging↗
PubMed1997

Analysis of proliferative activity of the parathyroid glands using proliferating cell nuclear antigen in patients with hyperparathyroidism.

To elucidate the cellular proliferative kinetics of the parathyroidal gland in patients with hyperparathyroidism, we investigated the expression of proliferating cell nuclear antigen (PCNA) in parathyroidal tissues using an immunohistochemical procedure. The PCNA labeling index (LI; maximum LI, maximal stained area; average LI, evenly distributed stained area) indicating cellular proliferative activity was defined as the number of PCNA-positive cells per 1000 parathyroid cells in the region of interest. We used these indexes to compare and investigate the proliferative activity of parathyroid cells under various conditions. The specimens used for the study were 42 parathyroid glands from 21 patients with primary hyperparathyroidism (19 cases of adenoma and 2 cases of primary hyperplasia due to multiple endocrine neoplasia type 1) and 129 parathyroid glands from 32 patients with secondary hyperparathyroidism. An additional 40 parathyroid glands resected during thyroid surgery of 30 normocalcemic patients were used as normal controls. In normally functioning parathyroids, a small number of cells in the growth phase were found. In primary hyperparathyroidism, proliferative activity was highest in the adenoma followed by primary hyperplasia. In contrast, the PCNA LIs showed a low value in the normal rim of the adenoma and normal glands resected as biopsy specimens from adenoma patients. We, therefore, assumed that proliferative activity was suppressed in these cells compared with that in normally functioning glands. In secondary hyperparathyroidism, when the cell component of the parathyroid tissues was divided into five types, PCNA immunoreactivity was lowest in the dark chief cells. Proliferative activity in cells of the oxyphil series was the same or higher than that in the clear chief cells or vacuolated chief cells. When classified according to the structure of the parathyroid glands, cell proliferation was significantly higher in the nodular type than in the diffuse type (maximum LI, 176 +/- 231 vs. 38.3 +/- 55.7; average LI, 120 +/- 188 vs. 24.8 +/- 43.5; mean +/- SD; P < 0.001). More PCNA-immunoreactive cells were found in autotransplanted glands with recurrence than in glands resected during the initial surgery. To summarize the PCNA expression classified according to the pathological types of hyperparathyroidism, the PCNA LIs were highest in secondary hyperplasia (maximum LI, 144 +/- 212; average LI, 96.0 +/- 169) and adenoma (maximum LI, 102 +/- 81.7; average LI, 67.5 +/- 67.7), followed by primary hyperplasia (maximum LI, 25.0 +/- 25.4; average LI, 19.2 +/- 22.2) and normal glands (maximum LI, 13.6 +/- 23.9; average LI, 4.40 +/- 8.90). These findings suggest that the cellular proliferative kinetics of the parathyroid gland differ depending on the type of hyperparathyroidism, glandular structure, and cell components. As the detection method of intranuclear expression of PCNA in cells is too sensitive, we should be careful not to overestimate the number of cells in the proliferative cycle. However, these results could not have been obtained using a conventional method such as DNA analysis by flow cytometry.

Adenoma↗
PubMed1976

Primary diffuse microscopical hyperplasia of the parathyroid glands: surgical importance.

In two of 182 patients with verified primary hyperparathyroidism, microscopical hyperplasia was present in all parathyroid glands that were normal in size or only slightly enlarged. All parathyroid glands in another two patients showed microscopical hyperplasia and varied from a normal size of 190 mg. In seven additional patients, microscopical hyperplasia was present in one, several, or all parathyroid glands, which varied in weight from normal to 350 mg. Familial hyperparathyroidism or multiple endocrine neoplasia was evident in five of 11 patients. Contributing to difficulties was the experience in five patients in whom removal of mildly enlarged parathyroid glands corrected hypercalcemia, but definite microscopical abnormalities were not evident by routine histologic study of the glands. Thus, there appears to be a spectrum of abnormalities relative to size and microscopical changes in parathyroid glands of patients with primary hyperparathyroidism. The surgeon should be aware of these patterns of parathyroid hyperplasia that require a search for a fifth parathyroid gland and a subtotal parathyroidectomy.

Adult↗
PubMed2005

Usefulness of combination of high-resolution ultrasonography and dual-phase dual-isotope iodine 123/technetium Tc 99m sestamibi scintigraphy for the preoperative localization of hyperplastic parathyroid glands in renal hyperparathyroidism.

BACKGROUND: The usefulness of both dual-phase dual-isotope iodine 123 ( 123 I)/technetium Tc 99m ( 99m Tc) sestamibi scintigraphy and ultrasonography for the detection of hyperplastic parathyroid glands secondary to renal hyperparathyroidism is rarely addressed; most studies focus on primary hyperparathyroidism. However, it may be crucial to identify and accurately localize hyperplastic glands before surgery. METHODS: To study the usefulness of high-resolution ultrasonography (performed by both the radiologist and surgeon) and dual-phase dual-isotope 123 I/ 99m Tc sestamibi scintigraphy in patients with renal hyperparathyroidism, a series of 20 patients consecutively referred for parathyroidectomy was studied prospectively. Results of both examinations, independently scored, were correlated with surgical and histopathologic findings for each hyperplastic parathyroid gland localization. RESULTS: All parathyroid glands except 1 were found during primary surgery consisting of a subtotal parathyroidectomy (success rate, 99%). The missed gland was removed successfully 1 month later. Neither supernumerary nor ectopic glands were found. Mean weight of totally removed parathyroid glands was 633 mg. Ultrasonography detected 75% of hyperplastic parathyroid glands; dual-phase 123 I/ 99m Tc sestamibi scintigraphy, 66%; and a combination of both, 88%. Most missed glands at scintigraphy corresponded to superior glands, whereas false-negative results at ultrasonography correlated with low gland weight. CONCLUSION: Combined ultrasonography and 123 I/ 99m Tc sestamibi scintigraphy should be considered for routine use to localize hyperplastic parathyroid glands in patients with renal hyperparathyroidism undergoing surgery. We suggest performing scintigraphy first, before ultrasonography, to guide the radiologist to areas of hyperfunctioning glands. In our experience, this proved very helpful in achieving a high surgical success rate in patients with renal hyperparathyroidism, especially when the surgeon visualizes the parathyroid glands at ultrasonography.

Adult↗
PubMedDate not supplied

Excision of a mediastinal parathyroid gland with use of video-assisted thoracoscopy, intraoperative 99mTc-sestamibi scanning, and intraoperative monitoring of intact parathyroid hormone.

OBJECTIVE: To report the complementary use of video-assisted thoracoscopic surgery (VATS) and intraoperative 99mTc-sestamibi scanning for persistent secondary hyperparathyroidism due to a mediastinal supernumerary parathyroid gland. METHODS: We describe a patient with recurrent secondary hyperparathyroidism attributable to a mediastinal parathyroid gland who underwent parathyroidectomy with use of VATS, intraoperative 99mTc-sestamibi scanning (gamma probe), and intraoperative monitoring of intact parathyroid hormone (iPTH). RESULTS: A 32-year-old man with chronic renal failure who had undergone a 4-gland parathyroidectomy with autotransplantation 14 years previously presented with symptomatic hypercalcemia. A preoperative single-photon emission computed tomographic (SPECT) sestamibi scan revealed a focus of mediastinal uptake, suggestive of an intrathymic gland. The patient underwent a cervical exploration, and the previously reimplanted parathyroid gland and the thymus were resected. iPTH levels failed to normalize, and the operation was terminated. A repeated SPECT scan again revealed an area of mediastinal uptake. Computed tomographic scan of the chest showed a mediastinal gland adjacent to the aortic arch. VATS and intra-operative sestamibi scanning aided in localization of the ectopic parathyroid gland. After removal of the hyperplastic gland, iPTH levels decreased appropriately. CONCLUSION: In reoperative parathyroidectomy involving mediastinal glands, VATS, complemented by gamma probe localization and iPTH monitoring, may be used to minimize the operative dissection needed to cure hyperparathyroidism.

Adult↗
PubMed1990

Stromal fat content of the parathyroid gland.

The proportion of stromal fat cells to parenchymal cells in 100 normal parathyroid glands was determined by the image analyzing computer technique. The parathyroid glands were resected at the time of thyroidectomy in 86 patients with thyroid tumors. None of the patients had any evidence of parathyroid dysfunction preoperatively. In the histologic sections of the parathyroid glands, the average percentage of stromal fat cell content was 38%. The percentage of stromal fat cells was correlated with the age and the body constitution of the patients, but the percentages of fat cells varied widely among glands in the given age and body constitution ranges. It was therefore not possible to discriminate a normal parathyroid gland from an abnormal gland solely on the basis of microscopic determination of stromal fat cell content.

Adipose Tissue↗
PubMed2025

Spatial transcriptomic analysis of mouse parathyroid gland cells expressing an activating variant of Gcm2.

Glial cells missing 2 (GCM2) is an essential transcription factor for the development of parathyroid glands. Germline GCM2 variants that repress or enhance transcriptional activity predispose a subset of patients to hypoparathyroidism or hyperparathyroidism, respectively. A recurrent germline heterozygous activating missense variant of GCM2, p.Y394S has been identified in some patients with primary hyperparathyroidism. A genetically engineered knock-in mouse model of this variant corresponding to p.Y392S in the mouse Gcm2 gene (Gcm2 +/Y392S) did not show obvious parathyroid tumors. However, in GCM2-binding site mediated luciferase reporter assays in HEK293 cells, the mouse and the human variant both exhibited enhanced transcriptional activity. Therefore, we assessed the effect of this variant on gene expression in vivo in parathyroid glands from Gcm2 +/Y392S and WT mice. Using the 10x Genomics Visium platform, spatially resolved transcriptomic analysis was performed on formalin-fixed and paraffin-embedded (FFPE) tracheal tissue sections of Gcm2 +/Y392S and WT mice to capture RNA from parathyroid glands together with other cell types in the tissue sections. Transcriptome sequence data analysis detected 8 different clusters in the tissue sections based on similarity of gene expression profiles. Cluster-1, which contained parathyroid gland cells expressing Pth and Gcm2, was further evaluated for transcripts that were differentially expressed more than 2-fold in Gcm2 +/Y392S compared to WT. Increased transcript level of Lgals3 (galectin-3) was seen in Gcm2 +/Y392S parathyroid gland cells which is among markers of parathyroid carcinoma. Galectin-3 protein was detected in available FFPE human parathyroid samples of patients with germline heterozygous activating GCM2 variants, p.Y394S (n&#x2009;=&#x2009;4/10) or p.L379Q (n&#x2009;=&#x2009;2/2). These results indicate a potential for growth and malignancy of parathyroid glands expressing GCM2 variants. The transcriptomic data of mouse parathyroid gland cells generated in this study can serve as a valuable resource for investigating genes and pathways in normal or abnormal parathyroid gland growth and physiology.

GCM2, gene↗
PubMed1984

Preoperative localization of enlarged parathyroid glands.

Nine patients suspected of having parathyroid adenoma or hyperplasia on the basis of laboratory tests were examined by semiselective venous sampling for parathyroid hormone after unsuccessful neck explorations. Two pathologic parathyroid glands were found at re-operation. Only one was suspected preoperatively on the basis of venous sampling. Twenty patients suspected of having parathyroid adenoma or hyperplasia on the basis of the laboratory tests were examined by real-time sonography. Twelve adenomas and ten hyperplastic glands were found at operation. All the adenomas and hyperplastic parathyroid glands were preoperatively discovered with ultrasonography, but there were also three false-positive findings.

Adenoma↗
PubMed2006

Do parathyroid glands from individuals of different age and gender contain lymph vessels?

Whereas lymph vessels in some endocrine glands have been thoroughly investigated, data on these vessels in human parathyroid glands are often contradictory and deficient in available literature. Therefore, the aim of this study was to histomorphologically investigate whether lymph vessels could be found in human parathyroid glands postnatally and, if so, whether their presence was age- and gender-dependent. A total of 44 parathyroid glands from subjects of both genders, aged 4-90 years, were studied. The glands were divided into three groups. Those from the 1st and the 2nd age group demonstrated similar morphological structure of parenchyma with predominant chief cells with pale-staining cytoplasm, while the frequency of lymph vessels was lower in the 2nd group. Unlike in these groups, chief cells with dark- staining cytoplasm predominated in the glandular parenchyma of the 3rd age group where lymph vessels were not found in any of the examined glands. The frequency of lymph vessels in parathyroid glands was almost the same for both genders. Histomorphologic occurrence of lymph vessels coincided with the presence of endocrine cells with pale-staining cytoplasm, which allowed the assumption that lymph vessels were also one of the signs of functional activity of human parathyroid glands.

Adolescent↗
PubMed1994

Effects of prostaglandin E2 on the ultrastructure of the golden hamster parathyroid gland.

The effects of different ages on large vacuolar bodies in the parathyroid glands of golden hamsters after administration of prostaglandin E2 (PGE2) were investigated. In the parathyroid glands of the young and senile animals 15 min and the senile animals 60 min after administration of PGE2, the mean serum calcium concentration was significantly higher when compared to that of the young and senile control animals, respectively. In the experimental adult animals 60 min after administration of PGE2, the serum calcium concentration was seen to increase. In the parathyroid glands of the young animals 15 min and the adult and senile animals 60 min after administration of PGE2, the percent area occupied by large vacuolar bodies was significantly increased when compared to that of the young, adult and senile control animals, respectively. These findings suggest that the percent area occupied by large vacuolar bodies is increased in response to hypercalcemia induced by PGE2. It is thought that in the parathyroid glands suppressed by hypercalcemia there is a relationship between the percent area occupied by large vacuolar bodies and aging.

Aging↗
PubMed1996

Paraganglioma: an unusual tumour of the parathyroid gland.

A case of paraganglioma arising within a parathyroid gland is reported. The lesion was an incidental finding in a block dissection of neck performed for squamous carcinoma of the pharynx. A well-circumscribed lesion, exhibiting the characteristic pathological features of a paraganglioma, was embedded within the right inferior parathyroid gland. Due to its location, the chief histological differential diagnosis was an unusual variant of parathyroid adenoma. Immunohistochemistry and electron microscopy assisted in reaching a diagnosis. This, as far as we are aware, is the first reported case of a paraganglioma of the parathyroid gland.

Aged↗
PubMed1988

Immunohistochemical study of nodular hyperplastic parathyroid glands in patients with secondary hyperparathyroidism.

Thirty-seven nodular hyperplastic parathyroid glands obtained by subtotal parathyroidectomy from 11 haemodialysed patients with secondary hyperparathyroidism were examined both pathologically and immunohistochemically. Four consecutive sections of the largest section-surface of each gland were subject to 4 different stains (haematoxyline-eosin, Grimelius, and the immunohistochemical stains for parathyroid hormone and chromogranin A) for comparison of each nodule. It was found that the major part of each nodule consisted of a single cell type with a single pattern of cells. These reacted uniformly to each stain. The mechanism involved in the storage and secretion of the secretory granule appeared to be regulated at the nodule and not at the cell level. The results suggest that the nodules may come from a monoclonal proliferation of a single parathyroid cell. Our present light microscopic immunohistochemical study, failed to demonstrate completely identical immunoreactive positivity of each nodule or each parathyroid cell to PTH. Chromogranin A or secretory protein-I did not indicate the coexistence of PTH and SP-I in the same secretory granule, which was in good agreement with the electron microscopic immunocytochemical study of Arps using bovine parathyroid glands. Our present study, however, provides good evidence that chromogranin A positivity is demonstrable in the human parathyroid gland outside the adrenal medulla and sympathetic nerves.

Humans↗
PubMed2000

Ultrasound of the thyroid and parathyroid glands.

The superficial position of thyroid and parathyroid glands facilitates the use of diagnostic ultrasound (US) as an imaging technique. Techniques of image acquisition and interpretation are described in detail. Size and morphology of glands can be defined easily. The most important use of US guided biopsy in relation to thyroid and parathyroid glands is to increase diagnostic accuracy.

Humans↗