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PubMed1975

Human parathyroid autotransplantation: proved function by radioimmunoassay of plasma parathyroid hormone.

The possibility of transplanting parathyroid gland fragments into accessible muscle as functioning autografts in the human being has been supported but unproved. During operations in the thyrocervical area, the parathyroid glands frequently are removed, either intentionally or inadvertently. We have had occasion to transplant slices of parathyroid glands in five instances; four parathyroid glands were proved to be normal, and a benign adenoma appeared in the fifth. The parathyroid gland was positioned in a muscular bed in the patient's forearm. Plasma parathyroid hormone (PTH) measurements by radioimmunoassay were made from the implant venous effluent. The venous outflow from the contralateral arm was used for control. We have concluded that parathyroid tissue can be transplanted, does function, and might be capable of providing calcium homeostasis.

Adenoma↗

PubMed2004

Fine needle aspiration and intraparathyroid intact parathyroid hormone measurement for reoperative parathyroid surgery.

Some authors have praised the value of fine needle aspiration (FNA) with measurement of intraparathyroid intact parathyroid hormone (iPTH) for localization of the hypersecreting gland(s) in recurrent or persistent primary hyperparathyroidism (HPT). The aim of the present study was to determinate whether FNA for iPTH assay is an effective procedure to distinguish between normal and hypersecreting parathyroid glands. We performed a prospective study of 170 patients who underwent cervicotomy. They were divided into three groups: group A, 50 patients with thyroid diseases; group B, 100 patients with primary HPT; group C, 20 patients with secondary HPT. We performed intraoperative FNA for iPTH measurement from the thyroid, and from the normal and enlarged parathyroid glands, and we compared the different intraglandular iPTH assays. In group A, the intraparathyroid iPTH level was < 1000 pg/ml in 68% of the patients. In group B, in the pathological parathyroid gland iPTH was > 1000 in 88%; conversely, in the normal adjacent parathyroid glands it was < 1000 in 79%. In group C, intraparathyroid iPTH of enlarged glands was > 1000 in 80%. Intrathyroid iPTH was < 100 pg/ml in 96% for the three groups. We conclude that FNA for intraglandular iPTH measurement is an effective tool for distinguishing between normal and pathological parathyroid glands in the setting of primary HPT (p < 0.05), and between thyroid and parathyroid glands in groups A and B. But the procedure should be carried out in conjunction with the sestamibi scan and ultrasonography before surgical reintervention.

Adenoma↗

PubMed1993

Acute change in parathyroid function in primary hyperparathyroidism following ultrasonically guided ethanol injection into solitary parathyroid adenomas.

Ultrasonically guided percutaneous injection of 96% ethanol into solitary parathyroid tumours in patients with primary hyperparathyroidism may be used as an alternative to surgery in selected patients. Contrary to surgical parathyroidectomy, the acute changes in parathyroid function following ultrasound-guided chemical parathyroidectomy have never been described. Seven consecutive and highly selected patients with primary hyperparathyroidism were treated with ultrasonically guided injection of ethanol (96%) into solitary and biopsy-verified parathyroid tumours. Basic treatment included a maximum of three injections separated by intervals of 24 h. In six of the seven patients normal serum values of ionized calcium were achieved within 36-120 h (median 36 h) and normal serum values of intact parathyroid hormone within 6-78 h (median 24 h). Three patients received two injections and three patients three injections. One patient remained hypercalcaemic in spite of three injections. Subsequent surgery showed the patient to have two parathyroid adenomas, of which only one had been detected ultrasonically. The present study has demonstrate a fast normalization of parathyroid function following two to three ethanol injections into solitary parathyroid tumors in selected patients with primary hyperparathyroidism.

Adenoma↗

PubMed1988

Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy.

Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.

Animals↗

PubMedDate not supplied

[Intraoperative extemporaneous examination of the parathyroid gland: what is the role of the pathologist in parathyroid pathology?].

Hyperparathyroidism (HPT), once considered a rare disease, is nowadays observed and diagnosed more frequently. Consequently, surgical treatment of HPT is often performed with good therapeutic results. The success of parathyroid surgery depends mainly on the accuracy of histopathologic diagnosis through intraoperative examination of frozen tissue specimens. Yet, parathyroid gland pathology is very complex and some of its topics even controversial. Terminology and clinico-pathological concepts in this field are constantly changing and even basic characteristics such as weight, stromal fat content and "normal " histologic patterns of these glands are still actively discussed. The pathologist must often determine, merely by studying a small bioptic specimen, not only the parathyroidal (or non-parathyroidal) origin of the examined tissue, but also the histological "normal" or "abnormality" of the tissue. In carrying out his work the experienced pathologist takes on an important task and responsibility in distinguishing between normal, early hyperplastic (asymmetric), hyperplastic or adenomatous parathyroid glands. New diagnostic technical approaches (such as Electron Microscopy, intracellular fat morphometric evaluation, parenchymal cell mass study by density gradient, etc.) enhance the possibility of reaching a reliable pathologic diagnosis, but they do not solve all the present problems and sometimes can even lead the pathologist astray. Presently the diagnosis and treatment of primary HPT should be considered an open and current problem inasmuch as definite criteria to be followed in distinguishing between normal or single enlarged glands microscopically are still lacking. Neither the degree of accuracy of intraoperative frozen section examination during parathyroid surgery nor the possibility of misleading observations in such a study has been fully evaluated. A close cooperation between the pathologist and head and neck surgeon is of utmost importance to assure the best therapeutical results obtainable from parathyroid surgery in HPT.

Adenoma↗

PubMed2005

Validation study of intraoperative fine-needle aspiration of parathyroid tissue with measurement of parathyroid hormone levels using the rapid intraoperative assay.

BACKGROUND: Surgical treatment of hyperparathyroidism relies on the ability to accurately identify parathyroid tissue. The use of intraoperative fine-needle aspiration (FNA) with measurement of intact parathyroid hormone level (iPTH-FNA) has been suggested as a useful adjunct and is evaluated in this pilot study. METHODS: An institutional review board-approved retrospective review was performed on patients undergoing parathyroid exploration for primary hyperparathyroidism who also underwent selective FNA at the end of the procedure. FNA was performed on excised parathyroid tissue, ipsilateral thyroid tissue, and muscle. RESULTS: Ten patients underwent FNA. Mean iPTH-FNA values were 1559.6 pg/mL (range, 675-1775) for parathyroid, 51.4 pg/mL(range, 10-248) for thyroid, and 34.1 pg/mL (range, 14-128) for muscle. All iPTH-FNA assay results were significantly higher for parathyroid tissue than for either thyroid tissue (P < 0.05) or muscle (P < 0.05). There were no significant iPTH-FNA assay differences between thyroid and muscle (P = 0.09). CONCLUSIONS: Intraoperative FNA of parathyroid tissue with the rapid iPTH assay can correctly identify parathyroid tissue. It may prove to be a useful surgical adjunct in the treatment of hyperparathyroidism.

Journal Article↗

PubMed2006

Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels.

Clinical studies have been performed to determine the effect of cinacalcet HCl (cinacalcet), an allosteric modulator of the calcium-sensing receptor (CaR), on primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism of uremia (SHPT). However, no in vitro studies on human parathyroid cells have been reported to date. In this study, the inhibitory effect of cinacalcet on PTH secretion was analyzed in primary cultured parathyroid cells obtained from patients. The investigation involved three PHPT and three SHPT patients subjected to therapeutic parathyroidectomy. Notably, all SHPT patients were resistant to intravenous vitamin D analogue therapy. Removed parathyroid tumors were used for immunohistochemistry and parathyroid cell primary culture. Immunohistochemical analyses revealed diminished expression of CaR and vitamin D receptor (VDR) in all parathyroid tumors. PTH secretion from cultured parathyroid cells of PHPT and SHPT patients was suppressed by extracellular Ca2+ and cinacalcet in a dose-dependent manner. Rates of suppression of PTH secretion in PHPT and SHPT by cinacalcet (1000 nmol/l) were 61% +/- 21% and 61% +/- 19%, respectively. Cinacalcet demonstrates significant potency in the suppression of PTH secretion in primary cultured human parathyroid cells in vitro, despite reduced levels of the target protein, CaR. Data from this in vitro analysis support the clinical application of cinacalcet in PHPT and SHPT therapy.

Cinacalcet↗

PubMed2006

A prospective evaluation of novel methods to intraoperatively distinguish parathyroid tissue utilizing a parathyroid hormone assay.

BACKGROUND: Frozen section analysis has traditionally been used to confirm the identity of parathyroid tissue intraoperatively; however, it is time-consuming and costly and requires the excision of a significant portion of tissue. An intraoperative biopsy and analysis with a parathyroid hormone (PTH) assay is a possible alternative; however, this technique has not been perfected. METHODS: Two hundred twenty-three tissue specimens were collected prospectively from patients undergoing neck exploration. Each specimen was sampled intraoperatively using three different biopsy techniques: a fine-needle aspiration (FNA) with 10 passes of a needle (FNA10), a FNA with 20 passes of a needle (FNA20), and a tissue biopsy of approximately 1.0 mm3 (BIOPSY). The PTH concentration of each sample was determined via the Elecsys 1010 PTH immunoassay. The final tissue diagnosis was determined by histology or operative data. RESULTS: Parathyroid samples from all techniques had higher median PTH concentrations than nonparathyroid samples. However, the accuracies for the detection of parathyroid tissue varied markedly (PTH cutoff of 1000 pg/ml): the accuracies of the FNA10 and FNA20 were 71 and 80%, respectively, while the BIOPSY was 99% accurate. CONCLUSIONS: This is the first prospective study evaluating multiple methods to diagnose parathyroid tissue intraoperatively using a rapid PTH assay. We conclusively show that the BIOPSY technique is 99% accurate for the diagnosis of parathyroid tissue, and therefore, should be the method of choice when the intraoperative confirmation of parathyroid tissue is needed.

Adult↗

PubMed2000

Genetic ablation of parathyroid glands reveals another source of parathyroid hormone.

The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression is restricted to the parathyroid glands. Here we show that Gcm2-deficient mice lack parathyroid glands and exhibit a biological hypoparathyroidism, identifying Gcm2 as a master regulatory gene of parathyroid gland development. Unlike PTH receptor-deficient mice, however, Gcm2-deficient mice are viable and fertile, and have only a mildly abnormal bone phenotype. Despite their lack of parathyroid glands, Gcm2-deficient mice have PTH serum levels identical to those of wild-type mice, as do parathyroidectomized wild-type animals. Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH. Thus, Gcm2 deletion uncovers an auxiliary mechanism for the regulation of calcium homeostasis in the absence of parathyroid glands. We propose that this backup mechanism may be a general feature of endocrine regulation.

Animals↗

PubMed2000

Transferrin-mediated uptake of aluminium by human parathyroid cells results in reduced parathyroid hormone secretion.

BACKGROUND: The present study investigates whether aluminium-transferrin (Al-Tf) uptake by Tf receptor-mediated endocytosis induces hypoparathyroidism and thus might contribute to the increasing prevalence of adynamic bone disease (ABD) in the current dialysis population. METHODS AND RESULTS: Human parathyroid glands as well as in vitro cultured human parathyroid cells were shown to express Tf receptors. Five-day-old cultures of parathyroid cells were incubated for 48 h in serum-free DMEM/F12 supplemented with 12 microM apo-Tf: 12 microM Tf to which 150 microg/l Al or 150 microg/l Al-citrate (Al-ci) was bound. The amount of Al taken up by the parathyroid cells either as Al-Tf or Al-ci did not differ. However, incubation of cell cultures with Al-Tf showed a significant proportional decrease (mean+/-SEM, -23.1+/-4.5%) in iPTH secretion as compared to the reference apo-Tf cultures. Al-ci did not suppress PTH secretion (+3.4+/-6.5%). The Al uptake after incubation with Al-Tf was found to be dose-dependent. With regard to iPTH secretion, a tendency toward a dose response relationship was observed. Northern blot analysis of parathyroid cells incubated in 12 microM apo-Tf or 12 microM Al-Tf demonstrated that the PTH mRNA synthesis was unaffected by the Tf-mediated uptake of Al. These observations suggest an effect of Al on PTH release rather than on PTH synthesis. Since the cytoskeleton can play an important role in the release of secretory vesicles, the influence of Al on the structure of actin, beta-tubulin and vimentin was investigated by confocal microscopy. Comparison of cultures incubated with apo-Tf and Al-Tf revealed no difference in the organization of these cytoskeletal proteins in relation to the inhibitory effect of Al-Tf on PTH secretion. CONCLUSION: In summary, data in the present paper demonstrate that the (i) human parathyroid gland/parathyroid cells exhibit Tf receptors; (ii) Al-Tf complex is taken up by the parathyroid gland in a dose-dependent manner; and (iii) uptake of Al by Tf receptor-mediated endocytosis reduces the secretion of PTH but not its synthesis. These in vitro findings allow us to suggest that Tf receptor-mediated uptake of Al might, besides other factors such as vitamin D, high calcium dialysate or CaCO(3) intake, play a role in the development of hypoparathyroidism associated with ABD. The exact mechanism by which Al-Tf suppresses iPTH secretion remains to be elucidated.

Aluminum↗

PubMed1998

Intraoperative confirmation of parathyroid tissue during parathyroid exploration: a retrospective evaluation of the frozen section.

Although the frozen section is widely used to identify tissue type during parathyroid exploration in patients with hyperparathyroidism, questions regarding its accuracy have been raised. Frozen section error has been identified as a significant factor contributing to surgical failure. The purpose of this study was to establish the accuracy of frozen section in this setting and to identify pitfalls underlying frozen section error. The final pathologic diagnoses were compared with the paired frozen section diagnoses for all patients who underwent parathyroid exploration at this institution in the period between 1984 and 1997. For those cases in which a discrepancy was identified, the original histopathology slides and the medical records were reviewed. Of the 1579 frozen sections, a definitive and accurate diagnosis could not be determined in 20 cases (1.3%); in 7 (0.4%), the frozen section diagnosis was deferred, and in the other 13 cases, the frozen section diagnosis was incorrect. Overall accuracy rate was 99.2% after deferred cases were excluded. Frozen section artifact, sampling error, and judgmental error contributed to deferred or incorrect diagnoses. Several features confounded the distinction between parathyroid and thyroid tissue in 10 cases: the coexistence of parathyroid and nodular thyroid disease; intrathyroidal parathyroid glands showing conspicuous follicle formations or abundant oncocytic cells; and thyroid nodules with fatty stroma. The frozen section is a highly reliable means of identifying tissue type during parathyroid exploration. In exceptional cases, however, the distinction between parathyroid and thyroid tissue may not be possible owing to a striking overlap seen at the clinical, gross, and microscopic levels.

Artifacts↗

PubMed1978

Human parathyroid cryopreservation: in vitro testing of function by parathyroid hormone release.

The functional viability of cryopreserved human parathyroid tissue was assessed by determining suppressibility of parathyroid hormone release by evaluation of ambient calcium concentration. Parathyroid hormone release from dispersed human parathyroid cells prepared from both fresh tissue and tissue cryopreserved for up to 200 days was suppressed 0-90% in response to four-fold increases in calcium concentration. In the tissue that demonstrated suppression precryopreservation, the suppression curve was similar in form postcryopreservation. The ability to retain functional integrity within human parathyroid cells by cryopreservation, allows preservation for periods of time probably sufficient to determine the presence of the aparathyroid state, and allows for subsequent successful parathyroid autotransplantation. This technique has particular applicability to patients reoperated upon for persistent hyperparathyroidism where the remaining amount of normal parathyroid tissue is obscure or unknown.

Calcium↗

PubMed1979

Subcellular distributions of parathyroid hormone, hormonal precursors, and parathyroid secretory protein.

Distributions of parathyroid hormone (PTH), proparathyroid hormone (ProPTH), preproparathyroid hormone (PreProPTH), and parathyroid secretory protein (PSP) were analyzed in subcellular fractions prepared from homogenates of bovine parathyroid glands. Slices of bovine parathyroid glands were incubated with radiolabeled amino acids for 3--30 min to selectively label newly synthesized proteins. Subcellular fractions were prepared from homogenates of the gland slices by differential centrifugation. Newly synthesized labeled hormonal polypeptides in the fractions were analyzed by electrophoresis on polyacrylamide gels, and total amounts of PTH and ProPTH (previously formed and newly synthesized) were determined by immunoassay. Ninety percent of total immunoreactive, 70--80% of newly synthesized PTH, ProPTH, and PreProPTH, and 50% of PSP were found in sedimentable particulate fractions. The low speed (800 X g) pellet, which consisted predominantly of cell debris and nuclei with adherent remnants of cytoplasm, contained 30--50% of the ProPTH and PTH. The intermediate speed (10,000 X g) pellet, which contained granules, was relatively enriched in PTH. Most particulate-associated hormone could be solubilized by treatment with deoxycholate (DOC) 98% and 97% of radiolabeled and 93% and 83% of immunoreactive ProPTH and PTH, respectively, in particulates sedimenting at 10,000 and 105,000 X g were rendered DOC-soluble. Approximately 50% of the PTH and ProPTH in the particulates resisted digestion by combined trypsin and chymotrypsin, whereas PreProPTH was completely susceptible to proteolysis. Up to 50% of the radiolabeled PTH and ProPTH added exogenously to parathyroid gland slices before homogenization became associated with the particulate fractions, and 70--80% or radiolabeled PreProPTH added to the subcellular fractions readily associated with the sedimentable material. The results indicate that in homogenates of parathyroid glands, PTH, ProPTH, PreProPTH, and PSP are associated with particulate structures. Furthermore, up to 50% of the association of ProPTH, PTH, and PSP with particulate fractions seems to be nonsepcific and occurs during the disruption of the tissues. The remaining 50% or more of hormonal protein is presumably sequestered within membrane-limited structures, such as microsomal vesicles. The complete susceptibility in particulate fractions of newly synthesized PreProPTH, but not of ProPTH, to limited proteolysis indicates that the two precursors are located in different subcellular compartments and suggests that PreProPTH is converted to ProPTH before its entry into the intracisternal space of the endoplasmic reticulum. Alternatively, the PreProPTH identified in parathyroid gland slices may represent polypeptide chains synthesized in the cell sol on polyribosomes that are not attached to endoplasmic reticulum but are adsorbed nonspecifically to the particulate fraction of the cell during the process of tissue homogenization.

Animals↗

PubMed1989

Combined effects of dexamethasone and 1,25-dihydroxyvitamin D3 on parathyroid hormone secretion in cultured bovine parathyroid cells.

The present studies investigate the effects of glucocorticoids on the function of the parathyroid glands using primary cultures of bovine parathyroid cells. Treatment of parathyroid cell cultures with dexamethasone for 48 h caused a dose-dependent stimulation of PTH secretion. The minimal concentration of dexamethasone required for a significant stimulation of PTH secretion was 0.1 nM. The stimulatory effect of dexamethasone on the secretion of PTH was found within 12 h of treatment with 100 nM dexamethasone. The steroids deoxycorticosterone and cortexolone, which do not have glucocorticoid activity were without effect of PTH secretion. Since glucocorticoids may modulate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in other tissues, additional studies were performed to evaluate the interactions of glucocorticoids and 1,25-(OH)2D3. Addition of 1,25-(OH)2D3 to parathyroid cell cultures for 48 h significantly suppressed PTH secretion. In the presence of dexamethasone, however, 1,25-(OH)2D3 also significantly decreased PTH secretion, although it did not reduce PTH secretion to control levels. The treatment of parathyroid cell cultures with 100 nM dexamethasone did not affect the parathyroid cell content of 1,25-(OH)2D3 receptors. In summary, these studies indicate that glucocorticoids significantly increase the secretion of PTH in vitro. This stimulatory effect can be inhibited by 1,25-(OH)2D3. The parathyroid gland is an additional site of physiological antagonism of glucocorticoids and 1,25-(OH)2D3.

Animals↗

PubMed2005

Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells.

CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. OBJECTIVE: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. METHODS: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. RESULTS: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. CONCLUSIONS: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.

Calcium↗

PubMed1981

Immunocytological evidence for parathyroid hormone in human fetal parathyroid glands.

Immunostaining with antiserum to bovine parathyroid hormone (PTH) was used to delineate the immunoreactive PTH (iPTH)-containing cells of parathyroid glands from 1 anencephalic and 29 normal human fetuses. The antiserum (GPO 3) cross-reacted with human PTH and recognized the carboxyl-terminal fragments of the PTH molecule. No iPTH-containing cells were observed in the parathyroid glands of the 6 fetuses younger than 10 weeks, in spite of the fact that organized parathyroid glands were identified by histological methods. By contrast, iPTH-containing cells were observed in all fetuses older than 10 weeks of gestation, including the anencephalic fetus. All cells were immunoreactive either at the cellular periphery or as a more diffuse cytoplasmic staining around the nucleus. No immunoreactive cells were observed in the thyroid or thymic parenchyma. The specificity of the immunocytological reaction was tested by the usual procedures. Previous in vitro studies suggested that parathyroid function might be active at 12 weeks of gestation. Our data suggest that iPTH is synthetized by parathyroid glands as as early as 10 weeks of gestation and is also present in the anencephalic fetus. The physiological significance of the early presence of PTH within the fetal parathyroid glands remains to be established.

Female↗

PubMed2006

Endothelin-1 regulates parathyroid hormone expression of human parathyroid cells.

OBJECTIVE: Parathyroid cells synthesize and release endothelin-1 (ET-1). ET-1 displays an in vitro inhibitory effect on basal parathyroid hormone (PTH) secretion and also counteracts PTH hypersecretion stimulated by low calcium. Such effects are further demonstrated in vivo, independent of the changes in calcitonin. We propose that ET-1 may regulate the pathogenesis of uremic hyperparathyroidism. However, this was not directly demonstrated in human parathyroid glands. DESIGN: Hyperplastic parathyroid glands are obtained from the surgical operation for uremic hyperparathyroidism. Cells are isolated by enzyme digestion and treated with ET-1, and are assessed for PTH mRNA expression. PTH in the plasma and the medium is measured by a newly developed method to detect the whole PTH (1-84). PATIENTS: Uremic patients with severe secondary hyperparathyroidism and ultrasonography-proved hypertrophy of parathyroid glands received elective surgical approaches under general anesthesia. The resected glands were immediately taken to the laboratory for fresh isolation. MEASUREMENTS: Following ET-1 treatment, PTH mRNA expression is evaluated by RT-PCR method. ET-1 is detected with radioimmunoassay kit and PTH is measured by a new commercially available Duo PTH kit. RESULTS: ET-1 exhibited a dose-dependent inhibitory effect (from 10(-12) - 10(-7) M) on PTH mRNA expression of parathyroid cells, either in the basal or in the low-calcium-stimulated states. Release of PTH into the medium is also gradually inhibited by the increase in ET-1 concentrations. CONCLUSIONS: Our results demonstrate that ET-1 attenuates PTH mRNA expression in freshly isolated human parathyroid cells, and PTH release is also decreased. This result is consistent with our previously reported in vitro and in vivo experiments.

Adult↗

PubMed1977

Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on the ultrastructure of parathyroid glands and plasma immunoreactive parathyroid hormone in pregnant cows fed a low calcium diet.

The long term (70 days) effects of administering ethane-1-hydroxy-1,1-diphosphonate (EHDP) (4 mg. per kg. per day) on parathyroid function was investigated in pregnant cows fed a low calcium diet. Serum calcium and phosphorus were significantly lower at parturition and postpartum in EHDP-treated cows compared to pregnant control cows fed the low calcium diet. Plasma immunoreactive parathyroid hormone levels were similar prepartum, at parturition, and postpartum in cows administered EHDP and control cows. Immediately available calcium reserves were greater preparation in control cows than in cows receiving EHDP as indicated by a more rapid rate of return of serum calcium toward normal levels following ethylenediaminetetraacetic acid (EDTA)-induced hypocalcemia approximately 10 days prepartum. EHDP-treated cows responded to the hypocalcemic challenge with similar changes in plasma immunoreactive parathyroid hormone levels as in control cows; however, urinary hydroxyproline excretion increased at certain intervals only in control cows. Ultrastructurally, chief cells in parathyroid glands of both groups of cows were in an active stage of the secretory cycle with well developed organelles concerned with hormonela synthesis. Chief cells in cows administered EHDP were degranulated and contained fewer secretory granules in response to the hypocalcemia than those in control cows. Chief cells in EHDP-treated cows often had prominent perinuclear accumulations of microfilaments, scattered vacuolated mitochondria, and lysosomal bodies in the cytoplasm. Thyroid C-cells were densely granulated and thyroid calcitonin content was similar in both groups of cows. The principal defect in calcium homeostasis of EHDP-treated cows appeared to be an impairment both in bone calcium mobilization and bone matrix catabolism in response to the secretion of parathyroid hormone. In vitro uptake of 45Ca by duodenal mucosa and urinary excretion of cyclic adenosine monophosphate were similar in both groups of cows. The ability of the parathyroid glands to synthesize and secrete parathyroid hormone in response to hypocalcemia induced either by EDTA or associated with parturition was not impaired by the administration of EHDP.

Animals↗