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PubMed1992

Ultrastructure of the water-clear cell in the rabbit parathyroid gland.

The ultrastructure of water-clear cells has been described in human hyperplastic parathyroid glands. However, previous studies have failed to demonstrate this type of cell in normal human or other vertebrate parathyroid glands. Upon recently recognizing water-clear cells in the parathyroid glands of the golden hamster, we intended to examine the occurrence of these cells in other animals. In the present study the parathyroid glands of about one-year-old rabbits were observed by electron microscopy. Water-clear cells containing numerous vacuoles were demonstrated dispersed among the chief cells. The cells were generally situated close to the basal lamina of perivascular space which lay against the capillary vessel and were attached by desmosomes to the chief cells. Irregularly shaped vacuoles in the water-clear cells resembled dilated cisternae of the granular endoplasmic reticulum in the chief cells. Several ribosomes could be seen attached to the membrane of some of the irregularly shaped vacuoles. It is conceivable that the water-clear cells are transformed from the chief cells.

Animals↗

PubMed1988

Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism.

Parathyroid hormone (PTH) release and cytoplasmic calcium concentrations were investigated at ambient calcium concentrations of 0.5-3.0 mmol/l in dispersed parathyroid cells from 44 hypercalcaemic patients with primary or uraemic hyperparathyroidism (HPT). In comparison with parathyroid cells from adult cattle, release of PTH by human preparations was reduced and values of the ambient calcium concentration causing half-maximal inhibition of PTH release (median effective dose, ED50) were significantly increased. Half-maximal inhibition of PTH release was obtained with concentrations of cytoplasmic calcium almost identical to the concentrations of ionized calcium in the plasma of the individual patients. Cytoplasmic concentrations of calcium in the parathyroid cells were inversely related to release of PTH. Concentrations of cytoplasmic calcium were significantly lower in human than in bovine cells and the ED50 for ambient calcium increase on cytoplasmic calcium was raised to the same extent as the ED50 for ambient calcium inhibition of PTH release in human compared with bovine cells. The magnitude of the increased ED50 for ambient calcium inhibition of PTH release and increase of cytoplasmic calcium concentration was similar in adenomas and sporadic as well as hereditary primary hyperplasias, but the secretion was the least aberrant in uraemic hyperplasias, although they had by far the largest glandular mass. Serum concentrations of total calcium before surgery correlated with the ED50 for ambient calcium effects of PTH release and cytoplasmic calcium, but not with glandular weight. These findings demonstrate a universally abnormal regulation of cytoplasmic calcium in HPT and its importance for PTH release, and that disturbance of cytoplasmic calcium rather than the increased glandular mass contributes to the hypercalcaemia in adenomatous and hyperplastic HPT.

Calcium↗

PubMedDate not supplied

An ectopic parathyroid gland in the left axillary region: case report.

This is a review of ectopic localizations of the parathyroid gland in one case. A hard mobile mass (2 x 2.5 cm) was detected on the right side of the neck of a patient who had previously been given a diagnosis of hyperparathyroidism. Computed tomography showed an adenoma (25 x 35 mm) in the paratracheal region on the right side of the neck. Scintigraphy revealed an activity increase on the right side of the neck and in the left axillary region. Blood measurements were as follows: Ca, 12.7 mEq/l; parathyroid hormone (PTH), 235 U/l; and alkaline phosphatase (ALP), 776 U/l. The patient was operated on to remove the lesions located in the cervical and left axillary regions. Histopathological examination revealed that the lesion in the right cervical region was a parathyroid adenoma, whereas the lesion in the left axillary region was normal parathyroid gland tissue. Parathyroid glands may indicate ectopic locations in very different regions. We think the case presented here is the first case with this axillary location. Scintigraphy, alone or combined with other methods, may be used to determine ectopic localizations.

Adenoma↗

PubMed2003

Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism.

BACKGROUND: Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size. METHODS: Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis. RESULTS: Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05). CONCLUSIONS: These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment.

Antimetabolites↗

PubMedDate not supplied

Long-term response of cultured rat parathyroid glands to calcium and calcitriol: the effect of cryopreservation.

AIM: This study aimed to investigate the longest period in which parathyroid glands cultured in vitro maintained their viability and functionality in order to study the response of the glands to factors that exert their main action in the long term (1-7 days). METHODS: Rat parathyroid glands from 104 Wistar rats were used. Cell viability was measured by flow cytometry for 7 days. Parathyroid tissue functionality was determined by parathyroid hormone (PTH) secretion in basal conditions and in the response of the glands to calcium and calcitriol. Calcium sensing receptor (CaR) synthesis was determined measuring protein levels by immunohistochemistry. Parathyroid glands were cryopreserved to study them in the same way as fresh tissue. RESULTS: Intact parathyroid glands maintained their cell viability >80% until the 6th day in culture, while the functional capacity was limited to 4 days: PTH release was stable for 4 days, whilst from the 5th day onwards, PTH secretion reduced to undetectable levels. Parathyroid glands responded accurately when calcium was reduced in the culture medium; a mean increase >50% in PTH secretion was observed. No differences were observed in CaR levels before and after the culture period. PTH synthesis and secretion inhibition was observed when the parathyroid glands were cultured with calcitriol; this inhibition achieved 90% after 4 days in culture. Cryopreserved parathyroid glands maintained their viability, but partially lost their functionality, as they were unable to respond to calcium. CONCLUSIONS: Intact parathyroid glands cultured in vitro maintained their functionality and their capacity to respond to their effectors for longer periods than in previously developed studies. It seems that part of this capacity is lost after cryopreservation. Nevertheless, this long-term culture model can be useful to study the response of the parathyroid glands.

Animals↗

PubMed2001

Preliminary evaluation of endocrine cells in the rat respiratory tract after thyroid and parathyroid gland removal.

The complete thyroid and parathyroid gland removal leads to the abrupt reduction of calcitonin, which can be a factor stimulating growth and intensified activity of APUD system cells in the respiratory tract. Thus, neuroendocrine cells in the lungs and trachea in rats after thyroid and parathyroid removal were evaluated. Paraffin specimens of the examined organs were stained with H+E and impregnated with silver. Calcitonin, synaptophysin, somatostatin, and neuronal-specific enolase were detected immunohistochemically by the use of rabbit specific antibodies. Antibodies used in the study immunostained neuroendocrine cells of the examined organs. Rats with removed thyroid and parathyroid glands presented weakened reaction compared to the control group.

APUD Cells↗

PubMedDate not supplied

[Intraoperative identification of parathyroid glands with methylene blue (author's transl)].

Identification of parathyroid glands during surgery for treatment of hyperparathyroidism remains difficult. The staining with methylene blue was first described by Dudley. Twenty-one patients were explored. Thirty to sixty minutes before surgical incision, an intravenous perfusion of methylene blue was started. The dose varied between 5 to 10 mg per kg. Thirty-seven enlarged glands were found of which 33 were obviously stained; 13 showed some color that could not be attributed with certainty to the dye; 1 adenome was not stained at all. In 89.2% of the cases the staining had the favorable effect of shortening the operation. Only 4 normal glands showed the blue stain. The affinity for methylene blue is thus mainly found in pathological parathyroid glands.

Adenoma↗

PubMed2001

Langerhans cell histiocytosis involving the thyroid and parathyroid glands.

Langerhans cell histiocytosis (LCH) is a rare illness, and the disease afflicting the thyroid gland is very uncommon, even in the presence of multisystem involvement. In this report, we document histologically, for the first time, concurrent involvement of the thyroid and parathyroid glands by LCH. A young Chinese woman with a history of diabetes insipidus and hypogonadism underwent a total thyroidectomy for enlarged thyroid gland secondary to LCH causing airway obstruction. Microscopic examination of the excised specimen disclosed CD1a- and S-100-positive LCH cells involving the thyroid and parathyroid glands. In a patient with LCH affecting the thyroid gland, parathyroid gland disease should be suspected when the serum calcium levels are depressed in association with an inappropriate serum parathyroid hormone level, such as a normal parathyroid hormone level in this case.

Adult↗

PubMed1997

Effects of short-term treatment with CaCl2 or EDTA on the parathyroid glands in pregnant golden hamsters, with special reference to large vacuolar bodies.

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.

Animals↗

PubMed1995

[Hyperplasia and adenoma of the ectopic parathyroid gland].

The frequency of the ectopic parathyroid glands has been reported to be 7-46% by anatomists or surgeons, while the proper frequency is still unknown. Recently the diagnostic methods of hyperparathyroidism have been developed, and many surgeons select total parathyroidectomy for renal hyperparathyroidism. Therefore the frequency of the ectopic glands has been supposed to be higher than that recognized previously. We investigated 97 patients with renal hyperparathyroidism, and detected 60 ectopic glands in 34 patients (35.1%). The ectopic glands existed in the mediastinum, intrathyroid, carotid sheath, post-pharynx, para-esophagus, and other regions. We describe the features of procedures for detecting ectopic glands. Using non-invasive examination, including ultrasonography, scintigraphy (T1 201-Tc 99 m), and MRI, will be a great assistance in the diagnostic procedures.

Adenoma↗

PubMed1996

1,25-dihydroxyvitamin D3 and 22-oxacalcitriol prevent the decrease in vitamin D receptor content in the parathyroid glands of uremic rats.

Decreased content of the 1,25-dihydroxyvitamin D3 receptor (VDR) in parathyroid glands from patients and animals with chronic renal failure has been implicated in the pathogenesis of secondary hyperparathyroidism. In these studies, we examined the regulation of VDR by 1,25-dihydroxyvitamin D3 (1,25-D3) and 22-oxacalcitriol (OCT) in parathyroid glands of uremic rats. After eight weeks of renal failure, VDR content in parathyroid glands of uremic rats was decreased (400 +/- 42 vs. 729 +/- 47 fmol/mg protein in normal control rats, P < 0.05) and strongly correlated with serum 1,25-D3 levels (r = 0.829, P = 0.0001). Treatment with either 1,25-D3 or OCT prevented the decrease in VDR. We conclude that low serum 1,25-D3 levels, at least in part, account for the decrease in VDR content in parathyroid glands of uremic rats and that treatment with 1,25-D3 or OCT prevents this decrease ameliorating the development of secondary hyperparathyroidism.

Animals↗

PubMed2004

Parathyroid gland function in the uremic rabbit.

Rabbits with renal failure have been reported to be hypercalcemic and to have decreased parathyroid hormone (PTH) concentrations. Thus, it would seem that uremic rabbits are resistant to secondary hyperparathyroidism (HPT). The work reported here was designed to investigate parathyroid gland function in uremic rabbits and the effect of diets with different calcium (Ca) and phosphorus (P) content. The relationship between PTH and ionized calcium (Ca2+), parathyroid gland size and parathyroid cell cycle were studied in three groups of rabbits: Group I, rabbits with normal renal function on a standard diet (Ca = 1.2%, P = 0.6%); Group II, partially nephrectomized rabbits on a standard diet; and Group III, partially nephrectomized rabbits on a low Ca (0.6%)-high P (1.2%) diet. Group I rabbits had baseline Ca2+ = 1.71 +/- 0.05 mmol/l and PTH = 26.9 +/- 3.2 pg/ml. During hypo- and hypercalcemic stimulation PTH reached maximal values (PTHmax) of 94.4 +/- 5.5 pg/ml and minimal concentrations (PTHmin) of 3.2 +/- 0.2 pg/ml. Rabbits from Group II were hypercalcemic (baseline Ca2+ = 2.03 +/- 0.06 mmol/l) and had very low PTH levels (1.7 +/- 0.5 pg/ml); however, they reached a PTHmax that was similar to Group I, 92 +/- 8.7 pg/ml. Group III rabbits were hypocalcemic (baseline Ca2+ = 1.22 +/- 0.08 mmol/l) and had very high basal PTH levels (739 +/- 155 pg/ml). Their PTHmax and PTHmin were 801 +/- 169.4 pg/ml and 102.2 +/- 22.2 pg/ml, respectively. Both parathyroid gland size and parathyroid cell proliferation were increased in Group III. In conclusion, our results show that the Ca and P content of the diet markedly influence PTH secretion in the uremic rabbit and that when placed on a low Ca-high P diet uremic rabbits develop secondary HPT.

Analysis of Variance↗

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↗

PubMed1987

Calcium-calmodulin-dependent protein kinase in hyperplastic human parathyroid glands.

The function of the parathyroid gland is closely linked to intracellular and extracellular Ca2+ concentrations. As a step toward understanding the mechanism of action of Ca2+ on the parathyroid, we examined hyperplastic human parathyroid tissue for Ca2+ and calmodulin-dependent protein kinase activity. In parathyroid homogenates, Ca2+ stimulates the phosphorylation of substrate protein in the presence of calmodulin or phospholipid. The calmodulin (CaM)-stimulated activity is present in a soluble fraction of parathyroid and can be separated from other protein kinase activities by gel filtration chromatography. The concentration dependence of CaM kinase on Ca2+ and CaM was determined using the gel filtration. The Ka values for CaM and calcium were 100 nM and 5 microM, respectively. The fraction containing the CaM kinase activity had a calculated mol wt of 5.5 X 10(5). It contained a protein with a mol wt of 4.9 X 10(4) whose phosphorylation was Ca2+ CaM dependent and a CaM-binding protein of mol wt 4.9 X 10(4) which we suggest may be the catalytic subunit of a type II Ca2+-CaM dependent protein kinase. Hyperplastic human parathyroid tissue contains a type II Ca2+-CaM dependent protein kinase which may serve an important function in Ca2+-directed metabolism.

Calcium↗

PubMed1998

Appropriate timing and velocity of infusion for the selective staining of parathyroid glands by intravenous methylene blue.

BACKGROUND: Intraoperative parathyroid gland (PTG) identification by selective staining using methylene blue dye (MB) infusion has been shown effective but the degree of gland staining is inconsistent. METHODS: The effect of timing and rate of MB infusion on gland uptake was investigated in a canine model by infusing MB either rapidly over 3 to 5 minutes (n = 8) or slowly over 30 minutes (n = 4). The pattern of dye uptake in an exposed PTG was determined by standardized serial photography. RESULTS: Earliest uptake occurred between 10 and 20 minutes after infusion, and maximum uptake averaged 21 minutes, earlier than previously described. Rate of infusion did not affect staining. CONCLUSIONS: This rapid uptake of methylene blue by the parathyroid glands suggests that its selective intraoperative use when glands are difficult to locate intraoperatively, rather than a routine preoperative infusion, is possible without significant operative delay. Clinical experience has confirmed this impression.

Animals↗

PubMed1982

Parathyroid gland response to epinephrine: a rate-sensitivity mechanism.

A model for parathyroid gland response to an epinephrine infusion is proposed. It is based on direct measurements of the parathyroid hormone (PTH) secretion rate as measured directly after cannulation of the venous drainage of single superior parathyroid glands of calves. When epinephrine was infused into a jugular vein, a large increase of PTH secretion rate was observed at the beginning of the infusion. The PTH secretion rate thereafter fell, but it was still significantly above the control rate. At the end of the epinephrine infusion a sharp decrease was observed when the infusion was terminated. These observations are consistent with a rate-sensitive control mechanism. Calculation of the parameters yielded a model, which was then linked with a kinetic model for PTH distribution. Simulation studies were undertaken to predict plasma PTH concentration in response to an epinephrine infusion. Good agreement was found between predicted results and previously published work. The role of this rate-sensitive mechanism in the parathyroid gland is discussed.

Animals↗

PubMed1988

Further evidence for a parathyroid hormone-related protein in fetal parathyroid glands of sheep.

Extracts of ovine fetal parathyroid glands contained a substance in addition to parathyroid hormone (PTH) which could not be neutralized by antiserum against PTH in a cytochemical bioassay. This substance reacted similarly to human parathyroid hormone-related protein, the humoral hypercalcaemic factor associated with malignancy in man. The ovine fetal PTHrP may be responsible for maintaining the fetus hypercalcaemic relative to the mother.

Animals↗

PubMed1992

Effects of starvation on the water-clear cell in the golden hamster parathyroid gland.

Changes of the water-clear cells of the parathyroid glands in adult and senile golden hamsters 2 and 5 days after starvation were investigated. The ultrastructure of the water-clear cells of the parathyroid glands in the starved adult and senile animals almost resembled that of the control adult and senile animals. However, lipid droplets were very numerous in the water-clear cells in the adult and senile animals after starvation. It is considered that starvation affects functional activity in the water-clear cells of the parathyroid gland.

Age Factors↗