Ultrastructural study of calcium-containing precipitation in human parathyroid glands

Using the potassium pyroantimonate technique for ultrastructural localization of cations and X-ray elemental analysis with both energy dispersive and wave-length dispersive systems, calcium-containing precipitates were found in normal, hyperplastic and adenomatous human parathyroid glands. Differences were observed between oxyphil cells, and suppressed, stimulated and active chief cells in the content and localization of intracellular precipitation. The oxyphil cells and suppressed chief cells possessed precipitates mainly in nuclei and medium-sized and large mitochondria, whereas the stimulated chief cells possessed precipitates in normal-appearing and morphologically altered mitochondria, and in smooth-surfaced vacuoles and cytosol. The active chief cells usually showed a rather sparse precipitation.     

Prospective biochemical and scintigraphic evaluation of autografted normal parathyroid glands in patients undergoing thyroid operations

Recent reports suggest that oral choline supplement may alter the cerebral choline/creatine (Cho/Cr) ratio and might be used to treat neurodegenerative disorders of cholinergic transmission. Using both 1H and 31P MRS, we reexamined the Cho/Cr ratio and quantified cerebral choline and its major constituents: phosphoethanolamine (PE), phosphorylcholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC). In the four brain locations examined, no significant increases in Cho/Cr, [Cho], or in its major constituents were found in response to an oral challenge of 50 mg/kg of choline bitartrate. Oral choline did not significantly affect human cerebral metabolism in the short term.     

Secretion of parathyroid hormone by abnormal human parathyroid glands in vitro

Radiation survival curves for Lewis lung tumours in the lungs ranging in size from 0-5 to 20 mm3 have been obtained, and a size-dependent variation in hypoxic fraction was found. Cell-survival studies following treatment of various sizes of s.c. tumours indicated that the effects of 60Co gamma-rays and the chemotherapeutic agents 1,3-bas(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide are all size-dependent. Large pulmonary nodules which had regressed but had not been cured by cyclophosphamide regrew with a radiosensitivity that was characteristic of previously untreated tumours. The results give additional experimental support to the clinical interest in early adjuvant therapy of micrometastases, and sequential combined modality therapy for larger tumours.     

Ultrasonography of the thyroid and parathyroid glands

High-resolution thyroid and parathyroid ultrasonography can play an integral part in the diagnosis and management of patients with clinically undifferentiated cervical masses, thyroid carcinomas or adenomas, and primary parathyroid hyperplasia or neoplasia. Because the study is inexpensive, noninvasive, and easily performed, ultrasonography can be performed as a screening test early in the evaluation of a patient, and ultrasound findings can corroborate the results of other diagnostic procedures, leading to a more accurate diagnosis.     

Cortisol stimulation of parathyroid hormone secretion by rat parathyroid glands in organ culture

Addition of cortisol (10(-6) to 10(-8) M) and related glucocorticoid congeners to cultures of rat parathyroid glands stimulated dose-related increases in parathyroid hormone secretion; the addition of deoxycorticosterone or cortexolone was without effect. Cortexolone, however, inhibited the stimulatory activity of cortisol when both were added to the culture medium. This direct stimulatory effect of cortisol on parathyroid gland secretion may account in part for the increased concentration of parathyroid hormone in the serum of cortisol-treated animals.     

Localization of abnormal parathyroid glands of the mediastinum with MR imaging

PURPOSE: To determine the sensitivity of magnetic resonance (MR) imaging for preoperative localization of abnormal parathyroid glands in the mediastinum and to compare the sensitivity of MR imaging with those of scintigraphy and ultrasonography (US). MATERIALS AND METHODS: The prospective sensitivity of MR imaging was compared with those of thallium-technetium scintigraphy and US in 25 patients in whom the abnormal gland was located in the mediastinum at surgery. RESULTS: MR imaging had a much higher sensitivity (22 of 25 cases [88%]) than did scintigraphy (11 of 19 cases [58%]) or US (three of 24 cases [12%]). The most common locations for the mediastinal gland were intrathymic (eight of 25 cases) and paraesophageal (six of 25 cases) sites. CONCLUSION: MR imaging should be considered the modality of choice for preoperative localization in this group of patients.     

Surgical significance of supernumerary parathyroid glands in renal hyperparathyroidism

In secondary hyperparathyroidism (2HPT) fundamentally all parathyroid glands, including supernumerary glands, become hyperplastic, and stimulation of parathyroid glands continues after parathyroidectomy (PTx). Therefore supernumerary glands have special significance during surgery for 2HPT, whether persistent or recurrent HPT. In the present study 570 patients underwent initial total PTx with a forearm autograft. The frequency, type, location, histopathology, and clinical significance of the supernumerary glands were evaluated. At the initial operation 90 supernumerary glands were removed from 82 to 570 patients (14.4%); 12 patients (2.1%) required extirpation of supernumerary glands for persistent/recurrent HPT. Altogether 104 supernumerary glands were identified at operation in 94 of the 570 patients (16.5%). Among these 104 glands, 25 (24.0%) were of the rudimentary, or split, type and 79 (76.0%) of the proper type. Supernumerary glands were most frequently identified in the thymic tongue (53/104, 51.0%); 32 (60.4%) of these 53 glands were identified only microscopically. In 6 of the 570 cases (1.1%), reoperation was required for persistent HPT due to supernumerary glands located in the mediastinum, and 6 patients underwent neck reexploration for recurrence. Histopathologically, 61 of 104 (58.7%) supernumerary glands, including 36 glands recognized only microscopically, showed diffuse hyperplasia, and 43 (41.3%) displayed nodular hyperplasia. Residual small supernumerary glands with diffuse hyperplasia have the potential to be transformed to nodular hyperplasia during long-term hemodialysis. Therefore all parathyroid glands including supernumerary glands should, if possible, be removed at the initial operation. Routine removal of the thymic tongue and careful examination of the regions surrounding the lower poles of the thyroid, especially on the left side, are important steps in the surgical treatment.     

Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism

Serum parathyroid hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional parathyroid gland mass rather than disturbances in calcium-sensing by the parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.     

Ultrastructural localization of microliths in salivary glands of cat

Although microliths occur in normal human salivary glands and may be an aetiological factor of sialadenitis, little is known of their natural history. In an attempt to remedy this, we investigated a large archival collection of normal and experimental feline parotid, submandibular and sublingual salivary glands. In submandibular and sublingual glands, microliths were detected ultrastructurally in: all types of acinar secretory cells; myoepithelial cells; ductal cells; lumina; intercellular spaces; basement membrane; stroma; macrophages; multinuclear giant cells; and neutrophils. Microliths were not detected ultrastructurally in parotid glands. Microliths appear to form in acinar cells during autophagy and in stagnant secretory material in lumina. Microliths appear to be removed by secretion in the saliva, discharge from cells laterally and basally, and engulfment by macrophages. There appears to be a turnover of microliths, which possibly is upset by secretory inactivity with a resulting accumulation that leads to localized obstruction and sialadenitis.     

Ultrastructural changes of Drosophila larval and prepupal salivary glands cultured in vitro with ecdysone

Alterations in the ultrastructure of in vitro cultured larval salivary glands of Drosophila melanogaster in response to the steroid hormone ecdysone were studied in relation to complex changes in puffing patterns. We found that the changes in the fine structure of cultured glands reflected progression of the puffing pattern, and they paralleled those seen in vivo. We observed that glue secretion by exocytosis, the main function of salivary glands, took place between puff stage 5 (PS5) and PS7. Glue could not be expectorated under culture conditions but was slowly released from the lumen through a duct into the medium. After the cultured glands reached PS13/PS14, further progress of puffing and fine structural alterations required that the ecdysteroid titer be transiently extremely low or absent. Under in vitro conditions we did not observe the putative new secretory program(s) described for glands in vivo after PS12. However, ultrastructural changes which unambiguously indicated that an autohistolytic process had begun in vitro started to appear after PS17. Many salivary gland cells developed numerous features of progressive self-degradation between PS18 and PS21. Actual degradation of salivary glands in vivo seemed to be rapid, but in vitro degradation was never completed, probably due to a lack of exogenous factors from the hemolymph. Manipulations of ecdysone titer in vitro in the culture medium, known during the larval puffing cycle to cause premature induction of developmentally specific puffing patterns, did not affect the normal development of ultrastructural features of the cytoplasm and nucleus.     

Altered adenylate cyclase kinetics in hyperfunctioning human parathyroid glands

Current evidence suggests that parathyroid gland adenylate cyclase is involved in the control of parathyroid hormone (PTH) secretion. Thus, the altered control of PTH release in hyperparathyroidism may relate to altered adenylate cyclase activation. Therefore, we examined adenylate cyclase kinetics in membrane preparations from hyperfunctioning human parathyroid glands and normal human and bovine parathyroid tissues. There were no differences in the affinity for ATP between enzymes of normal and pathological tissue. However, the enzyme in 10 hyperfunctioning glands showed increased affinity for Mg++. The activation constant for Mg++ (KaMg) of adenylate cyclase in normal human glands was 10.6 +/- 2 mM, a value not different from that of normal bovine parathyroid tissue (9.5 +/- 1 mM). In contrast, the adenylate cyclase in membrane preparations from three of four hyperplastic and six of seven adenomatous human glands showed a markedly reduced KaMg, ranging from 0.85-1.64 mM and from 1.58-6.46 mM, respectively. In one adenoma and one hyperplastic gland, the Ka of the enzyme for Mg++ was close to normal. The addition of guanylylimidodiphosphate or GTP to the incubation mixture increased, in a dose-dependent manner, the apparent KaMg of the enzyme in the abnormal tissue toward normal, suggesting a defective nucleotide regulatory site in the adenylate cyclase of hyperparathyroid glands. In addition, the hyperparathyroid gland enzyme was less susceptible to inhibition by calcium, requiring 0.7-1 mM Ca++ for 50% inhibition, whereas comparable inhibition of the normal adenylate cyclase was seen at 0.22-0.28 mM Ca++. We conclude that the abnormal control of PTH secretion in hyperparathyroidism may be related, at least in part, to alterations in the characteristics of parathyroid gland adenylate cyclase.     

The fine structure of the parathyroid glands of rats with disuse osteoporosis

A series of 246 patients with scoliosis and attempted fusion had exploration performed six months later in order to detect and treat any pseudarthrosis at an early stage and so prevent subsequent loss of correction. Bilateral or unilateral pseudarthroses occurred in 25 per cent and were of three types--definite, hairline and doubtful. Single unilateral pseudarthroses accounted for 6 per cent and were of little if any clinical significance. The hairline pseudarthroses could not be seen radiologically and were easily missed at exploration. In general the pseudarthroses were least common in the more rigid parts of the spine and in curves which by nature of their aetiology or long duration had become most rigid. Neither the initial severity of the curve nor the degree of correction obtained before the initial attempted fusion had any apparent effect on the incidence. Follow-up for an average of four years has shown that a pseudarthrosis is of little significance with regard to the ultimate result provided it is recognised early and repaired.     

Distribution of the solitary adenoma over the parathyroid glands

One hundred and ten patients with primary hyperparathyroidism were studied, in which a normal parathyroid gland was found on the same side as an adenoma (both confirmed by histological examination), and the upper or lower location could clearly be defined during surgery. The distribution of the adenomas over the upper and lower glands was unequal: 61.8 per cent in the superior versus 38.2 per cent in the inferior position. Statistical analysis revealed that this is not a random distribution (p = 0.013). The explanation of this relative predilection is unknown. The finding should not influence the surgical procedure for primary hyperparathyroidism.     

Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.     

The role of ultrasonography in the diagnosis of enlarged parathyroid glands

The ultrasonographic diagnosis of parathyroid glands was introduced by the Japanese in 1975. Only after more perfect machines have been introduced, first of all by advancement of "real-time" technique, this method started being used as a routine. The paper shows results of ultrasonographic investigation in 200 patients separated into two groups. In the first group 100 patients were examined with a clinical suspect of primary hyperparathyroidism from which in 30 the existence of parathyroid gland adenoma was diagnosed. Scintigraphy of parathyroid glands was performed in the smaller group of patients; the comparison of these two methods was done, and in 77.7% cases coincidence was found. In the group of 10 operated patients comparison of the two mentioned methods was carried out, with surgical or pathohistologic findings and the coincidence was complete. In the second group 100 patients were examined belonging to the chronical program of hemodialysis, from which in 24 cases existence of swollen parathyroid glands was found. Comparison of ultrasonographic and scintigraphic findings was also done and the coincidence was 68.75%. At the end, the importance of ultrasonography in the first diagnostic stage of swollen parathyroid glands was pointed out.