Gary K. Hargis

Pheochromocytoma Causing Excessive Parathyroid Hormone Production and Hypercalcemia

Abstract A young man presented with clinical and laboratory manifestations of pheochromocytoma. He also had hypercalcemia and high serum parathyroid hormone concentrations. Surgical removal of the ...

Parathyroid hormone secretion: Effect of estradiol and progesterone

Previous studies have shown that estrogen therapy in postmenopausal women results in an increase in serum immunoreactive parathyroid hormone (iPTH) levels. It has been assumed that this effect of estrogen on PTH secretion is indirect, being mediated via mild hypocalcemia resulting from an inhibition of bone resorption. We evaluated the direct effect of 17 beta-estradiol (E2) and of progesterone (Prog) on secretion of PTH from bovine parathyroid tissue in vitro. Both E2 and Prog caused a significant stimulation of PTH secretion within one hour, which was progressive for the three-hour observation period. The responses were dose-related from 10(-7) to 5 X 10(-10) mol/L. There was no PTH response to 10(-7) mol/L alpha-E2, 3-methoxy estriol, estrone, testosterone, or 20-alpha-hydroxy progesterone, indicating specificity of the responses to E2 and Prog. There was a minimal PTH secretory response to 10(-6) mol/L cortisol and 10(-6) mol/L estrone. The E2 receptor antagonist tamoxifen did not inhibit the E2 effect on PTH secretion. This observation plus the rapid PTH response suggests that this hormonal effect may not be via the conventional intracellular E2 receptor. Therefore, E2 and Prog can stimulate PTH secretion by rapid, direct, and specific effects on parathyroid cells. These gonadal hormones may, therefore, be important in calcium homeostasis via their direct stimulatory effect on PTH secretion.

Role of calcium and beta-adrenergic system in control of parathyroid hormone secretion.

Summary In the rat, EDTA and isoproterenol stimulated PTH secretion, whereas high calcium and propranolol inhibited it. The stimulatory effects of EDTA and isoproterenol were still evident and unaltered in the presence of blocks induced by propranolol and high calcium, respectively. The findings suggest that: (i) both calcium and β-adrenergic stimuli affect PTH secretion; and (ii) the two influences affect the PTH secretion by separate initial pathways. We thank Mrs. Margaret Sosa for her secretarial assistance.

Effect of Ethanol on Parathyroid Hormone and Calcitonin Secretion in Man

Summary Ingestion of 0.8 g/kg ethanol in 1 hr by normal man caused significant increases in both serum PTH and plasma CT concentrations, with peak values of 139% of baseline at 2 hr for PTH and of 138% at 3 hr for CT. Serum Ca did not change during the period of observation. Incubation of bovine parathyroid slices in 1.25 mM Ca Eagle media with 0.05% or 0.3% ethanol caused significant increases in PTH secretion to 122% and 166% of baseline respectively. Therefore: (1) in vitro, ethanol can be demonstrated to directly stimulate PTH secretion, (2) in vivo, ethanol ingestion induces an increase in PTH without detectable hypocalcemia, suggesting (a) prompt PTH secretion and action to compensate for a hypocalcemic effect of ethanol, so that actual hypocalcemia is not detectable, and/or (b) direct parathyroid stimulation. Though the exact mechanisms are unclear, the data indicate that ethanol, in amounts often ingested by social drinkers, increases both PTH and CT secretion, and therefore may modify Ca homeostasis.

Thyrocalcitonin: Cytological Localization by Immunofluorescence

Thyrocalcitonin was detected in the cytoplasm of all epithelial cells of the thyroid gland of the pig, by means of antibody fluorescence. It was present in those cells whlich normally elaborate thyroglobulin but was not present in the follicular colloid.

Vitamin A stimulation of parathyroid hormone: interactions with calcium, hydrocortisone, and vitamin E in bovine parathyroid tissues and effects of vitamin A in man

Abstract. The effect of vitamin A, a membrane surface‐active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10‐6 to 10‐9 mol/l in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10‐5 mol/l and 10‐6 mol/l, and vitamin E, 10‐5 mol/l, antagonized vitamin A‐induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues.

Mechanisms of Glucocorticoid-Induced Osteopenia: Role of Parathyroid Glands

Summary Intact and PTX rats previously injected with 45Ca received cortisol, 5 mg/kg/day, for 17 weeks. Bone resorption as determined by serum and fecal 45Ca and bone 45Ca specific activity were reduced by cortisol in the PTX rats and showed a similar tendency in intact rats. In spite of this, the bone mass, as determined by ash content, was reduced by cortisol in both the intact and PTX animals. The data show that (i) cortisol, 5 mg/kg/day, produces osteopenia by inhibition of bone formation, and (ii) the presence of parathyroid glands is not essential for the production of this osteopenia. The authors thank Roberta A. Weber for her technical assistance, and Joanne C. Vaccaro for her secretarial assistance in the preparation of this manuscript.

Evidence for thyrocalcitonin in man.

Summary and conclusions The response to a hypercalcemic stimulus was studied in normal subjects and in treated hypo thyroid patients. There was no difference between the groups in the fasting plasma calcium or the plasma calcium increment immediately following the calcium infusion. However, the disappearance of the plasma calcium increment was markedly prolonged in the treated hypo-thyroid patients. These observations are interpreted as indirect evidence for the presence and homeostatic function of thyrocalcitonin in man, and a deficiency of thyrocalcitonin in patients with reduced or absent functional thyroid tissue. The full physiological significance of thyrocalcitonin in human calcium homeostasis is not clear.

The Interactions Between Vitamin A, Vinblastine, and Cytochalasin B in Parathyroid Hormone Secretion

Summary The role of, and interrelationships between, microtubules, microfilaments, and membrane active agents in the secretion of parathyroid hormone were determined utilizing VB, a microtubule disrupter, CB, a microfilament disrupter, and Vit A, an agent known to interact with membranes. Parathyroid tissue pieces were incubated for 180 min in the presence of VB, CB, and Vit A, alone or in combination. VB alone consistently inhibited parathyroid hormone secretion. While Vit A alone stimulated the mean parathyroid hormone secretion rate, VB markedly inhibited this effect. CB alone did not change secretion in the first 30 min of incubation but thereafter stimulated secretion. In contrast to the delayed effect of CB alone, Vit A plus CB together increased the PTH secretion rate during the first 30 min, and their effects were at least additive at 120 and 180 min of incubation. Assuming that the actions of the agents tested are reasonably specific and that immunoreactive PTH in media appropriately reflects secretion of intact hormone, our results suggest that: (a) Vit A increases PTH secretion perhaps through an interaction with the cell or secretion granule membrane; (b) microtubules or microtubular-like proteins facilitate PTH secretion; (c) microfilaments may retard the release of PTH; (d) there is a close interrelationship between membrane, microtubular protein, and microfilament function.

Effect of the parasympathetic system on secretion of parathyroid hormone

This study evaluated the effect of parasympathetic agonists and antagonists on immunoreactive (i) PTH secretion in vitro and on serum iPTH in vivo in rats. In in vitro studies pilocarpine or bethanechol significantly inhibited PTH secretion. This inhibition was blocked by the simultaneous addition of atropine to the incubation medium. In in vivo studies, the cholinergic agonists pilocarpine and bethanechol and the cholinergic antagonist atropine were administered to rats by IV infusion. Blood was obtained before and again after two hours of infusion for analysis of iPTH. Pilocarpine or bethanechol significantly decreased serum iPTH. This inhibition by either agent was blocked by the simultaneous administration of atropine. Administration of atropine alone significantly increased serum iPTH above baseline. This stimulation of basal serum iPTH by parasympathetic blockade suggests that even basal PTH secretion may be influenced by endogenous parasympathetic tone. Therefore, the following conclusions were reached: (1) parasympathetic influences inhibit PTH secretion, and (2) endogenous parasympathetic tone may be an inhibitory modulator of basal secretion of PTH.