Non-autonomy of parathyroid hormone secretion in acute primary hyperparathyroidism

ABSTRACT In 22 of 28 cases of primary hyperparathyroidism (PHP) the rise in the serum immunoreactive parathyroid hormone (IRPTH or PTH) level observed in response to lowering of the serum calcium by EDTA, exceeded that obtained in 8 control subjects. In 5 of these 22 patients who were studied again after parathyroidectomy the supranormal response was abolished. Fifteen of these 22 hyper-responsive PHP patients had basal IRPTH levels not exceeding the highest level in the controls and that of other groups of patients investigated (idiopathic hypercalciuria, non-parathyroid hypercalcaemia, operated PHP). Fourteen of the 22 hyper-reactive patients with PHP did not show hypocalcaemia during the infusion of EDTA. The extent of the release of PTH elicited by EDTA in cases of PHP does not as yet allow a prediction of the amount of pathological parathyroid tissue present, although all the PHP patients showing a normal release of PTH had a relatively small mass of parathyroid tissue (up to about 1 g) subsequently removed. In 9 cases of nephrolithiasis (8 of whom had idiopathic hypercalciuria) and in 7 cases of non-parathyroid hypercalcaemia, a normal PTH release was found.

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Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism

Acta Endocrinologica ◽

10.1530/eje.1.02007 ◽

2005 ◽

Vol 153 (4) ◽

pp. 587-594 ◽

Cited By ~ 28

Author(s):

Takehisa Kawata ◽

Yasuo Imanishi ◽

Keisuke Kobayashi ◽

Takao Kenko ◽

Michihito Wada ◽

...

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Secondary Hyperparathyroidism ◽

Murine Model ◽

Hormone Secretion ◽

Suppressive Effect ◽

Receptor Expression ◽

Parathyroid Glands ◽

Calcium Sensing Receptor ◽

Calcium Sensing

Cinacalcet HCl, an allosteric modulator of the calcium-sensing receptor (CaR), has recently been approved for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, due to its suppressive effect on parathyroid hormone (PTH) secretion. Although cinacalcet’s effects in patients with primary and secondary hyperparathyroidism have been reported, the crucial relationship between the effect of calcimimetics and CaR expression on the parathyroid glands requires better understanding. To investigate its suppressive effect on PTH secretion in primary hyperparathyroidism, in which hypercalcemia may already have stimulated considerable CaR activity, we investigated the effect of cinacalcet HCl on PTH-cyclin D1 transgenic mice (PC2 mice), a model of primary hyperparathyroidism with hypo-expression of CaR on their parathyroid glands. A single administration of 30 mg/kg body weight (BW) of cinacalcet HCl significantly suppressed serum calcium (Ca) levels 2 h after administration in 65- to 85-week-old PC2 mice with chronic biochemical hyperparathyroidism. The percentage reduction in serum PTH was significantly correlated with CaR hypo-expression in the parathyroid glands. In older PC2 mice (93–99 weeks old) with advanced hyperparathyroidism, serum Ca and PTH levels were not suppressed by 30 mg cinacalcet HCl/kg. However, serum Ca and PTH levels were significantly suppressed by 100 mg/kg of cinacalcet HCl, suggesting that higher doses of this compound could overcome severe hyperparathyroidism. To conclude, cinacalcet HCl demonstrated potency in a murine model of primary hyperparathyroidism in spite of any presumed endogenous CaR activation by hypercalcemia and hypo-expression of CaR in the parathyroid glands.

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Postoperative studies on parathyroid hormone secretion in patients operated on for primary hyperparathyroidism

Clinica Chimica Acta ◽

10.1016/0009-8981(93)90198-d ◽

1993 ◽

Vol 219 (1-2) ◽

pp. 67-77 ◽

Cited By ~ 1

Author(s):

Anders Bergenfelz ◽

Nils E. Nordén ◽

Bo Ahrén

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Hormone Secretion

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Primary hyperparathyroidism

10.1093/med/9780199568741.003.0187 ◽

2018 ◽

Author(s):

John Newell-Price ◽

Alia Munir ◽

Miguel Debono

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Bone Mineralization ◽

Hormone Secretion ◽

Normal Serum ◽

Renal Physiology ◽

Calcium Sensing ◽

Inhibitory Feedback ◽

Normal Serum Calcium ◽

Solitary Adenoma

Primary hyperparathyroidism is a disorder of bone mineralization and renal physiology due to excess parathyroid hormone secretion. Parathyroid hormone (PTH) is produced and released by the parathyroid chief cells, under regulation of the G- protein-coupled calcium-sensing receptor. Primary hyperparathyroidism occurs when there is a loss of the inhibitory feedback of PTH release by extracellular calcium. The rise in PTH levels is initially associated with a normal serum calcium, and then over time with hypercalcaemia. The most common cause of primary hyperparathyroidism is a benign solitary adenoma (80%). Other causes include multiple adenomas and hyperplasia. This chapter reviews the causes, clinical features, and management of primary hyperparathyroidism.

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THE EFFECT OF CALCIUM AND DIBUTYRYL-cAMP ON THE SECRETION OF PARATHYROID HORMONE BY HUMAN PARATHYROID ADENOMAS IN ORGAN CULTURE

Acta Endocrinologica ◽

10.1530/acta.0.0850541 ◽

1977 ◽

Vol 85 (3) ◽

pp. 541-547 ◽

Cited By ~ 13

Author(s):

M. Dietel ◽

G. Dorn ◽

R. Montz ◽

E. Altenähr

Keyword(s):

Parathyroid Hormone ◽

Primary Hyperparathyroidism ◽

Organ Culture ◽

Inverse Relationship ◽

Calcium Concentration ◽

Culture Medium ◽

Hormone Secretion ◽

Dibutyryl Camp ◽

Parathyroid Adenomas ◽

Immunoreactive Parathyroid Hormone

ABSTRACT The effect of different calcium concentrations as well as dibutyryl-cyclic adenosine 3′,5′-monophosphate (DB-cAMP) on the secretion of parathyroid hormone by human parathyroid adenomas taken from patients with primary hyperparathyroidism (pHPT) was studied in organ culture. Their influence on the release of hormone was determined. The tissue was incubated in culture medium for 4 h; the medium was changed hourly and analyzed for immunoreactive parathyroid hormone (PTH) by radioimmunoassay. The hormone secretion showed an inverse relationship to different calcium concentrations in the medium and could be stimulated independently of the calcium concentration by adding DB-cAMP. These results suggest that the examined parathyroid adenomas are sensitive to physiological stimuli.

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