Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia

S. J. Marx, A. M. Spiegel, M. A. Levine, Allen M. Spiegel, R. D. Lasker, A. C. Santora, R. W. Downs, G. D. Aurbach

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

In familial hypocalciuric hypercalcemia, the parathyroid and kidney may be insensitive to extracellular calcium ions. Evidence of such insensitivity in the mechanisms that control hormone secretion and cell proliferation in the parathyroid glands is summarized. Data on renal function can also be explained by insensitivity to extracellular calcium. Beck et al. showed that in hypoparathyroid rats the response of urinary cyclic AMP to the administration of parathyroid hormone was diminished at progressively higher concentrations of serum calcium. The exaggerated response of cyclic AMP to parathyroid hormone in familial hypocalciuric hypercalcemia may similarly reflect renal insensitivity to the inhibitory effects of hypercalcemia. The conservation of urine-concentrating ability by the kidney in familial hypocalciuric hypercalcemia may show an insensitivity to the nephrotoxic effects of chronic hypercalcemia. Furthermore, the avid tubular resorption of calcium, which persists even when parathyroidectomy has led to otherwise typical features of hypoparathyroidism, also indicates a disturbance in the ability of renal cells to recognize or transport calcium. The explanation of the underlying mechanism, however, remains incomplete. Dysfunction of a single metabolic pathway should account for the defect in calcium metabolism in the parathyroid and kidney in familial hypocalciuric hypercalcemia. The fact that the degree of hypercalcemia is different in selected families and the fact that certain persons may carry related genes without even expressing hypercalcemia suggests that there is a series of related mutations.

Original languageEnglish (US)
Pages (from-to)416-426
Number of pages11
JournalNew England Journal of Medicine
Volume307
Issue number7
StatePublished - 1982
Externally publishedYes

Fingerprint

Hyperplasia
Hypercalcemia
Calcium
Kidney
Parathyroid Hormone
Cyclic AMP
Kidney Concentrating Ability
Hypoparathyroidism
Parathyroidectomy
Parathyroid Glands
Metabolic Networks and Pathways
Hypocalciuric hypercalcemia, familial, type 1
Cell Proliferation
Hormones
Ions
Mutation
Serum
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Marx, S. J., Spiegel, A. M., Levine, M. A., Spiegel, A. M., Lasker, R. D., Santora, A. C., ... Aurbach, G. D. (1982). Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia. New England Journal of Medicine, 307(7), 416-426.

Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia. / Marx, S. J.; Spiegel, A. M.; Levine, M. A.; Spiegel, Allen M.; Lasker, R. D.; Santora, A. C.; Downs, R. W.; Aurbach, G. D.

In: New England Journal of Medicine, Vol. 307, No. 7, 1982, p. 416-426.

Research output: Contribution to journalArticle

Marx, SJ, Spiegel, AM, Levine, MA, Spiegel, AM, Lasker, RD, Santora, AC, Downs, RW & Aurbach, GD 1982, 'Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia', New England Journal of Medicine, vol. 307, no. 7, pp. 416-426.
Marx, S. J. ; Spiegel, A. M. ; Levine, M. A. ; Spiegel, Allen M. ; Lasker, R. D. ; Santora, A. C. ; Downs, R. W. ; Aurbach, G. D. / Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia. In: New England Journal of Medicine. 1982 ; Vol. 307, No. 7. pp. 416-426.
@article{43c137cb4e9b4f4691b64b3470058b74,
title = "Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia",
abstract = "In familial hypocalciuric hypercalcemia, the parathyroid and kidney may be insensitive to extracellular calcium ions. Evidence of such insensitivity in the mechanisms that control hormone secretion and cell proliferation in the parathyroid glands is summarized. Data on renal function can also be explained by insensitivity to extracellular calcium. Beck et al. showed that in hypoparathyroid rats the response of urinary cyclic AMP to the administration of parathyroid hormone was diminished at progressively higher concentrations of serum calcium. The exaggerated response of cyclic AMP to parathyroid hormone in familial hypocalciuric hypercalcemia may similarly reflect renal insensitivity to the inhibitory effects of hypercalcemia. The conservation of urine-concentrating ability by the kidney in familial hypocalciuric hypercalcemia may show an insensitivity to the nephrotoxic effects of chronic hypercalcemia. Furthermore, the avid tubular resorption of calcium, which persists even when parathyroidectomy has led to otherwise typical features of hypoparathyroidism, also indicates a disturbance in the ability of renal cells to recognize or transport calcium. The explanation of the underlying mechanism, however, remains incomplete. Dysfunction of a single metabolic pathway should account for the defect in calcium metabolism in the parathyroid and kidney in familial hypocalciuric hypercalcemia. The fact that the degree of hypercalcemia is different in selected families and the fact that certain persons may carry related genes without even expressing hypercalcemia suggests that there is a series of related mutations.",
author = "Marx, {S. J.} and Spiegel, {A. M.} and Levine, {M. A.} and Spiegel, {Allen M.} and Lasker, {R. D.} and Santora, {A. C.} and Downs, {R. W.} and Aurbach, {G. D.}",
year = "1982",
language = "English (US)",
volume = "307",
pages = "416--426",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "7",

}

TY - JOUR

T1 - Familial hypocalciuric hypercalcemia. The relation to primary parathyroid hyperplasia

AU - Marx, S. J.

AU - Spiegel, A. M.

AU - Levine, M. A.

AU - Spiegel, Allen M.

AU - Lasker, R. D.

AU - Santora, A. C.

AU - Downs, R. W.

AU - Aurbach, G. D.

PY - 1982

Y1 - 1982

N2 - In familial hypocalciuric hypercalcemia, the parathyroid and kidney may be insensitive to extracellular calcium ions. Evidence of such insensitivity in the mechanisms that control hormone secretion and cell proliferation in the parathyroid glands is summarized. Data on renal function can also be explained by insensitivity to extracellular calcium. Beck et al. showed that in hypoparathyroid rats the response of urinary cyclic AMP to the administration of parathyroid hormone was diminished at progressively higher concentrations of serum calcium. The exaggerated response of cyclic AMP to parathyroid hormone in familial hypocalciuric hypercalcemia may similarly reflect renal insensitivity to the inhibitory effects of hypercalcemia. The conservation of urine-concentrating ability by the kidney in familial hypocalciuric hypercalcemia may show an insensitivity to the nephrotoxic effects of chronic hypercalcemia. Furthermore, the avid tubular resorption of calcium, which persists even when parathyroidectomy has led to otherwise typical features of hypoparathyroidism, also indicates a disturbance in the ability of renal cells to recognize or transport calcium. The explanation of the underlying mechanism, however, remains incomplete. Dysfunction of a single metabolic pathway should account for the defect in calcium metabolism in the parathyroid and kidney in familial hypocalciuric hypercalcemia. The fact that the degree of hypercalcemia is different in selected families and the fact that certain persons may carry related genes without even expressing hypercalcemia suggests that there is a series of related mutations.

AB - In familial hypocalciuric hypercalcemia, the parathyroid and kidney may be insensitive to extracellular calcium ions. Evidence of such insensitivity in the mechanisms that control hormone secretion and cell proliferation in the parathyroid glands is summarized. Data on renal function can also be explained by insensitivity to extracellular calcium. Beck et al. showed that in hypoparathyroid rats the response of urinary cyclic AMP to the administration of parathyroid hormone was diminished at progressively higher concentrations of serum calcium. The exaggerated response of cyclic AMP to parathyroid hormone in familial hypocalciuric hypercalcemia may similarly reflect renal insensitivity to the inhibitory effects of hypercalcemia. The conservation of urine-concentrating ability by the kidney in familial hypocalciuric hypercalcemia may show an insensitivity to the nephrotoxic effects of chronic hypercalcemia. Furthermore, the avid tubular resorption of calcium, which persists even when parathyroidectomy has led to otherwise typical features of hypoparathyroidism, also indicates a disturbance in the ability of renal cells to recognize or transport calcium. The explanation of the underlying mechanism, however, remains incomplete. Dysfunction of a single metabolic pathway should account for the defect in calcium metabolism in the parathyroid and kidney in familial hypocalciuric hypercalcemia. The fact that the degree of hypercalcemia is different in selected families and the fact that certain persons may carry related genes without even expressing hypercalcemia suggests that there is a series of related mutations.

UR - http://www.scopus.com/inward/record.url?scp=0020316902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020316902&partnerID=8YFLogxK

M3 - Article

C2 - 7045673

AN - SCOPUS:0020316902

VL - 307

SP - 416

EP - 426

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 7

ER -