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Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology

CONTEXT: Familial hypocalciuric hypercalcemia (FHH) causes lifelong hypercalcemia that even persists after subtotal parathyroidectomy. Symptoms are usually mild. Past recommendations have often been for monitoring and against surgical or pharmacologic treatments. METHODS: Review of publications abou...

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Autor principal: Marx, Stephen J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673268/
https://www.ncbi.nlm.nih.gov/pubmed/28945857
http://dx.doi.org/10.1210/jc.2017-01606
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author Marx, Stephen J.
author_facet Marx, Stephen J.
author_sort Marx, Stephen J.
collection PubMed
description CONTEXT: Familial hypocalciuric hypercalcemia (FHH) causes lifelong hypercalcemia that even persists after subtotal parathyroidectomy. Symptoms are usually mild. Past recommendations have often been for monitoring and against surgical or pharmacologic treatments. METHODS: Review of publications about FHH, calcium-sensing receptors (CaSRs), and calcimimetics. RESULTS: FHH reflects heterozygous germline mutation of CASR, GNA11, or AP2S1. These mutations inactivate the CaSRs in the parathyroid cell. Thereby, they shift the serum calcium set point to higher values and cause hypercalcemia. Calcimimetic drugs enhance the effects of calcium on the CaSRs and thereby inhibit the parathyroid cell. Calcimimetic drugs are indicated in adults with primary hyperparathyroidism without a good surgical option. Calcimimetic safety and efficacy are not established in children younger than age 18 years. Recent case reports have described treatment of FHH with calcimimetics. Success was classified as combinations of subjective improvements and decreases of serum calcium levels, but not necessarily into the normal range. Treatment was successful in 14 of 16 cases (88%). CONCLUSION: Deductions based on these case reports have limitations. For example, failures of therapy may not have been reported. Cost of the drug might be rate limiting. Calcimimetics can be offered to adults with FHH and those in whom the serum calcium level is >0.25 mM (1 mg/dL) beyond the upper limit of normal or with possible symptoms of hypercalcemia. Calcimimetics can now be offered to more adults with FHH.
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spelling pubmed-56732682018-11-01 Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology Marx, Stephen J. J Clin Endocrinol Metab Perspectives in Endocrinology CONTEXT: Familial hypocalciuric hypercalcemia (FHH) causes lifelong hypercalcemia that even persists after subtotal parathyroidectomy. Symptoms are usually mild. Past recommendations have often been for monitoring and against surgical or pharmacologic treatments. METHODS: Review of publications about FHH, calcium-sensing receptors (CaSRs), and calcimimetics. RESULTS: FHH reflects heterozygous germline mutation of CASR, GNA11, or AP2S1. These mutations inactivate the CaSRs in the parathyroid cell. Thereby, they shift the serum calcium set point to higher values and cause hypercalcemia. Calcimimetic drugs enhance the effects of calcium on the CaSRs and thereby inhibit the parathyroid cell. Calcimimetic drugs are indicated in adults with primary hyperparathyroidism without a good surgical option. Calcimimetic safety and efficacy are not established in children younger than age 18 years. Recent case reports have described treatment of FHH with calcimimetics. Success was classified as combinations of subjective improvements and decreases of serum calcium levels, but not necessarily into the normal range. Treatment was successful in 14 of 16 cases (88%). CONCLUSION: Deductions based on these case reports have limitations. For example, failures of therapy may not have been reported. Cost of the drug might be rate limiting. Calcimimetics can be offered to adults with FHH and those in whom the serum calcium level is >0.25 mM (1 mg/dL) beyond the upper limit of normal or with possible symptoms of hypercalcemia. Calcimimetics can now be offered to more adults with FHH. Endocrine Society 2017-09-18 /pmc/articles/PMC5673268/ /pubmed/28945857 http://dx.doi.org/10.1210/jc.2017-01606 Text en
spellingShingle Perspectives in Endocrinology
Marx, Stephen J.
Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology
title Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology
title_full Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology
title_fullStr Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology
title_full_unstemmed Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology
title_short Calcimimetic Use in Familial Hypocalciuric Hypercalcemia—A Perspective in Endocrinology
title_sort calcimimetic use in familial hypocalciuric hypercalcemia—a perspective in endocrinology
topic Perspectives in Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673268/
https://www.ncbi.nlm.nih.gov/pubmed/28945857
http://dx.doi.org/10.1210/jc.2017-01606
work_keys_str_mv AT marxstephenj calcimimeticuseinfamilialhypocalciurichypercalcemiaaperspectiveinendocrinology