2020
Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism
Minisola S, Arnold A, Belaya Z, Brandi ML, Clarke BL, Hannan FM, Hofbauer LC, Insogna KL, Lacroix A, Liberman U, Palermo A, Pepe J, Rizzoli R, Wermers R, Thakker RV. Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism. Journal Of Bone And Mineral Research 2020, 37: 2315-2329. PMID: 36245271, PMCID: PMC10092691, DOI: 10.1002/jbmr.4665.Peer-Reviewed Original ResearchConceptsPrimary hyperparathyroidismFamilial hypocalciuric hypercalcemiaMultiple endocrine neoplasia syndromeCalcium-containing kidney stonesIntestinal calcium hyperabsorptionMore parathyroid glandsParathyroid hormone levelsAsymptomatic primary hyperparathyroidismCalcium-sensing receptorEndocrine neoplasia syndromeNeonatal severe hyperparathyroidismHyperparathyroidism-jaw tumor syndromeJaw tumor syndromeCalcium hyperabsorptionPostmenopausal womenSevere hyperparathyroidismParathyroid hormoneSerum calciumHypocalciuric hypercalcemiaPathophysiologic basisParathyroid cellsParathyroid glandsHormone levelsFiltered loadMetabolic factors
2018
Primary Hyperparathyroidism
Insogna KL. Primary Hyperparathyroidism. New England Journal Of Medicine 2018, 379: 1050-1059. PMID: 30207907, DOI: 10.1056/nejmcp1714213.BooksThe contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function
Koduru SV, Sun BH, Walker JM, Zhu M, Simpson C, Dhodapkar M, Insogna KL. The contribution of cross-talk between the cell-surface proteins CD36 and CD47–TSP-1 in osteoclast formation and function. Journal Of Biological Chemistry 2018, 293: 15055-15069. PMID: 30082316, PMCID: PMC6166722, DOI: 10.1074/jbc.ra117.000633.Peer-Reviewed Original ResearchConceptsOsteoclast formationTSP-1Competitive NO synthase inhibitorPro-osteoclastogenic effectAntibody-mediated blockadeNitroarginine methyl esterNO synthase inhibitorNitric Oxide SignalingPTH infusionDifferentiation 47Parathyroid hormoneBone resorptionFemale miceHypercalcemic responseOsteoclast maturationSynthase inhibitorResorptive activitySynthetic agonistsCD36Osteoclast progenitorsMiceInhibitory effectCD47OsteoclastsWT osteoblasts
2014
Denosumab for Treatment of Hypercalcemia of Malignancy
Hu MI, Glezerman IG, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Zorsky P, Tosi D, Bessudo A, Jaccard A, Tonini G, Ying W, Braun A, Jain RK. Denosumab for Treatment of Hypercalcemia of Malignancy. The Journal Of Clinical Endocrinology & Metabolism 2014, 99: 3144-3152. PMID: 24915117, PMCID: PMC4154084, DOI: 10.1210/jc.2014-1001.Peer-Reviewed Original ResearchConceptsHypercalcemia of malignancyProportion of patientsDay 10Serum calciumBone resorptionCommon serious adverse eventsMedian response durationSerious adverse eventsSerum calcium levelsTreatment of hypercalcemiaDuration of responseNew treatment optionsBisphosphonate therapyPrimary endpointSecondary endpointsAdverse eventsBisphosphonate treatmentDurable responsesComplete responseAdvanced cancerTreatment optionsHematologic malignanciesResponse durationDenosumabCalcium levels
2013
Denosumab for Patients With Persistent or Relapsed Hypercalcemia of Malignancy Despite Recent Bisphosphonate Treatment
Hu MI, Glezerman I, Leboulleux S, Insogna K, Gucalp R, Misiorowski W, Yu B, Ying W, Jain RK. Denosumab for Patients With Persistent or Relapsed Hypercalcemia of Malignancy Despite Recent Bisphosphonate Treatment. Journal Of The National Cancer Institute 2013, 105: 1417-1420. PMID: 23990665, PMCID: PMC3776443, DOI: 10.1093/jnci/djt225.Peer-Reviewed Original ResearchConceptsHypercalcemia of malignancyBisphosphonate treatmentResponse durationDay 10Albumin-corrected serum calciumTumor-induced bone resorptionIntravenous bisphosphonate treatmentPrespecified interim analysisMedian response durationProportion of patientsKaplan-Meier methodNew treatment optionsDenosumab initiationIntravenous bisphosphonatesSubcutaneous denosumabPrimary endpointRenal failureComplete responseSerum calciumTreatment optionsHCM patientsBone resorptionDenosumabInterim analysisPatients
2002
Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*
Wysolmerski JJ, Dann PR, Zelazny E, Dunbar ME, Insogna KL, Guise TA, Perkins AS. Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*. Journal Of Bone And Mineral Research 2002, 17: 1164-1170. PMID: 12096830, DOI: 10.1359/jbmr.2002.17.7.1164.Peer-Reviewed Original ResearchConceptsBone metastasesBreast cancer cellsCancer cellsTransgenic miceTumor-bearing transgenic miceParathyroid hormone-related proteinPrimary breast cancerProduction of PTHrPHormone-related proteinWild-type littermatesEffects of PTHrPCause hypercalcemiaWild-type controlsVisceral metastasesSkeletal metastasesParathyroid hormoneBone resorptionArterial circulationBreast cancerDMBA treatmentMammary carcinogenImmunodeficient miceMammary tumorigenesisMurine modelHigh incidence
1992
A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets
Sullivan W, Carpenter T, Glorieux F, Travers R, Insogna K. A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. The Journal Of Clinical Endocrinology & Metabolism 1992, 75: 879-885. PMID: 1517380, DOI: 10.1210/jcem.75.3.1517380.Peer-Reviewed Original ResearchConceptsSymptomatic adultsOral phosphateOsteoid volumeCessation of therapyUrinary calcium excretionSymptomatic adult patientsMean serum phosphateDihydroxyvitamin D3 therapyMineral apposition rateCalcium excretionD3 therapyRenal insufficiencyTertiary hyperparathyroidismAdult patientsDrug regimenJoint painMost patientsPretreatment serumProspective trialClinical courseSerum phosphateSymptom scoresBone biopsyCombined administrationCurrent treatment
1991
Treatment of Sarcoidosis-Associated Hypercalcemia With Ketoconazole
Bia M, Insogna K. Treatment of Sarcoidosis-Associated Hypercalcemia With Ketoconazole. American Journal Of Kidney Diseases 1991, 18: 702-705. PMID: 1962657, DOI: 10.1016/s0272-6386(12)80613-5.Peer-Reviewed Original ResearchMeSH KeywordsCalcitriolCalciumHumansHypercalcemiaKetoconazoleKidney Failure, ChronicMaleMiddle AgedPrednisoneSarcoidosisConceptsAngiotensin-converting enzyme levelsACE levelsSide effectsLong-term side effectsDihydroxyvitamin D levelsLiver function testsSymptom-free intervalSerum ACE levelsSerum testosterone levelsSerum cortisol levelsLong-term usePatient's hypercalcemiaCorticosteroid treatmentDisease activityKetoconazole therapySerum creatinineFunction testsPersistent elevationD levelsRapid recurrenceCalcium metabolismKetoconazole treatmentTestosterone levelsHypercalcemiaLarge dose
1990
Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase
Brown G, Morris C, Mitnick M, Insogna K. Treatment of humoral hypercalcemia of malignancy in rats with inhibitors of carbonic anhydrase. Journal Of Bone And Mineral Research 1990, 5: 1037-1041. PMID: 1964358, DOI: 10.1002/jbmr.5650051007.Peer-Reviewed Original ResearchConceptsSerum calciumBone resorptionHumoral hypercalcemiaCarbonic anhydrase inhibitorsNephrogenous cyclic AMP excretionCyclic AMP excretionMean serum calciumOsteoclastic bone resorptionDrug-treated animalsLeydig cell tumorMechanism of actionUrine phosphorusUrine calciumSerum phosphorusCell tumorsAcetazolamide treatmentHypercalcemiaSignificant fallFisher ratsObserved hypercalcemiaResorptionDirect inhibitionSignificant riseMalignancyRats
1989
Humoral Hypercalcemia of Malignancy: The Role of Parathyroid Hormone-related Protein
Insogna K. Humoral Hypercalcemia of Malignancy: The Role of Parathyroid Hormone-related Protein. Endocrinology And Metabolism Clinics Of North America 1989, 18: 779-794. PMID: 2673773, DOI: 10.1016/s0889-8529(18)30366-9.BooksConceptsMalignancy-associated hypercalcemiaHumoral hypercalcemiaRenal tubular calcium reabsorptionParathyroid hormone-related proteinIntense bone resorptionTubular calcium reabsorptionTumor-derived factorsCentral pathogenic roleHormone-related proteinTumor-derived tissueCalcium reabsorptionBone resorptionPathogenic roleCommon causeHypercalcemiaExperimental modelHHMDevelopment of antiseraMalignancyPTHrPAnalysis of mRNAAntiserumPreliminary studySyndromeAmino-terminal polypeptide
1988
Isolation of 16,000-Dalton Parathyroid Hormone-Like Proteins from Two Animal Tumors Causing Humoral Hypercalcemia of Malignancy*
Weir EC, Burtis WJ, Morris CA, Brady TG, Insogna KL. Isolation of 16,000-Dalton Parathyroid Hormone-Like Proteins from Two Animal Tumors Causing Humoral Hypercalcemia of Malignancy*. Endocrinology 1988, 123: 2744-2751. PMID: 3197642, DOI: 10.1210/endo-123-6-2744.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAmino Acid SequenceAmino AcidsAnimalsDogsHumansHypercalcemiaLeydig Cell TumorMaleMolecular Sequence DataMolecular WeightNeoplasm ProteinsNeoplasmsParathyroid Hormone-Related ProteinRatsRats, Inbred F344Sequence Homology, Nucleic AcidSweat Gland NeoplasmsTesticular NeoplasmsConceptsPTH-like proteinAnimal tumorsPTH-like peptideHumoral hypercalcemiaParathyroid hormone-like proteinSynthetic human PTHLeydig cell tumorHuman PTH-like peptideHormone-like proteinTransplantable animal tumorsCell adenocarcinomaCanine proteinCell tumorsResponsible mediatorsHuman PTHImmunoradiometric assayTumorsHuman tumorsAdenylate cyclaseLike peptidesAnal sacHypercalcemiaBone cellsMalignancyPotent activatorRenal phosphate transport in humoral hypercalcemia of malignancy
Sartori L, Insogna KL, Barrett PQ. Renal phosphate transport in humoral hypercalcemia of malignancy. American Journal Of Physiology 1988, 255: f1078-f1084. PMID: 2974244, DOI: 10.1152/ajprenal.1988.255.6.f1078.Peer-Reviewed Original ResearchConceptsLeydig cell tumorHumoral hypercalcemiaOnset of hypercalcemiaTumor-bearing animalsPhosphate metabolismRenal phosphate transportCortical brush border membraneParathyroid hormoneDaily injectionsTumor transplantationCell tumorsDichloromethylene diphosphonateMicrovillus membrane vesiclesRenal cortexRenal cortical brush border membraneSodium-dependent phosphate uptakeFisher ratsAnimal modelsPersistent impairmentHypercalcemiaLow-affinity systemBrush border membraneSpecific decreaseMalignancyRatsHumoral Hypercalcemia of Cancer
Flier J, Underhill L, Broadus A, Mangin M, Ikeda K, Insogna K, Weir E, Burtis W, Stewart A. Humoral Hypercalcemia of Cancer. New England Journal Of Medicine 1988, 319: 556-563. PMID: 3043221, DOI: 10.1056/nejm198809013190906.BooksIdentification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy.
Ikeda K, Mangin M, Dreyer BE, Webb AC, Posillico JT, Stewart AF, Bander NH, Weir EC, Insogna KL, Broadus AE. Identification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy. Journal Of Clinical Investigation 1988, 81: 2010-2014. PMID: 2454953, PMCID: PMC442656, DOI: 10.1172/jci113551.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCloning, MolecularHumansHypercalcemiaKidney NeoplasmsMolecular Sequence DataNeoplasm ProteinsNucleic Acid HybridizationParaneoplastic SyndromesParathyroid HormoneParathyroid Hormone-Related ProteinPoly ARNARNA, MessengerRNA, NeoplasmSequence Homology, Nucleic AcidTranscription, GeneticConceptsPTH-like peptideParathyroid hormone-like peptideAnimal tumorsHumoral hypercalcemiaHormone-like peptideSyndrome of HHMVariety of humanHuman PTH-like peptideSimilar histological typeHistological typeHuman PTHTumor typesTumorsHHMHypercalcemiaMalignancySyndromeMessenger RNAMRNAWide spectrumHumansPeptidesMammalian speciesRNAPTHIn vitro adenylate cyclase-stimulating activity predicts the occurrence of humoral hypercalcemia of malignancy in nude mice.
Weir EC, Insogna KL, Brownstein DG, Bander NH, Broadus AE. In vitro adenylate cyclase-stimulating activity predicts the occurrence of humoral hypercalcemia of malignancy in nude mice. Journal Of Clinical Investigation 1988, 81: 818-821. PMID: 3343341, PMCID: PMC442531, DOI: 10.1172/jci113389.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityNude miceHumoral hypercalcemiaSyndrome of HHMMean tumor sizeReliable predictive markersHuman renal carcinoma cell linesCyclase-stimulating activityCell linesRenal carcinoma cell linesCultured tumor cellsHypercalcemic animalsTumor sizeCarcinoma cell linesPredictive markerBone resorptionTumor extractsTumor cellsMiceNormocalcemic animalsPotential mediatorsHypercalcemiaHHMCell assayMalignancyHumoral hypercalcemia of malignancy.
Burtis WJ, Wu TL, Insogna KL, Stewart AF. Humoral hypercalcemia of malignancy. Annals Of Internal Medicine 1988, 108: 454-7. PMID: 3277518, DOI: 10.7326/0003-4819-108-3-454.BooksSYNTHETIC AND PARTIALLY-PURIFIED ADENYLATE CYCLASE-STIMULATING PROTEINS FROM TUMORS ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY INHIBIT PHOSPHATE TRANSPORT IN A PTH-RESPONSIVE RENAL CELL LINE
SARTORI L, WEIR EC, STEWART AF, BROADUS AE, MANGIN M, BARRETT PQ, INSOGNA KL. SYNTHETIC AND PARTIALLY-PURIFIED ADENYLATE CYCLASE-STIMULATING PROTEINS FROM TUMORS ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY INHIBIT PHOSPHATE TRANSPORT IN A PTH-RESPONSIVE RENAL CELL LINE. The Journal Of Clinical Endocrinology & Metabolism 1988, 66: 459-461. PMID: 3339117, DOI: 10.1210/jcem-66-2-459.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityHumoral hypercalcemiaPhosphate metabolismCyclase-stimulating activityCell linesSodium-dependent phosphate transportRenal cell linesEpithelial cell lineTumor productsTumor decreaseRenal epithelial cellsRenal epithelial cell lineAmino acid peptidePhosphate transportHypercalcemiaAnimal tumorsTumorsHuman tumorsEpithelial cellsHHMMalignancyNaPiTInhibitory activityMinutes exposureEpithelial monolayersHumoral Hypercalcemia of Malignancy in Canine Lymphosarcoma*
Weir EC, Norrdin RW, Matus RE, Brooks MB, Broadus AE, Mitnick M, Johnston SD, Insogna KL. Humoral Hypercalcemia of Malignancy in Canine Lymphosarcoma*. Endocrinology 1988, 122: 602-608. PMID: 2828006, DOI: 10.1210/endo-122-2-602.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityHypercalcemic dogsCanine lymphosarcomaFractional phosphorus excretionEvidence of tumorQuantitative bone histomorphometryBone-resorbing factorsImmunoreactive PTH levelsPathogenesis of hypercalcemiaIliac crest biopsiesTumor tissue extractsCyclase-stimulating activityBone histomorphometric findingsCalcium excretionPTH levelsHumoral hypercalcemiaDihydroxyvitamin DBone resorptionHistomorphometric findingsBone histomorphometryPTH receptorBiopsy siteCrest biopsiesTumor extractsCompensatory increaseSynthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats.
Stewart AF, Mangin M, Wu T, Goumas D, Insogna KL, Burtis WJ, Broadus AE. Synthetic human parathyroid hormone-like protein stimulates bone resorption and causes hypercalcemia in rats. Journal Of Clinical Investigation 1988, 81: 596-600. PMID: 3339131, PMCID: PMC329608, DOI: 10.1172/jci113358.Peer-Reviewed Original ResearchConceptsBone-resorbing agentsMicrograms/hParathyroid hormone-like proteinFetal rat long bonesAdenylate cyclasePotent bone-resorbing agentHormone-like proteinRat long bonesMembrane adenylate cyclaseSerum calciumHumoral hypercalcemiaOsmotic minipumpsBone resorptionPotent agonistLong bonesSuch synthetic peptidesHypercalcemiaRatsDlVivo bioactivityCyclaseSynthetic peptidesAgentsMinipumpsPatients
1987
CO-PURIFICATION OF TRANSFORMING GROWTH FACTOR LIKE ACTIVITY WITH PTH-LIKE AND BONE-RESORBING ACTIVITIES FROM A TUMOR ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY
INSOGNA K, WEIR E, WU T, STEWART A, BROADUS A, BURTIS W, CENTRELLA M. CO-PURIFICATION OF TRANSFORMING GROWTH FACTOR LIKE ACTIVITY WITH PTH-LIKE AND BONE-RESORBING ACTIVITIES FROM A TUMOR ASSOCIATED WITH HUMORAL HYPERCALCEMIA OF MALIGNANCY. Endocrinology 1987, 120: 2183-2185. PMID: 3494596, DOI: 10.1210/endo-120-5-2183.Peer-Reviewed Original ResearchConceptsAdenylate cyclase-stimulating activityBone-resorbing factorsBone-resorbing activityHumoral hypercalcemiaGrowth factor beta-like activityPTH-like proteinLeydig cell tumorReverse-phase HPLC stepsBeta-like activityCyclase-stimulating activityGrowth factor betaCell tumorsResponsible mediatorsGrowth factor activityTumor extractsFisher ratsAnimal modelsFactor betaTumor tissueSingle fractionGrowth factorHypercalcemiaMalignancyPTHSequential treatment