Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

OBJECTIVE Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostic tests for this condition in clinical practice. PARTICIPANTS Interested professional societies selected a representative for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed. The conclusions were then circulated to the participating professional societies. EVIDENCE Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. CONSENSUS PROCESS Consensus was achieved by a group meeting. Statements were prepared by all authors, with comments relating to accuracy from the diagnosis subgroup and by representatives from the participating professional societies. CONCLUSIONS We conclude that: 1) reference ranges should be established for serum PTH in vitamin D-replete healthy individuals; 2) second- and third-generation PTH assays are both helpful in the diagnosis of PHPT; 3) DNA sequence testing can be useful in familial hyperparathyroidism or hypercalcemia; 4) normocalcemic PHPT is a variant of the more common presentation of PHPT with hypercalcemia; 5) serum 25-hydroxyvitamin D levels should be measured and, if vitamin D insufficiency is present, it should be treated as part of any management course; and 6) the estimated glomerular filtration rate should be used to determine the level of kidney function in PHPT: an estimated glomerular filtration rate of less than 60 ml/min.1.73 m2 should be a benchmark for decisions about surgery in established asymptomatic PHPT.

[1]  J. Souberbielle,et al.  Lessons from second- and third-generation parathyroid hormone assays in primary hyperparathyroidism , 2008, Journal of endocrinological investigation.

[2]  M. Drezner,et al.  Correlation among 25-hydroxy-vitamin D assays. , 2008, The Journal of clinical endocrinology and metabolism.

[3]  E. Brown,et al.  Familial Benign Hypocalciuric Hypercalcemia and Neonatal Primary Hyperparathyroidism , 2008 .

[4]  S. Silverberg Vitamin D Deficiency and Primary Hyperparathyroidism , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  R. Zahradnik,et al.  Parathyroid hormone fragments inhibit active hormone and hypocalcemia-induced 1,25(OH)2D synthesis. , 2007, Kidney international.

[6]  M. Rubin,et al.  An N-terminal molecular form of parathyroid hormone (PTH) distinct from hPTH(1 84) is overproduced in parathyroid carcinoma. , 2007, Clinical chemistry.

[7]  Louise Izatt,et al.  Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. , 2007, The Journal of clinical endocrinology and metabolism.

[8]  E. Brown,et al.  Clinical lessons from the calcium-sensing receptor , 2007, Nature Clinical Practice Endocrinology &Metabolism.

[9]  National Kidney Foundation K-DOQI: Clinical practice guidelines for bone metabolism and disease in chronic kidney disease , 2007 .

[10]  A. Shao,et al.  Risk assessment for vitamin D. , 2007, The American journal of clinical nutrition.

[11]  G. Divine,et al.  Prevalence of vitamin D depletion among subjects seeking advice on osteoporosis: a five-year cross-sectional study with public health implications , 2007, Osteoporosis International.

[12]  H. Höfler,et al.  Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans , 2006, Proceedings of the National Academy of Sciences.

[13]  P. Houillier,et al.  Inter-method variability in PTH measurement: implication for the care of CKD patients. , 2006, Kidney international.

[14]  W. Willett,et al.  Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. , 2006, The American journal of clinical nutrition.

[15]  J. Aloia,et al.  Reference range for serum parathyroid hormone. , 2006, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[16]  J. Souberbielle,et al.  Unexpected serum parathyroid hormone profiles in some patients with primary hyperparathyroidism. , 2006, Clinical chemistry.

[17]  J. Souberbielle,et al.  Practical considerations in PTH testing. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[18]  J. Souberbielle,et al.  Third- or second-generation parathyroid hormone assays: a remaining debate in the diagnosis of primary hyperparathyroidism. , 2005, The Journal of clinical endocrinology and metabolism.

[19]  G. Sigurdsson,et al.  Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake. , 2005, JAMA.

[20]  L. Ferrucci,et al.  25(OH)D Serum levels decline with age earlier in women than in men and less efficiently prevent compensatory hyperparathyroidism in older adults. , 2005, The journals of gerontology. Series A, Biological sciences and medical sciences.

[21]  P. Vestergaard,et al.  Vitamin D status, seasonal variations, parathyroid adenoma weight and bone mineral density in primary hyperparathyroidism , 2005, Clinical endocrinology.

[22]  M. Holick,et al.  Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. , 2005, The Journal of clinical endocrinology and metabolism.

[23]  C. Lazure,et al.  Structure of non-(1-84) PTH fragments secreted by parathyroid glands in primary and secondary hyperparathyroidism. , 2005, Kidney international.

[24]  T. Cantor Editorials: Parathyroid Hormone Assay Drift: An Unappreciated Problem in Dialysis Patient Management , 2005, Seminars in dialysis.

[25]  S. Marx Molecular genetics of multiple endocrine neoplasia types 1 and 2 , 2005, Nature Reviews Cancer.

[26]  I. Reid,et al.  Vitamin D repletion in patients with primary hyperparathyroidism and coexistent vitamin D insufficiency. , 2005, The Journal of clinical endocrinology and metabolism.

[27]  P. D'amour,et al.  Evolution of the parathyroid hormone (PTH) assay--importance of circulating PTH immunoheterogeneity and of its regulation. , 2005, Clinical laboratory.

[28]  C. Albert,et al.  Evidence that the amino-terminal composition of non-(1-84) parathyroid hormone fragments starts before position 19. , 2005, Clinical chemistry.

[29]  G. Divine,et al.  Randomized controlled clinical trial of surgery versus no surgery in patients with mild asymptomatic primary hyperparathyroidism. , 2004, The Journal of clinical endocrinology and metabolism.

[30]  J. Berry,et al.  How accurate are assays for 25-hydroxyvitamin D? Data from the international vitamin D external quality assessment scheme. , 2004, Clinical chemistry.

[31]  P. N. Rao,et al.  Imaging for kidney stones , 2004, World Journal of Urology.

[32]  E. Romagnoli,et al.  Potential clinical utility of a new IRMA for parathyroid hormone in postmenopausal patients with primary hyperparathyroidism. , 2004, Clinical chemistry.

[33]  J. Carpten,et al.  Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. , 2004, The Journal of clinical endocrinology and metabolism.

[34]  J. Carpten,et al.  Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. , 2003, The New England journal of medicine.

[35]  Keith C. Norris,et al.  K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[36]  S. Silverberg,et al.  Clinical utility of an immunoradiometric assay for parathyroid hormone (1-84) in primary hyperparathyroidism. , 2003, The Journal of clinical endocrinology and metabolism.

[37]  Cecilia A. Hale,et al.  Calcium Absorption Varies within the Reference Range for Serum 25-Hydroxyvitamin D , 2003, Journal of the American College of Nutrition.

[38]  A. Prentice,et al.  In a population study, can parathyroid hormone aid the definition of adequate vitamin D status? A study of people aged 65 years and over from the British National Diet and Nutrition Survey , 2003, Osteoporosis International.

[39]  R. Vieth,et al.  Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. , 2003, The Journal of clinical endocrinology and metabolism.

[40]  J. Rastad,et al.  Summary statement from a workshop on asymptomatic primary hyperparathyroidism: a perspective for the 21st century. , 2002, The Journal of clinical endocrinology and metabolism.

[41]  F. Collins,et al.  Hyperparathyroidism in hereditary syndromes: special expressions and special managements. , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[42]  A. Mithal,et al.  Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: a global perspective. , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[43]  M. Schlichting,et al.  Combined Calcium and Vitamin D3 Supplementation in Elderly Women: Confirmation of Reversal of Secondary Hyperparathyroidism and Hip Fracture Risk: The Decalyos II Study , 2002, Osteoporosis International.

[44]  W. Simonds,et al.  Familial Isolated Hyperparathyroidism: Clinical and Genetic Characteristics of 36 Kindreds , 2002, Medicine.

[45]  B. Ponder,et al.  Guidelines for diagnosis and therapy of MEN type 1 and type 2. , 2001, The Journal of clinical endocrinology and metabolism.

[46]  P. Lips,et al.  Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. , 2001, Endocrine reviews.

[47]  E. Baulieu,et al.  Vitamin D status and redefining serum parathyroid hormone reference range in the elderly. , 2001, The Journal of clinical endocrinology and metabolism.

[48]  Sudhaker D. Rao,et al.  Development of a Novel Immunoradiometric Assay Exclusively for Biologically Active Whole Parathyroid Hormone 1–84: Implications for Improvement of Accurate Assessment of Parathyroid Function , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[49]  L. Nguyen-Yamamoto,et al.  Synthetic carboxyl-terminal fragments of parathyroid hormone (PTH) decrease ionized calcium concentration in rats by acting on a receptor different from the PTH/PTH-related peptide receptor. , 2001, Endocrinology.

[50]  D. DeLong,et al.  Nonenhanced helical CT and US in the emergency evaluation of patients with renal colic: prospective comparison. , 2000, Radiology.

[51]  B. Dawson-Hughes,et al.  Vitamin D insufficiency and hyperparathyroidism in a low income, multiracial, elderly population. , 2000, The Journal of clinical endocrinology and metabolism.

[52]  M. Holick,et al.  Decreased bioavailability of vitamin D in obesity. , 2000, The American journal of clinical nutrition.

[53]  A. Dusso,et al.  A novel mechanism for skeletal resistance in uremia. , 2000, Kidney international.

[54]  J. Rastad,et al.  Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor. , 2000, Journal of Clinical Endocrinology and Metabolism.

[55]  Md. Hasan Raza Ansari,et al.  Effect of vitamin D nutrition on parathyroid adenoma weight: pathogenetic and clinical implications. , 2000, The Journal of clinical endocrinology and metabolism.

[56]  D. Dempster,et al.  The effects of vitamin D insufficiency in patients with primary hyperparathyroidism. , 1999, The American journal of medicine.

[57]  H. Jüppner,et al.  A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: implications for PTH measurements in renal failure. , 1999, The Journal of clinical endocrinology and metabolism.

[58]  E. Siris,et al.  A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. , 1999, The New England journal of medicine.

[59]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[60]  J. Coresh,et al.  Serum creatinine levels in the US population: third National Health and Nutrition Examination Survey. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[61]  C. Lazure,et al.  A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples. , 1998, Clinical chemistry.

[62]  M. Holick,et al.  Redefining vitamin D insufficiency , 1998, The Lancet.

[63]  J. Gallagher,et al.  Dietary calcium and vitamin D intake in elderly women: effect on serum parathyroid hormone and vitamin D metabolites. , 1998, The American journal of clinical nutrition.

[64]  E. Gunter,et al.  Hypovitaminosis D in medical inpatients. , 1998, The New England journal of medicine.

[65]  G E Dallal,et al.  Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. , 1997, The New England journal of medicine.

[66]  P. Galan,et al.  Prevalence of Vitamin D Insufficiency in an Adult Normal Population , 1997, Osteoporosis International.

[67]  R. Vieth,et al.  Seasonal Prevalence of Vitamin D Deficiency in Institutionalized Older Adults , 1997, Journal of the American Geriatrics Society.

[68]  B. Dawson-Hughes,et al.  Plasma calcidiol, season, and serum parathyroid hormone concentrations in healthy elderly men and women. , 1997, The American journal of clinical nutrition.

[69]  R. Lepage,et al.  Carboxyl-terminal fragments of parathyroid hormone are not secreted preferentially in primary hyperparathyroidism as they are in other hypercalcemic conditions. , 1993, The Journal of clinical endocrinology and metabolism.

[70]  R. Freaney,et al.  Secondary hyperparathyroidism in elderly people: combined effect of renal insufficiency and vitamin D deficiency. , 1993, The American journal of clinical nutrition.

[71]  F Duboeuf,et al.  Vitamin D3 and calcium to prevent hip fractures in elderly women. , 1992, The New England journal of medicine.

[72]  Bernard F. King,et al.  Role of ultrasound in medical management of patients with renal stone disease , 1992, Urologic radiology.

[73]  M. H. Gault,et al.  Predicting glomerular function from adjusted serum creatinine. , 1992, Nephron.

[74]  A. Toi,et al.  The evaluation of suspected renal colic: ultrasound scan versus excretory urography. , 1989, Annals of emergency medicine.

[75]  P. Delmas,et al.  The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. , 1988, The Journal of clinical endocrinology and metabolism.

[76]  P. Adams,et al.  Metabolic inactivation of vitamin D is enhanced in primary hyperparathyroidism. , 1987, Clinical science.

[77]  Brennan,et al.  Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. , 1987, Clinical chemistry.

[78]  S. Epstein,et al.  Evidence for alteration of the vitamin D-endocrine system in obese subjects. , 1985, The Journal of clinical investigation.

[79]  M. H. Gault,et al.  Prediction of creatinine clearance from serum creatinine. , 1975, Nephron.

[80]  S. Stanbury,et al.  Parathyroid function in human vitamin D deficiency and vitamin D deficiency in primary hyperparathyroidism. , 1974, The American journal of medicine.