Evaluation and management of primary hyperparathyroidism: summary statement and guidelines from the fifth international workshop

The last international guidelines on the evaluation and management of primary hyperparathyroidism (PHPT) were published in 2014. Research since that time has led to new insights into epidemiology, pathophysiology, diagnosis, measurements, genetics, outcomes, presentations, new imaging modalities, target and other organ systems, pregnancy, evaluation, and management. Advances in all these areas are demonstrated by the reference list in which the majority of listings were published after the last set of guidelines. It was thus, timely to convene an international group of over 50 experts to review these advances in our knowledge. Four Task Forces considered: 1. Epidemiology, Pathophysiology, and Genetics; 2. Classical and Nonclassical Features; 3. Surgical Aspects; and 4. Management. For Task Force 4 on the Management of PHPT, Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology addressed surgical management of asymptomatic PHPT and non-surgical medical management of PHPT. The findings of this systematic review that applied GRADE methods to randomized trials are published as part of this series. Task Force 4 also reviewed a much larger body of new knowledge from observations studies that did not specifically fit the criteria of GRADE methodology. The full reports of these 4 Task Forces immediately follow this summary statement. Distilling the essence of all deliberations of all Task Force reports and Methodological reviews, we offer, in this summary statement, evidence-based recommendations and guidelines for the evaluation and management of PHPT. Different from the conclusions of the last workshop, these deliberations have led to revisions of renal guidelines and more evidence for the other recommendations. The accompanying papers present an in-depth discussion of topics summarized in this report. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Hyperparathyroidism: Time to reconsider current clinical decision paradigms?

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Strontium Ranelate - A Novel Therapy for Osteoporosis or a Permutation of the Same?

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Calcium and bone disorders during pregnancy and lactation

Studies of pregnant women indicate that the fetal calcium demand is met largely by intestinal calcium absorption, which from early pregnancy onward more than doubles. The studies of biochemical markers of bone turnover, DXA, and ultrasound are inconclusive, but suggest that the maternal skeleton also contributes calcium to the developing fetus. In contrast, during lactation, skeletal calcium resorption is the dominant mechanism by which calcium is supplied to the breast milk; renal calcium conservation is also apparent. Lactation produces an obligatory skeletal calcium loss regardless of maternal calcium intake, but the calcium is completely restored to the skeleton after weaning through mechanisms that are not understood. The adaptations during pregnancy and lactation lead to novel presentations and management issues for known disorders of calcium and bone metabolism, such as primary hyperparathyroidism, hypoparathyroidism, and vitamin D deficiency. Finally, although some women experience fragility fractures as a consequence of pregnancy or lactation, in most women the changes in calcium and bone metabolism during pregnancy and lactation are normal and without adverse consequences in the long-term. © 2005 Elsevier Inc. 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Dermatologic manifestations of parathyroid-related disorders

Dermatologic manifestations of parathyroid-related disorders, although rare in sporadic cases, are not uncommon in familial syndromes. Patients with familial hyperparathyroidism have several types of skin lesions. In multiple endocrine neoplasia 1, patients commonly have angiofibromas (85percent) and collagenomas (70percent), lesions that show loss of one 11q13 allele, the molecular abnormality in multiple endocrine neoplasia 1. They can also present with lipomas or café-au-lait spots. Cutaneous amyloidosis, an entity that can occur sporadically, has been described in multiple endocrine neoplasia 2a and is usually localized to the interscapular area. Metastatic calcification is an entity commonly encountered in patients with hyperparathyroidism and renal failure. It can be complicated by infections and necrosis. It is best treated by controlling hypercalcemia, hyperphosphatemia, hyperparathyroidism, antibiotics, and analgesia. Parathyroidectomy is reserved for refractory cases. Hypoparathyroidism presenting in the context of polyglandular failure type 1 is characterized by mucocutaneous candidiasis. Pseudohypoparathyroidism, an inherited disorder with end-organ unresponsiveness to parathyroid hormone, is characterized by Albright hereditary osteodystrophy. Patients present with short stature, round facies, brachydactyly, and short fourth or fifth metacarpals. © 2006 Elsevier Inc. All rights reserved.AGUS Z, UPTODATE CD ROM 14 1; AKINSOTO OPA, POLYGLANDULAR AUTOIM; Aksoylar S, 2004, J PEDIATR ENDOCR MET, V17, P1031; ANDREW A, UPTODATE CD ROM 14 1; Angelis M, 1997, SURGERY, V122, P1083, DOI 10.1016-S0039-6060(97)90212-9; ARGAWAL SK, 2004, ANN NY ACAD SCI, V1014, P189; Aslan Y, 1999, TURKISH J PEDIATR, V41, P253; Bilezikian JP, 2005, J INTERN MED, V257, P6, DOI 10.1111-j.1365-2796.2004.01422.x; Bilezikian JP, 2002, J CLIN ENDOCR METAB, V87, P5353, DOI 10.1210-jc.2002-021370; Bittencourt RCA, 2001, J AM ACAD DERMATOL, V45, P731, DOI 10.1067-mjd.2001.116223; BROWN EM, 1995, NEW ENGL J MED, V333, P234; Brucculeri M, 2005, SEMIN DIALYSIS, V18, P431, DOI 10.1111-j.1525-139X.2005.00082.x; CECCHERINI I, 1994, J ENDOCRINOL INVEST, V17, P201; Chou FF, 2000, J AM COLL SURGEONS, V190, P65, DOI 10.1016-S1072-7515(99)00212-4; Cicone JS, 2004, AM J KIDNEY DIS, V43, P1104, DOI 10.1053-j.ajkd.2004.03.018; Dagher Hikmat N, 2002, Endocr Pract, V8, P47; DIAZ R, 1999, HDB PHYSL 7, V3; Eddy MC, 2000, J BONE MINER RES, V15, P2074, DOI 10.1359-jbmr.2000.15.11.2074; FISCHER AH, 1995, HUM PATHOL, V26, P1055, DOI 10.1016-0046-8177(95)90266-X; FULEIHAN GE, UPTODATE CD ROM 14 1; FULEIHAN GE, 2002, PRINCIPLES BONE BIOL, P1031; Gueydan M, 2002, ANN ENDOCRINOL-PARIS, V63, P502; Hafner J, 1998, VASA-J VASCULAR DIS, V27, P137; HAFNER J, 1995, J AM ACAD DERMATOL, V33, P954, DOI 10.1016-0190-9622(95)90286-4; Jabbour SA, 2003, AM J CLIN DERMATOL, V4, P315, DOI 10.2165-00128071-200304050-00003; KIRKPATRICK CH, 1994, J AM ACAD DERMATOL, V31, pS14, DOI 10.1016-S0190-9622(08)81260-1; KRONENBERG HM, 2001, PARATHYROIDS, P17, DOI 10.1016-B978-012098651-4-50004-3; Lee Y, 2005, BRIT J DERMATOL, V152, P591, DOI 10.1111-j.1365-2133.2005.06460.x; LEONHARDT JM, 2003, FITZPATRICKS DERMATO, P1662; Marx SJ, 2005, J INTERN MED, V257, P2, DOI 10.1111-j.1365-2796.2004.01419.x; Mirza I, 2001, ARCH PATHOL LAB MED, V125, P1351; Oh Dennis H., 1999, Journal of the American Academy of Dermatology, V40, P979, DOI 10.1016-S0190-9622(99)70087-3; Pack S, 1998, J INVEST DERMATOL, V110, P438, DOI 10.1046-j.1523-1747.1998.00140.x; PALLER A, 2003, FITZPATRICKS DERMATO, P835; Podymow T, 2001, NEPHROL DIAL TRANSPL, V16, P2176, DOI 10.1093-ndt-16.11.2176; SELYE H, 1962, CALCIPHYLAXIS, P1; Sharma VK, 2004, J EUR ACAD DERMATOL, V18, P641, DOI 10.1111-j.1468-3083.2004.01013.x; STAHLEBACKDAHL M, 1989, J INTERN MED, V225, P411; Tope WD, 2001, LASER SURG MED, V29, P78, DOI 10.1002-lsm.1090; Verga U, 2003, CLIN ENDOCRINOL, V59, P156, DOI 10.1046-j.1365-2265.2003.01782.x; Walsh JS, 2003, FITZPATRICKS DERMATO, P1490; Zouboulis CC, 1996, BRIT J DERMATOL, V135, P617, DOI 10.1111-j.1365-2133.1996.tb03844.x98

Measurement of Parathyroid Hormone

Biologically active parathyroid hormone (PTH) circulates predominantly as an 84 amino acid peptide in humans with normal renal function. However, large aminoterminally truncated PTH(1-84) fragments (ntPTH(1-84)) that are readily detectable with most first generation immunometric PTH assays may also affect bone metabolism and calcium homeostasis. Some of these ntPTH(1-84) fragments exhibit an elution profile on high performance liquid chromatography (HPLC), which is indistinguishable from that of synthetic PTH(7-84). This hormonal fragment was recently shown through in vitro experiments to be the predominant form of PTH secreted by the parathyroid glands. Furthermore, it appears to have hypocalcemic properties in vivo and to inhibit ostoclastic bone resorption and the formation of mature ostoclasts in vitro. At present, it is uncertain whether important differences in disease states can be revealed by comparing results obtained with first generation immunometric assays (detection of PTH(1-84) and ntPTH(1-84)) with those obtained with newer, second generation assays (detection of PTH(1-84) alone). While most immunometric PTH assay systems are appropriate for the diagnosis of primary hyperparathyroidism, it appears plausible that immunometric assays designed to detect only PTH(1-84) will be more useful for certain diagnostic studies, that is, for monitoring PTH concentrations intra-operatively and for assessing the pulsatility of PTH secretion. In addition, the ability to distinguish between the relative concentrations of ntPTH(1-84) and PTH(1-84) may reveal previously unsuspected biological roles of ntPTH(1-84) fragments in patients with end stage renal disease and-or other disorders involving PTH. © 2006 Elsevier Inc. All rights reserved.

Endocrine and musculoskeletal abnormalities in patients with Down syndrome

Down syndrome has a prevalence of one in 500 to one in 1,000 live births and is the most common cause of mental retardation. Most patients are treated in childhood and adolescence for mental or growth retardation. Studies that evaluate bone mass in Down syndrome are limited, and many are small case series in pediatric and adult populations who live either in the community or in residential institutions. Several environmental and hormonal factors contribute to low bone mineral density in such patients. Muscle hypotonia, low amounts of physical activity, poor calcium and vitamin D intakes, hypogonadism, growth retardation and thyroid dysfunction contribute to substantial impairments in skeletal maturation and bone-mass accrual that predispose these patients to fragility fractures. Here, we review indications and limitations of bone-mass measurements in children, summarize the endocrine and skeletal abnormalities in patients presenting with Down syndrome, and review studies that investigate therapeutic strategies for such patients. © 2009 Macmillan Publishers Limited. 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Vitamin D: A growing perspective

Vitamin D deficiency has been widely reported in all age groups in recent years. Rickets has never been eradicated in developed countries, and it most commonly affects children from recent immigrant groups. There is much evidence that current vitamin D guidelines for the neonatal period, 5-10 μ g (200-400 IU)-day, prevent rickets at the typical calcium intakes in developed countries. The annual incidence of vitamin D-deficiency rickets in developed countries ranges between 2.9 and 7.5 cases per 100,000 children. The prevalence of vitamin D deficiency in mothers and their neonates is remarkable, and the results of one study suggest that third-trimester 25-hydroxyvitamin D (25(OH)D) is associated with fetal bone mineral accrual that may affect prepubertal bone mass accumulation. Beyond infancy, the evidence indicates that 5 μ g (200 IU)-day of vitamin D has little effect on vitamin D status as measured by the serum 25(OH)D concentration. Two randomized clinical trials show that higher vitamin D intake improves one-year gain in bone density in adolescent girls. The functions of vitamin D extend beyond bone to include immune system regulation and anti-proliferative effects on cells. Early life vitamin D inadequacy is implicated in the risk of bone disease, autoimmune disease, and certain cancers later in life; however, long-term interventional studies do not exist to validate the widespread implementation of greater vitamin D consumption. Here we review the available data concerning vitamin D status and health effects of vitamin D in pregnancy through to and including adolescence. 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Vitamin D in endometriosis: A causative or confounding factor?

Objective The aim of this paper is to review the evidence from studies that evaluated the relationship between vitamin D and endometriosis. Design Comprehensive review. Materials and Methods Systematic literature search in Medline for relevant publications from 1946 until June 2013. Results Endometriosis risk may be influenced by dietary vitamin D intake and plasma hydroxyvitamin D concentration. Vitamin D receptor and vitamin D metabolizing enzymes, 24-hydroxylase and 1-α hydroxylase, are found in the normal cycling endometrium and also in the eutopic and ectopic endometrium of women with endometriosis. The endometrium is a target of 1, 25 dihydroxyvitamin D actions through regulation of specific genes and via immunomodulation. The endometrium in endometriosis expresses dysregulation of some vitamin D enzymes and receptors. If vitamin D and its metabolites are implicated in endometriosis-associated infertility, it is likely through interference with HOXA10 gene expression. The Gc2 phenotype of vitamin D binding protein is prevalent in women with endometriosis and may be implicated in its pathogenesis. In a mouse model, Elocalcitol, a VDR-agonist was shown to reduce the development of endometriotic lesions and recurrence. Conclusion A biological plausibility for a role of vitamin D, as an immunomodulator and anti-inflammatory agent, in the pathogenesis and treatment of endometriosis is suggested in this article, but is difficult to illustrate due to sparse evidence from human studies limited primarily to case-control studies. A significant knowledge gap precludes the establishment of a clear cause-effect relationship. 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Geographic and ethnic disparities in osteoporotic fractures

Osteoporotic fractures are a major worldwide epidemic. Here, we review global variability, ethnic differences and secular changes in osteoporotic fractures. Worldwide, age-standardized incidence rates of hip fracture vary 200-fold in women and 140-fold in men when comparing the country in which incidence rates are the highest with that in which they are the lowest. Median age-standardized rates are highest in North America and Europe, followed by Asia, Middle East, Oceania, Latin America and Africa. Globally, rates of hip fracture are greater in women than in men, with an average ratio of 1-42:1. The incidence of radiographic vertebral fractures is much higher than that of hip fractures, whereas the incidence rates of clinical vertebral fractures mirror hip fracture rates in most countries. Methodological challenges of defining and ascertaining vertebral fractures limit the interpretation of these data. Secular declines in hip fracture rates have been reported in populations from North America, Europe and Oceania. These declines are especially notable in women, suggesting that reproductive factors might contribute to this reduction. By contrast, hip fracture rates are increasing in parts of Asia and Latin America. Global indicators of health, education and socioeconomic status are positively correlated with fracture rates suggesting that lifestyles in developed countries might contribute to hip fracture. Improvements in fracture assessment, in particular for nonhip fractures, and identification of factors that contribute to this variability might substantially influence our understanding of osteoporotic fracture aetiology and provide new avenues for prevention. © 2014 Macmillan Publishers Limited. 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