Context Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD... Show moreContext Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic disorder. Incidence and prevalence are not well-studied. Epidemiological research is complicated by the rarity of FD/MAS, absence of registries, heterogeneous presentation, and possibly asymptomatic phenotype. FD/MAS may present with FGF23-mediated hypophosphatemia, of which the epidemiology is also unclear.Objective Evaluate incidence and prevalence of FD/MAS and FD/MAS-related hypophosphatemia.Methods This cohort study based on the nationwide Danish National Patient Registry from 1995-2018, included patients identified by ICD-10 codes M85.0 (monostotic FD [MFD]) and Q78.1 (polyostotic FD [PFD]/MAS). Incidence rates and prevalence were calculated and stratified by sex, age, calendar period, and diagnosis code. Cases were screened for FD-associated hypophosphatemia by diagnosis code E.83 (disorder of mineral metabolism) and dispatched vitamin D analogues.Results A total of 408 patients were identified, 269 with MFD (66%), 139 with PFD/MAS (34%), comparable between sexes. Incidence of FD/MAS demonstrated increasing secular trend with a rate of 3.6 per 1 000 000 person-years (95% CI: 2.9, 4.5) in 2015-2018. Incidence peaked between age 11 and 20. Prevalence of FD/MAS increased over time to 61.0 (95% CI: 54.6, 67.4) per 1 000 000 persons in 2018. The incidence rate of MFD was 1.5-fold that of PFD/MAS in the first decade, rising to 2.5-fold in the last decade. No FD/MAS cases were registered with diagnosis code or treatment for hypophosphatemia.Conclusion FD/MAS is rare, diagnosis peaks during adolescence without sex predominance, and MFD is most prevalent. Hypophosphatemia may be underdiagnosed and undertreated, or it may be underregistered, comparing this study to literature. Show less
This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and... Show moreThis European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders in 2019 were discussed during two virtual workshops in 2021 and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosis of familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represents areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborn children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed at a broader clinical audience and were developed with the focus on endocrinologists in training. Show less
Mantovani, G.; Bastepe, M.; Monk, D.; Sanctis, L. de; Thiele, S.; Ahmed, S.F.; ... ; Linglart, A. 2020
Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity,... Show morePatients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care. Show less
Endocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the... Show moreEndocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the management of commonly encountered calcium metabolic problems and osteoporosis. Non-urgent elective appointments should be postponed, and remote consultations and digital health solutions promoted. Patients should be empowered to self-manage their conditions safely. Patients, their caregivers and healthcare providers should be directed to assured national or international online resources and specific patient groups. For patients in acute hospital settings, existing emergency guidance on the management of hyper- and hypo-calcaemia should be followed. An approach to osteoporosis management is outlined. IV zoledronic acid infusions can be delayed for 6-9 months during the pandemic. Patients established on denosumab, teriparatide and abaloparatide should continue planned therapy. In the event of supply issues with teriparatide or abaloparatide, pausing this treatment in the short term is likely to be relatively harmless, whereas delaying denosumab may cause an immediate increased risk of fracture. The challenge of this pandemic will act as a catalyst to innovate within our management of metabolic bone and mineral disorders to ensure best use of resources and resilience of healthcare systems in its aftermath. Show less
PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including... Show morePARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including parathyroid cancer (PC), and hypoparathyroidism (HypoPT). The discussions and consensus statements from the first PARAT workshop (September 2018) are reviewed. PHPT has a high prevalence in Western communities, yet evidence is sparse concerning the natural history and whether morbidity and long-term outcomes are related to hypercalcemia or plasma PTH concentrations or both. Cardiovascular mortality and prevalence of low energy fractures are increased, whereas quality of life is decreased, although their reversibility by treatment of PHPT has not been convincingly demonstrated. PC is a rare cause of PHPT, with increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity and optimal treatments. For example, similar to 20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized care, such as different forms of immunotherapy or targeted therapy. HypoPT, a designated orphan disease, is associated with a high risk of symptoms and complications. Most cases are secondary to neck surgery. However, there is a need to better understand the relation between disease biomarkers and intellectual function and to establish the role of PTH in target tissues, as these may facilitate the appropriate use of PTH substitution therapy. Management of parathyroid disorders is challenging, and PARAT has highlighted the need for international transdisciplinary scientific and educational studies in advancing in this field. Show less
Mantovani, G.; Bastepe, M.; Monk, D.; Sanctis, L. de; Thiele, S.; Usardi, A.; ... ; Linglart, A. 2018
This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders... Show moreThis Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders. Show less
Mantovani, G.; Bastepe, M.; Monk, D.; Sanctis, L.; Thiele, S.; Usardi, A.; ... ; Linglart, A. 2018
