Rare diseases of phosphate and calcium metabolism: Crossing glances between nephrology and endocrinology.

Rare diseases of phosphate/calcium metabolism correspond to a wide and heterogeneous spectrum of diseases. Recent knowledge in physiology and genetics has made it possible to better characterize them and to propose attractive therapeutic approaches based on the underlying pathophysiology. These diseases are often at the interface between nephrology and endocrinology. In this spirit of a multidisciplinary care, each specialty can bring its own critical point of view and its own specificities to improve patient care. The objective of this manuscript is to "read" with a nephrologist's point of view the main frameworks of diseases of phosphate/calcium metabolism, to illustrate the three crucial messages of nephro-protection sent to endocrinologists. First, calciuria must be interpreted both in absolute value (concentration hypercalciuria) and in ratio (flow hypercalciuria). Second, renal monitoring of therapies inducing hypercalciuria on kidneys with normal renal function (e.g. active vitamin D analogs or teriparatide) should be systematic. Last, hyperphosphatemia, often latent in hypoparathyroidism and pseudo-hypoparathyroidism, should be detected and at least benefit from dietary measures, in the context of Western diets rich in phosphate hidden in food additives.

ENDOCRINOLOGY IN THE TIME OF COVID-19: Management of calcium metabolic disorders and osteoporosis.

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 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.

Calcium Metabolic Disorders in Pregnancy: Primary Hyperparathyroidism, Pregnancy-Induced Osteoporosis, and Vitamin D Deficiency in Pregnancy.

Physiologic changes during pregnancy include calcium, phosphate, and calciotropic hormone status. Calcium metabolic disorders are rare in pregnancy and management with close calcium and vitamin D control and supplementation. Primary hyperparathyroidism is mostly asymptomatic and does not affect conception or pregnancy. It requires control of plasma calcium levels. Surgical intervention may be indicated. Data on severe cases are missing. Osteoporosis in or before pregnancy is rare but usually diagnosed from fractures. Medical treatment other than supplementation is contraindicated. Vitamin D deficiency is common and may affect conception and increase complications. Current evidence does not prove vitamin D supplements effective in improving outcomes.

Impacts of parathyroidectomy on calcium and phosphorus metabolism disorder, arterial calcification and arterial stiffness in haemodialysis patients.

BACKGROUND: Secondary hyperparathyroidism (SHPT) and calcium and phosphorus metabolism disorder are important complications in haemodialysis patients. Parathyroidectomy (PTX) may prevent or delay the progress of vascular calcification in haemodialysis patients. OBJECTIVE: To investigate the impacts of PTX on calcium and phosphorus metabolism, arterial calcification and arterial stiffness in haemodialysis patients with SHPT. METHODS: Twenty-one SHPT-haemodialysis patients were selected for PTX. The preoperative and postoperative 1-year scores of coronary artery calcification were measured via multislice spiral CT, along with the brachial-ankle pulse wave velocity (baPWV), and preoperative and postoperative 1-year indexes such as calcium, phosphorus, calcium-phosphorus product concentration and parathyroid hormone (PTH) level were compared. RESULTS: Compared with the preoperative score, the postoperative 1-year coronary artery calcification score was significantly reduced; the mean baPWVs of the bilateral limbs were reduced; and the levels of serum calcium, phosphorus, calcium-phosphorus product concentration and PTH were all reduced; all differences were statistically significant (P < 0.05). CONCLUSIONS: PTX can be used to correct calcium and phosphorus metabolism disorder, reduce arterial calcification, and improve arterial stiffness.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder.

Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder / Reversão da calcinose tumoral urêmica pela otimização do tratamento clínico da desordem do metabolismo ósseo e mineral

Abstract Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Resumo A calcinose tumoral é um tipo raro de calcificação extraóssea caracterizada por grandes massas císticas e elásticas contendo depósitos de fosfato de cálcio. A condição é mais prevalente no tecido periarticular e preserva estruturas osteoarticulares. A elevação do produtos cálcio-fósforo e o hiperparatireoidismo secundário grave estão presentes na maioria dos pacientes com calcinose tumoral urêmica (UTC). O relato de caso em questão refere-se a um homem de 22 anos, branco, obeso, com doença renal crônica secundária à glomerulonefrite crônica, em diálise peritoneal ambulatorial contínua (CAPD), que apresentou aparecimento de tumores indolores na face medial do quinto quirodáctilio e braço esquerdo. A calcinose tumoral foi confirmada por biópsia do bíceps esquerdo. O paciente apresentava baixa adesão à CAPD. Foi transferido para a modalidade de diálise peritoneal e depois iniciou tratamento por hemodiálise. Apesar da persistência do hiperparatireoidismo grave, houve redução progressiva da UTC, com resolução próxima do seu desaparecimento completo. Há 1 ano o paciente foi submetido a transplante renal, doador falecido, e apresentou melhora do hiperparatiroidismo secundário. A UTC deve ser incluída na elucidação de calcificação periarticular de pacientes em diálise. Os achados laboratoriais relevantes, tais como hiperparatiroidismo secundário e elevação dos produtos cálcio-fósforo na presença de calcificação periarticular, devem chamar a atenção para o diagnóstico da UTC.

[Cognitive Function and Calcium. The link between dementia and bone and calcium metabolism disorders].

Bone and calcium metabolism disorders are closely linked with dementia. Screening for dementia is important since chronic hypercalcemia and hypocalcemia resulting from parathyroid function abnormalities can become a cause of dementia onset. In recent years, it has become clear that vitamin D deficiencies inducing cardiovascular disease and other factors are involved in the pathogenesis of various diseases that in turn become risk factors in dementia, especially Alzheimer's disease. Moreover, osteoporosis and dementia both commonly occur among the elderly. Treating dementia patients for osteoporosis is important since fragility fractures, especially femoral neck fractures, resulting from osteoporosis greatly affect the prognosis of patients with dementia.

Synthesis and characterization of collagen/hydroxyapatite: magnetite composite material for bone cancer treatment.

Our purpose was obtaining and characterizing a complex composite system with multifunctional role: bone graft material and hyperthermia generator necessary for bone cancer therapy. The designed system was a magnetite enriched collagen/hydroxyapatite composite material, obtained by a co-precipitation method. Due to the applied electromagnetic field the magnetite will induce hyperthermia and cause tumoral cell apoptosis. The complex bone graft system was characterised by XRD, FTIR and SEM, while the hyperthermia was quantify by measuring the temperature increase due to the applied alternative electromagnetical field.

[Fahr's syndrome: two case report]. / Syndrome de Fahr: à propos de deux cas.

INTRODUCTION: Fahr's syndrome is characterized by symmetrical and bilateral intracerebral calcifications, located in the basal ganglia and mostly associated with a phosphorus calcium metabolism disorder. It must be distinguished from genetic or sporadic Fahr's disease. OBSERVATIONS: We report two cases of this syndrome, the first was revealed by psychotic and cognitive disorders and the other by epilepsy. In both cases, brain imaging and biology resulted in the diagnosis of Fahr's syndrome. The outcome was favorable after treatment in both cases. CONCLUSION: These two observations illustrate various clinical signs of Fahr's syndrome.

Management of neonatal endocrinopathies--best practice guidelines.

Neonatal emergencies are uncommon, but may lead to significant morbidity and mortality if not recognised and managed promptly. Disorders of sex development, hypoglycaemia, thyrotoxicosis and calcium balance are discussed, with emphasis on the clinical assessment, investigations and management of these disorders in the acute setting.

Disorders of calcium metabolism.

Hypocalcaemia not associated with hypoalbuminaemia or 25(OH)-Vitamin D deficiency is rare and should be referred to a specialist clinic. 25(OH)-Vitamin D deficiency can often be treated safely by GPs, unless it is associated with renal impairment and secondary hyperparathyroidism, in which case a nephrology referral is required. An endocrine referral is required if deficiency is associated with pregnancy, co-existent primary hyperparathyroidism or the patient is receiving warfarin. The key role of the GP in managing hypercalcaemia is to distinguish between malignant and parathyroid causes in order to make the appropriate specialist referral (oncology, endocrine or renal). Severe hypercalcaemia (greater than 3.5 mmol/L or hypercalcaemia with dehydration, abdominal pain or reduced consciousness is a medical emergency.

Role of calcium-sensing receptor in mineral ion metabolism and inherited disorders of calcium-sensing.

The extracellular calcium-sensing receptor (CaR), a G protein-coupled receptor that resides on the parathyroid cell surface negatively regulates secretion of parathyroid hormone (PTH). The CaR is functionally expressed in bone, kidney, and gut--the three major calcium-translocating organs involved in calcium homeostasis. Further studies are needed to define fully the homeostatic roles of the CaR in tissues that are involved in systemic extracellular calcium [Ca(2+)](o) homeostasis. The role of the CaR in regulating calcium metabolism has been greatly clarified by the identification and studies of genetically determined disorders that either activate or inactivate the receptor. Antibodies to the CaR that either activate or inactivate it produce syndromes resembling the corresponding genetic diseases. Expression of the CaR is significantly reduced in primary and secondary hyperparathyroidism, which could contribute to the defective [Ca(2+)](o)-sensing in these conditions. Calcimimetics act as CaR agonists or allosteric activators and thereby potentiate the effects of [Ca(2+)](o) on parathyroid cell function. This kind of pharmacological manipulation of the CaR is now used for the treatment of hyperparathyroid states, whereby the calcimimetics increase the activation of the CaR at any given level of extracellular calcium. Calcimimetics are also an effective element in the treatment of secondary hyperparathyroidism, particularly in dialysis patients, by virtue of reducing plasma levels of PTH, calcium and phosphate.

Medical evaluation and treatment of urolithiasis.

Nephrolithiasis is responsible for 1 in 1000 to 1 in 7600 pediatric hospital admissions annually throughout the United States. Seventy-five percent of children with nephrolithiasis have an identifiable predisposition to stone formation. This article reviews the different causes and disease states associated with nephrolithiasis in the pediatric population. The initial evaluation and the metabolic evaluation of children with nephrolithiasis are reviewed. Treatment modalities for the different stone types are also described.

[Changes of control of disorders of calcium and phosphorus metabolism in Lithuanian hemodialysis centers 1996-2003]. / Kalcio ir fosforo apykaitos sutrikimu kontroles pokyciai Lietuvos hemodializes centruose 1996-2003 m.

The aim of the study was to evaluate the changes of the rate of disorders of calcium and phosphorus metabolism and their control in patients on hemodialysis (HD) in Lithuania in 1996-2003. Every December during this period we visited all HD centers of Lithuania and collected data on calcium-phosphorus metabolism in HD patients. 51.8% of HD patients in 1999 and 44.6% in 2003 had hyperphosphatemia (>1.8 mmol/l) (p<0.05). The mean phosphate concentration was 1.82+/-0.56 mmol/l in 2003 (p<0.05, comparing with 1.95+/-0.72 mmol/l in 1999 and 1.9+/-0.72 mmol/l in 2001). 7.1% of HD patients had hypocalcemia in 2003 and 7.8% hypercalcemia. Serum parathyroid hormone level was investigated only in 27.3% of HD patients in 1999 and 84.8% in 2003 (p<0.05). Use of alfacalcidol significantly decreased from 77.5% in 1998 to 29.4% in 2003, when the evaluation of serum parathyroid hormone increased (r=-0.911, p=0.03). Serum parathyroid hormone level was not analyzed for 59.8% of patients who used alfacalcidol and 59.4% of them had hyperphosphatemia in 1999 (6.3% and 32.9% in 2003, respectively; p<0.05). 10.7% of these patients had hypercalcemia in 2003. In summary, the correction of disorders of calcium and phosphorus metabolism in HD patients was insufficient but ameliorative. Monitoring of serum parathyroid hormone increased significantly during 1997-2003. The percentage of the precarious use of alfacalcidol decreased significantly when the evaluation of serum parathyroid hormone level became regular.

Endocrine disorders in the neonate.

There is a significant amount of knowledge that has been gained in recent years in the study of endocrine disorders in the newborn. The explosion of genetic data shedding light on the origins of endocrine disease has expanded the level of diagnostic evaluation and management of these infants. This article provides a general review of endocrine disorders as they present in a newborn.