Persistent hypercalcaemia associated with two pathogenic variants in the CYP24A1 gene and a parathyroid adenoma-a case report and review.

Introduction: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)2D3. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild. Aim of the study: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases. Case presentation: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively). Conclusions: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.

Management of hypoparathyroidism: a Position Statement of the Expert Group of the Polish Society of Endocrinology.

Over the past few years, there have been significant advances in our understanding of hypoparathyroidism (HypoPT) in terms of its epidemiology, clinical presentation, etiology, and skeletal and renal complications. Moreover, the available treatment options for HypoPT have changed. This position statement of the Expert Group of the Polish Society of Endocrinology summarizes the current state of knowledge and provides recommendations for optimal management to assist clinicians in the diagnosis, treatment, and monitoring of HypoPT in Poland. The specific aspects of HypoPT management in children, pregnant and lactating women, and patients with chronic kidney disease are also discussed. HypoPT is a rare disorder characterized by hypocalcemia and the lack or deficiency of parathyroid hormone (PTH). Hypoparathyroidism can be associated with complications, including nephrocalcinosis, nephrolithiasis, renal insufficiency, cataract, seizures, cardiac arrhythmia, depression, and an increased risk of infection. Minimizing complications of HypoPT requires careful evaluation and close monitoring of laboratory parameters. Conventional management of HypoPT has focused on maintaining serum calcium levels using oral calcium and active vitamin D. However, this approach is limited because it does not restore normal PTH function, is often associated with inadequate biochemical control, and raises concerns as to long-term side effects. HypoPT is the only classic endocrine insufficiency that is not commonly treated with the substitution of the missing hormone. Recently, recombinant human PTH(1-84) has become available, offering hope that the use of the missing hormone in the treatment of HypoPT will help achieve better control and reduce the risk of complications. However, this treatment is currently unavailable in Poland.

Guidelines for the diagnosis and management of osteoporosis in Poland. Update 2022.

Guidelines to provide an update of the previously published Polish recommendations for the management of women and men with osteoporosis have been developed in line with advances in medical knowledge, evidence-based data, and new concepts in diagnostic and therapeutic strategies. A Working Group of experts from the Multidisciplinary Osteoporosis Forum and from the National Institute of Geriatrics, Rheumatology, and Rehabilitation in Warsaw performed a thorough comprehensive review of current relevant publications in the field (including all age groups of people and management of secondary osteoporosis), and they evaluated epidemiological data on osteoporosis in Poland and the existing standards of care and costs. A voting panel of all co-authors assessed and discussed the quality of evidence to formulate 29 specific recommendations and voted independently the strength of each recommendation. This updated practice guidance highlights a new algorithm of the diagnostic and therapeutic procedures for individuals at high and very high fracture risk and presents a spectrum of general management and the use of medication including anabolic therapy. Furthermore, the paper discusses the strategy of primary and secondary fracture prevention, detection of fragility fractures in the population, and points to vital elements for improving management of osteoporosis in Poland.

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

The Effect of a Single High Dose of Vitamin D on Serum Levels of Its Metabolites in the Elderly.

BACKGROUND: Vitamin D is a dietary micronutrient responsible for calcium and phosphorus metabolism and multiple extraskeletal actions. The assessment of vitamin D status is commonly based on measurement of 25(OH)D total concentration in serum. However, the usage of liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique allows to reliably assess a panel of vitamin D metabolites in serum or plasma, which may help to investigate the metabolic paths of vitamin D, especially in populations at risk of deficiency. METHODS: A randomized, two-arms, open study was conducted on 58 patients (28 female and 30 male; aged from 61 to 96 years old). The primary aim was to assess the effects of a single, high, oral dose of vitamin D3 (120,000 IU) on serum 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, 3-epi-25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3/25(OH)D3 ratio, and 25(OH)D3/3-epi-25(OH)D3 ratio concentration (measured by LC-MS/MS) at baseline, 3 days and 7 days after administration, compared to control group. The secondary aim was assessment of influence of percentage of fat tissue on serum metabolites of vitamin D and their changes after bolus dose. RESULTS: 56.6% study group attained a serum 25(OH)D3 concentration >30 ng/mL. All subjects, except for one patient achieved a serum 25(OH)D3 concentration >20 ng/mL after administration. No one exceed reference value of vitamin D (30-50 ng/mL). Among participants who received vitamin D3 there were significant increase in 25(OH)D3, 3-epi-25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3 on 3rd day after administration. 24,25(OH)2D3 concentration gradually grew, achieving the highest concentration on 7th day. The percentage increase of 25(OH)D3 was negatively correlated with baseline 25(OH)D3 (r = -0.688, p = 0.001). Positive correlation between percentage increase in 25(OH)D3 and a percentage increase serum concentration of 24,25(OH)2D3 (r = 0.954, p < 0.001), 3-epi-25(OH)D3 (r = 8.03, p < 0.001) and 1,25(OH)2D3 (r = 0.789, p <0.001) were found. None of the study participants developed hypercalcemia. The baseline concentration of analyzed metabolites of vitamin D in serum and their percentage increase were neither dependent on BMI nor percentage of fat tissue. CONCLUSIONS: High dose of vitamin D rapidly increases 25(OH)D3 concentration in the elderly patients. The response to the bolus of vitamin D includes activation of 3-epimerase, followed by production of 24,25(OH)2D3, which protects from excessive increase of active form of vitamin D.

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature.

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin D hormone calcitriol and may thus particularly trigger hypercalcemia in affected patients. We present a case report and a narrative review of pregnant women with CYP24A1 mutations (13 women with 29 pregnancies) outlining the laboratory and clinical characteristics during pregnancy and postpartum and the applied treatment approaches. In general, pregnancy triggered hypercalcemia in the affected women and obstetric complications were frequently reported. Conclusions on drugs to treat hypercalcemia during pregnancy are extremely limited and do not show clear evidence of efficacy. Strictly avoiding vitamin D supplementation seems to be effective in preventing or reducing the degree of hypercalcemia. Our case of a 24-year-old woman who presented with hypercalcemia in the 24th gestational week delivered a healthy baby and hypercalcemia resolved while breastfeeding. Pathogenic mutations of CYP24A1 mutations are rare but should be considered in the context of vitamin D supplementation during pregnancy.

Osteitis Fibrosa Cystica.

Osteitis fibrosa cystica is a rare presentation of both primary and secondary hyperparathyroidism. In this perspective, we provide a historical backdrop to this form of parathyroid disease and contend that this clinical presentation of excess parathyroid hormone, particularly in primary hyperparathyroidism, is still seen today. In view of its rarity and the way it typically presents, the diagnosis of metastatic cancer is often the first diagnostic impression. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Vitamin D supplementation guidelines.

Research carried out during the past two-decades extended the understanding of actions of vitamin D, from regulating calcium and phosphate absorption and bone metabolism to many pleiotropic actions in organs and tissues in the body. Most observational and ecological studies report association of higher serum 25-hydroxyvitamin D [25(OH)D] concentrations with improved outcomes for several chronic, communicable and non-communicable diseases. Consequently, numerous agencies and scientific organizations have developed recommendations for vitamin D supplementation and guidance on optimal serum 25(OH)D concentrations. The bone-centric guidelines recommend a target 25(OH)D concentration of 20ng/mL (50nmol/L), and age-dependent daily vitamin D doses of 400-800IU. The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30ng/mL (75nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses ranging between 400 and 2000IU/day. The wise and balanced choice of the recommendations to follow depends on one's individual health outcome concerns, age, body weight, latitude of residence, dietary and cultural habits, making the regional or nationwide guidelines more applicable in clinical practice. While natural sources of vitamin D can raise 25(OH)D concentrations, relative to dietary preferences and latitude of residence, in the context of general population, these sources are regarded ineffective to maintain the year-round 25(OH)D concentrations in the range of 30-50ng/mL (75-125nmol/L). Vitamin D self-administration related adverse effects, such as hypercalcemia and hypercalciuria are rare, and usually result from taking extremely high doses of vitamin D for a prolonged time.

Guidelines for the diagnosis and management of osteoporosis in Poland : Update 2017.

In the rapidly ageing society in Poland, osteoporosis is a growing epidemiological problem, and osteoporosis-related fractures are a cause of chronic disability and considerable increase of death risk. It turns out that 80 to 90% of patients suffering from osteoporosis, including osteoporosis accompanied by fractures, do not receive adequate pharmacotherapy. In this paper, a Guideline Working Group of experts from the Multidisciplinary Osteoporosis Forum update the existing Polish guidelines concerning the diagnosis and management of osteoporosis (last revised in 2013), taking account of the latest literature, availability and reimbursement of drugs, and current health care organisation. In the revised guidelines, we still postulate that tasks are divided between primary care doctors (stage I) and specialists in osteoporosis management (stage II). We emphasise the necessity of early initiation of pharmacotherapy and rehabilitation in all patients with low-energy fractures. We recommend that the 10-year fracture risk should be estimated in all patients (including those without fractures) who are over 50 years of age, and that the Polish threshold for therapeutic intervention should be adopted: ≥ 10% for FRAX PL calculator. We add strategies of drug choice and therapy monitoring with imaging, and densitometric and biochemical diagnostics. We define basic guidelines concerning prevention of falls, rehabilitation, and dietary procedures, and elimination of environmental and other fracture risk factors. We point to two vital elements for improving osteoporosis management: 1) strategy of supervision over fractures management - Fracture Liaison Service (FLS), and, optimally, 2) strategies of short-term monitoring of the therapeutic efficacy with the use of biochemical markers.

Osteitis fibrosa cystica-a forgotten radiological feature of primary hyperparathyroidism.

Although bone disease and stone disease are the universally accepted classical manifestations of primary hyperparathyroidism, clinical parathyroid bone disease is rarely seen today in the United States (<5% of patients) and Western Europe. Nevertheless, in a given patient, classical skeletal involvement can be the first sign of primary hyperparathyroidism, but not recognized because it is not usually included, anymore, in the differential diagnosis of this manifestation of skeletal disease. We describe four cases of primary hyperparathyroidism in which the first clinical manifestation of the disease was a pathological fracture that masqueraded as a malignancy. The presence of large osteolytic lesions gave rise to the initial diagnosis of a primary or metastatic cancer. In none of the reported cases was primary hyperparathyroidism with osteitis fibrosa considered as the diagnosis. It would seem to us that this course is best explained by the fact that in many countries such manifestations of primary hyperparathyroidism have become a rarity. In fact, the incidence of osteitis fibrosa among patients with primary hyperparathyroidism in the US is estimated as so rare, that in majority of medical centers routine x-ray examinations of the bones in these patients is not recommended. The X-ray or computed tomography scan findings of osteitis fibrosa cystica include lytic or multilobular cystic changes. Multiple bony lesions representing brown tumors may be misdiagnosed on computed tomography scan as metastatic carcinoma, bone cysts, osteosarcoma, and especially giant-cell tumor. Distinguishing between primary hyperparathyroidism and malignancy is made readily by the concomitant measurement of parathyroid hormone which in primary hyperparathyroidism, again, will be markedly elevated. In the hypercalcemias of malignancy, such elevations of parathyroid hormone are virtually never seen. CONCLUSION: When radiographic evidence of a lytic lesion and hypercalcemia are present, primary hyperparathyroidism should always be considered in the differential diagnosis.

Osteoporosis in men.

Osteoporotic fractures are the leading cause of morbidity and mortality among aging men. 30% of all hip fractures occur in men, and mortality resulting from not only the hip fracture, but also the spine and other major osteoporotic fractures, is significantly higher in men than in women. As in women, hypogonadism is the best documented risk factor for developing osteoporosis in men. In older men, testosterone levels are negatively correlated with the risk of fractures, and it seems that this age-related testosterone deficiency should not be considered as one of the many causes of secondary osteoporosis, rather one of the major and most important mechanisms of senile osteoporosis. Acute hypogonadism induced by ablation treatment for prostate cancer (surgical or pharmacological castration, antiandrogen therapy) is associated with an extremely high risk of fracture. Other documented causes of bone loss in men are cigarette smoking and alcohol abuse, and a number of diseases that require corticosteroid treatment. Pharmacotherapy of osteoporosis should be recommended to all men with a diagnosed osteoporotic fracture and all men with a high 10-year absolute fracture risk (FRAXTM). Not all drugs registered for the treatment of postmenopausal osteoporosis have been registered for the treatment of osteoporosis in men, and others have not been the subject of long-term and costly clinical trials required for such registration. The risk reduction of new fractures was documented only for treatment with zoledronic acid. Risedronate, strontium ranelate, teriparatide, and denosumab in men increase in bone mineral density comparable to that seen in postmenopausal women.

Cinacalcet as symptomatic treatment of hypercalcaemia in primary hyperparathyroidism prior to surgery.

INTRIDUCTION: The aim of presented study was to assess the efficacy of cinacalcet in reducing serum calcium concentrations in primary hyperparathyroid (PHPT) patients with hypercalcaemia exceeding 12.5 mg/dL, awaiting parathyroidectomy. MATERIAL AND METHODS: The study included 23 patients with PHPT with hypercalcaemia > 12.5 mg/dL, qualified for surgery. We recorded clinical and biochemical data at baseline, and after every week of treatment. We also monitored adverse events. Cinacalcet was adminis-tered in increasing doses until the corrected serum calcium concentration was 11.3 mg/dL or less, the patient reached the highest possible dosage of 90 mg four times daily, or the patient experienced an adverse event that precluded further dosage increases. RESULTS: The primary end point of reduction in corrected serum calcium concentration to 11.3 mg/dL was achieved in 19 patients (83%), and normocalcaemia (S-Ca < 10.3 mg/dL) was achieved in 55% of patients. The medication was usually well tolerated (83.4%). Most common adverse events were nausea and vomiting, especially at the beginning of therapy; however, only one patient withdrew from the study because of adverse events. CONCLUSION: Cinacalcet rapidly reduced serum calcium in PHPT patients with severe hypercalcaemia and can be useful as a short-term pretreatment prior to surgery, allowing the completion of diagnostics and safe awaiting for operation.

Cinacalcet normalizes serum calcium in a double-blind randomized, placebo-controlled study in patients with primary hyperparathyroidism with contraindications to surgery.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is diagnosed by the presence of hypercalcemia and elevated or nonsuppressed parathyroid hormone (PTH) levels. Although surgery is usually curative, some individuals fail or are unable or unwilling to undergo parathyroidectomy. In such individuals, targeted medical therapy may be of value. Cinacalcet normalized calcium level and lowered PTH in patients with PHPT in several phase 2 and open-label studies. We compared cinacalcet and placebo in subjects with PHPT unable to undergo parathyroidectomy. DESIGN: Phase 3, double-blind, multi centere, randomized, placebo-controlled study. METHODS: Sixty-seven subjects (78% women) with moderate PHPT were randomized (1:1) to cinacalcet or placebo for ≤28 weeks. MAIN OUTCOME MEASURE: Achievement of a normal mean corrected total serum calcium concentration of ≤10.3 mg/dl (2.575 mmol/l). RESULTS: Baseline median (quartile 1 (Q1), Q3) serum PTH was 164.0 (131.0, 211.0) pg/ml and mean (s.d.) serum Ca was 11.77 (0.46) mg/dl. Serum Ca normalized (≤10.3 mg/dl) in 75.8% of cinacalcet- vs 0% of placebo-treated subjects (P<0.001). Corrected serum Ca decreased by ≥1.0 mg/dl from baseline in 84.8% of cinacalcet- vs 5.9% of placebo-treated subjects (P<0.001). Least squares mean (s.e.m.) plasma PTH change from baseline was -23.80% (4.18%) (cinacalcet) vs -1.01% (4.05%) (placebo) (P<0.001). Similar numbers of subjects in the cinacalcet and placebo groups reported adverse events (AEs) (27 vs 20) and serious AEs (three vs four). Most commonly reported AEs were nausea and muscle spasms. CONCLUSIONS: These results demonstrate that cinacalcet normalizes serum calcium in this PHPT population and appears to be well tolerated.

Denosumab for treatment of hypercalcemia of malignancy.

CONTEXT: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy. OBJECTIVE: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening. INTERVENTION: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients with CSC ≤11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ≤10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study. RESULTS: Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64%) reached CSC ≤11.5 mg/dL, and 12 patients (33%) reached CSC ≤10.8 mg/dL. During the study, 23 patients (70%) reached CSC ≤11.5 mg/dL, and 21 patients (64%) reached CSC ≤10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients, 9%). CONCLUSIONS: In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in 64% of patients within 10 days, inducing durable responses. Denosumab may offer a new treatment option for HCM.

Polish guidelines for the diagnosis and management of osteoporosis: a review of 2013 update.

To decrease the risk of osteoporotic fractures in Poland, the Multidisciplinary Osteoporotic Forum has set up a joint Working Group including the representatives of the Polish Associations of Orthopedics and Traumatology, Rehabilitation, Gerontology, Rheumatology, Family Medicine, Diabetology, Laboratory Diagnostics, Andropause and Menopause, Endocrinology, Radiology, and the STENKO group as well as experts in the fields of rheumatology, obstetrics, and geriatrics to update the Polish guidelines for the diagnosis and management of osteoporosis in men and postmenopausal women in Poland. The assessment of fracture risk and intervention thresholds was made using the FRAX® calculation tool for Poland. The strength of recommendations was evaluated according to the principles of the Scottish Intercollegiate Guidelines Network and the results have been approved by national consultants. Finally, the Working Group has formulated the updated guidelines and recommended two -step diagnostic and therapeutic procedures. The first stage applies to family physicians or general practitioners and involves the assessment of fracture risk using the FRAX®-BMI to identify patients at high risk of fractures. An osteoporotic fracture remains an absolute indication both for the general practitioner and specialist to implement treatment. At the second stage, the specialist (in an osteoporosis or other specialty clinic) should review the primary or secondary causes of fracture risk, confirm the diagnosis, and introduce an appropriate treatment and monitoring. In patients (men aged >50 years and postmenopausal women) without low-energy fractures, the absolute risk of fractures exceeding 10% should be considered an indication for treatment. The Polish guidelines were compared with other international guidelines in terms of diagnostic measures, pharmacotherapy, as well as calcium and vitamin D supplementation.

FGF23 Producing Mesenchymal Tumor.

A 40-year-old patient was referred to Clinic of Endocrinology due to hypophosphatemia causing pain, cramps, and weakness of muscles. Moreover, his bone mineral density was very low. The previous treatment with phosphorus and active vitamin D metabolites was ineffective. In lab tests the hypophosphatemia, hyperphosphaturia, and elevated FGF23 levels were found. Somatostatin receptor scintigraphy (SRS) showed increased radiotracer uptake in the right maxillary sinus and CT scans confirmed presence of tumor in this localization. Biopsy and cytological examination created suspicion of mesenchymal tumor-glomangiopericytoma. Waiting for surgery the patient was treated with long acting Somatostatine analogue, and directly before operation short acting Octreotide and intravenous phosphorus were used. Histology confirmed the cytological diagnosis and the phosphatemia return to normal values in 10 days after the tumor removal.

Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe - recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency.

INTRODUCTION: Adequate Vitamin D intake and its concentration in serum are important for bone health and calcium-phosphate metabolism as well as for optimal function of many organs and tissues. Documented trends in lifestyle, nutritional habits and physical activity appear to be associated with moderate or severe Vitamin D deficits resulting in health problems. Most epidemiological studies suggest that Vitamin D deficiency is prevalent among Central European populations. Concern about this problem led to the organising of a conference focused on overcoming Vitamin D deficiency. METHODS: After reviewing the epidemiological evidence and relevant literature, a Polish multidisciplinary group formulated theses on recommendations for Vitamin D screening and supplementation in the general population. These theses were subsequently sent to Scientific Committee members of the 'Vitamin D - minimum, maximum, optimum' conference for evaluation based on a ten-point scale.With 550 international attendees, the meeting 'Vitamin D - minimum, maximum, optimum' was held on October 19-20, 2012 in Warsaw(Poland). Most recent scientific evidence of both skeletal and non-skeletal effects of Vitamin D as well as the results of panellists' voting were reviewed and discussed during eight plenary sessions and two workshops. RESULTS: Based on many polemical discussions, including post-conference networking, the key opinion leaders established ranges of serum 25-hydroxyVitamin D concentration indicating Vitamin D deficiency [< 20 ng/mL (< 50 nmol/L)], suboptimal status [20-30 ng/mL(50-75 nmol/L)], and target concentration for optimal Vitamin D effects [30-50 ng/mL (75-125 nmol/L)]. General practical guidelines regarding supplementation and updated recommendations for prophylactic Vitamin D intakes in Central European neonates, infants, children and adolescents as well as in adults (including recommendations for pregnant and breastfeeding women and the elderly) were developed. CONCLUSIONS: Improving the Vitamin D status of children, adolescents, adults and the elderly must be included in the priorities of physicians,healthcare professionals and healthcare regulating bodies. The present paper offers elaborated consensus on supplementation guidance and population strategies for Vitamin D in Central Europe.