Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address this issue by providing respective recommendations for adults, developed by a European expert panel, using the Delphi method to reach consensus. Increasing the awareness of vitamin D deficiency and efforts to harmonize vitamin D guidelines should be pursued. We argue against a general screening for vitamin D deficiency but suggest 25-hydroxyvitamin D (25(OH)D) testing in certain risk groups. We recommend a vitamin D supplementation dose of 800 to 2000 international units (IU) per day for adults who want to ensure a sufficient vitamin D status. These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses (e.g., 6000 IU per day) may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing, with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after at least 6 to 12 weeks in certain risk groups (e.g., patients with malabsorption syndromes) by measurement of serum 25(OH)D, with the aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L).

This 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.

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height >2s.d.above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were ≥10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23,P=0.02).AIPmutations occurred in 29%; microduplication at Xq26.3 – X-linked acrogigantism (X-LAG) – occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG,AIPmutated and genetically negative patient groups.AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden.AIPmutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases.

Due to continuous aging of population and increase in the number of elderly people, osteoporosis became socially significant disease leading to disability, increasing mortality and thereby putting an additional burden on the public healthcare system.Screening to identify groups with a high probability of fracture is recommended using the FRAX^®Tool for all postmenopausal women and men over 50 years old (А1). In the presense of major pathological fractures (hip, spine, multiple fractures) it is recommended to diagnose osteoporosis and prescribe treatment regardless of the results of spine and hip double X-ray absorptiometry (DXA) or FRAX^®(B2).It is recommended to evaluate C-terminal telopeptide when prescribing antiresorptive therapy and procollagen type 1 N-terminal propeptide (P1NP) when prescribing anabolic therapy to patients receiving osteoporosis treatment at baseline and 3 months after the start of therapy in order to assess the effectiveness of treatment early and adherence to the therapy (А2). It is recommended to diagnose osteoporosis and prescribe treatment to patients with high individual 10-year probability of major pathological fractures (FRAX^®) regardless of the results of spine and hip DXA (В3).It is recommended to diagnose osteoporosis and prescribe treatment with a decrease in BMD, measured by DXA, by 2.5 or more T-score standard deviations in femoral neck, and/or in total hip, and/or in lumbar vertebrae, in postmenopausal women and men over 50 years old (А2).It is recommended to prescribe bisphosphonates, denosumab or teriparatide to prevent pathological fractures and increase BMD in patients with postmenopausal osteoporosis, osteoporosis in men, glucocorticoid-induced osteoporosis (А2). When the clinical effect of therapy in osteoporotic patients without pathological fractures is achieved (BMD T-score > -2.0 SD in femoral neck and absence of new fractures), it is recommended to interrupt bisphosphonates therapy for 1-2 years with subsequent follow-up (B2). In patients with vertebral fractures, hip fractures or multiple fractures, it is recommended to continue ceaseless long-term treatment of osteoporosis (В3).All drugs for the treatment of osteoporosis are recommended to be prescribed in combination with calcium and cholecalciferol (А2). In order to reduce the risk of recurrent fractures by prescribing osteoporosis therapy timely and maintaining long-term follow-up of patients over 50 years old with pathological fractures, it is recommended to create Fracture Liaison Services (В2).

Screening using the Fracture Risk Assessment Tool (FRAX) is recommended in all postmenopausal woman and mеn over 50 (A1) in order to identify individuals with high probability of fractures. It is recommended to diagnose osteoporosis and start treatment in patients with fragility fracture of large bones of the skeleton and/or high individual probability of major fragility fractures (FRAX) and/or detected decrease in bone mineral density (BMD) up to –2.5 T-score as assessed by DXA in the femoral neck and/or lumbar vertebrae (A1). Patients with back pain, lifetime height loss of 4 cm or height loss of 2 cm since a previous medical examination, those who receive glucocorticoids, patients with long lasting decompensated type 2 diabetes mellitus, or those receiving insulin therapy, as well as patients who were previously diagnosed with fragility fractures at the other sites are advised to underwent standard lateral X-ray imaging of the spine (Th4—L5) in order to verify the presence of compression vertebral fractures (B1). Dual-energy X-ray absorptiometry (DXA) is recommended for individuals whose 10-year probability of major osteoporotic fracture (FRAX) falls within the medium risk group (B1). It is recommended to include the trabecular bone score (TBS) the FRAX algorithm in order to improve the sensitivity of this method (B1). Laboratory testing is recommended for the differential diagnosis with other causes of increased skeletal fragility in all patients with newly diagnosed osteoporosis and when previously prescribed antiosteoporostic treatment was ineffective (B1). Bisphosphonates (BPs), antibodies to receptor activator of nuclear factor kappa-beta ligand (RANKL) (denosumab), or parathyroid hormone analogue (teriparatide) are equally recommended to prevent fragility fractures and increase BMD in patients with osteoporosis (A1). Denosumab is also recommended to prevent BMD loss and fractures in females receiving aromatase inhibitors therapy for breast cancer and males with prostate cancer receiving hormone-deprivation therapy and having no bone metastases (A1). Since teriparatide has the anabolic effect, it is recommended as the first line treatment in patients with severe osteoporosis having history of vertebral fractures, in the individuals with very high risk of fragility fractures, or in the cases when antiresorptive treatment was ineffective (B1). All medications for treatment of osteoporosis are recommended in combination with calcium and vitamin D supplements (A1).