Atypical parathyroid adenomas represent a group of intermediate form of parathyroid neoplasms of uncertain malignant potential which show some atypical histological features that represent a ...challenge for the differential diagnosis with parathyroid carcinomas. They may occur as sporadic or as a part of hereditary syndromes. The molecular signature of these neoplasms is still unknown and the germline CDC73 mutations appears to be the most common anomaly in this setting suggesting that these cases might represent variants of the hyperparathyroidism-jaw tumor syndrome. The identification of markers predicting the outcome is of great importance to guide an adequate postoperative monitoring and, the same time, relieve of the anxiety of relatively strict monitoring patients not at risk. This review will summarize the current knowledge of the clinical, biochemical, molecular and histological profile of atypical parathyroid adenomas.
Abstract
The etiology of endemic rickets was discovered a century ago. Vitamin D is the precursor of 25-hydroxyvitamin D and other metabolites, including 1,25(OH)2D, the ligand for the vitamin D ...receptor (VDR). The effects of the vitamin D endocrine system on bone and its growth plate are primarily indirect and mediated by its effect on intestinal calcium transport and serum calcium and phosphate homeostasis. Rickets and osteomalacia can be prevented by daily supplements of 400 IU of vitamin D. Vitamin D deficiency (serum 25-hydroxyvitamin D <50 nmol/L) accelerates bone turnover, bone loss, and osteoporotic fractures. These risks can be reduced by 800 IU of vitamin D together with an appropriate calcium intake, given to institutionalized or vitamin D–deficient elderly subjects. VDR and vitamin D metabolic enzymes are widely expressed. Numerous genetic, molecular, cellular, and animal studies strongly suggest that vitamin D signaling has many extraskeletal effects. These include regulation of cell proliferation, immune and muscle function, skin differentiation, and reproduction, as well as vascular and metabolic properties. From observational studies in human subjects, poor vitamin D status is associated with nearly all diseases predicted by these extraskeletal actions. Results of randomized controlled trials and Mendelian randomization studies are supportive of vitamin D supplementation in reducing the incidence of some diseases, but, globally, conclusions are mixed. These findings point to a need for continued ongoing and future basic and clinical studies to better define whether vitamin D status can be optimized to improve many aspects of human health. Vitamin D deficiency enhances the risk of osteoporotic fractures and is associated with many diseases. We review what is established and what is plausible regarding the health effects of vitamin D.
Abstract Graves' disease (GD) is an autoimmune disorder involving the thyroid gland, typically characterized by the presence of circulating autoantibodies that bind to and stimulate the thyroid ...hormone receptor (TSHR), resulting in hyperthyroidism and goiter. Organs other than the thyroid can also be affected, leading to the extrathyroidal manifestations of GD, namely Graves' ophthalmopathy, which is observed in ~ 50% of patients, and Graves' dermopathy and acropachy, which are quite rare. Presumably, the extrathyroidal manifestations of GD are due to autoimmunity against antigens common to the thyroid and other affected organs. Although its exact etiology remains to be completely understood, GD is believed to result from a complex interaction between genetic susceptibility and environmental factors. Clinically, GD is characterized by the manifestations of thyrotoxicosis as well as by its extrathyroidal features when present, the latter making the diagnosis almost unmistakable. In the absence of ophthalmopathy, the diagnosis is generally based on the association of hyperthyroidism and usually diffuse goiter confirmed with serum anti-TSHR autoantibodies (TRAbs). Hyperthyroidism is generally treated with anti-thyroid drugs, but a common long term treatment strategy in patients relapsing after a course of anti-thyroid drugs (60-70%), implies the use of radioactive iodine or surgery.
Classic endocrine feedback loops ensure the regulation of blood calcium. Calcium in the extracellular fluid (ECF) binds and activates the calcium sensing receptor (CaSR) on the parathyroid cells, ...leading to an increase in intracellular calcium. This in turn leads to a reduced parathyroid hormone (PTH) release. Hypocalcemia leads to the opposite sequence of events, namely, lowered intracellular calcium and increased PTH production and secretion. PTH rapidly increases renal calcium reabsorption and, over hours to days, enhances osteoclastic bone resorption and liberates both calcium and phosphate from the skeleton. PTH also increases fibroblast growth factor 23 (FGF23) release from mature osteoblasts and osteocytes. PTH stimulates the renal conversion of 25-hydroxyvitamin D (25OHD) to 1,25(OH)2D, likely over several hours, which in turn will augment intestinal calcium absorption. Prolonged hypocalcemia and exposure to elevated PTH may also result in 1,25(OH)2D-mediated calcium and phosphorus release from bone. These effects restore the ECF calcium to normal and inhibit further production of PTH and 1,25(OH)2D. Additionally, FGF23 can be released from bone by 1,25(OH)2D and can in turn reduce 1,25(OH)2D concentrations. FGF23 has also been reported to decrease PTH production. When ECF calcium is in the hypercalcemic range, PTH secretion is reduced and renal 1,25(OH)2D production is decreased. In addition, the elevated calcium per se stimulates the renal CaSR, thus inducing calciuria. Therefore, suppression of PTH release and 1,25(OH)2D synthesis and stimulation of the renal CaSR lead to reduced renal calcium reabsorption, decreased skeletal calcium release, and decreased intestinal calcium absorption, resulting in the normalization of the elevated ECF calcium.
Objective:
Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The only available definitive therapy is parathyroidectomy, which is appropriate to consider in all patients. ...The purpose of this report is to provide an update on calcium and vitamin D supplementation and medical management for those patients with PHPT who cannot or do not want to undergo surgery.
Methods:
Questions were developed by the International Task Force on PHPT. A comprehensive literature search was undertaken, and relevant articles published between 2008 and 2013 were reviewed in detail. The questions were addressed by the panel of experts, and consensus was established at the time of the workshop.
Conclusions:
The recommended calcium intake in patients with PHPT should follow guidelines established for all individuals. It is not recommended to limit calcium intake in patients with PHPT who do not undergo surgery. Patients with low serum 25-hydroxyvitamin D should be repleted with doses of vitamin D aiming to bring serum 25-hydroxyvitamin D levels to ≥ 50 nmol/L (20 ng/mL) at a minimum, but a goal of ≥75 nmol/L (30 ng/mL) also is reasonable. Pharmacological approaches are available and should be reserved for those patients in whom it is desirable to lower the serum calcium, increase BMD, or both. For the control of hypercalcemia, cinacalcet is the treatment of choice. Cinacalcet reduces serum calcium concentrations to normal in many cases, but has only a modest effect on serum PTH levels. However, bone mineral density (BMD) does not change. To improve BMD, bisphosphonate therapy is recommended. The best evidence is for the use of alendronate, which improves BMD at the lumbar spine without altering the serum calcium concentration. To reduce the serum calcium and improve BMD, combination therapy with both agents is reasonable, but strong evidence for the efficacy of that approach is lacking.
Objective:
Asymptomatic primary hyperparathyroidism (PHPT) is routinely encountered in clinical practices of endocrinology throughout the world. This report distills an update of current information ...about diagnostics, clinical features, and management of this disease into a set of revised guidelines.
Participants:
Participants, representing an international constituency, with interest and expertise in various facets of asymptomatic PHPT constituted four Workshop Panels that developed key questions to be addressed. They then convened in an open 3-day conference September 19–21, 2013, in Florence, Italy, when a series of presentations and discussions addressed these questions. A smaller subcommittee, the Expert Panel, then met in closed session to reach an evidence-based consensus on how to address the questions and data that were aired in the open forum.
Evidence:
Preceding the conference, each question was addressed by a relevant, extensive literature search. All presentations and deliberations of the Workshop Panels and the Expert Panel were based upon the latest information gleaned from this literature search.
Consensus Process:
The expert panel considered all the evidence provided by the individual Workshop Panels and then came to consensus.
Conclusion:
In view of new findings since the last International Workshop on the Management of Asymptomatic PHPT, guidelines for management have been revised. The revised guidelines include: 1) recommendations for more extensive evaluation of the skeletal and renal systems; 2) skeletal and/or renal involvement as determined by further evaluation to become part of the guidelines for surgery; and 3) more specific guidelines for monitoring those who do not meet guidelines for parathyroid surgery. These guidelines should help endocrinologists and surgeons caring for patients with PHPT. A blueprint for future research is proposed to foster additional investigation into issues that remain uncertain or controversial.
The 4
th
International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. ...Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended. Specifically, in comparison to healthy populations, higher levels of vitamin D and greater amounts of vitamin D were deemed necessary in osteoporosis, diabetes mellitus, obesity (particularly after bariatric surgery), and in those treated with glucocorticoids. Emerging and still open issues were related to target vitamin D levels and the role of vitamin D supplementation in COVID-19 since low vitamin D may predispose to SARS-CoV-2 infection and to worse COVID-19 outcomes. Finally, whereas oral daily cholecalciferol appears to be the preferred choice for vitamin D supplementation in the general population, and in most clinical conditions, active vitamin D analogs may be indicated in patients with hypoparathyroidism and severe kidney and liver insufficiency. Parenteral vitamin D administration could be helpful in malabsorption syndromes or in states of vitamin D resistance.
Specific guidelines for desired levels of vitamin D should be tailored to the different conditions affecting vitamin D metabolism with the goal to define disease-specific normative values.
Background
This paper reports results from the 5th International Conference “Controversies in Vitamin D” that was held in Stresa, Italy, 15–18 September 2021. The conference is part of this series ...that started in 2017 and has been conducted annually since. The objective of these conferences is to identify timely and controversial topics related to Vitamin D. Dissemination of the results of the conference through publications in peer-reviewed journals is an important means by which the most up to date information can be shared with physicians, investigators, and other health care professionals. Vitamin D and aging, the subject of this paper was featured at the conference.
Methods
Participants were selected to review available literature on assigned topics related to vitamin D and aging and to present their findings with illustrative material, the intent of which was to stimulate discussion and to arrive at a consensus. The presentations were directed towards the following areas: impact of aging on vitamin D production and levels; skeletal effects of vitamin D deficiency in the older population; falls and vitamin D in the aging; potential extra skeletal effects of vitamin D; and strategies to prevent vitamin D deficiency. A final topic was related to how vitamin D might influence the efficacy of vaccines for Covid-19.
Results
Hypovitaminosis D can lead to several skeletal and extra-skeletal outcomes. Older adults are at risk for vitamin D deficiency as both production and metabolism of vitamin D change with aging due to factors, such as reduced sun exposure and reduced production capacity of the skin. Skeletal consequences of these age-related changes can include reduced bone mineral density, osteomalacia and fractures. Potential extra-skeletal effects can include added risks for falls, reduced muscle strength, diabetes, cancer, and cardiovascular disease. Strategies to avoid these vitamin D deficiency-related negative outcomes include sun exposure, food fortification, and supplementation. While aging does not diminish sufficient reserve capacity for cutaneous vitamin D production, concerns about skin cancers and practical matters for the institutionalized elderly limit this option. Supplementation with vitamin D is the best option either pharmacologically or through food fortification. Regardless of treatment strategies, interventions to restore sufficient vitamin D status will show positive results only in those who are truly deficient. Thus, treatment goals should focus on avoiding 25(OH)D serum levels <30 nmol/l, with a goal to reach levels >50 nmol/l.
Conclusions
The results of this conference has led to consensus on several issues. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate Vitamin D status should be to reach a serum level of 25(OH)D >50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of Vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are Vitamin Ddeficient. Of three possible strategies to establish vitamin D sufficiency – sunshine exposure, food fortification, and supplementation – the latter seems to be the most effective and practical in the aging population.
Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves' disease, though severe forms are rare. Management of GO is often suboptimal, largely because available treatments do not ...target pathogenic mechanisms of the disease. Treatment should rely on a thorough assessment of the activity and severity of GO and its impact on the patient's quality of life. Local measures (artificial tears, ointments and dark glasses) and control of risk factors for progression (smoking and thyroid dysfunction) are recommended for all patients. In mild GO, a watchful strategy is usually sufficient, but a 6-month course of selenium supplementation is effective in improving mild manifestations and preventing progression to more severe forms. High-dose glucocorticoids (GCs), preferably via the intravenous route, are the first line of treatment for moderate-to-severe and active GO. The optimal cumulative dose appears to be 4.5-5 g of methylprednisolone, but higher doses (up to 8 g) can be used for more severe forms. Shared decision-making is recommended for selecting second-line treatments, including a second course of intravenous GCs, oral GCs combined with orbital radiotherapy or cyclosporine, rituximab or watchful waiting. Rehabilitative treatment (orbital decompression surgery, squint surgery or eyelid surgery) is needed in the majority of patients when GO has been conservatively managed and inactivated by immunosuppressive treatment.
TSH suppressive therapy and bone Brancatella, Alessandro; Marcocci, Claudio
Endocrine Connections,
07/2020, Letnik:
9, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Thyroid hormones stimulate bone turnover in adults by increasing osteoclastic bone resorption. TSH suppressive therapy is usually applied in patients with differentiated thyroid cancer (DTC) to ...improve the disease outcome. Over the last decades several authors have closely monitored the potential harm suffered by the skeletal system. Several studies and meta-analyses have shown that chronic TSH suppressive therapy is safe in premenopausal women and men. Conversely, in postmenopausal women TSH suppressive therapy is associated with a decrease of bone mineral density, deterioration of bone architecture (quantitative CT, QCT; trabecular bone score, TBS), and, possibly, an increased risk of fractures. The TSH receptor is expressed in bone cells and the results of experimental studies in TSH receptor knockout mice and humans on whether low TSH levels, as opposed to solely high thyroid hormone levels, might contribute to bone loss in endogenous or exogenous thyrotoxicosis remain controversial. Recent guidelines on the use of TSH suppressive therapy in patients with DTC give value not only to its benefit on the outcome of the disease, but also to the risks associated with exogenous thyrotoxicosis, namely menopause, osteopenia or osteoporosis, age >60 years, and history of atrial fibrillation. Bone health (BMD and/or preferably TBS) should be evaluated in postmenopausal women under chronic TSH suppressive therapy or in those patients planning to be treated for several years. Antiresorptive therapy could also be considered in selected cases (increased risk of fracture or significant decline of BMD/TBS during therapy) to prevent bone loss.
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