The Medical Benefits of Vitamin K2 on Calcium-Related Disorders.

BACKGROUND: Due to the potentially crucial role of vitamin K2 in calcium metabolism, a deficit can disrupt many mechanisms, resulting in an array of different issues, such as broken bones, stiff arteries and poor fertility. Although there has been existing research, the potential of vitamin K2 as a treatment for conditions including cerebral palsy, parathyroid disease, heart disease and gastrointestinal disease is unknown. This review discusses the biochemistry of vitamin K and the metabolism of calcium, followed by an analysis of the current literature available on vitamin K2 and its prospects. METHODS: Using public libraries including PubMed and Wiley, we searched for existing research on the metabolism and use of vitamin K2 that has been conducted in the preceding two decades. RESULTS: Data indicated that vitamin K2 had a positive impact on osteoporosis, cardiovascular disease, parathyroid disorders, cerebral palsy and sperm motility. CONCLUSION: Due to the existence of confounding variables and limitations in the quality and volume of research conducted, further investigation must be done to see whether the beneficial effects seen are reproducible and must assess the viability of vitamin K2 as treatment in isolation for these conditions.

MANAGEMENT OF ENDOCRINE DISEASE: Unmet therapeutic, educational and scientific needs in parathyroid disorders.

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 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, 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 an increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity, and optimal treatments. For example, ~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.

Non-functional parathyroid cyst--diagnostic pitfall: A case-report.

INTRODUCTION: Parathyroid cysts are relative rare and they may be misdiagnosed with thyroid nodules. Parathyroid cysts are characterized by elevated level of parathyroid hormone (PTH) in cystic fluid. CASE REPORT. We reported about middle-aged woman with palpable node in the left thyroid lobe. Ultrasound showed anechoic 40 x 25 mm lesion in the left thyroid lobe. Fine needle aspiration (FNA) obtained 13 mL colorless, watery cystic fluid. PTH value in cystic fluid was ten fold more in comparison with serum PTH. Serum PTH was slightly elevated, D vitamin was under the reference range, serum calcium and phosphorus were normal as well as thyroid hormones. Thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb) were not detected. Radionuclide parathyroid scintigraphy indicated at physiological metaiodbenzyl-guamidine (MIBG) distribution. After six monthsof vitamin D supplementation, serum calcium, phosphorus, vitamin D and PTH were normal. This finding was indicative that was a nonfunctional parathyroid cyst. CONCLUSION: This case report points out that thyroid cystic lesions with thin walls, and reverberation in ultrasound, must be observed as a potential parathyroid cyst. These cysts require caution during diagnostic aspiration because of danger of hypercalcemic crises due to FNA, which can be a life-threatening condition.

A report from the endocrine society's 94th annual meeting & expo (June 23-26 - Houston, Texas, USA).

At temperatures above 100 degrees Fahrenheit, but chilly air conditioning inside the George R. Brown convention center, Houston was the endocrine capital of America during June 2012, with the ENDO EXPO 2012 meeting calling attendees from all the states and abroad. Endocrinology is a highly varied specialty, ranging from hormonal disturbances of the pituitary (and in fact acromegaly and Cushing's syndrome were among the stars of this year's meeting therapy-wise) to diabetes, female hormonal disorders and endocrine-mediated malignancies, to mention only a few. New and investigational treatments for these conditions are summarized in the following report, based on the oral and poster presentations during the meeting.

Update in osteoporosis and metabolic bone disorders.

Considerable progress has been made in the development and testing of agents to treat osteoporosis. Most impressive are reports on new antiresorptive agents--both bisphosphonates (ibandronate and zoledronic acid) and monoclonal antibodies (MAbs) (denosumab) directed against receptor activator of nuclear factor kappaB-ligand, a key molecule in the control of commitment and activation of osteoclasts. Bisphosphonates promise convenience and potency at slowing bone loss, whereas denosumab offers powerful suppression of resorption and rapid offset of action. Attention is also shifting from the osteoclast as a target for new therapies to the osteoblast and the osteocyte, with its complex network within the depths of bone. Wnt signaling through the frizzled receptor and its coreceptor, the low-density lipoprotein receptor related protein-5, appears from both molecular and in vivo evidence to be a pivotal pathway for modulating osteoblastic activity, bone formation, and bone strength. The recently identified product of the SOST gene or sclerostin has also been shown to block Wnt signaling. Sclerostin is produced by the osteocytes buried in the bone and is a new target to treat bone loss. Clinical trial reports indicate that the calcimimetic cinacalcet can effectively treat PTH hypersecretion due to primary and secondary hyperparathyroidism and parathyroid carcinoma. Lastly, it is now recognized that the matrix protein dentin matrix protein-1 enhances the release of the phosphate-regulating factor fibroblast growth factor 23 and that mutations in dentin matrix protein-1 play a causative role in a form of hypophosphatemic rickets.

Complications of ultrasound guided percutaneous ethanol injection therapy of the thyroid and parathyroid glands.

OBJECTIVES: Since 1990 percutaneous ethanol injection therapy (PEIT) has been applied clinically as a treatment strategy for focal and diffuse autonomy of the thyroid, for cystic lesions and for ablation of parathyroid hyperplasia (PEA). There are some additional indications currently under consideration as for example inoperable advanced cancer of the thyroid. Since its inception PEIT and PEA have been regarded as an effective, inexpensive and low risk procedure. MATERIAL AND METHODS: We discuss mild and severe complications of these methods reported in literature and the first case so far of a severe ethyl toxic necrosis of the larynx and adjacent skin in a patient treated with PEIT by a radiologist. RESULTS: To date, no serious side effects have been reported in connection with these therapies. Some authors conclude that the side effects are in no way negligible and caution and routine should be exercised when using PEIT or PEA. Most complications have been transient in nature. The complication of ethyl toxic necrosis of the larynx was serious and the patient was admitted to hospital, treated conservatively and ten month later microsurgically. Voice thus could be restored to almost normal. CONCLUSIONS: PEIT for focal and diffuse autonomy, for cystic lesions of the thyroid, for thyroid hyperplasia and PEA for parathyroid hyperplasia are methods which are inexpensive and can be performed on an ambulatory base. These are the methods of choice if surgical intervention or radioiodine therapies are not practicable out of medical reasons or by refusal of the patient. The patient must be informed about possible severe complications. The examiner should have substantial experience in these methods. If complications an early opinion of a specialist is required.

Calcium-sensing receptors.

It is now known that variations in extracellular calcium concentration exert diverse physiologic effects in a variety of tissues that are mediated by a calcium-sensing receptor (CaSRs). In parathyroid tissue, the CaSR represents the molecular mechanism by which parathyroid cells detect changes in blood ionized calcium concentration, modulate parathyroid hormone (PTH) secretion accordingly, and thus maintain serum calcium levels within a narrow physiologic range. In the kidney, the CaSR regulates renal calcium excretion and influences the transepithelial movement of water and other electrolytes. More generally, activation of the CaSR represents an important signal transduction pathway in intestine, placenta, brain, and perhaps bone. Some of these actions involve cell cycle regulation, changes that may be relevant to understanding the pathogenesis of parathyroid gland hyperplasia in secondary hyperparathyroidism caused by chronic kidney disease. The CaSR represents an appealing target for therapeutic agents designed to modify parathyroid gland function in vivo, offering the prospect of novel therapies for selected disorders of bone and mineral metabolism. Other receptors capable of responding to extracellular calcium ions also have been identified, but the functional importance of these interactions remains to be determined.

Ultrasonographic diagnosis of parathyroid glands and percutaneous ethanol injection therapy.

The first choice for imaging diagnosis of parathyroid gland (PTG) abnormalities is ultrasonography with a high-frequency probe. The patient must be positioned correctly when performing either imaging or percutaneous ethanol injection (PEIT) of the PTG. The enlarged PTGs are examined by ultrasonic tomography using 3D measurements, and it is important to evaluate blood flow; the PTGs are hypervascular in comparison with a nodular lesion of the thyroid. Based on the 3D data, the estimated volume of the gland is calculated (a x b x c x pi/6), from which the volume of ethanol to be injected is determined. The operator performing the puncture should be skilled in interventional ultrasonography, including needle biopsy of superficial organs, because when the PTG enlargement is advanced, ethanol must be injected in several steps while checking for residual blood flow. After locating the tip of the needle by ultrasonography, the ethanol is injected, the jet echoes that spread from the tip of the needle are confirmed, and when there is no leakage from the gland, a volume of ethanol corresponding to approximately 50% of the volume of the enlarged gland is injected. If residual blood flow is observed, additional ethanol is injected at the site. After completion of PEIT of the PTG, colour Doppler imaging is repeated and, if there is no blood flow, then the procedure is considered to be successful.

Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients.

Percutaneous ethanol injection therapy (PEIT) of the parathyroid was originally introduced as an alternative to surgical parathyroidectomy. After the recent elucidation of the pathogenesis of parathyroid hyperplasia in uraemia, 'selective PEIT of the parathyroid glands' was developed, in which enlarged parathyroid glands with nodular hyperplasia are 'selectively' destroyed by ethanol injection, and other glands with diffuse hyperplasia are then managed by medical therapy. The 'Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients' proposed by the Japanese Society for Parathyroid Intervention are presented, including indications, techniques, and post-PEIT management. These guidelines also apply to direct injection therapy using drugs other than ethanol, such as calcitriol and 22-oxacalcitriol.

Cooperative multi-modal sensing and therapeutic implications of the extracellular Ca(2+) sensing receptor.

The extracellular Ca(2+)-sensing receptor (CaR) is an unusual member of the diverse superfamily of seven-transmembrane domain G-protein-coupled receptors. Originally identified as the receptor providing the calciostat for extracellular ionized Ca(2+) ¿[Ca(2+)](o)¿, the CaR corrects small changes in [Ca(2+)](o) by regulating the secretion of the hormone that controls Ca(2+) fluxes between the blood and Ca(2+) stores in bone, and between blood and the urine. Now, research is beginning to reveal the structure and function of its unusually large N-terminal head. In addition to its role as a divalent and polyvalent cation sensor, recent studies indicate that the receptor also responds sensitively to changes in ionic strength and pH. Furthermore, new work indicates that the CaR is subject to allosteric activation by L-amino acids.

Percutaneous ethanol injection therapy in the treatment of thyroid and parathyroid diseases.

Relevant English language articles published from 1966 to 1995 regarding ethanol therapy in the treatment of thyroid and parathyroid diseases were identified through a MEDLINE search and manual searches of identified articles. The sclerosing properties of ethanol have been recognized for many years and have offered interventional possibilities in the management of various benign as well as malignant lesions. The mechanism of action of ethanol appears to be related to a direct coagulative necrosis and local partial or complete small vessel thrombosis. Ultrasound-guided percutaneous ethanol injection therapy (PEIT) is rapid and performed on an out-patient basis and has now gained wide acceptance due to the accumulating evidence of the efficacy and safety of this therapeutic tool. Yet, there is a lack of prospective, randomized clinical trials comparing PEIT with 131I therapy or surgery with regard to its effects, especially long-term ones and it should therefore still be considered an experimental procedure. In benign endocrine diseases, PEIT has shown promising results in the treatment of autonomous thyroid nodules, benign solitary cold solid as well as cystic thyroid nodules and parathyroid tumours. Its use in pretoxic and toxic thyroid nodules has been evaluated in several uncontrolled studies, all demonstrating a high success rate in spite of the large number of treatments needed. So far efficacy and cost-effectiveness seem inferior to 131I and surgery. Short-term results of PEIT in benign cystic thyroid nodules are convincing with a high cure rate, but no controlled studies with long-term results are available. Preliminary results suggest that PEIT could become an alternative to surgical excision or levothyroxine therapy in the symptomatic solid cold benign thyroid nodule. Ultrasound-guided PEIT of parathyroid tumours has proven to be a useful method in highly selected patients in whom surgery has been found non-attractive and medical treatment ineffective. However, no prospective randomized trials have been published comparing the results of PEIT in parathyroid tumours with conventional surgical and medical treatments. PEIT has never been tested against standard therapy, but seems inferior to 131I and surgery. Side-effects caused by ethanol injection are generally few and transient and are related to the injection into solid nodules rather than cysts. Ethanol injection into solid profund nodules may seriously jeopardize subsequent surgery because of perinodular fibrosis. As an experimental procedure, not yet evaluated sufficiently, it should be reserved for patients who cannot or will not undergo standard therapy. Caution in routine use is advisable.

Pharmacologic management of patients with diseases of the endocrine system.

Endocrine disorders are commonly seen in the general population. This article discusses the physiology, pathogenesis, and the medical and dental management of patients with thyroid, parathyroid, and pituitary gland disorders. In addition, the pharmacologic treatment, common side effects, and dental drug interactions of concern are discussed.

[Glucocorticoid therapy in endocrine disease].

Natural and synthetic glucocorticoids have been used not merely to manage chronic and acute adrenocortical insufficiency as replacement therapy, but to manage a wide variety of conditions as pharmacological agents. In endocrine disease, they are also used to achieve pharmacological effects, not necessarily related to normal physiological roles. In general, the desired effects is suppression of immune reactivity or inflammatory process. According to these effects, they are used to manage Graves' ophthalmopathy and subacute thyroiditis. They are also given to manage thyroid storm and hyperparathyroid crisis.

[Some endocrinological and therapeutic problems from the geriatric aspect]. / Zu einigen endokrinologisch-therapeutischen Problemen unter geriatrischem Aspekt

Age-specific criteria must be taken into consideration in the treatment of hormonal dysregulations during senescence and senium. A general transmission of the endocrine conditions of younger periods of life to the senium is not possible and induces the possibilities of complications which are demonstrated at the example of the thyroidal and parathyroidal metabolism. The course of endocrine crises is the severer the older the patients concerned are. Dealing with the pathophysiological findings, the author demonstrates and explains therapeutic standards according to own experiences.