Tissue-engineered parathyroid gland and its regulatory secretion of parathyroid hormone.

Parathyroid glands (PTGs) are important endocrine organs being mainly responsible for the secretion of parathyroid hormone (PTH) to regulate the balance of calcium (Ca) /phosphorus (P) ions in the body. Once PTGs get injured or removed, their resulting defect or loss of PTH secretion should disturb the level of Ca/P in blood, thus damaging other related organs (bone, kidney, etc.) and even causing death. Recently, tissue-engineered PTGs (TE-PTGs) have attracted lots of attention as a potential treatment for the related diseases of PTGs caused by hypoparathyroidism and hyperparathyroidism, including tetany, muscle cramp, nephrolithiasis, nephrocalcinosis, and osteoporosis. Although great progress has been made in the establishment of TE-PTGs with an effective strategy to integrate the key factors of cells and biomaterials, its regulatory secretion of PTH to mimic its natural rhythms in the body remains a huge challenge. This review comprehensively describes an overview of PTGs from physiology and pathology to cytobiology and tissue engineering. The state of the arts in TE-PTGs and the feasible strategies to regulate PTH secretion behaviors are highlighted to provide an important foundation for further investigation.

Epidemiology and management of parathyroid gland disorders in Spain over 15 years: A retrospective multicentre analysis.

Parathyroid gland disorders are rare conditions with an incidence that displays great variability among populations. Its direct influence in calcium homeostasis originates variable symptoms that affect bone remodelling among other processes. This study aimed to provide data on the epidemiology and characteristics of patients admitted with these disorders in Spain between 2003 and 2017, and to analyse disease management and direct medical costs. Medical records in which a disorder of the parathyroid gland was registered as the admission motive were extracted from a nationwide hospital-discharge database via the Spanish Ministry of Health. Records from 12,903 patients were obtained, with predominance of female patients (74.70%) and of admissions due to hyperparathyroidism (90.23%). The number of patients admitted per year increased over the study period along the incidence of these disorders. The year 2017 incidence of hyperparathyroidism was 2.95 per 10,000, 4.03 per 10,000 in females and 1.37 in males; the same year, the incidence of hypoparathyroidism was 0.17 per 10,000. Length of hospital stay was significantly extended in patients with hypoparathyroidism (7.16 days), admitted mostly due to emergencies. Heart failure was diagnosed in more than 20% of admissions in patients with secondary and tertiary hyperparathyroidism and hypoparathyroidism, while this last group displayed the highest levels of mineral metabolism disruption. Parathyroidectomy was performed in 78.95% of all admissions for primary hyperparathyroidism. The total annual direct medical cost parathyroid gland disorders has increased over the study period, due to the increase of the costs associated to hyperparathyroidism, whereas the cost per patient remained relatively stable, with an average of €3,748, €3,430 and €3,737 for patients with hyperparathyroidism, hypoparathyroidism and other disorders of the parathyroid gland, respectively. This study provides novel data to extend the scarce available knowledge on parathyroid gland disorders' epidemiology and management in Spain.

Management of immune-related adverse events in endocrine organs induced by immune checkpoint inhibitors: clinical guidelines of the Japan Endocrine Society.

Immune checkpoint inhibitors (ICIs) have become a promising treatment for advanced malignancies. However, these drugs can induce immune-related adverse events (irAEs) in several organs, including skin, gastrointestinal tract, liver, muscle, nerve, and endocrine organs. Endocrine irAEs comprise hypopituitarism, primary adrenal insufficiency, thyroid dysfunction, hypoparathyroidism, and type 1 diabetes mellitus. These conditions have the potential to lead to life-threatening consequences, such as adrenal crisis, thyroid storm, severe hypocalcemia, and diabetic ketoacidosis. It is therefore important that both endocrinologists and oncologists understand the clinical features of each endocrine irAE to manage them appropriately. This opinion paper provides the guidelines of the Japan Endocrine Society and in part the Japan Diabetes Society for the management of endocrine irAEs induced by ICIs.

The Parathyroid Gland and Heart Disease.

The parathyroid glands are critical to maintaining calcium homeostasis through actions of parathyroid hormone (PTH). Recent clinical and molecular research has shown that direct and indirect actions of PTH also affect the heart and vasculature through downstream actions of G protein-coupled receptors in the myocardium and endothelial cells. Patients with disorders of the parathyroid gland have higher incidences of hypertension, arrhythmias, left ventricular hypertrophy, heart failure, and calcific disease which translate into increased cardiac morbidity and mortality. Importantly, clinical research also suggests that early treatment of parathyroid disorders through medical or surgical management may reverse cardiovascular remodeling and mitigate cardiac risk factors.

Small nonfunctional parathyroid cysts: single institution experience.

Parathyroid cysts (PCs) account for less than 1% of all parathyroid lesions and are most commonly located along thyroid lobes, rarely at ectopic sites. PCs are important because they can pose a differential diagnostic challenge against other cystic formations of the neck. PCs can be functional (elevated serum parathyroid hormone level) and nonfunctional. Four cases of nonfunctional PCs are presented. All four female patients underwent physical examination and ultrasonography of the neck with ultrasound-guided fine-needle aspiration biopsy (UG-FNA). The material thus obtained was stained by the standard May-Grünwald-Giemsa method. Parathyroid hormone level was determined in aspirate and serum, along with serum levels of total calcium, inorganic phosphates. In two asymptomatic patients, remission occurred after initial aspiration biopsy; one patient had compression syndrome with vocal cord paresis that required surgical treatment; and one patient had cyst recurrence that was surgically removed. Cystic neck masses can pose a major differential diagnostic problem considering different approach, treatment method, and preoperative and postoperative follow up. Surgical treatment is necessary in case of functional and large nonfunctional PCs (due to compression syndrome), whereas individualized therapeutic approach is used in case of small nonfunctional PCs. Ultrasonography with UG-FNA, cytologic analysis of the material obtained, and determination of parathyroid hormone level in aspirate and serum are crucial for making an accurate diagnosis.

Deleción en el gen STX16 asociada a pseudohipoparatiroidismo / STX16 deletion associated to pseudohypoparathyroidism

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Multiple hormonal resistances: Diagnosis, evaluation and therapy.

Molecular alterations of cAMP-mediated signaling affect primarily the signaling of the PTH/PTHrp receptor, and, with different severities the signaling of other hormones, including TSH. The identification of PTH and other hormonal resistances implies to look for the genetic disorder supporting the metabolic disorder.

[Rare abnormalities of parathyroid gland function and parathyroid hormone receptor action]. / Rzadkie zaburzenia funkcji przytarczyc i dzialania receptorowego parathormonu.

The parathyroid glands, located near or within the posterior surface of the thyroid gland and secreting parathyroid hormone, are essential organs for the regulation of calcium and phosphate metabolism. As they are necessary to sustain life and maintain homeostasis, undetected or misdiagnosed parathyroid disorders may pose a significant threat to health outcomes, as their presence may increase morbidity and mortality in affected individuals. The clinical picture of some disorders associated with abnormal parathyroid hormone secretion and receptor action is sometimes complicated by coexisting abnormalities, and in these cases establishing the correct diagnosis is challenging. The remarkable progress of recent years in the area of hormonal assessment, imaging procedures and molecular biology, has resulted in a great improvement in the identification, differentiation and treatment of various parathyroid disorders and has made it possible to identify several new clinical entities. In this paper, we discuss the present state-of-art on the etiopathogenesis, clinical manifestations, diagnosis and treatment of chosen rare abnormalities of parathyroid gland function and parathyroid hormone receptor action.

A rare cystic lesion of the neck: parathyroid cyst.

Parathyroid cysts are rarely observed neck masses. Their physical examination is not specific and preoperative diagnosis is usually difficult. Imaging findings and ultrasound-guided fine-needle aspiration with hormone analysis evaluation are important diagnostic criteria. A 48-year-old female patient admitted to our hospital with a symptom of swelling on the left side of the neck was diagnosed with parathyroid cyst by imaging methods (ultrasonography, MRI, parathyroid scintigraphy) and laboratory findings. Fine-needle aspiration biopsy was performed and because of relapse on the follow-up sclerotherapy was planned. Our aim in this study was to present the radiological findings of this case of parathyroid cyst.

Parathyroid disorders.

Disorders of the parathyroid glands most commonly present with abnormalities of serum calcium. Patients with primary hyperparathyroidism, the most common cause of hypercalcemia in outpatients, are often asymptomatic or may have bone disease, nephrolithiasis, or neuromuscular symptoms. Patients with chronic kidney disease may develop secondary hyperparathyroidism with resultant chronic kidney disease-mineral and bone disorder. Hypoparathyroidism most often occurs after neck surgery; it can also be caused by autoimmune destruction of the glands and other less common problems. Evaluation of patients with abnormal serum calcium levels includes a history and physical examination; repeat measurement of serum calcium level; and measurement of creatinine, magnesium, vitamin D, and parathyroid hormone levels. The treatment for symptomatic primary hyperparathyroidism is parathyroidectomy. Management of asymptomatic primary hyperparathyroidism includes monitoring symptoms; serum calcium and creatinine levels; and bone mineral density. Patients with hypoparathyroidism require close monitoring and vitamin D (e.g., calcitriol) replacement.

Symptomatic nonfunctioning parathyroid cysts: role of simple aspiration and ethanol ablation.

OBJECTIVES: To evaluate the outcomes of simple aspiration and ethanol ablation in the management of symptomatic nonfunctioning parathyroid cyst (PC). METHODS: We performed simple aspirations for 12 PCs in 12 patients from March 1997 to June 2010. PC was diagnosed if the aspirated fluid was clear colorless and showed an elevated parathyroid hormone (PTH) level. Ethanol ablation (EA) was performed for recurrent PCs. Simple aspirations were performed using 23-gauge needles and EAs using 18-gauge needles with 99% ethanol under ultrasound (US) guidance. We evaluated cyst volume, cosmetic score, symptom score, and complications. RESULTS: Mean follow-up period of all patients was 19.2 ± 12.9 months (median, 15.0 months; range, 7-40 months). Simple aspiration was successful in four patients, and the mean volume reduction after simple aspiration was 98.2 ± 3.5% (range, 92.9-100%). In eight recurrent cases, EA resulted in a significant decrease in volume (P=0.012), as well as in cosmetic (P=0.011) and symptom (P=0.01) scores at last follow-up; however two cases of primary failure of EA was treated by repeat EA. No major complications occurred in any patient. CONCLUSIONS: For symptomatic nonfunctioning PCs, simple aspiration could be a first line procedure for diagnosis and treatment, while EA can be a subsequent treatment modality for recurrent cases.

Subclinical and asymptomatic parathyroid disease: implications of emerging data.

Primary hyperparathyroidism, a disorder in which there is a tendency for hypercalcaemia caused by autonomous overproduction of parathyroid hormone, is common, especially in postmenopausal women. Although parathyroidectomy is indicated for symptomatic patients, most individuals with the disorder are asymptomatic and without classic complications, such as renal stones and osteoporosis, at diagnosis. Consensus guidelines suggest which individuals might be suitable for medical follow-up rather than parathyroidectomy, but there are no long-term randomised controlled trials to support the safety of medical surveillance, and some patients progress with time. Data from observational studies suggest that cardiovascular morbidity and mortality are increased in patients with primary hyperparathyroidism, and might be predicted by parathyroid hormone concentrations, even in individuals with asymptomatic primary hyperparathyroidism. Whether parathyroidectomy improves cardiovascular outcomes in patients with asymptomatic primary hyperparathyroidism is unproven, but data suggest that surgery decreases fracture risk and might improve neuropsychological symptoms. Studies also show that patients with normocalcaemic (subclinical) hyperparathyroidism and hypoparathyroidism have a low risk of progression to overt disease, but their long-term risks are not defined. In this Review, we explore the increasing range of asymptomatic parathyroid disorders, focusing on current evidence about their natural history and potential complications, with a particular emphasis on primary hyperparathyroidism.

Parathyroid cysts: a clinical and radiological challenge.

Parathyroid cysts are rare causes of neck swelling accounting for 0.6% of thyroid and parathyroid lesions. They may be functional, resulting in the release of parathyroid hormone, or non-functional. Non-functional cysts may be cosmetically unacceptable or cause dysphagia, dyspnoea or recurrent laryngeal nerve palsy as a result of compression. This article presents a young woman who was diagnosed with a thyroid cyst both on examination and imaging. However, the final histology confirmed this to be parathyroid in origin and this should be considered in the differential of such neck swellings.

Parathyroid cyst, a rare cause of cystic cervical lesion. Case report.

Parathyroid cyst is a very rare abnormality. The diagnosis can be made based on ultrasound and the analysis of the aspirated cystic fluid for parathyroid hormone (PTH). We report the case of a nonfunctional parathyroid cyst in a 50-year-old female patient with an anterior neck mass. The patient was complaining of pain in the anterior cervical region, dysphagia, dyspnea and dysphonia started three weeks previously. Ultrasound demonstrated an anechoic and avascular lesion located in the left lobe of the thyroid. Fine needle aspiration (FNA) revealed a clear, colorless and watery cystic fluid, that showed a high concentration of parathyroid hormone (PTH) in both the native and the diluted content of the cyst, while serum PTH was normal, indicating a nonfunctional parathyroid cyst. The patient was in remission by percutaneous aspiration and there was no relapse of the parathyroid cyst after one-year follow-up.

Management of nonpsychiatric medical conditions presenting with psychiatric manifestations.

There is a significant dilemma when underlying medical disorders present as psychiatric conditions. It is important to identify the medical condition because treatment and management strategies need to be directed to the presenting symptoms and also to the underlying medical condition for successful treatment of the patient. Some systemic disorders present with psychiatric manifestations more often than others. The pattern of psychiatric disturbance seen may be specific for a particular medical disorder but may also be varied. Many drug formulations and medications also may produce psychiatric presentations. This article considers the management of nonpsychiatric medical conditions presenting with psychiatric manifestations.

The additional diagnostic value of a single-session combined scintigraphic and ultrasonographic examination in patients with thyroid and parathyroid diseases.

AIM: The aim of this study was to investigate the diagnostic efficacy and the clinical impact of scintigraphy combined with ultrasonography (USG) in the management of thyroid and parathyroid disorders in a large series of patients. METHODS: A total of 387 consecutive patients referred to the Nuclear Medicine Department of Hacettepe University in the period from January to September 2007 for investigating a thyroid (N. 339 patients: 232 females and 107 males, mean age+/-SD=48.9+/-13.6 years) or a parathyroid disease (N. 48 patients: 34 females and 14 males, mean age+/-SD=47.4+/-9.6 years) were prospectively evaluated, systematically performing both scintigraphy and USG in a single-day session. All the examinations were independently reviewed by two nuclear medicine physicians; in cases of discrepancy (3%) a final diagnosis was reached by consensus. For thyroid pathologies, USG results were considered to provide additional diagnostic information over scintigraphy: 1) if more nodules were identified; 2) if an irregular hyperactive area at scintigraphy suspicious for the presence of a nodule was clearly characterized at USG; 3) if a nodule missed at scintigraphy because of small size (<1 cm) was well depicted at USG, thus allowing an USG-guided fine needle aspiration cytology (FNAC) to reach a final diagnosis. For parathyroid pathologies, USG was considered to provide additional diagnostic information over scintigraphy if a low intensity radiotracer retention from the parathyroid suspected of being a parathyroid enlargement was clearly depicted at USG. In thyroid diseases, scintigraphy was considered to provide additional diagnostic information over USG, if the functional status of a diffuse or uni- or multi-nodular goiter were clearly defined at scintigraphy. In parathyroid diseases, scintigraphy was considered to provide additional diagnostic information over USG, if the differential diagnosis between a lymph node or a muscle or a vessel depicted at USG was clearly defined as a parathyroid enlargement at scintigraphy. Lastly, the clinical impact of the single-day combined scintigraphic/USG protocol was evaluated. RESULTS: USG. In the thyroid diseases group, USG was particularly useful: 1) to detect additional nodules in glands with suppressed thyroid tissue; 2) to disclose small thyroid nodules (<1 cm) in which it was possible to perform a USG-FNAC. In the parathyroid diseases group, USG was particularly useful for the detection of parathyroid enlargements not visualized at scintigraphy because characterized by a rapid wash-out of the radiotracer and thus by a low radioactivity intensity in the delayed scintigraphic images. Scintigraphy. In the thyroid diseases group, scintigraphy was particularly useful: 1) to diagnose a diffuse hyperfunctioning thyroid gland, and to differentiate in multinodular goiters the hyper- from the hypo-functioning nodules. In the hyperparathyroid diseases group, scintigraphy was particular useful in making a differential diagnosis between a true parathyroid enlargement vs. a lymph node or a muscle or a vessel as depicted at USG, and in cases with deeply or ectopically-positioned parathyroid glands. Combined imaging approach. Combined interpretation provided additional benefit in 225 of 339 patients (64.4%). Overall, using the combined scintigraphic/USG single-day protocol, in the thyroid diseases group the therapeutic strategy (drug therapy vs radioiodine therapy vs surgery) was changed in 176/225 patients (78.2%, P<0.001 by chi(2) of Pearson), and in the parathyroid disease group the therapeutic strategy (medical therapy vs surgery) was changed in 18/48 patients (37.5%, P<0.01 by chi2 test of Pearson). CONCLUSION: In agreement with some previous published experiences, the combined single-day scintigraphic/USG protocol systematically adopted in a large series of consecutive patients with thyroid and parathyroid diseases, enrolled in a limited period of time, proved to significantly increase the global diagnostic accuracy and to change the therapeutic strategy in more than two third of patients with a thyroid disease and in more than one third of patients with a parathyroid disease.