[The history of the parathyroid glands - A contribution to the history of the parathyroid glands, their anatomy, function and their diseases.] / Die Geschichte der Nebenschilddrüsen ­ Ein Beitrag zur Historie der Nebenschilddrüsen, zu ihrer Anatomie, Funktion und ihren Erkrankungen.

The article reviews the scientific history of the parathyroid gland beginning with its first detection by Ivar Victor Sandström. Following his meticulous anatomical and histological description (1880) it took years of meandering work by many pathologists, physiologists and surgeons to uncover its complex contributions to calcium regulation in the body and associated diseases. Finally some aspects of the current status in treating hyper- and hypoparathyroidism are delineated.

Fisiología de las glándulas paratiroides. Disfunción y parámetros funcionales de laboratorio en paratiroides / Physiology of de parathyroid glands. Disfunction and functional parameters of paratyroid laboratory

El calcio y el fósforo están implicados en importantes funciones del organismo, tanto a nivel intracelular como extracelular. Por ello, deben existir mecanismos reguladores que mantengan las concentraciones de calcio y fósforo en sus intervalos de normalidad. El objetivo de este artículo es revisar la fisiología de la glándula paratiroides, así como el papel de la vitamina D y del factor de crecimiento de fibroblatos 23 (FGF 23) en el metabolismo fosfocálcico y también interpretar las alteraciones analíticas para el adecuado estudio de las patologías del metabolismo fosfocálcio

Calcium and Phosphorus are involved in important functions of the organism, both intracellular and extracellular. Therefore, there must be regulatory mechanisms that maintain calcium and phosphorus concentrations at their normal intervals. The objective of this article is to review the physiology of the parathyroid gland, as well as the role of vitamin D and Fibroblast Growth Factor 23 (FGF 23) in phosphocalcic metabolism and also interpret analytical alterations for the proper study of pathologies of phosphocalcium metabolism

The impact of near infrared fluorescence imaging on parathyroid function after total thyroidectomy.

BACKGROUND: Compared with conventional thyroidectomy, hypocalcemia rate was reported to be lower after total thyroidectomy (TT) utilizing near infrared fluorescence imaging (NIFI). The aim of this study is to evaluate the impact of NIFI on postoperative parathyroid function after TT. METHODS: This was a retrospective institutional review board-approved study comparing 100 patients who underwent TT with NIFI guidance and 200 patients without, by the same surgeon. Clinical parameters were compared using χ2 and t test. RESULTS: Average number of parathyroid glands identified intraoperatively was similar between two groups. However, rate of incidental parathyroidectomy was higher in conventional (14%) versus NIFI group (6%) (P = .039), despite similar (4% vs 6%, respectively) autotransplantation rates (P = .562). Incidences of transient (6.5% vs 5.0%) and permanent (0.5% vs 0%) hypocalcemia were not statistically different between conventional and NIFI groups (P = NS). CONCLUSION: The use of NIFI during thyroidectomy may decrease the rate of incidental parathyroidectomy by increasing the ability of the surgeon to recognize parathyroid glands with fluorescent contrast distinction. Nevertheless, in contrary to recent reports in literature, postoperative hypocalcemia rate was not altered compared with conventional technique, suggesting that preservation of parathyroid vasculature, rather than an augmented ability to detect the glands, may dominantly affect postoperative function.

The inferior parathyroid glands preserved in site recover faster than the superior parathyroid glands preserved in site after thyroid surgery for carcinoma.

Due to the great difficulty in being preserved in site for the variable positions, the inferior parathyroid glands were advised to being routinely autotransplanted to prevent permanent hypoparathyroidism. The aim of this study was to compare the performance in the function of the superior parathyroid glands preserved in site with that of the inferior parathyroid glands preserved in site.We conducted a retrospective study including patients who underwent thyroid surgery for papillary thyroid carcinoma at our department between January 2014 and June 2018. According to the number and original position of the autoplastic parathyroid gland(s), patients were divided into group 1 (1 superior parathyroid gland), group 2 (1 inferior parathyroid glands), group 3 (1 superior parathyroid gland and 1 inferior parathyroid gland) and group 4 (2 inferior parathyroid glands). The postoperative complications and serum parathyroid hormone and calcium were analyzed.A total of 368 patients were included in the study, among them 27, 243, 40, and 58 patients were divided into group 1, group 2, group 3, and group 4, respectively. Compared with those in group 2, the serum parathyroid hormones were higher at 1 week (2.98 ±â€Š1.52 vs 2.42 ±â€Š0.89, P = .049) and 2 weeks (3.49 ±â€Š1.42 vs 2.8 ±â€Š0.81, P = .019) postoperatively in group 1. There was also significantly different in the serum parathyroid hormone at 2 weeks postoperatively between group 3 and group 4 (2.95 ±â€Š0.98 vs 2.58 ±â€Š0.82, P = .047).The inferior parathyroid glands preserved in site recover faster than the superior parathyroid glands preserved in site.

Pediatric parathyroid disease.

Parathyroid glands are critical for calcium and phosphate homeostasis. Parathyroid disease is relatively rare in the pediatric population, but there are some important pediatric-specific considerations and conditions. This article reviews parathyroid physiology, disorders of hyper- and hypo- function, operative management, and uniquely pediatric diagnoses such as neonatal severe hyperparathyroidism. Advances in preoperative imaging, intra-operative gland identification, and management of post-thyroidectomy hypocalcemia are also presented in detail. This article combines a review of fundamentals with recent advances in care, emphasizing pediatric-specific publications.

Impact of incidental parathyroidectomy and mediastinal-recurrent cellular and lymph-node dissection on parathyroid function after total thyroidectomy.

OBJECTIVES: To determine the impact of incidental parathyroidectomy and mediastinal-recurrent cellular and lymph-node dissection on parathyroid function after total thyroidectomy. MATERIAL AND METHODS: A single-center retrospective study was conducted for a 5-year period in a university hospital center, including 605 patients undergoing total thyroidectomy, 52 of whom had mediastinal-recurrent cellular and lymph-node dissection. ENDPOINTS: The main endpoint was intraoperative number of parathyroid glands as predictor of parathyroid hormone (PTH) level and postoperative hypocalcemia. The secondary endpoint was the correlation between associated mediastinal-recurrent cellular and lymph-node dissection and incidental parathyroidectomy and its impact on PTH level and calcemia in the immediate postoperative period and at 1 month. RESULTS: 161 patients (26.61%) showed hypocalcemia in the immediate postoperative period and 12 (1.98%) at 1 month. Mediastinal-recurrent cellular and lymph-node dissection increased incidental parathyroidectomy risk 4.6-fold. Mediastinal-recurrent cellular and lymph-node dissection was associated with a statistically "suggestive" decrease in day-1 calcemia (P=0.03), and no significant decrease at 1 month (P=0.52). Incidental parathyroidectomy (6.7% of cases with parathyroidectomy versus 1.3% without) did not significantly increase the rate of early hypocalcemia (P=0.28), but was associated with a "suggestive" worsening at 1 month (P=0.02). CONCLUSION: Hypocalcemia after total thyroidectomy is a complex, probably multifactorial issue. Systematic parathyroid gland identification is not recommended due to the increased risk of gland lesion, mainly by devascularization. Incidental parathyroidectomy may induce hypocalcemia at 1 month postoperatively (statistically "suggestive" association).

Mechanisms Involved in the Relationship between Low Calcium Intake and High Blood Pressure.

There is increasing epidemiologic and animal evidence that a low calcium diet increases blood pressure. The aim of this review is to compile the information on the link between low calcium intake and blood pressure. Calcium intake may regulate blood pressure by modifying intracellular calcium in vascular smooth muscle cells and by varying vascular volume through the renin-angiotensin-aldosterone system. Low calcium intake produces a rise of parathyroid gland activity. The parathyroid hormone increases intracellular calcium in vascular smooth muscles resulting in vasoconstriction. Parathyroidectomized animals did not show an increase in blood pressure when fed a low calcium diet as did sham-operated animals. Low calcium intake also increases the synthesis of calcitriol in a direct manner or mediated by parathyroid hormone (PTH). Calcitriol increases intracellular calcium in vascular smooth muscle cells. Both low calcium intake and PTH may stimulate renin release and consequently angiotensin II and aldosterone synthesis. We are willing with this review to promote discussions and contributions to achieve a better understanding of these mechanisms, and if required, the design of future studies.

Comparison Of The Effects Of Focus Harmonic Scalpel And Conventional Haemostasis On Parathyroid Function In Thyroid Surgery.

BACKGROUND: Protection of parathyroid is very important in thyroid surgery. Our aim was to compare the effect of Focus Harmonic Scalpel and Conventional Haemostasis on parathyroid function in thyroid surgery. METHODS: To analyse the clinical data of patients in our hospital from November 2011-December 2015 retrospectively. Operations have been performed with Focus Harmonic Scalpel in thyroid surgery since May 2013. Seventy-four patients with nodular goitre constituted Harmonic Scalpel group and Conventional Haemostasis group, and so did 139 patients with thyroid papillary carcinoma. Clinical data were compared such as age, gender, thyroid volume, operation procedure, preoperative parathyroid hormone and serum calcium concentration between the two groups. The differences between the two groups were observed in serum calcium concentration, parathyroid hormone concentration, incidence of transient hypocalcaemia and hypoparathyroidism after operation. RESULTS: The preoperative data showed no significant difference between Harmonic Scalpel group and Conventional Haemostasis group. No significant difference existed in postoperative clinic data at six a.m. the first day after operation between the two groups for patients with nodular goitre. The incidence of transient hypoparathyroidism and hypocalcaemia in Harmonic Scalpel group were less than that in Conventional Haemostasis group in thyroid surgery. Significant differences existed in the mean of serum calcium concentration and incidence of transient hypocalcaemia between the two groups for thyroid papillary carcinoma statistically. CONCLUSION: Focus Harmonic Scalpel has certain advantages than conventional Haemostasis in protecting parathyroid glands, reducing the incidence of transient hypoparathyroidism and hypocalcaemia in thyroid surgery, especially for patients with thyroid cancer.

The diagnostic value of parathyroid hormone washout in primary hyperparathyroidism patients with negative or equivocal 99 m Tc-MIBI results.

BACKGROUND AND OBJECTIVES: The accurate identification of hyper functioning parathyroid gland is needed for definitive surgical treatment in primary hyperparathyroidism. Ultrasonography and 99mTechnetium sestamibi scintigraphy are the two most used methods with varying sensitivities. This study aimed to assess the value of parathyroid hormone (PTH) assay in preoperative ultrasound guided fine needle aspiration (FNA)-PTH washout fluid to verify the correct localisation of lesions with negative or inconclusive scintigraphy results. METHODS: We evaluated data of 28 lesions in 21 patients who underwent US-guided parathyroid fine-needle aspiration (FNA) with PTH washout, retrospectively. The PTH washout results and the reports of parathyroid surgery and imaging studies were reviewed. RESULTS: Of operated 28 lesions 23 had positive and 5 had negative washout results. The median FNA-PTH washout was 2315.5 pg/ ml (min-max: 12.3-6978 pg/ ml). The calculated sensitivity of FNA-PTH washout was 85.7% and the specifity was 28.6%. The positive and negative predictive values were 78.3% and 40.0%, respectively. CONCLUSIONS: FNA-PTH can be used to establish the nature of the lesion, discriminate parathyroid gland from thyroid lesions or cervical lymph nodes, improving the surgical outcomes. It can be used to localise parathyroid lesions preoperatively when negative or discordant ultrasound and scintigraphy findings are obtained.

Epidemiology of parathyroid disorders.

Parathyroid disorders are not as uncommon as once believed. Both hyper- and hypoparathyroidism are more prevalent in women, but for different reasons. The female preponderance seen in primary hyperparathyroidism may be pathogenically linked, as it is more common after menopause. By contrast, higher prevalence of hypoparathyroidism in women is related to thyroid surgery, which is performed more frequently in women; thus the female to male ratio of hyper- and hypoparathyroidism is about 3:1 and 4:1 respectively. For similar reasons, the mean age of patients with hypoparathyroidism, on average, is a decade lower than that of patients with primary hyperparathyroidism. Furthermore, primary hyperparathyroidism is the third most common endocrine disorder after diabetes and thyroid disorders, but the prevalence of hypoparathyroidism is about 34 fold lower than that of primary hyperparathyroidism. Current epidemiological data is reasonable for primary hyperparathyroidism, but inadequate for hypoparathyroidism. Further concerted efforts should be undertaken to better define the distribution, determinants and disease burden of both disorders in order to prioritize practice guidelines, disease management strategies, and research agendas.

Growing Human Parathyroids in a Microphysiological System: A Novel Approach to Understanding and Developing New Treatments for Hyperparathyroidism.

We developed a novel model for studying hyperparathyroidism by growing ex vivo 3-dimensional human parathyroids as part of a microphysiological system (MPS) that mimics human physiology. The purpose of this study was to validate the parathyroid portion of the MPS. We prospectively collected parathyroid tissue from 46 patients with hyperparathyroidism for growth into pseudoglands. We evaluated pseudogland architecture and calcium responsiveness. Following 2 weeks in culture, dispersed cells successfully coalesced into pseudoglands ∼500-700 µm in diameter that mimicked the appearance of normal parathyroid glands. Functionally, they also appeared similar to intact parathyroids in terms of organization and calcium-sensing receptor expression. Immunohistochemical staining for calcium-sensing receptor revealed 240-450/cell units of mean fluorescence intensity within the pseudoglands. Finally, the pseudoglands showed varying levels of calcium responsiveness, indicated by changes in parathyroid hormone (PTH) levels. In summary, we successfully piloted the development of a novel MPS for studying the effects of hyperparathyroidism on human organ systems. We are currently evaluating the effect of PTH on adverse remodeling of tissue engineered cardiac, skeletal, and bone tissue within the MPS.

Physiology of Parathyroid Hormone.

Parathyroid hormone (PTH) is the major secretory product of the parathyroid glands, and in hypocalcemic conditions, can enhance renal calcium reabsorption, increase active vitamin D production to increase intestinal calcium absorption, and mobilize calcium from bone by increasing turnover, mainly but not exclusively in cortical bone. PTH has therefore found clinical use as replacement therapy in hypoparathyroidism. PTH also may have a physiologic role in augmenting bone formation, particularly in trabecular and to some extent in cortical bone. This action has been applied to the clinic to provide anabolic therapy for osteoporosis.

Alkaline Phosphatases in the Complex Chronic Kidney Disease-Mineral and Bone Disorders.

Alkaline phosphatases (APs) remove the phosphate (dephosphorylation) needed in multiple metabolic processes (from many molecules such as proteins, nucleotides, or pyrophosphate). Therefore, APs are important for bone mineralization but paradoxically they can also be deleterious for other processes, such as vascular calcification and the increasingly known cross-talk between bone and vessels. A proper balance between beneficial and harmful activities is further complicated in the context of chronic kidney disease (CKD). In this narrative review, we will briefly update the complexity of the enzyme, including its different isoforms such as the bone-specific alkaline phosphatase or the most recently discovered B1x. We will also analyze the correlations and potential discrepancies with parathyroid hormone and bone turnover and, most importantly, the valuable recent associations of AP's with cardiovascular disease and/or vascular calcification, and survival. Finally, a basic knowledge of the synthetic and degradation pathways of APs promises to open new therapeutic strategies for the treatment of the CKD-Mineral and Bone Disorder (CKD-MBD) in the near future, as well as for other processes such as sepsis, acute kidney injury, inflammation, endothelial dysfunction, metabolic syndrome or, in diabetes, cardiovascular complications. However, no studies have been done using APs as a primary therapeutic target for clinical outcomes, and therefore, AP's levels cannot yet be used alone as an isolated primary target in the treatment of CKD-MBD. Nonetheless, its diagnostic and prognostic potential should be underlined.

PARATHYROID FUNCTION AFTER TOTAL THYROIDECTOMY: A RANDOMIZED CLINICAL TRIAL CONCERNING THE INFLUENCE OF THE SURGICAL TECHNIQUE.

OBJECTIVE: Thyroidectomy impairs parathyroid function, even if it does not necessarily lead to postoperative clinical hypocalcemia. This study was prospective and evaluated the parathyroid hormone (PTH) function in nonclinically symptomatic patients after total thyroidectomy performed by two different techniques. METHODS: Prospective randomized clinical trial including 269 patients undergoing classic or harmonic scalpel total thyroidectomy. Pre-operatively and at 48 hours, biochemical analysis was performed. Simultaneously, a sodium bicarbonate test (SBT) was performed. RESULTS: Calcium and PTH were altered for both groups ( P<.001). During SBT at 3 minutes after infusion, PTH rose and reached its maximum for both groups ( P<.001) and then decreased at 5 minutes ( P<.001 and P = .004) and at 10 minutes ( P = .006 and P = .043) before returning to baseline levels. At 5 and 10 minutes of the SBT, some differences were observed between the groups. The difference in clinically obvious parathyroid dysfunction between groups was not significant, but there was a difference in the peak PTH levels after bicarbonate stimulation. Similarly, total secretion during the test, as well as total secretion for the first 10 minutes, was practically the same for the two groups. Additionally, partial subclinical postoperative hypoparathyroidism was clearly more common in the harmonic scalpel thyroidectomy group ( P<.001). CONCLUSION: SBT demonstrated more impairment in the harmonic scalpel group, as parathyroid function was altered after thyroidectomy. ABBREVIATIONS: HSTT = harmonic scalpel total thyroidectomy PTH = parathyroid hormone SBIT = sodium bicarbonate infusion test.

Causes and pathophysiology of hypoparathyroidism.

Hypoparathyroidism, a disorder characterized by hypocalcemia ensuing from inadequate parathyroid hormone secretion, is a rather rare disorder caused by multiple etiologies. When not caused by inadvertent damage or removal of the parathyroids during neck surgery, it is usually genetically determined. Epidemiological figures of this disease are still scarce and mainly limited to countries where non-anonymous databases are available and to surgical case series. Both the surgical and non-surgical forms pose diagnostic challenges. For surgical hypoparathyroidism, transient forms have to be ruled out even in the long term, in order to avoid unnecessary chronic replacement therapy with calcium and calcitriol. Regarding non-surgical hypoparathyroidism, once referred to as idiopathic, a systematic clinically and genetically-driven approach to define the precise diagnosis have to be pursued. In the case of syndromic hypoparathyroidism, patients have to be screened for associated abnormalities. Autoimmune, non-genetic hypoparathyroidism is still a diagnosis of exclusion, since no specific autoantibodies are specific for this condition.

Enhanced identification and functional protective role of carbon nanoparticles on parathyroid in thyroid cancer surgery: A retrospective Chinese population study.

The aim of this study was to determine the effects of nanocarbon particles in combination with meticulous capsular dissection on enhancing the identification and protecting the function of parathyroid glands in thyroid cancer surgery.The data of 97 patients with papillary thyroid tumors diagnosed and treated at the Second Affiliated Hospital, Harbin Medical University between January 2014 and February 2015 were reviewed. Data regarding the sex, age, calcium and parathyroid hormone (PTH) levels, tumor size, multifocality, T stage, and extrathyroid invasion were collected. The incidence of surgeries in which the parathyroid glands were cut mistakenly, the concentration of serum calcium and parathyroid hormone before surgery (baseline) and after surgery on days 1, 3, and 7, and 1 and 6 months in the patients of the two groups (the nanocarbon and control groups) were analyzed.Fifty-two patients underwent meticulous capsular dissection combined with nanocarbon treatment (nanocarbon group), and 45 underwent meticulous capsular dissection alone (control group). The nanocarbon group showed a significantly higher total and average number of revealed parathyroid glands (average number is the mean for different individuals have different number) and a lower incidence of the parathyroid glands being mistakenly cut, in addition to a lower level of hypoparathyroidism than control group following surgery (P < 0.05). Serum calcium and PTH levels were significantly lower in patients from both groups after surgery on days 1, 3, and 7 and after 1 month, compared with the preoperative levels (P < 0.05). Compared with the control group, the serum calcium and PTH levels were significantly higher in the nanocarbon group after surgery on days 1, 3, 7, than in the control group.Treatment with nanocarbon in combination with meticulous capsular dissection can significantly facilitate the identification of the parathyroid in thyroid cancer surgery, reduce the risk of mistakenly cutting the parathyroid, and reduce the incidence of postoperative hypoparathyroidism.

The history of the parathyroid surgery.

The authors conducted a review of the major aspects of progression of knowledge about the surgical treatment of hyperparathyroidism. Through literature review, we analyzed articles on the history of the evolution of anatomical, physiological, pathological and surgical knowledge of the parathyroid glands. Because of their unique anatomical features, the parathyroid glands were the last of the endocrine glands to be discovered, which greatly hindered proper treatment until the first decades of the twentieth century. Technological developments in the last 30 years greatly facilitated the location of the glands and hyperparathyroidism surgery. However, an experienced and dedicated surgeon is still essential to the excellence of treatment. RESUMO Os autores fizeram uma revisão dos principais aspectos históricos da progressão do conhecimento sobre o tratamento cirúrgico do hiperparatireoidismo. Por meio de revisão bibliográfica, foram analisados artigos selecionados sobre a história da evolução do conhecimento anatômico, fisiológico, patológico e cirúrgico das glândulas paratireoides. Devido às suas características anatômicas peculiares, as paratireoides foram as últimas das glândulas endócrinas a serem descobertas, o que dificultou sobremaneira seu tratamento adequado até as primeiras décadas do Século XX. A evolução tecnológica ocorrida nos últimos 30 anos facilitou sobremaneira a localização das glândulas e a cirurgia do hiperparatireoidismo. Contudo, um cirurgião experiente e dedicado ao tratamento dessa enfermidade ainda é fundamental para a excelência do tratamento.

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation.

The avian thymus and parathyroids (T/PT) common primordium derives from the endoderm of the third and fourth pharyngeal pouches (3/4PP). The molecular mechanisms that govern T/PT development are not fully understood. Here we study the effects of Notch and Hedgehog (Hh) signalling modulation during common primordium development using in vitro, in vivo and in ovo approaches. The impairment of Notch activity reduced Foxn1/thymus-fated and Gcm2/Pth/parathyroid-fated domains in the 3/4PP and further compromised the development of the parathyroid glands. When Hh signalling was abolished, we observed a reduction in the Gata3/Gcm2- and Lfng-expression domains at the median/anterior and median/posterior territories of the pouches, respectively. In contrast, the Foxn1 expression-domain at the dorsal tip of the pouches expanded ventrally into the Lfng-expression domain. This study offers novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner.

[The progress in application of parathyroid hormone in craniomaxillofacial bone regeneration study].

Parathyroid hormone(PTH)is synthesized and secreted by chief cell of Gley's glands which possesses dual functions of catabolism and anabolism. It regulates the proliferation and differentiation of multiple cell lines including osteoblast, osteoclast and skeletal lining cells. Furthermore, PTH activates various signaling pathways which control calcium, phosphorous' metabolism and bone conversion, accelerating the bone regeneration and reconstruction. However, the study of PTH in craniomaxillofacial bone regeneration is relatively less and whether the role of parathyroid glands and the mechanism of ossification are consistent with the long bone or not needs further investigation. This review focuses on the progress of PTH in craniomaxillofacial bone regeneration in recent years.

The history of the parathyroid surgery / A história da cirurgia das paratireoides

ABSTRACT The authors conducted a review of the major aspects of progression of knowledge about the surgical treatment of hyperparathyroidism. Through literature review, we analyzed articles on the history of the evolution of anatomical, physiological, pathological and surgical knowledge of the parathyroid glands. Because of their unique anatomical features, the parathyroid glands were the last of the endocrine glands to be discovered, which greatly hindered proper treatment until the first decades of the twentieth century. Technological developments in the last 30 years greatly facilitated the location of the glands and hyperparathyroidism surgery. However, an experienced and dedicated surgeon is still essential to the excellence of treatment.

RESUMO Os autores fizeram uma revisão dos principais aspectos históricos da progressão do conhecimento sobre o tratamento cirúrgico do hiperparatireoidismo. Por meio de revisão bibliográfica, foram analisados artigos selecionados sobre a história da evolução do conhecimento anatômico, fisiológico, patológico e cirúrgico das glândulas paratireoides. Devido às suas características anatômicas peculiares, as paratireoides foram as últimas das glândulas endócrinas a serem descobertas, o que dificultou sobremaneira seu tratamento adequado até as primeiras décadas do Século XX. A evolução tecnológica ocorrida nos últimos 30 anos facilitou sobremaneira a localização das glândulas e a cirurgia do hiperparatireoidismo. Contudo, um cirurgião experiente e dedicado ao tratamento dessa enfermidade ainda é fundamental para a excelência do tratamento.