CHARACTERISTICS OF NON-RENAL NORMOCALCIEMIC HYPERPARATHYROIDISM IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / ДОСЛІДЖЕННЯ ОСОБЛИВОСТЕЙ НЕРЕНАЛЬНОГО НОРМОКАЛЬЦІЄМІЧНОГО ГІПЕРПАРАТИРЕОЗУ У ОСІБ, ПОСТРАЖДАЛИХ ВНАСЛІДОК АВАРІЇ НА ЧАЕС.

OBJECTIVE: to assess the hormonal and metabolic disorders in the Chernobyl nuclear power plant (ChNPP) accident survivors (AS), having got secondary normocalcemic non-renal hyperparathyroidism (HPT) in the late period upon exposure to ionizing radiation (IR). MATERIALS AND METHODS: The routine clinical, anthropometric, instrumental (thyroid and parathyroid diagnosticultrasound), laboratory (biochemical, hormonal), statistical methods were applied. In both prospective (n = 48, control group n = 19) and retrospective studies the data of 2,234 subjects including 1,372 irradiated adults (862 non-irradiated persons in the control group) were evaluated. Clinical consequences of exposure to IR on the endocrine system were evaluated in ChNPP AS. RESULTS: High prevalence of vitamin D lack or deficiency was established retrospectively in 81.8 % of the ChNPP AS and in 89.5 % of the control group subjects. In general, there was neither effect of exposure to IR on the vitamin D status in study subjects, nor any difference between the study groups. According to diagnostic ultrasound patterns the parathyroid hyperplasia was diagnosed in 629 cases (28.2 %). Among the ChNPP AS it was found in 32.7 % of cases (n = 450) vs. 20.7 % (p > 0.005) in the control group (a 1.6-fold difference). HPT diagnosed as serum parathyroid hormone content > 65 ng/ml was diagnosed in 123 cases (21.1 %) i.e. in almost every fifth person. Increased serum level of parathyroid hormone was found in the 94 ChNPP AS and in 25 persons of the comparison group. In other words, the frequency of HPT was 23.7 % among the AS being significantly more than in the comparison group (13.2 %, p < 0.005). Frequency of normocalcemic non-renal HPT was slightly different by years of observation with a trend to the year-by-year increase. CONCLUSIONS: High prevalence of vitamin D lack or deficiency was established in the ChNPP AS, being however independent of exposure to IR. Frequency of parathyroid hyperplasia/adenoma was 1.6 times higher in the irradiated subjects than in persons of the control group. Annual increase in frequency of the non-renal normocalcemic HPT was also revealed reaching nowadays 23.7 % among the AS, which is significantly higher than in the comparison group.

Effect of Microdissection of Inferior Thyroid Artery on Post-operative Hypocalcemia in Total Thyroidectomy.

Hypocalcemia is one of the most common complication after bilateral thyroid surgery. Reported rates range from 5 to 35% and 0.5 to 4.4% for transient and permanent hypocalcemia respectively. Various methods have been devised to reduce the post-operative hypocalcemia and range from modification of surgical techniques to use of loops and avoidance of inadverant neck dissections. We conducted a randomised control trial of 50 patients divided into two groups, to evaluate the effect of microdissection and ligation of distal branches of inferior thyroid artery (group B) on incidence of temporary and permanent hypocalcaemia in patients of total thyroidectomy versus its ligation distally close to the thyroid capsule(group A). Postoperative mean total serum calcium levels were lower in group A as compared to group B (9.13 mg/dl vs. 9.33 mg/dl at 24 h; 8.77 vs. 9.10 at 3rd day and 8.58 vs. 8.96 mg/dl on 10 th day) with p > 0.05. The value of ionized serum calcium as recorded on 3rd day was 4.39 mg/dl for group A and 4.72 mg/dl for group B with p value ≤ 0.001 (Table 2). 19 patients in group A required calcium supplementation for 6 months with incidence of transient hypocalcemia at 76% while 11 patients in group B had calcium supplementation for 6 months with incidence of 40% and difference was significant statistically. Microdissection technique is better for preventing the temporary hypocalcemia and hence decreasing the hospital visits of the patient when compared to the ligation of inferior thyroid artery distally close to the thyroid gland. The incidence of permanent hypocalcemia doesn't varies significantly between both techniques.

Telocytes/CD34+ Stromal Cells in the Normal, Hyperplastic, and Adenomatous Human Parathyroid Glands.

Telocytes/CD34+ stromal cells (TCs/CD34+ SCs) have been studied in numerous organs and tissues, but their presence and characteristics in the parathyroid glands have not been explored. Using immunological and ultrastructural procedures, we assess the location, arrangement, and behavior of TCs/CD34+ SCs in normal human parathyroids, during their development and in their most frequent pathologic conditions. In normal parathyroids, TCs/CD34+ SCs show a small somatic body and long thin processes with a moniliform aspect, form labyrinthine systems, connect other neighboring TCs/CD34+ SCs, vessels, adipocytes, and parenchymal cells directly or by extracellular vesicles, and associate with collagen I. TCs/CD34+ SCs and collagen I are absent around vessels and adipocytes within parenchymal clusters. In developing parathyroids, TCs/CD34+ SC surround small parenchymal nests and adipocytes. In hyperplastic parathyroids, TCs/CD34+ SCs are prominent in some thickened internodular septa and surround small extraglandular parenchymal cell nests. TCs/CD34+ SCs are present in delimiting regions with compressed parathyroids and their capsule in adenomas but absent in most adenomatous tissue. In conclusion, TCs/CD34+ SCs are an important cellular component in the human parathyroid stroma, except around vessels within parenchymal nests. They show typical characteristics, including those of connecting cells, are present in developing parathyroids, and participate in the most frequent parathyroid pathology, including hyperplastic and adenomatous parathyroids.

First Application of the Orbeye™ 4K 3D Exoscope in Recurrent Papillary Thyroid Cancer Surgery.

Reoperation for recurrent papillary thyroid cancer (RPTC) is much more complex than primary surgery is, with a higher rate of complications. We describe, for the first time, the use of the Orbeye™ surgical microscope/exoscope for the treatment of RPTC with lymphadenectomy. This system offers 4K, three-dimensional magnified and illuminated imaging without the need for eyepieces. Magnification of the field of view facilitates a more precise dissection, preserving the anatomical structure. Currently, the Orbeye™ is regularly used in neurosurgery; however, its potential in conventional open surgery has not yet been fully exploited. Owing to its magnification capacity, the Orbeye™ exoscope is a valuable tool to help surgeons identify and preserve the integrity of the recurrent laryngeal nerves and parathyroids during thyroid surgery.

Semiquantitative assessment of 99mTc-MIBI uptake in parathyroids of secondary hyperparathyroidism patients with chronic renal failure.

Objective: To explore the valuably influential factors and improve the diagnostic accuracy and efficiency of 99mTc-methoxyisobutylisonitrile (MIBI) uptake in parathyroids of secondary hyperparathyroidism (SHPT) patients with chronic renal failure (CRF). Methods: The correlation analysis was performed between clinical indices related to CRF and 99mTc-MIBI uptake intensity TBR (the gray value mean ratio between the parathyroid target and the bilateral neck background, semiquantitatively calculated with ImageJ software). All clinical indices and TBRs were compared by a three- or two-level grouping method of MIBI uptake, which was visually qualitatively assessed. The three-level grouping method comprised slight, medium, and high groups with little, faint, and distinct MIBI concentration in parathyroids, respectively. The two-level grouping method comprised insignificant and significant groups with TBR greater than or less than 0.49-0.71, respectively. Results: MIBI uptake was significantly positively related to patient age, CRF course, hemodialysis vintage, serum parathyroid hormone (PTH), and alkaline phosphatase (AKP) but was significantly negatively related to serum uric acid (UA). MIBI washout was significantly positively related to patient age but was significantly negatively related to serum phosphorus (P) and calcium (Ca) × P. Oral administration of calcitriol and calcium could significantly reduce the MIBI uptake. MIBI uptake tendency might alter. Such seven indices, namely the MIBI uptake, CRF course, hemodialysis vintage, serum AKP, calcium, cysteine proteinase inhibitor C, and PTH, were comparable between the slight and medium groups but were significantly different between the slight and high groups or between the medium and high groups. The above seven indices plus blood urea nitrogen/creatinine were all significantly different between the insignificant and significant groups. All above significances were with P < 0.05. Conclusions: Patient age, CRF course, hemodialysis vintage, serum PTH, AKP, UA, phosphorus, Ca × P, oral administration of calcitriol and calcium, and parathyroids themselves can significantly influence MIBI uptake in parathyroids of SHPT patients with CRF. The two-level grouping method of MIBI intensity should be adopted to qualitatively diagnose the MIBI uptake.

Limited contribution of indocyanine green (ICG) angiography for the detection of parathyroid glands and their vascularization during total thyroidectomy: A STROBE observational study.

INTRODUCTION: In total thyroidectomy, indocyanine green (ICG) angiography has mainly been evaluated at end of procedure to predict postoperative hypoparathyroidism. By using it during surgery, we sought to determine whether it could also be an aid to the surgeon. OBJECTIVE: To determine whether ICG used intraoperatively in total thyroidectomy modified the surgical procedure. MATERIAL AND METHOD: Thirty-two patients who underwent ICG angiography during total thyroidectomy were included in our single-center retrospective study. The number of parathyroid (PT) glands visualized in white light and on ICG angiography was collected, as well as PT vitality of at end of surgery according to these two modalities. Vitality scores were 0 (no vascularity), 1 (moderately vascularized) or 2 (well vascularized). Postoperative calcemia at D1, D2 and D7 was analyzed. RESULTS: In the 32 operations, the surgical procedure was modified in 10 cases (31%). The average number of PTs detected was 2.4 (77 PT) on ICG angiography and 2 (65 PT) in white light. Eleven patients (37.5%) had postoperative hypocalcemia. Cumulative vitality scores at end of procedure were 3.75/8 and 3.37/8 in white light and on ICG angiography respectively (P=0.648). The use of the device did not predict the occurrence of postoperative hypocalcemia. CONCLUSION: Indocyanine green angiography used in thyroid surgery could assist the surgeon in the identification of PT glands, sparing them in one third of cases.

The latest anatomical discovery: the parathyroid glands or Glandulae parathyreoideae of Owen-Sandström-Gley.

In 1852, Owen, a prominent British anatomist, described the parathyroid glands. While dissecting a rhinoceros, he noted a small compact yellow body, attached to the thyroid. Virchow and later Remak described the human parathyroids around 1960, but credit for the first complete description goes to the Sandström in 1980. More than a decade later Gley, showed that it was the removal of the parathyroids that accounted for the tetany that followed thyroidectomy. The association of parathyroid pathology and skeletal abnormalities was made in 1914 by Erdheim and Schlagenhaufer, and Mandl, was the first surgeon to successfully treat a case of osteitis fibrosa by surgical removal of a parathyroid adenoma in 1925. The most extensive work on hyperparathyroidism was done in the 1930s by Albright form Boston, who described parathyroid hyperplasia, and differentiated between primary, secondary and tertiary hyperparathyroidism. Progresses in anatomy, physiology and surgery of the parathyroid glands, have contributed to various effective modalities of diagnosis and treatment.

En 1852, Owen, un destacado anatomista británico, describió las glándulas paratiroides. Mientras realizaba la disección de un rinoceronte indio, observó un pequeño cuerpo amarillo compacto, unido a la tiroides. Virchow, y más tarde Remak, describieron las paratiroides humanas alrededor de 1860, pero el crédito por la primera descripción completa es para Sandström en 1880. Más de una década después, Gley demostró que era la eliminación de las paratiroides lo que explicaba la tetania después de la tiroidectomía. La asociación de la patología paratiroidea y las anomalías esqueléticas fue establecida en 1914 por Erdheim y Schlagenhaufer, y Mandl fue el primer cirujano en tratar con éxito un caso de osteítis fibrosa mediante la extirpación quirúrgica de un adenoma paratiroideo en 1925. El trabajo más extenso sobre el hiperparatiroidismo fue realizado en la década de 1930 por Albright, en Boston, quien describió la hiperplasia paratiroidea y la diferenció del hiperparatiroidismo primario, secundario y terciario. Los avances en anatomía, fisiología y cirugía de las glándulas paratiroides han contribuido a diversas modalidades efectivas de diagnóstico y tratamiento.

CLINICAL-METABOLIC AND HORMONAL RELATIONSHIPS BETWEEN PARATHYROID DISEASE AND OTHER NON-CANCEROUS ENDOCRINE DISORDERS IN THE CHORNOBYL NPP ACCIDENT SURVIVORS. / KLINIKO-METABOLIChNI TA GORMONAL'NI VZAIeMOZV'IaZKY MIZh PATOLOGIIeIu PRYShchYTOPODIBNYKh ZALOZ TA INShYMY NEZLOIaKISNYMY ENDOKRYNNYMY ZAKhVORIuVANNIaMY U POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: to investigate the clinical, hormonal-metabolic and structural features of parathyroid injuries in sur-vivors exposed to ionizing radiation after the Chornobyl NPP accident in adulthood and childhood, both with theirconnections to other non-cancerous endocrine disorders, and to establish the respective interhormonal and dys-metabolic relationships. MATERIALS AND METHODS: Clinical effects of ionizing radiation on the endocrine system in persons affected by theChornobyl NPP accident (n = 224) and their descendants (n = 146), compared with the general population sample(n = 70) were the study object. All patients underwent the ultrasound thyroid and parathyroid examination. Thegenerally recognized clinical, anthropometric (body weight, height, thigh volume, body mass index), instrumental(ultrasound examination of thyroid and parathyroid glands), laboratory (biochemical, hormonal), and statisticalmethods were applied. Parametric and nonparametric statistical methods were used in data processing. The value ofp < 0.05 was considered a statistically significant. RESULTS: No significant difference was found in the incidence of carbohydrate metabolic disorders in the ChornobylNPP (ChNPP) accident consequences clean-up workers (ACCUW), evacuees from the NPP 30-km exclusion zone, res-idents of radiologically contaminated areas and in the control group in whom the parathyroid hyperplasia wasdetected. There was a significant increase in the incidence of arterial hypertension among ACCUW who had parathy-roid hyperplasia (76.9%) vs. the control group (51.2%). In cases of parathyoid hyperplasia the vitamin D levels weresignificantly lower than without it. Vitamin D insufficiency/deficiency was found in 94% of the surveyed subjects.The average level of parathyroid hormone in blood serum was significantly higher in the ACCUW of «iodine¼ period withdiagnosed parathyroid hyperplasia than in the control group: (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml,p < 0.05. Results of multivariative analysis indicated a strong association of vitamin 25(OH)D insufficiency/defi-ciency with development of thyroid disease, carbohydrate metabolic disorders, cardiovascular disease, osteo-penia/osteoporosis. parathyroid ultrasound scan was at that an effective diagnostic method for primary screeningfor parathyroid hyperplasia and regular monitoring of the treatment efficiency. When examining children bornto parents irradiated after the ChNPPA the parathyroid hyperplasia (58%) and low serum content of vitamin D(11.6 ± 3.5) nmol / l were most often found in children living on radiologically contaminated territories (RCT).A strong correlation was established between the HOMA insulin resistance index and serum content of vitamin D(r = 0.65), parathyroid hormone (r = 0.60), and free thyroxine (r = 0.68) in the group of children born to parents irra-diated after the ChNPPA, having got chronic autoimmune thyroiditis, which indicated a relationship between thy-roid function, impaired carbohydrate and fat metabolism and the state of parathyroids. CONCLUSIONS: No difference in the incidence of carbohydrate metabolic disorders was found in the ChNPP ACCUW,evacuees from the 30-km exclusion zone, and residents of radiologically contaminated territories in whom parathy-roid hyperplasia was detected vs. the control group. Patients with parathyroid hyperplasia were found to be defi-cient in vitamin D in 94% of cases, and level of latter was significantly lower than under the normal parathyroid size.There was a significant increase in the incidence of diagnosed arterial hypertension among ACCUW who had parathy-roid hyperplasia vs. the control group: (76.9 ± 3.5)% vs. (51.2 ± 3.7)%. According to multivariate analysis a strongassociation between the vitamin 25(OH)D insufficiency/deficiency and development of thyroid disease, carbohydratemetabolic disorders, cardiovascular disease, and osteopenia/osteoporosis was established. The average level of pa-rathyroid hormone in the blood serum of the ChNPP ACCUW of the «iodine¼ period with diagnosed parathyroid hyper-plasia was significantly higher (57.2 ± 2.87) pg / ml against (32.74 ± 3.58) pg / ml; p <0,05) in the control group.

EZH2 is required for parathyroid and thymic development through differentiation of the third pharyngeal pouch endoderm.

The Ezh2 gene encodes a histone methyltransferase of the polycomb repressive complex 2 that methylates histone H3 lysine 27. In this study, we investigated whether EZH2 has a role in the development of the pharyngeal apparatus and whether it regulates the expression of the Tbx1 gene, which encodes a key transcription factor required in pharyngeal development. To these ends, we performed genetic in vivo experiments with mouse embryos and used mouse embryonic stem cell (ESC)-based protocols to probe endoderm and cardiogenic mesoderm differentiation. Results showed that EZH2 occupies the Tbx1 gene locus in mouse embryos, and that suppression of EZH2 was associated with reduced expression of Tbx1 in differentiated mouse ESCs. Conditional deletion of Ezh2 in the Tbx1 expression domain, which includes the pharyngeal endoderm, did not cause cardiac defects but revealed that the gene has an important role in the morphogenesis of the third pharyngeal pouch (PP). We found that in conditionally deleted embryos the third PP was hypoplastic, had reduced expression of Tbx1, lacked the expression of Gcm2, a gene that marks the parathyroid domain, but expressed FoxN1, a gene marking the thymic domain. Consistently, the parathyroids did not develop, and the thymus was hypoplastic. Thus, Ezh2 is required for parathyroid and thymic development, probably through a function in the pouch endoderm. This discovery also provides a novel interpretational key for the finding of Ezh2 activating mutations in hyperparathyroidism and parathyroid cancer.

Effect of etelcalcetide on parathyroid hormone secretion by primary hyperparathyroidism patient-derived primary parathyroid cells.

INTRODUCTION: Etelcalcetide (Parsabiv®, AMG 416/ONO-5163) is a novel allosteric modulator for the calcium-sensing receptor approved for hemodialysis patients with secondary hyperparathyroidism of uremia. Etelcalcetide reduced parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism of uremia in clinical studies. However, its direct effect on parathyroid hormone secretion in human parathyroid cells remains unknown. This study aimed to determine if etelcalcetide suppresses parathyroid hormone secretion by human parathyroid cells in vitro. MATERIALS AND METHODS: We prepared primary cell cultures from human parathyroid tissue and determined calcium-sensing receptor expression levels by immunohistochemistry. Pathyroid tumors were removed from fourteen patients with primary hyperparathyrodism. Parathyroid tissue was dispersed with collagenase, resuspended in culture medium, incubated for 2 h with etelcalcetide and Ca2+, and the medium was then collected. Final etelcalcetide concentrations in the medium were 0.005-50 µmol/L. Levels of human parathyroid hormone in the medium were determined by enzyme-linked immunosorbent assay. RESULTS: In eight of the fourteen parathyroid cell cultures, extracellular Ca2+ reduced parathyroid hormone levels. In four of the eight parathyroid cell cultures which responded extracellular Ca2+, etelcalcetide reduced hormone secretion with the 50% effective concentrations of 0.57, 20.8, 0.42, and 0.57 µmol/L. Expression levels of the calcium-sensing receptor were significantly lower in primary hyperparathyroidism patient-derived parathyroid tissues compared with controls. CONCLUSION: This is the first report that etelcalcetide directly reduced parathyroid hormone secretion from the primary cultured human parathyroid cells from patients with primary hyperparathyroidism. To verify this conclusion, further studies are needed using secondary hyperparathyroidism patient-derived parathyroid cells.

[Ectopic hyperparathyroidism. Detection of mediastinal localization]. / Hiperparatiroidismo ectópico. Detección de la localización mediastinal.

The ectopic parathyroid tissue is a frequent cause of recurrent hyperparathyroidism (HPT), accounting 16% in primary HPT and 14% in secondary cases. Although intrathoracic ectopic glands represent 25-35% of all ectopic cases, only 2% requires thoracic surgery. The aim of this study is to report a case series of patients with ectopic mediastinal HPT treated by thoracic approach in a private institution in Argentina. This is a retrospective analysis from January 2006 to June 2019. All patients diagnosed with ectopic hyperparathyroidism who required a thoracic surgical approach were included. During this period, 728 patients with primary HPT and secondary HPT were treated. Six with primary HPT and 3 with secondary HPT required a thoracic approach. Six video-assisted thoracoscopy surgeries (VATS) and 3 sternotomies were performed. None of them presented serious posoperative complications. Frozen section biopsy was used in all cases. iPTH was measured in 8 cases, with a mean drop of 65% after 15 minutes. Final pathology reports confirmed 5 adenomas and 4 hyperplasias. Our case series reported an incidence of 1.65% (12/728) mediastinal parathyroids, while 1.24% (9/728) received surgical treatment at our institution. Intraoperative frozen section and PTHi are useful to confirm the diagnosis and to avoid recurrences. Although VATS is a safe and efficient treatment option, it depends on surgical training and availability. In terms of diagnostic imaging resources, sestamibi remains the current gold standard. However, 18F-choline PET/CT may arise as a new diagnostic tool. The possibility of obtaining evidence-based conclusions requires studies with higher number of patients.

El tejido paratiroideo ectópico es una causa frecuente de recurrencia del hiperparatiroidismo (HPT) siendo de 16% en primarios y 14% en secundarios. La localización intratorácica representa el 20-35%, pero solo un 2% requiere una cirugía torácica. El objetivo fue analizar una cohorte de pacientes con diagnóstico de HPT mediastinal operados en un hospital de alta complejidad de Argentina. Se realizó un estudio retrospectivo de todos los operados por HPT entre enero de 2006 y julio 2019 en ese hospital. Se incluyeron aquellos que requirieron acceso torácico por HPT ectópico. En este período se trataron 728 pacientes con HPT primario y secundario. Seis con primario y 3 con secundario requirieron cirugía torácica. Se realizaron 6 videotoracoscopias (VATS) y 3 esternotomías, sin complicaciones graves. Se utilizó biopsia por congelación en todos y dosaje de paratohormona intraoperatoria (PTHi) en 8 casos, que descendió en promedio 65% respecto al valor basal. Se confirmaron 5 adenomas y 4 hiperplasias. La enfermedad paratiroi dea mediastinal representó el 1.65% (12/728), mientras que recibieron tratamiento quirúrgico en nuestra institución 1.24% (9/728). La biopsia por congelación y el descenso de PTHi resultan útiles para confirmar el foco y eventualmente disminuir el riesgo de recurrencia. La VATS es segura pero depende del entrenamiento y de la disponibilidad en el medio asistencial. Si bien el sestamibi es el método con mayor sensibilidad, se propone el uso de 18F-colina PET/TC ante la sospecha de HPT ectópico. La posibilidad de obtener conclusiones basadas en la evidencia requiere de estudios con mayor número de pacientes.

Hiperparatiroidismo ectópico: Detección de la localización mediastinal / Ectopic hyperparathyroidism. Detection of mediastinal localization

El tejido paratiroideo ectópico es una causa frecuente de recurrencia del hiperparatiroidismo (HPT) siendo de 16% en primarios y 14% en secundarios. La localización intratorácica representa el 20-35%, pero solo un 2% requiere una cirugía torácica. El objetivo fue analizar una cohorte de pacientes con diagnóstico de HPT mediastinal operados en un hospital de alta complejidad de Argentina. Se realizó un estudio retrospectivo de todos los operados por HPT entre enero de 2006 y julio 2019 en ese hospital. Se incluyeron aquellos que requirieron acceso torácico por HPT ectópico. En este período se trataron 728 pacientes con HPT primario y secundario. Seis con primario y 3 con secundario requirieron cirugía torácica. Se realizaron 6 videotoracoscopias (VATS) y 3 esternotomías, sin complicaciones graves. Se utilizó biopsia por congelación en todos y dosaje de paratohormona intraoperatoria (PTHi) en 8 casos, que descendió en promedio 65% respecto al valor basal. Se confirmaron 5 adenomas y 4 hiperplasias. La enfermedad paratiroi dea mediastinal representó el 1.65% (12/728), mientras que recibieron tratamiento quirúrgico en nuestra institución 1.24% (9/728). La biopsia por congelación y el descenso de PTHi resultan útiles para confirmar el foco y eventualmente disminuir el riesgo de recurrencia. La VATS es segura pero depende del entrenamiento y de la disponibilidad en el medio asistencial. Si bien el sestamibi es el método con mayor sensibilidad, se propone el uso de 18F-colina PET/TC ante la sospecha de HPT ectópico. La posibilidad de obtener conclusiones basadas en la evidencia requiere de estudios con mayor número de pacientes.

The ectopic parathyroid tissue is a frequent cause of recurrent hyperparathyroidism (HPT), accounting 16% in primary HPT and 14% in secondary cases. Although intrathoracic ectopic glands represent 25-35% of all ectopic cases, only 2% requires thoracic surgery. The aim of this study is to report a case series of patients with ectopic mediastinal HPT treated by thoracic approach in a private institution in Argentina. This is a retrospective analysis from January 2006 to June 2019. All patients diagnosed with ectopic hyperparathyroidism who required a thoracic surgical approach were included. During this period, 728 patients with primary HPT and secondary HPT were treated. Six with primary HPT and 3 with secondary HPT required a thoracic approach. Six video-assisted thoracoscopy surgeries (VATS) and 3 sternotomies were performed. None of them presented serious posoperative complications. Frozen section biopsy was used in all cases. iPTH was measured in 8 cases, with a mean drop of 65% after 15 minutes. Final pathology reports confirmed 5 adenomas and 4 hyperplasias. Our case series reported an incidence of 1.65% (12/728) mediastinal parathyroids, while 1.24% (9/728) received surgical treatment at our institution. Intraoperative frozen section and PTHi are useful to confirm the diagnosis and to avoid recurrences. Although VATS is a safe and efficient treatment option, it depends on surgical training and availability. In terms of diagnostic imaging resources, sestamibi remains the current gold standard. However, 18F-choline PET/CT may arise as a new diagnostic tool. The possibility of obtaining evidence-based conclusions requires studies with higher number of patients.

[HYPERPARATHYROIDISM AND PARATHYROID LESIONS IN THE ChNPP ACCIDENT SURVIVORS]. / GIPERPARATYREOZ TA URAZhENNIa PRYShchYTOPODIBNYKh ZALOZ U OSIB, OPROMINENYKh VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: Study of the status of parathyroid glands in individuals exposed to ionizing radiation as a result of the ChNPP accident and comparison with the general population of Ukraine. MATERIALS AND METHODS: Subjects exposed as a result of the ChNPP accident (n = 1,348) and people from the general population of Ukraine (n=655) were examined. Diagnostic ultrasound scan of thyroid and parathyroid glands (PTG) was conducted in all study subjects. The technique of parathyroid ultrasound screening was developed, which led to an increase in the efficiency of their imaging. Additionally, the 25-hydroxyvitamin D (25(OH)D), parathyroid hor- mone, ionized calcium and some other parameters were selectively assayed in serum. RESULTS: High incidence of parathyroid hyperplasia was detected 27-32 years after the irradiation in persons ex- posed as a result of the ChNPP accident, especially in evacuees from the 30-km exclusion zone (71.4%; χ2Yates' = 24.1; р = 0) and residents of radilogically contaminated territories (41.7%; χ2Yates' = 6.45; p < 0.01) having no primary hyperparathyroidism. High prevalence of vitamin D insufficiency and deficiency was revealed in all study subgroups, namely in 83.1 % of the general population of Ukraine along with a bit better vitamin D status in the ChNPP acci- dent survivors i.e. the vitamin insufficiency and deficiency was found in 78.7 % of them. Incidence of hyperparathy- roidism, predominantly of the secondary (normocalcemic) one, was 33.8 % among persons exposed as a result of the ChNPP accident (p > 0.3) being somewhat higher than in the general population of Ukraine (26.1%), despite above- mentioned better supply of vitamin D. CONCLUSIONS: There is a widespread insufficiency or deficiency of vitamin D (over 78.7%) in the population of Ukraine in general providing an unfavorable background for the higher prevalence of health disorders associated with calcium and phosphorus metabolism. The latter features parathyroid hyperplasia and musculosceletal, immune, cardiovascular, and endocrine system comorbidities. Such disorders should exacerbate with a secondary increase in parathyroid hormone secretion (26.1 %). Higher incidence of normocalcemic hyperparathyroidism (33.8% versus 26.1%) against a background of better vitamin D status among irradiated individuals indicates the existence of other factors, where the past combined effects of Chornobyl radioactive fallout and external parathyroid exposure are most likely to be involved. This could explain the greater number of cases of parathyroid hyperplasia and hyper- parathyroidism among the exposed subjects. However the additional precise studies are required here with clarifi- cation of the personal data in population groups of the ChNPP accident survivors. Participants of the ChNPP acci- dent clean-up work in the «iodine period¼ of 1986 are of especial concern here. Besides that, the study population should be expanded with inclusion of subjects exposed in prenatal period.

The Value of Imaging of the Parathyroid Glands in Secondary Hyperparathyroidism.

It is estimated that up to 90% of patients with chronic kidney disease develop secondary hyperparathyroidism (sHPT). Although the disease has multiple manifestations, the most important pathological feature, from the point of view of increased mortality, is represented by the ectopic arterial, myocardial and cardiac valvular calcifications. The calcifications are progressive and lead to high blood pressure, left ventricular hypertrophy, atrio-ventricular blocks, angina and myocardial infarction. Therefore the risk of cardio-vascular events is increased. Failure of drug therapy to control disease progression is an indication for parathyroidectomy. In sHPT all parathyroid glands are affected, hence the need to detect 4 glands intraoperatively, by bilateral cervical exploration. However, considering the possibility of ectopic localization of these glands as well as the possibility of some supernumerary glands, it is desirable to have an imagistic map as accurate as possible, thus avoiding the risk of postoperative recurrence. The available imaging investigations are represented by the ultrasound of the cervical region, the parathyroid scintigraphy and those of the second line - CT or MRI examination. If in primary hyperparathyroidism, where there is only one parathyroid adenoma (or two), the preoperative imaging results are satisfactory, in sHPT there are many cases in which the imaging does not reveal all four parathyroid glands.

The Use of Percutaneous Ultrasound-Guided Radiofrequency Heat Ablation for Treatment of Primary Hyperparathyroidism in Eight Dogs: Outcome and Complications.

Percutaneous ultrasound-guided radiofrequency heat-ablation (UG-RHA) is a therapeutic option for dogs with primary hyperparathyroidism (PHPTH) but information about its outcome is still controversial. This retrospective study aimed to evaluate the outcome and complications of UG-RHA in dogs with PHPTH. The medical records of dogs with PHPTH submitted to UG-RHA between June 2012 and September 2015 in a French referral center were retrospectively reviewed. Eight cases were included. No sex predisposition was found. The median age at diagnosis was 12 years. The most common clinical sign was polyuria/polydipsia. All of the dogs were hypercalcaemic prior to UG-RHA, and all showed a parathyroid nodule identified upon cervical ultrasound. UG-RHA was uneventful, allowing a successful resolution of hypercalcemia in all dogs (8/8). Six out of eight dogs did not receive vitamin D supplementation either pre- or post-procedure. From these, three dogs developed biochemical hypocalcemia, but only one required therapy. Other short-term complications included Horner's syndrome (1/8) and aspiration bronchopneumonia, which led to cardio-respiratory arrest in one large-breed dog (1/8). Long-term complications were scarce, with no recurrence reported in all of the cases that were assessed in follow-up (4/7). This study demonstrates that UG-RHA has few short or long-term complications, and it is a good therapeutic alternative for dogs with PHPTH.

Shear wave elastography in the diagnostics of parathyroid adenomas-new application of the method.

PURPOSE: Shear wave elastography (SWE) was described as valuable tool in the diagnostics of distinct types of thyroid lesions, thyroiditis and several other non-thyroidal conditions, such as liver inflammation and fibrosis or diagnostics of breast lesions. The aim of the current study was to assess the appearance of parathyroid adenomas in SWE and to check prospectively if SWE can be valuable additional tool in the diagnostics of pathologically enlarged parathyroids. METHODS: Patients with parathyroid adenomas confirmed by histopathology were included. Subjects with benign thyroid lesions were enrolled to the control group. Elasticity of parathyroid adenomas and benign thyroid nodules was measured and compared. RESULTS: Sixty five patients with parathyroid adenomas and 35 patients with 51 benign thyroid nodules were included. Parathyroid adenomas where significantly more elastic than benign thyroid nodules-mean elasticity of the lesion was 5.2 ± 7.2 vs. 24.3 ± 33.8 kPa, respectively. Relative mean elasticity (in comparison with surrounding thyroid tissue) was 0.30 ± 0.36 and 2.8 ± 3.9, respectively. CONCLUSIONS: SWE can be useful tool in the diagnostics of parathyroid adenomas. Enlarged parathyroids are significantly more elastic than benign thyroid lesions. Low elasticity of the lesion constitutes feature with high negative prognostic value, allowing for reliable exclusion of suspicion of parathyroid adenomas.

Incidentalomas paratiroideos: un nuevo diagnóstico, un nuevo problema. Prevalencia en Argentina / Parathyroid incidentaloma: a new diagnosis, a new problem. Prevalence in Argentina

Los incidentalomas paratiroideos (IP) fueron descriptos como hallazgos intraquirúrgicos y luego en estudios ecográficos de tiroides. Escasos estudios se han realizado, por lo que su incidencia no es clara. Más aún, la presencia de una imagen hipoecogénica en topografía paratiroidea puede también ser tejido tiroideo o linfático. Se evaluaron retrospectivamente las historias clínicas de 7 años buscando los pacientes en los que se diagnosticó un IP durante una ecografía tiroidea. Se diagnosticó IP en 24 pacientes (4,0% del total). Tenían hipotiroidismo autoinmune 21 pacientes y nódulos tiroideos 3 pacientes. En 10 casos la lesión fue única y en 14 eran 2 o más. En la evolución se repitió la ecografía en 13 pacientes, hallando imágenes similares a la primera en todas. La calcemia y la PTH fueron normales en 23 pacientes, pero en una de ellas, con una imagen de 6 mm, hubo PTH levemente elevada con calcemia normal, que luego se elevó, y se diagnosticó adenoma paratiroideo. El hallazgo de IP parece cada vez más frecuente; nuestra incidencia del 4% como imágenes compatibles (sin confirmar la naturaleza paratiroidea) es más alta que las escasas publicaciones existentes sobre el tema. Es posible que muchas no presenten cambios ni ecográficos ni de laboratorio, pero otros casos, como el hallado en una de nuestras 24 pacientes, pueden ser un estadio inicial de hiperparatiroidismo primario, por lo que el seguimiento es aconsejable.

Parathyroid incidentalomas (PI) were first described as intraoperative findings and then in ultrasound thyroid scan studies. Few studies have been performed to investigate this, so their incidence is unclear. Moreover, the presence of a hypo-echogenic image in parathy- roid topography may also be thyroid or lymphatic tissue. A retrospective evaluation was performed on the seven-year clinical records of patients in whom a PI was diagnosed during a thyroid ultrasound scan. PI was diagnosed in 24 patients (4.0%). Twenty one patients had autoimmune hypothyroidism and 3 patients had thyroid nodules. In 10 cases the lesion was unique, and in 14 cases there were two or more lesions. During follow-up, ultrasound was repeated in 13 patients, and all showe findings. Serum calcium and PTH were normal in 23 patients, but in one of them, with an image of a lesion of 6 mm, PTH was slightly elevated, with normal serum calcium. Later, hypercalcaemia was detected and a parathyroid adenoma was diagnosed. The incidence of PI seems to be increasing, with our rate of 4% of compatible images (without confirming the parathyroid origin of the lesion) is higher than that reported in the few existing publications on the subject. Many patients with PI may not present with biochemical abnormalities, but as our experience shows, these lesions may represent the first stage of primary hyperparathyroidism; therefore careful follow-up is advisable.

Comparison of scintigraphy and ultrasound imaging in patients with primary, secondary and tertiary hyperparathyroidism - own experience.

BACKGROUND: The imaging techniques most commonly used in the diagnosis of hyperparathyroidisms are ultrasound and scintigraphy. The diagnostic algorithms vary, depending mainly on the population, and experience of physicians. AIM: Aim of the present research was to determine the usefulness of parathyroid scintigraphy and ultrasonography in patients diagnosed for hyperparathyroidism in own material. MATERIAL AND METHOD: In the present research, 96 operated patients with documented primary, secondary and tertiary hyperparathyroidism were retrospectively analyzed. All patients underwent a 99mTc hexakis-2-methoxyisobutylisonitrile scintigraphy of the neck with the use of subtraction and two-phase examinations. Ultrasonography of the neck was performed in all the patients in B mode 2D presentation. A total number of 172 parathyroid glands were analyzed. RESULTS: The sensitivity and specificity of scintigraphy was 68% and 60%, respectively. The sensitivity of ultrasound was 49% and specificity 85%. Both techniques allowed visualization of 76 parathyroid glands. Ultrasound revealed 19 glands that were not visible in scintigraphy. Scintigraphy showed 76 parathyroid glands that were not visualized on ultrasound. Having combined the results of scintigraphy and ultrasound, the sensitivity of 76% and specificity of 50% were obtained. Considering the ability to locate the parathyroid glands in both techniques as a positive result, the sensitivity decreased to 37% and specificity rose to 95%. CONCLUSIONS: Scintigraphy showed greater sensitivity than ultrasound in the localization of enlarged parathyroid glands. Ultrasound, in turn, was characterized by a higher specificity. The combined use of scintigraphy and ultrasonography allowed to obtain the specificity of 95%. In the light of obtained results, scintigraphy and ultrasonography are complementary and should be used together.

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.

Hyperparathyroidism in octogenarians: A plea for ambulatory minimally invasive surgery under local anesthesia.

BACKGROUND: With the current aging of the world's population, diagnosis of primary hyperparathyroidism is being reported in increasingly older patients, with the associated functional symptomatology exacerbating the vicissitudes of age. This retrospective study was designed to establish functional improvements in older patients following parathyroid adenomectomy under local anesthesia as outpatient surgery. MATERIALS AND METHODS: Data were collected from 53 patients aged 80 years or older who underwent a minimally invasive parathyroid adenomectomy. All patients underwent a preoperative ultrasound, scintigraphy, and were monitored for the effectiveness of the procedure according to intra- and postdosage of parathyroid hormone (PTH) at 5min, 2h and 4h. RESULTS: Mean preoperative serum calcium level was 2.8mmol/L (112mg/L) and mean PTH was 180pg/ml. Thirty-eight patients were operated under local anesthesia using minimally invasive surgery and 18 patients were operated under general anesthesia. In 26 cases, the procedure was planned on an outpatient basis but could only be carried out in 21 patients. Fifty-one patients had normal serum calcium and PTH levels during the immediate postoperative period. Two patients were reoperated under general anesthesia, since immediate postoperative PTH did not return to normal. Four patients died due to reasons unrelated to hyperparathyroidism. Five patients were lost to follow-up six months to two years postsurgery. Of the 44 patients (83%) with long-term monitoring for PTH, none had recurrence of biological hyperparathyroidism. Excluding the three asymptomatic patients, 38 of the 41 symptomatic patients (93%) with long-term follow-up were considering themselves as "improved" or "strongly improved" after the intervention, notably with respect to fatigue, muscle and bone pain. Two patients (4.9%) reported no difference and one patient (2.4%) said her condition had worsened and regretted having undergone surgery. CONCLUSION: In patients 80 years or older, minimally invasive surgery as an outpatient under local anesthesia offered an excellent risk/benefit ratio given its many advantages: simplicity, speed, absence of general anesthesia, ease of monitoring, direct voice control intraoperatively, very low morbidity, effectiveness in treating primary hyperparathyroidism in more than 95% of first intention patients, and the possibility of immediate or delayed recovery in the event of multiglandular disease going unnoticed.