Impact of hyperparathyroidism on allograft histology and function after kidney transplantation: Rethinking its causal role in graft dysfunction.

INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.

Insights into Hyperparathyroidism-Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours.

A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.

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.

Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1 / Paratireoides supranumerárias em hiperparatireoidismo primário associado a neoplasia endócrina múltipla tipo 1

OBJECTIVE: To evaluate frequency, anatomic presentation, and quantities of supernumerary parathyroids glands in patients with primary hyperparathyroidism (HPT1) associated with multiple endocrine neoplasia type 1 (MEN1), as well as the importance of thymectomy, and the benefits of localizing examinations for those glands. METHODS: Forty-one patients with hyperparathyroidism associated with MEN1 who underwent parathyroidectomy between 1997 and 2007 were retrospectively studied. The location and number of supernumerary parathyroids were reviewed, as well as whether cervical ultrasound and parathyroid SESTAMIBI scan (MIBI) were useful diagnostic tools. RESULTS: In five patients (12.2%) a supernumerary gland was identified. In three of these cases (40%), the glands were near the thyroid gland and were found during the procedure. None of the imaging examinations were able to detect supernumerary parathyroids. In one case, only the pathologic examination could find a microscopic fifth gland in the thymus. In the last case, the supernumerary gland was resected through a sternotomy after a recurrence of hyperparathyroidism, ten years after the initial four-gland parathyroidectomy without thymectomy. MIBI was capable of detecting this gland, but only in the recurrent setting. Cervical ultrasound did not detect any supernumerary glands. CONCLUSION: The frequency of supernumerary parathyroid gland in the HPT1/MEN1 patients studied (12.2%) was significant. Surgeons should be aware of the need to search for supernumerary glands during neck exploration, besides the thymus. Imaging examinations were not useful in the pre-surgical location of these glands, and one case presented a recurrence of hyperparathyroidism.

OBJETIVO: Avaliação da frequência, da localização anatômica e do número de paratireoides extranumerárias em pacientes com hiperparatireoidismo primário (HPT1) associado a neoplasia endócrina múltipla tipo 1(NEM1), além da avaliação da importância da timectomia e da utilidade dos exames radiológicos para localização destes. MÉTODOS: Foram avaliados de forma retrospectiva 41 pacientes portadores de NEM1 com HPT1 submetidos a paratireoidectomia entre 1997 e 2007. O número de glândulas supranumerárias encontradas e a sua localização foram revisados, assim como a utilidade do ultrassom cervical e do SESTAMIBI (MIBI) de paratireoide como ferramentas diagnósticas. RESULTADOS: Em cinco pacientes (12,2%) foram identificadas glândulas supranumerárias. Em três destes (40%), as glândulas estavam próximas à glândula tireoide e foram encontradas durante a exploração cirúrgica. Os exames de imagem não foram úteis para a localização destas glândulas. Em um caso, apenas o exame anatomopatológico foi capaz de encontrar uma glândula extranumerária microscópica localizada no timo. No último caso, uma quinta glândula foi ressecada por meio de esternotomia após a recidiva do hiperparatireoidismo, cerca de 10 anos após a paratireoidectomia realizada sem timectomia na ocasião. Neste caso o MIBI detectou esta paratireoide apenas após a recidiva da doença. Em nenhum dos casos o ultrassom cervical foi capaz de detectar glândulas extranumerárias. CONCLUSÃO: A frequência de paratireoides supranumerárias em nossa casuística foi significativa (12,2%). Durante a exploração cervical, o cirurgião deve estar atento para localizar glândulas extranumerárias além do timo. Exames de imagem não foram úteis na localização préoperatória dessas glândulas, e em um caso houve recidiva do hiperparatireoidismo.

Adenoma de paratireóide diagnosticado por punção aspirativa por agulha fina: relato de caso / Parathyroid adenoma diagnosed by fine needle aspiration cytology: a case report

Os autores relatam o caso de uma paciente com hiperparatireoidismo primário causado por adenoma de paratireóide diagnosticado através de punção aspirativa por agulha fina (PAAF) no pré-operatório. A paratireóide aumentada foi visualizada pela ultra-sonografia (US) e submetida à PAAF, que foi compatível com adenoma de paratireóide. Realizou-se a remoção cirúrgica do adenoma e o histopatológico resultou concordante com a citologia. Este relato destaca a importância da localização e do diagnóstico citológico pré-operatório das lesões de paratireóide para proporcionar uma abordagem cirúrgica menos agressiva.

The authors report a patients case with primary hyperparathyroidism caused by parathyroid adenoma that was diagnosed by fine needle aspiration cytology (FNAC) in the preoperative. The increased parathyroid was visualized by the ultrasonography and submitted to FNAC that was compatible with parathyroid adenoma. The surgical removal of adenoma was accomplished and the histopathologic was concordant with the cytology. This report detaches the importance of the location and preoperative cytological diagnosis of the parathyroid lesions in providing a less aggressive surgical approach.

Hiperparatiroidismo / Hyperparathyroidism

El calcio es esencial para varias funciones del cuerpo, incluyendo la contracción muscular, la conducción nerviosa y el funcionamiento apropiado de muchas enzimas. La mayor parte del calcio del cuerpo se almacena en los huesos, pero también se encuentra en las células y en la sangre. El organismo controla con "toda precisión" la cantidad de calcio tanto en la célula como en la sangre. Para mantener este equilibrio entra en competencia la hormona para tiroidea, secretada por las glándulas paratiroidea. La actividad de las glándulas paratiroideas está controlada por el nivel de calcio libre (ionizado) de la sangre. El descenso de los niveles de este calcio estimula la síntesis y secreción de hormonas paratiroideas, si la cantidad de calcio libre en sangre aumenta, estamos frente a una alteración metabólica "La Hipercalcemia" la cual consiste en una concentración elevada de calcio en sangre superior a 10.5 miligramos por decilitro de sangre, la que puede ser causada por aumento en la ingestión de calcio, pero la causa más común de la hipercalcemia es el "Hiperparatiroidismo", el cual se debe a la hipersecreción de hormonas paratiroideas. Esta alteración puede deberse a un adenoma paratiroide (80%). Hiperplasia primaria (15%). Carcinoma paratiroide (5%). Fenómeno secundario típico de los pacientes con insuficiencia renal crónica. El hiperparatiroidismo puede manifestarse en la cavidad bucal en forma de hiperplasia gingival y lesiones osteolíticas de los maxilares (Tumores pardos) que son asintomáticas. El objetivo de este trabajo es realizar una revisión bibliográfica actualizada sobre esta patología y resaltar la importancia que representan las manifestaciones orales de esta patología sistémica para el odontólogo en general, especialmente para el cirujano oral y maxilofacial.

Afecçöes cirurgicas das glandulas paratiroides / Surgical affections of parathyroid glands

O autor faz uma revisao da literatura sobre o hiperparatiroidismo primario, apresenta um caso de carcinoma funcionante da paratiroide inferior direita e descreve a tecnica cirugica

Surgical management of hyperparathyroidism. A 24 years experience

Our 24 years experience in the surgical treatment of 130 patients with primary hyperparathyroidism was presented. A single adenoma of the parathyroid glands was the predominant lesion. The lower parathyroid glands were more frequently the site of the adenoma, with the right lower gland presenting the highest incidence. The incidence of hyperplasia and carcinoma is similar to the reported literature. The offending glands were identified in the vast majority of the patients. The number of complications is significantly low with a zero surgical mortality. The utilization of preoperative localizing test is not recommended for the initial neck exploration. Satisfactory results can be obtained with a minimal work up

Hiperparatiroidismo primario neonatal severo: presentación de un caso y revisión de la literatura / Neonatal severe primary hyperparathyroidism: report of a case and review of the literature

Se presenta el caso de un neonato en quien se diagnostica hiperparatiroidismo primario neonatal severo, basados en la presencia de hipercalcemia severa con hipofosfatemia concomitante y valores elevados de parathormona. Se hace una revisión de la literatura mundial y nacional sobre el tema y se analiza el diagnóstico diferencial de esta rara entidad

Cuatro casos de cáncer de paratiroides / Four cases of parathyroid carcinoma

El carcinoma de paratiroides es una causa poco frecuente de hiperparatiroidismo primario, con una prevalancia que oscila entre 0.5 y 4 por ciento. Estas neoplasias tienen un curso agresivo por lo que es importante establecer un diagnóstico oportuno y realizar tratamiento quirúrgico precoz. En el Instituto Nacional de la Nutrición en un periodo de siete años, se realizaron 88 cirugías por hiperparatiroidismo primario, encontrándose en cuatro casos un carcinoma de paratiroides (prevalencia del 4.5 por ciento). Presentamos aquí las características clínicas, diagnóstico, tratamiento y evolución de estos pacientes

Carcinoma paratiroideo

La incidencia de hiperparatiroidismo causado por carcinoma de paratiroides (CP) ha sido estimada en soló 0.5 a 5 por ciento (1-11). Por esto se ha recomendado informar todos los casos que se detecten con el fin de elaborar un registro internacional que mejore el conocimiento sobre esta rara entidad. En este artículo se presentan dos pacientes con hiperpartiroidismo por CP evaluados por nuestro servicio, y con base en ellos se hace una corta revisión del tema.