Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism / Paratireoidectomia: ainda a melhor escolha para o tratamento do hiperparatireoidismo secundário grave

Abstract Introduction: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. Methods: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). Results: In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. Conclusion: PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Resumo Introdução: O manejo do hiperparat-ireoidismo secundário (HPTS) é uma tarefa desafiadora com diversos fatores que contribuem para o fracasso do tratamento. A terapia calcimimética revolucionou o manejo do HPTS, levando a alterações nas indicações e no momento apropriado da paratireoidectomia (PTX) em todo o mundo. Métodos: Comparamos taxas de resposta às abordagens clínica vs. cirúrgica do HPTS em pacientes em diálise de manutenção (DRC 5D) e pacientes transplantados renais (TxR). Foi realizada uma análise retrospectiva dos achados de um ano de acompanhamento. Pacientes com DRC 5D foram divididos em 3 grupos de acordo com a estratégia de tratamento: paratireoidectomia, manejo clínico sem cinacalcete (denominado padrão - P) e com cinacalcete (P + CIN). Os pacientes com TxR foram divididos em 3 grupos: PTX, CIN (uso de cinacalcete) e observação (OBS). Resultados: Na DRC 5D, encontramos uma redução significativa do paratormônio (PTH) em todos os grupos. Apesar de todos os grupos apresentarem um PTH mais elevado no início do estudo, identificamos uma redução mais acentuada no grupo PTX. Com relação ao HPTS grave, a diferença entre os grupos foi evidentemente maior: 31%, 14% e 80% dos grupos P, P + CIN e PTX atingiram níveis adequados de PTH, respectivamente (p< 0,0001). Com relação à população TxR, embora a diferença não tenha sido tão impressionante, também foi observada uma taxa maior de sucesso no grupo PTX. Conclusão: A PTX ainda parece ser a melhor escolha de tratamento para o HPTS, especialmente em pacientes com doenças prolongadas em cenários sem recursos.

Parathyroidectomy: still the best choice for the management of severe secondary hyperparathyroidism.

INTRODUCTION: Management of secondary hyperparathyroidism (SHPT) is a challenging endeavor with several factors contruibuting to treatment failure. Calcimimetic therapy has revolutionized the management of SHPT, leading to changes in indications and appropriate timing of parathyroidectomy (PTX) around the world. METHODS: We compared response rates to clinical vs. surgical approaches to SHPT in patients on maintenance dialysis (CKD 5D) and in kidney transplant patients (Ktx). A retrospective analysis of the one-year follow-up findings was carried out. CKD 5D patients were divided into 3 groups according to treatment strategy: parathyroidectomy, clinical management without cinacalcet (named standard - STD) and with cinacalcet (STD + CIN). Ktx patients were divided into 3 groups: PTX, CIN (cinacalcet use), and observation (OBS). RESULTS: In CKD 5D we found a significant parathormone (PTH) decrease in all groups. Despite all groups had a higher PTH at baseline, we identified a more pronounced reduction in the PTX group. Regarding severe SHPT, the difference among groups was evidently wider: 31%, 14% and 80% of STD, STD + CIN, and PTX groups reached adequate PTH levels, respectively (p<0.0001). Concerning the Ktx population, although the difference was not so impressive, a higher rate of success in the PTX group was also observed. CONCLUSION: PTX still seems to be the best treatment choice for SHPT, especially in patients with prolonged diseases in unresourceful scenarios.

Time to Recurrence as a Prognostic Factor in Parathyroid Carcinoma.

Background: Parathyroid carcinoma (PC) is a rare and challenging disease without clearly understood prognostic factors. Adequate management can improve outcomes. Characteristics of patients treated for PC over time and factors affecting prognosis were analyzed. Methods: Retrospective cohort study including surgically treated patients for PC between 2000 and 2021. If malignancy was suspected, free-margin resection was performed. Demographic, clinical, laboratory, surgical, pathological, and follow-up characteristics were assessed. Results: Seventeen patients were included. Mean tumor size was 32.5 mm, with 64.7% staged as pT1/pT2. None had lymph node involvement at admission, and 2 had distant metastases. Parathyroidectomy with ipsilateral thyroidectomy was performed in 82.2%. Mean postoperative calcium levels were different between patients who developed recurrence vs those who did not (P = .03). Six patients (40%) had no recurrence during follow-up, 2 (13.3%) only regional, 3 (20%) only distant, and 4 (26.6%) both regional and distant. At 5 and 10 years, 79% and 56% of patients were alive, respectively. Median disease-free survival was 70 months. Neither Tumor, Nodule, Metastasis system nor largest tumor dimension (P = .29 and P = .74, respectively) were predictive of death. En bloc resection was not superior to other surgical modalities (P = .97). Time between initial treatment and development of recurrence negatively impacted overall survival rate at 36 months (P = .01). Conclusion: Patients with PC can survive for decades and have indolent disease course. Free margins seem to be the most important factor in initial surgery. Recurrence was common (60%), but patients with disease recurrence within 36 months of initial surgery had a lower survival rate.

Outcomes of Early Versus Late Tracheostomy in Patients With COVID-19: A Multinational Cohort Study.

Timing of tracheostomy in patients with COVID-19 has attracted substantial attention. Initial guidelines recommended delaying or avoiding tracheostomy due to the potential for particle aerosolization and theoretical risk to providers. However, early tracheostomy could improve patient outcomes and alleviate resource shortages. This study compares outcomes in a diverse population of hospitalized COVID-19 patients who underwent tracheostomy either "early" (within 14 d of intubation) or "late" (more than 14 d after intubation). DESIGN: International multi-institute retrospective cohort study. SETTING: Thirteen hospitals in Bolivia, Brazil, Spain, and the United States. PATIENTS: Hospitalized patients with COVID-19 undergoing early or late tracheostomy between March 1, 2020, and March 31, 2021. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 549 patients from 13 hospitals in four countries were included in the final analysis. Multivariable regression analysis showed that early tracheostomy was associated with a 12-day decrease in time on mechanical ventilation (95% CI, -16 to -8; p < 0.001). Further, ICU and hospital lengths of stay in patients undergoing early tracheostomy were 15 days (95% CI, -23 to -9 d; p < 0.001) and 22 days (95% CI, -31 to -12 d) shorter, respectively. In contrast, early tracheostomy patients experienced lower risk-adjusted survival at 30-day post-admission (hazard ratio, 3.0; 95% CI, 1.8-5.2). Differences in 90-day post-admission survival were not identified. CONCLUSIONS: COVID-19 patients undergoing tracheostomy within 14 days of intubation have reduced ventilator dependence as well as reduced lengths of stay. However, early tracheostomy patients experienced lower 30-day survival. Future efforts should identify patients most likely to benefit from early tracheostomy while accounting for location-specific capacity.

Impact of parathyroidectomy on quality of life in multiple endocrine neoplasia type 1.

Background: Potential influences of parathyroidectomy (PTx) on the quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown. Method: Short Form 36 Health Survey Questionnaire was prospectively applied to 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft) before, 6 and 12 months after surgery. Parameters that were analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume. Results: Asymptomatic patients were younger (30 vs 38 years; P = 0.04) and presented higher QoL scores than symptomatic ones: Physical Component Summary score (PCS) 92.5 vs 61.2, P = 0.0051; Mental Component Summary score (MCS) 82.0 vs 56.0, P = 0.04. In both groups, QoL remained stable 1 year after PTx, independently of the number of comorbidities. Preoperative general pain was negatively correlated with PCS (r = -0.60, P = 0.0004) and MCS (r = -0.57, P = 0.0009). Also, moderate/intense pain was progressively (6/12 months) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12 months although remnant parathyroid tissue volume did have a positive correlation (P = 0.0490; r = 0.3625) to PCS 12 months after surgery. Patients with one to two comorbidities had as pre-PTx PCS (P = 0.0015) as 12 months and post-PTx PCS (P = 0.0031) and MCS (P = 0.0365) better than patients with three to four comorbidities. Conclusion: A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated with this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target organs and avoiding potential negative impact on QoL.

PTH Spikes During Surgical Treatment for Secondary and Tertiary Hyperparathyroidism: A Prospective Observational Study.

BACKGROUND: The aim of the present study was to determine whether PTH spikes in renal hyperparathyroidism can interfere with the interpretation of intraoperative PTH monitoring and to determine its frequency and characteristics. METHODS: This was a prospective observational study of consecutive patients who underwent surgical treatment in a single tertiary institution. Patients were divided into two groups: spike and no spike. Patients with secondary and tertiary hyperparathyroidism were analyzed separately. Intraoperative PTH monitoring by venous serial samples: two samples were taken before the excision of the parathyroid gland, and two others were taken after resection. RESULTS: PTH spikes occurred in 23.5% (53 of 226), and their occurrence was similar between secondary and tertiary hyperparathyroidism patients (p = 0.074). The relative PTH spike intensity was higher in transplanted patients than in dialysis patients (55 vs. 20%, p = 0.029). A characteristic of the secondary hyperparathyroidism patients was the highest frequency of surgical failure (23 vs. 7.5%, p = 0.016) and the higher occurrence of supernumerary glands in the spike group (23 vs. 10.3%, p = 0.035). Supernumerary parathyroid was associated with surgical failure [19.1 (6.5-55.7) odds ratio [confidence interval], p < 0.001). In the studies evaluating the diagnostic test validity for patients on dialysis and experiencing spikes, the most significant impacts were in the sensitivity, accuracy, and negative predictive value of the method. CONCLUSIONS: PTH spikes occurred in up to 23.5% of renal hyperparathyroidism surgical treatments and can negatively influence the intraoperative parathyroid hormone monitoring. Regarding the phenomenon of PTH spikes, it is prudent to think about the possibility of a hyperplastic supernumerary gland.

Primary hyperparathyroidism: Disease of diverse genetic, symptomatic, and biochemical phenotypes.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Parathyroid hormone levels after parathyroidectomy for secondary hyperparathyroidism.

OBJECTIVE: The parathormone level after parathyroidectomy in dialysis patients are of interest. Low levels may require cryopreserved tissue implantation; however, the resection is necessary in case of recurrence. We analyzed post parathyroidectomy parathormone levels in renal hyperparathyroidism. METHODS: Prospective observation of postoperative parathormone levels over defined periods in a cohort of dialysis patients that underwent total parathyroidectomy and immediate forearm autograft from 2008 to 2010, at a single tertiary care hospital. RESULTS: Of 33 patients, parathormone levels until 36 months could be divided into four patterns. Patients with stable function (Pattern 1) show relatively constant levels after two months (67% of the cases). Early function and later failure (Pattern 2) were an initial function with marked parathormone reduction before one year (18%). Graft recurrence (Pattern 3) showed a progressive increase of parathormone in four cases (12%). Complete graft failure (Pattern 4) was a nonfunctioning implant at any period, which was observed in one patient (3%). Parathormone levels of Pattern 3 became statistically different of Pattern 1 at 36 months. CONCLUSIONS: Patients that underwent the total parathyroidectomy and autograft present four different graft function patterns with a possible varied therapeutic management.

Parathyroid hormone levels after parathyroidectomy for secondary hyperparathyroidism

SUMMARY OBJECTIVE: The parathormone level after parathyroidectomy in dialysis patients are of interest. Low levels may require cryopreserved tissue implantation; however, the resection is necessary in case of recurrence. We analyzed post parathyroidectomy parathormone levels in renal hyperparathyroidism. METHODS: Prospective observation of postoperative parathormone levels over defined periods in a cohort of dialysis patients that underwent total parathyroidectomy and immediate forearm autograft from 2008 to 2010, at a single tertiary care hospital. RESULTS: Of 33 patients, parathormone levels until 36 months could be divided into four patterns. Patients with stable function (Pattern 1) show relatively constant levels after two months (67% of the cases). Early function and later failure (Pattern 2) were an initial function with marked parathormone reduction before one year (18%). Graft recurrence (Pattern 3) showed a progressive increase of parathormone in four cases (12%). Complete graft failure (Pattern 4) was a nonfunctioning implant at any period, which was observed in one patient (3%). Parathormone levels of Pattern 3 became statistically different of Pattern 1 at 36 months. CONCLUSIONS: Patients that underwent the total parathyroidectomy and autograft present four different graft function patterns with a possible varied therapeutic management.

Delayed sampling of intraoperative parathormone may be unnecessary during parathyroidectomy in kidney-transplanted and dialysis patients.

INTRODUCTION: Some authors advise in favor of delayed sampling of intraoperative parathormone testing (ioPTH) during parathyroidectomy in dialysis and kidney-transplanted patients. The aim of the present study was to evaluate the intensity and the role of delayed sampling in the interpretation of ioPTH during parathyroidectomy in dialysis patients (2HPT) and successful kidney-transplanted patients (3HPT) compared to those in single parathyroid adenoma patients (1HPT). METHODS: This was a retrospective study of ioPTH profiles in patients with 1HPT, 2HPT, and 3HPT operated on in a single institution. Samples were taken at baseline ioPTH (sampling at the beginning of the operation), ioPTH-10 min (10 minutes after excision of the parathyroid glands), and ioPTH-15 min (15 minutes after excision of the parathyroid glands). The values were compared to baseline. RESULTS: Median percentage values of ioPTH compared to baseline (100%) were as follows: 1HPT, ioPTH-10 min = 20% and ioPTH-15 min = 16%; 2HPT, ioPTH-10 min = 14% and ioPTH-15 min = 12%; 3HPT, ioPTH-10 min = 18% and ioPTH-15 min = 15%. DISCUSSION: The reduction was equally effective at 10 minutes in all groups. In successful cases, ioPTH decreases satisfactorily 10 minutes after parathyroid glands excision in dialysis and transplanted patients, despite significant differences in kidney function. The postponed sampling of ioPTH appears to be unnecessary.

Acute and long-term kidney function after parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: In kidney transplant patients, parathyroidectomy is associated with an acute decrease in renal function. Acute and chronic effects of parathyroidectomy on renal function have not been extensively studied in primary hyperparathyroidism (PHPT). METHODS: This retrospective cohort study included 494 patients undergoing parathyroidectomy for PHPT. Acute renal changes were evaluated daily until day 4 post-parathyroidectomy and were stratified according to acute kidney injury (AKI) criteria. Biochemical assessment included serum creatinine, total and ionized calcium, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD). The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We compared preoperative and postoperative renal function up to 5 years of follow-up. RESULTS: A total of 391 (79.1%) patients were female, and 422 (85.4%) were non-African American. The median age was 58 years old. The median (first and third quartiles) preoperative serum creatinine, PTH and total calcium levels were 0.81 mg/dL (0.68-1.01), 154.5 pg/mL (106-238.5), and 10.9 mg/dL (10.3-11.5), respectively. The median (first and third quartiles) preoperative eGFR was 86 mL/min/1.73 m2 (65-101.3). After surgery, the median acute decrease in the eGFR was 21 mL/min/1.73 m2 (p<0.0001). Acutely, 41.1% of patients developed stage 1 AKI, 5.9% developed stage 2 AKI, and 1.8% developed stage 3 AKI. The acute eGFR decrease (%) was correlated with age and PTH, calcium and preoperative creatinine levels in univariate analysis. Multivariate analysis showed that the acute change was related to age and preoperative values of ionized calcium, phosphorus and creatinine. The change at 12 months was related to sex, preoperative creatinine and 25OHD. Permanent reduction in the eGFR occurred in 60.7% of patients after an acute episode. CONCLUSION: There was significant acute impairment in renal function after parathyroidectomy for PHPT, and almost half of the patients met the criteria for AKI. Significant eGFR recovery was observed during the first month after surgery, but a small permanent reduction may occur. Patients treated for PHPT seemed to present with prominent renal dysfunction compared to patients who underwent thyroidectomy.

Critical analysis of the intraoperative parathyroid hormone decrease during parathyroidectomy for secondary and tertiary hyperparathyroidism.

BACKGROUND: This study aims to determine whether intraoperative parathyroid hormone monitoring helps to predict early surgical outcomes in patients with renal hyperparathyroidism and evaluate the impact on decision making during surgery. METHODS: A prospective study was conducted. Serial samples of the intraoperative parathyroid hormone were collected; 2 of these were taken before the excision, and 2 were taken after the planned parathyroid resection (10 minutes and 15 minutes). We tested the criterion of an intraoperative parathyroid hormone percentage decay ≥80% of the highest value of the basal samples as a predictor of success. RESULTS: Of the 228 patients, parathyroidectomy achieved success in 92.1%. In patients with secondary hyperparathyroidism, the failure group showed a tendency to stabilize or even increase the intraoperative parathyroid hormone values from the 10-minute measure (577 pg/mL) to the 15-minute measure (535 pg/mL) (P = .903). Conversely, intraoperative parathyroid hormone continued to drop in those with a successful outcome: 245 pg/mL (10 minutes) and 206 pg/mL (15 minutes) (P < .001). The failure group had a significantly lower percentage decay (P < .001) from baseline when compared with the success group. The intraoperative parathyroid hormone influenced the surgical management in up to 7% of the cases. The intraoperative parathyroid hormone dosage method showed an accuracy of 86%, a sensitivity of 88%, and specificity of 67%. CONCLUSION: In patients with renal hyperparathyroidism undergoing parathyroidectomy, the use of intraoperative parathyroid hormone may help to predict an early therapeutic outcome with high sensitivity and accuracy by indicating the operation's success when there is an 80% reduction of baseline intraoperative parathyroid hormone 15 minutes after removal of the enlarged glands, an associated continuous decrease in serum intraoperative parathyroid hormone levels between 10 and 15 minutes, and achievement of plasma target values <500 pg/mL.

Recommendations for head and neck surgical procedures during the COVID-19 pandemic.

The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread exponentially worldwide. In Brazil, the number of infected people diagnosed has been increasing and, as in other countries, it has been associated with a high risk of contamination in healthcare teams. For healthcare professionals, the full use of personal protective equipment (PPE) is mandatory, such as wearing surgical or filtering facepiece class 2 (FFP2) masks, waterproof aprons, gloves, and goggles, in addition to training in care processes. A reduction in the number of face-to-face visits and non-essential elective procedures is also recommended. However, surgery should not be postponed in the case of the most essential elective indications (mostly associated with head and neck cancers). As malignant tumors of the head and neck are clinically time sensitive, neither consultations for these tumors nor their treatment should be postponed. Postponing surgical treatment can result in a change in the disease stage and alter an individual's chance of survival. In this situation, planning of all treatments must begin with the request for, in addition to routine examinations, a nasal swab polymerase chain reaction for SARS-CoV-2 and chest computed tomography. Only if the results of these tests are positive or if fever or other symptoms suggestive of COVID-19 are present should the surgical procedure be postponed until the patient completely recovers. This is mandatory not only because of the risk of contamination of the surgical team but also because of the increased risk of postoperative complications and high risk of death. During this pandemic, the most effective safety measures are social distancing for the general public and the adequate availability and use of PPE in the healthcare field. The treatment of other chronic diseases, such as cancer, should be continued, as the damming of cases of these diseases will have a deleterious effect on the public healthcare system.