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.

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.

Parathyroidectomy in patients with chronic kidney disease: Impacts of different techniques on the biochemical and clinical evolution of secondary hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTx) decreases the mortality rate of refractory secondary hyperparathyroidism (rSHP) due to chronic kidney disease. A consensus regarding which techniques of PTx are associated with better outcomes is not available. The aims of this study are to evaluate the clinical and laboratory evolution of 49 hemodialysis patients with rSHP who underwent PTx using different techniques. METHODS: Patients underwent subtotal PTx (sub-PTx) or total PTx with autotransplantation (AT) of 45 (PTx-AT45) or 90 parathyroid fragments (PTx-AT90) and were followed for 12 months. We analyzed the expression of proliferating cell nuclear antigen (PCNA), calcium-sensing receptor (CasR), vitamin D receptor (VDR), fibroblast growth factor receptor-1 (FGFR1), sodium-dependent phosphate cotransporter-1 (PIT1), and Klotho in parathyroid glands. RESULTS: Baseline median serum intact parathyroid hormone (iPTH) levels were 1,466 (1,087-2,125) pg/mL; vascular calcification scores correlated with serum iPTH (r = 0.529; P = .002) and serum phosphate levels (r = 0.389; P = .028); and Klotho expression was negatively correlated with serum phosphate levels (r = -0.4; P = .01). After 12 months, serum iPTH and alkaline phosphatase levels were significantly controlled in all groups, as was bone pain. The proportions of patients with serum iPTH levels within the ranges recommended by Kidney Disease: Improving Global Outcomes were similar among the treatment groups. During the hungry bone disease (HBS), patients received 3,786 g (1,412-7,580) of elemental calcium, and a trend toward a positive correlation between the cumulative calcium load at the end of follow up and VC score post-PTx was noted (r = 0.390; P = .06). Two cases evolved to clinically uncontrolled hyperparathyroidism in the sub-PTx group. The expression patterns of PCNA, VDR, CasR, PIT1, FGFR1, and Klotho in parathyroid glands did not correlate with serum systemic iPTH levels or the duration of HBS. CONCLUSIONS: All 3 operative techniques were effective at controlling rSHP, both in clinical and laboratory terms. Neither the quantity nor quality of parathyroid fragments influenced serum systemic iPTH and AT-iPTH levels. The cumulative calcium load appeared to correlate with the VC score and may have affected its progression. The effects of phosphate restriction on Klotho expression in human parathyroid glands and the subsequent decrease in FGF23 resistance must be addressed in further studies.

Early postoperative parathormone sampling and prognosis after total parathyroidectomy in secondary hyperparathyroidism.

INTRODUCTION: There is possibility of a supernumerary hyperplastic parathyroid gland in dialysis patients after total parathyroidectomy and autograft in dialysis patients. OBJECTIVE: To test if the early postoperative measure of parathyroid hormone (PTH) can identify persistent hyperparathyroidism. METHODS: A prospective cohort of dialysis patients submitted to parathyroidectomy had PTH measured up to one week after operation. The absolute value and the relative decrease were analyzed according to clinical outcome of satisfactory control of secondary hyperparathyroidism or persistence. RESULTS: Of 51 cases, preoperative PTH varied from 425 to 6,964 pg/mL (median 2,103 pg/mL). Postoperatively, PTH was undetectable in 28 cases (54.9%). In eight individuals (15.7%) the PTH was lower than 16 pg/mL, in 10 (19.6%) the PTH values were between 16 and 87pg/mL, and in five (9.8%), PTH was higher than 87 pg/mL. Undetectable PTH was more common in patients with preoperative PTH below the median (p = 0.0002). There was a significant correlation between preoperative PTH and early postoperative PTH (Spearman R = 0.42, p = 0.002). A relative decrease superior to 95% was associated to satisfactory clinical outcome. A relative decrease less than 80% was associated to persistent disease, despite initial postoperative hypocalcemia. CONCLUSION: Measurement of PTH in the first days after parathyroidectomy in dialysis patients may suggest good clinical outcome if a decrease of at least 95% of the preoperative value is observed. Less than 80% PTH decrease is highly suggestive of residual hyperfunctioning parathyroid tissue with persistent hyperparathyroidism, and an early reintervention may be considered.

The deceptive concept of hypoparathyroidism and recurrence after parathyroidectomy in dialysis patients: are we offering a Procrustean bed to some patients?

OBJECTIVE:: to analyze the frequency of hypoparathyroidism and of its recurrence after parathyroidectomy in dialysis patients according to different existing classifications. METHODS:: we conducted a retrospective study of 107 consecutive dialysis patients undergoing total parathyroidectomy with immediate autograft in a tertiary hospital from 2006 to 2010. We studied the changes in PTH levels in the postoperative period over time. Were grouped patients according to different PTH levels targets recommended according to the dosage method and by the American and Japanese Nephrology Societies, and by an International Experts Consortium. RESULTS:: after parathyroidectomy, there was sustained reduction in serum calcium and phosphatemia. The median value of PTH decreased from 1904pg/ml to 55pg/ml in 12 months. Depending on the considered target level, the proportion of patients below the target ranged between 17% and 87%. On the other hand, the proportion of patients with levels above the target ranged from 3% to 37%. CONCLUSION:: the application of different recommendations for PTH levels after parathyroidectomy in dialysis patients may lead to incorrect classifications of hypoparathyroidism or recurrent hyperparathyroidism and resultin discordant therapeutic conducts. OBJETIVO:: analisar as frequências de hipoparatireoidismo e de recidiva do hiperparatireoidismo após paratireoidectomia em pacientes dialíticos de acordo com diferentes classificações existentes. MÉTODOS:: estudo retrospectivo de 107 pacientes dialíticos consecutivamente submetidos à paratireoidectomia total com autoenxerto imediato em um hospital terciário no período de 2006 a 2010. A variação dos níveis de PTH no pós-operatório foi estudada ao longo do tempo. Os pacientes foram agrupados de acordo com diferentes metas de níveis de PTH recomendados de acordo com o método de dosagem e pelas sociedades de nefrologia americana, japonesa e de um consórcio internacional de especialistas. RESULTADOS:: após a paratireoidectomia, houve redução sustentada da calcemia e fosfatemia. O valor mediano do PTH reduziu-se de 1904pg/ml para 55pg/ml, em 12 meses. Dependendo do nível alvo considerado, a proporção de pacientes abaixo da meta variou entre 17% e 87%. Ao contrário, a proporção de pacientes com níveis acima da meta variou de 3% a 37%. CONCLUSÃO:: O emprego de diferentes recomendações de níveis de PTH em pacientes dialíticos após paratireoidectomia pode levar a classificações incorretas de hipoparatireoidismo ou hiperparatireoidismo recidivado e implicar em condutas terapêuticas discordantes.

Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center.

Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.

[Functional results of parathyroid autotransplantation in one single pocket for treatment of secondary hyperparathyroidism].

OBJECTIVE: To evaluate the operation and surgical time of autotransplanted parathyroid in a single site comparing it to the implant performed in five and twenty locations. METHODS: Patients who underwent total parotidectomy with auto implant (Ptx-AI) for secondary and tertiary hyperparathyroidism were evaluated in groups of 20 implant sites (A), 5 sites (B) and single site (C), compared as for Functional Status (FE) of the implant and the surgical time of the procedure. Four functional states were determined according to the systemic level of PTH: 1-below normal, 2-normal, 3-high, no more than three times and 4 - more than three times higher. RESULTS: There were 349 patients subjected to Ptx-AI for renal hyperparathyroidism from 1994 to 2009. For the functional study, 101 patients were eligible for the following observations: group A (n = 30) - 16.6% EF1, 50% EF2, 23.3% EF3 and 10%EF4; group B (n = 41) - 14.6% EF1, 58.5% EF2, 22% EF3 and 4.9% EF4; Group C (n = 30) - 17% EF1, 57% EF2, 20%EF3 and 6% EF4 (p = 0.9, x²). But in group C the mean operative time of implant was statistically lower (7.9 minutes) compared to the average of 5 site (18.6 minutes) and 20-site (44 minutes) implants in 66 evaluated patients (p<0,0001, ANOVA). CONCLUSION: The self-implantation in a single site decreases the operative time without changing its functionality.

Análise da efetividade de três métodos de imagem -ressonância magnética, ultra-sonografia e cintilografia com 99mTc-MIBI - na localização pré-operatória da paratireoide em pacientes com hiperparatireoidismo primário / Efectivity analysis of three methods of imaging - magnetic ressonance, ultrasound and 99m Tc-MIBI cintilography - in preoperative parathyroid localization in patients with primary hyperparathyroidism

Introdução: No tratamento cirúrgico do hiperparatiroidismo primário a localização pré-operatória da glândula acometida é importante, pois permite uma abordagem menos invasiva. Os exames mais utilizados para localizar adenomas de paratireoide são a cintilografia com 99mTc sestamibi (MIBI), a ultrassonografia (US) e a ressonância magnética (RM). Nos casos de localização atípica do adenoma ou associação com patologias tireoidianas, a US pode perder sua acurácia sendo imprescindível a associação com outros métodos. Objetivo: Identificar a sensibilidade, especificidade, valores preditivos positivo e negativo na localização pré-operatória do adenoma de paratireoide de cada exame de imagem isoladamente. Método: Estudo de coorte retrospectivo analisando 40 prontuários médicos de pacientes com diagnóstico de hiperparatireoidismo primário submetidos a paratireoidectomia. Os pacientes foram submetidos a exames localizatórios (cintilografia com Tc99 sestamibi, ultra-sonografia e ressonância magnética). A análise objetivou identificar a sensibilidade, especificidade, valores preditivos positivo e negativo na localização pré-operatória do adenoma de paratireoide de cada exame de imagem isoladamente. Os achados cirúrgicos e histopatológicos foram o padrão-ouro. Resultados: A US apresentou uma sensibilidade de 63%, especificidade de 98%, valor preditivo positivo de 90% e valor preditivo negativo de 89%. A MIBI apresentou uma sensibilidade de 86%, especificidade de 99%, valor preditivo positivo de 96% e valor preditivo negativo de 95%. A RM apresentou uma sensibilidade de 57%, especificidade de 95%, valor preditivo positivo de 80% e valor preditivo negativo de 87%. Conclusão: A cintilografia com TC99 sestamibi é o exame localizatório com melhor sensibilidade e especificidade para identificar adenomas de paratireoide.

Introduction: It is important to allow a less invasive approach to localize preoperatively the adenoma in surgical management of primary hyperparathyroidism. The most common used methods are radionuclide imaging with 99mTc sestamibi (MIBI), ultrasound (US) an magnetic resonance imaging (MRI). In cases of atypical site adenomas or in association with thyroid diseases US can have less accuracy and it?s necessary the association with other imaging methods. Objective: To identify sensibility, specificity, positive and negative predictive values of each individual imaging method in preoperative location of parathyroid adenoma. Method: Retrospective cohort with 40 patients with primary hyperparathyroidism submitted to surgical treatment. The patients underwent localizatory methods (radionuclide imaging with Tc99 sestamibi, ultrasound and magnetic resonance imaging). The study identified sensibility, specificity, positive and negative predictive values of each individual method in preoperative location of parathyroid adenoma. Surgical and histological findings are the gold standart. Results: US has sensibility of 63%, specificity of 98%, positive predictive value of 905 and negative predictive value of 89%. MIBI has sensibility of 86%, specificity of 99%, positive predictive value of 96% and negative predictive value of 95%. MRI has sensibility of 57%, specificity of 95%, positive predictive value of 80% and negative predictive value of 87%. Conclusion: Radionuclide imaging with Tc99 sestamibi is the most sensible and specific imaging method for location of parathyroid adenomas.

Análise crítica dos exames iniciais de seguimento pós-tireoidectomia total por carcinoma bem diferenciado / Analysis of the initial follow-up exams after total thyroidectomy for well-differentiated, low risk thyroid cancer

Introdução: a incidência do câncer de tireóide tem aumentado nos últimos anos devido ao aumento do diagnóstico precoce. Considerando a tireoidectomia total como parte do tratamento, o seguimento [e realizado inicialmene com a pesquisa de corpo inteiro (PCI), dosagem sérica tireoglobulina (Tg) estimulada pelo hormônio tireo-estimulante (TSH) e sem estímulo. Objetivo: análise da importância relativa dos três exames na detecção de doença e indicação de terapia complementar conforme conduta do serviço. Pacientes e Método: estudados retrospectivamente os dados (gênero, idade, tipo histológico, tamanho do tumor, PCI e Tg com e sem estímulo de TSH) referentes aos pacientes operados por carcinoma bem diferenciado de tireóide entre 1999 e 2004, excluindo tipos histológicos mais agressivos, tumores > 4cm, extensão extratireoidiana e dosagem positiva para anticorpos anti-Tg. Os pacientes foram analisados em dois grupos (tumores com menos de 1cm e entre 1 e 4cm), sendo calculada sensibilidade dos exames em relação ao padrão-ouro (PCI associado a Tg estimulada). Resultados: dos 85 pacientes, 81 eram mulheres e 4 eram homens, com idade m[edia 44 anos. A sensibilidade da PCI e da Tg sem estímulo foi de 26,9%, enquanto a da Tg estimulada foi de 92,2%. Entre os tumores < 1cm, a sensibilidade da PCI foi de 16,6%, a da Tg sem estímulo foi de 33,3% e da Tg com estímulo de TSH foi de 100%. Discussão: O carcinoma bem diferenciado de tireóide tem excelente prognóstico para o grupo de baixo risco. A tireoglobulina estimulada foi o exame mais sensível em todos os grupos, com sensibilidade de 100% nos tumores menores que 1cm. A interpretação dos exames de seguimento deve ser individualizada e a indicação de ablação de restos tireóideos não deve ser aplicada em todos os pacientes

Intruduction: the incidence of thyroid cancer has been rising in the last years due to the improvement of early diagnosis. Considering the total thyroidectomy as part of the treatment, the follow-up can be performed with total body scan and thyroglobulin measurement, with and without TSH stimulation. Objective: to analyze the relative importance of each exam in detecting disease and the indication of complementary therapy as routine. Patients and methods: retrospective review of patients' charts, which underwent total thyroidectomy as part of the treatment for well-differentiated thyroid cancer, including gender, age, histologic subtype, size of tumor, total body scan, thyroglobulin with and without TSH stimulus. The patients with aggressive histologic subtypes, tumors > 4cm, extra-thyroid extension, and anti-thyroglobulin antibodies were excluded. The patients were analyzed in two groups- tumors < 1cm and between 1 and 4cm. The sensibility of each exam was calculated in relation to gold-standard total body scan associated with thyroglobulin. Results: 85 patients were studied, being 81 women and 4 men, with median age of 44 years-old. The sensibility of Tg without stimulus and total body scan were 26.9% and the sensibility of stimulated Tg was 92.2%. The sensibility of total body scan, Tg without stimulus and Tg with TSH stimulus was, respectively, 16.6%, 33.3% and 100%. Discussion: the well-differentiated thyroid cancer has excellent prognosis in the low-risk group. Stimulated thyroglobulin was the most sensitive exam in all groups, with a sensibility of 100% in the group with tumors < 1cm. Follow-up exams interpretation must be individualized and the ablation must not be applied for all patients