Hypoparathyroidism After Total Thyroidectomy: Importance of the Intraoperative Management of the Parathyroid Glands.

BACKGROUND: Total thyroidectomy is the most common surgical procedure for the treatment of thyroid diseases. Postoperative hypocalcemia/hypoparathyroidism is the most frequent complication after total thyroidectomy. The aim of this study was to evaluate the rate of postoperative hypocalcemia and permanent hypoparathyroidism after total thyroidectomy in order to identify potential risk factors and to evaluate the impact of parathyroid autotransplantation. PATIENTS AND METHODS: We performed a retrospective analysis of 1018 patients who underwent total thyroidectomy at our institution between 2000 and 2016. Medical records were reviewed to analyze patient features, clinical presentation, management and postoperative complications. Descriptive and inferential statistics were employed based on the natural scaling of each included variable. Statistical significance was set at p ≤ 0.05. RESULTS: Mean ± SD age was 46.79 ± 15.9 years; 112 (11.7%) were males and 844 (88.3%) females. A total of 642 (67.2%) patients underwent surgery for malignant disease. The rate of postoperative hypocalcemia, transient, protracted and permanent hypoparathyroidism was 32.8%, 14.43%, 18.4% and 3.9%, respectively. Permanent hypoparathyroidism was significantly associated with the number of parathyroid glands remaining in situ (4 glands: 2.5%, 3 glands: 3.8%, 1-2 glands: 13.3%; p ˂ 0.0001) [OR for 1-2 glands in situ = 5.32, CI 95% 2.61-10.82]. Other risk factors related to permanent hypoparathyroidism were obesity (OR 3.56, CI 95% 1.79-7.07), concomitant level VI lymph node dissection (OR 3.04, CI 95% 1.46-6.37) and incidental parathyroidectomy without autotransplantation (OR 3.6, CI 95% 1.85-7.02). CONCLUSIONS: Identification and in situ preservation of at least three parathyroid glands were associated with a lower rate of postoperative hypocalcemia (30.4%) and permanent postoperative hypoparathyroidism (2.79%).

[Intrathyroidal location of parathyroid glands. Atypical presentation of multiple endocrine neoplasia type 1 syndrome]. / Localización intratiroidea de glándulas paratiroides. Presentación atípica del síndrome de neoplasia endocrina múltiple tipo 1.

BACKGROUND: The most common manifestation of MEN 1 syndrome is primary hyperparathyroidism (PHPT) with parathyroid multiglandular affectation. The intrathyroidal situation represents 3-4% of all glands, and it is the second most frequent location in the cervical ectopias. CLINICAL CASE: 11 year old patient, with a family history of MEN1 syndrome and carrier of this same mutation. Patient presents HPTP with osteopenia. The cervical ultrasound shows three compatible images with pathological parathyroid glands (bilateral lower and upper left). The Scan and MRI are normal. Bone densitometry displays data on osteopenia. The patient is surgically intervened, only the upper parathyroid glands are located and removed, after this implantation is performed on the forearm, to prevent the possible devascularization in the dissection of the other glands. However, osteopenia persists and an elevated PTH, therefore new diagnostic tests are held which seem to show two lower parathyroid glands with intrathyroidal location. The patient is reoperated. A subtotal parathyroidectomy of the lower right gland and the resection of the left gland is performed, with the use of intraoperative ultrasound and placement of harpoon. The intraoperative pathology study confirms parathyroid tissue in both cases. DISCUSSION: It is necessary to locate the parathyroid glands preoperatively in order to alert us of the existence of topographical and ectopia abnormalities, as well as their intrathyroidal location (0.5-3.6%). CONCLUSION: The intraoperative ultrasound can be a complement to the experience of the endocrine surgeon for the localization of the parathyroid glands and therefore can help determine the best surgical strategy for each clinical case.

Microencapsulation of Parathyroid Cells for the Treatment of Hypoparathyroidism.

Cell encapsulation is an alternative to avoid rejection of grafted tissue, thus bringing an interesting alternative in cell therapy. It is particularly relevant in ailments where only the implant of small quantities of tissues is warranted. In such circumstances, the use of immunosuppressive therapy in patients implanted with tissues from donors is debatable, yet unavoidable at present in order to prevent rejection and/or sensitization of the host to the tissue, in turn jeopardizing the success of successive implants. Hence, a new line of thought, which aims to provide an immunoprivileged site for the grafted tissue, while at the same time insure its nutrition, as well as its survival and continued function, appears as a most attractive possibility. To achieve these goals, cells or tissues harvested for transplant could be encapsulated in biologically compatible matrices. Among the matrices currently in existence, sodium alginate is the most widely used polymer for tissue encapsulation.In the present chapter, we present a technique used to encapsulate parathyroid tissue, for use as cell transplant therapy in patients with secondary hypoparathyroidism. With this procedure, implanted tissue survives and remains functional for up to 18 months.

Parathyroid responsiveness during hypocalcemia after total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism. / Responsividade paratireoideana à hipocalcemia após paratireoidectomia total com autoimplante em portadores de hiperparatireoidismo associado à doença renal crônica.

INTRODUCTION: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management. OBJECTIVE: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT. METHODS: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery. RESULTS: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693). CONCLUSION: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels.

Responsividade paratireoideana à hipocalcemia após paratireoidectomia total com autoimplante em portadores de hiperparatireoidismo associado à doença renal crônica / Parathyroid responsiveness during hypocalcemia after total parathyroidectomy and autotransplantation in patients with renal hyperparathyroidism

Resumo Introdução: O hiperparatireoidismo é uma complicação frequente da doença renal crônica (DRC). A paratireoidectomia (PTX) total com autotransplante (AT) de tecido paratireoideano é uma opção terapêutica para os indivíduos que não respondem ao manejo clínico. Objetivo: Avaliar a resposta do tecido paratireoideano enxertado durante hipocalcemia induzida em pacientes portadores de DRC submetidos à PTX total com AT. Métodos: Dezoito pacientes portadores de hiperparatiroidismo associado à DRC foram submetidos à PTX total com AT de tecido paratireoideano selecionado por estereomicroscopia entre Abril e Outubro de 2008 em nosso serviço. Onze indivíduos (oito com transplante renal funcionante, 2 em diálise peritoneal e 1 em hemodiálise) apresentavam boa condição clínica e foram elegíveis para o teste. Induziu-se hipocalcemia por infusão de bicarbonato de sódio em 5 controles normais e nos pacientes 6-12 meses após a PTX. Resultados: A hipocalcemia determinou um aumento importante dos níveis de PTH intacto (iPTH) no grupo controle 4 minutos após a infusão de bicarbonato. Nos pacientes, houve uma redução significativa do cálcio ionizado [de 1,17 ± 0,12 para 1,09 ± 0,11 (media ± EP) mmol/L] no 4º minuto (p < 0,001) ilustrando o nadir do teste. No 10º minuto não houve elevação do cálcio ionizado comparado ao 4º minuto (p = 0,451). Os níveis de iPTH foram de 34,8 ± 18,6 para 34,1 ± 18,8 pg/mL (valor basal semelhante ao 4º minuto p = 0,087) e se mantiveram no 10º minuto (33,3 ± 19,6 pg/mL p = 0,693). Conclusão: Em pacientes portadores de DRC testados 6-12 meses depois da cirurgia, o enxerto de tecido paratireoideano revelou incapacidade de resposta à hipocalcemia induzida por bicarbonato sem mudança dos níveis de iPTH.

Abstract Introduction: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management. Objective: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT. Methods: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery. Results: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693). Conclusion: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels.

[Allogeneic parathyroid: 2-year follow-up]. / Alotrasplante de paratiroides: seguimiento a 2 años.

BACKGROUND: Hypoparathyroidism is one of the most frequent complications of neck surgery. The treatment is currently medical; however this involves several complications secondary to high doses of calcium and vitamin D, thus making parathyroid allotransplantation a good management option. MATERIAL AND METHODS: Patients with hypoparathyroidism were selected in the April-December period of 2011 in the general surgical clinic. They were between 16 and 65 years, and ingested high doses of calcium. The donors were patients with primary and secondary hyperparathyroidism, and the transplants were performed in relation to blood group and human leucocyte antigen. RESULTS: Five parathyroid allografts were performed. All the patients had iatrogenic hypoparathyroidism, all women with a mean age of 49.8 years. The graft was implanted under local anaesthesia in the non-dominant forearm. Four of the patients are so far considered functional due to the increase in paratohormone, and demonstrating its function by scintigraphy with sestamibi. One of the patients showed no increase in paratohormone or imaging studies that demonstrate its functionality. After a two year follow up the graft remains functional but with with oral calcium intake at a lower dose than before transplantation. None of the patients had immunosuppression side effects. CONCLUSIONS: In this study, allogeneic unrelated living parathyroid transplant with an immunosuppressive regimen of six months has proven to be a safe alternative treatment to improve quality of life by decreasing the excessive calcium intake and improving physical activity with adequate graft survival at 24 months follow up.

Thyroidectomy with parathyroid implantation: is it an easy technique?

Background: Feline hyperthyroidism is the most common endocrine disorder in cats. Cats may not reach the diseasecontrol and/or have side effects with medical therapy. Thyroidectomy is a definitive treatment and the only option whenradioactive iodine is not available. Extracapsular thyroidectomy with transplantation of the external parathyroid gland isthe surgical technique that minimizes the risk of postoperative hypocalcemia when it is compared to others. The aim ofthis study is report the difficulty in visualizing parathyroid gland during extracapsular thyroidectomy with transplantationof the external parathyroid gland technique in hyperthyroid cats.Materials, Methods & Results: Thirty hyperthyroid cats were evaluated and submitted to extracapsular thyroidectomywith transplantation of the external parathyroid gland. Blood samples were collected to hematologic, biochemical andhormonal (total thyroxine) analysis. On physical examination, at least one cervical thyroid lobe was palpable. Cats weretreated with methimazole. Thyroidectomy was recommended when adverse effects of medication occurred or medicalhormonal stabilization was not achieved. The excised thyroid and a sample of external parathyroid gland were histologically examined. Thirteen castrated males and seventeen spayed female cats in age ranging from eight to nineteen years(mean age 13.3 years) were indicated to surgery. Twenty three cats were Brazilian domestic short hair, six were Siameseand one was Oriental. Thyroid palpable cervical nodule was unilateral in eight cats and bilateral in twenty two cats. Thereasons for surgery included adverse effects of methimazole (14/30), difficulty in medicating, owners’ interest in surgicaltreatment (6/30) and inability to stabilize with medical management (10/30). None developed any anesthetic or postoperative complications. The...

Thyroidectomy with parathyroid implantation: is it an easy technique?

Background: Feline hyperthyroidism is the most common endocrine disorder in cats. Cats may not reach the diseasecontrol and/or have side effects with medical therapy. Thyroidectomy is a definitive treatment and the only option whenradioactive iodine is not available. Extracapsular thyroidectomy with transplantation of the external parathyroid gland isthe surgical technique that minimizes the risk of postoperative hypocalcemia when it is compared to others. The aim ofthis study is report the difficulty in visualizing parathyroid gland during extracapsular thyroidectomy with transplantationof the external parathyroid gland technique in hyperthyroid cats.Materials, Methods & Results: Thirty hyperthyroid cats were evaluated and submitted to extracapsular thyroidectomywith transplantation of the external parathyroid gland. Blood samples were collected to hematologic, biochemical andhormonal (total thyroxine) analysis. On physical examination, at least one cervical thyroid lobe was palpable. Cats weretreated with methimazole. Thyroidectomy was recommended when adverse effects of medication occurred or medicalhormonal stabilization was not achieved. The excised thyroid and a sample of external parathyroid gland were histologically examined. Thirteen castrated males and seventeen spayed female cats in age ranging from eight to nineteen years(mean age 13.3 years) were indicated to surgery. Twenty three cats were Brazilian domestic short hair, six were Siameseand one was Oriental. Thyroid palpable cervical nodule was unilateral in eight cats and bilateral in twenty two cats. Thereasons for surgery included adverse effects of methimazole (14/30), difficulty in medicating, owners interest in surgicaltreatment (6/30) and inability to stabilize with medical management (10/30). None developed any anesthetic or postoperative complications. The...(AU)

Successful parathyroid tissue autograft after 3 years of cryopreservation: a case report.

After a total parathyroidectomy, well-established protocols for the cryopreservation of parathyroid tissue and for the delayed autograft of this tissue exist, especially in cases of secondary hiperparathyroidism (HPT) or familial or sporadic parathyroid hyperplasia. Although delayed autografts are effective, the published success rates vary from 10% to 83%. There are numerous factors that influence the viability, and therefore the success, of an autograft, including cryopreservation time. Certain authors believe that the tissue is only viable for 24 months, but there is no consensus on how long the parathyroid tissue can be preserved. A 63-year-old male who was diagnosed with sporadic multiple endocrine neoplasia type 1 and primary hyperparathyroidism, and was submitted to a total parathyroidectomy and an autograft in the forearm. The implant failed, and the patient developed severe hypoparathyroidism in the months following the surgery. Thirty-six months after the total parathyroidectomy, the cryopreserved autograft was successfully transplanted, and hypoparathyroidism was reversed (most recent systemic parathyroid hormone, PTH, of 36 pg/mL, and total calcium of 9.1 mg/dL; no oral calcium supplementation). The case presented here indicates that cryopreserved parathyroid tissue may remain viable after 24 months in storage, and may retain the capacity to reverse permanent postsurgical hypoparathyroidism. These data provide reasonable evidence that the time limit for cryopreservation remains undetermined and that additional research would be valuable.

Successful parathyroid tissue autograft after 3 years of cryopreservation: a case report / Implante bem-sucedido de paratireoide criopreservada por 3 anos: relato de caso

After a total parathyroidectomy, well-established protocols for the cryopreservation of parathyroid tissue and for the delayed autograft of this tissue exist, especially in cases of secondary hiperparathyroidism (HPT) or familial or sporadic parathyroid hyperplasia. Although delayed autografts are effective, the published success rates vary from 10% to 83%. There are numerous factors that influence the viability, and therefore the success, of an autograft, including cryopreservation time. Certain authors believe that the tissue is only viable for 24 months, but there is no consensus on how long the parathyroid tissue can be preserved. A 63-year-old male who was diagnosed with sporadic multiple endocrine neoplasia type 1 and primary hyperparathyroidism, and was submitted to a total parathyroidectomy and an autograft in the forearm. The implant failed, and the patient developed severe hypoparathyroidism in the months following the surgery. Thirty-six months after the total parathyroidectomy, the cryopreserved autograft was successfully transplanted, and hypoparathyroidism was reversed (most recent systemic parathyroid hormone, PTH, of 36 pg/mL, and total calcium of 9.1 mg/dL; no oral calcium supplementation). The case presented here indicates that cryopreserved parathyroid tissue may remain viable after 24 months in storage, and may retain the capacity to reverse permanent postsurgical hypoparathyroidism. These data provide reasonable evidence that the time limit for cryopreservation remains undetermined and that additional research would be valuable. Arq Bras Endocrinol Metab. 2014;58(3):313-6.

O implante de tecido paratireoideano criopreservado após paratireoidectomia total é um procedimento bem estabelecido e, embora tenha sua eficácia comprovada, as taxas de sucesso variam de 10% a 83% na literatura. O tempo de criopreservação é um dos diversos fatores relacionados ao sucesso do implante. Alguns autores defendem que o tecido permanece viável até 24 meses de criopreservação, no entanto, não há consenso. Homem de 63 anos diagnosticado com neoplasia endócrina múltipla tipo I e hiperparatireoidismo primário foi submetido a paratireoidectomia total e autoimplante em membro superior. O implante falhou e o paciente desenvolveu hipoparatireoidismo. Após 36 meses da paratireoidectomia total, foi realizado o implante de paratireoide criopreservada, com sucesso. O hipoparatireoidismo foi revertido e o paciente permanece sem suplementação de cálcio e PTH sistêmico de 36 pg/mL e cálcio total de 9,1 mg/dL. O caso apresentado mostra que o tecido paratireoideano criopreservado pode permanecer viável após 24 meses e há possibilidade de reverter o hipoparatireoidismo pós-cirúrgico. Isso traz evidência de que o tempo limite de criopreservação permanece incerto e que novas pesquisas seriam de grande valia. Arq Bras Endocrinol Metab. 2014;58(3):313-6.

Local ethanol injection for the treatment of deltoid parathyroid cell hyperplasia.

Secondary hyperparathyroidism (SHPT) is a serious complication in dialysis patients and is routinely managed with medical therapy. Refractory disease is usually treated either surgically or by local ethanol injection into the parathyroid glands. Total parathyroidectomy with deltoid implant can be successful; however, recurrent, resistant disease is not uncommon. Local ethanol injection was applied to the deltoid autoimplant of a patient with recurrent, resistant SHPT, which had not been resolved with surgical treatment. Serum intact parathyroid hormone (iPTH) levels subsequently decreased from 1,400 to 219 pg/dl and remained stable for the next 6 months. To our knowledge, this procedure has not been previously described in the literature. Local injection of ethanol may represent an interesting alternative to surgery for the treatment of deltoid parathyroid cell hyperplasia in patients in which surgical treatment is not an option.

Intraoperative PTH cutoff definition to predict successful parathyroidectomy in secondary and tertiary hyperparathyroidism.

UNLABELLED: In order to improve success rates in surgery of renal hyperparathyroidism, we evaluated intraoperative PTH (IOPTH) measurement utility. METHOD: 86 patients underwent total parathyroidectomy with intramuscular presternal autotransplantation from 04/2000 to 10/2009 and were followed for 26.5 months on average (prospective cohort). Patients were divided in secondary (SHPT) and tertiary hyperparathyroidism (THPT). SHPT group was composed by patients under dialysis treatment, THPT group included renal grafted ones. IOPTH (Elecsys-PTH-Immunoassay/Roche) was measured at anesthesia induction (IOPTH-0') and 20 minutes (IOPTH-20') after parathyroidectomy. RESULTS: 80.2% (69/86) presented with 80% decrease or more in the IOPTH-20' and all were cured. In 11/86 patients (12.7%), a lower IOPTH-20' drop (70-79%) was observed, and 2 of them (18.1%) failed to cure. 6/86 (6.9%) patients presented IO-PTH-20' decrease of less than 70%: two were cured, in three a supernumerary/ectopic parathyroid was found and removed, and in one of these six patients, surgery was finished after 4-gland excision and the patient failure to cure. CONCLUSION: IOPTH-20' decrease of 80% or more compared to IOPTH-0' predicts cure in all renal patients throughout follow-up. A decay of less than 70% points to missed or hyperfunctioning supernumerary gland and is predictive of surgical failure in 66.6%. A marginal IOPTH drop of 70-79% leaves the decision whether or not surgery should be continued up to the experienced surgeon.

Definição de valores de corte para medida de PTH intraoperatório no tratamento cirúrgico do hiperparatiroidismo secundário e terciário / Intraoperative PTH cutoff definition to predict successful parathyroidectomy in secondary and tertiary hyperparathyroidism

Avaliamos medida de PTH intraoperatório (IO-PTH) no intuito de melhorar índices de sucesso no tratamento cirúrgico do hiperparatiroidismo associado à doença renal. MÉTODO: Oitenta e seis pacientes realizaram paratiroidectomia total com autoimplante em musculatura pré-esternal entre abril de 2000 e outubro de 2009 com 26,5 meses de seguimento em média, prospectivo. Foram divididos em dois grupos: hiperparatiroidismo secundário (HPS) - pacientes em diálise e hiperparatiroidismo terciário (HPT) - transplantados renais. Medido IO-PTH (Elecsys-PTH-Immunoassay/Roche) na indução anestésica (IOPTH-0') e 20 minutos (IOPTH-20') após a retirada das paratireoides. RESULTADOS: 80,2% (69/86) do total de pacientes apresentaram queda de 80% ou mais do IOPTH-20' e todos se curaram. Em 11/86 (12,7%) pacientes, foi observada queda entre 70-79%, sendo que dois (18,1%) deles evoluíram com falha cirúrgica. 6/86 (6,9%) pacientes apresentaram redução de IOPTH-20' menor do que 70%: dois foram curados; três apresentaram paratireoide supranumerária/ectópica que foi localizada e removida; um paciente evoluiu com persistência da doença após término da cirurgia com a retirada de quatro paratireoides. CONCLUSÃO: Queda do IOPTH-20' de 80% ou mais foi preditor de cura em todos os pacientes renais durante o período avaliado. Redução menor que 70% sugere paratireoide hiperfuncionante não reconhecida/supranumerária, sendo preditor de falha cirúrgica em 66.6%. A queda marginal de 70%-79% delega ao cirurgião experiente a decisão de continuar ou não o procedimento cirúrgico.

In order to improve success rates in surgery of renal hyperparathyroidism, we evaluated intraoperative PTH (IOPTH) measurement utility. METHOD: 86 patients underwent total parathyroidectomy with intramuscular presternal autotransplantation from 04/2000 to 10/2009 and were followed for 26.5 months on average (prospective cohort). Patients were divided in secondary (SHPT) and tertiary hyperparathyroidism (THPT). SHPT group was composed by patients under dialysis treatment, THPT group included renal grafted ones. IOPTH (Elecsys-PTH-Immunoassay/Roche) was measured at anesthesia induction (IOPTH-0') and 20 minutes (IOPTH-20') after parathyroidectomy. RESULTS: 80.2% (69/86) presented with 80% decrease or more in the IOPTH-20' and all were cured. In 11/86 patients (12.7%), a lower IOPTH-20' drop (70-79%) was observed, and 2 of them (18.1%) failed to cure. 6/86 (6.9%) patients presented IO-PTH-20' decrease of less than 70%: two were cured, in three a supernumerary/ectopic parathyroid was found and removed, and in one of these six patients, surgery was finished after 4-gland excision and the patient failure to cure. CONCLUSION: IOPTH-20' decrease of 80% or more compared to IOPTH-0' predicts cure in all renal patients throughout follow-up. A decay of less than 70% points to missed or hyperfunctioning supernumerary gland and is predictive of surgical failure in 66.6%. A marginal IOPTH drop of 70-79% leaves the decision whether or not surgery should be continued up to the experienced surgeon.

Caracterización de línea celular de paratiroides humana (RCPTH) y evaluación de tumorigenicidad en ratones NOD/SCID / Characterization of human parathyroid cell line (RCPTH) and tumorigenicity evaluation in NOD/SCID

Background: Cell therapy could be an alternative for the treatment of hypoparathyroidism. Therefore efforts have been made to establish a cell line of parathyroid cells. Aim: To establish a continuous functional and non-tumorigenic human parathyroid cell line. Material and Methods: Nineteen tissue samples from 15 patients subjected to parathyroidectomy due to primary or secondary hyperparathyroidism were obtained. Functional, morphological and tumorigenic properties of the obtained cells were analyzed. Results: After two months of culture in conditions of immortalization, cells had an exponential growth without experiencing senescence. Therefore, more than 200 sub cultures have been performed. The cell line was denominated RCPTH. Morphological characterization showed monolayer growth with contact inhibition and a duplication time of 30 hours. On light microscopy, pleomorphism and low number of mitoses were observed. Cells accumulated glycogen, expressed calcium sensing receptor and had positive PTH cytoplasmic clusters. The line secreted PTH initially but subsequently, PTH production became undetectable. The cell line did not have tumor or metastatic growth. Conclusions: A parathyroid cell line has been established. The lack of PTH production is a problem that will require the search for mechanisms to activate it.

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.

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.

Effects of time on ultrastructural integrity of parathyroid tissue before cryopreservation.

BACKGROUND: Cryopreservation of parathyroid tissue is used in the surgical treatment of secondary hyperparathyroidism. After surgical resection, the tissue is temporarily maintained in a cell culture solution until it arrives at the specialized laboratory where the cryopreservation process will take place. The present study evaluates the time that the human hyperplastic parathyroid gland tissue can wait before cryopreservation, based on parathyroid cell ultrastructural integrity. METHODS: This prospective study included 11 patients who underwent total parathyroidectomy with heterotopic autotransplantation and cryopreservation of parathyroid tissue fragments. Part of the tissue was kept in cell culture solution at 4 °C. Five time periods between 2 and 24 h were defined, and parathyroid fragments were kept in the solution for that length of time. At the end of each period, the fragments were removed from the transport solution, fixed, and prepared for ultrathin sections. RESULTS: Of the 11 cases studied, 10 showed ultrastructural findings consistent with cellular viability in tissue fragments that remained in the transport solution up to 12 h. Electron microscopy revealed that cell adhesion and the integrity of plasma membranes, nuclei, and mitochondria were preserved in one case for up to 24 h. Changes in mitochondrial structure represented the most constant ultrastructural damage seen in the cases studied, in addition to the presence of edema and cell vacuoles. CONCLUSIONS: Analysis of the ultrastructure of hyperplastic parathyroid gland tissue showed that ultrastructural integrity was in most cases properly maintained in fragments stored up to 12 h in a cell culture solution at 4 °C.

[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.

Resultados funcionais do auto-implante de paratireóides em loja única no tratamento do hiperparatireoidismo secundário / Functional results of parathyroid autotransplantation in one single pocket for treatment of secondary hyperparathyroidism

OBJETIVO: Avaliar o funcionamento e tempo cirúrgico do auto-implante de paratireóide em loja única comparando-o ao implante realizado em cinco e vinte lojas. MÉTODOS: Pacientes submetidos à parotidectomia total com auto implante (Ptx-AI) por hiperparatireoidismo secundário e terciário foram avaliados em grupos de implantes em 20 lojas (A), cinco lojas (B) e loja única (C), em relação ao Estado Funcional (EF) do implante e ao tempo cirúrgico deste. Foram determinados quatro Estados Funcionais de acordo com o nível sistêmico de PTH: 1-abaixo do normal; 2-normal; 3- elevado não mais que três vezes; 4- elevado mais que três vezes. RESULTADOS: Foram submetidos a Ptx-AI 349 pacientes, por hiperparatireoidismo renal, entre 1994 a 2009. Para o estudo funcional foram elegíveis 101 pacientes com as seguintes observações: grupo A (n=30) - EF1 16,6 por cento, EF2 50 por cento, EF3 23,3 por cento e EF4 10 por cento; grupo B (n=41) - EF1 14,6 por cento, EF2 58,5 por cento, EF3 22 por cento e EF4 4,9 por cento; Grupo C (n=30) - EF1 17 por cento, EF2 57 por cento, EF3 20 por cento e EF4 6 por cento (p=0,9, x²). Porém no grupo C, o tempo cirúrgico médio do implante foi estatisticamente mais rápida (7,9 minutos) em relação à média em cinco lojas (18,6 minutos) e 20 lojas (44 minutos), em 66 pacientes avaliados (p<0,0001, ANOVA). CONCLUSÃO: O auto-implante em loja única diminui o tempo cirúrgico sem alterar a funcionalidade do mesmo.

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 percent EF1, 50 percent EF2, 23.3 percent EF3 and 10 percentEF4; group B (n = 41) - 14.6 percent EF1, 58.5 percent EF2, 22 percent EF3 and 4.9 percent EF4; Group C (n = 30) - 17 percent EF1, 57 percent EF2, 20 percentEF3 and 6 percent 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.

Allotransplant of microencapsulated parathyroid tissue in severe postsurgical hypoparathyroidism: a case report.

The last therapeutic alternative in severe postsurgical hypoparathyroidism is allotransplantation of microencapsulated parathyroid cells. With this technique, it is possible to implant cells or tissue of parathyroid origin to replace them in such patients, without immusupression. We report an allotransplant of parathyroid tissue in a patient with continous endovenous requirement of calcium to survive. The microencapsulation was carried out with a commercial sodium alginate. We implant 23 microspheres in the nondominant forearm and 40 microspheres in the leg in a second attempt. In this article, we show functionality of the graft for at least 20 months without requirement of endovenous calcium. We report this procedure as a therapeutical alternative in severe hypoparathyroidism.