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.

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.

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.

Germline mutation landscape of multiple endocrine neoplasia type 1 using full gene next-generation sequencing.

Background Loss-of-function germline MEN1 gene mutations account for 75-95% of patients with multiple endocrine neoplasia type 1 (MEN1). It has been postulated that mutations in non-coding regions of MEN1 might occur in some of the remaining patients; however, this hypothesis has not yet been fully investigated. Objective To sequence for the entire MEN1 including promoter, exons and introns in a large MEN1 cohort and determine the mutation profile. Methods and patients A target next-generation sequencing (tNGS) assay comprising 7.2 kb of the full MEN1 was developed to investigate germline mutations in 76 unrelated MEN1 probands (49 familial, 27 sporadic). tNGS results were validated by Sanger sequencing (SS), and multiplex ligation-dependent probe amplification (MLPA) assay was applied when no mutations were identifiable by both tNGS and SS. Results Germline MEN1 variants were verified in coding region and splicing sites of 57/76 patients (74%) by both tNGS and SS (100% reproducibility). Thirty-eight different pathogenic or likely pathogenic variants were identified, including 13 new and six recurrent variants. Three large deletions were detected by MLPA only. No mutation was detected in 16 patients. In untranslated, regulatory or in deep intronic MEN1 regions of the 76 MEN1 cases, no point or short indel pathogenic variants were found in untranslated, although 33 benign/likely benign and three new VUS variants were detected. Conclusions Our study documents that point or short indel mutations in non-coding regions of MEN1 are very rare events. Also, tNGS proved to be a highly effective technology for routine genetic MEN1 testing.

Quality of life after surgery in secondary hyperparathyroidism, comparing subtotal parathyroidectomy with total parathyroidectomy with immediate parathyroid autograft: Prospective randomized trial.

BACKGROUND: No prospective randomized data exist about the impact of various strategies of parathyroidectomy in secondary hyperparathyroidism patients on quality of life and its possible relationship with metabolic status after the operation. METHOD: In a prospective randomized trial, the Short Form 36 Health Survey Questionnaire was applied to 69 patients undergoing parathyroidectomy through various approaches: subtotal parathyroidectomy (n = 23), total parathyroidectomy (PTx) with autotransplantation of 45 fragments (n = 25) and PTx with autotransplantation of 90 fragments (n = 21). The questionnaire was completed at three moments: (1) preoperatively, (2) 6 months after surgery, and (3) 12 months after surgery. RESULTS: Quality of life improved significantly in the physical component summary score in all three groups. Subtotal parathyroidectomy scores changed from 30.6 preoperatively to 51.7 6 months after surgery and 53.7 12 months after surgery. Total arathyroidectomy with autotransplantation of 45 fragments scores changed from 33.8 preoperatively to 52.6 6 months after surgery and 55.2 12 months after surgery. Total parathyroidectomy with autotransplantation of 90 fragments scores changed from 31.8 preoperatively to 50.5 6 months after surgery and 55.2 12 months after surgery (all groups P < .0001). No significant difference was detected in the physical component summary score change among the three groups. The physical component summary score was negatively correlated to age, parathormone, and alkaline phosphatase preoperatively. CONCLUSION: Parathyroidectomy significantly improves quality of life in hemodialysis patients with secondary hyperparathyroidism, regardless of the type of operation.

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.

Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1.

Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1 related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.

Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2.

We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.

Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1.

The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm) on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months) improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation.

Biochemical, bone and renal patterns in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Primary hyperparathyroidism associated with multiple endocrine neoplasia type I (hyperparathyroidism/multiple endocrine neoplasia type 1) differs in many aspects from sporadic hyperparathyroidism, which is the most frequently occurring form of hyperparathyroidism. Bone mineral density has frequently been studied in sporadic hyperparathyroidism but it has very rarely been examined in cases of hyperparathyroidism/multiple endocrine neoplasia type 1. Cortical bone mineral density in hyperparathyroidism/multiple endocrine neoplasia type 1 cases has only recently been examined, and early, severe and frequent bone mineral losses have been documented at this site. Early bone mineral losses are highly prevalent in the trabecular bone of patients with hyperparathyroidism/multiple endocrine neoplasia type 1. In summary, bone mineral disease in multiple endocrine neoplasia type 1related hyperparathyroidism is an early, frequent and severe disturbance, occurring in both the cortical and trabecular bones. In addition, renal complications secondary to sporadic hyperparathyroidism are often studied, but very little work has been done on this issue in hyperparathyroidism/multiple endocrine neoplasia type 1. It has been recently verified that early, frequent, and severe renal lesions occur in patients with hyperparathyroidism/multiple endocrine neoplasia type 1, which may lead to increased morbidity and mortality. In this article we review the few available studies on bone mineral and renal disturbances in the setting of hyperparathyroidism/multiple endocrine neoplasia type 1. We performed a meta-analysis of the available data on bone mineral and renal disease in cases of multiple endocrine neoplasia type 1-related hyperparathyroidism.

Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2

We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.

Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1

The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm) on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months) improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation.

Oral mucosal melanoma of the mandibular gingiva: a case report.

Oral mucosal melanoma is rare and is reported to be more aggressive than cutaneous melanoma. The incidence of oral mucosal melanoma peaks at 41 to 60 years of age and the male to female ratio is 2 to 1. Preferred sites in the oral mucosa include the hard palate and maxillary alveolar crests. Risk factors have not been clearly identified, but melanotic pigmentation is present in one-third of patients prior to the diagnosis of melanoma. We report an unusual case of oral mucosal melanoma of the mandibular gingiva with the main characteristics of an in situ lesion and areas of superficial invasion in a 45-year-old woman. The patient was treated with surgical resection of the lesion and a 54-month follow-up shows no evidence of recurrence. Oral mucosal melanomas are aggressive neoplasms that may arise from prior pigmented lesions in the oral mucosa. Classification of these tumors is not well-established and the main prognostic factor appears to be lymph node compromise. The main treatment modality is surgical resection.

Early-onset, progressive, frequent, extensive, and severe bone mineral and renal complications in multiple endocrine neoplasia type 1-associated primary hyperparathyroidism.

Differences in bone mineral density (BMD) patterns have been recently reported between multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) and sporadic primary HPT. However, studies on the early and later outcomes of bone/renal complications in HPT/MEN1 are lacking. In this cross-sectional study, performed in a tertiary academic hospital, 36 patients cases with uncontrolled HPT from 8 unrelated MEN1 families underwent dual-energy X-ray absorptiometry (DXA) scanning of the proximal one-third of the distal radius (1/3DR), femoral neck, total hip, and lumbar spine (LS). The mean age of the patients was 38.9 ± 14.5 years. Parathyroid hormone (PTH)/calcium values were mildly elevated despite an overall high percentage of bone demineralization (77.8%). In the younger group (<50 years of age), demineralization in the 1/3DR was more frequent, more severe, and occurred earlier (40%; Z-score -1.81 ± 0.26). The older group (>50 years of age) had a higher frequency of bone demineralization at all sites (p < .005) and a larger number of affected bone sites (p < .0001), and BMD was more severely compromised in the 1/3DR (p = .007) and LS (p = .002). BMD values were lower in symptomatic (88.9%) than in asymptomatic HPT patients (p < .006). Patients with long-standing HPT (>10 years) and gastrinoma/HPT presented significantly lower 1/3DR BMD values. Urolithiasis occurred earlier (<30 years) and more frequently (75%) and was associated with related renal comorbidities (50%) and renal insufficiency in the older group (33%). Bone mineral- and urolithiasis-related renal complications in HPT/MEN1 are early-onset, frequent, extensive, severe, and progressive. These data should be considered in the individualized clinical/surgical management of patients with MEN1-associated HPT.

Bone mineral density analysis in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 after total parathyroidectomy.

OBJECTIVE: Limited data have been reported on the effect of parathyroidectomy (PTx) on bone mineral density (BMD) in the setting of patients with hyperparathyroidism (HPT) associated with multiple endocrine neoplasia type 1 (MEN1). This study investigates the impact of total PTx on BMD in patients with HPT/MEN1. DESIGN AND PATIENTS: A case series study was performed in a tertiary academic hospital. A total of 16 HPT/MEN1 patients from six families harbouring MEN1 germline mutations were subjected to total PTx followed by parathyroid auto-implant in the forearm. MEASUREMENTS: Bone mineral density values were assessed using dual-energy X-ray absorptiometry. RESULTS: Before PTx, reduced BMD (Z-score <-2.0) was highly prevalent in the proximal one-third of the distal radius (1/3 DR) (50%), lumbar spine (LS) (43.7%), ultradistal radius (UDR) (43.7%), femoral neck (FN) (25%) and total femur (TF) (18.7%) in the patients. Fifteen months after PTx, we observed a BMD improvement in the LS (from 0.843 to 0.909 g/cm(2); +8.4%, P = 0.001), FN (from 0.745 to 0.798 g/cm(2); +7.7%, P = 0.0001) and TF (from 0.818 to 0.874 g/cm(2); +6.9%, P < 0.0001). No significant change was noticed in the 1/3 DR and UDR after PTx. CONCLUSIONS: This data confirmed BMD recovery in the LS and FN after PTx in HPT/MEN1 patients. We also documented a significant BMD increase in the TF and no change in both the 1/3 DR and UDR BMD after PTx. Our data suggest that LS and proximal femur are the most informative sites to evaluate the short-term BMD outcome after PTx in HPT/MEN1 subjects.

How to minimize complications in thyroid surgery?

BACKGROUND: In ancient times, operations on the thyroid gland caused unacceptable morbidity and mortality. Only after the landmark work of Kocher, the technical principles of thyroidectomy were solidly established, and are still valid nowadays. METHODS: Revision article on practical suggestions to decrease morbidity associated with thyroidectomy, as well as warning against common pitfalls that the surgeon may encounter. RESULTS: The following subjects are objectively addressed: how to manage upper airway obstruction, how to avoid non-esthetic scars and how to recognize the most prevalent anatomic variations concerning the recurrent nerve, the external branch of the superior laryngeal nerve and the parathyroid glands, in order to decrease operative morbidity. CONCLUSION: The Head and Neck Surgeon must be fully aware of the complex anatomy of the central visceral compartment of the neck, as well as must be prepared to handle some complications of thyroidectomy that can be life-threatening.

Associação de carcinoma papilífero da tireóide e hiperparatireoidismo / Association of papillary thyroid carcinoma and hyperparathyroidism

OBJETIVO: A ocorrência de carcinoma papilífero da tireóide (CPT) em doentes com hiperparatireoidismo (HPT) suscita dúvidas quanto a ser apenas coincidência ou apresentar relação causal. O objetivo deste trabalho é verificar se a incidência de CPT em diferentes formas de HPT é semelhante entre si e à incidência de CPT em achados de necropsias, assim como em doentes submetidos à tireoidectomia na mesma região. MÉTODO: Os dados de 222 pacientes consecutivos tratados por HPT foram revistos e foi analisada a incidência de CPT. Os pacientes foram estratificados em HPT primário (107) e HPT secundário (115). Os laudos anatomopatológicos foram revistos, a incidência de CPT foi pesquisada e suas características nesses indivíduos foram estudadas. Esses dados foram comparados a dados encontrados em casos de necrópsia e em 89 casos de bócio compressivo/mergulhante. Empregou-se o teste exato de Fisher e o teste t não pareado. RESULTADOS: Os laudos foram passíveis de análise em 103 casos de HPT primário, com 10 pacientes com CPT (9,7 por cento) e em 111 portadores de HPT secundário, com três CPT associados (2,7 por cento). Houve diferença entre o HPT primário e HPT secundário (p=0,04). Essa diferença também foi significativa em relação aos 1 por cento de CPT achados em necrópsia na região (p=0,0001). Não houve diferença com relação à incidência de 11,2 por cento de CPT no grupo operado por compressão e também em relação às características dos tumores, apesar de haver 80 por cento de multicentricidade no CPT de doentes com HPT primário. CONCLUSÕES: A ocorrência de CPT em HPT primário é maior que em HPT secundário e que em achados de necropsia.

BACKGROUND: Association of papillary thyroid carcinoma (PTC) and hyperparathyroidism (HPT) has not been clearly defined. The incidence of PTC in different types of HPT and necropsy or patients submitted to thyroidectomy in the same region is analyzed to verify if this association is casual or not. METHODS: Data of 222 consecutive patients operated for HPT were reviewed and incidence of PTC was defined. Patients were analyzed as primary HPT (107) and secondary (115). The incidence of PTC was compared to that found in necropsy and to that observed in 89 patients with compressive multinodular goiter submitted to thyroidectomy. Statistical analysis included Fisher's exact test and Student's t test. RESULTS: Pathology reports were available in 103 cases of primary HPT, and in 10 patients PTC was detected (9.7 percent). In 111 secondary HPT patients, PTC was found in three (2.7 percent), with statistical significant difference between primary and secondary HPT (p=0.04). This difference was also significant of the 1 percent incidence of PTC found in necropsy in the same area (p=0.0001). No difference was observed in relation to the incidence of 11.2 percent of PTC found in patients operated for compressive goiter. Tumor characteristics were not statistically different, although multicentricity was detected in 80 percent of PTC of patients with primary HPT. CONCLUSION: The incidence of PTC was elevated in patients with primary HPT, in relation to necropsy or secondary HPT cases.

IL-1beta, TNF-alpha, TGF-beta, and bFGF expression in bone biopsies before and after parathyroidectomy.

BACKGROUND: There is growing evidence pointing to an involvement of cytokines and growth factors in renal osteodystrophy. In this study, the expression of interleukin-l beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and basic fibroblast growth factor (bFGF) in bone biopsies taken from uremic patients before and 1 year after parathyroidectomy (PTX) was evaluated. Biochemical features and histomorphometric outcome were also studied. METHODS: Iliac bone biopsies were taken before and 1 year after PTX in nine uremic patients with severe hyperparathyroidism (HPT). Immunohistochemical techniques were used to identify the expression of IL-1 beta, TNF-alpha, TGF-beta, and bFGF in these bone samples. RESULTS: At the time of the second bone biopsy, the mean serum total alkaline phosphatase activity was normal, whereas mean serum intact parathyroid hormone (iPTH) level was slightly above the upper limit of normal values. Histomorphometric analysis showed a decrease in resorption parameters and static bone formation parameters after PTX. Dynamically, mineral apposition rate (MAR) and mineralization surface (MS/BS) decreased significantly. There was a marked local expression of IL-1beta, TNF-alpha, TGF-beta, and bFGF in bone biopsies before PTX, particularly in fibrous tissue and resorption areas. One year after PTX, IL-1beta decreased from 23.6 +/- 7.5% to 9.9 +/- 3.1%, TNF-alpha from 4.5 +/- 1.5% to 0.7 +/- 0.8%, TGF-beta from 49.6 +/- 9.8% to 15.2 +/- 4.6%, and bFGF from 50.9 +/- 12.7% to 12.9 +/- 7.9% (P < 0.001). A significant correlation was documented between cytokines and growth factors expression in bone with iPTH levels before and after PTX (P < 0.05). CONCLUSIONS: Based on these results, we suggest that IL-1beta, TNF-alpha, TGF-beta, and bFGF are involved in bone remodeling regulation, acting as local effectors, possibly under the control of PTH.