Use of Teriparatide in Hyperphosphatemic Familial Tumor Calcinosis: Evaluating the Interaction Between FGF23 and PTH on the Phosphaturic Effect.

Hyperphosphatemic familial tumor calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and calcium and phosphorus crystal deposition. It occurs due to the loss of function of FGF23. Herein, we report a case of a 50-year-old woman diagnosed with HFTC (homozygous variant in the GALNT3 gene, c.803_804 C insertion) with a history of ectopic calcifications in the past 30 years. Laboratory tests on admission were as follows: phosphate (P) 7.1 mg/dL (Normal range (NR) 2.5-4.5 mg/dL), FGF23 c-terminal 2050 RU/mL (NR < 150 RU/mL), and intact FGF23 (iFGF23) 18.93 pg/mL (NR 12.0-69.0 pg/mL). Treatment with acetazolamide, sevelamer, and a phosphorus-restricted diet was started, but phosphatemia remained high and calcifications continued to progress. In an attempt to further decrease P, a 36-day cycle of teriparatide (TPTD) 20 mcg twice daily was added, decreasing P from 6.2 to 5.2 mg/dL and increasing the 1.25(OH)2 vitamin D by 34.2%. As urinalysis was not feasible at the end of the 36-day cycle, a second cycle was performed for another 28 days, producing a similar decrease in P (from 6.4 to 5.5 mg/mL) and an evident decrease in the rate of tubular reabsorption of P (from 97.2 to 85.3%), however, accompanied by a worrying increase in calciuria. The use of TPTD 20 mcg twice daily in a patient with genetic resistance to FGF23 (HFTC) was associated with consistent increase in phosphaturia and reduction in phosphatemia, in addition to an increase in calcitriol. The resulting hypercalciuria precludes the therapeutic use of TPTD in HFTC and suggests an important role of FGF23, not only in phosphate homeostasis but also in avoiding any excess of calcitriol.

Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHPT): A Useful Tool?

Primary Hyperparathyroidism (PHPT) often leads to bone loss, even in its asymptomatic presentations. Trabecular Bone Score (TBS) is a method to assess the trabecular bone structure of the spine. This study aimed to evaluate TBS measurements combined with Dual X-ray Absorptiometry (DXA) values in the search for more accurate bone fragility risk assessment among PHPT patients. From 2017 to 2019, patients diagnosed with PHPT (n = 64), before surgery, were invited to participate in this study. Bone mineral density (BMD) by DXA at the lumbar spine, total hip, femoral neck, distal third radius, and TBS were determined in patients and controls (n = 63). The vertebral fracture was defined using the Genant method in vertebral images by DXA and vertebral fracture assessment (VFA). Patients and controls did not differ in age, sex, menopausal status, or body mass index (BMI). The PHPT patients presented significantly lower BMD values than the controls in all sites evaluated. The TBS measurements were also statistically lower in PHPT patients than controls (mean TBS PHPT = 1.233 vs TBS controls = 1.280, p = 0.044). Osteoporosis was observed in 50% of PHPT patients and 26.6% of controls (p = 0.02). However, lumbar spine T-Score < -2.5 was observed only in 21.8% of PHPT patients. Vertebral fractures were detected in nine individuals (14%) from the PHPT group and four (6.3%) in the controls (p = 0.24). The TBS area under the curve (AUC) was higher than DXA AUC in all sites, for vertebral fracture assessment. The TBS AUC was significant in the PHPT group (0.75, 95% CI 0.62 - 0.88, p = 0.02) and not significant in the DXA analysis. The ROC curve showed that TBS values < 1.187 are associated with a significantly higher risk of vertebral fracture among PHPT patients (p = 0.02). The TBS used as a complement to DXA measurements is a useful tool which may better assess fragility risk among PHPT patients.

Factors affecting vitamin D status in different populations in the city of São Paulo, Brazil: the São PAulo vitamin D Evaluation Study (SPADES).

BACKGROUND: Hypovitaminosis D is a common condition among elderly individuals in temperate-climate countries, with a clear seasonal variation on 25 hydroxyvitamin D [(25(OH)D] levels, increasing after summer and decreasing after winter, but there are few data from sunny countries such as Brazil. We aimed to evaluate 25-hydroxyvitamin D concentrations and its determining factors, in individuals in the city of São Paulo belonging to different age groups and presenting different sun exposure habits. METHODS: 591 people were included as follows: 177 were living in institutions (NURSING HOMES, NH, 76.2 ± 9.0 years), 243 were individuals from the community (COMMUNITY DWELLINGS, CD, 79.6 ± 5.3 years), 99 were enrolled in physical activity program designed for the elderly (PHYSICAL ACTIVITY, PA, 67.6 ± 5.4 years) and 72 were young (YOUNG, 23.9 ± 2.8 years). Ionized calcium, PTH, 25(OH)D, creatinine and albumin were evaluated. ANOVA, Mann-Whitney and Kruskal Wallis tests, Pearson Linear Correlation and Multiple Regression were used in the statistical analysis. RESULTS: 25(OH)D mean values during winter for the different groups were 36.1 ± 21.2 nmol/L (NH), 44.1 ± 24.0 nmol/L (CD), 78.9 ± 30.9 nmol/L (PA) and 69.6 ± 26.2 nmol/L (YOUNG) (p < 0.001) while during summer they were 42.1 ± 25.9 nmol/L, 59.1 ± 29.6 nmol/L, 91.6 ± 31.7 nmol/L and 103.6 ± 29.3 nmol/L, respectively (p < 0.001). The equation which predicts PTH values based on 25(OH)D concentration is PTH = 10 + 104.24.e-(vitD-12.5)/62.36 and the 25(OH)D value above which correlation with PTH is lost is 75.0 nmol/L. In a multiple regression analysis having 25(OH)D concentration as the depending variable, the determining factors were PTH, ionized calcium and month of the year (p < 0.05). CONCLUSIONS: Much lower 25(OH)D values were found for the older individuals when compared to younger individuals. This finding is possibly due to age and habit-related differences in sunlight exposure. The existence of seasonal effects on 25(OH)D concentration throughout the year was evident for all the groups studied, except for the nursing home group. According to our data, PTH values tend to plateau above 75 nmol/L.

Levels of bioavailable, and free forms of 25(OH)D after supplementation with vitamin D3 in primary hyperparathyroidism.

The 25 hydroxyvitamin D [25(OH)D] is the major metabolite for ascertaining vitamin D status, which circulates bound to a specific carrier (vitamin D-binding protein - VDBP). A portion that circulates unbound vary according to the VDBP genotype. This study evaluates the behavior of different forms of 25(OH)D, before and after supplementation with 14,000 IU of vitamin D3, weekly for 12 weeks, in individuals with primary hyperparathyroidism and controls. Fifty-six patients with active primary hyperparathyroidism (PHPT) and 64 paired controls (CTRL), not taking vitamin D3 for the last three months, were enrolled. The genetic isotypes of VDBP were determined to calculate bioavailable and free 25(OH)D. A p < 0.05 was considered significant. There were no statistical differences in free, bioavailable, and total 25(OH)D levels between PHPT and CTRL groups at baseline. The distribution of VDBP haplotypes 1s/1s, 1f/1f, 1s/1f, 2/2, 1s/2, and 1f/2 was similar between groups. After supplementation, all three forms of 25(OH)D proportionally increased within each group, although the percentage increment was lower in the PHPT group (p < 0.05). Total 25(OH)D is better correlated with PTH in the PHPT group than bioavailable and free 25(OH)D (r = -0.41; p < 0.05). The concentrations of total, free, and bioavailable 25(OH)D were similar in both PHPT and CTRL groups, and all forms increased proportionally after supplementation, although this increment percentage was higher in the CTRL group, with a subsequent reduction of PTH and AP. Total 25(OH)D correlated better with PTH than other forms, suggesting no advantages in measuring free or bioavailable 25(OH)D in these situations.

Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

OBJECTIVE: To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. SUBJECTS AND METHODS: 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. RESULTS: One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. CONCLUSION: PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

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.

Autotransplant tissue selection criteria with or without stereomicroscopy in parathyroidectomy for treatment of renal hyperparathyroidism.

INTRODUCTION: Several methods have been proposed to improve operative success in renal hyperparathyroidism. OBJECTIVE: To evaluate stereomicroscopy in parathyroid tissue selection for total parathyroidectomy with autotransplantation in secondary (SHPT)/tertiary (THPT) hyperparathyroidism. METHODS: 118 renal patients underwent surgery from April of 2000 to October 2009. They were divided into two groups: G1, 66 patients operated from April of 2000 to May of 2005, with tissue selection based on macroscopic observation; G2, 52 patients operated from March of 2008 to October 2009 with stereomicroscopy for tissue selection searching for the presence of adipose cells. All surgeries were performed by the same surgeon. Patients presented SHPT (dialysis treatment) or THPT (renal-grafted). Follow-up was 12-36 months. Intra-operative parathyroid hormone (PTH) was measured in 100/118 (84.7%) patients. RESULTS: Data are presented as means. G1 included 66 patients (38 SHPT, 24 females/14 males; 40.0 years of age; 28 THPT, 14 females/14 males; 44 years of age). G2 included 52 patients (29 SHPT, 11 females/18 males; 50.7 years of age; 23 THPT, 13 females/10 males, 44.4 years of age). SHPT patients from G2 presented preoperative serum calcium higher than those of SHPT patients in G1 (p<0.05), suggesting a more severe disease. Definitive hypoparathyroidism was found in seven of 118 patients (5.9%). Graft-dependent recurrence occurred in four patients, two in each group. All occurred in dialysis patients. CONCLUSION: Stereomicroscopy in SHPT/THPT surgical treatment may be a useful tool to standardize parathyroid tissue selection.

Prediction of bone mass changes after successful parathyroidectomy using biochemical markers of bone metabolism in primary hyperparathyroidism: is it clinically useful?

ABSTRACT Objective To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. Subjects and methods 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. Results One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. Conclusion PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

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.

Parathyroid carcinoma and hungry bone syndrome.

We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.

Parathyroid hormone: an early predictor of symptomatic hypocalcemia after total thyroidectomy.

OBJECTIVE: The purpose of this study was to evaluate if the measurement of peri-operative parathyroid hormone (PTH) is able to identify patients with increased risk of developing symptoms of hypocalcemia. SUBJECTS AND METHODS: Forty patients who underwent total thyroidectomy were studied prospectively. Ionized serum calcium and PTH were measured after induction of anesthesia, one hour (PTH1) and one day after surgery (PTH24). Patients were evaluated for symptoms of hypocalcemia and treated with calcium and vitamin D supplementation as necessary. RESULTS: Symptomatic hypocalcemia developed in 16 patients. Symptomatic patients had significant lower PTH1 and greater drops in PTH levels. The selection of 12.1 ng/L as PTH1 level cutoff level divided patients with and without symptoms with 93.7% sensitivity and 91.6% specificity. The selection of 73.5% as the cutoff value for PTH decrease resulted in 91.6% sensitivity and 87.5% specificity. CONCLUSION: PTH1 levels and the drop in PTH levels are reliable predictors of developing symptomatic hypocalcemia after total thyroidectomy.

The effects of discontinuing long term alendronate therapy in a clinical practice setting.

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7%) in G1 and one (5.2%) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

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.

Autotransplant tissue selection criteria with or without stereomicroscopy in parathyroidectomy for treatment of renal hyperparathyroidism / Influência do critério de seleção de tecido paratiroideano com ou sem estereomicroscopia para autoimplante no resultado do tratamento cirúrgico do hiperparatiroidismo associado a doença renal crônica

INTRODUCTION: Several methods have been proposed to improve operative success in renal hyperparathyroidism. OBJECTIVE: To evaluate stereomicroscopy in parathyroid tissue selection for total parathyroidectomy with autotransplantation in secondary (SHPT)/tertiary (THPT) hyperparathyroidism. METHODS: 118 renal patients underwent surgery from April of 2000 to October 2009. They were divided into two groups: G1, 66 patients operated from April of 2000 to May of 2005, with tissue selection based on macroscopic observation; G2, 52 patients operated from March of 2008 to October 2009 with stereomicroscopy for tissue selection searching for the presence of adipose cells. All surgeries were performed by the same surgeon. Patients presented SHPT (dialysis treatment) or THPT (renal-grafted). Follow-up was 12-36 months. Intra-operative parathyroid hormone (PTH) was measured in 100/118 (84.7%) patients. RESULTS: Data are presented as means. G1 included 66 patients (38 SHPT, 24 females/14 males; 40.0 years of age; 28 THPT, 14 females/14 males; 44 years of age). G2 included 52 patients (29 SHPT, 11 females/18 males; 50.7 years of age; 23 THPT, 13 females/10 males, 44.4 years of age). SHPT patients from G2 presented preoperative serum calcium higher than those of SHPT patients in G1 (p < 0.05), suggesting a more severe disease. Definitive hypoparathyroidism was found in seven of 118 patients (5.9%). Graft-dependent recurrence occurred in four patients, two in each group. All occurred in dialysis patients. CONCLUSION: Stereomicroscopy in SHPT/THPT surgical treatment may be a useful tool to standardize parathyroid tissue selection. .

INTRODUÇÃO: Diversos métodos têm sido propostos com intuito de melhorar índices de sucesso cirúrgico no tratamento do hiperparatiroidismo associado à doença renal crônica (DRC). OBJETIVOS: Avaliar uso do estereomicroscópio na seleção de tecido paratiroideano na paratiroidectomia total com autoimplante em pacientes com DRC. MÉTODOS: 118 pacientes DRC operados entre 04/2000-10/2009 foram divididos em: G1-66 pacientes operados entre 04/2000-05/2005 cuja seleção de tecido foi realizada por método convencional (macroscopia); G2-52 pacientes operados entre 03/2008-10/2009, cuja seleção de tecido foi realizada com uso da estereomicroscopia: Leica-Stereomicroscope (amplificação: 10×-80×). Pacientes foram ainda categorizados em hiperparatiroidismo secundário (HPS) ou terciário (HPT) (HPS-diálise/HPT-transplantados renais). Seguimento pós-operatório: 12-36 meses. PTH intraoperatório medido 100/118 pacientes (84.7%). Todos pacientes foram operados pelo mesmo cirurgião. RESULTADOS: Dados em média. G1, 66 pacientes (38 HPS, 24f/14m; 40 anos; 28 HPT, 14f/14m; 44 anos). G2, 52 pacientes (29 HPS, 11f/18m; 50,7 anos; 23 HPT, 13f/10m; 44,4 anos). Pacientes dialíticos do G2 apresentaram cálcio pré-operatório maior que G1 (p < 0,05), sugerindo doença mais severa. Hipoparatiroidismo definitivo: 7/118 (5,9%) pacientes: G1, 4/66 (6%); G2, 3/52 (5,7%). Recorrência do hiperparatiroidismo no autoimplante: 4 pacientes, 2 em cada grupo. Todas foram em pacientes em diálise. CONCLUSÃO: Estereomicroscopia no tratamento do hiperparatiroidismo associado à DRC é útil na padronização da técnica de seleção de tecido para o autoimplante. .

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.

Parathyroid carcinoma and hungry bone syndrome / Carcinoma de paratiroide e fome óssea

We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.

O presente artigo descreve o relato de dois pacientes com carcinoma de paratiroide que apresentavam valores intensamente elevados de cálcio sérico e de PTH, associado a doença óssea e presença de nódulo cervical palpável ao diagnóstico. Ambos foram submetidos à paratiroidectomia, sendo que um evoluiu com metástases pulmonares. Hipocalcemia importante foi observada após a paratiroidectomia em um paciente e somente após remoção cirúrgica das metástases pulmonares em outro. Ambos necessitaram de reposição endovenosa de cálcio, revelando, assim, o estado de fome óssea (FO). A presença da FO usualmente reflete rápida mineralização óssea após correção do hiperparatiroidismo; assim, quanto mais severa a doença óssea previa à cirurgia, maior será a FO observada no pós-operatório desses pacientes. Embora inicialmente considerada um evento indesejável, a FO representa a bem-sucedida remoção cirúrgica do tecido paratiroideano hipersecretor. Fome óssea deve ser esperada no pós-operatório do tratamento cirúrgico bem-sucedido do carcinoma de paratiroide.

Parathyroid hormone: an early predictor of symptomatic hypocalcemia after total thyroidectomy / Hormônio da paratireoide: um preditor precoce da hipocalcemia sintomática após a tireoidectomia total

OBJECTIVE: The purpose of this study was to evaluate if the measurement of peri-operative parathyroid hormone (PTH) is able to identify patients with increased risk of developing symptoms of hypocalcemia. SUBJECTS AND METHODS: Forty patients who underwent total thyroidectomy were studied prospectively. Ionized serum calcium and PTH were measured after induction of anesthesia, one hour (PTH1) and one day after surgery (PTH24). Patients were evaluated for symptoms of hypocalcemia and treated with calcium and vitamin D supplementation as necessary. RESULTS: Symptomatic hypocalcemia developed in 16 patients. Symptomatic patients had significant lower PTH1 and greater drops in PTH levels. The selection of 12.1 ng/L as PTH1 level cutoff level divided patients with and without symptoms with 93.7% sensitivity and 91.6% specificity. The selection of 73.5% as the cutoff value for PTH decrease resulted in 91.6% sensitivity and 87.5% specificity. CONCLUSION: PTH1 levels and the drop in PTH levels are reliable predictors of developing symptomatic hypocalcemia after total thyroidectomy.

OBJETIVO: O objetivo deste estudo é avaliar se a medida perioperatória do hormônio da paratireoide (PTH) pode identificar os pacientes com maior risco de desenvolver sintomas de hipocalcemia. SUJEITOS E MÉTODOS: Foram estudados quarenta pacientes submetidos à tireodiectomia total. A medida do cálcio sérico e do PTH foi feita após a indução anestésica, uma hora (PTH1) e um dia após a cirurgia. Os pacientes foram avaliados quanto à presença de sintomas de hipocalcemia e tratados com suplementação de cálcio e vitamina D quando necessário. RESULTADOS: Dezesseis pacientes apresentaram sintomas de hipocalcemia. Os pacientes sintomáticos apresentaram PTH1 significantemente menor e queda no PTH significativamente maior. Usando o valor de 12,1 ng/L como corte, conseguimos distinguir pacientes com e sem sintomas de hipocalcemia com sensibilidade de 93,7% e especificidade de 91,6%. Utilizando como corte a queda de 73,5% no valor do PTH, temos sensibilidade de 91,6% e especificidade de 87,5%. CONCLUSÃO: O PTH1 e a queda no PTH são bons preditores de hipocalcemia no pós-operatório de tireoidectomia total.

The effects of discontinuing long term alendronate therapy in a clinical practice setting / Efeitos da retirada do uso prolongado de alendronato na prática clínica

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7 percent) in G1 and one (5.2 percent) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

OBJETIVO: Avaliar a evolução dos marcadores de metabolismo ósseo (MMO) e da densidade mineral óssea (DMO) após cinco anos de uso de alendronato em mulheres osteoporóticas na pós-menopausa. SUJEITOS E MÉTODOS: 40 pacientes (pct) osteoporóticas, na pós-menopausa, em uso de alendronato (10 mg/dia) por pelo menos 5 anos (Grupo 1 − G1) tiveram o uso do bisfosfonato suspenso. O grupo 2 (G2): 25 mulheres na pós-menopausa, em uso de alendronato (10 mg/dia) há pelo menos 1 ano. Grupo 3 (G3): 23 pct osteoporóticas, controles ainda sem tratamento. G1 e G2 submeteram-se à avaliação da DMO por DXA (basal e após 12 meses de seguimento). Todas as pct colheram amostras basais de CTX e P1NP, e G1 e G2 submeteram-se a coletas trimestrais de CTX e P1NP durante 1 ano. Resultados foram analisados por ANOVA on ranks e Mann-Whitney. RESULTADOS: Níveis médios de DMO não variaram em G1 ou G2 durante o estudo; no entanto, 16 pct (45,7 por cento) no G1 e 1 pct (5,2 por cento) no G2 apresentaram redução clinicamente significativa de DMO (P < 0,001). Níveis basais de CTX e P1NP não diferiram entre G1 e G2, com ambos inferiores aos níveis de G3. Em G1, observou-se elevação significativa de CTX e P1NP após 3 meses. Os níveis de CTX e P1NP em G2 permaneceram estáveis durante todo o seguimento. CONCLUSÃO: Não parece haver supressão excessiva do metabolismo ósseo na prática clínica. A suspensão temporária do alendronato após seu uso prolongado pode não ser segura.