Differential diagnosis between secondary hyperparathyroidism and aluminum intoxication in uremic patients: Usefulness of99mTc-pyrophosphate bone scintigraphy

Forty-one patients in chronic end-stage renal failure and 4 patients with a functioning kidney transplant presented with spontaneous hypercalcemia or intolerance to vitamin D₃ sterols and/or oral calcium supplements. Bone iliac crest biopsy with aluminum staining and Tc-pyrophosphate bone scintigraphy with determination of Fogelman score were performed in all cases. Two patients had aluminum-induced osteomalacia (AL O). Thirty-eight biopsies showed renal osteodystrophy (secondary hyperparathyroidism or various combinations of osteitis fibrosa and osteomalacia): 19 with positive staining for aluminum (RO + AL) and 19 without aluminum deposits (RO). The series also comprised 2 cases of pure osteomalacia (OM), 2 cases of osteoporosis (OP), and 1 case of osteoporosis with aluminum accumulation (OP + AL). Mean Fogelman score in RO patients (9.1±0.3) was significantly higher than in all other categories (5.9±0.5 for RO + AL, and scores ranging from 0 to 8 in the last 7 patients,p<0.01). Patients with massive aluminum accumulation in bone (>75% of the total trabecular surface) showed no or very low uptake of the isotope by the skeleton. Fogelman scores of 9 or higher were always associated with histological secondary hyperparathyroidism.^99mTc-pyrophosphate bone scintigraphy is helpful to distinguish aluminum intoxication from secondary hyperparathyroidism in uremic patients.

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Resumen Cuarenta y un pacientes en falla renal crónica terminal y 4 pacientes con trasplantes renales funcionantes se presentaron con hipercalcemia espontánea o intolerancia a los esteroles de la vitamina D₃ y/o los suplementos de calcio. Se realizaron biopsias óseas de cresta ilíaca con tinción para aluminio y escintigrafía ósea con Tc-pirofosfato y determinación del puntaje de Fogelman en la totalidad de los casos. Dos pacientes presentaban osteomalacia inducida por aluminio. Treinta y ocho biopsias mostraron osteodistrofia renal (hiperparatiroidismo secundario o diversas combinaciones de oteitis fibrosa y osteomalacia): 19 con tinción para aluminio positiva y 19 sin depósitos demostrables de aluminión. Esta série también comprende 2 casos de osteomalacia pura, 2 casos de osteoporosis, y un caso de osteoporosis con acumulación de aluminio. El promedio del puntaje de Fogelman en los pacientes sin depósitos de aluminio (9.1±0.3) apareció significativamente mayor que en todas las otras categorías (5.9±0.5 para los del grupo con depósitos de aluminio y puntajes entre 0 y 8 en los últimos 7 pacientes,p< 0.01). Pacientes con acumulación masiva de aluminio en huesos (>75% de la superficie trabecular total) demostraron captación nula o muy baja del isótopo por el esqueleto. Todos los pacientes con puntajes de Fogelman de 9 o más presentaron hiperparatiroidismo secundario histológico. La escintigrafía ósea con^99mTc-pirofosfato es de utilidad en la diferenciación de la intoxicación por aluminio del hiperparatioridismo secundario en pacientes urémicos.

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Résumé Quarante et un patients avec une insuffisance rénale terminale et 4 patients ayant eu une transplantation rénale présentaient une hypercalcémie spontanée ou une intolérance aux composés stérols, de vitamine D₃ et/ou une supplémentation orale en calcium. Une biopsie de la crête iliaque avec coloration à l'aluminium et une scintigraphie osseuse au pyrophosphate de Technétium avec détermination du score de Fogelman ont été obtenus dans tous les cas. Deux patients avec une ostéomalacie induite par l'aluminium. Trente-huit biopsies montraient des signes d'ostéodystrophie rénale (OR) (hyperparathyroïdie secondaire ou combinaisons diverses ostéite fibreuse et d'ostéomalacie). Dix-neuf patients étaient aluminium positifs (OR + AL) alors que 19 autres n'avaient pas de dépôts d'aluminium (OR); il y avait également 2 cas d'ostéomalacie pure (OM), 2 cas d'ostéoporose (OP), et un cas d'ostéoporose avec accumulation d'aluminium (OP + AL). Les scores moyens de Fogelman étaient statistiquement plus élévés chez les patients OR (9.1±0.3, moyen±ETM) que dans toutes les autres catégories (5.9±0.5 pour OR + AL; scores entre 0 et 8 chez les 7 derniers patients;p<0.01). Les patients ayant une accumulation massive d'aluminium dans l'os (>75% de la surface trabéculaire totale) ne fixaient aucun isotope ou très peu au niveau du squelette. Les scores de Fogelman à 9 ou plus étaient toujours associés à un hyperparathyroïdisme secondaire histologique. La scintigraphie osseuse au Technétium 99m permet de distinguer l'intoxication à l'aluminium de l'hyperparathyroïdie.

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Presented at the International Association of Endocrine Surgeons in Sydney, Australia, September, 1987.

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Supported by the Fondation David et Alice van Buuren and grant no. 3.4517.84 of the Fonds de la Recherche Scientifique Médicale.     

Postoperative variations of bone turnover markers in uremic patients with secondary hyperparathyroidism after parathyroidectomy

Objective To study shortdated postoperative variation characteristics of bone turnover markers (BTMs) in uremic patients with secondary hyperparathyroidism (SHPT) underwent parathyroidectomy (PTX). Methods A total of 19 uremic patients with SHPT underwent successful PTX, hospitalized in the Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University from January 2017 to April 2017, were enrolled in the study. The operative model for all enrolled patients was total parathyroidectomy with forearm autotransplantation. The baseline epidemiological and clinical data before PTX and the levels of serum intact parathyroid hormone (iPTH) and serum BTMs after PTX (in the 1st, 3rd and 7th postoperative day) were collected. The correlations between serum iPTH and serum BTMs before PTX and the trend analysis of serum BTMs after PTX were studied. Results The levels of serum iPTH, serum alkaline phosphatase (ALP), serum type Ⅰcollagen cross-linked C-telopeptides (CTX) and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) before PTX were increased, in turn, (1512.4±612.0) ng/L, 267.4(153.1, 424.2) U/L, (5.78±1.15) μg/L and (8.79±4.61) IU/L. Positive correlations between ALP and iPTH (r=0.577, P=0.010), TRACP-5b and iPTH (r=0.640, P=0.003), and ALP and TRACP-5b (r=0.698, P=0.001) were found. The serum levels of ALP increased, while the serum levels of CTX and TRACP-5b decreased within 7 days after PTX. Conclusions Renal osteodystrophy (ROD) with high bone turnover rate is common in uremic patients with severe SHPT. The activities of osteoblast and osteoclast are up-regulated in coupling with positive correlations to serum levels of iPTH. Increased activities of osteoblast and decreased activities of osteoclast were found shortdated postoperatively.     

Use of calcimimetics in uremic patients with secondary hyperparathyroidism: review

Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The activation of this receptor by small changes in extracellular ionized calcium (ec(Ca2+)) regulates PTH, calcitonin secretion, urinary calcium excretion, and ultimately, bone turnover. The cloning of this CaR and the discovery of mutations making the receptor less or more sensitive to calcium allowed a better understanding of several hereditary disorders characterized either by hyperparathyroidism or hypoparathyroidism. This CaR became an ideal target for the development of compounds, the calcimimetics, able to amplify the sensitivity of the CaR to ec(Ca2+) suppressing PTH levels with a resultant fall in blood Ca2+. The first clinical studies with first-generation calcimimetic agents have demonstrated their efficacy lowering plasma intact PTH concentration in uremic patients with secondary hyperparathyroidism. However, the low bioavailability of these first calcimimetics predicts a difficult clinical utilization. The second-generation calcimimetic AMG-073, with a better pharmacokinetic profile, appears to be effective and safe for the treatment of secondary hyperparathyroidism, producing suppression of PTH levels with a simultaneous reduction in serum phosphorus levels and the calcium X phosphorus product. The advantage of controlling PTH secretion without the complications related to hypercalcemia, hyperphosphatemia, and increased calcium X phosphorus product is very promising.     

肾性甲状旁腺功能亢进外科治疗术前高频彩超和99m Tc-MIBI双时相显像的应用

目的肾性甲状旁腺机能亢进是继发性骨质疏松中的一种,随着透析技术的普及而增多的严重影响患者生活质量的疾病,外科手术治疗可以迅速缓解病情。探讨联合应用高频彩超和99mTc-MIBI双时相显像技术,在甲状旁腺切除术(Parathyroidectomy,PTX)术前定位诊断中的价值。方法回顾性分析38例进行了PTX患者的高频彩超和99mTc-MIBI双时相显像结果,与术后病理结果进行比较,评价二者在术前诊断和定位中的敏感性和特异性。结果高频彩超的敏感性和特异性分别为56.9%和78.6%;而MIBI为53.9%和80.0%。统计学分析显示二者之间无显著性差异(P0.05)。在所有38例患者中,外科共切除的甲状旁腺腺体127枚,其中高频彩超检测到的占65枚(51.2%);MIBI检测到68枚的占(53.5%)。联合应用高频彩超和MIBI检测甲状旁腺的数目为82枚(64.6%),较单用其中之一显现率更高(P0.05)。高频彩超和MIBI发现的下极甲状旁腺的数目较上级显现率更高(P0.05),但二者之间无显著性差异。结论联合应用高频彩超和99mTc-MIBI双时相显像技术可提高继发性甲旁亢患者术前定位诊断的敏感性和特异性,对指导外科手术有较高价值。     

Race is a major determinant of secondary hyperparathyroidism in uremic patients

In the general population, blacks have higher parathyroid gland mass and circulating parathyroid hormone (PTH) levels than whites. This may predispose black patients to more severe parathyroid disease when renal failure develops. Therefore, racial differences in the severity of uremic hyperparathyroidism were examined in a population of patients with end-stage renal disease (ESRD). Among ESRD patients receiving hemodialysis or peritoneal dialysis, two or more values of intact PTH (immunoradiometric assay, pg/ml) obtained at least 90 d apart were available in 1270 prevalent cases (61.1% blacks, 51% males, and 31.1% diabetic), including 466 incident cases with onset of ESRD after 1993. Maximum PTH levels were analyzed as a function of race, gender, age, diabetic status, and levels of serum calcium, phosphorus, alkaline phosphatase, and aluminum. Using a stepwise multiple regression model, the determinants of maximum PTH in the order of their importance were black race, serum phosphorus, absence of diabetes, younger age, serum calcium, and female gender. The maximum PTH levels averaged 641.7 in blacks and 346.0 in whites after adjusting for age, gender, diabetic status, serum calcium, and phosphorus (P < 0.0001). In blacks compared with whites, the odds ratio (95% confidence interval) for adynamic bone disease (maximum PTH <150 pg/ml) was 0.26 (0.17 to 0.41), whereas the odds ratio for hyperparathyroid bone disease (mean PTH >500 pg/ml) was 4.4 (2.10 to 9.25). Race is a major independent determinant of uremic secondary hyperparathyroidism. Among ESRD patients, blacks may be at an increased risk for hyperparathyroid bone disease and whites for adynamic bone disease.     

尿毒症继发甲状旁腺功能亢进的特点及外科治疗

继发性甲状旁腺功能亢进（SHPT）是慢性肾功能衰竭的重要并发症,SHPT患者甲状旁腺呈非对称性增大并伴有结节形成,甲状旁腺组织中Ca^2＋敏感受体基因、维生素D受体基因有异常表达.SHPT可致患者出现骨痛、骨骼畸形、甲状旁腺激素和碱性磷酸酶水平增高、骨纤维囊性变、弥漫性脱钙等表现,严重者可出现胸骨畸形、压缩性骨折、心脏瓣膜钙化等。对于存在甲状旁腺激素显著增高、甲状旁腺增大、纤维性骨炎或高度骨代谢运转以及内科治疗无效等情况者杠般建议行外科治疗。甲状旁腺全切前臂自体移植对晚期肾性SHPT是非常有效的治疗方法。手术的关键是要切除所有的甲状旁腺,使用质地柔软的弥漫性增生的组织进行移植。切除的甲状旁腺数一般为2-4枚,若有多余腺体,应在初次手术时切除。术后应进行钙替代治疗。甲状旁腺切除前臂自体移植可显著改善SHPT患者的临床症状和生化参数。持续性和复发性HPT的发生率一般为0-10％。持续性HPT的主要原因为纵隔甲状旁腺,复发的原因常为前臂自体移植物增生、多余腺体、剩余增生腺体、周围组织中旁腺组织的种植、旁腺癌的转移等。为防止术后发生持续性或复发性HPT．在初次手术时要切除所有的腺体以及胸腺舌,手术后应定期随访。根据患者血甲状旁腺激素水平、核素及影像学检查可诊断移植物依赖性复发。     

Apoptosis in parathyroid hyperplasia of patients with primary or secondary uremic hyperparathyroidism

BACKGROUND: Chronic oversecretion of parathyroid hormone (PTH) is associated with parathyroid hyperplasia, reflecting a disturbed balance between cell proliferation and apoptosis. This study addressed the unsolved issue of apoptosis in hyperparathyroidism. METHODS: Parathyroid glands from 19 patients with primary (1 degrees ) and 11 patients with secondary (2 degrees ) uremic hyperparathyroidism, as well as 13 normal parathyroid glands, were examined. Apoptosis was evaluated by terminal deoxynucleotidyl transferase (Tdt)-mediated dUTP nick end-labeling assay (TUNEL). Because the apoptotic process is regulated by several oncoproteins, the expression of Bcl-2 and Bax was analyzed by immunohistochemistry. RESULTS: The numbers of apoptotic cells in 1 degrees parathyroid adenoma (0.99 +/- 0.03 per 1000 cells, mean +/- SE, P < 0.009) and 2 degrees parathyroid hyperplasia (1.20 +/- 0.54 per 1000 cells, P < 0.005) were significantly higher than in normal parathyroid tissue (0.13 +/- 0. 06 per 1000 cells). Light microscopy examination of hyperplastic parathyroid tissue from a uremic patient showed the presence of nuclei with dense chromatin characteristic of apoptosis. Bcl-2 staining was strong in normal tissues but weak or negative in several sections of 1 degrees and 2 degrees hyperparathyroid tissues, mostly in nodular areas. Bax staining was homogeneous in normal tissue but patchy in several hyperplastic tissues. CONCLUSION: These results suggest that hyperparathyroidism is associated with a compensatory increase in apoptosis, possibly favored by a diminished Bcl-2/Bax ratio. This renders highly improbable the hypothesis that parathyroid hyperplasia is due to a decreased rate of apoptosis.     

Effect of parathyroidectomy on anemia and cardiac function in uremic patients with secondary hyperparathyroidism

Objective To explore the effect of total parathyroidectomy (PTX) with forearm autograft on the anemia and cardiac function in uremic patients with secondary hyperparathyroidism (SHPT). Methods The clinical data of 130 uremic patients who received PTX with forearm autograft in the First Affiliated Hospital of Zhejiang University from October 2010 to December 2015 were retrospectively analyzed. The changes of anemia and echocardiogram before and after operation were compared. According to the presence of left ventricular hypertrophy (LVH) before operation, the patients were divided into LVH group and non-LVH group. Echocardiographic indexes before and one year after operation of the two groups were compared. Results (1) Three months and one year after operation, hemoglobin and hematocrit increased while erythropoietin average usage decreased significantly (P＜0.01). (2) Compared with preoperative period, the dry weight was significantly increased one year after operation, and the cardiac function indexes including left ventricular end diastolic diameter (LVDd), interventricular septum end diastolic thickness (IVSd), left ventricular posterior wall end diastolic thickness (LVPWd), interventricular septum systolic thickness (IVSs), left ventricular systolic diameter (LVDs), left ventricular myocardial mass (LVM), and left ventricular myocardial mass index (LVMI) decreased significantly (P＜0.05). (3) In the non-LVH group, only IVSs decreased one year after operation (P＜0.05). In the LVH group, LVDs, LVDd, LVPWd, LVM, LVMI and IVSs were decreased significantly one year after operation than those in preoperative period (P＜0.05). Conclusions PTX with forearm autograft is an effective treatment for uremic patients with SHPT significantly improving anemia and left ventricular structure and function, especially for patients with ventricular hypertrophy in preoperative.     

Management of secondary hyperparathyroidism in uremic patients: the role of the new vitamin D analogs

Secondary hyperparathyroidism - a common comorbid condition in patients with chronic renal insufficiency - is considered a consequence of critical determinants such as hypocalcemia, phosphate retention and reduced levels of calcitriol production. In this complex mechanism, the skeletal apparatus and the nonskeletal targets such as vascular and heart valves are often involved, thus explaining the increased risk of cardiovascular morbidity and mortality of uremic patients. In this review we will focus on the major role played by Calcitriol deficiency as a trigger of secondary hyperparathyroidism and the crucial need for obiquitous vitamin D receptor activation in order to have an optimal PTH control and to obtain a modulation between inhibitors and inducers of soft tissue calcification. This review will also elucidate the possible role of paricalcitol - a new vitamin D analog - in conditioning morbidity and mortality of patients on renal replacement therapy (RRT).     

Impact of thyroid nodular disease on 99mTc-sestamibi scintigraphy in patients with primary hyperparathyroidism

Background  

Primary hyperparathyroidism with coexisting thyroid nodular disease (TND) has been considered a contraindication for selective parathyroidectomy because the low sensitivity of preoperative localization studies, especially 99^mTc-sestamibi scanning (MIBI) and ultrasound. The aim of this study was to assess the impact of concomitant TND in the preoperative image studies.     

Quantitative bone scintigraphy: usefulness in the survey of patients treated for bone metastasis of prostatic cancer

The purpose of this study was to develop a quantitative bone scintigraphy (QBS) method in order to evaluate the evolution of bone metastases in patients treated for disseminated prostatic cancer. Data obtained by whole body scintigraphy after injection of 99mTc-methylene diphosphonate enabled us to define three indexes, GR, R1 and R2. They respectively represent the amount of activity retained in the bones, in the metastatic sites and in pathological sites related to the global activity of the skeleton. Repeated QBSs have been performed on 59 patients with prostatic carcinoma treated for bone metastasis with hormonal therapy. Results of QBS are well correlated to clinical findings, particularly pain evolution. In addition, the calculated indexes of QBS made it possible to distinguish three groups of patients according to regression, stabilization or evolution of their lesions under hormonal therapy. QBS seems to be a sensitive and useful test for the evaluation of the therapeutic efficiency on bone metastases from prostatic carcinoma.     

Usefulness of preoperative Tc-mibi parathyroid scintigraphy in secondary hyperparathyroidism

Background and aims The usefulness of Tc-mibi parathyroid scintigraphy (Tc-PS) in planning parathyroidectomy for secondary hyperparathyroidism is not well known. The aim of this study was to review our experience with Tc-PS concerning: (1) the identification of hyperplastic glands, (2) detection of major ectopias and (3) prevention of recurrences. Patients and methods Thirty-three consecutive patients undergoing first-time subtotal parathyroidectomy for renal hyperparathyroidism had a dual-phase planar Tc-PS performed, and glands were classified as detected, weak, or not detected. The number and position of visualized glands were determined. Parathyroid weight, histology, and their relationship to Tc-PS were recorded after surgery. Results Of 132 potential glands, 48 (35%) were localized on the Tc-PS and 128 (96.9%) were identified intraoperatively. Tc-PS positive/weak glands were heavier than nonlocalized glands. Tc-PS contributed to successful surgery in four patients with a single difficult gland each (three retrieved from the neck and one—fifth gland—requiring mediastinotomy). There was one persistence (3%) because of a missed fourth undescended inferior parathyroid gland. Two recurrences 2 years after surgery were due to a fifth thoracic gland not shown in the preoperative Tc-PS. Conclusions Preoperative Tc-PS helped in the intraoperative identification of moderate or major ectopias in 4/33 patients but was not useful to prevent recurrences from highly ectopic glands not visualized before first-time surgery. Presented at the 2nd Biennial Congress of the ESES, May 2006, Krakow, Poland.     

Long-term intravenous calcitriol in secondary hyperparathyroidism: the role of technetium-99m-MIBI scintigraphy in predicting the response to treatment

BACKGROUND: Despite the effectiveness of intravenous calcitriol in suppressing parathyroid hormone secretion in patients with uremic hyperparathyroidism, 50% of the patients remain refractory to this treatment. There are conflicting reports regarding the factors that can predict the response to treatment. Technetium-99m-MIBI scintigraphy was found to be correlated with functional activity of the parathyroid gland. METHODS: We, retrospectively, evaluated 16 chronic hemodialysis patients, who were maintained on i.v. calcitriol for 36 months or longer, and who had MIBI scan either at the start of, or within the first 6 months of starting calcitriol. Nine patients had a positive uptake (+ve group), and 7 patients had a negative uptake (-ve group). All patients had an elevated iPTH (iPTH > 300 pg/ml) at the start of treatment. RESULTS: The percentage reduction of iPTH in the (-ve) and the (+ve) groups was 65% versus 45% at 12 months, and 65% versus 10% at 36 months respectively. In long-term follow-up of 36 months, all the patients in the (-ve) group responded to calcitriol; while 8 of the 9 patients (89%) in the (+ve) group didn't respond. The difference in response between the 2 groups was statistically significant (p<0.001). CONCLUSION: We conclude that MIBI scan is a reliable technique in predicting the response to treatment with i.v. calcitriol in patients with secondary hyperparathyroidism.     

Total parathyroidectomy with forearm autograft in the treatment of uremic patients with secondary hyperparathyroidism

Objective To analyze the efficacy and safety of total parathyroidectomy (PTX) with forearm autograft in uremic patients with secondary hyperparathyroidism (SHPT). Methods One hundred and eighteen cases undergoing PTX with forearm autograft in our hospital from 2001-2010 were included in this study. Their preoperative and postoperative serum intact parathyroid hormone (iPTH), biochemistry tests (total calcium,inorganic phosphate and alkaline phosphate) were collected and postoperative symptom relief, complications and recurrence were investigated. Results Of all the 118 cases, 32 underwent endoscopic surgery and 86 open surgery. The surgery was performed successfully in 110 cases (93.2%) and one case died in perioperative period. Thyroid carcinoma was diagnosed during surgery in 2 cases and radical operation was performed at the same time. Temporary injury of recurrent laryngeal nerve was found in nine cases (7.6%). Postoperative hypocalcemia was frequently seen in 108 cases (91.5%) and it was effectively controlled by postoperative calcium administration. After operation, bone pain and itching were alleviated, and weakness, anemia and malnutrition status were improved in all the cases who received successful surgery. The postoperative levels of serum iPTH (P＜0.01), calcium (P＜0.01), phosphorus (P＜0.01) and calcium×phosphorus (P＜0.01) were decreased significantly than those in preoperative period. A long-term follow-up of over 3 years was carried out in 21 cases. Six cases recurred, among them, 4 cases relieved after removal of autografted parethroid tissue, and another two cases received the second operation. The longest follow-up period lasted for 9 years in two cases without recurrence. Conclusions PTX with forearm autograft is safe and effective in the treatment for uremic patients with SHPT. No severe complication is found during the long-term follow-up period.     

Race is a major determinant of secondary hyperparathyroidism in uremic patients: comparative study of Blacks and Hispanics

BACKGROUND: Racial differences in bone and mineral metabolism are characterized by higher circulating intact parathyroid hormone levels (iPTH) in Black vs. White patients with end-stage renal disease (ESRD). The susceptibility of Hispanic patients to secondary hyperparathyroidism is not known. METHOD: This is a cross-sectional study that compares bone and mineral parameters of 48 Black and 61 Hispanic ESRD patients attending a single outpatient hemodialysis center. RESULT: The mean iPTH level was significantly higher in Blacks vs. Hispanics, despite similar levels of serum bone-specific alkaline phosphatase (BSAP), calcium, phosphorus and similar dosages of vitamin D analogs. After adjusting for independent variables including age, diabetic status and plasma levels of C-reactive protein, phosphorus and albumin significant predictors of iPTH were race (p < 0.01), gender (p < 0.05), serum calcium (p < 0.05), BSAP (p < 0.0001) and doses of vitamin D analogs (p < 0.001). Adjusted predictors of serum BSAP were PTH (p < 0.0001), gender (p = 0.01) and serum albumin (p < 0.005), but not race. There was no significant difference in serum BSAP between Blacks and Hispanics despite 60% higher iPTH levels in Blacks. CONCLUSIONS: Amongst ESRD patients, Blacks have higher iPTH levels compared with Hispanics despite similar BSAP levels, these finding support the emerging evidence of racial/ethnic differences in response of bone to PTH action.     

Plasma insulin-like growth factors and bone formation in uremic hyperparathyroidism

Bone formation in uremia is considered to be regulated in part by parathyroid hormone (PTH). However, while low levels of immunoreactive PTH are usually associated with low rates of bone formation in uremia, elevated PTH levels do not always correlate with increased bone formation. In an attempt to identify other factors that may regulate bone formation in uremic patients, we measured plasma immunoreactive insulin-like growth factors (IGF-I and IGF-II) in 15 patients who did not have aluminum-associated reductions in bone formation. Plasma levels of IGF-I but not PTH, were significantly higher in patients with high rates of bone formation when compared to patients with low or normal bone formation (P less than 0.02). While the bone formation rate at the tissue level correlated significantly with plasma PTH (r = 0.53, P less than 0.05) and IGF-I (r = 0.67, P less than 0.01), only for plasma IGF-I were there significant correlations with bone apposition (r = 0.57, P less than 0.05) and bone formation rate at the BMU level (r = 0.62, P less than 0.02), parameters which reflect mineralization activity at the cellular level. Among the static histologic parameters, osteoblastic osteoid correlated only with plasma PTH (r = 0.76, P less than 0.001), while osteoclast number correlated with both PTH (r = 0.56, P less than 0.05) and IGF-I (r = 0.67, P less than 0.01). There were no correlations between IGF-II levels and bone histology. From these data we suggest that IGF-I may promote bone formation in uremic patients with hyperparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

局部药物注射治疗难治性继发性甲状旁腺功能亢进

目的观察高频彩色超声引导下,对尿毒症继发性甲状旁腺功能亢进（SHPT）患者行甲状旁腺经皮注射无水酒精治疗（PEIT）的疗效;了解^99mTc-甲氧基异丁基异晴（MIBI）双时相平面显像核医学检查对PEIT的作用。方法依据免疫反应性甲状旁腺素（iPTH）值,将35例尿毒症患者分为轻、中、重度增高组,使用活性维生素D3口服（常规剂量或冲击剂量）治疗,筛选出的难治性SHPT患者,所有息者均行甲状旁腺高频彩色超声、^99mTc—MIBI核医学检查,随机分为甲、乙两组．其中甲组所有患者全部行PEIT,乙组2例排除异位甲状旁腺增大后行PEIT治疗。以高频彩超及iPTH检查随访。结果甲、乙两组患者甲状旁腺局部PEIT的有效率分别为66％和100％。结论高频彩色超声引导下甲状旁腺局部PEIT对难治性SHPT是一种行之有效的治疗方法;^99mTc-MIBI核医学检查可以筛选适宜行PEIT的患者,提高该治疗的有效率。     

Two-phase scintigraphy with technetium 99m-sestamibi in patients with hyperparathyroidism due to chronic renal failure

BACKGROUND: The objective of the current study was to study different functional and anatomic features of the hyperplastic gland and clinical and biochemical characteristics of renal hyperparathyroidism (HPT) patients and their relationship with the scintigraphic detection of parathyroid glands. METHODS: A retrospective study was performed of 40 patients with chronic renal failure (CRF) who underwent cervical surgery for HPT. Weight, histology, and localization of hyperplastic glands were recorded. Parathyroid cell proliferation was assessed by percentage of S-phase cells. Double-phase scintigraphy with technetium 99m-sestamibi and serum parathyroid intact hormone (PTHi), creatinine, calcium, and phosphate levels were performed. RESULTS: Detection of hyperplastic parathyroid glands by 99mTc-sestamibi scintigraphy was associated with the weight and inferior localization of the glands. The functionality of the glands as reflected in serum PTHi and phosphorus levels was associated with the number of glands detected. CONCLUSION: Double-phase 99mTc-sestamibi scintigraphy is of limited usefulness in patients with renal HPT. Detection of hyperplastic parathyroid glands in patients with CRF depends on the weight and inferior localization of the glands. Serum PTHi, phosphorus and creatine levels are associated with the number of glands detected by means of 99mTc-sestamibi scintigraphy.