人胚甲状旁腺细胞移植治疗甲状旁腺功能低下症

目的　探讨人胚甲状旁腺细胞移植治疗甲状旁腺功能减退症的临床意义。　方法　将培养的人胚甲状旁腺细胞在B超引导下移植到 6例甲状旁腺功能减退症患者的肾周围脂脂囊中。应用放射免疫方法测定患者术前、术后血中甲状旁腺激素 (PTH)及钙水平 ,并进行自身对照 ,对疗效进行评价。　结果　 6例患者在接受人胚甲状旁腺细胞移植前 ,血钙及PTH平均水平分别为 (1 6 3±0 12 )mmol/L及 (1 36± 0 2 1)ng/L ;接受移植 3d后分别为 (1 77± 0 2 2 )mmol/L及 (9 5 3± 2 2 1)ng/L ,两者差异有显著性意义 (P <0 0 1) ;6d后达正常水平 ,临床症状逐渐减轻至消失 ;术后观察 9～ 12个月病情保持稳定。　结论　培养的人胚甲状旁腺细胞肾周围脂肪囊内移植是治疗甲状旁腺功能减退症的一种较理想的新方法     

Assessment of parathyroid autotransplantation for preservation of parathyroid function after total thyroidectomy

BACKGROUND: Hypoparathyroidism with permanent hypocalcemia is a well-recognized complication after thyroid surgery. AIM: This study was conducted to assess the role of immediate parathyroid autotransplantation in the preservation of parathyroid function after total thyroidectomy. PATIENTS AND METHODS: Twenty-eight patients had autotransplantation of parathyroid glands resected or devascularized during total thyroidectomy. Data were collected prospectively regarding demographics, indication for surgery, operative procedure, pathologic diagnosis, number of glands transplanted, and subsequent course. Thyroid nodules were evaluated by ultrasonography, radionuclide scanning, and/or fine-needle aspiration cytology. All patients had serum ionized calcium, phosphorus, and intact parathyroid hormone (PTH) levels measured preoperatively and monitored regularly postoperatively for a period of 14 weeks and again at 6 months after operation. Patients were categorized into three groups according to the number of glands transplanted: one (group 1, n = 6), two (group 2, n = 14), or three glands (group 3, n = 8). In three other volunteers, one parathyroid gland was transplanted in the brachioradialis and subjected to electron microscopy 1, 2, and 4 weeks after transplantation. RESULTS: Total thyroidectomy was performed for malignant disease in 16 patients (57.1%) and for benign disease in 12 (42.9%) patients. All patients reverted to asymptomatic normocalcemia without the need for any medications within 4 to 14 weeks. Normal levels of serum markers were regained slower when one gland was transplanted compared with two or three glands (P <.01). Electron microscopic examination showed evidence of ischemic degeneration in the transplanted tissues 1 week postoperatively. Regeneration started by the second week and coincided with normalization of PTH levels. Optimum resting and nearly normal status of parathyroid tissue was achieved by the fourth week. CONCLUSIONS: This study showed that active PTH production coincides with regeneration of parathyroid cells and that autotransplantation of at least two resected or devascularized glands during total thyroidectomy nearly eliminates permanent postoperative hypoparathyroidism, thus improving the safety of total thyroidectomy performed for malignant or benign disease.     

微囊化新生猪甲状旁腺细胞异种移植的实验研究

目的 探讨微囊化新生猪甲状旁腺细胞异种移植治疗大鼠甲状旁腺功能低下症的效果。方法 应用微囊化技术，制备微囊化（海藻酸钠－聚赖氨酸－海藻酸钠生物微胶囊）新生猪甲状旁腺细胞，32只去甲状旁腺的Wistar大鼠随机分成微囊组、非微囊组、空囊组和对照组，分别移植微囊化新生猪甲状旁腺细胞、甲状旁腺细胞、空微囊及生理盐水。移植后监测血钙及甲状旁腺素水平40周，40周后回收移植物，透射电镜检查。结果 移植后，微囊组大鼠血钙及甲状旁腺素水平恢复到正常范围内，直至观察结束时（40周），透射电镜检查显示移植物存活良好；非微囊组、空囊组和对照组大鼠的血钙及甲状旁腺素水平无改善。结论 微囊化新生猪甲状旁腺细胞异种移植在不用免疫抑制剂情况下，可以在大鼠体内存活，且有功能；海藻酸钠－聚赖氨酸－海藻酸钠生物微胶囊对免疫活性细胞及抗体具有屏蔽作用。     

Preoperative evaluation of microencapsulated human parathyroid tissue aids selection of the optimal bioartificial graft for human parathyroid allotransplantation

Allotransplantation of microencapsulated parathyroid tissue is a promising approach to the treatment of permanent hypoparathyroidism. Preoperative assessment of the quality of microencapsulated parathyroid tissue could facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation. Parathyroid tissue from patients with secondary hyperparathyroidism (n = 15) was processed mechanically or enzymatically (collagenase type II). Tissue particles and single cells/cell clusters were routinely microencapsulated with amitogenic Ba(2+) alginate. Parathyroid secretion dynamics in response to stimulation of nonencapsulated and microencapsulated parathyroid tissue with Ca(2+) were evaluated in a perifusion system. The stability of the different types of microcapsule was assessed using an osmotic pressure test. Mechanical cutting of parathyroid tissue led to peripheral necrosis of tissue particles and impaired their vitality. Collagenase digestion, in contrast, resulted in single cells and cell clusters without peripheral necrosis. The quality of microencapsulation of single cells/cell clusters was significantly better than that of tissue particles (deformed and imperfect capsules). Microencapsulation itself did not decrease cell vitality. Nonencapsulated and microencapsulated tissue particles and single cells/cell clusters from different donors maintained their own levels of response to stimulation with low Ca(2+). Microcapsules containing tissue particles showed poor stability compared with those containing single cells/cell clusters. Preoperative evaluation of microencapsulated parathyroid tissue can disclose differences in vitality and function and thus facilitate selection of the optimal bioartifical graft for human parathyroid allotransplantation.     

Selective parathyroid auto‐transplantation during thyroidectomy

Aim: Permanent hypoparathyroidism is a debilitating morbidity following thyroidectomy and parathyroid auto‐transplantation has been shown to be effective in preventing permanent hypoparathyroidism. Controversy exists regarding the benefit of routine versus selective auto‐transplantation. We evaluate the outcome of selective parathyroid auto‐transplantation in our hospital. Methods: A retrospective study was conducted to assess the incidence of postoperative hypocalcaemia. Indication for parathyroid auto‐transplant was doubtful viability of parathyroid gland during thyroidectomy. From 1 July 2000 to 30 June 2005, all patients who underwent total, subtotal and completion thyroidectomy were included. Other outcome measures including recurrent laryngeal nerve injury and operative time were also analyzed. Results: A total of 170 bilateral or completion thyroidectomies were performed within this period. Total, subtotal, and completion total thyroidectomies were performed in 103 (60.6%), 62 (36.5%), and five (2.9%) patients, respectively. Median age was 45 years (range 19–82). One hundred and twenty‐four patients (73%) had benign thyroid disease, and 46 patients (27%) had thyroid carcinoma. Parathyroid auto‐transplant was performed in 35 patients (20.6%). Mean operation time was 204 min (range 95–510 min). There was no difference in the operation time between the patients with parathyroid auto‐transplant and those without auto‐transplant (217 vs 200 min, P = 0.229). Transient hypocalcaemia occurred in 31 patients (18.2%) whereas two patients had permanent hypocalcaemia (1.2%). Permanent recurrent laryngeal nerve injury occurred in one patient (0.6%). Conclusions: The adoption of selective parathyroid auto‐transplant during thyroidectomy achieves an extremely low incidence of permanent hypoparathyroidism without excessive transient hypoparathyroidism.     

Early postoperative PTH levels as a predictor of hypocalcaemia and facilitating safe early discharge after total thyroidectomy

OBJECTIVE: Hypocalcaemia after total or completion thyroidectomy has traditionally required 48 hours or longer inpatient monitoring of serum calcium levels. The use of parathyroid hormone (PTH) levels to predict postoperative hypocalcaemia is well established. This study aimed to measure the impact of a management plan based on postoperative PTH on achieving safe early discharge after thyroidectomy. METHODS: A prospective cohort study of 76 patients undergoing total or completion thyroidectomy was performed. Serum PTH level was measured 4-12 hours postoperatively and used to stratify patients into three groups: normal PTH (> 12 pg/mL), undetectable PTH (< 3 pg/mL) and intermediate PTH (4-11 pg/mL). A subgroup analysis was performed on a cohort of patients after a change in the management philosophy aiming for day 1 discharge based on the postoperative PTH. RESULTS: Seventy-five percent of eligible patients were successfully discharged on day 1 with no complications or readmissions; 21% of patients had intermediate or undetectable PTH levels and were monitored for 48 hours. No patient required intravenous calcium and no patient suffered permanent hypoparathyroidism. CONCLUSION: A single PTH measurement at 4-12 hours postoperatively allows for accurate prediction of patients at risk of hypocalcaemia. Patients with a normal postoperative PTH level can be safely discharged on the first postoperative day.     

ROUTINE AUTOTRANSPLANTATION OF AT LEAST ONE PARATHYROID GLAND DURING TOTAL THYROIDECTOMY MAY REDUCE PERMANENT HYPOPARATHYROIDISM TO ZERO

Background : Permanent hypoparathyroidism, although a recognized complication of total thyroidectomy, is an outcome that all endocrine surgeons try to avoid. Methods : To minimize the risk of postoperative hypoparathyroidism a strategy was developed of routine autotransplantation of at least one parathyroid gland into the ipsilateral sternomastoid muscle during every total thyroidectomy. One hundred consecutive patients undergoing total thyroidectomy were included in the study. Serum calcium and albumin levels were measured pre-operatively, on the first 2 postoperative days, and after 2 weeks, or until return to normal serum calcium levels without calcium supplementation. If patients developed biochemical evidence or symptoms of hypocalcaemia postoperatively, a calcium replacement was administered according to defined protocol. Results : In 74 cases one parathyroid gland was autotransplanted: 44 for inadvertent removal or anatomical reasons, 19 because of devascularization (assessed by a cut through the gland’s capsule and evaluation of the capillary bleeding pattern), and 11 by protocol. In 25 cases, two or more glands were autotransplanted. Fourteen patients developed symptoms of hypocalcaemia and received calcium supplementation, as did another 13 asymptomatic patients with only biochemical evidence of hypocalcaemia. At follow-up 3 months postoperatively the incidence of permanent hypoparathyroidism was zero, with all patients being normocalcaemic without calcium supplementation. Conclusions : This strategy, easily adopted by any experienced surgeon, has the potential to eliminate permanent hypoparathyroidism following total thyroidectomy.     

Serum intact parathyroid hormone as a predictor of hypocalcaemia after total thyroidectomy

BACKGROUND: Hypocalcaemia from hypoparathyroidism is a complication of total thyroidectomy. The aim of the present study was to determine whether an early postoperative level of serum parathyroid hormone (PTH) after total thyroidectomy predicts the development of significant hypocalcaemia and the need for treatment. METHODS: Patients undergoing total thyroidectomy had their serum level of intact PTH checked 1 h after removal of the thyroid gland. Serum calcium level was checked on the following morning. Oral calcium and/or calcitriol was commenced if the patient developed hypocalcaemic symptoms, or if the corrected serum calcium level was <2.0 mmol/L. RESULTS: Seventy-nine patients were included in the present study. Thirteen patients had symptoms of hypocalcaemia on postoperative days 1 or 2 and 66 patients remained asymptomatic. The postoperative intact PTH, day 1 calcium and day 2 calcium was 0.32 +/- 0.60 pmol/L, 2.01 +/- 0.11 mmol/L, and 2.02 +/- 0.16 mmol/L, respectively, for the symptomatic group and 1.98 +/- 1.25, 2.21 +/- 0.13, and 2.19 +/- 0.14, respectively, for the asymptomatic group. Calcium support was given to 25 patients, of whom 14 also required calcitriol. CONCLUSION: Serum PTH 1-h after total thyroidectomy is a reliable predictor of hypocalcaemia and can allow safe early discharge of patients from hospital.     

全甲状腺切除术后甲状旁腺的功能监测

目的 评估全甲状腺切除术后甲状旁腺功能减退症发生情况,探索早期预测术后低钙血症的方法.方法 对124例患者(甲状腺癌46例、结节性甲状腺肿78例)行全甲状腺切除术,恶性患者加行淋巴结清扫术,术前、术后1 h、1 d、2 d检测血钙和血PTH,观察术后甲状旁腺功能减退症发生情况,并用受试者工作特征曲线研究低钙血症早期预测指标.结果 58例发生术后暂时性甲状旁腺功能减退症(46.8%),甲状腺癌组22例(47.8%),结节性甲状腺肿组36例(46.2%),两组之间无明显差异(λ2=0.033,P=0.857);1例发生永久性甲状旁腺功能减退症(0.8%),发生在甲状腺癌组.术后90例(72.6%)出现血钙下降,58例(46.8%)出现血PTH下降,40例(32.3%)出现低钙症状.甲状腺癌组术后血钙(F=21.358,P=0.000)、血PTH(F=18.253,P=0.000)下降程度重于结节性甲状腺肿组,术后1 h血PTH下降百分比可很好的预测有临床症状的低钙血症(曲线下面积为0.933),以PTH下降76.6%作为分界点,此时预测有临床症状的低钙血症的敏感性为89.7%,特异性为87.9%. 结论全甲状腺切除术加行淋巴结清扫会加重术后血钙、血PTH下降程度但不会增加甲状旁腺功能减退症发生率;术后1 h血PTH下降百分比可预测低钙血症的发生.     

Thyroid,parathyroid hormones and calcium homeostasis

The thyroid gland secretes thyroxine (T4) and triiodothyronine (T3) in response to thyroid-stimulating hormone release from the anterior pituitary gland. Iodine is essential for the synthesis of thyroid hormones. T4 and T3 increase the basal metabolic rate, heat production, and help to maintain normal growth and development. Serum calcium levels are under very tight control. The majority of calcium is found in bones. Calcium and phosphate levels are maintained by four hormones – parathyroid hormone (PTH), calcitonin, vitamin D and fibroblast growth factor 23. PTH is produced by the parathyroid glands and its secretion is determined by serum calcium levels.     

Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells

Serum autoantibodies directed toward antigenic determinants on the surface of human parathyroid cells (PTAb-CS) have been demonstrated in a subset (8 of 23) of adult patients with idiopathic hypoparathyroidism (IHP). In sera from 3 of 8 patients with PTAb-CS, binding of these autoantibodies to their respective parathyroid cell surface antigen(s) resulted in marked inhibition of parathyroid hormone (PTH) secretion in an in vitro dispersed human parathyroid cell (dPTC) system. In 1 subject evaluated longitudinally, circulating levels of PTAb-CS, and the magnitude of the inhibitory effect on PTH secretion, temporally correlated with the clinical course of the hypoparathyroidism. These findings suggest a causative role for antibodies directed against cell surface antigens in parathyroid dysfunction in some cases of "autoimmune" hypoparathyroidism.     

Allotransplantation of Cryopreserved Parathyroid Tissue for Severe Hypocalcemia in a Renal Transplant Recipient

We report the successful allotransplantation of cryopreserved parathyroid tissue to reverse hypocalcemia in a kidney transplant recipient. A 36‐year‐old male received a second deceased donor kidney transplant, and 6 weeks later developed severe bilateral leg numbness and weakness, inability to walk, acute pain in the left knee and wrist tetany. His total calcium was 2.6 mg/dL and parathormone level 5 pg/mL (normal 10–60 pg/mL). He underwent allotransplantation of parathyroid tissue cryopreserved for 8 months into his left brachioradialis muscle. Immunosuppression included tacrolimus (target C₀ 10–12 ng/mL), mycophenolate mofetil and steroids. Within 2 weeks, the left knee pain, leg weakness and numbness resolved, and by 1 month he could walk normally. After a peak at month 2, his parathyroid hormone (PTH) level fell to <10 pg/mL; therefore at month 3 he received a second parathyroid transplant from the same donor. Eight months later (11 months after initial graft) he has a total calcium of 9.3 mg/dL, PTH level 15 pg/mL and is clinically asymptomatic. The amount of parathyroid tissue needed to render a patient normocalcemic is not known. In our case, the need for second transplant suggests that the amount of tissue transferred for an allograft may need to be substantially greater than for an autograft.     

Does the number of autotransplanted parathyroid glands affect postoperative hypoparathyroidism and serum parathyroid hormone levels?

BackgroundTo investigate how number of autotransplanted parathyroid glands (PGs) affects the incidence of postoperative hypoparathyroidism and the recovery of parathyroid function.MethodsA systematic search was performed in the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. The evaluated indices included the incidence of postoperative transient and permanent hypoparathyroidism and parathyroid hormone (PTH) levels during follow-up.ResultsTwenty articles with 7291 patients were included. A higher incidence of transient hypoparathyroidism was found in the PG autotransplantation group than in the preservation group (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.90, 2.96). However, there was no significant difference between the two groups regarding permanent hypoparathyroidism (OR: 1.17; 95% CI: 0.71, 1.91). Parathyroid hormone (PTH) levels in the PG autotransplantation group changed significantly more than the preservation group at postoperative 1-day and 1-month, but became similar at the 6-month, 1-year and 2-year follow-up. Autotransplantation of 2 and 3 PGs demonstrated a higher incidence of transient hypoparathyroidism than 1 PG (OR: 2.09; 95% CI: 1.41, 3.11 and OR: 9.70; 95% CI: 2.11, 44.39, respectively), but no significant difference was observed between the autotransplantation of 3 and 2 PGs (OR: 0.99; 95% CI: 0.03, 29.06). Additionally, the incidence of permanent hypoparathyroidism was not significantly different when different number of PGs was autotransplanted.ConclusionsPG autotransplantation is an effective mid- and long-term strategy for the preservation of parathyroid function. Although transient hypoparathyroidism was positively correlated with the number of autotransplanted PGs, no remarkable correlation was observed for permanent hypoparathyroidism.     

Recombinant PTH therapy for severe hypoparathyroidism after kidney transplantation in pre‐transplant parathyroidectomized patients: review of the literature and a case report

Although transient hypocalcemia following kidney transplantation can occur, severe refractory hypocalcemia is uncommon. We report a case of a 31‐yr‐old highly sensitized man with end‐stage renal disease caused by reflux nephropathy, who received an expanded criteria deceased donor kidney transplant. The post‐transplant course was significant for profound hypocalcemia despite treatment with large doses of calcium and vitamin D, in the setting of severe hypoparathyroidism following a subtotal parathyroidectomy three yr prior to the transplant. His course was also complicated by suboptimal allograft function with significant new vascular changes seen in the allograft biopsy by seven wk post‐transplant. Teriparatide (recombinant parathyroid hormone) injections were initiated (up to three times daily) with improvement in the vascular changes and a decrease in calcium phosphate calcification in biopsy, as well as reduction in hypercalciuria, restoration of calcium phosphate homeostasis and stabilization of allograft function. We describe six other cases of post‐transplant hypoparathyroidism, with five of six having decreased allograft function and three of those five demonstrating significant accelerated vascular changes on biopsy. We discuss the use of teriparatide injections for the treatment of renal transplant recipients with impaired renal function in the setting of hypoparathyroidism.     

Parathyroid autotransplantation with total thyroidectomy for thyroid carcinoma: long-term follow-up of grafted parathyroid function.

BACKGROUND: Permanent hypoparathyroidism is a major complication of thyroidectomy. Autotransplantation of parathyroid glands has been attempted to prevent this complication. However, no direct data have been available to assess grafted parathyroid function after long-term follow-up in terms of the serum intact parathyroid hormone (PTH) concentration. METHODS: Eighty-four consecutive patients with differentiated thyroid carcinoma who underwent total thyroidectomy and bilateral modified neck dissection from 1992 to 1996 were enrolled. They concomitantly underwent total parathyroidectomy and autotransplantation of all parathyroid glands to the pectoralis major muscle. The serum intact PTH concentration was periodically measured as an index of grafted parathyroid function. RESULTS: The mean follow-up was 34 months. In all autotransplanted patients serum intact PTH concentrations fell below detectable limits immediately after surgery. They were restored to the normal range within 1 month postoperatively and were maintained during observation in 80 (95%) of 84 patients. Seventy-eight of 80 patients with normal intact PTH values were normocalcemic without any treatment and the remainder were normocalcemic with 1 microgram of 1 alpha-vitamin D3. Four hypoparathyroid patients were normocalcemic with 2 micrograms of 1 alpha-vitamin D3. The postoperative average serum intact PTH concentration of patients having more than 2 autotransplanted parathyroid glands was almost equal to that of patients with preservation of the parathyroid glands in situ. The incidence of permanent hypoparathyroidism was inversely correlated with the number of autotransplanted parathyroid glands. CONCLUSIONS: The recovery patterns of the intact PTH concentration indicate that the glands were grafted successfully and functioned for a long period. This feasible method of parathyroid autotransplantation bears comparison with the previous reports in terms of the incidence of permanent postoperative hypoparathyroidism, and it can be performed simply and is reproducible.     

Intraparathyroid cyst: a tumour of branchial origin and a possible pitfall for targeted parathyroid surgery

Background: Parathyroid cysts account for 0.5% of parathyroid pathologies. They usually contain sky‐high levels of parathyroid hormone (PTH) but are not necessarily associated with primary hyperparathyroidism (PHPT). Their origin is subject to debate. We provide evidence for a branchial origin and illustrate some potential problems they pose for targeted parathyroid surgery. Methods: The present study is a single institution retrospective study of 1702 parathyroid and 10 021 thyroid operations performed over a period of 12 years (1990?2001). Twenty‐three cases of parathyroid cyst were found: three palpable neck masses, four cases associated with PHPT and 16 incidental findings at the time of thyroid surgery. Intracystic PTH measurements and immunostaining of the lining wall of the cyst were obtained in 16 out of 23 and 18 out of 23 cases, respectively. Results: Intracystic PTH levels were elevated in 15 out of 16 cases (average 3877, range 36 000?23 pg\mL). The wall of the cyst stained positively for epithelial cuboidal cell markers (CK +ve) and negatively for PTH (PTH ?ve) in 18 out of 18 cases. In only one quarter of the cases associated with PHPT was the cyst the hypersecreting gland, nevertheless it contained less than the average PTH level (1440 vs 3877) and did not take up sestamibi. Results were conflicting in the other three cases. Histological studies on the present series suggest a branchial pouch origin. Conclusion: Despite containing high levels of PTH, parathyroid cysts are of branchial origin and when associated with PHPT are rarely responsible for the disease. Targeted parathyroid surgery should not rely only on ultrasound and intraparathyroid PTH measurements.     

Prediction of Permanent Hypoparathyroidism after Total Thyroidectomy

Background

Hypoparathyroidism is a common complication with thyroid surgery. The ability to predict a high risk of permanent hypoparathyroidism is important for individual prognosis and follow-up.

Methods

Permanent hypoparathyroidism, defined as continuing need for vitamin D medication at 1-year post-operatively, was investigated in patients after total thyroidectomy. Blood levels of calcium and parathyroid hormone (PTH) were measured intra-operatively, the day after surgery and at 1 month post-operatively. Logistic regression analysis was performed to investigate the risk of vitamin D treatment at last follow-up, calculated as odds ratios (ORs) with 95 % confidence intervals (CIs). Patients were followed until cessation of vitamin D and/or calcium medication, until death, loss to follow-up, or end of follow-up, whichever came first.

Results

A total of 519 patients were included. The median (range) follow-up in patients unable to cease vitamin D was 2.7 (1.2–10.3) years. The rate of permanent hypoparathyroidism was 10/519, 1.9 %. Parathyroid auto-transplantation was performed in 90/519 (17.3 %) patients. None of these developed permanent hypoparathyroidism, nor did any patient with normal PTH day 1 (>1.6 pmol/l or 15 pg/ml). The adjusted risk (OR, 95 % CI) for permanent hypoparathyroidism for log PTH on day 1 was 0.25 (0.13–0.50). In patients not auto-transplanted and with unmeasurable PTH day 1 (<0.7 pmol/l or 6.6 pg/ml), 8/42 (19.2 %) developed permanent hypoparathyroidism.

Conclusions

Auto-transplantation protects against permanent hypoparathyroidism, whereas low PTH day 1 is associated with high risk.     

Australian Endocrine Surgeons Guidelines AES06/01. Postoperative parathyroid hormone measurement and early discharge after total thyroidectomy: analysis of Australian data and management recommendations

Background: The risk of hypocalcaemia after thyroidectomy has traditionally mandated inpatient monitoring for signs and symptoms as well as frequent measurement of serum calcium levels. In recent years there has been much interest in the published work about the use of intact parathyroid hormone (PTH) to better predict hypocalcaemia after thyroidectomy. Although generally accurate, the use of intact parathyroid hormone in Australia has not become widespread. On behalf of the Australian Endocrine Surgeons an analysis of Australian data on the use of PTH levels to predict hypocalcaemia after thyroidectomy was carried out. The data were analysed with a view to making recommendations about the use of this test in clinical practice and the feasibility of achieving safe early discharge for patients. Methods: Four recently published or presented Australian studies on the use of early postoperative PTH levels after total or completion thyroidectomy to predict post‐thyroidectomy hypocalcaemia were analysed. Patients were stratified into either normal or low PTH groups as defined by the normal ranges set by each laboratory and rates of hypocalcaemia were analysed. Results: A total of 458 patients were examined. Seventy‐six per cent of the patients had PTH in the normal range and hypocalcaemia (serum‐corrected calcium cCa²⁺ < 2.00 mmol/L) occurred in 17.9% of patients. Sensitivity, specificity and positive predictive values of a normal postoperative PTH level as a predictor of normocalcaemia are 92.6, 70.7 and 92.3%, respectively. Low PTH as a predictor of hypocalcaemia is poor. The overall sensitivity, specificity and positive predictive values are 70.7, 92.6 and 71.6%, respectively. Conclusion: Normal postoperative PTH levels accurately predict normocalcaemia after total or completion thyroidectomy. PTH levels should ideally be drawn 4 h postoperatively and patients with PTH in the normal range can be safely discharged on the first postoperative day. Use of oral calcium supplements, either as needed or routinely, will avoid mild symptoms that may develop in 7% without treatment.     

Excessive Decrease in Serum Magnesium After Total Thyroidectomy for Graves’ Disease Is Related to Development of Permanent Hypocalcemia

Background

Transient postoperative hypocalcemia is one of the most common complications after thyroidectomy. Permanent hypocalcemia, however, is rare, but usually requires life-long treatment and follow-up. The risk of permanent hypocalcemia has been shown to be significantly higher in patients with Graves’ disease. In the present study we evaluated short-term and long-term changes in serum calcium, phosphate, magnesium, and parathyroid hormone (PTH) levels in order to characterize subjects at risk of postoperative hypoparathyroidism.

Methods

Forty patients who underwent total thyroidectomy for Graves’ disease were included in the study. Calcium, phosphate, magnesium, and PTH were measured before surgery and regularly during the year that followed.

Results

Postoperative hypocalcemia was seen in 21/40 (53 %) patients. Undetectable PTH (<0.6 pmol/L) was registered in 11/40 (27 %) patients. All patients with measurable PTH 6–48 h after operation regained normal calcium. Of those with undetectable PTH after 6–48 h, four developed permanent hypocalcemia. We found a significantly lower serum calcium level before operation in patients who developed permanent hypocalcemia compared to those who did not (p < 0.001). We also found a significant correlation between the decrease in serum magnesium from time 0 to 48 h after operation and permanent hypocalcemia (p = 0.015).

Conclusions

Serum calcium prior to operation, serum PTH, and degree of decrease in magnesium levels in serum 48 h after operation may predict development of permanent hypocalcemia. Magnesium plays an important role in calcium homeostasis via stimulation of PTH secretion and modulation of PTH receptor sensitivity. Both mechanisms may have played a role for the findings reported in this article.     

Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl.

BACKGROUND: Patients with secondary hyperparathyroidism often require therapy that provides long-term control of parathyroid hormone concentrations without increasing calcium and phosphorus concentrations. Cinacalcet modulates the calcium-sensing receptor on the parathyroid gland to reduce secretion of parathyroid hormone and lower serum calcium, phosphorus and calcium-phosphorus product in haemodialysis patients. METHODS: Dialysis patients with secondary hyperparathyroidism [parathyroid hormone (PTH) level > or =300 pg/ml] who were enrolled in one of four phase 2 placebo-controlled studies were eligible to enroll in an open-label extension study in which all patients received cinacalcet. For this extension study, cinacalcet was initiated at 30 mg in all patients and the dose was escalated to a maximum of 180 mg once daily if PTH concentrations were >250 pg/ml. Use of concomitant vitamin D sterols and phosphate binders was not restricted. RESULTS: The analysis of all patients (n = 59) completing 100 weeks of cinacalcet treatment showed long-term control of PTH and calcium-phosphorus product. Approximately 55% achieved a PTH concentration < or =300 pg/ml at the week-100 study visit, and approximately 60% had at least a 30% reduction in PTH from baseline. Serum calcium, phosphorus and the calcium-phosphorus product did not increase during the study. Concomitant vitamin D sterol and phosphate binder therapy remained stable. Cinacalcet was safe and generally well tolerated at doses up to 180 mg/day. CONCLUSIONS: In this long-term study, cinacalcet effectively sustained reductions in PTH for up to 3 years without increasing concentrations of serum calcium, phosphorus or calcium-phosphorus product.