The effects of calcium homeostasis and thyroidectomy: Postoperative hypocalcaemia complicating thyroid surgery

Hypocalcaemia is the most common complication of total or completion thyroidectomies and the reported incidence of this potentially fatal condition varies widely in the literature. Hypocalcaemia develops between two to five days after thyroid surgery. This raises three main issues, namely increased patient hospital stay, the risk of patient discharge before the condition develops and an assessment of its risk influences the timing of patient discharge. For these reasons, a model for predicting which patients require calcium post-surgery is required. The proposed benefits of such a model include a reduced length of stay, reduced risk of re-admission and the opportunity to commence calcium supplements before the onset of symptoms of hypocalcaemia.

This study defines a patient requiring postoperative calcium supplements as either having an adjusted calcium measurement below 2.0 mmol/L at any time up to one year following surgery or being administered calcium supplements after presenting clinical signs (Trousseau’s sign or Chvostek’s sign) or symptoms (such as perioral numbness) of hypocalcaemia. A retrospective study of patient records and pathology results of patients having undergone either total or completion thyroidectomy at either The Geelong Hospital or St. John of God Hospital during the years 2001 – 2008 was undertaken.

The statistical association between the patient outcome of requiring postoperative calcium supplements and a number of commonly evaluated categorical risk factors (including age, gender and procedure) were evaluated. Novel categorical risk factors (such as patient smoker status and medications at admission) were also investigated. Receiver-Operating Characteristic curve models were generated to evaluate the ability of biochemical markers to predict which patients require postoperative calcium supplements. Models based on calcium, parathormone, phosphate, magnesium, thyroxine, triiodothyronine and thyroid stimulating hormone measurements were investigated.

One hundred and eighty patients undergoing total or completion thyroidectomy at The Geelong Hospital or St. John of God Hospital during the years 2001 – 2008 are included in the current study. The mean age at surgery was 51.3 years and the female-to-male ratio was 5.2:1. There were 145 total thyroidectomies performed and 35 completion thyroidectomies. The median length of hospital stay was 3.0 days. Forty-two patients developed an adjusted calcium measurement below 2.0 mmol/L within one week of surgery and fourteen patients showed signs of hypocalcaemia and were commenced on calcium supplement therapy.

Risk categories for which there were no statistically significant associations with the patient outcome include: gender, age at surgery, procedure, number of parathyroid glands excised, duration of surgery, patient smoker status, blood group, the use of medications and the presence of co-morbidities concurrent with surgery.

This study identifies a patient management model based on the early prediction of which patients require postoperative calcium supplements. A single PTH measurement at 6 - 8 hours post-surgery below 1.1 ρmol/L identified all patients requiring postoperative calcium supplements (100 % sensitivity) and ruled out 85.7 % of patients not requiring postoperative calcium supplements. Implementing this model would facilitate the safe discharge on the day of surgery of patients undergoing completion thyroidectomy before 11:00AM. All other patients could be discharged on the first postoperative day, with a PTH measurement below 1.1 ρmol/L at 18 – 24 hours identifying with 91 % sensitivity which patients require postoperative calcium supplements.

A second finding of the study lends support to Hungry Bone Syndrome as a mechanism by which hypocalcaemia complicates thyroid surgery. Whilst no statistically significant association could be identified, it was found that patients suffering from Graves’ disease required postoperative calcium supplements at a rate that was elevated as compared to all other thyroid pathologies. This finding is also supported by statistical models generated from thyroid hormone measurements for the detection of which patients require postoperative calcium supplements.

低钙血症（Hypocalcaemia）是全甲状腺切除术及完成性甲状腺切除术最常见的术后并发症，且这一潜在致命病症的文献报道发病率差异巨大。该病症通常于甲状腺术后2~5天发作，由此引发三大核心问题：患者住院时长延长、患者可能在病症发作前即被出院，以及风险评估会影响患者出院时机。基于上述原因，亟需构建一款可预测术后需补钙患者的模型。此类模型的预期收益包括缩短住院时长、降低再入院风险，以及可在低钙血症症状出现前启动补钙治疗。

本研究将术后需补钙患者定义为以下两类人群：一是术后任意时间点（最长至术后1年）的校正血钙检测值低于2.0 mmol/L者；二是出现低钙血症相关临床体征（特鲁索征（Trousseau’s sign）或霍夫斯特克征（Chvostek’s sign））或症状（如口周麻木）后接受补钙治疗者。本研究回顾性分析了2001年至2008年间，在吉隆医院（The Geelong Hospital）及圣约翰天主医院（St. John of God Hospital）接受全甲状腺切除术或完成性甲状腺切除术患者的病历与病理检验结果。

本研究分析了术后需补钙这一结局与多项常用分类危险因素（包括年龄、性别、手术方式）之间的统计学关联，同时也探究了新型分类危险因素（如患者吸烟状态、入院用药情况）。研究构建了受试者工作特征（Receiver-Operating Characteristic）曲线模型，以评估各类生物标志物预测术后需补钙患者的效能；同时针对血钙、甲状旁腺激素（parathormone）、磷酸盐、镁、甲状腺素（thyroxine）、三碘甲状腺原氨酸（triiodothyronine）及促甲状腺激素（thyroid stimulating hormone）的检测结果构建模型并进行分析。

本研究共纳入2001年至2008年间在吉隆医院及圣约翰天主医院接受全甲状腺切除术或完成性甲状腺切除术的180例患者。患者手术时的平均年龄为51.3岁，男女比例为5.2:1。其中全甲状腺切除术145例，完成性甲状腺切除术35例；患者住院时长的中位数为3.0天。术后1周内，共有42例患者的校正血钙检测值低于2.0 mmol/L，14例患者出现低钙血症体征并启动补钙治疗。

未发现与术后需补钙结局存在统计学显著关联的危险因素类别包括：性别、手术时年龄、手术方式、切除甲状旁腺数目、手术时长、患者吸烟状态、血型、用药情况及手术合并症情况。

本研究构建了基于术后需补钙患者早期预测的患者管理模型。术后6~8小时单次检测甲状旁腺激素（PTH）值低于1.1 ρmol/L时，可识别出所有需术后补钙的患者（灵敏度达100%），并可排除85.7%无需补钙的患者。应用该模型可使上午11点前接受完成性甲状腺切除术的患者于手术当日安全出院；其余患者可于术后第1日出院，此时术后18~24小时检测PTH值低于1.1 ρmol/L时，可识别出91%需术后补钙的患者。

本研究的第二项发现为“饥饿骨综合征”（Hungry Bone Syndrome）作为甲状腺术后并发低钙血症的机制提供了支持。尽管未发现统计学显著关联，但研究发现格雷夫斯病（Graves’ disease）患者术后需补钙的比例显著高于其他甲状腺病变患者。这一结果也得到了基于甲状腺激素检测结果构建的术后需补钙患者预测模型的佐证。