Early Postoperative PTH Levels as a Predictor of Hypocalcaemia and

Original Article

Early Postoperative PTH Levels as a Predictor of Hypocalcaemia and Facilitating Safe Early Discharge After Total Thyroidectomy Simon Grodski and Stephen Farrell, Department of Surgery, Endocrine Surgery Unit, St. Vincent’s Hospital Melbourne, Victoria, Australia.

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. [Asian J Surg 2007;30(3):178–82] Key Words: hypocalcaemia, parathyroid hormone, serum calcium, thyroidectomy

Introduction Major complications of thyroidectomy such as postoperative haemorrhage, recurrent laryngeal nerve palsy and permanent hypoparathyroidism occur in less than 2% of patients in expert hands.1 Temporary hypocalcaemia occurs in 1% to more than 50%2–4 of patients after undergoing total thyroidectomy or completion thyroidectomy. Hypocalcaemia causes a spectrum of symptoms ranging from mild paraesthesia and tingling to distressing cramps, tetany and convulsions. Thyrotoxicosis, cancer and

retrosternal goitre have all been shown to be associated with increased incidence of hypocalcaemia.5 Hypocalcaemia typically presents within the first 2 days postoperatively, but the nadir may be as delayed as day 4.6 It is routine practice to monitor patients for hypocalcaemia and measure serum calcium levels.7 The standard management at our institution after total thyroidectomy or completion thyroidectomy has been to monitor patients for hypocalcaemia for 48 hours postoperatively. Calcium replacement therapy is administered if corrected calcium levels (cCa2+) drop below 2.00 mmol/L or patients develop

Address correspondence and reprint requests to Dr Simon Grodski, 14 Bent Street, East Malvern, Victoria 3145, Australia. E-mail: [email protected] ● Date of acceptance: 12 September 2006 © 2007 Elsevier. All rights reserved.

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symptoms of hypocalcaemia. Symptomatic hypocalcaemia can usually be treated with oral calcium and vitamin D supplements, but occasionally intravenous calcium is required for severe symptoms. The use of serum parathyroid hormone (PTH) levels postoperatively7–14 to predict hypocalcaemia after thyroidectomy has been extensively published in the literature. Only Payne et al have published on the successful early discharge of patients based on PTH results.15 The present study investigated the use of a single serum PTH level taken 4–12 hours post-thyroidectomy as a tool for predicting hypocalcaemia. We then used this information to develop a management plan to allow safe, early discharge of patients not at risk of hypocalcaemia. A secondary aim of the study was to investigate if the number of parathyroid glands identified at operation or the use of parathyroid autotransplantation influenced postoperative PTH level.

Methods All patients who underwent total or completion thyroidectomy operated on by a single surgeon at St. Vincent’s Hospital Melbourne Endocrine Surgery Unit over a 20-month period were studied. 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. It was felt that postoperative PTH levels accurately predicted hypocalcaemia after total thyroidectomy and patients with normal PTH levels were not at risk of developing significant and progressive hypocalcaemic symptoms. Given this, patients with normal postoperative PTH levels could be safely discharged on the first postoperative day without the need for ongoing calcium monitoring. Patients were managed based on a PTH level 4–12 hours after thyroidectomy, blood was drawn and PTH level was measured on the Immulite 2000 machine (DPC Biomedics, Los Angeles, CA, USA). Patients were stratified into three groups based on their PTH level: PTH in the normal range (> 12 pg/mL), PTH in an intermediate range (4–11 pg/mL), and undetectable PTH (< 3 pg/mL). A bilateral total thyroidectomy or total completion thyroidectomy was performed in all cases. Our approach to the parathyroid glands is to routinely identify and preserve superior glands, their viability is checked (visual assessment followed by incising the gland to observe capillary bleeding if doubtful viability), and nonviable glands are autotransplanted. Inferior glands are not sought if


remote from the thyroid capsule. Nonviable parathyroid glands are diced into < 1 mm pieces and mixed with 0.5–1 mL of normal saline. The mixture is then injected into the sternomastoid muscle in one or more pockets and marked with a surgical clip. We routinely perform bilateral superficial cervical plexus block with 20 mL ropivacaine 0.75%. Drains are not used. Patients with a normal PTH were aimed for discharge on the first postoperative day without calcium supplements. Patients with undetectable PTH were commenced on calcium and calcitriol replacement. Patients with an intermediate PTH were monitored for 48 hours for hypocalcaemia. Postoperative clinical assessment was undertaken every 6 hours, with assessment for tingling, numbness and cramps as well as eliciting Chvostek and Trousseau’s signs. Calcium levels were measured on the first postoperative morning and then repeated if PTH level was not in the normal range. All patients were reviewed 1–2 weeks postoperatively.

Results In total, 76 patients were studied (Figure 1). There were 58 patients with normal PTH (76%), six of whom developed mild transient hypocalcaemia (cCa2+, 1.96–2.00 mmol/L)— they all remained asymptomatic and required no treatment. Six patients had intermediate PTH, of whom four developed hypocalcaemia requiring treatment and two remained normocalcaemic. Twelve patients had an undetectable PTH: two were placed on oral calcium and calcitriol, thus avoiding hypocalcaemia; the remaining 10 patients developed hypocalcaemia and required treatment with calcium and calcitriol. Overall, the rate of temporary hypocalcaemia (cCa2+ < 2.0 mmol/L) was 26%; a further two patients with low PTH levels were treated with calcium and vitamin D supplements, avoiding possible hypocalcaemia. No patient suffered permanent hypoparathyroidism and no patient required intravenous calcium replacement. From May to December 2005, a change in management philosophy was made. Patients were managed based on their PTH level with the aim of discharging patients with a normal PTH on postoperative day 1. A total of 28 patients were treated in this period, 22 of whom had a normal PTH level. One patient had cCa2+ of 1.99 mmol/L and no treatment was required. Only one patient had an intermediate PTH level, remaining normocalcaemic.

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70

Patients, n

60 50 40 30 20 10 0 Normal PTH

Intermediate PTH

cCa > 2.00 mmol/L

Undetectable PTH

cCa < 2.00 mmol/L

Figure 1. Postoperative parathyroid hormone (PTH) results and rates of biochemical hypocalcaemia. 16 14 Patients, n

12 10 8 6 4 2 0 Day 1 discharge Normal PTH

Day 2 discharge Low PTH

Figure 2. Patients achieving day 1 discharge during study period based on postoperative parathyroid hormone (PTH) levels. Patients discharged on day 2 were both planned due to low PTH levels and patients failing to achieve day 1 discharge despite normal PTH levels.

Five patients had an undetectable PTH level, and all were treated with oral calcium and calcitriol. Of 22 patients with a normal PTH level, two were not considered for early discharge (severe cardiomyopathy and arrhythmias due to amiodarone thyrotoxicosis in 1 and synchronous transsphenoidal pituitary surgery in 1). Of the remaining patients, 75% were successfully discharged home on day 1 (Figure 2). A normal postoperative PTH level was a significant predictor of discharge on day 1 when compared with the group of patients with low or undetectable PTH levels using Fisher’s exact test (p < 0.01). There were five patients in the normal group who met the criteria but could not be discharged on day 1 and who were discharged on the second postoperative day instead. Three patients had social factors confounding

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early discharge (no means of transport or no family support at home) and two patients suffered postoperative nausea and vomiting that made day 1 discharge inappropriate. All five patients occurred early in the trial and it is felt that improved education of patients and ward staff has led to a greater acceptance of early discharge. Nausea was treated early and discharge planning was improved, leading to increased day 1 discharge rates later in the series. Additionally, six patients with low PTH and not eligible for day 1 discharge were discharged on day 2. Two parathyroid glands were identified in 16 cases, including two completion thyroidectomies. Three parathyroid glands were identified in seven cases and four parathyroid glands were identified in five cases. Identification of more than two parathyroid glands did not predict normal postoperative PTH levels (Fisher’s exact test, p = 0.58). Twenty-one patients had autotransplantation of parathyroid glands; in 16 cases, a single gland was transplanted; and in five cases, two glands were transplanted. All seven patients who did not receive autotransplantation of parathyroid glands had normal postoperative PTH levels. Conversely, all patients with postoperative parathyroid insufficiency received parathyroid autotransplantation (and subsequently recovered). Despite this, the use of parathyroid gland autotransplantation as a predictor of postoperative hypoparathyroidism did not achieve statistical significance (Fisher’s exact test, p = 0.14).

Discussion The aetiology of hypocalcaemia is complex and multifactorial. Hypoparathyroidism as a result of inadvertent devascularization, excision or trauma to the parathyroid glands during surgery is a major factor in causing postthyroidectomy hypocalcaemia.6 The intimate relation between the thyroid and parathyroid glands and their blood supplies makes sound surgical technique essential to minimize parathyroid trauma. Other factors, however, contribute to postoperative hypocalcaemia, such as haemodilution, increased urinary calcium excretion, calcitonin release, thyrotoxicosis and osteodystrophy.16 This study confirmed that intraoperative factors cannot accurately predict hypocalcaemia or low postoperative PTH levels. It has previously been noted that autotransplantation of parathyroid glands is associated with increased temporary hypocalcaemia but decreased


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permanent hypocalcaemia.4,17 This is a function of the pathology necessitating parathyroid autotransplantation rather then the transplant itself. Selective autotransplantation has enabled us to maintain a zero rate of permanent hypoparathyroidism over the 20 months and 74 patients of this study. The use of autotransplantation itself, however, is not an accurate predictor of low postoperative PTH levels or the need for calcium supplementation. Preservation of parathyroid glands in situ has been advocated as a means of avoiding hypocalcaemia.6,16 We did not find identification and preservation of parathyroid glands to be an accurate predictor of postoperative PTH levels and, although we advocate careful identification and preservation of parathyroid glands when possible, this cannot be relied upon for normocalcaemia. Although early discharge after total thyroidectomy has been reported,18 the uniform use of oral calcium and vitamin D supplementation is both costly and may delay the diagnosis of hypoparathyroidism. Such a practice relies on significant infrastructure and outpatient support. The risk of delayed symptoms of both hypo- and hypercalcaemia makes such a practice unappealing to many clinicians. The use of calcium supplements alone may reduce the incidence of hypocalcaemic symptoms, aiding early discharge after thyroidectomy, but some patients are at risk of progressive and severe hypocalcaemia if not closely monitored post-discharge. Payne et al are the only other group to publish on the successful impact of postthyroidectomy PTH measurements.19 They were able to demonstrate that the use of early PTH and calcium levels could predict patients not at risk of hypocalcaemia, allowing them to discharge their patients home sooner. Our study was also able to achieve day 1 discharge in a significant number of our patients and confirm that PTH can be used to facilitate safe, early discharge. An undetectable PTH level was associated with hypocalcaemia in all but two patients—both of whom were treated with calcium and vitamin D supplements before hypocalcaemia developed. In our experience, an undetectable PTH level after thyroidectomy is an accurate predictor of hypocalcaemia, and these patients should be placed on calcium and vitamin D supplements early in order to avoid symptoms of hypocalcaemia. Patients with intermediate PTH levels provide an area of uncertainty. Over the period of our analysis, six patients fell into this group; four developed hypocalcaemia and two did not.


These patients must be monitored for hypocalcaemia and treated accordingly. Hypocalcaemia is a source of significant morbidity and cost after total thyroidectomy. This study demonstrates that early postoperative PTH can accurately predict patients not at risk of hypocalcaemia. It is especially important in our practice, where patients sometimes travel several hundred kilometres for their surgery, to ensure that symptomatic hypocalcaemia does not occur after discharge. The ability to accurately predict patients not at risk of hypocalcaemia allows us to safely institute early discharge for many of our patients. By using the PTH result to tailor oral calcium and vitamin D supplementation, we are able to better manage post-thyroidectomy hypoparathyroidism.

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