Langenbecks Arch Surg (2007) 392:699702 DOI 10.

1007/s00423-007-0180-7

ORIGINAL ARTICLE

Intraoperative parathormone measurement from the internal jugular vein predicts post-thyroidectomy hypocalcaemia
Isaac M. Cranshaw & David Moss & Erica Whineray-Kelly & C. Richard Harman

Received: 9 October 2006 / Accepted: 16 February 2007 / Published online: 21 March 2007 # Springer-Verlag 2007

Abstract Background The most common significant complication of total thyroidectomy is hypoparathyroidism. Intraoperative prediction of which patients are likely to be affected would allow both intraoperative and postoperative interventions to be utilised in these patients. Selection of these patients is essential if we are to be successful at discharging total thyroidectomy patients on the first postoperative day. We investigated the utility of intraoperative parathormone measurement from the internal jugular vein at predicting postoperative hypocalcaemia. Materials and methods Prospective collection of data was done on 45 consecutive total thyroidectomy patients. Preoperative calcium, intraoperative parathormone and postoperative calcium and parathormone were collected. The accuracy of intraoperative parathormone in predicting those with postoperative hypocalcaemia was assessed. Results Intraoperative parathormone of less than 2 pmol l1 had a sensitivity of 100% and a specificity of 95% in predicting those with postoperative hypocalcaemia. An intraoperative sample less than 2 pmol l1 was a highly significant predictor (p<0.0001) of postoperative hypocalcaemia.

Conclusion Intraoperative assessment of parathormone is an accurate predictor of those patients who will become hypoparathyroid in the postoperative period. Intraoperative prediction allows for targeted autotransplantation of glands in those at risk and selected early institution of postoperative supplementation in these patients. Patients not identified as at risk can be safely discharged. Keywords Thyroidectomy . Hypocalcaemia . Parathormone

Introduction Thyroid surgery is a common surgical procedure with generally low morbidity [13]. Of the significant postoperative complications, hypoparathyroidism (temporary and permanent) is the most common [16]. Temporary hypoparathyroidism has been reported in up to 20% of patients and can lead to severe postoperative hypocalcaemia. Permanent hypoparathyroidism is less common at and is widely accepted to occur in less than 1% of cases [16]. The standard approach to diagnosis has been close postoperative monitoring of serum calcium, particularly in those patients known to be at greater risk of postoperative hypocalcaemia (recurrent goitre, retrosternal goitre, graves disease, associated neck dissection) [1, 57]. This requires prolonged postoperative stay to identify patients with hypoparathyroidism before the introduction of calcium and vitamin D supplementation for those affected. A further period of monitoring is then required to confirm return to a normocalcaemic state. Some units have a policy of routine autotransplantation and/or routine calcium and vitamin D supplementation. Routine autotransplantation has been associated with higher rates of temporary hypocalcaemia [810]. However, it has

Presented at the Annual Scientific Congress of the Royal Australasian College of Surgeons, Melbourne Australia, May 2005. I. M. Cranshaw : D. Moss : E. Whineray-Kelly : C. R. Harman Department of Surgery, Northshore Hospital, Takapuna, Auckland, New Zealand Present address: I. M. Cranshaw (*) 13 Ardmore Rd, Auckland 1011, New Zealand e-mail: izak@ihug.co.nz

DO00180; No of Pages

700 Table 1 Indication for total thyroidectomy Indication Multinodular goitre Papillary carcinoma Graves disease Follicular carcinoma Follicular adenoma Hashimotos Number (%) 26 (58) 7 (16) 7 (16) 3 (6) 1 (2) 1 (2)

Langenbecks Arch Surg (2007) 392:699702

been shown to be effective in reducing rates of permanent hypocalcaemia to close to zero [10, 11]. There have been reports that postoperative measures of parathormone (PTH) accurately predict subsequent hypocalcaemia in patients after thyroidectomy. These measurements were usually made on the day after surgery from peripheral veins [12, 13]. Selection of patients at risk for postoperative hypoparathyroidism is essential if we are to successfully discharge total thyroidectomy patients on the first postoperative day. Identification of these patients during surgery would allow for techniques such as autotransplantation of parathyroid tissue to be more effectively targeted and for early implementation of calcium supplements to allow early discharge. The utility of PTH levels taken intraoperatively has been reported previously [14, 15]. A study from Lo et al. [15] showed that a fall in PTH measured with a quick PTH analyser in the theatre was accurate in predicting those patients who required postoperative calcium replacement. They predicted that patients with a percentage fall of greater than 75% subsequently became significantly hypocalcaemic and required supplementation. We designed this study to assess whether intraoperative assessment of PTH from the internal jugular vein (IPTHIJV) would predict postoperative hypoparathyroidism and therefore allow intraoperative intervention as well as the institution of targeted postoperative treatment of hypoparathyroidism. We chose the internal jugular vein (IJV) because it is easily accessible at the time of thyroid surgery, and the parathyroid glands drain directly into it.

Serum calcium was measured at the preoperative check and on the first postoperative day and at the 2-week postoperative clinic visit. PTH was taken from the IJV before resection of the gland commencing when and 5 min after resection was completed. A peripheral PTH was taken on the first postoperative day. PTH was measured using an Advia Centaur TM biochemical analyser. The intact PTH assay is a two-site sandwich chemiluminescence assay that takes 21 min to perform and costs NZ$18 (10). Patients were deemed to be hypoparathyroid on the basis of day 1 calcium less than 2.00 mmol/l or if they were symptomatic (peripheral parasthesia, positive Chvosteks sign, carpopedal spasm). Patients with these criteria were commenced on calcium and vitamin D replacement and were monitored with serial outpatient calcium measures. Statistical analysis was performed using Graphpad Insite software and p values were calculated according to Fishers exact test.

Results The indications for thyroidectomy in the study patients are shown in Table 1. The majority of our patients had multinodular goitre (58%), with papillary carcinoma (16%) and Graves disease (16%) also being common pathologies. The median time for a result from the time the blood was taken from the internal jugular for the post-thyroidectomy result was 34 min. This included a fixed test time of 21 min and a median transport time of 13 min. Times ranged from 24 to 65 min. Of the 44 patients included in the analysis, seven had an IPTHIJV level <2.0 pmol l1. These were considered as positive tests for the purpose of analysis, and rates of hypocalcaemia postoperatively were compared between this group and those with an IPTHIJV of 2 pmol l1 or greater. Of the seven patients with IPTHIJV <2 pmolL1, five had subsequent postoperative hypocalcaemia and required supplementation. Three patients had glands autotransplanted due to a combination of low IPTHIJV and a visibly ischaemic gland. All these patients required temporary replacement from between 2 and 8 weeks. All of these patients eventually had supplementation successfully with-

Materials and methods Forty-five consecutive patients were included in the study protocol from July 2002 to November 2003. Patients were deemed eligible if they were presenting for total thyroidectomy, completion thyroidectomy or treatment of recurrent goitre. One patient was excluded from the trial, as she was already hypoparathyroid and receiving calcium supplementation after a previous thyroid surgery.
Table 2 Rates of postoperative hypocalcaemia by IPTHIJV value IPTHIJV value IPTHIJV <2 pmol l1 IPTHIJV 2 pmol l1 + Postoperative hypocalcaemia 5/7 0/37 Percentage p value

71 0

<0.0001

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drawn. Of the 37 patients with IPTHIJV of 2 pmolL1 or greater, none developed postoperative hypocalcaemia. These results are summarised in Table 2. Analysis shows that a IPTHIJV <2 pmol l1 predicts postoperative hypocalcaemia requiring treatment (p < 0.0001) with a sensitivity of 100% and a specificity of 95%. Importantly, the negative predictive value is 100%, indicating that no cases of postoperative hypocalcaemia were missed.

Discussion As postoperative hypocalcaemia is a common and troubling complication of total thyroidectomy, there are advantages to the thyroid surgeon in being able to predict accurately those patients who will suffer from it. With a move to shorter postoperative stays in most units for total thyroidectomy patients, the ability to identify those patients who require calcium supplementation at the time of surgery allows their treatment to be started on the same day. This will stop the inevitable drop in calcium during the first 48 h post-surgery and allow these patients to be discharged home the day after surgery rather than remaining in hospital for their calcium levels to return to normal. More importantly, the majority of patients who will not develop hypocalcaemia can be accurately predicted and safely discharged without serial calcium testing and without unnecessary calcium supplementation. Our study has found that using a level of 2 pmol l1 was very accurate at predicting those patients who were able to be discharged early; however, this level may vary between units due to differences in the type of analysis and should be validated for individual units. Of the seven patients with PTH less than this cutoff, five required supplementation, but two were normocalcaemic on the first postoperative day and did not go on to require any supplementation. We assume that their glands regained normal function within the first 24 h. The strength of this type of test is to accurately identify those patients who do not require intervention and can be safely discharged without further tests. An intraoperative test offers an advantage over early postoperative PTH measurement in that it allows identification of those patients at risk of postoperative hypocalcaemia whilst they are still in the theatre. This allows targeted autotransplantation of ischaemic glands for those patients at risk of postoperative hypocalcaemia (as was performed in three cases), thereby reducing their risk of permanent hypoparathyroidism [11]. More importantly, in addition, those patients who have an adequate level of PTH on intraoperative measure would not be subjected to unnecessary gland autotransplantation and its inherent increased risk of temporary postoperative hypocalcaemia.

We believe that the introduction of a routine intraoperative measure of parathyroid hormone will decrease the number of postoperative investigations and allow for shorter inpatient hospital stays. Our technique does not require investment in an expensive dedicated quick PTH analyser, so it is suited to smaller units where this degree of capital expenditure cannot be justified for a relatively small number of cases. We intend to implement a single postresection IPTHIJV sample as a predictor of postoperative hypocalcaemia in our unit. This will be the subject of further prospective data collection and analysis of cost effectiveness and accuracy outcomes. In conclusion, intraoperative assessment of PTH is an accurate predictor of those total thyroidectomy patients who will become significantly hypoparathyroid in the postoperative period. Intraoperative prediction allows for targeted autotransplantation of glands in those at risk and early institution of postoperative supplementation in these patients. This technique allows the thyroid surgeon to confidently predict those who will develop postoperative hypocalcaemia and those who can be safely discharged without further treatment or investigation.

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