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Mortality in patients with permanent hypoparathyroidism after total thyroidectomy. BJS 2018; 105: 1313-1318.

Published: 17th April 2018

Authors: M. Almquist, K. Ivarsson, E. Nordenström, A. Bergenfelz

Background

Permanent hypoparathyroidism remains the most common adverse outcome after total thyroidectomy, but long‐term effects of hypoparathyroidism are unknown. The aim was to investigate mortality in patients with permanent hypoparathyroidism after total thyroidectomy.

Method

Data from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery were linked with the Swedish National Prescription Register for Pharmaceuticals and the Swedish National Inpatient Register. Patients who underwent total thyroidectomy between 1 July 2005 and 30 June 2014 for benign thyroid disease, and who used active vitamin D for at least 6 months after surgery, were classified as having permanent hypoparathyroidism and included in the study cohort. Risk of death was assessed using Cox regression analysis, adjusting for age, sex, thyrotoxicosis and co‐morbidity.

Results

There were 4899 patients, with a mean(s.d.) age of 46·3(15·8) years; 83·1 per cent were women, and 2932 patients (59·8 per cent) had thyrotoxicosis. In all, 246 patients (5·2 per cent) were classified as having permanent hypoparathyroidism. Mean(s.d.) follow‐up was 4·4(2·4) years, and 109 patients (2·2 per cent) died during follow‐up. Compared with patients without permanent hypoparathyroidism, the risk of death was significantly higher among patients with permanent hypoparathyroidism after total thyroidectomy (adjusted hazard ratio 2·09, 95 per cent c.i. 1·04 to 4·20).

Conclusion

Permanent hypoparathyroidism after total thyroidectomy for benign disease is common and associated with an increased risk of death.

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2 Comments

Karin Amrein

5 months ago

We read with interest the recent paper on mortality in patients with postoperative hypoparathyroidism (PH) including 109 deaths in a cohort of 4,899 thyroidectomy patients (1). The authors report a high rate of PH (n=246, 5%) besides a surprising 2-fold increase in mortality in patients with PH (unadjusted: 1.77; 95%CI: 0.90-3.51, adjusted: 2.09, 95%CI 1.04-4.20) in this study compared to patients who did not develop PH. These important findings suggest that PH is a frequent and serious complication after total thyroidectomy. Of note, patients with thyroid cancer were excluded.

We disagree with the paradox hypothesis that the increased mortality “might be related to the use of large, supraphysiological doses of active vitamin D“, as a recent analysis from the large Danish hypoparathyroidism cohort focusing on biochemical data found that a higher daily dose of activated vitamin D was associated with a lower mortality (OR 0.33; 95% CI, 0.17 to 0.64) (2). Importantly, factors that were associated with higher mortality included high phosphate levels, a high calcium-phosphate product, episodes of hypercalcemia and disease duration (2). Therefore, these factors should be analyzed in the present study. It would also be of interest to identify specific causes of death and we suggest analysis for renal disease (3). It appears reasonable that deficiency in a biologically important hormone such as PTH may come with risks including increased morbidity and mortality. The current disturbing results will certainly contribute to take PH more serious and improve the described “empathy gap“ (4).

Karin Amrein
Jens Bollerslev

Division of Endocrinology and Diabetology
Medical University of Graz
Graz
Austria
karin.amrein@yahoo.de

References:
1. Almquist M, Ivarsson K, Nordenstrom E, Bergenfelz A, (2018) Mortality in patients with permanent hypoparathyroidism after total thyroidectomy. Br J Surg
2. Underbjerg L, Sikjaer T, Rejnmark L, (2017) Long-Term Complications in Patients With Hypoparathyroidism Evaluated by Biochemical Findings: A Case-Control Study. J Bone Miner Res
3. Underbjerg L, Sikjaer T, Mosekilde L, Rejnmark L, (2013) Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study. J Bone Miner Res 28: 2277-2285.
4. Cho NL, Moalem J, Chen L, Lubitz CC, Moore FD, Jr., Ruan DT, (2014) Surgeons and patients disagree on the potential consequences from hypoparathyroidism. Endocr Pract 20: 427-446.

    Martin Almquist

    3 months ago

    We very much appreciate the interest by Drs Amrein and Bollerslev in our work on mortality in patients with postoperative hypoparathyroidism. We thank them for pointing out the results of a study that indicates that treatment with high dose of active vitamin D is associated with a lower risk of death. That study differs from our study in how patients were selected; in our study only thyroidectomised patients were included. This might perhaps explain the observed differences in risk.

    Drs Amrein and Bollerslev suggest that we include levels of calcium and phosphate, episodes of hypercalcemia and disease duration in our analysis. We have already accounted for disease duration in the Cox model. We believe inclusion of any hypercalcemic episodes and calcium/phosphate levels would indeed be valuable, but it is unfortunately impossible, since we do not have this information in our dataset. Furthermore, in Sweden, these patients are in clinical practice followed by different specialities (surgeons, endocrinologists, general practitioners, among others), with no predefined algorithm for follow-up. Collection of these data would require a manual search of the medical records of all 4899 patients with a high probability for a substantial number of missing data.

    We do intend to further explore potential explanations for the observed association between hypoparathyroidism and death, and as Drs Amrein and Bollerslev point out, it is possible that hypoparathyroidism is associated with increased risk of renal insufficiency.

    We believe that the Swedish Cause of Death Register is less reliable due to the low autopsy frequency. Therefore we refrained from using that data in the present analysis.

    We do agree that low PTH per se could explain the increased mortality that we observed, and this potential explanation has also been emphasised by us in the manuscript. We also agree that permanent hypoparathyroidism most likely is a much more serious complication of total thyroidectomy than previously thought. Therefore, it is important to keep this complication as low as possible, and it is our opinion that patients with permanent hypoparathyroidism should be cared for by a specialist in endocrinology.

    Martin Almquist
    martin.almquist@med.lu.se