Low postoperative levels of intact parathyroid hormone (IPTH), female sex and the presence of malignant neoplasm appear to predict hypocalcemia after total thyroidectomy, according to a new study published in JAMA Otolaryngology–Head & Neck Surgery.1
The researchers sought to improve consistent identification of patients who are at risk for developing hypocalcemia. This will allow surgeons to confidently select which patients can undergo these procedures on an outpatient or short-stay basis, and which need calcium supplementation therapy and inpatient observation, they wrote.
This retrospective study examined medical records of 304 patients who underwent total thyroidectomy with or without central neck dissection between February 1, 2010 and November 30, 2012.
Mild postoperative hypocalcemia, defined as at least one postoperative serum calcium level of less than 8.4 mg/dL but not value less than 8.0 mg/dL, occurred in 68 patients (22.4%). Significant postoperative hypocalcemia, defined as a postoperative serum calcium level of less than 8.0 mg/dL or developing hypocalcemia-related symptoms, occurred in 91 patients (29.9%).
Significant hypocalcemia was associated with postoperative IPTH level (P<.001). Male patients had less risk for developing mild (odds ratio [OR]=0.37; 95% CI, 0.16-0.85) or significant (OR=0.57; 95% CI, 0.09-0.78) hypocalcemia, according to multivariate analysis.
The risk for developing significant hypocalcemia was decreased by 43% with each 10-pg/mL increase in postoperative IPTH level (P<.001). Also, each 10-pg/mL increase in postoperative IPTH level resulted in an 18% decreased risk for hospitalization beyond 24 hours (P=.03).
The risk for mild hypocalcemia increased by 27% in the presence of malignant neoplasm (P=.02). For each parathyroid gland inadvertently resected or autotransplanted, the risk for lower IPTH levels progressively increased.
Male sex and African American race were independent predictors of higher IPTH levels, according to the study results.
The researchers also developed a clinical algorithm for determining which patients are at risk for hypocalcemia. In the algorithm, low-risk patients are males with IPTH ≥20 pg/mL or females with IPTH ≥30 pg/mL who have no obvious parathyroid glands removed. These low-risk patients were considered safe to discharge on the same day.
The algorithm defines intermediate-risk male patients as those with IPTH levels <20 pg/mL, while intermediate-risk female patients have IPTH levels <30 pg/mL and/or one to two parathyroid glands removed and/or a thyroid malignant neoplasm. For these patients, calcium levels should be monitored every 6 to 8 hours and their treatment should be determined based on whether the calcium slope is positive or negative.
High-risk patients were defined as males with IPTH levels of less than 10 pg/mL or females with IPTH levels of ≤20 pg/mL and/or more than two parathyroid glands removed. If these patients have no symptoms, they should receive oral calcium and calcitriol supplementation. If they have symptoms, then they should receive intravenous calcium or oral calcium and calcitriol supplementation, depending on clinical findings. Their calcium level should also be monitored every 6 to 8 hours to determine further treatment.
The authors urged clinicians to consider sex, postoperative IPTH levels and the indication for thyroidectomy when seeking to stratify patients.
The importance of this study lies primarily in the realm of health economics, as the authors sought to incorporate pre- or postoperative factors into an algorithm to stratify patients into risk categories for early hypocalcemia after total thyroidectomy. The key factors identified did not include postop vitamin D, but the authors did not explore if ultra-low 25-hydoxy vitamin D, say <15 nmol/L, might predispose a patient to hypocalcemia.
A big difference exists between “discharge from specialist unit” and “discharge into the community.” Many of the factors affecting the latter may be out of the control of hospitalists. So it remains unclear just how transferable these data will be to other clinical circumstances, particularly in the context of older, more frail patients with comorbidities.
Moreover, a key omission from the dataset relates to patients undergoing completion thyroidectomy following cancer diagnosis in histology of unilateral thyroid lobectomy. This would have been of great interest.
It is also striking that 44 of 304 (14.5%) cases underwent total thyroidectomy for non-standard indications (thyroid nodule and Hashimoto’s thyroiditis).
So for medical- or community-based thyroidologists/physicians, possibly the most important lesson is that the best way to minimize hypocalcemia (and other) risk is not just to ensure that the procedure is done by a high-volume surgeon, supported by an excellent team, but also that to ensure that total thyroidectomy is only undertaken for a recognized indication.
It remains to be addressed whether careful preop patient preparation (e.g., ensure vitamin D levels are above 50 nmol/L and avoid ubiquitous magnesium-wasting agents such as diuretics and proton pump inhibitors in the lead-up to surgery) could make a meaningful dent in the fairly high rates of hypocalcaemia observed in this study.
Richard Quinton, MD
Endocrinology & Metabolism Service
Newcastle upon-Tyne Hospitals & University
University of Colorado School of Medicine