High Rate of Calcium-alkali Syndrome Linked to Post-surgery Hypoparathyroidism, Study Suggests

People with hypoparathyroidism after surgical removal of the thyroid may develop calcium-alkali syndrome (CAS) — particularly if they are given high doses of vitamin D as a part of post-surgical care, a new study suggests.

These findings highlight a need for routine surveillance of calcium levels following thyroid removal, the researchers said.

Titled “Calcium-Alkali Syndrome Associated with Hypoparathyroidism Following Total Thyroidectomy,” the study was published in the American Journal of Nephrology. 

The thyroid gland plays an important role in regulating calcium levels in the body. In people who develop hypoparathyroidism after thyroidectomy, or the surgical removal of the thyroid, calcium and active vitamin D supplements are often given to maintain calcium levels within a normal range.

However, use of these supplements can result in CAS, also called milk-alkali syndrome. This condition is characterized by the combination of hypercalcemia, or elevated blood calcium levels, alkalosis — which refers to a blood pH higher than normal, or alkaline — and damage to the kidneys.

Although the occurrence of CAS in people with post-thyroidectomy hypoparathyroidism is well-known, the frequency of the condition and its associated risk factors in this population remain unclear.

To learn more, the researchers followed 27 individuals (59.3% female, mean age 60.2 years) who underwent total thyroidectomy at St. Marianna University Hospital, in Japan, between 2010 and 2013.

The results showed that the highest calcium concentration in the blood occurred at a median of about 11 months (326 days, range 78–869 days). Almost half of the patients showed peak levels of calcium within one year following surgery.

At the time of peak calcium levels, 15 individuals (55.6%) had hypercalcemia, 19 (70.3%) had alkalosis, and 12 (44.4%) had kidney impairment. These conditions tended to co-occur. For example, a significantly greater percentage of people with, rather than without hypercalcemia also had alkalosis (86.7% vs. 50.0%) and kidney impairment (73.3% vs. 8.3%).

“Hypercalcemia developed very frequently in cases of postsurgical hypoparathyroidism after total thyroidectomy and could occur at any time,” the researchers said.

Patients with kidney impairment showed a greater frequency of preexisting chronic kidney disease (CKD) (66.7% vs. 20%) and hypercalcemia (91.7 vs. 26.7%) than those without renal dysfunction.

Nine participants (33%) had CAS, the study found. Compared with those who did not develop this condition, those with CAS were on significantly higher doses of active vitamin D supplement (alfacalcidol), had significantly greater degree of alkalosis, and demonstrated a greater decrease in kidney function.

Other clinical features, including body mass index, cancer type, dosage of calcium lactate, and use of nonsteroidal anti-inflammatory drugs did not differ significantly between those with or without CAS.

People who developed CAS tended to be older than those who did not (67.1 vs. 56.7 years), but this difference was not statistically significant

“Based on our findings, and the aspect of feasibility, we recommend that [blood calcium levels] should be measured every 2–3 months even after the regimen has been stabilized, especially in the elderly and those who have CKD and take high doses of active vitamin D,” the researchers said.

Yet, they added that as the number of patients was small, this single-center analysis “might not be representative of other patients with postsurgical hypoparathyroidism.” As such, future studies are needed to validate these results, the researchers said.