Depression, Anxiety Associated with Osteocalcin, Cortisol in Hyperparathyroidism

Mature woman with depression.
Anxiety and depression in people with hyperparathyroidism may be related to levels of 2 key hormones in the body, according to researchers.

Serum levels of both cortisol and osteocalcin may be associated with symptoms of anxiety and depression in patients with primary hyperparathyroidism, according to research results published in Frontiers in Endocrinology.

To date, the relationships between cortisol changes and osteocalcin concentrations in primary hyperparathyroidism, as well as their relationships and psychological features in this patient population, have not been evaluated. To address this, researchers analyzed the potential interaction between these hormones and emotional health.

Psychological questionnaires were administered between August 2020 and December 2020 and obtained for 38 of 52 patients. Between 2011 and 2020, 192 patients — including the 38 with completed questionnaires — were evaluated retrospectively. Patients who met inclusion criteria were included in the current study.

Because only 38 patients received psychological evaluation, the researchers performed a sensitivity analysis between patients who took these tests and those who did not. Results indicated that there were no between-group differences in age, sex, disease duration, body weight or height, body mass index (BMI), systolic blood pressure, heart rate, bone mineral density (BMD), serum parathyroid hormone (PTH) concentration, vitamin D, albumin, glycated hemoglobin, and phosphorus. Serum calcium concentration, though, was higher in these patients.

Scores of the Short Form Survey (SF-36) mental components were 74.04±23.32 for social function, 72.74±18.71 for mental health, 57.76±22.17 for vitality, and 66.67 (range, 0-100) for role of emotion. State-Trait Anxiety Inventory-State (STAI-S) score was 35.43±11.56, STAI-Trait (T) score was 37.39±10.34, and Beck Depression Inventory (BDI) score was 5 (range, 0-46). Of the 38 patients who completed questionnaires, 50% with a STAI-S score of 32.2 or higher were in a state of anxiety, while 60.5% of those with a STAI-T score of 31.8 or greater had developing anxiety.

The investigators also evaluated the association between serum PTH, calcium, osteocalcin, and cortisol concentrations with psychological performance. Results of a bivariate model indicated that cortisol concentration at 8:00 was “significantly and negatively correlated” with social function. Serum osteocalcin concentration was also significantly and negatively correlated with BDI, while serum PTH and calcium were not correlated with any questionnaire scores. After controlling for age, sex, and disease duration, the cortisol correlation remained true.

Further adjustments for PTH, vitamin D, phosphorus, and calcium showed a continued significant and negative correlation with cortisol at 8:00 and social function score.

The researchers found that osteocalcin was associated with PTH and was marginally associated with calcium; cortisol was not associated with either of these parameters.

Further tests were conducted to see if the findings could be replicated in a larger sample size. The researchers evaluated relations between osteocalcin, cortisol, PTH, and calcium in a group of 192 patients with primary hyperparathyroidism. Mean age of this cohort was 52.7±13.8 years; 76.6% were women.

Results indicated that in terms of bone biochemical markers, serum concentrations of calcium, type I procollagen amino-terminal peptide (PINP), and collagen I telopeptide-b (b-CTX) were all increased, while phosphorus was significantly decreased. The percentage of patients in the upper tertile of osteocalcin concentration was also increased with an increase in PTH concentration, while serum vitamin D and BMD level each declined significantly.

When grouping patients by serum calcium concentration tertile, serum PTH, PINP, b-CTX, and the percentages of patients with upper tertile osteocalcin concentration were all significantly increased, while serum phosphorous and BMD were significantly decreased.

Results of a bivariate correlation model between serum PTH, osteocalcin, and cortisol concentration showed that serum PTH was both positively and significantly correlated with serum osteocalcin; after controlling for age, sex, and disease duration, the PTH correlation with serum osteocalcin concentration was still positive and significant.

Study limitations included the lack of comparison between postoperative and preoperative serum concentrations and psychological questionnaires, the small sample size, the potential for selection bias, and a lack of measurement of body water distribution in patients treated with water repletion.

“In this study, it was demonstrated that serum levels of [osteocalcin] and cortisol were independently associated with the development of psychological symptoms in [patients with primary hyperparathyroidism],” the researchers concluded. “More basic and clinical studies are needed to test and verify this observation.”


Wang S-M, He Y, Zhu M-T, et al. The associations of serum osteocalcin and cortisol levels with the psychological performance in primary hyperparathyroidism patients. Front Endocrinol. 2021;12:692722. doi:10.3389/fendo.2021.692722