Abstract
Background:
Hyperparathyroidism (HPT) occurs in about 1% of the general population. Previous studies have suggested that the incidence is higher in those patients with thyroid disease who are undergoing thyroid surgery. The study purpose was to examine the incidence of concomitant HPT in patients already undergoing a thyroid procedure and to identify risk factors.
Materials and Methods:
A prospective database of all patients who had thyroidectomy by the endocrine surgery team was reviewed between August 2012 and April 2020. Per institutional protocol, all patients having thyroid surgery were screened for concomitant hyperparathyroidism. ANOVA/T-Test and Chi-square were conducted to compare those with and without hyperparathyroidism.
Results:
The median age was 43 and 79% were female. Of the 481 patients undergoing thyroidectomy, 31 (6%) had HPT. The mean pre-operative calcium and parathyroid hormone levels were 10±0 mg/dL and 67±5 pg/mL, respectively. When comparing the groups, patients with concomitant HPT were older (53±4 vs. 42±1 years, p=0.005). African American race was a significant risk factor for concomitant HPT. While African Americans represented only 29% of those undergoing surgery, 58% of those with concomitant HPT were African American (p=0.007).
Conclusion:
In patients having thyroid surgery, concomitant HPT was present in 6% of the population, higher than estimated general population prevalence. While we understand that primary HPT incidence increases with age, to our knowledge, this is the first report to document that African Americans are at a higher risk for concomitant HPT with thyroid disease. Thus, routine screening for hyperparathyroidism in patients undergoing thyroid surgery, especially in vulnerable populations, such as the older and African American population, is beneficial.
Keywords: concomitant hyperparathyroidism, African American, age, thyroid surgery
INTRODUCTION:
Primary hyperparathyroidism is defined as a condition that stems from excessive activity of one or more parathyroid glands, thus creating more parathyroid hormone (PTH) and subsequently increasing calcium and lowering phosphorus blood levels1,2,3. Currently, primary hyperparathyroidism (PHPT) is a hormonal disorder whose prevalence is approximately 1–2% in the United States of America, and since surgery remains the most cost-effective long-term strategy, the majority of these patients are referred for surgery,5,6. Thyroid nodular disease is frequently associated with PHPT, occurring in 22%– 70% of such patients7,8,9. Prior research has stated the incidence of concomitant hyperparathyroidism in patients with thyroid disease requiring surgery to be 5%10. The incidence of PHPT increases with age and is higher in women and African Americans than in men and other racial groups, respectively11. Thus, by analyzing age, gender, and race as possible risk factors in concomitant hyperparathyroidism patients undergoing thyroid surgery, we look to gain a better understanding of this specific population. The aim of this study was to characterize the thyroidectomy patient population with concomitant hyperparathyroidism by finding its incidence and associated risk factors.
MATERIALS AND METHODS:
A prospective database of all patients who had a thyroid operation (completion thyroidectomy, thyroid lobectomy, or total thyroidectomy) between August 2012 and April 2020 at the University of Alabama at Birmingham was reviewed. Per institutional protocol, all patients having thyroid surgery were screened for concomitant hyperparathyroidism, defined as elevated calcium (>10.4 mg/dL) and PTH (>75 pg/mL) and/or normocalcemic patients with inappropriately normal or elevated PTH levels. The screening laboratories were ordered pre-operatively by the surgical team as part of the surgical laboratories, such included calcium, PTH, and phosphorus levels. Patients diagnosed with hyperparathyroidism underwent a parathyroidectomy simultaneous with their thyroid operation. Patient demographics, pre-operative calcium, PTH, Creatinine, Thyroid Stimulating Hormone (TSH), and Free T4 levels (FT4), and pathology were reviewed. ANOVA/T-Test and Chi-square were performed using Microsoft® Excel® and IBM® SPSS® software. Results were reported as mean ± standard error of the mean, and values of p<0.05 were considered significant. This was a retrospective cohort study that received IRB approval for waiver of consent.
RESULTS:
Patient demographics
The median age was 43 and 79% were female. Of the 481 patients undergoing thyroidectomy, 31 (6%) had hyperparathyroidism. When comparing the groups, patients with concomitant hyperparathyroidism were older (53±4 vs. 42±1 years, p=0.005). (Table 1) Importantly, African American race was a significant risk factor for concomitant hyperparathyroidism. While African Americans were only 29% of patients having thyroid surgery, 58% of those with concomitant hyperparathyroidism were African American (p=0.007).
Table 1.
Demographics of the population studied.
| Demographics | HPT | No HPT | Total | p-value |
|---|---|---|---|---|
| N | 31 | 450 | 481 | |
| Race | 0.007 | |||
| American Indian | 0% | 0.2% | 0.2% | |
| Asian | 3% | 1% | 1% | |
| Black / African American | 58% | 27% | 29% | |
| White / Caucasian | 39% | 59% | 57% | |
| Hispanic | 0% | 2% | 2% | |
| Age (years; at time of surgery) | 0.005 | |||
| Median | 59 | 42 | 43 | |
| Std. Error of Mean | 3.5 | 0.9 | 0.9 | |
| Minimum | 11 | 6 | 6 | |
| Maximum | 76 | 86 | 86 | |
| Gender | 0.458 | |||
| Female | 84% | 78% | 79% | |
| Male | 16% | 22% | 21% |
Abbreviations: HPT = Hyperparathyroidism, No HPT = No Hyperparathyroidism
Laboratory Values
The mean pre-operative calcium and parathyroid hormone levels were 10±0 mg/dL (normal <10.4 mg/dL) and 67±5 pg/mL, respectively. (Table 2) Patients with concomitant hyperparathyroidism had higher mean pre-operative calcium than patients without hyperparathyroidism (p=0.000), 10.4±0.1 versus 9.6±0.0 mg/dL. The same phenomenon was observed for mean pre-operative PTH levels (p=0.000), 214.0±58.7 for concomitant hyperparathyroidism patients compared with patients lacking concomitant hyperparathyroidism 54.9±2.0 pg/mL. Also, mean pre-operative creatinine levels were higher (p=0.000) in concomitant hyperparathyroidism patients than in patients without it, 1.13±0.2 and 0.76±0.0 mg/dL, respectively. There was no significance found for the mean pre-operative TSH and FT4 levels in between the groups analyzed (p=0.38 and p=0.61, respectively).
Table 2.
Pre-operative laboratory values.
| Pre-op Lab Values | HPT | No HPT | p-value |
|---|---|---|---|
| Calcium (mg/dL) | 0.0000 | ||
| Mean | 10.4 | 9.6 | |
| Std. Error of Mean | 0.13 | 0.02 | |
| Parathyroid Hormone (pg/mL) | 0.0000 | ||
| Mean | 214.0 | 54.9 | |
| Std. Error of Mean | 58.7 | 2.0 | |
| Creatinine (mg/dL) | 0.0000 | ||
| Mean | 1.1 | 0.8 | |
| Std. Error of Mean | 0.2 | 0.02 | |
| Thyroid Stimulating Hormone (mU/L) | 0.378 | ||
| Mean | 1.6 | 2.5 | |
| Std. Error of Mean | 0.2 | 0.3 | |
| Free T4 (ng/dL) | 0.605 | ||
| Mean | 1.1 | 1.7 | |
| Std. Error of Mean | 0.2 | 0.3 |
Abbreviations: HPT = Hyperparathyroidism, No HPT = No Hyperparathyroidism
Thyroid pathology
In terms of thyroid pathology, Graves’ disease was much less prevalent in patients with concomitant hyperparathyroidism versus those with other surgical indications (p=0.05). Medullary Thyroid Cancer (MTC) presented a higher prevalence in patients with concomitant hyperparathyroidism versus those without hyperparathyroidism (p=0.01). Papillary Thyroid Cancer was the only pathology found statistically significant in between ethnicities, Caucasians (22%) versus the AA (11.7%) population (p=0.012).
DISCUSSION:
Hyperparathyroidism and thyroid disease are very common6,12,13. This study’s findings centered around the identification of advanced age and African American race as risk factors for patients undergoing thyroid surgery with concomitant hyperparathyroidism. In addition, the incidence of concomitant hyperparathyroidism in patients undergoing thyroidectomy was found to be higher than accepted rates within the general population. Understanding this phenomenon should lead the surgical team to not only screen for concomitant PHPT in these patients, but also to have heightened suspicion in those of older age and African American race.
Not surprisingly, a study of multiple endocrine neoplasia type 2A patients revealed a 35% rate of hyperparathyroidism in those that had MTC, where PHPT is an associated disease process14,15. As is substantiated with the higher prevalence of MTC in concomitant hyperparathyroidism patients found in our study. However, other studies have looked at the association of concomitant HPT in patients with other thyroid pathologies. Literature states that primary hyperparathyroidism rarely coexists with Grave’s disease16. Nevertheless, several cases have also reported the simultaneous occurrence of primary hyperparathyroidism and Grave’s disease16, 17, 18. This discrepancy in the literature is yet to be clarified as our findings indicated less prevalence of Graves pathology coexisting with concomitant hyperparathyroidism. This highlights the importance of screening for PHPT in the workup of thyroid pathologies.
Previous research about primary hyperparathyroidism has already revealed gender discrepancies, where females are disproportionately affected, and our findings support this. A previous study found the incidence of primary hyperparathyroidism to be highest among African Americans. The same study stated that racial differences with respect to the incidence of primary hyperparathyroidism seemed to become more pronounced among older patients11. These findings substantiate the fact that there is a higher incidence of primary hyperparathyroidism found in older patients and in African Americans, however our study focused on concomitant hyperparathyroidism in patients undergoing thyroid surgery in order to fill the information gap for this population. A number of previous studies have already presented primary hyperparathyroidism as having a higher incidence in older patients19, 20. Other studies have also found that African American patients with primary hyperparathyroidism present with more severe disease, thus studying this ethnic group was pertinent and especially in the population we chose to analyze.
Some limitations of the study presented include that all patients were from a single institution, thus showing possible selection bias. Also, the data collection was done retrospectively, limiting the conclusion’s representation of the general population. For determination of the extent to which our results can be generalized, we recommend replication of this work at other institutions.
CONCLUSION:
In patients having thyroid surgery, concomitant hyperparathyroidism was present in 6% of the population, higher than that reported in the general population. To our knowledge, this is the first report to document that African Americans are at a higher risk for concomitant hyperparathyroidism. Older age also presents as a risk factor for concomitant hyperparathyroidism. Thus, routine screening for hyperparathyroidism in patients undergoing thyroid surgery is especially in vulnerable populations, such as the older and African American population, beneficial.
HIGHLIGHTS:
Incidence of concomitant hyperparathyroidism in patients having thyroid surgery is 6%
African Americans and older thyroidectomy patients are at a higher risk of developing concomitant hyperparathyroidism
Monitoring hyperparathyroidism in at risk populations will enhance patient quality care
ACKNOWLEDGEMENTS:
DISCLOSURES:
This study was supported by the National Institutes of Health [T35DK116670].
Footnotes
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