Abstract
The goal of this study was to examine healthcare burden, hospitalizations, mortality, and healthcare cost utilization from hyperthyroidism to further our understanding of the effect of changes in thyroid disease management over the past decade. This was a retrospective longitudinal trends study involving hospitalizations for hyperthyroidism in the US from 2008 to 2018. We trended crude hospitalization rate, estimated incidence of hospitalizations, trends in inpatient mortality rate, mean length of hospital stay, and mean total hospital cost of patients with hyperthyroidism. The number of hyperthyroid hospitalizations decreased from 12,689 in 2008 to 9110 in 2018 (28.2%) (P trend <0.001), with a decrease of crude hospitalization rate from 33 to 25 per 100,000 hospitalizations. The estimated incidence rate of hospitalization in patients with hyperthyroidism decreased from 441 to 288 per 100,000 adults with hyperthyroidism. There was, however, no difference in adjusted mortality in hospitalizations over the study period. Although there has been a significant reduction in hospitalizations due to hyperthyroidism in the US, there has been no significant change in mortality during hospitalizations. This may represent improving outpatient management of hyperthyroidism. However, this improvement has not translated to outcomes in the hospital setting.
Keywords: Hospitalizations, hyperthyroidism, mortality
The prevalence of hyperthyroidism in the United States is estimated to be 1.2% to 1.3%.1,2 Hyperthyroidism is a broad diagnosis that can be divided into subgroups based on etiology. The etiology may be based on the degree of radioiodine uptake. Another classification includes conditions with little or no uptake, indicating the release of preformed hormone secondary to inflammation or destruction of the thyroid gland.3–5 There is limited literature on patients who are hospitalized due to hyperthyroidism. Patients are usually hospitalized due to dysfunction of other organ systems associated with hyperthyroidism, including cardiac complications.1,6 There is also limited literature on the longitudinal trends in hyperthyroidism prevalence and outcomes. This study analyzed the prevalence and outcomes of hospitalizations due to hyperthyroidism over the last decade to provide epidemiologic information regarding the impact of recent changes in healthcare policies and provisions for this group.
METHODS
This was a retrospective longitudinal trends study involving hospitalizations for hyperthyroidism in the US from 2008 to 2018. Data were sourced from the Nationwide Inpatient Sample (NIS) for the studied years. The NIS is an all-payer database of hospital inpatient stays derived from billing data submitted by hospitals to statewide data organizations across the US, covering more than 97% of the US population.7 This dataset is weighted to obtain US national estimates.8 Databases before 2016 were coded using the International Classification of Diseases, Ninth Revision, Clinical Modification/Procedure Coding System (ICD-9-CM/PCS). Databases from 2016 were coded using the ICD-10-CM/PCS. We obtained total adult hospitalizations from the NIS databases. The US population estimates were obtained from the US Census Bureau Population Division.9,10
The study included NIS 2008, 2010, 2012, 2014, 2016, and 2018 databases. We searched for hospitalizations with a principal discharge diagnosis of hyperthyroidism using ICD codes 242.X and E05.X. We excluded hospitalizations involving patients <18 years and elective hospitalizations. The NIS includes variables on patient demographics, including age, sex, race, median household income by income quartiles, and primary payer. It also contains hospital-specific variables including bed size, teaching status, and location. We assessed the comorbidity burden using Sundararajan’s adaptation of the modified Deyo’s Charlson Comorbidity Index (CCI). This modification groups CCI into four groups based on increasing risk for mortality. It has been adapted to population-based research. A score of >3 has about a 25% 10-year mortality, while a score of 2 or 1 has a 10% and 4% 10-year mortality, respectively. This cutoff point was chosen as a means of assessment of the increased risk of mortality.11
We highlighted the biodemographic trends over time of hyperthyroidism hospitalizations. We calculated the crude hospitalization rate for hyperthyroidism per 100,000 hospitalizations, and the incidence of hyperthyroidism hospitalizations per 100,000 adult population with hyperthyroidism during each calendar year. We analyzed trends in hospital mortality rate, mean length of hospital stay, and mean total hospital cost using multivariate logistic trend analysis. We also obtained mean total hospital cost using the Healthcare Cost and Utilization Project cost-to-charge ratio files and adjusted for inflation using the Medical Expenditure Panel Survey index for hospital care, with 2018 as the reference point.12,13
Stata® Version 16 software (StataCorp, College Station, TX) was used for data analysis. The prevalence of hyperthyroidism hospitalizations was calculated following NIS methodology for disease incidence and prevalence.14 The crude hospitalization rate was calculated by dividing total hyperthyroidism hospitalizations by total hospitalizations for each calendar year studied and expressed per 100,000 hospitalizations. The incidence of hyperthyroidism hospitalizations per 100,000 population with hyperthyroidism was obtained by dividing the total number of hyperthyroidism hospitalizations by the estimated total US adult population with hyperthyroidism. The estimated adult population was obtained by calculating 1.25% of the US adult population according to prevalence obtained from a literature review.1,2 We used multivariate regression analysis to calculate the odds of trend in mortality, length of stay, and total hospital cost following adjustment for age, sex, race, grouped CCI, insurance type, mean household income, and hospital characteristics.
The NIS database lacks patient and hospital level identifiers. This study, therefore, did not require Cook County Health institutional review board approval. The NIS is publicly available and can be obtained from a central distributor.
RESULTS
Overall, the number of hyperthyroid hospitalizations decreased from 12,689 in 2008 to 9110 in 2018 (28.2%) (P trend <0.001) (Table 1, Figure 1). The crude hospitalization rate decreased from 33 to 25 per 100,000 adult hospitalizations over the study period. There was also a significant decrease in the estimated incidence of hyperthyroidism hospitalizations from 441 to 288 per 100,000 adults with hyperthyroidism. The mean age over the period ranged from 47.1 to 49.7 years. Most of the hospitalizations involved women and whites. Over the decade, a rising trend in the proportion of patients with a Charlson index >1 was observed. There was a trend toward an increasing use of Medicaid as the primary payer. There was no statistically significant change in adjusted inpatient mortality in patients admitted for hyperthyroidism over the study period (P trend = 0.73). In addition, there were no statistically significant changes in length of stay or total hospital cost over the decade (Table 2, Figure 2).
Table 1.
Biodemographic characteristics of hospitalizations for hyperthyroidism
| Variables | 2008 | 2010 | 2012 | 2014 | 2016 | 2018 |
|---|---|---|---|---|---|---|
| Total hospitalizations | 12,689 | 12,224 | 11,165 | 9500 | 9010 | 9110 |
| Crude rate* | 33 | 32 | 31 | 27 | 25 | 25 |
| HTX hospitalization incidence | 441 | 417 | 376 | 311 | 289 | 288 |
| Mean age ± SE (years) | 49.7 ± 0.5 | 48.3 ± 0.5 | 48.2 ± 0.4 | 47.8 ± 0.4 | 47.1 ± 0.4 | 48.3 ± 0.4 |
| Women | 76.7% | 79.0% | 77.5% | 75.8% | 76.3% | 74.9% |
| Racial distribution | ||||||
| White | 44.4% | 43.0% | 48.1% | 44.8% | 41.4% | 41.3% |
| Black | 19.6% | 26.2% | 25.1% | 28.8% | 31.6% | 31.3% |
| Hispanic | 9.7% | 13.2% | 13.1% | 13.9% | 14.2% | 14.7% |
| Others | 26.3% | 17.5% | 13.7% | 12.5% | 12.8% | 12.7% |
| Charlson Comorbidity Index score | ||||||
| 0 | 61.4% | 60.9% | 60.9% | 59.1% | 54.5% | 50.4% |
| 1 | 25.5% | 24.9% | 23.9% | 25.9% | 25.0% | 26.0% |
| 2 | 8.0% | 8.6% | 8.4% | 8.4% | 10.2% | 11.6% |
| ≥3 | 5.1% | 5.6% | 6.8% | 6.6% | 10.3% | 12.0% |
| Primary payer | ||||||
| Medicare | 17.2% | 22.7% | 21.3% | 29.0% | 31.8% | 29.5% |
| Medicaid | 25.6% | 23.6% | 25.3% | 25.0% | 23.1% | 26.3% |
| Private | 45.8% | 37.4% | 37.3% | 32.4% | 33.2% | 31.7% |
| Uninsured | 11.4% | 16.3% | 16.0% | 13.6% | 12.0% | 12.5% |
*Per 100,000 total yearly hospitalization.
HTX indicates hyperthyroidism; SE, standard error of mean.
Figure 1.
Trends in hyperthyroidism hospitalizations.
Table 2.
Outcomes for hospitalizations in patients with hyperthyroidism
| Outcome | 2008 | 2010 | 2012 | 2014 | 2016 | 2018 |
|---|---|---|---|---|---|---|
| Inpatient mortality | 0.43% | 0.62% | 0.45% | 0.58% | 0.22% | 0.77% |
| Mean length of stay (days) | 3.7 | 3.3 | 3.2 | 3.5 | 3.7 | 3.6 |
| Mean total hospital cost ($) | 9372 | 8828 | 8997 | 9112 | 9508 | 9481 |
Figure 2.
Healthcare cost utilization trend in hyperthyroidism hospitalizations.
DISCUSSION
We found that women are significantly more likely to be hospitalized for hyperthyroidism. This is expected due to the higher prevalence of hyperthyroidism in women. Younger women are more likely to have Graves’ disease, and older women are more likely to have toxic nodular goiter.2,5 The percentage of the US population with antithyroid antibodies increased each decade in women but did not significantly increase in men after the fourth decade of life.2
Over the past 10 years, there has been a significant increase in patients hospitalized for hyperthyroidism with a CCI score >1. This shows a trend toward an increasing comorbid burden in patients with hyperthyroidism. The risk of mortality increases with comorbid conditions like concurrent heart failure, where patients who have abnormal thyroid function can have a 60% higher risk of mortality.15–17 Osuna et al found that about 55% to 75% of patients who had new-onset atrial fibrillation secondary to hyperthyroidism would have spontaneous resolution after their thyroid hormone levels were controlled.6 Hyperthyroidism can cause an increase in systolic blood pressure and hypertension18 and also affects other organs, leading to its known association with other comorbid diseases. Hyperthyroidism can cause increased ventilatory drive and decreased maximal inspiratory and expiratory pressures. Hyperthyroidism may lead to pulmonary hypertension.19–21 Hyperthyroidism-induced neuropsychiatric complications including encephalopathy are also a common precipitant of hospitalization, especially in elderly patients with hyperthyroidism. The rise in comorbidities among patients with hyperthyroidism, however, did not result in a significant change in hospital mortality, likely from improved medical management of conditions like heart failure and atrial fibrillation, with literature demonstrating decreased mortality in patients with these conditions.22–24
There was a decrease in the crude hospitalization rate as well as the estimated incidence rate for hospitalization in patients with hyperthyroidism. There are likely multiple factors for this apparent decrease in hospitalizations without a significant decrease in the overall frequency of hyperthyroidism. One of the primary factors is likely better outpatient management of hyperthyroidism, leading to a reduction in hospitalizations due to thyrotoxicosis and its complications.1 Before 2005, the most popular method for treatment of Graves’ disease in the US was radioactive iodine, whereas many other countries preferred antithyroid drugs for management.25,26 Patients treated with radioactive iodine or surgery are likely to become hypothyroid compared to patients who received pharmacotherapy. This may also account for declining hospitalizations in the US.
Patients hospitalized for hyperthyroidism tended to be insured by Medicaid. One contributing factor may be the expansion of Medicaid after the Affordable Care Act. Specifically, 37 states expanded eligibility to people up to 138% of the federal poverty line.27 On a similar note, a study found that patients’ median income was inversely correlated with the rate of hospitalization for complicated thyrotoxicosis.28 The literature relating hyperthyroidism treatment in the outpatient or inpatient setting to insurance type is sparse, but significant work has shown that low-income status and lack of insurance have a negative impact on health status.29 It is difficult to compare outcomes between insurance types due to substantial confounding variables, but it has been demonstrated that patients with private insurance have fewer emergency department visits and more office visits.30 More frequent office visits could help patients with hyperthyroidism manage their condition and reduce the probability that they get hospitalized for the condition. This fits with the trend that patients with a lower income were more likely to be hospitalized for hyperthyroidism and indicates that addressing healthcare disparities based on income or insurance could help reduce hospitalization rates for hyperthyroidism.
Our study had several limitations. Data from the NIS are subject to nonrandomization. We could not determine if hyperthyroidism was newly diagnosed or a chronic diagnosis during the hospitalization. The NIS reports information on hospitalizations rather than individual patients. The NIS also does not include information about antithyroid medications, thyroid function tests, antibody results, or radiologic results. We could not determine the clinical features resulting in hospitalization. The NIS also uses ICD-10 codes to report hospitalizations and therefore coding-related errors are possible.
In conclusion, although there has been a significant reduction in hospitalizations due to hyperthyroidism, there has been no significant change in mortality. Overall, the reduction in hospitalizations is a good sign for the future of hyperthyroid management, but more focus could be directed toward improving the morbidity and mortality of patients with hyperthyroidism during acute hospitalizations. This could lead to a reduction in mortality, which has been noted in hospitalizations for other medical conditions.
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