Modeling the Relationship of Age With Hypocalcemia Following Total Thyroidectomy: A NSQIP Analysis

ABSTRACT

Objective

To characterize the relationship between age and hypocalcemia risk following total thyroidectomy and identify critical age‐related transition points across the lifespan.

Methods

The American College of Surgeons National Surgical Quality Improvement Program Thyroidectomy Targeted database was queried for 21,109 adult patients (18+) from 2016 to 2023 who underwent total thyroidectomy. Multivariate regressions utilizing age, sex, race/ethnicity, BMI, surgical specialty, ASA classification, and surgical indication were used to assess odds of hypocalcemia within 30 days of surgery. Additionally, age‐stratified analyses, generalized additive modeling (GAM), and segmented regression were used to assess odds of hypocalcemia.

Results

Age was independently associated with 2% decreased odds of hypocalcemia per year older (OR, 0.98; 95% CI, 0.98–0.99; p‐value < 0.001). GAM and systematic evaluation of 1,683,217 segmented regression models identified six key inflection points at ages 26, 35, 39, 51, 54, and 71, with hypocalcemia risk characterized by sharp changes at these transition points and gradual changes between them. Inflection points in early adulthood were the most consistent across models, while those in older age showed greater variability, suggesting increasing physiological heterogeneity with advancing age. Risk stabilized after age 65 with no significant differences between consecutive age groups.

Conclusion

Hypocalcemia risk following total thyroidectomy follows a nonlinear age‐dependent pattern with identifiable transitions, challenging simple continuous or categorical age modeling. Risk stabilizes after the mid‐sixties, though very elderly patients should not be assumed to have lower risk due to advanced age alone. These findings support development of age‐tailored risk stratification tools for more personalized perioperative calcium management.

Level of Evidence

4.

1. Introduction

Thyroid disorders are common, affecting over 12% of the US population over their lifetime and are diverse in classification, treatment, and outcomes [1]. In malignancies, initial treatment is typically surgical, though new medical therapies are emerging [2, 3]. In benign conditions, management options are more varied, including thyroidectomy, radioactive iodine, and radiofrequency ablation [4, 5, 6]. While thyroidectomy is the most definitive option for both benign and malignant conditions, there are surgical risks, one being hypocalcemia [7, 8, 9, 10].

Hypocalcemia commonly occurs following total thyroidectomy and can be transient or permanent [10, 11]. Transient hypocalcemia results from temporary parathyroid blood flow disruption, whereas permanent hypocalcemia arises following parathyroid destruction or removal [12, 13]. Rates of transient hypocalcemia are estimated at 20%–30%, and permanent hypocalcemia at 1%–3% [13, 14, 15, 16, 17, 18]. While permanent hypocalcemia receives more attention due to requiring lifelong supplementation, transient hypocalcemia affects more patients and presents similarly, with symptoms ranging from mild paresthesia and cramps to severe symptoms like seizures and heart failure [13, 19]. Therefore, identifying risk factors is essential.

Investigation into the role of demographic factors on hypocalcemia risk has revealed several trends. One notable factor often investigated is age, but the literature varies on age's effect with some reporting no effect, others claiming increasing age is protective, and others reporting increasing age as a risk factor [10, 16, 20, 21, 22, 23, 24, 25, 26]. Regardless, studies have rarely investigated age's effect beyond simple linear modeling or stratification at a single age‐of‐interest, leaving a gap as to whether age has a continuous effect or if risk varies across the lifespan [16, 23, 24, 25]. Considering the many known nuances of calcium homeostasis and parathyroid function across the lifespan, including shifts in bone mineral density, parathyroid hormone dynamics, and vitamin D metabolism, age's relationship with hypocalcemia risk is likely more complex than prior studies have captured [27, 28, 29, 30, 31, 32, 33, 34]. Therefore, this study aims to determine whether hypocalcemia risk changes consistently with age or varies at specific milestones, and we hypothesize that age plays a nonlinear, modifying role but that, overall, increasing age is protective.

2. Materials and Methods

This retrospective cohort study follows the STROBE reporting guideline. No institutional review board approval was needed as the database consists of publicly available deidentified data.

2.1. Database

This study utilized the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), a national database containing demographic variables, surgical characteristics, treatment modalities, and outcomes. NSQIP comprises hundreds of hospitals across the US, allowing for accurate demographic representation and improving generalizability. Participating hospitals, spanning academic, community, and ambulatory surgery centers, enroll surgical cases meeting standardized inclusion criteria, and data are abstracted directly from the medical record by trained Surgical Clinical Reviewers, with periodic inter‐rater reliability audits to ensure data quality. Sites select cases using a systematic 8‐day cycle process, giving each day of the week an equal chance of case inclusion. The Thyroidectomy Targeted participant use files from 2016–2023 were used for their thyroidectomy‐specific variables including primary indication, pathology, and hypocalcemia outcomes.

2.2. Characteristic and Outcome Definitions

NSQIP was queried for adults (18+) who underwent total thyroidectomy using Current Procedural Terminology (CPT) codes 60240 or 60271. Patients who underwent concurrent parathyroidectomy (CPT 60500 or 60502) were excluded.

Patients were categorized based on seven factors: age (continuous), sex (male as comparator, female as reference), race (Black or African American, Hispanic, Asian or Pacific Islander, and Other/Unknown as comparators, White as reference), BMI (Underweight, Overweight, and Obese as comparators, Normal Range as reference), surgical specialty (otolaryngology as comparator, non‐otolaryngology as reference), ASA classification (ASA 2, ASA 3, ASA 4/5 as comparators, ASA 1 as reference), surgical indication (Malignancy, Single Nodule, Multinodular Goiter, and Other Benign Indication as comparators, Graves' Disease (GD) as reference), and postoperative calcium and/or vitamin D replacement (oral, oral vitamin D, and both oral calcium and vitamin D as comparators, no replacement as reference). Patients were also stratified into age groups for further analysis to identify potential transition points where hypocalcemia risk may change more markedly.

Postoperative hypocalcemia was defined per NSQIP criteria as a patient being evaluated for, treated for, or described as having signs or symptoms of low serum calcium within 30 days of surgery. This included perioral or peripheral paresthesias, Chvostek or Trousseau sign, tetany, EKG changes, or clinical concern for hypocalcemia as the cause of presenting symptoms or signs. Importantly, routine postoperative supplementation was not considered treatment.

2.3. Statistical Analysis

Chi‐squared tests were performed to evaluate differences between those who did and did not experience hypocalcemia. Multivariate models were used to analyze relationships between the seven patient factors and hypocalcemia. Following initial analysis with age as a continuous variable, age‐stratified multivariate analyses were conducted with patients stratified into 5‐year age groups.

After the continuous and 5‐year group analyses, a two‐stage approach was used to identify critical age transitions across the lifespan. First, a generalized additive model (GAM) was fit across the full age range to explore potential nonlinear associations between age and hypocalcemia risk. The GAM allowed up to 10 knots to ensure sufficient flexibility in detecting candidate inflection points, identified by examining changes in slope and curvature of the fitted curve.

Combinations of candidate inflection points were then systematically evaluated in segmented regression models to determine the best‐fitting age parameterization. A maximum of 7 inflection points was used to balance thorough exploration with computational feasibility and clinical interpretability. Models were compared using the Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), which penalize excessive model complexity, ensuring only meaningful inflection points were retained. Log‐likelihood and pseudo‐R ² were examined as sensitivity measures, and candidate models were formally compared with a simple linear age model using likelihood ratio tests.

Using the inflection points from the best‐fitting model, linear, spline, and piecewise linear models were fit to visualize and interpret the relationship between age and hypocalcemia risk. Model fit was compared using AIC, likelihood ratio tests were used to compare spline and piecewise models with the linear model, and joint Wald tests assessed whether the identified inflection points in the piecewise model collectively improved model fit. Two‐sided p‐values were used for all tests with significance set at 0.05. Statistical analyses were performed using R version 4.5.1.

3. Results

A total of 21,109 adult patients were included. The most well represented groups were females (16,697, 79.1%), White patients (10,822, 51.3%), obese patients (10,481, 49.7%), general surgery patients (13,622, 64.5%), ASA 2 patients (11,491, 54.4%), patients with multinodular goiter as their indication (7843, 37.2%), and patients who received postoperative calcium and/or vitamin D (9442, 44.7%). Significant differences between those who did and did not experience postoperative hypocalcemia based on age, sex, race/ethnicity, BMI class (p = 0.003), surgical specialty, ASA classification (p = 0.048), indication for surgery, and postoperative replacement (p < 0.001 unless specified) (Table 1).

TABLE 1.

Patient characteristics stratified by hypocalcemia within 30 days.

Characteristic	No hypocalcemia, N = 19,173 (90.8%)	Hypocalcemia within 30 days, N = 1936 (9.2%)	p
Age	52.18 ± 15.17	47.30 ± 15.07	< 0.001
Sex			< 0.001
Female	15,029 (90.0%)	1668 (10.0%)
Male	4144 (93.9%)	268 (6.1%)
Race/Ethnicity			< 0.001
White	9903 (91.5%)	919 (8.5%)
Black	3408 (92.8%)	263 (7.2%)
Hispanic	1488 (88.5%)	193 (11.5%)
Asian or Pacific Islander	1211 (90.6%)	125 (9.4%)
Unknown/Other	3163 (87.9%)	436 (12.1%)
BMI Class			0.003
Normal Range	3944 (89.6%)	459 (10.4%)
Underweight	183 (87.6%)	26 (12.4%)
Overweight	5496 (91.4%)	520 (8.6%)
Obese	9550 (91.1%)	931 (8.9%)
Surgical Specialty			< 0.001
Otolaryngology	6690 (89.4%)	797 (10.6%)
Non‐Otolaryngology	12,483 (91.6%)	1139 (8.4%)
ASA Classification			0.048
ASA 1	553 (87.9%)	76 (12.1%)
ASA 2	10,422 (90.7%)	1069 (9.3%)
ASA 3	7698 (91.3%)	732 (8.7%)
ASA 4	453 (89.6%)	53 (10.4%)
ASA 5	1 (100.0%)	0 (0.0%)
ASA Unknown	46 (88.5%)	6 (11.5%)
Indication for Surgery			< 0.001
Graves' Disease	3192 (87.4%)	461 (12.6%)
Malignancy	6381 (90.2%)	692 (9.8%)
Single Nodule	1969 (92.8%)	154 (7.2%)
Multinodular Goiter	7242 (92.3%)	601 (7.7%)
Other Benign Indication	389 (93.3%)	28 (6.7%)
Postoperative Replacement			< 0.001
None	5099 (97.2%)	149 (2.8%)
Oral Calcium	4872 (91.7%)	439 (8.3%)
Oral Vitamin D	1053 (95.0%)	55 (5.0%)
Both Oral Calcium and Vitamin D	8149 (86.3%)	1293 (13.7%)

Note: Bolded values denote statistical significance (p < 0.05).

Among patients with malignancy as their indication, histologic subtype was papillary in 5875 (83.1%), follicular in 351 (5.0%), Hürthle cell in 105 (1.5%), medullary in 85 (1.2%), anaplastic or poorly differentiated in 48 (0.7%), other known malignancy (e.g., lymphoma, sarcoma) in 73 (1.0%), and type was not further specified for 536 (7.6%). For patients with GD, 3222 (88.2%) had GD alone and 431 (11.8%) had GD co‐existing goiter. Within patients with multinodular goiter, 6293 (80.2%) were multinodular alone, 971 (12.4%) had a substernal component, and 579 (7.4%) were classified as severe. Single nodule indications were uniformly benign. For other benign indications 383 (91.8%) were other or unknown, 22 (5.3%) were thyroiditis other than GD, and 12 (2.9%) were hyperthyroidism alone.

3.1. Multivariate Analysis

In the continuous model, patients had decreasing odds of hypocalcemia within 30 days of surgery (OR, 0.98; 95% CI, 0.98–0.99; p‐value < 0.001) for every year older (Table 2). Other findings of interest included that compared with women, men had markedly decreased odds of hypocalcemia (0.65, 0.57–0.75, p < 0.001), and that compared to White patients, Black patients had decreased odds of hypocalcemia (0.85, 0.73–0.98, p = 0.032), while in contrast Hispanic patients had increased odds of hypocalcemia (1.24, 1.04–1.46, p = 0.014). Interestingly, otolaryngologists had increased odds of hypocalcemia compared to non‐otolaryngologists (1.36, 1.23–1.50, p < 0.001). Neither BMI nor ASA had any effect on hypocalcemia on multivariate analysis. Indication for surgery had a large effect on odds of hypocalcemia with all indications, including malignancy (0.87, 0.76–1.00, p = 0.048), single nodule (0.73, 0.60–0.89, p = 0.002), multinodular goiter (0.77, 0.67–0.89, p < 0.001), and other benign indication (0.64, 0.42–0.94, p = 0.029), having decreased odds of hypocalcemia compared to patients with GD. Finally, compared to patients who received no postoperative calcium and/or vitamin D replacement, those who received oral calcium (3.45, 2.85–4.20, p < 0.001), oral vitamin D (2.02, 1.45–2.76, p < 0.001), and both oral calcium and vitamin D (5.74, 4.82–6.87, p < 0.001) all had markedly increased odds of hypocalcemia.

TABLE 2.

Multivariate logistic regression of hypocalcemia with age as a continuous variable.

Characteristic	OR	95% CI	p
Age	0.98	0.98, 0.99	< 0.001
Sex—Male	0.65	0.57, 0.75	< 0.001
Race/Ethnicity—Black	0.85	0.73, 0.98	0.032
Race/Ethnicity—Hispanic	1.24	1.04, 1.46	0.014
Race/Ethnicity—Asian or PI	1.18	0.96, 1.44	0.117
BMI—Underweight	1.15	0.73, 1.57	0.519
BMI—Overweight	0.90	0.79, 1.03	0.140
BMI—Obese	0.94	0.83, 1.07	0.331
Surgical Specialty—Otolaryngology	1.36	1.23, 1.50	< 0.001
ASA Classification—ASA 2	0.86	0.67, 1.13	0.265
ASA Classification—ASA 3	0.96	0.74, 1.27	0.794
ASA Classification—ASA 4/5	1.29	0.87, 1.91	0.207
Indication—Malignancy	0.87	0.76, 1.00	0.048
Indication—Single nodule	0.73	0.60, 0.89	0.002
Indication—Multinodular Goiter	0.77	0.67, 0.89	< 0.001
Indication—Other Benign Indication	0.64	0.42, 0.94	0.029
Postoperative Replacement—Calcium	3.45	2.85, 4.20	< 0.001
Postoperative Replacement—Vitamin D	2.02	1.45, 2.76	< 0.001
Postoperative Replacement—Both	5.74	4.82, 6.87	< 0.001

Note: Bolded values denote statistical significance (p < 0.05).

Age‐stratified analyses showed several interesting trends when stratified into 5 year increments (Table S1). There were no significant differences between the 18–24 and 25–29 year groups (1.16, 0.89–1.53, p = 0.278). However, significant differences emerged between the 25–29 and 35–39 year groups (0.68, 0.54–0.86, p = 0.001), while the 30–34 year comparison was not significant (0.79, 0.63–1.01, p = 0.058). No consecutive age groups were significantly different from age 30 onward, though groups separated by 10 to 20 years showed clear risk reduction, such as the 45–49 versus 30–34 year groups (0.73, 0.58–0.90, p = 0.004) and the 60–64 versus 40–44 year groups (0.68, 0.55–0.84, p < 0.001), supporting a gradual rather than abrupt decline that stabilizes by the mid‐sixties.

3.2. Generalized Additive Modeling and Nonlinear Age Associations

GAM was performed while controlling for all covariates to better isolate the effect of age on hypocalcemia risk. GAM allowing up to 10 knots yielded a total of 28 inflection points: 26, 29, 34, 35, 39, 41, 45, 47, 48, 49, 50, 51, 54, 55, 58, 61, 63, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 76. These were systematically evaluated in segmented regression models up to 7 inflection points, totaling 1,683,217 models. The top 50 models yielded from this thorough search are listed by AIC in Table S2.

The best model in terms of AIC, Log‐likelihood ratio, and Pseudo‐R ² had six inflection points at 26, 35, 39, 51, 54, and 71 years. To visualize these inflection points, we plotted the baseline linear model, a spline model, and a piecewise model with hinge‐terms from the best performing model (Figure 1). Of the top 50 models, all included age 26 as an inflection point, 96% included either age 34 or 35 (12% with 34, 84% with 35), and 92% included age 39. The findings in middle age remained very consistent, with ages 47–51 included in 82% of models (2% with 47, 4% with 48, 26% with 49, 24% with 50, and 26% with 51), and 76% had ages 54 or 55 (46% with 54, 30% with 55). Finally, older age had more variation in inflection points. While all models included inflection points somewhere between ages 65 and 73, often with multiple inflection points in this range, their relative frequencies were low: 24% included 65, 14% included 66, 16% included 67, 16% included 68, 14% included 69, 12% included 70, 16% included 71, 8% included 72, and 6% included 73. Fewer stable inflection points were observed across models at older ages.

FIGURE 1.

Adjusted probabilities of hypocalcemia following total thyroidectomy by age across three modeling approaches. Adjusted predicted probabilities of hypocalcemia plotted across age for linear (green), natural spline (blue), and piecewise (red) models, with shaded regions representing 95% confidence intervals. Black points with error bars represent adjusted predicted probabilities from the categorical age‐group model. All predictions are adjusted for covariates. Knots for the spline model and inflection points for the piecewise model are located at ages 26, 35, 39, 51, 54, and 71 years.

4. Discussion

Hypocalcemia is a common complication following total thyroidectomy, with approximately one in eleven affected in this study. While often transient, some patients develop persistent or permanent hypocalcemia requiring long‐term management [10, 13, 14, 19]. Prior studies have treated age only as a simple continuous or categorical variable, making this the first in‐depth analysis of age's impact on post‐thyroidectomy hypocalcemia risk [10, 16, 20, 21, 22, 23].

When treated as a continuous variable, age demonstrated a protective effect with odds decreasing 2% per year, consistent with most prior studies, though the continuous model obscures the complexity revealed by subsequent analyses [10, 16, 20, 21, 22, 23, 25, 35]. Age‐stratified analyses revealed more nuanced patterns. While no significant differences existed between the 18–24 and 25–29 year groups, a protective effect emerged by age 35–39. From ages 30 to 59, consecutive 5 year age groups showed no significant differences, yet groups separated by 10 to 20 years demonstrated substantial risk reduction suggesting gradual stepwise protection rather than discrete transitions. A transition emerged around age 60, and from age 65 onward, risk stabilized with no significant differences observed between consecutive age groups.

To better characterize these patterns, GAM was employed while controlling for covariates to isolate age's effect. The best performing model identified six inflection points with superior fit to both linear and standard categorical models. Certain inflection points demonstrated striking consistency across models, supporting genuine biological transitions rather than statistical artifacts.

The early adulthood inflection points at ages 26, 34–35, and 39 may reflect overlapping physiological processes. The transition at age 26 could represent the completion of skeletal maturation and peak bone mass attainment, during which calcium homeostasis may remain optimized for bone accretion rather than maintenance, potentially increasing vulnerability to postoperative calcium disturbances [27, 28, 29]. The subsequent inflection points at 34–35 and 39 may reflect stabilization of calcium regulatory mechanisms and declining metabolic demands, consistent with previous reports around the mid‐thirties [29, 30, 31]. Additionally, these ages correspond to periods when GD prevalence and severity begin to shift, with younger GD patients potentially having more aggressive phenotypes [36, 37, 38, 39].

The inflection points from 47–51 to 54–55 present a more complex interpretive challenge, as these ages do not correspond to obvious milestones in calcium metabolism or thyroid disease epidemiology. GD prevalence peaks in younger adulthood and declines with age, while structural thyroid pathology such as malignancy and multinodular goiter become increasingly common [39, 40, 41, 42, 43, 44, 45]. The inflection points around 50 to 55 may represent ranges where these epidemiological transitions become most pronounced, with protective effects emerging. Additionally, this age range may represent a period where accumulated changes in calcium homeostasis and parathyroid function become more pronounced [32, 33, 34]. Finally, surgeons may modify their approach for middle‐aged patients differently than for younger or older patients [17, 46].

While all models included inflection points between 65 and 73, these were distributed across multiple ages with lower frequencies than those identified earlier, suggesting less stable biological transitions and reflecting the increasing heterogeneity of the aging population. Some individuals at these ages may be physiologically robust with intact parathyroid reserve, while others may have accumulated comorbidities, medications, and physiological changes that affect calcium homeostasis. By the mid‐sixties, patients appear to have achieved maximum age‐related protection, and further aging neither increases nor decreases risk substantially. The stabilization may also reflect survivor bias, where patients healthy enough to undergo elective thyroidectomy in their seventies and eighties represent a select population with generally better physiological reserve.

In addition to the impact of age, surgical indication was found to be one of the most significant predictors of hypocalcemia. All surgical indications had significantly lower hypocalcemia risk compared to GD, reinforcing the particularly high‐risk nature of GD. While this study did not directly investigate whether hypocalcemia risk among GD patients varied across age, GD severity is known to vary with age, with younger patients tending to present with more aggressive hyperthyroid phenotypes, higher TRAb titers, and more pronounced thyroid enlargement, which complicate dissection and increase parathyroid devascularization risk [26, 37, 47, 48, 49]. This may contribute to the greater hypocalcemia risk seen in younger adults. As patients age, the epidemiology shifts away from GD toward structural pathology such as nodular goiter and malignancy, indications that carry substantially lower hypocalcemia risk in our data. This shift may therefore be a meaningful driver of the age‐related inflection points identified, particularly in early and middle adulthood, and further investigation into how age influences each indication individually is essential.

Several other factors also warrant brief mention. Men had 35% lower odds of hypocalcemia compared to women, consistent with prior literature [10, 11, 15, 20, 50]. Black patients had 15% lower odds compared to White patients, while Hispanic patients demonstrated 24% higher odds, though the association of race on hypocalcemia has been mixed [10, 20, 26, 35]. Patients managed by otolaryngologists had 36% higher odds of hypocalcemia compared to non‐otolaryngologists, potentially reflecting case complexity and comorbidity burden, supported by prior work demonstrating higher comorbidity burden among patients operated on by otolaryngologists [46]. Finally, patients receiving postoperative supplementation had markedly increased odds of hypocalcemia, almost certainly reflecting reverse causation rather than a causal effect of supplementation.

These findings carry direct clinical implications for perioperative management of patients undergoing total thyroidectomy. Current practice largely relies on simple categorical or continuous age adjustments, which this study demonstrates are insufficient. Clinicians should apply heightened surveillance and routine prophylactic calcium supplementation in younger adults, especially those age 26 and under as they have the highest risk of hypocalcemia. Even after 26, risk remains high and surveillance should be heightened and supplementation should be routine, particularly in those under 40 undergoing thyroidectomy for GD, as this subgroup carries the highest combined risk. Between 40 and 65, in the more heterogeneous middle age range, hypocalcemia risk gradually declines, but this should not be mistaken for license to disregard monitoring; indication and comorbidities should drive individualized risk assessment and supplementation decisions rather than age alone. In these patients, depending on their presentations, monitoring alone or in tandem with supplementation may be indicated, based on a combination of their risk factors and age. For patients over 65, risk stabilization means advanced age should not be used to reassure or deprioritize monitoring; these patients remain at risk, and their heterogeneity warrants individualized approaches. However, in these older patients monitoring alone may be sufficient with supplementation as an add‐on when indicated by labs. The inflection points identified here provide a framework for developing age‐tailored risk stratification tools that could standardize perioperative calcium protocols, reduce unnecessary supplementation, and concentrate resources toward those at genuinely elevated risk.

This study has several limitations that must be acknowledged. NSQIP only follows patients for 30 days after surgery, limiting our ability to distinguish transient from permanent hypocalcemia. Preoperative supplementation was also not captured, and future work should parse out disparities in protocols given differences in efficacy [23, 51, 52, 53, 54]. Additionally, this study is limited to adults, and pediatric populations may carry their own risk factors. Finally, while our models controlled for numerous confounders, residual confounding from unmeasured variables such as surgeon volume, institutional protocols, or disease severity remains possible. Indication for surgery was grouped into five categories to preserve statistical power, but these groupings do not capture within‐category heterogeneity, such as histologic subtype within malignancy or clinical severity within goiter, which may independently relate to hypocalcemia risk and should be examined in future work. Additionally, concurrent central neck dissection, performed in 3599 patients (17.0%), was not included as a separate covariate in our adjusted models. As this procedure is performed almost exclusively in the setting of malignancy, and indication for surgery, including malignant indication, was already adjusted for, it was excluded to avoid model overfitting. However, future studies should investigate the nuances of this relationship more directly.

These findings open several avenues for future investigation. First, validation in prospective cohorts is needed, with attention to whether patterns differ between transient and permanent hypocalcemia. Second, the biological mechanisms underlying these transitions warrant dedicated investigation, including examining age‐specific parathyroid hormone dynamics, vitamin D metabolism, and calcium homeostasis. Third, age‐tailored risk stratification tools incorporating these nonlinear effects should be prospectively tested to determine whether age‐specific supplementation protocols improve outcomes while reducing costs. Finally, focused investigation into high‐risk subgroups, particularly younger GD patients, and exploration of why risk stabilizes after age 65 could inform targeted interventions and clarify the limits of age‐related protection.

5. Conclusion

This study demonstrated that age exerts a small but potent protective effect on hypocalcemia risk following total thyroidectomy, with a nonlinear relationship and important implications for perioperative management. Hypocalcemia risk is characterized by key transition points with gradual changes between them, making complex risk assessment more useful than simple continuous or categorical models. Risk reduction appears most pronounced in early adulthood, potentially reflecting skeletal maturation and stabilization of calcium regulatory mechanisms, with middle age transitions likely corresponding to shifting thyroid disease epidemiology and parathyroid function. Very elderly patients should not be assumed to have lower risk simply due to advanced age, as stabilization after the mid‐sixties likely reflects physiological heterogeneity rather than continued protection. Prospective validation, elucidation of the underlying biological mechanisms, and development of age‐tailored risk stratification tools are important next steps toward a precisely managed, age‐stratified approach to perioperative calcium management following total thyroidectomy.

Funding

The authors have nothing to report.

Disclosure

No artificial intelligence tools were used in the preparation of this manuscript.

Conflicts of Interest

Dr. Chelius has received a stipend from the American Academy of Otolaryngology–Head and Neck Surgery outside the submitted work. The other authors declare no conflicts of interest.

Supporting information

Table S1: Multivariate analysis of hypocalcemia within 30 days of surgery stratified into 5 year groups.

Table S2: Top 50 models by Akaike Information Criterion with Bayesian Information Criterion, Log‐likelihood, Pseudo‐R2, and p‐value of model compared to linear model.

Abrahamson C. W., Chelius D. C., D'Souza J. N., Dimachkieh A. L., Sheyn A. M., and Rastatter J. C., “Modeling the Relationship of Age With Hypocalcemia Following Total Thyroidectomy: A NSQIP Analysis,” Laryngoscope Investigative Otolaryngology 11, no. 5 (2026): e70566, 10.1002/lio2.70566.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.