Diabetic and Nondiabetic Endocrine Emergencies: Clinical Spectrum and Outcomes From a Tertiary Care Center in North India.

Highlights • Diabetic ketoacidosis (DKA) was the most common endocrine emergency, with an annual incidence of 1.26 per 1000 emergency admissions • Hyperosmolar hyperglycemic state (HHS) and thyroid storm exhibited the highest mortality rates (50% and 100%, respectively) • Older age, renal dysfunction (estimated glomerular filtration rate), hypertension, and elevated plasma osmolality were significant predictors of mortality in DKA and HHS • Infections were the most frequent precipitating factor across endocrine emergencies, especially in DKA (52.4%) and HHS (87.5%) • Rhino-orbital-cerebral mucormycosis emerged as an important precipitating infection for DKA in patients with type 2 diabetes mellitus Clinical Relevance This study provides the first comprehensive prospective data from a low-resource Indian setting on diabetic and nondiabetic endocrine emergencies, highlighting mortality predictors and underscoring the need for early recognition and aggressive intervention in high-risk presentations such as hyperosmolar hyperglycemic state and thyroid storm.

Introduction

Endocrine emergencies are acute, life-threatening conditions resulting from dysfunctions in hormone-producing glands. Although they represent a small fraction of emergency department (ED) admissions, comprising approximately 1.5% of all hospital admissions according to western literature, 1 their nonspecific presentations often pose significant diagnostic challenges, leading to delays in treatment and increased morbidity and mortality. 2

Among endocrine emergencies, diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the most extensively studied due to their relatively higher incidence in patients with diabetes mellitus. The occurrence of DKA varies across populations, with incidences ranging from 4.6 to 8.0 per 1000 patients with diabetes annually, and mortality rates reported between 1% and 5% in developed settings. 3 , 4 Similarly, HHS, although less frequent, remains a critical emergency with mortality rates as high as 10% to 20%, primarily due to delayed diagnosis and older age at presentation. 5 Studies have emphasized the role of infections and noncompliance with insulin therapy, as major precipitating factors for DKA and HHS. 6

In contrast, data on nondiabetic endocrine emergencies, such as thyroid storm, myxedema coma, adrenal crisis, hypercalcemia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), and diabetes insipidus (DI), remain scarce in the literature. These conditions are predominantly described in isolated case reports or small case series, highlighting the paucity of comprehensive epidemiologic data. 7 , 8 , 9 For instance, thyroid storm, a rare but life-threatening complication of hyperthyroidism, has a reported mortality rate of up to 30% despite advancements in critical care. 10 Myxedema coma, the severe manifestation of hypothyroidism, is associated with mortality rates exceeding 40%, often due to delayed diagnosis. 11 Similarly, adrenal crisis, frequently triggered by stress or infection in patients with adrenal insufficiency, carries a high mortality risk without timely intervention. 12

Hypercalcemia, commonly caused by malignancies and primary hyperparathyroidism (PHPT), is another endocrine emergency requiring rapid management to prevent complications such as acute kidney injury (AKI) and altered sensorium. 13 Reports of SIADH and DI are sparse in the literature, with most available data limited to isolated clinical descriptions, emphasizing the need for larger studies to better understand these conditions. 14

The current literature from developing nations remains sparse, especially regarding the incidence, clinical features, and outcomes of these emergencies beyond diabetic cases. This gap hinders development of effective triage and treatment protocols.

This study aimed to address this void by analyzing the clinical spectrum and outcomes of endocrine emergencies at a tertiary care hospital in North India, with the objective of informing early recognition and management strategies.

Methods

Study Design and Setting

This study was designed as a longitudinal, prospective observational study conducted over 18 months, from July 2020 to December 2021. The research was carried out at the emergency ward of a tertiary care academic hospital in North India.

Patient Population

Consecutive patients aged ≥12 years admitted to the emergency ward with specific endocrine emergencies were included. The details of inclusion and exclusion criteria are presented in Supplementary Table 1. Eligible patients were counseled about the study, and written informed consent was obtained.

Although the study was conducted in a tertiary care academic hospital, it serves a predominantly rural and semiurban population with limited access to health care facilities. Many patients present late or after inadequate initial treatment, thereby reflecting a low-resource health care delivery context.

Specific endocrine emergencies included DKA, HHS, hypoglycemia, hypercalcemia, hypocalcemia, thyroid storm, myxedema coma, SIADH, and DI.

Data Collection

Detailed patient histories, including information on symptom onset, duration, etiology, and disease severity, were recorded. Comprehensive clinical examinations were conducted, and relevant biochemical, hematologic, hormonal, and radiological investigations were performed and documented using a standardized case record form. Each patient was closely monitored during their hospital stay, with outcomes noted as discharge, leaving against medical advice, or death. Emergencies such as pituitary apoplexy, Sheehan syndrome, adrenal crisis, and immune checkpoint inhibitor–related endocrinopathies either were not observed during the study period or were excluded due to insufficient numbers for meaningful analysis.

The study was approved by the Institutional Ethics Committee in accordance with the Declaration of Helsinki and Indian Council of Medical Research guidelines. Written informed consent was obtained from all participants or their legal representatives, with assurance of their right to withdraw without affecting their medical care.

Management Protocols

All patients received standard care based on institutional protocols aligned with national/international guidelines. DKA and HHS were managed with intravenous (IV) fluids, insulin infusions, and electrolyte correction. Thyroid storm was treated with beta-blockers, antithyroid drugs (propylthiouracil), Lugol’s iodine, and corticosteroids. Myxedema coma was managed with IV levothyroxine and hydrocortisone. Hypercalcemia was managed with hydration, calcitonin, bisphosphonates, and dialysis when indicated. SIADH was treated with fluid restriction and hypertonic saline when needed, and DI was treated with desmopressin.

Statistical Analysis

Data from all patients with endocrine emergencies admitted during the study period were compiled in Microsoft Excel and analyzed using SPSS version 22.0. After data cleaning to remove duplicates and irrelevant entries, the incidence of endocrine emergencies was calculated.

Continuous variables were expressed as means ± standard deviations for normally distributed data and as medians with IQRs for skewed data. Categorical variables were summarized as frequencies and percentages. Independent t test was used to compare means for normally distributed data, whereas the Mann-Whitney U test was applied for skewed distributions. A P value of ≤.05 was considered statistically significant, with a 95% confidence interval. Results were displayed using graphs and tables for clarity.

Results

This prospective study analyzed 212 cases of endocrine emergencies over an 18-month period, with a total incidence of 1.82 per 1000 ED admissions annually. The major endocrine emergencies identified were DKA, HHS, hypercalcemia, hypocalcemia, thyroid storm, myxedema coma, SIADH, and DI.

Incidence

DKA was the most frequent endocrine emergency, observed in 147 patients, accounting for 69.3% of all endocrine emergencies. This corresponds to an annual incidence of 1.26 per 1000 ED admissions. Hypercalcemia was the second most common emergency, documented in 24 patients (11.3%), with an incidence of 0.21 per 1000 ED admissions per year. Hypoglycemia occurred in 15 patients (7.1%), corresponding to an incidence of 0.13 per 1000 ED admissions annually. HHS was identified in 8 patients (3.8%), with an incidence of 0.07 per 1000 ED admissions. Thyroid storm, myxedema coma, and SIADH were each diagnosed in 3 patients (1.4%), corresponding to an incidence of 0.03 per 1000 ED admissions. DI was the least common, seen in 2 patients (0.9%), with an annual incidence of 0.02 per 1000 ED visits. A detailed summary of prevalence and incidence for each emergency is provided in Table 1 . Table 1 Incidence of Various Endocrine Emergencies Endocrine emergency No. of cases Incidence (/1000 ED admissions/y) Diabetic ketoacidosis 147 (69.3%) 1.26 Hyperosmolar hyperglycemic state 8 (3.8%) 0.07 Hypercalcemia 24 (11.3%) 0.21 Hypoglycemia 15 (7.1%) 0.13 Hypocalcemia 7 (3.3%) 0.06 Thyroid storm 3 (1.4%) 0.03 Myxedema coma 3 (1.4%) 0.03 SIADH 3 (1.4%) 0.03 Diabetes insipidus 2 (0.9%) 0.02 Total 212 (100%) 1.82 Abbreviations: ED = emergency department; SIADH = syndrome of inappropriate antidiuretic hormone secretion.

Demographics

The demographic characteristics varied significantly across the different emergencies. DKA emerged as the most common endocrine emergency, accounting for 147 cases (69.3% of all emergencies). The mean age of patients was 36.2 ± 18.2 years, with younger patients predominantly having type 1 diabetes mellitus (T1DM; 24.4 ± 10.4 years) compared with those with type 2 diabetes mellitus (T2DM; 54.9 ± 10.7 years). The sex distribution was nearly equal, with 50.3% males and 49.7% females ( Supplementary Tables 2 and 3 ).

The median estimated glomerular filtration rate (eGFR) for all patients with DKA was 52.4 mL/min/1.73 m 2 (IQR, 35.8-69.1 mL/min/1.73 m 2 ). Patients with T2DM had a lower median eGFR of 41.4 mL/min/1.73 m 2 (IQR, 28.5-53.2 mL/min/1.73 m 2 ), compared with 104.9 mL/min/1.73 m 2 (IQR, 80.2-122.5 mL/min/1.73 m 2 ) in patients with T1DM, reflecting significant renal impairment. The median serum creatinine level among patients with DKA was 1.2 mg/dL (IQR, 0.8-2.5 mg/dL). When stratified by diabetes type, patients with T2DM exhibited a higher median serum creatinine level of 1.8 mg/dL (IQR, 1.0-3.2 mg/dL) compared with patients with T1DM, who had a median of 1.0 mg/dL (IQR, 0.7-1.8 mg/dL). This difference was statistically significant ( P = .001). Elevated creatinine levels (>1.2 mg/dL) were observed in 71.9% of patients with T2DM, compared with 42.2% of patients with T1DM, indicating a significant disparity between the groups ( P < .001) ( Supplementary Table 4 ). Although a significant difference was observed between measured osmolality (314.06 ± 25.41 mmol/kg) and calculated effective osmolality (300.65 ± 21.82 mmol/kg, P = .039), our results and interpretations were primarily based on the calculated effective osmolality, because it better aligns with physiologic relevance.

HHS was a relatively rare emergency, with only 8 cases documented (3.8% of all emergencies), corresponding to an incidence of 0.07 per 1000 ED admissions per year. The mean age of patients was 55.1 ± 17.8 years, with a predominance of females (75%). All HHS cases were observed exclusively in patients with T2DM. Plasma osmolality was significantly higher in patients who did not survive (380.25 ± 23.17 mOsm/kg) than in survivors (343.50 ± 10.47 mOsm/kg, P = .029) (Table 2).

Hypercalcemia was identified in 24 cases (11.3% of all emergencies), with an incidence of 0.21 per 1000 ED admissions per year. The mean age of patients was 50.5 ± 16.2 years, with a slight female predominance (58.3%). PHPT (37.5%) and malignancy (16.7%) were the most common underlying causes. AKI was significantly more prevalent in patients with parathyroid hormone (PTH)-independent hypercalcemia (86.7% vs 11.1%, P < .001) ( Supplementary Table 5 ).

Hypoglycemia accounted for 15 cases (7.1% of all emergencies), corresponding to an incidence of 0.13 per 1000 ED admissions per year. The mean age of patients was 52.2 ± 18.0 years, with a slight female predominance (53.3%). Cases were evenly distributed between T1DM and T2DM, with 3 additional cases occurring in nondiabetic individuals due to insulin autoimmune syndrome and drug-induced hypoglycemia.

Thyroid storm was observed in 3 cases (1.4% of all emergencies), with an incidence of 0.03 per 1000 ED admissions per year. The mean age of patients was 62.0 ± 2.6 years, and all cases were reported in females. Similarly, myxedema coma was also rare, with 3 cases (1.4%) and an incidence of 0.03 per 1000 ED admissions per year. The mean age of patients was 33.3 ± 18.2 years, with a male predominance (66.7%). Primary hypothyroidism accounted for 66.7% of cases, whereas secondary hypothyroidism due to pituitary adenoma resection was responsible for the remainder.

SIADH was recorded in 3 cases (1.4%), corresponding to an incidence of 0.03 per 1000 ED admissions per year. The mean age was 23.3 ± 6.8 years, with equal sex distribution. Finally, DI was the least common endocrine emergency, with 2 cases (0.9%) and an incidence of 0.02 per 1000 ED admissions per year. The mean age of these patients was 25.5 ± 12.4 years, with an equal sex distribution.

In summary, diabetic emergencies (DKA and HHS) were the most prevalent, followed by hypercalcemia. Sex distribution varied significantly across conditions, with thyroid storm occurring exclusively in females. Age differences were notable, with younger patients more commonly affected by DKA and SIADH, whereas older individuals presented with hypercalcemia and thyroid storm.

Precipitating Factors of Endocrine Emergencies

In DKA, infections emerged as the most common precipitating factor, identified in 77 (52.4%) of 147 cases ( Fig. 1 ), with pneumonia, urosepsis, and rhino-orbital-cerebral mucormycosis being the primary infections. Notably, rhino-orbital-cerebral mucormycosis was observed in 9 (6.1%) of 147 patients with DKA , with a significantly higher occurrence in patients with T2DM (8 [14.0%] of 57) than in those with T1DM (1 [1.1%] of 90) ( P = .002) ( Fig. 2 ). Fig. 1 Distribution of precipitating factors in patients with diabetic ketoacidosis. MI = myocardial infarction. Fig. 2 Distribution of various infections in patients with diabetic ketoacidosis. ASOM = acute suppurative otitis media; CAP = community-acquired pneumonia.

Noncompliance with diabetes therapy, including irregular insulin administration or lack of follow-up, contributed to 26 cases (17.7%). New-onset diabetes was the initial presentation in 25 patients (17.0%) with DKA, with a significantly higher proportion in T1DM (22.2%) than inT2DM (8.8%) ( P = .034). Among patients with T1DM, the most common triggers were missed insulin doses (20%), infections (42.2%), and lipohypertrophy (11.1%). In contrast, patients with T2DM presented predominantly with infections (68.4%, P = .002), followed by glucocorticoid use (10.5%) and stroke (10.5%, P = .014). Additional triggers across the cohort included insufficient therapy (11.6%), binge alcohol use (2.7%), pancreatitis (1.4%), and myocardial infarction (0.7%) ( Table 3 ). Table 3 Summary of Precipitating Factors in Diabetic Ketoacidosis Precipitating factor Overall ( n = 147) T1DM ( n = 90) T2DM ( n = 57) P value Infection 77 (52.4%) 38 (42.2%) 39 (68.4%) .002 Missed insulin dosage 19 (12.9%) 18 (20.0%) 1 (1.8%) .001 Insufficient therapy 17 (11.6%) 9 (10.0%) 8 (14.0%) .456 Lipohypertrophy 10 (6.8%) 10 (11.1%) 0 (0.0%) .007 Newly diagnosed diabetes with no other precipitating factors 25 (17.0%) 20 (22.2%) 5 (8.8%) .034 Acute MI 1 (0.7%) 0 (0.0%) 1 (1.8%) .388 Stroke 7 (4.8%) 1 (1.1%) 6 (10.5%) .014 Binge alcohol 4 (2.7%) 3 (3.3%) 1 (1.8%) 1.000 Drugs (glucocorticoids) 8 (5.4%) 2 (2.2%) 6 (10.5%) .056 Pancreatitis 2 (1.4%) 0 (0.0%) 2 (3.5%) .149 Noncompliance 26 (17.7%) 18 (20.0%) 8 (14.0%) .356 Unknown 1 (0.7%) 1 (1.1%) 0 (0.0%) 1.000 MI = myocardial infarction; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus. Data are presented as numbers of cases (percentages within group). P values calculated using the X 2 or Fisher exact test as appropriate. P < .05 considered statistically significant.

In HHS, infections were also the predominant precipitant, contributing to 7 (87.5%) of 8 cases. The most common infections were urosepsis, community-acquired pneumonia, and acute gastroenteritis. Additional contributors included poor glycemic control and insulin omission. Notably, HHS was the first presentation of T2DM in 4 patients (50%), highlighting delayed diabetes recognition.

For hypercalcemia, the leading cause was PHPT (9 [37.5%] of 24), followed by multiple myeloma (20.8%), malignancies such as lymphoma and leukemia (16.7%), and granulomatous disorders (8.3%). Less common etiologies included vitamin D toxicity and idiopathic causes ( Fig. 3 ). Fig. 3 Distribution of etiologies of hypercalcemia. TB = tuberculosis.

Hypoglycemia was most frequently attributed to medication-related errors—notably, insulin overdoses and sulfonylurea use, which were responsible for 59.8% of cases. Other contributing factors included missed meals (26.7%), sepsis (33.3%), and chronic kidney disease, which impaired insulin clearance. Among the nondiabetic hypoglycemia cases, 2 were diagnosed with insulin autoimmune syndrome, confirmed by elevated endogenous insulin levels in the absence of exogenous insulin use, and 1 case resulted from accidental sulfonylurea ingestion in an elderly individual. All patients were managed with IV dextrose and close hemodynamic and glucose monitoring and achieved full recovery without recurrence during hospitalization.

In thyroid storm, the major triggers were infections, discontinuation of antithyroid medications, trauma, and iodinated contrast exposure. All 3 patients had multisystem involvement at presentation, leading to high mortality.

Myxedema coma was precipitated by infections—notably pneumonia and urinary tract infections—in all cases. Noncompliance with thyroxine therapy was an additional factor in 2 cases.

In SIADH, the primary triggers were central nervous system infections, such as tuberculous meningitis, and autoimmune diseases, including neuromyelitis optica spectrum disorder.

The 2 cases of DI were due to postoperative pituitary injury and neurosarcoidosis, both of which resulted in symptomatic hypernatremia, effectively managed with oral desmopressin.

Comparison Between DKA and HHS

A comparative analysis between DKA ( n = 147) and HHS ( n = 8) revealed several statistically significant differences. The proportion of patients with T2DM was significantly higher in the HHS group (100%) than in the DKA group (38.8%, P < .001). Although the mean age of patients with HHS (55.12 ± 17.8 years) was numerically higher than that of those with DKA (T2DM, 54.91 ± 10.7 years; T1DM. 24.39 ± 10.4 years), this difference was not formally compared due to subgroup stratification.

Patients with HHS had significantly higher levels of plasma glucose (720.88 ± 88.6 mg/dL vs 449.88 ± 121.3 mg/dL, P < .001), serum creatinine (3.71 ± 1.02 mg/dL vs 1.93 ± 1.26 mg/dL, P = .003), effective plasma osmolaslity (329.00 ± 21.6 mOsm/kg vs 300.04 ± 25.4 mOsm/kg, P = .002), and serum sodium (149.72 ± 5.4 mEq/L vs 137.76 ± 6.2 mEq/L, P < .001). The mean time to resolution was significantly prolonged in HHS (64.25 ± 38.3 hours) than in DKA (31.63 ± 15.4 hours, P = .016).

Although the mortality rate was numerically higher in HHS (50.0%) than in DKA (23.8%), the difference did not reach statistical significance ( P = .117), likely due to the small number of HHS cases ( Table 2 ). Table 2 Comparison of Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State Parameter DKA ( n = 147) HHS ( n = 8) P value Mean age (y) T1DM: 24.39 ± 10.4 T2DM: 54.91 ± 10.7 55.12 ± 17.8 … Proportion of T2DM cases (%) 57/147 (38.8%) 8/8 (100%) <.001 Mean plasma glucose level (mg/dL) 449.88 ± 121.3 720.88 ± 88.6 <.001 Mean serum creatinine level (mg/dL) 1.93 ± 1.26 3.71 ± 1.02 .003 Mean effective plasma osmolality (mOsm/kg) 300.04 ± 25.4 329.00 ± 21.6 .002 Mean serum sodium level (mEq/L) 137.76 ± 6.2 149.72 ± 5.4 <.001 Mean time to resolution (h) 31.63 ± 15.4 64.25 ± 38.3 .016 Mortality (%) 35/147 (23.8%) 4/8 (50%) .117 DKA = diabetic ketoacidosis; HHS = hyperosmolar hyperglycemic state; T2DM = type 2 diabetes mellitus. Data are presented as means ± standard deviation or numbers (%). P values were calculated using the independent t test or Fisher exact test as appropriate.

These findings underscore the more severe biochemical derangements and poorer outcomes associated with HHS compared with DKA, emphasizing the need for aggressive monitoring and management, especially in older patients with T2DM.

Outcomes of Endocrine Emergencies

Of 147 patients with DKA, 23.8% died, 70.7% were discharged, and 5.4% left against medical advice ( P = .017). Mortality was higher in T2DM (31.6%) than in T1DM (18.9%), although not statistically significant ( P = .078). Discharge rates were higher in T1DM (77.8%) than in T2DM (59.6%), ( Supplementary Table 6 ). Age was a significant predictor of mortality, with a mean age of 41.83 ± 19.09 years in those who died, compared with 34.47 ± 17.69 years in survivors ( P = .041). The median eGFR in patients who had mortality was 34.3 mL/min/1.73 m 2 , whereas it was 47.2 mL/min/1.73 m 2 in those who survived. Similarly, the median serum creatinine in patients who had mortality was 2.27 mg/dL, compared with 1.82 mg/dL in survivors, with a significant difference between the 2 groups ( P = .033) ( Supplementary Table 7 ). In our study, 50.0% of patients with T2DM with DKA who had hypertension experienced mortality, compared with 20.0% of those without hypertension, with a significant difference between the 2 groups (χ 2 = 5.627, P = .018). However, no statistically significant difference in mortality was observed with respect to other comorbidities (chronic kidney disease, cerebrovascular accident, and coronary artery disease). The mean effective plasma osmolality was significantly higher in patients who had mortality (310.29 ± 29.53 mOsm/L) than in survivors (297.64 ± 17.92 mOsm/L; W = 2496.500, P = .015).

The mean age and levels of serum sodium, serum urea, serum creatinine, plasma osmolality, and effective plasma osmolality were numerically higher in patients with HHS with mortality than in survivors ( Supplementary Table 8 ). However, only plasma osmolality was found to be significantly associated with mortality ( P < .05). The mean plasma osmolality level in patients who had mortality was 380.25 ± 23.17 mOsm/kg, compared with 343.50 ± 10.47 mOsm/kg in survivors, with a significant difference between the 2 groups ( P = .029)

Of the 24 hypercalcemia patients, 19 (79.2%) were discharged, 4 (16.7%) died, and 1 (4.2%) left against medical advice. There was no significant difference in outcomes between PTH-dependent hypercalcemia and PTH-independent hypercalcemia. Among the 4 patients who died, 1 had PHPT, 2 had malignancy (anaplastic large cell lymphoma and acute lymphoid leukemia), and 1 had granulomatous disease (sarcoidosis).

In hypoglycemia ( n = 15), the mortality rate was 13.3% (2 patients), primarily due to sepsis and nonresolving encephalopathy. Both patients had prolonged intubation and died of sepsis and ventilator-associated pneumonia, whereas the remaining 86.7% (13 of 15) of patients achieved full neurologic recovery and were discharged without any residual neurocognitive deficits.

The outcome for thyroid storm was universally poor, and all 3 patients died. All these cases experienced multisystem failure, with cardiovascular complications such as tachyarrhythmias and heart failure being the primary contributors to mortality, despite intensive care.

For myxedema coma, 1 patient succumbed to sepsis and multiorgan failure. However, the other 2 patients were discharged without any residual neurologic deficits following intensive care management.

In SIADH, all patients improved after treatment of the underlying cause, fluid restriction, and correction of hyponatremia and were successfully discharged.

Finally, both patients of DI responded well to oral desmopressin and were discharged without any long-term complications.

Discussion

This study provides a comprehensive analysis of endocrine emergencies in an Indian tertiary care center, with an overall incidence of 1.82 per 1000 ED admissions annually. This rate is lower than the incidence (1.5%) reported in western literature, 1 because we considered only those patients admitted in the emergency ward. Other contributing factors may include higher patient loads, a lower doctor-to-patient ratio, and ethnic variations. Despite being relatively rare, endocrine emergencies pose a significant burden to health care system due to their potential for life-threatening complications.

Prevalence and Distribution of Endocrine Emergencies

DKA emerged as the most common endocrine emergency, accounting for 69.3% of cases, with an annual incidence of 1.26 per 1000 ED admissions. These findings align with previous studies that identify DKA as the most frequent acute metabolic complication of diabetes, particularly in younger patients with T1DM. 15 , 16 The relatively high proportion of DKA cases in our cohort may, in part, be due to the inclusion of adolescents (≥12 years), among whom new-onset T1DM is common. This may have contributed to the skewed distribution of diabetic emergencies. In our study, DKA mortality was 23.8%, higher in T2DM than in T1DM, although not statistically significant. Age was a significant predictor of mortality, with a mean age of 41.83 ± 19.09 years in nonsurvivors. This is in concordance with previous studies reporting worse outcomes in older patients with T2DM due to comorbidities and delayed presentation. 4 , 17 Our study identified renal function, as measured by serum creatinine levels and eGFR, as a significant predictor of mortality in patients with DKA. Patients who succumbed had higher median serum creatinine levels and lower median eGFR than survivors, indicating that impaired renal function is correlated with increased mortality risk. This observation aligns with findings from Chen et al, 18 who reported that AKI serves as an independent risk factor for poor long-term renal outcomes and mortality in patients with DKA. In our study, hypertension was significantly associated with mortality in patients with T2DM with DKA, with 50.0% mortality in those with hypertension compared with 20.0% in those without ( P = .018). Similar to our finding, literature also suggests an increased risk of mortality in patients with DKA with comorbid hypertension. 18 In our study, higher effective plasma osmolality was significantly associated with mortality in patients with DKA, consistent with previous findings highlighting its role as a predictor of poor outcomes. 19

HHS was much less frequent, comprising 3.8% of the cases with an incidence of 0.07 per 1000 ED admissions annually. This lower prevalence is consistent with previous reports, 20 and it is notable that HHS occurred exclusively in older patients with T2DM of a mean age of 55 years. In our study, infection was the most common precipitating factor for HHS, observed in 87.5% of patients, whereas 12.5% had acute myocardial infarction, and 12.5% had noncompliance with medications. Similarly, Wu et al 21 (China) reported infections as the leading trigger (70.3%), followed by newly diagnosed diabetes (17.7%) and noncompliance (5.7%), whereas Chu et al 22 identified infections (57.1%) and poor compliance to medication (21%) as major contributors.

Hypercalcemia was the second most common endocrine emergency, observed in 11.3% of cases with an annual incidence of 0.21 per 1000 ED admissions. The most common causes were PHPT and malignancies, findings that are consistent with earlier studies. 23 , 24

Hypoglycemia accounted for 7.1% of cases, with an incidence of 0.13 per 1000 ED admissions annually. Our study, focused on severe hypoglycemia with altered sensorium (those required admission in emergency ward) in patients with diabetes and rare nondiabetic cases, identified 15 cases evenly distributed between T1DM and T2DM ( n = 6 in each group), along with instances due to insulin autoimmune syndrome and drug-induced hypoglycemia in nondiabetic individuals ( n = 3). In comparison, Kumar et al 25 reported a higher incidence (16.51/1000 ED visits/y) due to broader inclusion criteria, including all patients with an random blood glucose level of ≤60 mg/dL, regardless of symptoms. The most common precipitating factors for hypoglycemia in our study were recent changes in antidiabetic medication (40%), sepsis (33.3%), and missed meals (26.7%), with a mortality rate of 13.3%. Previous studies have reported lower mortality rates, ranging from 1.6% to 8.3%. 26 , 27 The lower mortality rates can be attributed to inclusion of cases with milder form of hypoglycemia in those studies. Of the 2 patients who died, both had nonresolving encephalopathy, prolonged intubation, and succumbed to sepsis and ventilator-associated pneumonia, whereas the remaining 13 patients recovered fully, with reversal of encephalopathy and no residual neurocognitive deficits.

Less common emergencies included thyroid storm, myxedema coma, and SIADH, each representing 1.4% of cases, with an annual incidence of 0.03 per 1000 ED admissions. Three cases of thyroid storm were identified in our study. All these 3 patients in our study died, reflecting a higher mortality than the 9.5% to 11% reported by previous studies. 28 The poor outcomes were attributed to adverse prognostic factors, such as advancing age of >60 years, cardiogenic shock, and central nervous system dysfunction, at presentation, and requirement for mechanical ventilation, as noted by Ono et al. 28 Similarly, 3 cases of myxedema coma were observed, with an annual incidence of 0.03 per 1000 ED admissions. Western literature estimates the incidence at approximately 0.22 per million per year. 29 One patient died, yielding a mortality rate of 33.3%, which falls within the 25% to 60% range reported in the literature. 30 DI was the rarest endocrine emergency, with only 2 cases (0.9%) and an incidence of 0.02 per 1000 ED admissions annually. These findings are in line with previous literature documenting the rarity of severe endocrine crises like thyroid storm and DI. 7 , 31

The high prevalence of DKA, particularly among younger patients with T1DM, underscores the critical need for effective diabetes education particularly education regarding sick day guideline and the importance of adherence to insulin therapy. Infections and noncompliance with treatment and infections were the primary precipitating factors in our cohort, consistent with prior studies. 32 Rhino-orbital-cerebral mucormycosis has been identified as a precipitating factor for DKA, particularly in patients with T2DM. This opportunistic fungal infection is facilitated by the acidotic and hyperglycemic milieu of DKA, which promotes impaired neutrophil chemotaxis and elevated free iron levels that enhance fungal proliferation. The association was particularly evident during the COVID-19 pandemic due to widespread corticosteroid use, immune dysregulation, and delays in glycemic control, leading to a surge in mucormycosis cases precipitating or coexisting with DKA. 33 , 34 Elevated serum creatinine levels were observed in 53.7% of DKA cases, with significantly higher levels in patients with T2DM, emphasizing the need for early recognition and management of AKI in these patients.

HHS, although less common, exhibited a significantly higher mortality rate (36.4%) than DKA (23.8%), reflecting the older age, severe dehydration, and multisystem involvement typically seen in HHS. Elevated serum osmolality emerged as a predictor of poor outcomes, which is consistent with the existing literature. 35 Recognized as the most severe acute complication of T2DM, HHS has reported mortality rates reaching as high as 30%, 35 highlighting the critical need for early diagnosis and intervention.

Hypercalcemia was predominantly observed in patients with PHPT (37.5%) and malignancy (16.7%), with an associated AKI incidence of 58.3%. AKI was particularly common in patients with PTH-independent hypercalcemia, likely due to mechanisms such as paraprotein-induced renal damage and nonsteroidal anti-inflammatory drugs use in malignancy associated hypercalcemia. This highlights the importance of tailored management strategies, including volume expansion, saline diuresis, calcitonin, and antiresorptive, to address both hypercalcemia and its underlying causes. 36

Hypoglycemia, although less common, remains a critical concern due to its potential for irreversible neurologic damage. Medication errors, such as insulin overdoses, were the leading causes in our cohort. Chronic kidney disease and missed meals were additional contributors, consistent with previous studies. 37 The risk of sepsis and nonresolving encephalopathy in severe cases warrants prompt recognition and management.

Thyroid storm and myxedema coma, although rare, were associated with high mortality rates. The universal poor outcomes in thyroid storm highlight the aggressive nature of this condition and the critical need for early diagnosis and intensive care. Common triggers included infections, trauma, and noncompliance with antithyroid therapy, consistent with prior reports. 10

SIADH and DI were rare but significant emergencies in our study. The lower frequency of hyponatremia in our study may be attributed to the inclusion of only severe symptomatic cases requiring admission, whereas less severe cases are typically worked up on an outpatient basis, reducing the overall incidence reported. SIADH was primarily triggered by central nervous system infections and autoimmune conditions, with all cases successfully treated through fluid restriction and correction of hyponatremia. DI, on the other hand, was often related to pituitary surgery, with excellent outcomes following desmopressin therapy.

No cases of severe hypokalemia attributable to endocrine emergencies were identified, likely reflecting its rarity in this specific subset of emergency presentations.

The findings from this study underscore the critical importance of early risk stratification in the ED. Identifying high-risk patients particularly those with advanced age, renal dysfunction, or elevated serum osmolality can guide prioritization of care, timely intensive care unit referral, and optimization of ED triage protocols.

Although our overall sample size was adequate, the number of patients in certain subgroups (eg, thyroid storm, myxedema coma, SIADH, and DI) was limited. This restricts the statistical power for subgroup-specific analysis, and thus, findings related to these conditions should be interpreted cautiously.

Outcomes and Mortality

The overall mortality was 16.7%, with highest rates in HHS and thyroid storm, reflecting severe presentations and older age. In contrast, SIADH and DI had no mortality, underscoring the effectiveness of timely, condition-specific management. Most DKA and hypercalcemia cases were successfully stabilized and discharged, reflecting the efficacy of standard treatment protocols.

Strength and Limitations

This study provides an in-depth analysis of endocrine emergencies in a tertiary care setting, highlighting their prevalence and management strategies. The large sample size employed enhances the reliability and applicability of the findings. By integrating prospective data collection methods, the study offers a comprehensive assessment of patient outcomes. The involvement of a multidisciplinary team including endocrinologists, emergency physicians, and intensivists ensures a thorough evaluation of each case.

The small sample size for certain emergencies in this study limits the generalizability of the results, highlighting the need for larger multicenter studies to validate the findings. Another limitation of our study is the lack of postdischarge follow-up, which precluded assessment of long-term outcomes such as recurrence, residual neurocognitive deficits, or quality of life. Future prospective multicentric studies should incorporate longitudinal follow-up to better understand recovery trajectories and late complications following endocrine emergencies. Because this was a single-center study conducted at a tertiary care hospital, the findings may not be generalizable to primary or secondary care centers or to regions with different resource settings and health care infrastructure. Lastly, the potential for observer bias exists, given that data collection and analysis were conducted by the same multidisciplinary team involved in patient care.

It is important to note that the COVID-19 pandemic coincided with the study period, during which health care resources were substantially diverted. This resulted in delayed hospital presentations, limited intensive care unit availability, and constrained diagnostic and therapeutic services. These factors may have contributed to the advanced stage of presentation and higher mortality observed in certain emergencies, particularly thyroid storm and HHS.

Our study did not evaluate genetic or inflammatory biomarkers that may influence the risk and severity of diabetic emergencies. Notably, the KCNJ11 rs5219 (E23K) alteration has been associated with increased diabetes risk via impaired insulin secretion, 38 whereas elevated galectin-3 levels reflect metabolic inflammation relevant to glycemic crises. 39 Additionally, red cell distribution width, a marker of oxidative stress and vascular inflammation, has shown prognostic value in diabetes but was not assessed. 40

Conclusion

This study examines the incidence and outcomes of endocrine emergencies in the ED. DKA is the most common and manageable condition, whereas HHS and thyroid storm, although less frequent, have higher mortality rates. In DKA, significant mortality predictors include age, serum osmolality, renal function, and hypertension in patients with T2DM. Elevated serum osmolality is a key predictor of poor outcomes in HHS. The high mortality associated with HHS and thyroid storm highlights the urgent need for standardized emergency protocols and early referral, especially in older adults with comorbidities. The good outcomes in SIADH and DI underscore the role of timely diagnosis and simple yet effective therapy in improving survival in these cases. These findings highlight the need for early recognition and prompt management, particularly in older patients and those with renal impairment. Further multicentered studies and long-term follow-up are essential to understand evolving trends in endocrine emergencies and optimize management strategies.

Disclosure

The authors have no conflicts of interest to disclose.

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Supplementary Material

Supplementary Material

Author Contributions

R.T. and V.J. are co-first authors. S.M., S.K.B., and D.P.D. conceptualized the research; R.T. and V.J. performed data curation; R.T. and V.J. performed formal analysis: S.M., S.K.B., and D.P.D. performed the study methodology; S.M., S.K.B., D.P.D. supervised the study; R.T. and V.J. wrote the manuscript; and R.T., V.J., S.M., S.K.B., and D.P.D. edited the manuscript. All authors reviewed and approved the final manuscript.

Ethical Approval

The study was approved by the Institutional Ethics Committee of the Postgraduate Institute of Medical Education and Research, Chandigarh (Approval No: INT/IEC/2020/SPL-1349), in accordance with the Declaration of Helsinki and Indian Council of Medical Research guidelines.

Consent to Participate

Informed consent was obtained from all patients or their legal representatives.