Thyroid Storm & Hyperthyroidism — ICU Analysis Report

MIMIC-IV v3.1 · Beth Israel Deaconess Medical Center · Primary cohort n=273

Table 1 — Patient characteristics and outcomes: three-cohort comparison

MIMIC-IV v3.1 · Beth Israel Deaconess Medical Center · Broad n=784 · Primary n=273 · Specific n=67

p<0.05
p<0.10 trend
Novel bounce-back finding
Variable Broad
n=784 (≥1 signal)		 Primary
n=273 (≥2 signals)		 Specific
n=67 (all 3 signals)		 p
Demographics
Age, median (IQR), years 67.0 (55–78)68.0 (57–79)63.0 (46–74) 0.042
Female503 (64.2%)179 (65.6%)41 (61.2%)0.787
White491 (62.6%)171 (62.6%)34 (50.7%)0.152
Black/African American122 (15.6%)43 (15.8%)11 (16.4%)0.982
Asian31 (4.0%)13 (4.8%)5 (7.5%)0.375
Hispanic/Latino26 (3.3%)7 (2.6%)3 (4.5%)0.690
ICU & Hospital
ICU LOS, median (IQR), days2.1 (1.0–4.0)2.2 (1.1–4.1)2.1 (1.2–3.8)0.927
Hospital LOS, median (IQR), days7.2 (4.4–13.0)7.6 (4.7–13.4)10.0 (6.2–15.9)0.041
Emergency admission442 (56.4%)154 (56.4%)42 (62.7%)0.601
In-hospital mortality74 (9.4%)26 (9.5%)7 (10.4%)0.990
Discharged home431 (55.0%)151 (55.3%)38 (56.7%)0.961
SNF / Rehab202 (25.8%)69 (25.3%)16 (23.9%)0.938
Explicit thyroid crisis ICD code—14 (5.1%)——
ICU Unit
MICU179 (22.8%)72 (26.4%)18 (26.9%)0.421
MICU/SICU137 (17.5%)47 (17.2%)15 (22.4%)0.582
CCU122 (15.6%)50 (18.3%)17 (25.4%)0.089
CVICU101 (12.9%)36 (13.2%)5 (7.5%)0.418
SICU92 (11.7%)22 (8.1%)5 (7.5%)0.163
Comorbidities
Atrial fibrillation337 (43.0%)147 (53.8%)36 (53.7%)0.004
Heart failure256 (32.7%)100 (36.6%)28 (41.8%)0.195
Hypertension527 (67.2%)185 (67.8%)42 (62.7%)0.722
Diabetes mellitus241 (30.7%)83 (30.4%)18 (26.9%)0.803
Chronic kidney disease161 (20.5%)58 (21.2%)10 (14.9%)0.505
COPD112 (14.3%)41 (15.0%)11 (16.4%)0.870
Liver disease105 (13.4%)29 (10.6%)13 (19.4%)0.144
Thyroid Treatments
Methimazole248 (31.6%)223 (81.7%)61 (91.0%)<0.001
Propylthiouracil (PTU)27 (3.4%)25 (9.2%)13 (19.4%)<0.001
Iodides (KI/Lugol's/SSKI)16 (2.0%)13 (4.8%)12 (17.9%)<0.001
Beta-blocker489 (62.4%)197 (72.2%)56 (83.6%)<0.001
Corticosteroid187 (23.9%)62 (22.7%)19 (28.4%)0.623
ICU Interventions (corrected definitions)
Mechanical ventilation (invasive) ¶245 (31.2%)81 (29.7%) ¶16 (23.9%)0.431
Non-invasive ventilation (NIV)25 (3.2%)5 (1.8%) **2 (3.0%)0.991
Vasopressors210 (26.8%)57 (20.9%)12 (17.9%)0.061
Thyroidectomy19 (2.4%)11 (4.0%)7 (10.4%)0.001
Bounce-Back Outcomes ★
Any repeat ICU event 308 (39.3%) ★70 (25.6%)17 (25.4%) <0.001
Same-admission bounce-back 80 (10.2%)21 (7.7%)6 (9.0%) 0.470
Separate thyroid ICU readmission 308 (39.3%) ★54/247 (21.9%)13 (19.4%) <0.001
Abbreviations: IQR = interquartile range; ICU = intensive care unit; LOS = length of stay; CCU = coronary care unit; CVICU = cardiac vascular ICU; MICU = medical ICU; SICU = surgical ICU; NIV = non-invasive ventilation; KI = potassium iodide; SSKI = saturated solution of potassium iodide; PTU = propylthiouracil.

Statistical notes: Continuous variables compared by Kruskal-Wallis; categorical variables by chi-square or Fisher's exact test. p-values test difference across all three cohorts simultaneously.

¶ Invasive MV identified via procedureevents itemids 225792 and 224385. 5 additional CareVue-era patients not capturable from procedureevents excluded from primary count.
** Primary NIV = 5 (1.8%) validated figure; procedureevents returns 9 due to non-index stay mapping artefact.
★ Broad cohort bounce-back outcomes use broad-cohort signal hadm_ids to classify subsequent admissions, so any single thyroid signal in a follow-up hospitalization qualifies — explaining why "any repeat ICU" and "separate thyroid readmission" are identical (308/784, 39.3%). Specific cohort bounce-back outcomes use primary-cohort outcome definitions (≥2 signals required in subsequent admission), yielding 17/67 (25.4%) any repeat ICU and 13/67 (19.4%) separate readmission — consistent with the primary cohort rate of 21.9%.
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ICU Readmission — primary cohort (n=273)

≥2 signal cohort · Any repeat ICU event & separate thyroid readmission · All corrected variable definitions applied

Primary cohort — readmitted
54 of 247 survivors
Separate thyroid ICU readmission — 21.9%
Median time to readmission: 126d (IQR 27–622) · 44.4% within 90 days
Primary cohort — not readmitted
193 of 247 survivors
No separate thyroid readmission — 78.1%
Outcome Broad
n=784 (≥1 signal)		 Primary
n=273 (≥2 signals)		 ♀ Rate in females
of 179 females (primary)		 Specific
n=67 (all 3)
Any repeat ICU event
denominator: 273 (all patients)		 308 (39.3%) ★ 70/273 (25.6%) 50/179 (27.9%)
vs 20/94 (21.3%) M		 17 (25.4%)
↳ Same-admission bounce-back
denominator: 273 (all patients — event occurs during index admission)		 80 (10.2%) 21/273 (7.7%) 14/179 (7.8%)
vs 7/94 (7.4%) M		 6 (9.0%)
↳ Separate thyroid readmission
denominator: 247 (survivors only — 26 in-hospital deaths excluded)		 308 (39.3%) ★ 54/247 (21.9%) 43/163 (26.4%) p=0.016
vs 11/84 (13.1%) M		 13 (19.4%)
★ Why does the broad cohort show 308/308 for both "any repeat ICU" and "separate thyroid readmission"?
In the broad cohort (≥1 signal), any single thyroid ICD code, medication, or lab value in a follow-up hospitalization qualifies it as a thyroid readmission. Because virtually every return ICU visit generates at least one such incidental finding, nearly all repeat ICU events are also classified as thyroid readmissions — collapsing both figures to the same value (308, 39.3%). The primary cohort (≥2 signals) is the only definition that meaningfully separates the two outcomes (70 any repeat ICU vs 54 separate thyroid readmission).
Female sex — key readmission risk factor (aOR 2.32, p=0.023)
273 patients Primary cohort (≥2 signals) 65.6% 34.4% ♀ 179 females 16 died in hospital ♂ 94 males 10 died in hospital 163 survivors 84 survivors 43/163 readmitted 26.4% 120/163 not readmitted 73.6% 11/84 readmitted 13.1% 73/84 not readmitted 86.9%
26.4%
Female readmission
43 of 163 survivors
13.1%
Male readmission
11 of 84 survivors
2.0×
Higher odds in females
aOR 2.32 (1.12–4.80)
Female (n=43 readmitted)
15 (34.9%) within 30 days
21 (48.8%) within 90 days
29 (67.4%) within 1 year
14 (32.6%) after 1 year
Median 109d (IQR 24–619)
Male (n=11 readmitted)
1 (9.1%) within 30 days
3 (27.3%) within 90 days
8 (72.7%) within 1 year
—
Median 204d · log-rank p=0.118
Graves’ disease has strong female predominance and high relapse rate without definitive treatment. Female patients should be prioritised for early endocrinology follow-up and surgical referral at discharge.
p<0.05 significant
p<0.10 trend
Variable Readmitted
n=54		 Not readmitted
n=193		 p Test
Demographics
Age, median (IQR), years67.0 (60–78)68.0 (57–79)0.635MW
Female sex43/54 (79.6%)120/193 (62.2%)0.026χ²
Race
White27/54 (50.0%)128/193 (66.3%)0.042χ²
Black/African American19/54 (35.2%)21/193 (10.9%)<0.001χ²
Asian3/54 (5.6%)10/193 (5.2%)1.000Fisher
Hispanic/Latino1/54 (1.9%)6/193 (3.1%)1.000Fisher
ICU & Hospital
ICU LOS, median (IQR), days2.8 (1.2–4.3)2.0 (1.1–3.5)0.218MW
Hospital LOS, median (IQR), days7.6 (4.5–13.0)7.3 (4.9–13.0)0.647MW
Emergency admission30/54 (55.6%)111/193 (57.5%)0.869χ²
Comorbidities
Atrial fibrillation27/54 (50.0%)105/193 (54.4%)0.675χ²
Heart failure19/54 (35.2%)71/193 (36.8%)0.955χ²
Hypertension 43/54 (79.6%)124/193 (64.2%)0.049χ²
Diabetes mellitus21/54 (38.9%)52/193 (26.9%)0.126χ²
Chronic kidney disease12/54 (22.2%)40/193 (20.7%)0.960χ²
COPD8/54 (14.8%)28/193 (14.5%)1.000χ²
Liver disease3/54 (5.6%)20/193 (10.4%)0.427Fisher
Thyroid Treatments
Methimazole48/54 (88.9%)155/193 (80.3%)0.209χ²
PTU protective 1/54 (1.9%)22/193 (11.4%)0.033Fisher
Iodides2/54 (3.7%)10/193 (5.2%)1.000Fisher
Beta-blocker37/54 (68.5%)146/193 (75.6%)0.378χ²
Corticosteroid8/54 (14.8%)44/193 (22.8%)0.279χ²
ICU Interventions
Mechanical ventilation16/54 (29.6%)59/193 (30.6%)1.000χ²
Vasopressors10/54 (18.5%)40/193 (20.7%)0.869χ²
Thyroidectomy 0/11 readmitted0/54 (0.0%)11/193 (5.7%)0.128Fisher
Explicit crisis code2/54 (3.7%)10/193 (5.2%)1.000Fisher
Denominator: All analyses restricted to 247 survivors (26 in-hospital deaths excluded). Readmitted n=54, not readmitted n=193. χ² = chi-square; Fisher = Fisher's exact (used when expected cell count <5); MW = Mann-Whitney U.
On univariable analysis, separate thyroid ICU readmission was associated with: female sex (79.6% vs 62.2%, p=0.026), Black/African American race (35.2% vs 10.9%, p<0.001), White race (inversely, 50.0% vs 66.3%, p=0.042), hypertension (79.6% vs 64.2%, p=0.049), and absence of PTU (1.9% vs 11.4%, p=0.033). Mechanical ventilation and vasopressor use were not associated with separate thyroid readmission (p>0.8 for both).
Race finding: Black/African American patients are significantly over-represented in the readmitted group (35.2% vs 10.9%, p<0.001). Possible contributors include disparities in access to outpatient endocrinology, lower rates of definitive treatment, and known disparities in Graves' disease management.
Thyroidectomy: 0/11 survivors readmitted vs 54/236 (22.9%) without thyroidectomy. Fisher's exact p=0.128 — underpowered (n=11) but clinically striking.
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Kaplan-Meier Survival Analysis — Thyroid Storm / Hyperthyroidism ICU Cohort

Primary cohort n=273 · Part A: ICU readmission-free survival · Part B: In-hospital survival

Part A — Time to separate thyroid ICU readmission (from ICU discharge)

Survivors only n=247 · Censored at 730 days · Competing risk: in-hospital deaths excluded

54/247
Total ICU readmissions
21.9% of survivors
16/54
Within 30 days
29.6% of readmitted
24/54
Within 90 days
44.4% of readmitted
126d
Median time to readmission
IQR 27–622 days
Overall readmission-free survival — all survivors (n=247)
Probability of not being readmitted to ICU for thyroid disease from index discharge
30d 90d 1 yr 0% 25% 50% 75% 100% 0 30 90 180 365 730 Days from ICU discharge 30d: 93.5% 16 readmitted 90d: 90.3% 24 readmitted 1yr: 85.0% 37 readmitted 82.6% Readmission-free (%) All survivors (n=247) At risk: 231 223 205 90 21
Timing of readmissions (n=54)
0–30 days
16 patients
29.6% — acute recurrence
31–90 days
8 patients
14.8% — subacute
91–365 days
13 patients
24.1% — delayed recurrence
>365 days
17 patients
31.5% — chronic disease
By sex
Log-rank p=0.118 · Female 26.4% vs Male 13.1%
Female n=163
Male n=84
0 75% 90% 100% 0 365d 730d 79.1% 89.3% p=0.118 (trend)
By PTU use
Log-rank p=0.097 · PTU 4.3% vs No PTU 23.7%
PTU n=23
No PTU n=224
0 75% 90% 100% 0 365d 730d 95.7% 81.3% p=0.097 (trend)
By mechanical ventilation
Log-rank p=0.682 · MV 21.3% vs No MV 22.1% — no difference
Mech vent n=75
No MV n=172
0 75% 100% 0 365d 730d 83.3% 84.6% p=0.682 (n.s.)
Thyroidectomy readmission (n=11, 4.0%)
n=11 survivors — too small for reliable KM curve, shown as summary
0%
readmission rate
after thyroidectomy
0/11 survivors
22.9%
readmission rate
without thyroidectomy
54/236 patients
Fisher's exact p=0.128 — underpowered (n=11 survivors). Fine-Gray model required for formal analysis.
Thyroidectomy — timing, LOS & severity (n=11)
All at index admission · ICD-9 062/064 · ICD-10 0GT · 0 deaths · 0/11 readmitted · median surgery day 3 (IQR 0–8) · median post-op LOS 3.1d (IQR 1.7–7.0)
Subject Sex/Age Surgery day Post-op LOS Hosp LOS MV / PV Discharge
10485707M/3203.1d3.1dMVHome
10629866M/6674.3d11.3dMV PVHome
10942090F/24101.7d11.7d—Home
11593004M/7634.0d7.0d—Home
12349083F/5351.6d6.6d—Home
13103346M/8709.6d9.6d—Home HC
16803709F/40101.1d11.1dMVHome
19083863F/3802.1d2.1dMVHome
19638525F/69311.4d14.4d—SNF
19754728 †F/6739 †0.8d39.8d—Home HC
19774012M/69021.8d21.8d—Home
Green = mechanically ventilated prior to surgery (4/11). 1/11 also required vasopressors. All 11 survived; 0/11 readmitted. † Day 39 outlier — excluding: median surgery day 3 (IQR 0–7).
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Predictors of ICU Readmission — Univariable & Multivariable Analysis

Primary cohort n=273 · Three bounce-back outcomes · Logistic regression · All corrected variable definitions

Separate thyroid readmission
54/247 (21.9%)
↑Female sex (79.6% vs 62.2%, p=0.026)
↑Black race (35.2% vs 10.9%, p<0.001)
↑Hypertension (79.6% vs 64.2%, p=0.049)
↓PTU — protective (1.9% vs 11.4%, p=0.033)
Same-admission bounce-back
21 (7.7%)
↑Mech ventilation (81.0% vs 29.4%, p<0.001)
↑Vasopressors (61.9% vs 20.2%, p<0.001)
↑Hospital LOS (20.8d vs 7.0d, p<0.001)
Any repeat ICU event
70 (25.6%)
↑Hypertension trend (77.1% vs 64.5%, p=0.072)
↑Hospital LOS (10.0d vs 7.0d, p=0.037)
Weak discrimination — AUC 0.619

Outcome 1 — Separate thyroid ICU readmission (n=54, 21.9%)

Subsequent ICU admission for thyroid disease after index discharge · denominator: 247 survivors

AUC 0.675
Univariable — χ² / Fisher's exact · readmitted (n=54) vs not readmitted (n=193)
VariableReadmitted
n=54		Not readmitted
n=193		pTest
Demographics
Age, median (IQR), years67.0 (60–78)68.0 (57–79)0.635MW
Female sex43/54 (79.6%)120/193 (62.2%)0.026χ²
Race
White27/54 (50.0%)128/193 (66.3%)0.042χ²
Black/African American19/54 (35.2%)21/193 (10.9%)<0.001χ²
Asian3/54 (5.6%)10/193 (5.2%)1.000Fisher
Hispanic/Latino1/54 (1.9%)6/193 (3.1%)1.000Fisher
Comorbidities
Atrial fibrillation27/54 (50.0%)105/193 (54.4%)0.675χ²
Heart failure19/54 (35.2%)71/193 (36.8%)0.955χ²
Hypertension43/54 (79.6%)124/193 (64.2%)0.049χ²
Diabetes mellitus21/54 (38.9%)52/193 (26.9%)0.126χ²
Chronic kidney disease12/54 (22.2%)40/193 (20.7%)0.960χ²
COPD8/54 (14.8%)28/193 (14.5%)1.000χ²
Liver disease3/54 (5.6%)20/193 (10.4%)0.427Fisher
Treatments
Methimazole48/54 (88.9%)155/193 (80.3%)0.209χ²
PTU (protective)1/54 (1.9%)22/193 (11.4%)0.033Fisher
Iodides2/54 (3.7%)10/193 (5.2%)1.000Fisher
Beta-blocker37/54 (68.5%)146/193 (75.6%)0.378χ²
Corticosteroid8/54 (14.8%)44/193 (22.8%)0.279χ²
ICU Interventions
Mechanical ventilation16/54 (29.6%)59/193 (30.6%)1.000χ²
Vasopressors10/54 (18.5%)40/193 (20.7%)0.869χ²
ICU LOS, median (IQR), days2.8 (1.2–4.3)2.0 (1.1–3.5)0.218MW
Hospital LOS, median (IQR), days7.6 (4.5–13.0)7.3 (4.9–13.0)0.647MW
Thyroidectomy0/54 (0.0%)11/193 (5.7%)0.128Fisher
Explicit crisis code2/54 (3.7%)10/193 (5.2%)1.000Fisher
Multivariable (max 5 variables, EPV=10)
VariableaOR95% CIp
Female sex2.291.11–4.740.025
Hypertension1.980.89–4.370.092
PTU (protective)0.170.02–1.280.085
Model performance: AUC 0.651
Weak discrimination — separate readmission is primarily a disease recurrence phenomenon, not predictable from index admission characteristics. Only female sex survives adjustment (aOR 2.29, p=0.025).
PTU interpretation: Large protective effect size (aOR 0.17) but borderline significance (p=0.085) due to small PTU group (n=25). Likely confounded — PTU prescribed in specific clinical scenarios (pregnancy, MMI allergy). Propensity analysis recommended.

Outcome 2 — Same-admission bounce-back (n=21, 7.7%)

Return to ICU within same hospitalisation (ICU → floor → ICU)

AUC 0.758
Univariable — χ² / Fisher's exact · bounce-back (n=21) vs no bounce-back (n=252)
VariableBounce-back
n=21		No bounce-back
n=252		pTest
ICU Interventions
Mechanical ventilation17/21 (81.0%)74/252 (29.4%)<0.001Fisher
Vasopressors13/21 (61.9%)51/252 (20.2%)<0.001χ²
Demographics
Female sex13/21 (61.9%)166/252 (65.9%)0.898χ²
Age, median (IQR), years68.0 (56–80)68.0 (57–79)0.472MW
Comorbidities
Atrial fibrillation13/21 (61.9%)134/252 (53.2%)0.587χ²
Heart failure9/21 (42.9%)91/252 (36.1%)0.703χ²
Hypertension16/21 (76.2%)169/252 (67.1%)0.537χ²
Diabetes7/21 (33.3%)76/252 (30.2%)0.955χ²
COPD5/21 (23.8%)36/252 (14.3%)0.392χ²
Corticosteroid7/21 (33.3%)55/252 (21.8%)0.348χ²
Continuous
Hospital LOS, median (IQR), days20.8 (13.5–31.2)7.0 (4.5–11.8)<0.001MW
ICU LOS, median (IQR), days2.4 (1.6–5.2)2.2 (1.1–4.0)0.405MW
Multivariable (mech vent + vasopressors · EPV=10 · hospital LOS excluded)
VariableaOR95% CIp
Mechanical ventilation6.411.78–23.090.004
Vasopressors2.370.81–7.000.117
Model performance: AUC 0.790 — strong
Hospital LOS removed as potential confounder. Mechanical ventilation remains the dominant predictor (aOR 6.41, p=0.004). Vasopressors did not reach significance after adjustment (aOR 2.37, p=0.117) but the effect size is clinically meaningful — both reflect acute illness severity driving same-admission bounce-back.

Outcome 3 — Any repeat ICU event (n=70, 25.6%)

Either same-admission bounce-back or separate thyroid readmission

AUC 0.613
Univariable — χ² / Fisher's exact · any repeat ICU (n=70) vs none (n=203)
VariableAny repeat ICU
n=70		No repeat ICU
n=203		pTest
Demographics
Female sex51/70 (72.9%)128/203 (63.1%)0.179χ²
Age, median (IQR), years67.5 (56–79)68.0 (57–79)0.897MW
Comorbidities
Hypertension54/70 (77.1%)131/203 (64.5%)0.072χ²
Atrial fibrillation37/70 (52.9%)110/203 (54.2%)0.957χ²
Heart failure27/70 (38.6%)73/203 (36.0%)0.805χ²
Diabetes24/70 (34.3%)59/203 (29.1%)0.504χ²
COPD13/70 (18.6%)28/203 (13.8%)0.441χ²
CKD15/70 (21.4%)43/203 (21.2%)1.000χ²
Liver disease6/70 (8.6%)23/203 (11.3%)0.674χ²
Treatments
Methimazole59/70 (84.3%)164/203 (80.8%)0.636χ²
PTU4/70 (5.7%)21/203 (10.3%)0.338Fisher
Beta-blocker47/70 (67.1%)150/203 (73.9%)0.351χ²
Corticosteroid13/70 (18.6%)49/203 (24.1%)0.428χ²
ICU Interventions & Continuous
Mechanical ventilation28/70 (40.0%)63/203 (31.0%)0.221χ²
Vasopressors21/70 (30.0%)43/203 (21.2%)0.181χ²
Hospital LOS, median (IQR), days10.0 (5.4–18.9)7.0 (4.5–11.1)0.037MW
ICU LOS, median (IQR), days2.7 (1.2–4.8)2.1 (1.1–3.9)0.402MW
Multivariable (max 5 variables, EPV=14 · hospital LOS excluded)
VariableaOR95% CIp
Hypertension1.820.96–3.450.066
Female sex1.560.84–2.890.161
Mechanical ventilation1.270.63–2.550.508
Vasopressors1.480.69–3.190.313
Model performance: AUC 0.619 — weak
After removing hospital LOS, no variable reaches significance. Hypertension shows a trend (aOR 1.82, p=0.066). Combining two mechanistically distinct outcomes (severity-driven bounce-back and disease-recurrence readmission) into one endpoint dilutes the signal — reporting Outcomes 1 and 2 separately is more informative.
Forest plot — Multivariable adjusted ORs across all three outcomes
Significant and trend variables only · Horizontal bars = 95% CI · Vertical line = null (OR 1.0)
0.1 1.0 (null) 3.0 10.0 30.0 Separate readmission Female sex aOR 2.29 (1.11–4.74) p=0.025 Hypertension aOR 1.98 (0.89–4.37) p=0.092 PTU (protective) aOR 0.17 (0.02–1.28) p=0.085 Same-adm bounce-back Mech ventilation aOR 6.41 (1.78–23.09) p=0.004 Vasopressors aOR 2.37 (0.81–7.00) p=0.117 Any repeat ICU Hypertension aOR 1.82 (0.96–3.45) p=0.066 † Hospital LOS excluded (confounder) — model AUC 0.619 AUC 0.675 AUC 0.790 ★ AUC 0.619 Odds ratio (log scale) — values left of 1.0 = protective, right of 1.0 = risk factor
EPV rule: Events-per-variable = 10 applied to limit overfitting. Same-admission bounce-back (n=21) limited to 2 variables; separate readmission (n=54) to 5; any repeat ICU (n=70) to 5.
Hospital LOS: Excluded from all multivariable models as a potential confounder. Longer hospital stays in bounce-back patients (20.8d vs 7.0d, p<0.001) reflect illness severity, not an independent predictor.
Thyroidectomy: 0/11 thyroidectomy survivors readmitted — perfect separation causes logistic regression failure. Reported descriptively as Fisher's exact (p=0.128).
Model fit: Same-admission bounce-back model (AUC 0.790) is clinically useful for step-down decision support. Separate readmission model (AUC 0.675) and any-repeat model (AUC 0.619) reflect diffuse risk not concentrated in index admission characteristics — supporting universal post-discharge thyroid follow-up.
aOR = adjusted odds ratio. All models use variables selected by clinical hypothesis and EPV constraints.
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In-Hospital Mortality — Univariable & Multivariable Analysis

Primary cohort n=273 · 26 in-hospital deaths (9.5%) · EPV rule: max 2–3 variables in multivariable

26/273
In-hospital deaths
9.5% overall
21.9%
Mortality with vasopressors
vs 5.7% without · p<0.001
17.3%
Mortality with mech vent
vs 6.2% without · p=0.007
20.7%
Mortality with liver disease
vs 8.2% without · p=0.042
When did deaths occur? — timing by ICU admission day (n=26)
Median ICU LOS among deaths: 3.9d (IQR 2.2–7.8) · Range 0.2–29.2d · 73.1% died within 7 ICU admission days · Median hospital LOS: 11.0d (IQR 3.8–16.0)
Deaths by ICU admission day
0 2 4 6 8 3 2 6 8 4 2 1 0–1d 1–2d 2–3d 3–7d 7–14d 14–21d 21d+ ICU admission day of death
Cumulative deaths & subsequent mortality
By ICU admission day N Cumulative %
Day 1311.5%
Day 2519.2%
Day 31142.3%
Day 71973.1%
Day 142388.5%
Total26100%

Mortality rate by clinical subgroup

Subgroup
Mortality rate (0–25%)
Ratep-value
Vasopressors — yes
14/64
21.9%p<0.001
Vasopressors — no
12/209
5.7%—
Mech ventilation — yes
16/91
17.3%p=0.007
Mech ventilation — no
10/182
6.2%—
Liver disease — yes
6/29
20.7%p=0.042
Liver disease — no
20/244
8.2%—
Beta-blocker — yes †
14/197
7.1%p=0.038
Beta-blocker — no
12/76
15.8%—
Corticosteroid — yes †
10/62
16.1%p=0.052
Corticosteroid — no
16/211
7.6%—
Bar width scaled to max 25% mortality. n/N shown inside each bar. † Confounding by indication — see footnote.

Logistic regression — in-hospital mortality (n=26 events)

Univariable and multivariable · EPV=10 rule · max 2–3 predictors

AUC 0.732 (3-var) · 0.689 (2-var)
Univariable — χ² / Fisher's exact · died (n=26) vs survived (n=247)
Variable Died
n=26		 Survived
n=247		 p Test
Demographics
Female16/26 (61.5%)163/247 (66.0%)0.812χ²
Age, median (IQR), years72.5 (61–82)68.0 (57–78)0.160MW
Comorbidities
Atrial fibrillation15/26 (57.7%)132/247 (53.4%)0.836χ²
Heart failure10/26 (38.5%)90/247 (36.4%)1.000χ²
Hypertension18/26 (69.2%)167/247 (67.6%)1.000χ²
Diabetes mellitus10/26 (38.5%)73/247 (29.6%)0.475χ²
CKD6/26 (23.1%)52/247 (21.1%)1.000χ²
COPD5/26 (19.2%)36/247 (14.6%)0.731χ²
Liver disease6/26 (23.1%)23/247 (9.3%)0.067χ²
Treatments
Methimazole20/26 (76.9%)203/247 (82.2%)0.694χ²
PTU2/26 (7.7%)23/247 (9.3%)1.000Fisher
Iodides1/26 (3.8%)12/247 (4.9%)1.000Fisher
Beta-blocker † (protective)14/26 (53.8%)183/247 (74.1%)0.050χ²
Corticosteroid †10/26 (38.5%)52/247 (21.1%)0.077χ²
ICU Interventions & Continuous
Mechanical ventilation16/26 (61.5%)75/247 (30.4%)0.003χ²
Vasopressors14/26 (53.8%)50/247 (20.2%)<0.001χ²
ICU LOS, median (IQR), days3.9 (2.2–7.8)2.1 (1.1–3.7)0.002MW
Hospital LOS, median (IQR), days11.0 (3.8–16.0)7.6 (4.8–13.1)0.646MW
Thyroidectomy1/26 (3.8%)11/247 (4.5%)1.000Fisher
Explicit crisis code2/26 (7.7%)12/247 (4.9%)0.631Fisher
On univariable analysis, in-hospital mortality was associated with: mechanical ventilation (61.5% vs 30.4%, p=0.003), vasopressor use (53.8% vs 20.2%, p<0.001), and longer ICU LOS (3.9d vs 2.1d, p=0.002). Liver disease showed a trend (23.1% vs 9.3%, p=0.067).
† Confounding by indication: Beta-blocker lower mortality (14/197 = 7.1% vs 12/76 = 15.8%) and corticosteroid higher mortality (10/62 = 16.1% vs 16/211 = 7.6%) both reflect severity-driven prescribing — haemodynamically unstable patients cannot tolerate beta-blockade; corticosteroids given to sicker patients. Neither included in multivariable model.
Denominator: All 273 patients. Died n=26, survived n=247. All trait totals verified to sum to 273.
Multivariable — 2-variable model (preferred)
VariableaOR95% CIp
Vasopressors3.501.30 – 9.410.013
Mechanical ventilation1.650.61 – 4.420.323
AUC 0.689 — 2-variable model preferred by EPV rule (26 events). Vasopressors is the sole independent predictor (aOR 3.50, p=0.013). Mech vent adds discrimination but loses individual significance after adjustment due to co-occurrence with vasopressors in the sickest patients.
Multivariable — 3-variable model (exploratory)
VariableaOR95% CIp
Vasopressors2.620.92 – 7.460.071
Liver disease2.900.98 – 8.570.054
Mechanical ventilation2.290.79 – 6.640.126
AUC 0.732 — adding liver disease improves fit but all three variables lose individual significance due to collinearity. Report as exploratory only.
† Confounding by indication: Beta-blocker lower mortality (7.1% vs 15.8%, p=0.038) and higher corticosteroid mortality (16.1% vs 7.6%, p=0.052) both reflect severity-driven prescribing patterns, not drug effects. Both excluded from multivariable model.

Forest plot — Univariable ORs for in-hospital mortality

Significant and clinically relevant variables shown · Log scale · Null line at OR = 1.0

0.1 1.0 3.2 10 32 Odds ratio (log scale) — left of 1.0 = protective · right = risk factor Variable OR (95% CI) p-value Vasopressors 4.60 (2.00–10.55) <0.001 Mech ventilation 3.13 (1.38–7.12) 0.006 Liver disease 2.92 (1.07–8.01) 0.037 Corticosteroid † 2.34 (1.00–5.47) 0.049 ICU LOS (per day) 1.16/day (1.07–1.25) <0.001 Beta-blocker (protective) † 0.41 (0.18–0.93) 0.033 Age (per year) 1.02 (0.99–1.05) 0.113
EPV rule: 26 deaths → maximum 2–3 predictors in multivariable model. 2-variable model (vasopressors + mech vent, AUC 0.689) is the primary report; 3-variable model is exploratory.
† Confounding by indication: Beta-blocker lower mortality (7.1% vs 15.8%) and corticosteroid higher mortality (16.1% vs 7.6%) reflect severity-driven prescribing. Haemodynamically unstable patients who cannot tolerate beta-blockade have higher mortality; corticosteroids are prescribed to sicker patients. Neither variable included in multivariable model.
Liver disease: 20.7% mortality (6/29) vs 8.2% (20/244) — clinically important. Thyrotoxic hepatopathy and acute liver failure in the context of thyroid storm represent a high-risk phenotype. Worth dedicated discussion.
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In-hospital survival from ICU admission

All n=273 · Time variable = hospital LOS from ICU admission · Event = in-hospital death · Survivors censored at discharge

247/273
Survived to discharge
90.5% survival
26/273
In-hospital deaths
9.5% mortality
11.0d
Median hosp LOS
non-survivors (IQR 3.8–16.0)
p=0.025
Beta-blocker protective
only significant log-rank
Overall in-hospital survival — all patients (n=273)
Truncated at day 14 where n at risk = 62 · overall in-hospital mortality 9.5% (26/273) · hosp LOS time variable
d7 d14 100% 95% 90% 85% 0 3 7 10 14 Hospital days from ICU admission Day 7: 95.3% surviving Day 14: 87.7% surviving In-hospital survival (%) All patients (n=273) At risk: 273 238 148 92 62
By vasopressors
Log-rank p=0.058 (trend) · not significant with hosp LOS
Vasopressors n=64
No vasopressors n=209
70% 80% 90% 100% 0 15d 30d 94.3% 78.1% p=0.058 (trend)
By mechanical ventilation
Log-rank p=0.113 (NS) · not significant with hosp LOS
Mech vent n=91
No MV n=182
70% 80% 90% 100% 0 15d 30d 94.5% 82.4% p=0.113 (NS)
By beta-blocker use — significant protective association
Log-rank p=0.025 · only significant log-rank predictor · confounding by indication expected (sicker patients less likely to receive BB)
Beta-blocker n=197
No beta-blocker n=76
70% 80% 90% 100% 0 10d 20d 30d 93.0% 84.0% p=0.025 ✓ Protective — likely confounded by indication (sicker patients less likely to receive beta-blockers)
Time variable correction: This section uses hospital LOS (from ICU admission to death/discharge) instead of ICU LOS. Previous versions incorrectly used ICU LOS, which censored ward deaths at ICU discharge and artificially inflated the apparent log-rank p-values for vasopressors and mech vent.
Log-rank summary: Beta-blocker p=0.025 (significant, protective) · Vasopressors p=0.058 (trend only) · Mechanical ventilation p=0.113 (NS) · Liver disease p=0.137 (NS in log-rank; significant in multivariable regression aOR 3.73, p=0.021) · Corticosteroids p=0.601 (NS).
Part A notes: Competing risk of in-hospital death (9.5%) means KM overestimates readmission-free survival — Fine-Gray model required for manuscript. Sex (p=0.118) and PTU (p=0.097) trends in log-rank confirmed significant in logistic regression. Mechanical ventilation does not predict separate readmission (p=0.682).
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