Critical Care Endocrinology Emergencies: Navigating Diagnostic Dilemmas and Therapeutic Challenges in the ICU

Dr Neeraj Manikath , claude.ai

Abstract

Endocrinological emergencies in the intensive care unit present unique diagnostic and therapeutic challenges that require rapid recognition and intervention. This review focuses on three critical areas where clinical decision-making is often complex: distinguishing thyroid storm from sick euthyroid syndrome, managing relative adrenal insufficiency in shock states, and recognizing SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis. We provide evidence-based guidance, clinical pearls, and practical management strategies to improve outcomes in these challenging scenarios.

Keywords: Thyroid storm, sick euthyroid syndrome, relative adrenal insufficiency, SGLT2 inhibitors, diabetic ketoacidosis, critical care endocrinology

Introduction

Endocrine emergencies in critical care settings demand immediate recognition and treatment, yet they often present diagnostic challenges that can lead to delayed or inappropriate therapy. The critically ill patient's physiological stress response creates a complex milieu where normal endocrine function is disrupted, making differentiation between pathological endocrine emergencies and adaptive responses particularly difficult.

This review addresses three high-stakes scenarios where clinical judgment and evidence-based medicine intersect: thyroid storm versus sick euthyroid syndrome, relative adrenal insufficiency in shock, and SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis (DKA). Each represents a paradigm where misdiagnosis can result in significant morbidity and mortality.

Thyroid Storm vs. Sick Euthyroid Syndrome: When to Treat?

Clinical Presentation and Diagnostic Challenge

Thyroid storm represents a life-threatening extreme of hyperthyroidism with mortality rates of 10-30% despite treatment¹. However, distinguishing thyroid storm from sick euthyroid syndrome (SES) in critically ill patients remains one of the most challenging diagnostic dilemmas in critical care endocrinology.

Clinical Pearl: The presence of fever, altered mental status, and cardiovascular instability in a patient with known or suspected hyperthyroidism should prompt immediate consideration of thyroid storm, regardless of thyroid function test results.

Pathophysiology

Thyroid storm occurs when excessive thyroid hormones overwhelm the body's compensatory mechanisms, leading to hypermetabolism and multi-organ dysfunction. The exact trigger mechanism remains unclear, but precipitating factors include:

Infection (most common)
Discontinuation of antithyroid medications
Iodine exposure
Surgery or trauma
Pregnancy/delivery

Sick euthyroid syndrome, conversely, represents an adaptive response to critical illness characterized by decreased peripheral conversion of T4 to T3, resulting in low T3 levels with variable T4 and TSH levels².

Diagnostic Approach

Laboratory Findings:

Thyroid Storm:

Suppressed TSH (<0.01 mU/L)
Elevated free T4 (typically >5 ng/dL)
Elevated or normal free T3
May have elevated total T4/T3 due to increased binding proteins

Sick Euthyroid Syndrome:

Variable TSH (low, normal, or slightly elevated)
Low or low-normal free T3
Variable free T4
Often low reverse T3

Oyster: Laboratory values alone cannot definitively distinguish thyroid storm from SES. Clinical correlation is paramount.

Burch-Wartofsky Point Scale (BWPS)

The BWPS remains the most widely used clinical scoring system:

Score Components:

Temperature: 99-99.9°F (5 points), 100-100.9°F (10 points), 101-101.9°F (15 points), etc.
CNS effects: Absent (0), mild agitation (10), delirium/psychosis (20), extreme lethargy/coma (30)
Tachycardia: 90-109 bpm (5 points), 110-119 bpm (10 points), etc.
Atrial fibrillation: Present (10 points)
Heart failure: Absent (0), mild (5), moderate (10), severe (15)
Precipitant history: Present (10 points)

Interpretation:

<25 points: Thyroid storm unlikely
25-44 points: Suggestive of impending storm
≥45 points: Highly suggestive of thyroid storm³

Clinical Hack: Don't wait for laboratory confirmation if BWPS ≥45 and clinical suspicion is high. Initiate treatment immediately.

Management Strategy

Immediate Treatment Protocol:

Beta-blockade: Propranolol 1-2 mg IV q5min or esmolol infusion
Antithyroid agents: Methimazole 20-30 mg PO/NG q8h or PTU 300-400 mg PO/NG q8h
Iodine blockade: Lugol's solution 4-8 drops PO q8h (give 1-2 hours after antithyroid agents)
Corticosteroids: Hydrocortisone 100-200 mg IV q8h
Supportive care: Aggressive fluid resuscitation, cooling measures, electrolyte correction

Pearl: Always give antithyroid medications before iodine to prevent paradoxical worsening from the Wolff-Chaikoff effect.

When to Treat: Decision Algorithm

Treat immediately if:

BWPS ≥45 with compatible clinical picture
Known hyperthyroidism + acute decompensation
Unexplained fever + tachycardia + altered mental status

Consider treatment if:

BWPS 25-44 with high clinical suspicion
Critically ill patient with suppressed TSH and elevated free hormones

Oyster: The decision to treat should never be delayed pending laboratory results. Clinical judgment supersedes laboratory values in acute management.

Relative Adrenal Insufficiency: Cortisol Thresholds in Shock

Definition and Pathophysiology

Relative adrenal insufficiency (RAI), also termed critical illness-related corticosteroid insufficiency (CIRCI), occurs when the adrenal glands fail to produce adequate cortisol relative to the stress of critical illness⁴. Unlike primary adrenal insufficiency, the hypothalamic-pituitary-adrenal (HPA) axis may be intact, but the response is insufficient for the degree of physiological stress.

Diagnostic Criteria

Current Consensus Criteria (2017 Guidelines)⁵:

Random Cortisol Levels:

<10 μg/dL (276 nmol/L): Suggests CIRCI
10-18 μg/dL (276-497 nmol/L): Indeterminate; consider clinical context
18 μg/dL (497 nmol/L): CIRCI unlikely

Cosyntropin Stimulation Test (250 μg IV):

Δ cortisol <9 μg/dL (248 nmol/L) at 60 minutes: Suggests CIRCI
Peak cortisol <18 μg/dL: Alternative criterion

Clinical Pearl: The cosyntropin stimulation test may not be reliable in acute critical illness due to altered protein binding and tissue sensitivity.

Patient Populations at Risk

High-risk scenarios:

Septic shock requiring vasopressors
ARDS with refractory hypoxemia
Major surgical stress
Traumatic brain injury
Prolonged mechanical ventilation
Previous steroid exposure/withdrawal

Clinical Manifestations

Hemodynamic:

Vasopressor-resistant hypotension
Increased fluid requirements
Cardiac dysfunction

Metabolic:

Hyponatremia
Hyperkalemia
Hypoglycemia
Eosinophilia (rare in critical illness)

Management Approach

Hydrocortisone Dosing Strategies:

Option 1: Continuous Infusion

Loading dose: 100 mg IV bolus
Maintenance: 200 mg/24h continuous infusion
Duration: 5-7 days with gradual taper

Option 2: Bolus Dosing

50 mg IV q6h for 5-7 days
Gradual taper over 3-5 days

Clinical Hack: Continuous infusion may provide more stable cortisol levels and potentially better outcomes than bolus dosing⁶.

Evidence-Based Recommendations

Septic Shock:

Consider hydrocortisone in patients requiring high-dose vasopressors
ADRENAL trial: 200 mg/day reduced time to shock reversal⁷
APROCCHSS trial: Hydrocortisone + fludrocortisone improved 90-day mortality⁸

Other Indications:

ARDS: Methylprednisolone may improve ventilator-free days if started early⁹
Post-cardiac surgery: Consider in vasopressor-dependent patients

Practical Management Tips

Pearl: Don't delay steroid administration for cosyntropin testing in hemodynamically unstable patients.

Monitoring Parameters:

Blood pressure and vasopressor requirements
Electrolytes (Na⁺, K⁺)
Blood glucose
Signs of infection (steroids may mask fever)

Tapering Strategy:

Begin taper when vasopressors are weaned
Reduce dose by 25-50% every 1-2 days
Monitor for rebound hypotension

SGLT2 Inhibitor-Associated Euglycemic DKA: Recognizing the Pitfall

Background and Epidemiology

SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) have revolutionized diabetes management but carry a unique risk of euglycemic diabetic ketoacidosis (euDKA)¹⁰. The incidence ranges from 0.16-0.76 per 1000 patient-years, but recognition is often delayed due to normal or only mildly elevated glucose levels.

Pathophysiology

Mechanism of euDKA:

Glucose lowering: SGLT2 inhibition reduces renal glucose reabsorption
Ketogenesis promotion:
- Reduced insulin levels due to lower glucose
- Increased glucagon secretion
- Enhanced lipolysis and β-oxidation
Renal ketone retention: Paradoxically, SGLT2 inhibitors may reduce ketone excretion

Precipitating Factors:

Prolonged fasting/poor oral intake
Intercurrent illness
Surgery (especially with NPO status)
Dehydration
Alcohol use
Pregnancy
Low-carbohydrate diets

Clinical Presentation

Classic Triad (often absent):

Polyuria, polydipsia, polyphagia may be minimal
Glucose typically <250 mg/dL (often <200 mg/dL)
Patients may appear relatively well initially

Red Flag Symptoms:

Nausea and vomiting
Abdominal pain
Dyspnea
Altered mental status (less common than in hyperglycemic DKA)
Fruity breath odor

Oyster: The absence of significant hyperglycemia can lead to misdiagnosis as gastroenteritis, acute abdomen, or respiratory illness.

Diagnostic Criteria

Laboratory Findings:

pH <7.30 or bicarbonate <18 mEq/L
Anion gap >12 mEq/L
Positive ketones (serum β-hydroxybutyrate >3 mmol/L or urine ketones)
Glucose <250 mg/dL (key differentiating feature)

Clinical Hack: Always check ketones in SGLT2 inhibitor users presenting with nausea, vomiting, or malaise, regardless of glucose level.

Management Protocol

Immediate Assessment:

Arterial blood gas
Comprehensive metabolic panel with anion gap
Serum or urine ketones
Point-of-care glucose

Treatment Algorithm:

Phase 1: Stabilization (0-6 hours)

IV access and fluid resuscitation
Normal saline 15-20 mL/kg/h initially
Discontinue SGLT2 inhibitor immediately
Begin insulin infusion: 0.1 units/kg/h IV

Phase 2: Ketone clearance (6-24 hours)

Continue insulin until anion gap normalizes and pH >7.30
Add dextrose 5-10% when glucose <250 mg/dL to prevent hypoglycemia
Monitor electrolytes q2-4h initially

Pearl: Unlike traditional DKA, glucose management is more challenging due to lower starting glucose levels. Early dextrose supplementation is often necessary.

Electrolyte Management:

Potassium: Replace aggressively (goal 4.0-5.0 mEq/L)
Phosphate: Replace if <2.5 mg/dL
Magnesium: Check and replace if low

Prevention Strategies

High-risk Situations:

Hold SGLT2 inhibitors 3-5 days before planned surgery
Advise patients to stop during illness with poor oral intake
Educate about ketone testing during sick days

Patient Education Points:

Never stop insulin (Type 1 diabetes)
Test ketones when feeling unwell
Maintain adequate carbohydrate intake
Seek medical attention for persistent nausea/vomiting

Transition and Follow-up

Criteria for ICU Discharge:

pH >7.30 and anion gap <12 mEq/L
Tolerating oral intake
Stable vital signs

Long-term Management:

Consider discontinuing SGLT2 inhibitor if recurrent episodes
Reassess diabetes management strategy
Enhanced patient education on recognition and prevention

Clinical Pearls and Practical Tips

Universal ICU Endocrine Principles

Always consider endocrine causes in unexplained hemodynamic instability
Clinical presentation trumps laboratory values in acute management
Early recognition and treatment improve outcomes significantly
Maintain high index of suspicion in high-risk populations

Diagnostic Shortcuts

Thyroid Storm:

Fever + tachycardia + altered mental status = treat first, confirm later
BWPS ≥45 with compatible clinical picture = immediate treatment

Relative Adrenal Insufficiency:

Vasopressor-resistant shock = consider steroid trial
Don't delay treatment for cosyntropin testing

SGLT2 euDKA:

Nausea + vomiting + SGLT2 use = check ketones regardless of glucose
Low glucose doesn't rule out DKA in SGLT2 users

Management Hacks

Thyroid Storm: Give PTU before iodine to prevent paradoxical worsening
Steroid Replacement: Continuous infusion may be superior to bolus dosing
euDKA: Early dextrose supplementation prevents hypoglycemia during treatment

Future Directions and Research Needs

Several areas require further investigation:

Biomarkers for early identification of endocrine emergencies
Personalized thresholds for steroid replacement based on individual stress responses
Risk stratification tools for SGLT2 inhibitor-associated complications
Optimal monitoring strategies in resource-limited settings

Conclusion

Endocrine emergencies in critical care require rapid recognition, clinical judgment, and evidence-based management. The three scenarios discussed—thyroid storm versus sick euthyroid syndrome, relative adrenal insufficiency, and SGLT2 inhibitor-associated euglycemic DKA—represent high-stakes situations where prompt intervention can be life-saving.

Key takeaways for critical care practitioners include: treating thyroid storm based on clinical suspicion rather than awaiting laboratory confirmation, considering steroid replacement in vasopressor-resistant shock, and maintaining vigilance for euglycemic DKA in SGLT2 inhibitor users. Success in managing these conditions relies on combining clinical acumen with evidence-based protocols while avoiding common diagnostic pitfalls.

As our understanding of critical care endocrinology continues to evolve, maintaining awareness of these challenging scenarios and their management principles will remain essential for optimal patient outcomes.

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Conflict of Interest: The authors declare no conflicts of interest.

Funding: No specific funding was received for this work.

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Thursday, August 14, 2025