Sunday, April 20, 2025

Acute Endocrinology in Critical Care

 Acute Endocrinology in Critical Care: A Comprehensive Review for Residents

 Dr Neeraj Manikath ,claude.ai

 Abstract

 

Endocrine emergencies represent a significant proportion of critical illness presentations in intensive care units (ICUs) and require prompt recognition and management to prevent adverse outcomes. This review provides critical care residents with an evidence-based approach to the diagnosis and management of common acute endocrine disorders encountered in the ICU setting. We discuss diabetic emergencies, thyroid crises, adrenal insufficiency, pituitary disorders, and electrolyte abnormalities with a focus on practical management strategies informed by recent literature and clinical guidelines.

 Introduction

Endocrine emergencies constitute a diverse group of conditions that can precipitate or complicate critical illness. The stress response to critical illness itself often leads to significant alterations in endocrine function, creating a complex interplay between primary endocrine disorders and adaptive or maladaptive responses to severe illness. Critical care physicians must be adept at recognizing these conditions, understanding their pathophysiology, and implementing timely interventions to optimize outcomes.

This review aims to provide a practical framework for the diagnosis and management of acute endocrine emergencies in the ICU setting, with a focus on the most commonly encountered conditions and recent evidence-based approaches to their management.

 

 Diabetic Emergencies

 Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis remains a common and potentially life-threatening complication of diabetes mellitus, particularly in type 1 diabetes. While mortality has decreased significantly over the past decades, it remains an important cause of morbidity and ICU admission.

 

 Pathophysiology

DKA results from absolute or relative insulin deficiency coupled with increased counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone), leading to hyperglycemia, ketogenesis, and metabolic acidosis. Critical illness can precipitate DKA through stress-induced counterregulatory hormone release and inflammatory cytokines that enhance insulin resistance.

 

 Diagnosis

The diagnostic criteria for DKA include:

- Hyperglycemia (glucose >250 mg/dL, though "euglycemic DKA" can occur with lower glucose levels, particularly in patients on SGLT2 inhibitors)

- Metabolic acidosis (pH <7.3, bicarbonate <18 mEq/L)

- Ketonemia or ketonuria

Laboratory assessments should include:

- Complete blood count (CBC)

- Comprehensive metabolic panel

- Blood glucose

- Serum ketones (β-hydroxybutyrate is preferred over acetoacetate)

- Arterial blood gas

- Urinalysis

- Cultures and imaging as indicated to identify precipitating causes

 

 Management

The cornerstone of DKA management follows these principles:

 1. Fluid Resuscitation: Initial fluid deficit in DKA typically ranges from 5-10 L. Begin with isotonic crystalloids (0.9% saline) at 15-20 mL/kg/hr for the first hour, then adjust rates based on hemodynamic monitoring.

 2. Insulin Therapy: After initial fluid resuscitation has begun, start an intravenous insulin infusion at 0.1 units/kg/hr. Continue until anion gap closure, then transition to subcutaneous insulin with an overlap period.

 3. Electrolyte Replacement:

   - Potassium: Replete when serum potassium <5.2 mEq/L to maintain levels between 4-5 mEq/L

   - Phosphate: Consider replacement for severe hypophosphatemia (<1.0 mg/dL)

   - Magnesium: Maintain normal levels

 4. Bicarbonate Therapy: Generally not recommended except in severe acidosis (pH <6.9) or when accompanied by hemodynamic instability despite adequate fluid resuscitation.

 5. Transition to Subcutaneous Insulin: When DKA has resolved (glucose <200 mg/dL, anion gap normalized, pH >7.3), transition to subcutaneous insulin with an overlap of 1-2 hours with IV insulin to prevent relapse.

 Recent studies suggest that lower rates of insulin infusion (0.05-0.1 units/kg/hr) may be as effective as traditional higher doses while reducing the risk of hypoglycemia and hypokalemia. Furthermore, rapid acting insulin analogues administered subcutaneously every 1-2 hours have shown similar efficacy to IV insulin in mild to moderate DKA, although IV insulin remains the standard for severe cases or patients with hemodynamic instability.

 

 Hyperosmolar Hyperglycemic State (HHS)

 

HHS typically affects elderly patients with type 2 diabetes and is characterized by severe hyperglycemia, hyperosmolality, and severe dehydration without significant ketoacidosis.

 

 Diagnosis

Diagnostic criteria include:

- Plasma glucose >600 mg/dL

- Serum osmolality >320 mOsm/kg

- Absence of significant ketosis/ketoacidosis

- Profound dehydration

 

 Management

Management principles are similar to DKA but with several important distinctions:

1. Fluid Resuscitation: More aggressive fluid replacement is often required due to more severe dehydration. Initial crystalloid selection should be guided by serum sodium (corrected for hyperglycemia).

2. Insulin Therapy: Lower insulin doses are typically needed compared to DKA. Starting at 0.05-0.1 units/kg/hr is appropriate, with a focus on gradual glucose reduction (50-75 mg/dL/hr) to avoid rapid osmolar shifts and cerebral edema.

3. Thromboprophylaxis: HHS carries a high risk of thrombotic complications; early initiation of prophylactic anticoagulation is recommended unless contraindicated.

 

 Hypoglycemia in the ICU

Iatrogenic hypoglycemia remains a significant concern in critically ill patients, particularly during intensive insulin therapy. Hypoglycemia is independently associated with increased mortality in ICU patients.

 

 Management

Treatment principles include:

- IV dextrose 50% (25g) for severe hypoglycemia

- Continuous glucose infusion may be required for prolonged hypoglycemia, particularly with long-acting insulin or sulfonylurea overdose

- Octreotide may be useful in sulfonylurea-induced hypoglycemia

Current guidelines recommend targeting blood glucose levels between 140-180 mg/dL in most critically ill patients, as this range balances the risks of hyperglycemia with those of hypoglycemia.

 

 Thyroid Emergencies

 

 Thyroid Storm

 

Thyroid storm represents the extreme manifestation of thyrotoxicosis and is associated with significant mortality (10-30%) even with optimal treatment.

 Diagnosis

Clinical diagnosis is based on the presence of severe thyrotoxicosis with evidence of systemic decompensation:

- Hyperthermia

- Tachycardia out of proportion to fever

- Central nervous system effects (agitation, delirium, psychosis, coma)

- Gastrointestinal dysfunction (nausea, vomiting, diarrhea)

- Cardiovascular dysfunction (heart failure, hypotension)

The Burch-Wartofsky Point Scale can help assess the probability of thyroid storm.

 

 Management

Treatment must be initiated based on clinical suspicion without waiting for laboratory confirmation:

1. Anti-thyroid drugs: Thionamides block new hormone synthesis.

   - Propylthiouracil (PTU): 600-1000 mg loading dose, then 200-250 mg every 4 hours

   - Methimazole: 60-80 mg loading dose, then 20-30 mg every 6 hours

   - PTU is preferred initially due to additional inhibition of peripheral T4 to T3 conversion

 

2. Iodine solutions: Inhibit thyroid hormone release (Wolff-Chaikoff effect)

   - Start 1 hour after thionamides to prevent iodine utilization for increased hormone synthesis

   - Lugol's solution (8 drops q6h) or potassium iodide (5 drops q6h)

3. Beta-blockers: Control adrenergic symptoms

   - Propranolol 60-80 mg orally every 4-6 hours or 1-2 mg IV q4h

   - Esmolol infusion is an alternative for better titration in hemodynamically unstable patients

4. Glucocorticoids: Inhibit peripheral conversion of T4 to T3 and treat potential relative adrenal insufficiency

   - Hydrocortisone 100 mg IV q8h or dexamethasone 2-4 mg IV q6h

5. Supportive care:

   - Aggressive cooling for hyperthermia

   - Fluid resuscitation

   - Nutritional support

   - Treatment of precipitating cause

Plasma exchange or plasmapheresis may be considered in refractory cases unresponsive to conventional therapy.

 Myxedema Coma

Myxedema coma is a rare but life-threatening manifestation of severe hypothyroidism with mortality rates of 20-50%.

Diagnosis

Clinical features include:

- Altered mental status

- Hypothermia

- Bradycardia

- Hypoventilation

- Non-pitting edema

- Delayed relaxation of deep tendon reflexes

Laboratory findings typically show:

- Elevated TSH (except in secondary hypothyroidism)

- Low free T4 and T3

- Hyponatremia

- Hypoglycemia

- Hypercapnia

 Management

1. Thyroid hormone replacement:

   - Levothyroxine (T4): 300-500 μg IV loading dose, followed by 50-100 μg IV daily

   - Consider adding liothyronine (T3) in patients with cardiovascular compromise: 5-20 μg IV q8h

2. Glucocorticoids:

   - Hydrocortisone 100 mg IV q8h until coexisting adrenal insufficiency is ruled out

3. Supportive care:

   - Passive rewarming (aggressive rewarming can cause vasodilation and cardiovascular collapse)

   - Cautious fluid resuscitation

   - Correction of electrolyte abnormalities

   - Ventilatory support as needed

   - Treatment of precipitating factors

 

 Adrenal Emergencies

 Adrenal Crisis

 

Adrenal crisis is a life-threatening emergency characterized by circulatory collapse and electrolyte abnormalities resulting from glucocorticoid deficiency.

 Diagnosis

Clinical features include:

- Hypotension refractory to fluids

- Abdominal pain, nausea, vomiting

- Fever

- Altered mental status

- Hyperpigmentation (in primary adrenal insufficiency)

Laboratory findings:

- Hyponatremia

- Hyperkalemia (primarily in primary adrenal insufficiency)

- Hypoglycemia

- Eosinophilia

- Elevated BUN/creatinine

Diagnosis is confirmed with random cortisol and ACTH levels, followed by ACTH stimulation test once the patient is stabilized. However, treatment should not be delayed pending test results.

 Management

1. Glucocorticoid replacement:

   - Hydrocortisone 100 mg IV bolus, followed by 50-100 mg IV q6-8h or continuous infusion of 200-300 mg/24h

   - Transition to oral replacement when patient is stable

2. Fluid resuscitation:

   - Normal saline 1-2 L in the first hour, followed by continuous infusion guided by hemodynamic parameters

3. Vasopressors:

   - May be required despite adequate fluid and steroid replacement

   - Norepinephrine is generally preferred

4. Electrolyte management:

   - Correct hypoglycemia with dextrose

   - Monitor and correct electrolyte abnormalities

5. Mineralocorticoid replacement:

   - Generally not needed during acute crisis management (high-dose hydrocortisone provides sufficient mineralocorticoid effect)

   - Add fludrocortisone 0.1 mg daily once hydrocortisone doses are below 50 mg/day in primary adrenal insufficiency

 Critical Illness-Related Corticosteroid Insufficiency (CIRCI)

CIRCI refers to inadequate corticosteroid activity relative to the severity of a patient's illness, resulting from dysfunction at any level of the hypothalamic-pituitary-adrenal (HPA) axis.

 Diagnosis

The diagnosis remains challenging due to:

- Variable cortisol cutoffs in different studies

- Effects of hypoalbuminemia on total cortisol measurements

- Variable cortisol response in different critical illnesses

The 2017 guidelines of the Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) suggest:

- Delta cortisol <9 μg/dL after cosyntropin 250 μg AND

- Random total cortisol <10 μg/dL

However, these criteria remain controversial, and clinical judgment is essential.

 Management

The use of corticosteroids in CIRCI remains controversial and should be guided by specific clinical scenarios:

1. Septic shock:

   - Consider hydrocortisone 200-300 mg/day in divided doses or continuous infusion for patients with refractory shock despite adequate fluid resuscitation and vasopressor support

   - Continue for 7 days or until vasopressors are discontinued

2. ARDS:

   - Consider methylprednisolone in moderate to severe ARDS

   - Initial dose 1 mg/kg/day, followed by gradual taper

3. Post-cardiac surgery vasoplegic shock:

   - Hydrocortisone may reduce vasopressor requirements and ICU length of stay

The ADRENAL trial (2018) showed no mortality benefit but faster shock resolution with hydrocortisone in septic shock, while the APROCCHSS trial (2018) demonstrated reduced mortality with the combination of hydrocortisone and fludrocortisone.

 Pituitary Emergencies

 Pituitary Apoplexy

 

Pituitary apoplexy is a medical emergency resulting from sudden hemorrhage or infarction of the pituitary gland, often within a pre-existing adenoma.

 Diagnosis

Clinical features include:

- Sudden onset of severe headache

- Visual disturbances (visual field defects, reduced acuity, ophthalmoplegia)

- Altered mental status

- Signs of meningeal irritation

- Features of hypopituitarism

Diagnosis is confirmed with urgent MRI showing hemorrhage or infarction in the pituitary gland.

 Management

1. Hormonal replacement:

   - Hydrocortisone 100 mg IV q6-8h (priority - adrenal crisis can be life-threatening)

   - Thyroid hormone replacement if secondary hypothyroidism is present

2. Neurosurgical evaluation:

   - Urgent decompression may be needed for severe visual impairment or declining consciousness

3. Supportive care:

   - Fluid and electrolyte management

   - Correction of other hormonal deficiencies once stabilized

 Syndrome of Inappropriate ADH Secretion (SIADH)

SIADH is a common cause of hyponatremia in critically ill patients and is characterized by inappropriate release of vasopressin leading to water retention.

 Diagnosis

Diagnostic criteria include:

- Hypotonic hyponatremia (serum Na⁺ <135 mEq/L)

- Decreased serum osmolality (<275 mOsm/kg)

- Inappropriate urine concentration (urine osmolality >100 mOsm/kg)

- Elevated urine sodium (>30 mEq/L with normal salt intake)

- Normal adrenal, thyroid, and kidney function

- Absence of diuretic use or significant hypovolemia

 Management

1. Mild asymptomatic hyponatremia (Na⁺ >125 mEq/L):

   - Fluid restriction (800-1000 mL/day)

2. Moderate symptomatic hyponatremia (Na⁺ 120-125 mEq/L):

   - Fluid restriction

   - Consider vasopressin receptor antagonists (vaptans) in chronic cases

3. Severe symptomatic hyponatremia (Na⁺ <120 mEq/L) or neurological symptoms:

   - Hypertonic saline (3%) 100-150 mL over 10-20 minutes, may repeat 2-3 times

   - Target correction rate: 4-6 mEq/L in first 24 hours to avoid osmotic demyelination syndrome

   - Consider continuous infusion with frequent electrolyte monitoring

4. Treat underlying cause when identified

 

 Electrolyte Disorders in Endocrine Emergencies

Hypercalcemia

Severe hypercalcemia (Ca²⁺ >14 mg/dL) represents a medical emergency requiring ICU admission. Common causes in the ICU include malignancy, primary hyperparathyroidism, and medication effects.

 Management

1. Aggressive hydration:

   - Normal saline 200-300 mL/hr initially, then adjusted based on volume status

   - Enhances calciuresis

2. Loop diuretics:

   - Once adequately hydrated, furosemide 20-40 mg IV q2-4h

   - Increases renal calcium excretion

3. Bisphosphonates:

   - Zoledronic acid 4 mg IV over 15-30 minutes

   - Onset of action within 24-48 hours

4. Calcitonin:

   - 4 IU/kg SC/IM q12h

   - Rapid but temporary effect (48-72 hours)

   - Useful as bridge therapy

5. Glucocorticoids:

   - Effective primarily in vitamin D-mediated or granulomatous causes

   - Hydrocortisone 200-300 mg/day or equivalent

6. Dialysis:

   - Consider in refractory cases or renal failure

 Hyponatremia

Hyponatremia is the most common electrolyte disorder in hospitalized patients and is associated with increased mortality.

 Management

Management depends on the etiology, severity, and chronicity:

1. Severe symptomatic hyponatremia (Na⁺ <120 mEq/L with neurological symptoms):

   - Hypertonic saline (3%) boluses: 100 mL over 10 minutes, repeat up to 3 times as needed

   - Target increase: 4-6 mEq/L in first 24 hours

   - Maximum correction rate: 8-10 mEq/L in 24 hours and 18 mEq/L in 48 hours

   - Frequent monitoring (every 2-4 hours)

2. Chronic hyponatremia (>48 hours):

   - More conservative correction to avoid osmotic demyelination syndrome

   - Target increase: <8 mEq/L in 24 hours

3. Hypervolemic hyponatremia:

   - Fluid restriction

   - Diuretics

   - Treatment of underlying cause (heart failure, cirrhosis)

   - Consider vaptans in appropriate patients

4. Hypovolemic hyponatremia:

   - Isotonic saline to restore volume status

   - Treatment of underlying cause

 Glucose Control in the ICU

 

Glycemic management remains a cornerstone of critical care. Following the publication of the NICE-SUGAR trial, which demonstrated increased mortality with intensive glucose control (81-108 mg/dL) compared to conventional control (<180 mg/dL), most guidelines now recommend targeting blood glucose levels between 140-180 mg/dL in critically ill patients.

 Insulin Protocols

- Computer-guided or nurse-driven protocols based on frequent monitoring improve glycemic control

- Subcutaneous insulin regimens are appropriate for stable patients tolerating enteral nutrition

- Continuous insulin infusions are preferred for:

  - Diabetic emergencies

  - NPO status or variable nutritional intake

  - Hemodynamic instability

  - Liver failure

  - Significant insulin resistance

 Special Considerations

1. Enteral nutrition interruptions:

   - Reduce insulin doses by 50-80% when feeds are interrupted

   - Consider dextrose infusion during prolonged interruptions

2. Steroid therapy:

   - Significant hyperglycemia may develop even in non-diabetic patients

   - Insulin requirements often increase dramatically

   - Consider separate "steroid-specific" insulin dosing

3. Continuous Renal Replacement Therapy (CRRT):

   - May reduce insulin requirements due to clearance of counterregulatory hormones

   - Dextrose-containing replacement fluids may increase glucose levels

 Conclusion

Endocrine emergencies in critical care require prompt recognition and management to optimize outcomes. A systematic approach to diagnosis and treatment, coupled with awareness of recent evidence and guidelines, allows critical care physicians to effectively manage these complex conditions. Future research focusing on individualized approaches to hormone replacement and targeted therapies holds promise for further improving outcomes in critically ill patients with endocrine disorders.

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