# Adrenal Crisis and Thyroid Storm

## Introduction

Adrenal crisis and thyroid storm represent two of the most dangerous endocrine emergencies encountered in the ED. Both are characterized by the failure of homeostatic hormonal regulation and rapid clinical deterioration. Adrenal crisis carries a mortality rate of up to 6 percent per episode, while untreated thyroid storm approaches 10 to 30 percent mortality. Recognition often requires a high index of suspicion, as presenting features overlap with sepsis, cardiovascular emergencies, and other critical illness.

## Adrenal Crisis

### Pathophysiology

The adrenal cortex produces cortisol (zona fasciculata), aldosterone (zona glomerulosa), and androgens (zona reticularis). Cortisol is essential for vascular tone, glucose homeostasis, immune modulation, and the stress response. Primary adrenal insufficiency (Addison's disease) results from destruction of the adrenal cortex, with autoimmune disease being the most common cause in developed nations and TB, HIV, and infiltrative disease predominating globally; both cortisol and aldosterone are deficient. Secondary adrenal insufficiency is caused by pituitary or hypothalamic failure and is most commonly iatrogenic from chronic exogenous glucocorticoid use and abrupt withdrawal; aldosterone is preserved because it is RAAS-dependent. Adrenal crisis occurs when physiologic cortisol demand exceeds supply, typically precipitated by an acute stressor such as infection, surgery, or trauma in a patient with unrecognized or undertreated adrenal insufficiency.

### Precipitating Factors

Common precipitants include acute illness (sepsis, pneumonia, gastroenteritis) in a patient on chronic steroids, abrupt discontinuation of chronic glucocorticoids (prednisone above 5 mg per day for more than 3 weeks), bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome from meningococcal sepsis), pituitary apoplexy, and surgery or trauma without stress-dose steroids in at-risk patients.

### Clinical Presentation

The hallmark finding is hypotension refractory to fluids and vasopressors. Other features include nausea, vomiting, and abdominal pain (which may mimic an acute abdomen), weakness, fatigue, altered mental status, and lethargy progressing to coma. Hypoglycemia occurs because cortisol is a counter-regulatory hormone. Electrolyte abnormalities include hyponatremia (from cortisol and aldosterone deficiency) and hyperkalemia (in primary insufficiency only, due to aldosterone deficiency). Hyperpigmentation of skin creases and mucous membranes may be present in chronic primary adrenal insufficiency from ACTH excess stimulating melanocytes, but this is not seen in secondary insufficiency or acute presentations.

<image>Clinical presentation diagram of adrenal crisis showing a patient with labeled features: hypotension unresponsive to vasopressors, hyperpigmentation of skin creases and mucous membranes, associated lab findings (hyponatremia, hyperkalemia, hypoglycemia), and common precipitating factors listed alongside</image>

### Diagnosis

Treatment should not be delayed to confirm the diagnosis, as empiric stress-dose steroids are safe and potentially life-saving. A random cortisol level below 3 mcg/dL is diagnostic, while levels of 3 to 15 mcg/dL are indeterminate in the critically ill. The ACTH stimulation test (cosyntropin 250 mcg IV, with cortisol measured at 0 and 60 minutes) confirms adrenal insufficiency if cortisol fails to rise above 18 mcg/dL. If testing is desired before treatment, cortisol and ACTH levels should be drawn, and dexamethasone (which does not cross-react with cortisol assays) should be given rather than hydrocortisone.

### Emergency Treatment

Treatment consists of hydrocortisone 100 mg IV bolus followed by 50 mg IV every 8 hours (or a continuous infusion of 200 mg over 24 hours). Aggressive IV fluid resuscitation with normal saline is required, often 2 to 3 liters in the first few hours. Dextrose (D50 or D10) is given for hypoglycemia. The precipitant must be treated, including broad-spectrum antibiotics if infection is suspected. Fludrocortisone (0.1 mg orally daily) provides mineralocorticoid replacement in primary adrenal insufficiency but is not urgent in the acute setting, as hydrocortisone at stress doses has mineralocorticoid activity. The response to steroids is typically rapid, occurring within hours, and persistent shock despite steroids should prompt evaluation for alternative diagnoses.

## Thyroid Storm

### Pathophysiology

Thyroid storm (thyrotoxic crisis) represents the extreme, decompensated end of hyperthyroidism. Excessive thyroid hormone (T3, T4) action produces hypermetabolism, increased catecholamine sensitivity, and multi-organ dysfunction. It typically occurs in patients with known or undiagnosed Graves' disease who encounter a precipitating event. Unlike simple thyrotoxicosis, thyroid storm involves systemic decompensation with end-organ dysfunction.

### Precipitating Factors

Common precipitants include infection or sepsis, surgery (especially thyroid surgery in unprepared patients), iodine load (IV contrast, amiodarone), abrupt discontinuation of antithyroid medications, DKA, trauma, stroke, pulmonary embolism, and pregnancy and delivery (postpartum thyroiditis).

### Clinical Presentation

Fever is prominent, with temperatures above 40 degrees Celsius (104 degrees Fahrenheit) being common and sometimes exceeding 41 degrees, often disproportionate to any underlying infection. Tachycardia is out of proportion to fever, and atrial fibrillation is present in 10 to 35 percent of cases. Altered mental status manifests as agitation, psychosis, delirium, seizures, or coma. GI symptoms include nausea, vomiting, diarrhea, abdominal pain, and jaundice (with hepatic dysfunction portending a poor prognosis). Cardiovascular collapse may present as high-output heart failure or cardiogenic shock in severe cases. Graves-specific findings such as lid lag, exophthalmos, and goiter may be present.

### Diagnosis -- Burch-Wartofsky Point Scale (BWPS)

The Burch-Wartofsky Point Scale is a clinical scoring system in which a score of 45 or above is highly suggestive of thyroid storm. Components include temperature, CNS effects, GI-hepatic dysfunction, heart rate, heart failure, atrial fibrillation, and precipitating event. Laboratory findings show elevated free T4, elevated total or free T3, and suppressed TSH, but levels do not reliably distinguish thyrotoxicosis from thyroid storm; the diagnosis is clinical. Thyroid storm is a clinical diagnosis with laboratory confirmation, and treatment should not be delayed for thyroid function tests.

<image>Burch-Wartofsky Point Scale reference chart showing scoring criteria for each category (thermoregulatory, CNS, GI-hepatic, cardiovascular) with point values and interpretation thresholds: below 25 unlikely, 25-44 impending storm, 45 or above consistent with thyroid storm</image>

### Emergency Treatment -- Ordered Sequence Matters

The first step is beta-adrenergic blockade. Propranolol is preferred at 60 to 80 mg orally every 4 to 6 hours or 0.5 to 1 mg IV slowly, as it additionally inhibits peripheral T4-to-T3 conversion. Esmolol drip (50 to 100 mcg/kg per minute) is used for hemodynamically unstable patients requiring titration. Beta-blockers treat tachycardia and hyperadrenergic symptoms, with caution in severe heart failure.

The second step blocks new thyroid hormone synthesis. Propylthiouracil (PTU) 500 to 1000 mg loading dose orally or via NG tube, then 250 mg every 4 hours, is preferred in thyroid storm because it also blocks peripheral T4-to-T3 conversion. Methimazole 20 mg orally or rectally every 4 to 6 hours is an alternative that does not block peripheral conversion but has fewer hepatotoxic side effects.

The third step blocks thyroid hormone release and must be given at least 1 hour after the thionamide to prevent iodine from being used as substrate for new hormone synthesis (the Wolff-Chaikoff effect). Lugol's solution (5 to 10 drops orally every 8 hours) or SSKI (5 drops every 6 hours) is used. Lithium carbonate (300 mg orally every 8 hours) is an alternative if iodine is contraindicated due to allergy.

The fourth step reduces peripheral conversion and provides immune modulation. Hydrocortisone 100 mg IV every 8 hours (or dexamethasone 2 mg IV every 6 hours) blocks T4-to-T3 peripheral conversion and treats potential concurrent adrenal insufficiency. Stress doses of steroids are standard of care in thyroid storm.

| Step | Agent | Dose | Mechanism |
|------|-------|------|-----------|
| 1. Beta-blockade | Propranolol | 60–80 mg PO q4–6h or 0.5–1 mg IV | Treats hyperadrenergic symptoms; also blocks T4→T3 conversion |
| 1. Beta-blockade (alt) | Esmolol | 50–100 mcg/kg/min IV drip | Titratable; use if hemodynamically unstable |
| 2. Block synthesis | PTU (preferred) | 500–1000 mg load, then 250 mg q4h PO/NG | Blocks synthesis AND peripheral T4→T3 conversion |
| 2. Block synthesis (alt) | Methimazole | 20 mg PO/PR q4–6h | Blocks synthesis only; fewer hepatotoxic effects |
| 3. Block release (≥1 hr after step 2) | Lugol's solution or SSKI | Lugol's 5–10 drops q8h; SSKI 5 drops q6h | Blocks hormone release (Wolff-Chaikoff effect) |
| 4. Block conversion | Hydrocortisone | 100 mg IV q8h | Blocks T4→T3 conversion; treats concurrent adrenal insufficiency |
| 5. Supportive | Cooling + acetaminophen | External cooling; avoid aspirin | Aspirin displaces T4 from binding proteins |

The fifth step is supportive care. Aggressive cooling for hyperthermia uses external cooling and acetaminophen, while aspirin is avoided because it displaces T4 from binding proteins and increases free hormone levels. IV fluid resuscitation addresses insensible losses and dehydration. The precipitating cause should be treated. Cholestyramine (4 grams orally four times daily) may reduce enterohepatic recirculation of thyroid hormone.

### Refractory Cases

Plasmapheresis or plasma exchange can rapidly remove circulating thyroid hormone in life-threatening, treatment-refractory cases. Emergent thyroidectomy after initial medical stabilization may be considered in rare, extreme cases.

<image>Step-by-step treatment flowchart for thyroid storm showing the timed sequence: beta-blocker first, thionamide at least 1 hour before iodine, concurrent glucocorticoids, and supportive cooling measures with specific drug names and doses at each step</image>

## Clinical Pearls

Adrenal crisis should be suspected in any patient with refractory hypotension, especially with a history of chronic steroid use -- hydrocortisone 100 mg IV should be given empirically, as it is safe and diagnostic delay can be fatal. Cortisol and ACTH should be drawn but treatment should never wait for lab confirmation. In thyroid storm, the sequence of medications matters: thionamide (PTU) must be given at least 1 hour before iodine to prevent fueling new hormone synthesis. Aspirin must be avoided in thyroid storm because it displaces thyroid hormone from binding proteins and can worsen thyrotoxicosis. High-dose glucocorticoids are indicated in both adrenal crisis and thyroid storm; when the endocrine diagnosis is uncertain, stress-dose steroids cover both conditions.

## References

1. Bornstein SR, et al. "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline." *Journal of Clinical Endocrinology & Metabolism*. 2016;101(2):364-389.
2. Rushworth RL, et al. "Adrenal Crisis." *New England Journal of Medicine*. 2019;381(9):852-861.
3. Akamizu T, et al. "Diagnostic Criteria, Clinical Features, and Incidence of Thyroid Storm Based on Nationwide Surveys." *Thyroid*. 2012;22(7):661-679.
4. Ross DS, et al. "2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism." *Thyroid*. 2016;26(10):1343-1421.