INTRODUCTION AND EPIDEMIOLOGY
Thyroid hormone affects all organ systems and is responsible for increasing metabolic rate, heart rate, and ventricle contractility, as well as muscle and central nervous system excitability. Two major types of thyroid hormones are thyroxine and triiodothyronine. Thyroxine is the major form of thyroid hormone. The ratio of thyroxine to triiodothyronine released in the blood is 20:1. Peripherally, thyroxine is converted to the active triiodothyronine, which is three to four times more potent than thyroxine.
Hyperthyroidism refers to excess circulating hormone resulting only from thyroid gland hyperfunction, whereas thyrotoxicosis refers to excess circulating thyroid hormone originating from any cause (including thyroid hormone overdose).
Thyroid storm is the extreme manifestation of thyrotoxicosis. This is an acute, severe, life-threatening hypermetabolic state of thyrotoxicosis caused either by excessive release of thyroid hormones causing adrenergic hyperactivity or altered peripheral response to thyroid hormone following the presence of one or more precipitants.
The mortality of thyroid storm without treatment is between 80% and 100%, and with treatment, it is between 15% and 50%.
Primary hyperthyroidism is caused by the excess production of thyroid hormones from the thyroid glands. Secondary hyperthyroidism is caused by the excess production of thyroid-releasing hormones or thyroid-stimulating hormones in the hypothalamus and pituitary, respectively (Tables 229-1 and 229-2).
| Primary Hyperthyroidism | |
| Graves’ disease (toxic diffuse goiter) (Figure 229-1) | Most common of all hyperthyroidism (85% of all cases) Associated with diffuse goiter, ophthalmopathy, and local dermopathy |
| Toxic multinodular goiter | Second most common cause of hyperthyroidism |
| Toxic nodular (adenoma) goiter (Figure 229-2) | An enlarged thyroid gland that contains a small rounded mass or masses called nodules with overproduction of thyroid hormone |
| Thyroiditis | Inflammation of the thyroid gland |
| Hashimoto’s thyroiditis | Initially gland is overactive (hyperthyroidism state), but this is usually followed by a state of hypothyroidism |
| Subacute painful thyroiditis (de Quervain’s thyroiditis) | |
| Subacute painless thyroiditis | |
| Radiation thyroiditis | |
| Secondary Hyperthyroidism | |
| Thyrotropin-secreting pituitary adenoma | Thyroid gland stimulated to produce hormones |
| Nonthyroidal Disease | |
| Ectopic thyroid tissue (struma ovarii)/teratoma | A rare form of mature teratoma that contains mostly thyroid tissue |
| Metastatic thyroid cancer | Stimulates production of thyroid hormones |
| Human chorionic gonadotropin | Secreting hydatidiform mole |
| Drug Induced | |
| Iodine | Iodine-induced thyrotoxicosis (called Jod-Basedow disease) After treatment of endemic goiter patients with iodine or stimulation of thyroid hormones from use of iodine-containing agents such as radiographic contrast agents |
| Amiodarone | Contains iodine; may cause either thyrotoxicosis or hypothyroidism |
α-Interferon Interleukin-2 | During treatment for other diseases, such as viral hepatitis and human immunodeficiency virus infection |
| Thyrotoxicosis factitia | Munchausen-like; thyroid hormone is taken by patient to fake illness |
| Ingestion of meat containing beef thyroid tissue | Cow thyroid tissue contains thyroid hormones |
| Excessive thyroid hormone ingestion | |
In the case of thyroid storm, the most common underlying cause of hyperthyroidism is Graves’ disease (85% of all hyperthyroidism cases in the United States). It is caused by the thyrotropin receptor antibodies that stimulate excess and uncontrolled thyroidal synthesis and secretion of thyroid hormones. It occurs most frequently in young women (10 times more common in women compared with men) at any age group.1
PATHOPHYSIOLOGY
The pathophysiologic mechanisms underlying the shift from uncomplicated thyrotoxicosis to thyroid storm are not entirely clear. However, they involve adrenergic hyperactivity either by increased release of thyroid hormones (with or without increased synthesis) or increased receptor sensitivity. Many of the signs and symptoms are related to adrenergic hyperactivity. Patients with thyroid storm reportedly have relatively higher levels of free thyroid hormones as opposed to those with uncomplicated thyrotoxicosis. The total thyroid hormone level may or may not be increased in these patients.
When there is excess of thyroid hormones, circulating thyroxin and triiodothyronine are taken into the cytoplasm of cells. Thyroxin is converted to its active form, triiodothyronine. Within the cytoplasm, the triiodothyronine then exerts its effect by passing into the nucleus and binding to thyroid hormone receptors or thyroid hormone–responsive elements to induce gene activation and transcription.2 The receptors receiving the hormone will stimulate changes specific to the tissue.
In the pituitary gland, thyroid hormones exert negative regulation on the transcription of the genes for the subunit and the common subunit of thyroid-stimulating hormone, resulting in thyroid-stimulating hormone suppression.
During thyroid storm, precipitants such as infection, stress, myocardial infarction, or trauma will multiply the effect of thyroid hormones by freeing thyroid hormones from their binding sites or increasing receptor sensitivity.
The precipitants of thyroid storm are as shown in Table 229-3. In some patients undergoing radioactive iodine therapy for hyperthyroidism, thyroid storm may ironically occur following treatment due to withdrawal of antithyroid drugs, release of thyroid hormones from damaged thyroid follicles, or the effect of radioactive iodine itself.
Systemic insult Infection Trauma General surgery Endocrinal insult Diabetic ketoacidosis Hyperosmolar coma Drug or hormone related Withdrawal of anti-thyroid medication Iodine administration Thyroid gland palpation Ingestion of thyroid hormone | Cardiovascular insult Myocardial infarction Cerebrovascular accidents Pulmonary embolism Obstetrics related Parturition Eclampsia Radioactive iodine therapy |
| Unknown cause in up to 25% of cases | |
CLINICAL FEATURES
The patient may only complain of constitutional symptoms such as generalized weakness and fatigue. Heat intolerance, diaphoresis, fever, voracious appetite but poor weight gain, anxiety, emotional lability, palpitations, diarrhea, and hair loss are common historical features. If there is a history of hyperthyroidism, ask about treatment and compliance with medication.
In general, patients often appear toxic and agitated. The signs and symptoms of hyperthyroidism patients are as shown in Table 229-4.
| Affected System | Symptoms | Signs |
|---|---|---|
| Constitutional | Lethargy Weakness Heat intolerance | Diaphoresis Fever Weight loss |
| Neuropsychiatric | Emotional lability Anxiety Confusion Coma Psychosis | Fine tremor Muscle wasting Hyperreflexia Periodic paralysis |
| Ophthalmologic | Diplopia Eye irritation | Lid lag Dry eyes Exophthalmos Ophthalmoplegia Conjunctival infection |
| Endocrine: thyroid gland (Figure 229-3) | Neck fullness Tenderness | Thyroid enlargement Bruit |
| Cardiorespiratory | Dyspnea Palpitations Chest pain | Widened pulse pressure Systolic hypertension Sinus tachycardia Atrial fibrillation or flutter High output heart failure |
| Gastrointestinal | Diarrhea Yellowish sclera | Hyperactive bowel sound Jaundice |
| Reproductive | Oligomenorrhea Decreased libido | Gynecomastia Telangiectasia |
| Gynecologic | Menorrhagia Irregularity | Sparse pubic hair |
| Hematologic | Pale skin | Anemia Leukocytosis |
| Dermatologic | Hair loss | Pretibial myxedema* Warm, moist skin Palmar erythema Onycholysis |
As for thyroid storm, the additional signs and symptoms apart from those evident in thyrotoxicosis are as shown in Table 229-5.
Fever is often present in thyroid storm and may be quite high. It may herald the onset of thyrotoxic crisis in previously uncomplicated disease. Palpitations, tachycardia, and dyspnea are common. A pleuropericardial rub may be heard. The direct inotropic and chronotropic effects of thyroid hormone on the heart cause increased blood volume, increased contractility, and increased cardiac output. Enhanced contractility produces elevations in systolic blood pressure and pulse pressure, leading to a dicrotic or water-hammer pulse. Atrial fibrillation occurs in 10% to 35% of thyrotoxicosis cases.3,4
The severity of exophthalmos does not necessarily parallel the magnitude of thyroid dysfunction but reflects the responsible autoimmune process. Not all hyperthyroidism patients present with goiter. A goiter is not present with exogenous administration of thyroid hormone and apathetic thyrotoxicosis. Likewise, the presence of a goiter does not necessarily confirm the diagnosis of thyrotoxicosis. Thyroid gland tenderness can be found in inflammatory conditions such as subacute thyroiditis.5
DIAGNOSING THYROID STORM
Thyroid storm is a clinical diagnosis for patients with preexisting hyperthyroidism. In determining whether or not a patient has thyroid storm, the main systems to concentrate on are the thermoregulatory system (rise in temperature), CV system (ranging from tachycardia to atrial fibrillation and congestive cardiac failure), CNS (ranging from being agitated to seizure), and the GI-hepatic system (ranging from nausea to vomiting and jaundice) (Table 229-5). Table 229-6 provides a scoring system for thyroid storm as compared with severe thyrotoxicosis. A score ≥45 is highly suggestive of thyroid storm. The system is sensitive in picking up thyroid storm but is not very specific.
| Diagnostic Parameters | Scoring Points |
|---|---|
1. Thermoregulatory dysfunction Temperature °C (°F) 37.2–37.7 (99–99.9) 37.7–38.3 (100–100.9) 38.3–38.8 (101–101.9) 38.9–39.4 (102–102.9) 39.4–39.9 (103–103.9) ≥40 (≥104.0) | 5 10 15 20 25 30 |
