Thyroid and Adrenal Disorders

Background and Importance

Hyperthyroidism is a condition caused by overproduction and increased circulation of thyroid hormone. The disorder runs the spectrum from subclinical hyperthyroidism to thyrotoxicosis and thyroid storm, a life-threatening disorder. Thyrotoxicosis is a hypermetabolic condition that results from elevated levels of thyroid hormones—triiodothyronine (T ₃ ) and thyroxine (T ₄ ). This can occur from hormone overproduction, increased thyroid hormone release from an injured gland, or exogenous thyroid hormone. For the purpose of this discussion, the terms hyperthyroidism and thyrotoxicosis are used interchangeably.

Anatomy, Physiology, and Pathophysiology

The normal adult thyroid gland is a highly vascular bilobar organ overlying the anterior trachea ( Fig. 117.1 ). The thyroid’s function is to secrete two iodinated hormones, T ₃ and T ₄ . Only about 20% of circulating T ₃ is directly secreted by the thyroid; the remainder is produced by peripheral conversion of T ₄ to the more biologically active T ₃ . The thyroid is the only endocrine gland that stores large quantities of hormone.

Hormone production is regulated by a negative feedback loop involving the hypothalamic-pituitary-thyroid axis ( Fig. 117.2 ). As the serum levels of T ₄ and T ₃ fall, the hypothalamus releases the tripeptide thyrotropin-releasing hormone (TRH), which in turn stimulates the anterior pituitary gland’s release of the polypeptide thyroid-stimulating hormone (TSH) from its thyrotroph cells. TSH then binds to epithelial cells on the thyroid gland, stimulating follicular cells to synthesize and secrete the thyroid hormones T ₄ and T ₃ . TRH release may also result from exercise, stress, malnutrition, hypoglycemia, and sleep.

The function of thyroid hormone is to influence the metabolism of cells by increasing their basal metabolic rate. It has a role in protein synthesis and functions together with other hormones necessary for normal growth and development. T ₃ and T ₄ increase the expression and sensitivity of β-adrenergic receptors, increasing the response to endogenous catecholamines.

T ₄ is a prohormone with only mild intrinsic activity; its deiodination produces T ₃ , the biologically active hormone. More than 99.5% of thyroid hormones are protein-bound in the serum to thyroxine-binding globulin (TBG) and other proteins, rendering them metabolically inactive. As a result, only free T ₄ and free T ₃ are clinically relevant.

Although iodide is a necessary substrate for thyroid hormone production, excess iodide can have two opposing effects. In the Wolff-Chaikoff effect, excess iodine inhibits the release of thyroid hormone from the gland by blocking iodide trapping and thyroglobulin iodination. This inhibition is transient, typically lasting only a matter of days. An iodine load can induce hyperthyroidism (Jod-Basedow effect) in some patients with multinodular goiter and occult Graves disease.

History and Physical Examination

Hyperthyroidism induces a hypermetabolic state and increases β-adrenergic activity. The resulting clinical manifestations range from vague constitutional symptoms to more organ-specific symptoms ( Box 117.1 ). Altered mental status and coma typify thyroid storm, the most severe manifestation of disease.

Hyperthyroidism in older adults often manifests in more subtle ways, often asymptomatic or with nonspecific symptoms of weight loss, shortness of breath, and/or dementia. Elders are more prone to cardiac manifestations of hyperthyroidism and may present with atrial fibrillation. Elders who smoke or have higher circulating thyroid hormone levels appear to have more severe symptoms. Thyrotoxic periodic paralysis is a rare manifestation that presents as a sudden and profound muscle weakness progressing to flaccid paralysis, similar to familial hypokalemic periodic paralysis.

Ophthalmopathy is a classic finding in Graves disease. Patients subsequently present with eyelid edema, hyperemia, conjunctival hyperemia, and chemosis. Graves ophthalmopathy is also associated with restrictive extraocular myopathy, and exophthalmos. As the disease progresses, patients may experience restriction of their upward gaze from infiltration of the inferior rectus muscle and visual loss from optic nerve involvement (compression by inflamed, enlarged orbital contents). Increased activity at the sympathetic innervation of the eyelids leads to widening of the palpebral fissures, resulting in the characteristic stare and lid lag of thyrotoxicosis.

Physical examination findings of hyperthyroidism depend largely on age ( Box 117.2 ). Younger patients typically present with signs of sympathetic stimulation, whereas older adults often lack the same adrenergic response and present with weight loss and fatigue, more consistent with apathetic hyperthyroidism. In Graves disease, patients uncommonly have classic pretibial myxedema, which are confluent, painless, reddish raised nodules and plaques over the pretibial area and dorsum of the feet, often described as orange skin. Hyperpigmentation and induration are present, but pitting is absent. Pretibial myxedema is often associated with Graves ophthalmopathy.

Tachycardia is the most common cardiac finding. Other findings include a widened pulse pressure, bounding peripheral pulses and, rarely, a friction rub heard along the left sternal border (Means-Lerman scratch). Atrial fibrillation is more common in elders, especially those over 65 years of age. Dilated cardiomyopathy may develop as a complication of a high cardiac output state. Patients can also develop primary pulmonary hypertension, as well as increased chamber size and poor right ventricular function.

Most hyperthyroid patients have an enlarged thyroid gland, especially in toxic multinodular goiter or Graves disease, although many elders with Graves disease have nonpalpable thyroids. Retrosternal enlargement can occur, making detection difficult while causing the obstructive symptoms discussed earlier. Facial and neck vein engorgement can be elicited when arms are elevated above the head (known as the Pemberton sign). The absence of thyroid enlargement should suggest exogenous (factitious) thyroiditis as well as ectopic thyroid hormone production, such as a hydatidiform mole or struma ovarii, an ovarian tumor composed of some thyroid tissue.

Thyroid Storm

Thyroid storm is a rare, life-threatening form of severe thyrotoxicosis, with multiorgan dysfunction and significantly higher mortality rates than thyrotoxicosis without storm. Although it can occur as the result of unrecognized or undertreated thyrotoxicosis, more often, it is an acute reaction to surgery, trauma, infection, iodine load or parturition in patients with preexisting hyperthyroidism. Other precipitants include acute myocardial infarction, pulmonary embolism, hyperemesis gravidarum, preeclampsia, and diabetic ketoacidosis. Untreated, mortality approaches 100%, but prompt recognition and therapy have lowered mortality to 10% to 30%. ^, Death in thyroid storm is caused by multiorgan dysfunction, congestive heart failure, respiratory failure, arrhythmias, disseminated intravascular coagulation, hypoxic brain insult, or sepsis.

The typical clinical manifestations of thyroid storm include marked pyrexia (104°–106°F [40°–41°C]), extreme tachycardia (often out of proportion to level of fever), and altered mental status. These findings, coupled with the clinical picture of a patient with hyperthyroidism, lid lag, stare, goiter, ophthalmopathy, and tremor, should alert the emergency clinician to the diagnosis. Cardiovascular collapse can result in congestive heart failure, hypotension, and cardiac arrhythmias. Hypotension can also result from volume depletion secondary to nausea, vomiting, and diarrhea. Abdominal pain is common; hepatic failure with cholestatic jaundice is less common but carries a poor prognosis. Thyroid storm is a clinical diagnosis, and no validated diagnostic criteria yet exist. However, a scoring system developed by Burch and Wartofsky in 1993 is repeatedly cited and utilized by practicing endocrinologists. Although the test characteristics (e.g., sensitivity and specificity) have not been published, it may help distinguish among thyrotoxicosis, impending thyroid storm, and frank thyroid storm ( Table 117.1 ).

Supportive Treatment

Supportive therapy for thyroid storm patients should include management of hyperthermia with cooling and acetaminophen. Aspirin should be avoided in thyrotoxic patients because it decreases the protein binding of T ₄ and T _3. Agitation is controlled with benzodiazepines. Fluid resuscitation is needed to compensate for insensible and gastrointestinal (GI) losses; dextrose-containing solutions are helpful because glycogen stores are often depleted. Electrolyte replacement is guided by laboratory values.

Symptomatic Treatment

Symptomatic treatment consists primarily of beta blockade to diminish the adrenergic response. Propranolol is the beta blocker of choice because it has the added benefit of blocking conversion of T ₄ to T ₃ ; its nonselective effects also improve tremor, weakness, hyperpyrexia, restlessness, irritability, and emotional lability. The onset of action after oral dosing is about 1 hour.

For more rapid beta blockade, propranolol can be administered intravenously (IV). A short-acting agent such as esmolol may be used when concerns about beta blockade exist, due to underlying asthma or COPD, or pulmonary edema from heart failure. In asthmatics, a β ₁ -selective drug such as esmolol or metoprolol may be considered.

If beta blockers are contraindicated, reserpine, 2.5 to 5 mg intramuscularly (IM) every 4 hours, is also an option. Patients should be closely monitored for hypotension, regardless of the agent used, because thyrotoxicosis can lower systemic vascular resistance and cause congestive heart failure. Patients who develop clinically significant heart failure should be treated with the usual medications for heart failure, including diuretics and angiotensin-converting enzyme inhibitors. Atrial fibrillation is often refractory to rate control until antithyroid therapy is instituted.