Selection from: Endocrine Emergencies

Selection from: Endocrine Emergencies

Introduction

Endocrine emergencies represent a group of potentially life-threatening conditions that are frequently overlooked, resulting in delays in both diagnosis and treatment, factors that further contribute to their already high associated mortality rates. As such, the true incidence of primary endocrine emergencies is not well defined, which is likely because the disease process is often not recognized. Although endocrine emergencies are often encountered in patients with a known endocrinopathy, the emergency may be the initial presentation in previously undiagnosed individuals. If these endocrine disorders are not rapidly identified or if specific treatment is delayed, significant complications or even death may occur. This review discusses the 4 most prevalent endocrine emergencies: thyroid storm, myxedema coma, diabetic ketoacidosis (DKA), and adrenal crisis. The incidence and clinical manifestations will be discussed, and the importance of prompt diagnosis and treatment will be highlighted.

Thyroid Storm

Description

Malignant or critical thyrotoxicosis, thyroid storm, is a life-threatening medical emergency in which excessive concentrations of thyroid hormone produce organ dysfunction. It is an uncommon manifestation of hyperthyroidism, occurring in less than 10% of patients hospitalized for thyrotoxicosis. However, it may be the presenting symptom of the condition and, if untreated, is associated with 80% to 90% mortality. Even with treatment, mortality from thyroid storm exceeds 20%. Recognition and immediate management is important in preventing the high morbidity and mortality associated with this disease.

A spectrum of thyroid dysfunction exists. Hyperthyroidism, or thyrotoxicosis, refers to disorders that result from overproduction and release of hormone from the thyroid gland. Thyrotoxicosis refers to any cause of excessive thyroid hormone concentration, whereas malignant thyrotoxicosis, or thyroid storm, represents an extreme manifestation of thyrotoxicosis with resultant end-organ dysfunction.[1]

Incidence

Thyroid storm can occur in both men and women of any age. However, it is more common in teenaged or young adult women. Although a history of hyperthyroidism is common, thyroid storm may be the initial manifestation in a significant number of patients. Thyroid storm can be precipitated by a variety of factors, including severe infection, diabetic ketoacidosis, surgery, trauma, and pulmonary thromboembolism. Direct trauma or surgical manipulation of the thyroid gland can also precipitate thyroid storm. Iodine, either from excessive ingestion, intravenous administration, or radiotherapy, has been reported to precipitate thyroid storm. It has also been described following discontinuation of antithyroid medications. Of interest, salicylates have been implicated in triggering thyroid storm by increasing the concentration of circulating free thyroid hormones to critical levels.[2]

Clinical Manifestation and Diagnosis

The clinical manifestations of thyroid storm are consistent with marked hypermetabolism resulting in multiorgan system dysfunction. The differential diagnosis of thyroid storm includes sepsis, central nervous system infection, anticholinergic or adrenergic intoxication, other endocrine dysfunction, and acute psychiatric illness. Symptoms include thermoregulatory dysfunction (high fever, warm moist skin, diaphoresis), neurologic manifestations (mental status changes, seizure, coma, psychosis, hyperreflexia, lid lag), cardiovascular dysregulation (atrial fibrillation, tachycardia, hypertension, congestive heart failure), respiratory distress (dyspnea, tachypnea), and gastrointestinal dysfunction (diarrhea, abdominal pain, nausea, vomiting).[3] The diagnosis of thyroid storm relies heavily on clinical suspicion. It is strongly suggested by the constellation of these symptoms and is confirmed by means of thyroid function tests (TFT). However, treatment should not be delayed for verification by laboratory tests. Thyroid stimulating hormone (TSH) levels are virtually undetectable (< 0.01 micro international units [mcIU]/L) with a concomitant elevation of free T4 and T3. Because of increased conversion of T4 to T3, the elevation of T3 is typically more dramatic. For this reason it is essential to measure both T3 and free T4 levels when thyroid storm is suspected. There are no differences in the results of TFT in patients with thyroid storm when compared with patients who have symptomatic hyperthyroidism, and levels of thyroid hormone cannot predict which patients will undergo decompensation from thyrotoxicosis to thyroid storm. The distinction is made clinically by documentation of acute organ dysfunction. Other laboratory abnormalities commonly seen are hypercalcemia from osteoclast-mediated bone resorption, elevated alkaline phosphatase caused by activated bone remodeling, and hyperglycemia secondary to enhanced glycogenolysis and increased circulation of catecholamines. Adrenal insufficiency, especially among patients with Graves disease, is common and should be evaluated prior to the initiation of treatment.[4]

Treatment

The treatment of thyroid storm involves 3 critical fundamentals. First, supportive care should be provided to minimize the secondary effects of organ failure. This should include respiratory and hemodynamic support and treatment of hyperthermia. Second, identification and treatment of the precipitating event is warranted to prevent further progression of disease. Third, and most critical, the release and effects of circulating thyroid hormone must be blocked. Inhibition of the peripheral conversion of T4 to T3 helps attenuate the effects of thyroid hormone. Propylthiouracil (PTU) blocks peripheral conversion of T4 to T3 and can be given as a 600- to 1000-mg loading dose, followed by 1200 mg/day divided into doses given every 4 to 6 hours. Methimazole can be used as an alternate agent but does not block peripheral T4 conversion. Both medications can be administered rectally if necessary. Peripheral thyroid hormone action as well as tachycardia and hypertension can be minimized by beta-blockers; typically propranolol administered intravenously initially in 1-mg increments every 10 to 15 minutes until symptoms are controlled or esmolol administered as a loading dose of 250-500 mcg/kg followed by an infusion of 50-100 mcg/kg/minute. Thyroid hormone release can be reduced by the administration of lithium, iodinated contrast, and corticosteroids. Hydrocortisone 100 mg given intravenously every 8 hours has been shown to improve outcomes in patients. Steroid therapy is also beneficial, given the common association with adrenal insufficiency. Iodine acts by inhibiting hormone release but should not be given until 1 hour after PTU administration. In refractory cases, plasmapheresis, plasma exchange, and peritoneal hemodialysis can be used to remove circulating thyroid hormone.[4] With appropriate treatment, clinic and biochemical improvement are typically seen within 24 hours. Full recovery usually occurs within a week of therapy.

Thyroid storm poses diagnostic and therapeutic challenges. Treatment is aimed at halting the thyrotoxic process at all levels. Prompt recognition and treatment is essential for successful management and is paramount to decreasing the high mortality associated with this disease.

Diabetic Ketoacidosis

Description

DKA is a potentially fatal acute metabolic complication of diabetes mellitus. It is characterized by the biochemical triad of hyperglycemia, ketonemia, and metabolic acidosis.

Incidence

DKA is typically associated with type 1 diabetes but may also occur in type 2 diabetes during periods of infection, trauma, cardiovascular injury, or other emergencies. It is more common in young people with type 1 diabetes and in females.[12] It may be the presenting manifestation of diabetes. DKA can be precipitated by many clinical situations. The most common include inadequate dosing of insulin and infection. Other causes include pancreatitis, cardiovascular disorders (myocardial infarction, stroke), and drug use (steroids, diuretics, vasopressors, antipsychotics, cocaine).

DKA results from severe alterations in carbohydrate, protein, and lipid metabolism. In simple terms, it is the consequence of severe cell starvation and death resulting from a relative or complete deficiency of insulin needed to transport glucose into the cells. Increased gluconeogenesis, increased glycogenolysis, and decreased use of glucose by the muscles, liver, and fat lead to profound metabolic derangements. Insulin deficiency promotes lipolysis. Lipolysis also plays a key role in promoting metabolic decompensation by providing the substrate for the formation of ketone bodies (acetone, beta-hydroxybutyric acid, and acetoacetic acid). Decreased clearance of ketone bodies leads to ketonemia and results in an anion gap metabolic acidosis.[13] There are also elevated levels of proinflammatory cytokines and procoagulant factors (C-reactive protein and interleukin-6 and -8) that predispose the patient to thrombosis.[14]

Clinical Manifestation and Diagnosis

Severe disease can develop in less than 24 hours after the onset of ketosis. Clinical manifestations include polyuria, polydipsia, polyphagia, and weakness. Glucosuria can lead to profound intravascular volume depletion, manifested by dry mucous membranes, flattened neck veins, tachycardia, hypotension, and orthostasis. Nausea and vomiting are common, occurring in up to 80% of patients. Abdominal pain occurs in 30% of individuals. Patients often have a fruity odor to their breath, resulting from elevated serum acetone. Tachypnea is

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