Table of Contents
-
Abstract
-
Practice Recommendations (key points from the issue)
-
Case Presentations
-
Critical Appraisal Of The Literature
-
Epidemiology, Etiology, And Pathophysiology
-
Epidemiology
-
Definitions And Etiology
-
Pathophysiology
-
Differential Diagnosis
-
Prehospital Care
-
ED Evaluation
-
Initial Approach
-
Important Historical Questions (From Patient, Medics, Witnesses, Family, And Other People)
-
Important Physical Findings
-
Diagnostic Studies
-
TSH, T4, T3
-
Other Diagnostic Tests
-
Electrocardiogram
-
Chest Radiography
-
Echocardiography
-
Computerized Tomography Head
-
Lumbar Puncture
-
Treatment
-
Myxedema Coma
-
Thyroid Storm
-
Special Circumstances
-
Respiratory Failure
-
Pediatrics
-
Neonatal Hypothyroidism
-
Neonatal Thyrotoxicosis
-
Pregnancy
-
Controversies/Cutting Edge
-
Cardiovascular Collapse
-
Radiation Emergencies
-
Screening
-
Disposition
-
Summary
-
Cost- And Time-Effective Strategies
-
Risk Management Pitfalls For Thyroid Emergencies
-
Case Conclusion
-
Clinical Pathway For Treatment Of Myxedema Coma
-
Clinical Pathway For Treatment Of Thyroid Storm
-
Tables And Figures
-
Differential Diagnosis In Thyroid Storm
-
Differential Diagnosis In Myxedema Coma
-
Field Diagnostic & Therapeutic Interventions In Thyroid Crises
-
Historical Questions In The Evaluation Of Thyroid Storm
-
Historical Questions In The Evaluation Of Myxedema Coma
-
Thyroid Laboratory Tests In Thyroid Disease
-
Three-Step Treatment of Thyroid Storm
-
References
Abstract
Although thyroid-related medical conditions are relatively common in the general population, the acute life-threatening thyroid emergency rarely presents. Both hyper- and hypothyroidism can contribute to the etiology of a number of critical ED presentations, ranging from acute psychosis to frank coma. With reported mortality rates ranging from 20% to 80% for the life-threatening, decompensated forms of hypo- and hyperthyroidism, myxedema and thyroid storm, respectively, it remains crucial that the emergency clinician be versed in their diagnosis and treatment.1,2
This issue of Emergency Medicine Practice reviews the fundamental principles of the management of thyroid emergencies using a focused, evidence-based approach to the literature. Although thyroid disorders constitute a wide-ranging clinical spectrum, this review will focus on the common final pathway of acutely decompensated hyper- and hypothyroidism, myxedema, and thyroid storm. Accurate diagnosis and the application of proven emergent treatments are critical in reducing the profound mortality rates related to both conditions.
Practice Recommendations (key points from the issue)
Click here to download a PDF of the Evidence-Based Practice Recommendations for this issue.
Case Presentations
Case #1: A 65-year-old woman is brought to the emergency department (ED) with altered level of consciousness and hypotension. Her neighbor found her on the kitchen floor. He checked on her because he hadn't seen her for 3 days. The patient is unable to provide any verbal history. Her vital signs are respiratory rate of 10 respirations per min, blood pressure of 90/60 mm Hg, temperature 35°C (95°F), and heart rate 50 beats per min. On physical examination, you see an obtunded woman in no apparent distress. You note a well-healed surgical scar on her anterior neck and that her left leg is shortened and externally rotated. The differential diagnosis of the presentation is long and complex, and you keep wondering if that scar on the neck has a bearing on her management.
Case #2: A 50-year-old man presents with complaints of a fever and "feeling anxious." The patient has had a productive cough, subjective fever, and myalgias for 7 days. Yesterday, he began to "feel anxious" and like his "heart was racing." His pas medical history is significant for a goiter that is still being evaluated. His vital signs are respiratory rate of 18 respirations per min, blood pressure of 160/80 mm Hg, temperature 38°C (100.4°F), and heart rate 140 beats per min. On physical examination, you note that the patient appears nontoxic. He has a tender goiter, a fine tremor of his hands, and an irregular heart rhythm. On his lung examination, there are left midfield rales. You suspect community-acquired pneumonia, but the tender goiter introduces management concerns.
Critical Appraisal Of The Literature
We performed a literature review through Ovid MEDLINE and PubMed using the terms hyperthyroidism, thyrotoxicosis, thyroid storm, hypothyroidism, and myxedema. We then performed a manual search of the resulting articles to find further relevant articles. The Endocrine Society has published an excellent clinical management guideline for hyperthyroidism and hypothyroidism as well as for the pregnant and postpartum population, but this does not address emergent intervention.3 Recent meta-analyses and randomized control trials tend to focus on the ideal pharmacological, radiotherapeutic, or surgical regimens for long-term therapy of hyperthyroidism, all of which are of limited importance to the emergency clinician. A number of case reports and case reviews exist as well for the more esoteric presentations associated with thyroid disorders.
Aside from the relatively recent development of intravenous thyroxine, the management of myxedema and thyroid storm has changed little since the mid twentieth century. Perhaps the most relevant papers to the practicing emergency clinician are the focused clinical reviews available on subtopics within the thyroid disease literature, including neonates, children, the elderly, antithyroid drugs, and mechanical ventilation principles.
Risk Management Pitfalls For Thyroid Emergencies
-
"I thought she was hypothermic because it was cold outside." The vast majority of cases of myxedema coma occur in the winter. The differential diagnosis of hypothermia includes myxedema coma. Do not dismiss all hypothermia to environmental causes.
-
"I didn't want to start thyroxine until I had laboratory test confirmation of her thyroid status." The use of IV thyroxine has not been shown to be harmful in euthyroid patients. Many facilities batch test their thyroid panels, and results may not be available for several days. If the clinical suspicion exists for myxedema coma, start treatment early. Delays in treatment result in increased mortality.
-
"She was hypotensive, so I started norepinephrine." Patients with myxedema coma tend to be hypotensive. The first therapy is fluid resuscitation, as these patients are hypovolemic. If patients remain hypotensive after fluid resuscitation, evaluate perfusion. If the patient is perfusing the end organs, continue supportive therapy. Evidence of impaired perfusion indicates the need for vasopressors. The vasopressor of choice is one with low a-adrenergic activity, such as dopamine. a-adrenergic vasopressors, such as norepinephrine and phenylephrine, can precipitate cardiovascular collapse in myxedema coma.
-
"She had altered mental status because she was septic." Although this is true in many cases, an ED physician should remember to consider the presence of decompensated thyroid conditions in patients with systemic illness. The diagnoses of myxedema coma and thyroid storm are clinical diagnoses. Therefore, the physician must suspect them to diagnose them.
-
"I sent a TSH. If it's low, I will treat him for thyroid storm." The acute decompensation of thyroid storm is not reflected in the laboratory tests for many hours after the onset of the clinical syndrome. Thyroid storm is a clinical diagnosis. The physician must diagnose thyroid storm based on history and physical examination findings.
-
"She's confused because she's old and sick." Systemic illness can cause decompensation in a geriatric patient's mental status. The ED physician should always consider the complicating factor of an underlying thyroid disorder in confused patients. This is especially true in geriatric women.
-
"I treated the patient as though she was septic because she had fever, tachycardia, hypertension, and altered mental status." This clinical picture is consistent with both thyroid storm and sepsis. Hypertension can be present in early sepsis, but hypotension is the hallmark of late sepsis. As the conditions can coincide, the ED physician should always consider the role of the thyroid in systemically ill patients.
-
"I gave the patient T3 for presumed myxedema coma because it works faster than T4." The onset of action is faster with T3 than T4. However, T3 has a higher risk of complications, including cardiac arrhythmias. The standard of care in myxedema coma is to administer T4 intravenously. If the physician only has access to T3, this can be administered.
-
"The patient has atrial fibrillation and congestive heart failure from thyroid storm. I gave the patient a diuretic for the heart failure and a calcium channel blocker for the heart rate." Patients with a fast heart rate and signs of heart failure may have high output heart failure, which means the heart rate is too fast for the heart to fill in diastole. So, the cardiac output is decreased. The left ventricle may have normal function or may be depressed in these instances. The treatment is to slow the heart rate and reassess the patient. In this sense, the calcium channel blocker is a good choice. However, a b-blocker is the preferred agent in thyroid storm, as it also treats the patient's symptoms of agitation and anxiety and other peripheral effects of thyroid hormone. Patients with thyroid storm are hypovolemic, even if they have pulmonary edema. The administration of a diuretic should be avoided if possible, as this worsens the dehydration and also worsens the cardiac output. When the heart rate has slowed, reassess the patient's oxygenation and ventilation status before administering a diuretic. In patients with underlying cardiac dysfunction complicating the case, the physician must use clinical judgment as to which agent to administer first.
-
"The patient has thyroid storm, so I gave iodine immediately to stop the production of thyroid hormone." Iodine is an important therapy in thyroid storm, but it must be given 2 h after an antithyroid medication (methimazole or PTU). If given before these medications, iodine will worsen the clinical picture by stimulating the release of increased amounts of thyroid hormone. A patient may not be in the ED long enough for the ED physician to administer this medication.
Tables And Figures
References
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.
-
Nayak B. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006;35(4):663-686. (Review)
-
Wall CR. Myxedema coma: diagnosis and treatment. Am Fam Physician. 2000;62(11):2485-2490. (Review)
-
Abalovich M, Amino N, Barbour LA, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. Thyroid. 2007;17(11):1159-1167. (Systematic review)
-
Vanderpump MPJ, Tunbridge WMG. Epidemiology and prevention of clinical and subclinical hypothyroidism. Thyroid. 2002;12(10):839-847.
-
Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol. 1977;7:481-493.
-
Canaris GJ, Manowitz NR, Mayor GM, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:526-534.
-
*McKeown NJ, Tews MC, Gossain VV, et al. Hyperthyroidism. Emerg Med Clin North Am. 2005 23(3): 669-685. (Review)
-
*Rodriquez I, Fluieters E, Perez-Mendez LF, Luna R, Paramo C, Garcia-Mayor RV. Factors associated with mortality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution. J Endocrinol. 2004;180(2):347-350. (Prospective, randomized; 11 patients)
-
Arlot S, Debussche J, Lalau TD, et al. Myxedema coma: a response of with oral and IV high dose levothyroxine. Intensive Care Med. 1991;17(1):16-18. (Prospective; 7 patients)
-
Wartofsky, L. Myxedema coma. In: The Thyroid, Braverman, LE, Utiger RD (Eds). Lippincott-Raven, Philadelphia, 1996, p. 871. (Review)
-
*Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 200635(4):663-686,vii.
-
Bianco AC, Salvatore D, Gereben B, et al. Biochemistry, cellular and molecular biology and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev. 2002;23(1):38-99. (Review)
-
*Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of thyroid hormone on cardiac function: the relative importance of heart rate, loading conditions, and myocardial contractility in the regulation of cardiac performance in human hyperthyroidism. J Clin Endocrinol Metab. 2002;87(3):968-974. (Review)
-
Von Olshausen K, Bischoff S, Kahaly G, et al. Cardiac arrhythmias and heart rate in hyperthyroidism. Am J Cardiol. 1989;63:930-933. (Prospective, case control; 87 patients)
-
*Klein I, Kaie O. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344(7):501-509. (Review)
-
Kahaly GJ, Niewswandt J, Wagner S, et al. Ineffective cardiorespiratory function in hyperthyroidism. J Clin Endocrinol Metab. 1998;83(11):4075-4078. (Prospective; 42 patients)
-
Zwillich CW, Ierson DJ, Hofeldt FD, Lufkin EG, Weil JV. Ventilatory control in myxedema and hypothyroidism. N Engl J Med. 1975;292(13):662-665. (Prospective cohort; 17 patients)
-
Benia M. Management of myxedematous respiratory failure: review of ventilation and weaning principles. Am J Med Sci. 2000;320(6):368-373. (Case presentation; 1 patient)
-
Sternlicht J, Wogan JM. Thyroid and adrenal disorders. In: Marx JA, Hockberger RS, Walls RM, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice. Mosby;2002. (Textbook chapter)
-
Rotman-Pikielny P, Borodin O, Zissin R, et al. Newly diagnosed thyrotoxicosis in hospitalized patients: clinical characteristics. QJM. 2008;101(11):871-874. (Retrospective review; 58 patients)
-
Kim DD, Young S, Cutfield R. A Survey of thyroid function test abnormalities in patients presenting with atrial fibrillation and flutter to a New Zealand district hospital. N Z Med J. 2008;121(1285):82-86. (Retrospective case review; 250 patients)
-
Trivalle C, Doucet J, Chassagne P, et al. Differences in the signs and symptoms of hyperthyroidism in older and younger patients. J Am Geriatr Soc. 1996;44(1):50-53.(Prospective cohort; 152 patients)
-
Gilbert FI Jr, Harada ASM. Graves‘ disease: influence of age on clinical findings. Arch Intern Med. 1988;148:626-631. (Prospective cohort; 880 patients)
-
Brownlie BE, Rae AM, Walshe JW, et al. Psychoses associated with thyrotoxicosis—‘thyrotoxic psychosis.' A report of 18 cases, with statistical analysis of incidence. Eur J Endocrinol. 2000;142(5):438-444. (Case series; 18 patients)
-
Norrelund H, Hove KY, Brems-Dalgaard E, et al. Muscle mass and function in patients with thyrotoxicosis before and during medical treatment. Clin Endocrinol (Oxf). 2000;53(4):540-541. (Longitudinal; 5 patients)
-
Kung A. Thyrotoxic periodic paralysis: a diagnostic challenge. J Clin Endocrinol Metab. 2006;91(7):2490-2495. (Systematic review)
-
McArthur JW, Rawson RW, Means JH, et al. Thyrotoxic crisis: an analysis of the thirty-six cases seen at the Massachusetts General Hospital during the past twenty-five years. JAMA. 1947;134:868-874. (Retrospective; 36 patients)
-
Mazzaferri EL, Skillman TG. Thyroid storm. A review of 22 episodes with special emphasis on the use of guanethidine. Arch Intern Med. 1969;124(6):684-690. (Retrospective; 22 patients)
-
Burch HB, Wartofsky L. Life threatening thyrotoxicosis. Endocrinol Metab Clin North Am. 1993;22:263-277.
-
Burch HB, Wartofsky L. Life threatening thyrotoxicosis. Endocrinol Metab Clin North Am. 1993;22:263. (Review)
-
Forester CF. Coma in myxedema coma. Report of a case and review of the world literature. Arch Intern Med. 1963;111:734-743. (Case report, review; 1 patient)
-
Kerber RE, Sherman B. Echocardiographic evaluation of pericardial effusion in myxedema: incidence and biochemical and clinical correlations. Circulation. 1975;52:823. (Prospective; 33 patients)
-
Smolar EN, Rubin JE, Avramides A, et al. Cardiac tamponade in primary myxedema and review of the literature. Am J Med Sci. 1976;272(3):345-352. (Case presentation, review)
-
Ritter FN. The effects of hypothyroidism on the ear, nose and throat: a clinical and experimental study. Laryngoscope. 1967;77:1427-1479. (Retrospective; 18 patients)
-
Bloomer H, Kyle LH. Myxedema: A reevaluation of clinical diagnosis based on eighty cases. Arch Intern Med. 1959;(4):234-241. (Retrospective; 80 patients)
-
Swanson JW, Kelly JJ, McConahey WM. Neurologic aspects of thyroid dysfunction. Mayo Clin Proc. 1981;56:504-512. (Review)
-
Sanders V. Neurologic manifestations of myxedema. N Engl J Med. 1962;266:547-522. (Review)
-
Neurophysiological changes in neurologically asymptomatic patient with hypothyroidisms: a prospective cohort study. J Clin Neurophysiol. 2006;23(6):568-572. (Prospective cohort; 23 patients)
-
Somay G, Oflazoqlu B, Us O, et al. Neuromuscular status of thyroid disease: a prospective clinical and electrodiagnostic study. Electromyogr Clin Neurophysiol. 2007;47(2):67-78. (Prospective, case control; 69 patients)
-
Olson CG. Myxedema coma in the elderly. J Am Board Fam Pract. 1995;8(5):376-382. (Review)
-
Senior RM, Birge SJ, Wessler S, et al. The recognition and management of myxedema coma. JAMA. 1971;217(1):61-65. (Review)
-
Jansen HJ, Doebe SR, Louwerse ES, et al. Status epilepticus caused by a myxoedema coma. Neth J Med. 2006;64:202. (Case report; 1 patient)
-
Zwillich DW, Ierson DJ, Hofeldt FD, et al. Ventilatory control in myxedema and hypothyroidism. N Engl J Med. 1975;292:662-665. (Prospective; 17 patients)
-
Iwasaki Y, Oisa Y, Yamauchi K, et al. Osmoregulation of plasma vasopressin in myxedema. J Clin Endocrinol Metab. 1990;70:534. (Prospective; 8 patients)
-
Brooks MH. Free thyroxine concentrations in thyroid storm. Ann Intern Med. 1980;93(5):694-697. (Prospective cohort; 40 patients)
-
Jacobs HS, Mackie DB, Eastman CJ, Ellis SM, Ekins RP, McHardy-Young S. Total and free triiodothyronine and thyroxine levels in thyroid storm and recurrent hyperthyroidism. Lancet. 1973;2(7823):236-238.
-
Spencer CA, Lai-Rosenfild AO, Guttler RB, et al. Thyrotropin secretion in thyrotoxic and thyroxine-treated patients. J Clin Endocrinol Metab. 1986;63:349-355. (Prospective; 56 patients)
-
Surks MI, Chopra IJ, Mariash CN, Nicoloff JT, Solomon DH. American Thyroid Association guidelines for use of laboratory testing in thyroid disorder. JAMA. 1990;63:1529-1532. (Expert opinion)
-
Ladenson PW, Singer PA, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000;160:1573-1575. (Expert opinion)
-
*Greco LK. Hypothyroid emergencies. Top Emerg Med. 2001;23(4)44-50. (Review)
-
Duick DS, Warren DW, Nicoloff JT, Otis CL, Croxson MS. Effect of single dose dexamethasone on the concentration of serum T3 in man. J Clin Endocrinol Metab. 1974;39:1151-1154.
-
Kristensen BO, Weeke J. Propranolol-induced increments in total and free serum thyroxine in patients with essential hypertension. Clin Pharmacol Ther. 1977;22:864-867. (Prospective; 15 patients)
-
Burgi H, Wimphfheimer C, Burger A, Zaunbauer W, Rosler H, Lemarchaud-Beraud T. Changes of circulating thyroxine, triiodothyronine and reverse triiodothyronine after radiographic contrast agents. J Clin Endocrinol Metab. 1976;43:1203-1210. (Prospective; 58 patients)
-
Burger A, Nicod DP, Lemarchaud-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxine and thyrotropin. J Clin Invest. 1976;58:255-259. (Prospective; 24 patients)
-
Cooper DS. Subclinical hypothyroidism. N Engl J Med. 2001;345(4)260-265. (Review)
-
Smith PJ, Surks MI. Multiple effects of 5,5,-diphenylhydantoin on the thyroid hormone system. Endocr Rev. 1984;5:514-524. (Review)
-
Onhauss EE, Burgi H, Burger A, Studer H. The effect of antipyrine, phenobarbital, and rifampin on thyroid hormone metabolism in man. Eur J Clin Invest. 1981;11:381-387.
-
Behnia M, Clay AS, Farber MO. Management of myxedematous respiratory failure: review of ventilation and weaning principles. Amer J Med Sci. 2000;320(6):368-373. (Review)
-
Sawin C, Geller A, Wolf PA. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med. 1994;331(19):1249-1252. (Prospective; 2007 patients)
-
Griswold D, Keating JH Jr. Cardiac dysfunction in hyperthyroidism: a study of 810 cases. Am Heart J. 1949;38:813-822. (Retrospective; 810 patients)
-
Sandler G, Wilson GM. The nature and prognosis of heart disease in thyrotoxicosis. Q J Med. 1959;28:347. (Review)
-
Van Olshausen K, Bischoff S, Kahaly G, Mohr-Kahaly S, Erbel R, Beyer J, Meyer J. Cardiac arrhythmias and heart rate in hyperthyroidism. Am J Cardiol. 1989;63:930-933. (Prospective; 16 patients)
-
Polikar R, Burger AG. The thyroid and the heart. Circulation. 1993;87:1435-1441. (Review)
-
Hylander B, Rosenqvist U. Treatment of myxoedema coma—factors assocatied with fatal outcome. Acta Endocrinol (Copenh). 1985;108(1):65-71. (Retrospective; 11 patients)
-
Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid. 1999;9:1167-1174.
-
Holvey DN, Goodner CJ, Nicoloff JT, Dowling JT. Treatment of myxedema coma with intravenous thyroxine. Arch Intern Med. 1964;113:89.
-
Hamilton MA, Stevenson LW, Fonarow GC, et al. Safety and hemodynamic effects of intravenous triiodothyronine in advanced congestive heart failure. Am J Cardiol. 1998:81(4):443-447.
-
Güden M, Akpinar B, SagÄŸbaÅŸ E, SanisoÄŸlu I, Cakali E, Bayindir O. Effects of intravenous triiodothyronine during coronary artery bypass surgery. Asian Cardiovasc Thorac Ann. 2002;10(3):219-222. (Prospective, randomized; 60 patients)
-
*Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. N Engl J Med. 1982;306(1):23-32.
-
Jonklaas J, Davidson B, Bhagat S, Soldin SJ. Triiodothyronine levels in athyreotic individuals during levothyroxine therapy. JAMA. 2008;299(7):769-777. (Prospective; 50 patients)
-
Holvey DN, Goodner CJ, Nicoloff JT, Dowling JT. Treatment of myxedema coma with intravenous thyroxine. Arch Intern Med. 1964;113:139-146.
-
Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: report of eight cases and literature survey. Thyroid. 1999;9:1167-1174.
-
Fonte et al. Successful treatment of myxedema coma with daily incremental dose of oral levothyroxine in an elderly female with compromised cardiovascular status. [abstract] Paper presented at: The Endocrine Society's Annual Meeting; June 12-15, 2008; San Francisco, CA.
-
Petersen K, Bengtsson C, Lapidus L, Lindstedt G, Nystrom E. Morbidity, mortality, and quality of life for patients treated with levothyroxine. Arch Intern Med. 1990;150(10):2077-2081. (Cohort)
-
Grozinsky-Glasberg S, Fraser A, Nahshoni E, Weizman A, Leibovici L. Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: meta-analysis of randomized controlled trials. J Clin Endocrinol Metab. 2006;91(7):2592-2599.
-
Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ Jr. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med. 1999;340(6):424-429. (Prospective; 33 patients)
-
Bunevicius R, Jakubonien N, Jurkevius R, Cernicat J, Lasas L, Prange AJ Jr. Thyroxine vs thyroxine plus triiodothyronine in treatment of hypothyroidism after thyroidectomy for Graves' disease. Endocrine. 2002;18(2):129-133. (Prospective, cross-over)
-
Stathatos N, Wartofsky L. Thyroid emergency: are you prepared? Accessed January 1, 2007 from http://www.emedmag.com/html/pre/cov/covers/021503.asp.
-
Thyroid Guidelines Committee. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;(6):457-469.
-
Kwaku MP, Burman KD. Myxedema Coma. J Intensive Care Med. 2007;22:224-231.
-
Wartofsky L. Myxedema coma. In: Braverman LE, Utiger RD, eds. Werner & Ingbar's The Thyroid. 8th ed. Philadelphia, PA: Lippincott; 2000:843-847.
-
Ngo AS, Lung Tan DC. Thyrotoxic heart disease. Resuscitation. 2006;70(2):287-290. (Case report)
-
Dalan R, Leow MC. Cardiovascular collapse associated with beta-blockade in thyroid storm. Exp Clin Endocrinol Diabetes. 2007;115(10):696. (Case series; 3 patients)
-
Sebe A, Satar S, Sari A. Thyroid storm induced by aspirin intoxication and the effect of hemodialysis: a case report. Adv Ther. 2004 May-June;21(3):173-177.
-
Ogilvy-Stuart AL. Neonatal thyroid disorders. Arch Dis Child Fetal Neonatal Ed. 2002;87:f165-f171. (Review)
-
Geffner DL, Azukizawa M, Hershman J. Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man. J Clin Invest. 1975;55:224-229. (Prospective)
-
Karpman B, Rapoport B, Filetti S, et al. Treatment of neonatal hyperthyroidism due to Graves' disease with sodium ipodate. J Clin Endocrinol Metab. 1987;64:119-123. (Case series)
-
Transue D, Chan J, Kaplan M. Management of neonatal Graves' disease with iopanoic acid. J Pediatr. 1992;121:472-474. (Case report; 1 patient)
-
Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341:549-555. (Case report; 1 patient)
-
Van Wassenaer AG, Kok JH, Endert E, et al. Thyroxine administration to infants of less than 30 weeks' gestational age does not increase plasma triiodothyronine concentrations. Acta Endocrinol. 1993;129:139-146. (Prospective)
-
Reuss ML, Paneth N, Lorenz JM, et al. Correlates of low thyroxine values at newborn screening among infants born before 32 weeks gestation. Early Hum Dev. 1997;1997;28:821-827. (Prospective; 365 patients)
-
Paul DA, Leef KH, Stefano JL, Bartoshesky L. Low serum thyroxine on initial newborn screening is associated with intraventricular hemorrhage and death in very low birth weight infants. Pediatrics. 1998;101:903-907. (Review; 342 patients)
-
Den Ouden AL, Kok JH, Verkerkp PH, Brand R, Verloove-Vanhorick SP. The relation between neonatal thyroxine levels and neurodevelopmental outcome at 5 and 9 years in a national cohort of very preterm and/or very low birth weight infants. Pediatr Res. 1996;39:142-145. (Prospective; 717 patients)
-
Meijer WJ, Verloove-Vanhorick SP, Brand R, et al. Transient hypothyroxinaemia associated with developmental delay in very preterm infants. Arch Dis Child. 1992;67:944-947. (Prospective; 563 patients)
-
Chowdhry P, Scanlon JW, Auerbach R, et al. Results of controlled double-blind study of thyroid replacement in very low birth weight premature infants with hypothyroxinaemia. Pediatrics. 1984;73:301-305. (Prospective; 563 patients)
-
Amato M, Pasquier S, Carasso A, et al. Postnatal thyroxine administration for idiopathic respiratory distress syndrome in preterm infants. Horm Res. 1988;29:301-305. (Prospective, randomized, controlled; 36 patients)
-
Vanhole C, Aerssens P, Naulaers G, et al. L-thyroxine treatment of preterm newborns: clinical and endocrine effects. Pediatr Res. 1997:42:87-92. (Prospective, randomized, double blind, controlled; 40 patients)
-
Van Wasenaer AG, Kok JH, De Vijlder JJ, et al. Effects of thyroxine supplementation on neurologic development in infants born at less than 30 weeks' gestation. N Engl J Med. 1997;42:87-92. (Prospective, randomized, double blind, controlled; 200 patients)
-
Crowther CA, Hiller JE, Haslam RR, et al. Australian collaborative trial of antenatal thyrotropin-releasing hormone: adverse effects at 12-month follow-up. Pediatrics. 1997;99:311-317. (Prospective, randomized, controlled; 1022 patients)
-
Rapaport R, Rose SR, Freemark M. Hypothyroxinemia in the preterm infant: the benefits and risks of thyroxine treatment. J Pediatr. 2001;139(2):182-188.
-
Hoffman WH, Sahasrananan P, Ferandos SS, et al. Transient thyrotoxicosis in an infant delivered to a long-acting stimulator (LATS)- and LATS protector-negative, thyroid stimulating antibody-positive woman with Hashimoto's thyroiditis. J Clin Endocrinol Metab. 1982;54:354-356. (Case report; 1 patient)
-
Schwab KO, Gerlich M, Broecker M, et al. Constitutively active germline mutation of the thyrotropin receptor gene as a cause of congenital hyperthyroidism. J Pediatr. 1997;131:899-904. (Case report; 1 patient)
-
De Roux N, Polka M, Couet J, et al. A neomutation of the thyroid-stimulating hormone receptor in a severe neonatal hyperthyroidism. J Clin Endocrinol Metab. 1996;81:2023-2026. (Case report; 1 patient)
-
Fisher DA. The thyroid. In: Kaplan SA, ed. Clinical Pediatric Endocrinology. Philadelphia, PA: WB Saunders; 1990;114-115. (Textbook chapter)
-
Tamaki H, Amino N, Aoza M, et al. Universal predictive criteria for neonatal overt thyrotoxicosis requiring treatment. Am J Perinatol. 1988;5:152-158. (Prospective; 35 patients)
-
Mortimer RH, Tyack SA, Galligan DA, et al. Graves' disease in pregnancy: TSH receptor binding inhibiting immunoglobulins and maternal and neonatal thyroid function. Clin Endocrinol. 1990;32:141-152.
-
Ramsay I. Fetal and neonatal hyperthyroidism. Contemp Rev Obstet Gynaecol. 1991;3:74-78. (Review)
-
Munro DS, Dirmikis SM, Humphries H, et al. The role of thyroid stimulating immunoglobulins of Graves' disease in neonatal thyrotoxicosis. Br J Obstet Gynaecol. 1978:85:837-843.
-
Samuel S, Pildes RS, Lewison M, et al. Neonatal hyperthyroidism in an infant born of an euthyroid mother. Am J Dis Child. 1971;121:440-443. (Case report; 1 patient)
-
Hollingsworth DH, Mabry CC. Congenital Graves' disease: four familial cases with long-term follow-up and perspective. Am J Dis Child. 1976;130:148-155. (Case series; 4 patients)
-
Mestman JH. Hyperthyroidism in pregnancy. Clin Obstet Gynecol. 1997;40:45-64. (Review)
-
Davis LE, Lucas MJ, Hankins GDV, et al. Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol. 1989;160:63-70. (Retrospective; 60 patients)
-
Zakarija M, McKenzie JM, Munro DS. Immunoglobulin G inhibitor of thyroid-stimulating antibody is a cause of delay in the onset of neonatal Graves' disease. J Clin Invest. 1983;72:1352-1356. (Prospective; 3 patients)
-
Zakarija M, McKenzie JM, Hoffman WH. Prediction and therapy of intrauterine and late-onset neonatal hyperthyroidism. J Clin Endocrinol Metab. 1986;62:368-371. (Prospective; 2 patients)
-
Li Pi Shan W, Hatzakorzian R, Sherman M, Backman SB. Upper airway compromise secondary to edema in Graves' disease. Can J Anaesth. 2006 Feb;53(2):183-187. (Case report; 1 patient)
-
Kadhim Al, Sheahan P, Timon C. Management of life-threatening airway obstruction caused by benign thyroid disease. J Laryngol Otol. 2006;120(12):1038-1041. (Retrospective; 5 patients)
-
Shaha AR, Burnett C, Alfonso A, Jaffe BM. Goiters and airway problems. Am J Surg. 1989;158(4):378-380. (Prospective, 120 patients)
-
Netterville JL, Coleman SC, Smith JC, et al. Management of substernal goiter. Laryngoscope. 1998;108(11, pt 1):1611-1617. (Retrospective; 150 patients)
-
Zwillich CW, Pierson DJ, Hofeldt FD, Lufkin DG, Weil JV. Ventilatory control in myxedema and hypothyroidism. N Engl J Med. 1975;292:662-665. (Prospective; 17 patients)
-
Lavard L, Ranlov R, Perrild H, et al. Incidence of juvenile thyrotoxicosis in Denmark, 1982-1988, A nationwide study. Eur J Endocrinol. 1994;130:565-568. (Retrospective; 56 patients)
-
Shulman DI, Muhar I, Jorgensen EV, et al. Autoimmune hyperthyroidism in prepubertal children and adolescents: comparison of clinical and biochemical features at diagnosis and response to medical therapy. Thyroid. 1997;7:755-760. (Retrospective; 100 patients)
-
Lazar L, Kalter-Leibovici O, Pertzelan A, et al. Thyrotoxicosis in prepubertal children compared with pubertal and postpubertal patients. J Clin Endocrinol Metab. 2000;85:3678-3682. (Prospective, case controlled; 40 patients)
-
Segni M, Lenoardi E, Mazzoncini B, et al. Special features of Graves' disease in early childhood. Thyroid. 1999;9:871-877. (Review)
-
Gruters A. Ocular manifestations in children and adolescents with thyrotoxicosis. Exp Clin Endocrinol Diabetes. 1999;107(suppl 5):S172-S174. (Review)
-
Chan W, Wong GW, Fan DS, et al. Ophthalmopathy in childhood Graves' disease. Br J Ophthalmol. 2002;86:740-742. (Review)
-
Birrell G, Cheetham T. Juvenile thyrotoxicosis; can we do better? Arch Dis Child. 2004;89:745-750. (Review)
-
Kadmon PM, Noto RB, Boney CM, et al. Thyroid storm in a child following radioactive iodine (RAI) therapy: a consequence of RAI versus withdrawal of antithyroid medication. J Clin Endocrinol Metab. 2001;86:1865-1867. (Case report; 1 patients)
-
Setian N. Hypothyroidism in children: diagnosis and treatment. J Pediatr (Rio J). 2007;83(5)(suppl):S209-S216. (Review)
-
Turhan NO, Kockar MC, Inegol I. Myxedematous coma in a laboring woman suggested a pre-eclamptic coma: a case report. Acta Obstet Gynecol Scand. 2004;83:1089-1096. (Case report; 1 patient)
-
Roti E, Minelli R, Salvi M. Clinical review of management of hyperthyroidism in the pregnant woman. J Clin Endocrinol Metab. 1996;81:1679. (Review)
-
Kyriazopoulou V, Michalaki M, Georgopoulos N, Vagenakis AG. Recommendations for thyroxine therapy during pregnancy. Expert Opin Pharmacother. 2008;9(3):421-427. (Review)
-
Mestman JH. Best practice and research. Clin Endocrinol Metab. 2004;18(2):2670288. (Review)
-
Takamura N, Nakamura Y, Ishigaki K, et al. Thyroid blockade during a radiation emergency in iodine-rich areas: effect of a stable-iodine dosage. J Radiat Res. 2004;45(2):201-204. (Prospective; 8 patients)
-
Jordan RM. Myxedema coma: pathophysiology, therapy, and factors affecting prognosis. Med Clin North Am. 1995;79(1):185-194.
-
Dutta P, Bhansali A, Masoodi SR, et al. Predictors of outcome in myxedema coma: a study from a tertiary care centre. Crit Care. 2008;12:R1. (Observational; 23 patients)
-
Rodriguez I, Fluiters E, Perez-Mendez LF, et al. Factors associated with mortality with myxedema coma: prospective study in 11 cases treated in a single institution. J Endocrinol. 2004;180:347-350. (Case series; 11 patients)
-
Brooks MH, Waldenstein SS. Free thyroxine in thyroid storm. Ann Intern Med. 1980;93(5):694-697. (Review)
-
Kaptein EM, Kletzsky OA, Spencer CA, Nicoloff JT. Effects of prolonged dopamine infusion on anterior pituitary function in normal males. J Clin Endocrinol Metab. 1980;51:488-491. (Prospective; 6 patients)