Coma and thyroid storm in apathetic thyrotoxicosis. (Case Histories).
ABSTRACT: We report the case of an 87-year-old woman with coma who was found to be in thyrotoxic crisis. The patient had a recent history of decreased mentation mentation
mental activity, state of mind. and apathy, and laboratory findings were found to be consistent with hyperthyroidism hyperthyroidism: see thyroid gland. . After a stormy course, the clinical condition recovered to baseline, with return of laboratory values to normal following antithyroid therapy. We provide the details of this rarely documented presentation of apathetic hyperthyroidism with thyroid storm and coma and review the characteristics of similar cases in the literature.
THYROID STORM is a relatively rare, yet potentially fatal syndrome. It can only be differentiated from uncomplicated thyrotoxicosis thyrotoxicosis /thy·ro·tox·i·co·sis/ (thi?ro-tok?si-ko´sis) a morbid condition due to overactivity of the thyroid gland; see Graves' disease.
n. on clinical basis, as laboratory findings are indistinguishable in both conditions. (1-3) It represents exaggerated clinical features of thyrotoxicosis that can rapidly be fatal unless recognized early and treated aggressively. (3)
Several atypical features for thyroid storm have been reported, of which apathy and coma are extremely rare. To the best of our knowledge, ours is only the second case in the worldwide literature and the first documented in the United States of apathetic thyrotoxicosis manifesting as thyroid storm and coma. We also found seven cases of thyrotoxic crisis in which coma was the initial manifestation and only six cases of apathetic thyrotoxicosis manifesting as thyroid storm.
An 87-year-old white woman was admitted for a gradual decline in mental status of 2 days' duration. The patient, whose medical history was significant for coronary artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. , bypass surgery, congestive heart failure congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time. , hypertension, and atrial fibrillation medicated medicated /med·i·cat·ed/ (med´i-kat?id) imbued with a medicinal substance.
contains a medicinal substance. by warfarin sodium (Coumadin) and digoxin digoxin: see digitalis. , also had a 1- to 2-month history of generalized weakness and loss of appetite loss of appetite Medtalk Anorexia, see there . She had no known history of any thyroid disease, recent surgeries, or iodine exposure. Her family denied history of tremulousness, anxiety, hyperactivity, or sweating.
On examination, the patient appeared ill, prostrated, and confused. Blood pressure was 190/120 mm Hg, pulse was 148/min and irregular, and respiratory rate was 20/min. Mucous membranes were dry and a pulse deficit of 20 was present. Neurologic examination was significant for depressed deep tendon reflexes and bilateral upgoing plantar reflexes. The remainder of the physical examination was unremarkable. The thyroid gland was not clinically appreciated.
Findings were either normal or negative for the following laboratory measurements: complete blood count, serum urea nitrogen, serum chloride, [CO.sub.2], creatinine, glucose, serum potassium, serum sodium, calcium, digoxin, ammonia, and lactate Lactate
A salt or ester of lactic acid (CH3CHOHCOOH). In lactates, the acidic hydrogen of the carboxyl group has been replaced by a metal or an organic radical. Lactates are optically active, with a chiral center at carbon 2. . Prothrombin time was 50.3 seconds (normal, 10.6 to 13.0 seconds) and international normalized ratio International Normalized Ratio Hematology A method of reporting prothrombin time–PT results for Pts receiving oral anticoagulant therapy; the INR is defined by the formula, PTPatient/PTMNPT was 23.8 (normal, 1.0 to 1.2). Ammonia and lactate levels were normal. Liver function tests Liver Function Tests Definition
Liver function tests, or LFTs, include tests for bilirubin, a breakdown product of hemoglobin, and ammonia, a protein byproduct that is normally converted into urea by the liver before being excreted by the kidneys. (LFTs) revealed the following values: aspartate aminotransferase 99 U/L U/L Upload
U/L Units/Litre (normal, 14 to 48 U/L), alanine aminotransferase 53 U/L (normal, 8 to 50 U/L), and total bilirubin Bilirubin
The predominant orange pigment of bile. It is the major metabolic breakdown product of heme, the prosthetic group of hemoglobin in red blood cells, and other chromoproteins such as myoglobin, cytochrome, and catalase. 2.9 mg/dL (normal, 0.3 to 1.1 mg/dL). A hepatitis panel, consisting of hepatitis A IgM, hepatitis B surface antigen hepatitis B surface antigen
n. Abbr. HBsAg
An antigen derived from the surface of the hepatitis B virus that is present in the blood in active hepatitis B infection. Also called Australia antigen. , hepatitis B core IgM, and hepatitis C antibodies, yielded negative results. Computed tomography of the head was significant only for generalized cortical atrophy and an old lacunar infarct. Electrocardiogram electrocardiogram /elec·tro·car·dio·gram/ (-kahr´de-o-gram?) a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle and detected at the body surface. showed atrial fibrillation with a fast ventricular response, a unifocal ventricular prema ture beat, and poor R-wave progression in the frontal leads.
The patient was admitted with the diagnosis of warfarininduced coagulopathy and a tentative diagnosis of metabolic encephalopathy. A few hours later, her mental status deteriorated and she became comatose co·ma·tose
1. Of, relating to, or affected with coma.
2. Marked by lethargy; torpid.
comatose (kō´m with no obvious precipitating factor. Temperature spikes of up to 103[degrees]F occurred with no obvious source, and the ventricular heart rate persisted at 124 to 140/min despite the use of intravenous digoxin and [beta]-blockers. Cardiac enzyme levels were positive for a non-Q-wave myocardial infarction. Blood cultures were negative for organisms. Thyroid function tests Thyroid Function Tests Definition
Thyroid function tests are blood tests used to evaluate how effectively the thyroid gland is working. These tests include the thyroid-stimulating hormone test (TSH), the thyroxine test (T4), the triiodothyronine test (TETs) revealed the following values: thyrotropin thyrotropin (thī'rätrō`pĭn) or thyroid-stimulating hormone (TSH), hormone released by the anterior pituitary gland that stimulates the thyroid gland to release thyroxine. 0.02 [micro]U/mL (normal, 0.27 to 4.62 [micro]IU/mL), thyroxine of 51.1 [micro]g/dL (normal, 4.6 to 12.0 [micro]g/dL), total triiodothyronine triiodothyronine /tri·io·do·thy·ro·nine/ (tri?i-o?do-thi´ro-nen) one of the thyroid hormones, an organic iodine-containing compound liberated from thyroglobulin by hydrolysis. It has several times the biological activity of thyroxine. of 534 ng/dL (normal, 80 to 200 ng/dL), and a thyroid hormone-binding index (TBI TBI 1. Thyroxine-binding index 2. Total body irradiation ) of <0.2 (normal, 0.8 to 1.3). A repeat of TFTs confirmed these figures. Thyroid ultrasonography ultrasonography /ul·tra·so·nog·ra·phy/ (-so-nog´rah-fe) the imaging of deep structures of the body by recording the echoes of pulses of ultrasonic waves directed into the tissues and reflected by tissue planes where there is a change in revealed an enlarged thyroid with multiple heterogeneous nodular nodular
marked with, or resembling, nodules.
see nodular fasciitis (below).
a firm painless nodular swelling, 0. masses b ilaterally, consistent with goiter goiter: see thyroid gland. . Thyroid-stimulating antibodies were 160% (normal, <130%). Antimicrosomal antibodies measured 75.2 U/mL (normal, <1.0 U/mL), and testing for antithyroglobulin antibodies yielded negative results.
Thyrotoxic crisis (thyroid storm) was diagnosed, and the patient was treated with propylthiouracil, Lugol's iodine, [beta]-blockers, steroids, and intravenous fluids. Follow up TFT (Thin Film Transistor) The term typically refers to active matrix screens on laptop computers. Active matrix LCD provides a sharper screen display and broader viewing angle than does passive matrix. See LCD and thin film.
TFT - Thin Film transistor results are listed in Table 1. Mental status started to improve slowly, with return to baseline and normalizadon of TFT results in 4 weeks. Results of LFTs and coagulation coagulation (kōăg'ylā`shən), the collecting into a mass of minute particles of a solid dispersed throughout a liquid (a sol), usually followed by the precipitation or abnormalities resolved in 1 to 2 weeks.
Thyroid storm or crisis represents exaggerated manifestations of thyrotoxicosis. (1) Cardinal features include fever, tachycardia (usually out of proportion to the degree of fever), central nervous system manifestations (varying from confusion to coma), and gastrointestinal dysfunction with nausea, vomiting, or even jaundice in severe cases, which usually denotes a poor prognosis. (2,3) Hyperglycemia hyperglycemia: see diabetes. , hypercalcemia Hypercalcemia Definition
Hypercalcemia is an abnormally high level of calcium in the blood, usually more than 10.5 milligrams per deciliter of blood. , and LFT LFT left frontotransverse (position of the fetus).
LFT Liver function tests, see there abnormalities are frequent findings.(3,4) A precipitating factor usually decompensates hyperthyroidism; this can be an infection, trauma, surgery, cerebrovascular accident, or even emotional stress. Most patients have obvious symptoms and signs of thyrotoxicosis and a history of untreated or partially treated hyperthyroidism. (3,5)
Apathetic thyrotoxicosis is an exceedingly rare presentation of thyroid storm. The clinical picture is one of apathy rather than hyperactivity, and cardiovascular manifestations may predominate (3) Although it is mainly a disease of the elderly, it has been reported in all age groups.
Prior to hospital admission, our patient had an apathetic picture and decreased mentation, and she subsequently became comatose. The diagnosis of thyroid storm was not considered initially because apathy and/or coma as a manifestation of thyroid crisis is extremely rare. Most patients with thyroid crisis have a history of untreated or partially treated hyperthyroidism. The absence of such a history in our patient made the diagnosis more difficult.
The first suspicion of thyrotoxicosis arose when uncontrolled atrial fibrillation did not respond to appropriate cardiac management. The very high levels of thyroid hormones, though not diagnostic of crisis, made the diagnosis more likely. The complete recovery of the patient's clinical condition with antithyroid therapy confirmed the diagnosis.
Our search in the literature revealed only 14 reports of thyroid storm in which apathy and/or coma was the initial manifestation (Table 2) (6-19) Of these, only one case of apathetic hyperthyroidism manifested with thyroid storm and coma. (6) The majority of these patients were of western origin, with a female predominance of 71.4%. All age groups were represented; however, it occurred most commonly between the fourth and the sixth decades. Common physical findings initially were tachycardia, occurring in almost all cases, with the exception of 1 patient reported to be in complete heart block (18) and fever, occurring in 11 of 14 patients initially and documented in most of the patients during their hospital stay.
Although the duration of treatment needed for full recovery varied from days to several weeks, one common finding shared by these patients was the positive response to the antithyroid therapy. Three patients (21%) had cardiac arrest during their hospital stay, two of whom died (14%).(11,16,19) The diagnosis of thyroid storm was made post mortem [Latin, After death.] Pertaining to matters occurring after death. A term generally applied to an autopsy or examination of a corpse in order to ascertain the cause of death or to the inquisition for that purpose by the Coroner . in only one patient. (11)
Conceding these atypical manifestations, our case, together with those previously reported, emphasizes the need for early consideration of thyroid storm in patients with uncontrolled atrial fibrillation in whom fever and confusion concomitantly develops. Also, the presence of atypical features such as apathy or coma should not defer one from contemplating the diagnosis.
TABLE 1. Results of Follow-up Thyroid Function Tests With Antithyroid Therapy Thyrotropin [T.sub.4] [T.sub.3] Hospital (N = 0.27 to 4.62) (N = 4.6 to 12.0) (N = 80 to 200) Day [micro]IU/mL [micro]g/dL ng/dL 1 0.02 51.1 534.0 8 0.01 28.3 130.3 9 0.01 19.9 108.4 14 0.02 15.6 83.3 23 0.19 11.1 95.5 32 0.68 11.0 106.0 Hospital TBI Day (N = 0.8 to 1.3) 1 < 0.2 8 0.50 9 - 14 0.67 23 - 32 0.91 [T.sub.4] = Thyroxine; [T.sub.3] = triiodothyronine; TBI = thyroid hormone-binding index; N = normal (reference) range. TABLE 2. Characteristics of Patients With Thyroid Storm With Initial Manifestations of Coma and/or Apathy Age (yr), History of Report Country Sex Hyperthyroidism Fever Seeri et al, (6) Canada 47, F * + 1978 Masambu, (7) Uganda 60, F - + 1979 Dodd et al, (8) UK 39, M - + 1980 Schermer US 52, M * + et al, (9) 1980 Laman et al, (10) Netherlands 31, F * + 1984 Howton et al, (11) US 32, M + + 1988 Aiello et al, (12) US 3 1/2, F - + 1989 Gilbert et al, (13) Australia 29, F * + 1992 Pugh et al, (14) UK 27, F * * 1994 Lee et al, (15) US 56, F + + 1997 Feroze et al, (16) UK 37, F - * 1997 Soares et al, (17) Portugal 70, M + + 1997 Ho et al, (18) Singapore 16, F + + 1998 Homma et al, (19) Japan 59, F - + 1999 Report Tachycardia Coma Apathy Seeri et al, (6) + + + 1978 Masambu, (7) + - + 1979 Dodd et al, (8) + - + 1980 Schermer + Stupor + et al, (9) 1980 Laman et al, (10) * + - 1984 Howton et al, (11) + + - 1988 Aiello et al, (12) + + - 1989 Gilbert et al, (13) + + - 1992 Pugh et al, (14) + + - 1994 Lee et al, (15) + Stupor - 1997 Feroze et al, (16) + Cardiac - 1997 arrest Soares et al, (17) + + * 1997 Ho et al, (18) - - - 1998 Homma et al, (19) + + - 1999 Other Clinical Goiter Report Features Present Seeri et al, (6) Asthenia, weight loss, + 1978 diarrhea Masambu, (7) Weakness, weight loss - 1979 Dodd et al, (8) Weight loss, abdominal pain - 1980 (mistaken for malignancy) Schermer Anasarca, heart failure, + et al, (9) 1980 thrombocytopenia Laman et al, (10) Tremors * 1984 Howton et al, (11) Behavior changes + 1988 Aiello et al, (12) Seizures, apnea * 1989 Gilbert et al, (13) Rhinorrhea, cough + 1992 Pugh et al, (14) After surgery, nausea - 1994 and vomiting Lee et al, (15) Status epilepticus, + 1997 stroke Feroze et al, (16) Acute left ventricular - 1997 hypertrophy, stroke Soares et al, (17) Tremors, ataxia, weakness, + 1997 weight loss, diarrhea Ho et al, (18) Jaundice, complete heart * 1998 block, heart failure, diarrhea Homma et al, (19) Hypoglycemia, tremors + 1999 Antithyroid Treatment Report Antibodies Duration Seeri et al, (6) + 6 wk 1978 Masambu, (7) * * 1979 Dodd et al, (8) + 1 mo 1980 Schermer * * et al, (9) 1980 Laman et al, (10) + 7 to 8 wk 1984 Howton et al, (11) * No treatment 1988 (patient died) Aiello et al, (12) + 10 days 1989 Gilbert et al, (13) * 10 days 1992 Pugh et al, (14) * 11 days 1994 Lee et al, (15) * 5 wk 1997 Feroze et al, (16) * * 1997 Soares et al, (17) + >4 wk 1997 Ho et al, (18) * 6 days 1998 Homma et al, (19) * Patient died 1999 + = Present; - = absent. * Data not mentioned in report or test not done.
(1.) Burch HB, wartofsky L: Life-threatening thyrotoxicosis: thyroid storm. Endocrinol Metab Clin North Am 1993; 22:263-277
(2.) Roth RN, McAuliffe MJ: Hyperthyroidism and thyroid storm. Emerg Med Clin North Am 1989; 7:873-883
(3.) Gavin LA: Thyroid crises. Med Clin North Am 1991; 75:179-193
(4.) de los Santos De Los Santos is a common surname in the Spanish language meaning of the saints.
(5.) Nicoloff JT: Thyroid storm and myxedema myxedema (mĭksədē`mə), condition associated with severe hypothyroidism and lack of thyroid hormone in the adult. In the child it is known as cretinism. coma. Med Clin North Am 1985; 69:1005-1017
(6.) Serri O, Gagnon RM, Goulet Y, et al: coma secondary to apathetic thyrotoxicosis. Can Med Assoc J 1978; 119:605-607
(7.) Masambu JK: Apathetic hyperthyroidism: a case report and review of the literature. East Afr Med J 1979; 56:344-346
(8.) Dodd MJ, Blacke DR: A case of apathetic thyrotoxicosis simulating malignant disease. Postgrad Med J 1980; 56:359-360
(9.) Schermer RM, Morley JE, Sharp B, et al: Apathetic thyroid storm associated with anasarca an·a·sar·ca
An accumulation of serous fluid in various tissues and cavities of the body.
ana·sar and thrombocytopenia Thrombocytopenia Definition
Thrombocytopenia is an abnormal drop in the number of blood cells involved in forming blood clots. These cells are called platelets. . (Letter.) JAMA JAMA
Journal of the American Medical Association 1980; 243:2485
(10.) Laman DM, Berghout A, Endtz LJ, et al: Thyroid crisis presenting as coma. Clin Nenrol Neurosurg 1984; 86:295-298
(11.) Howton JC: Thyroid storm presenting as coma. Ann Emerg Med 1988; 17:343-345
(12.) Aiello DP, DuPlessis AJ, Pattishall EG III, et al: Thyroid storm presenting with coma and seizures in a 3-year-old girl. Clin Pediatr (Phila) 1989; 28:571-574
(13.) Gilbert RE, Thomas GW, Hope RN, et al: Coma and thyroid dysfunction. Anaesth Intensive Care 1992; 20:86-87
(14.) Pugh S, Lalwani K, Awal A: Thyroid storm as a cause of loss of consciousness following anaesthesia for emergency caesarian caesarian
Variant of cesarean. section. Anaesthesia 1994; 49:35-37
(15.) Lee TG, Ha CK, Lim BH: Thyroid storm presenting as status epilepticus and stroke. (Letter) Postgrad Med J 1997; 73:61
(16.) Feroze M, May H: Apathetic thyrotoxicosis. Int J Clin Pract 1997; 51:332-333
(17.) Soares AD, Falcao LM, De Barros E: Hypothyroid Hypothyroid
Having too little thyroxin stimulation.
Mentioned in: Goiter
hypothyroid adjective Referring to hypothyroidism, see there coma and thyrotoxic crisis. Acta Med Port 1997; 10:837-843
(18.) Ho SC, Eng PH, Ding ZP, et al: Thyroid storm presenting as jaundice and complete heart block. Ann Acad Med Singapore 1998; 27:748-751
(19.) Homma M, Shimizu S, Ogata M, et al: Hypoglycemic hypoglycemic /hy·po·gly·ce·mic/ (-gli-sem´ik)
1. pertaining to, characterized by, or causing hypoglycemia.
2. an agent that lowers blood glucose levels. coma masquerading thyrotoxic storm. Intern Med (Japan) 1999; 38:871-874
RELATED ARTICLE: KEY POINTS
* Thyroid storm can be differentiated from uncomplicated thyrotoxicosis only on clinical grounds, not by laboratory values.
* Suspect hyperthyroidism in any patient with fever and atrial fibrillation that is not controlled with appropriate cardiac management.
* Apathy and coma are very rare manifestations of thyroid storm; however, these should not preclude consideration of the diagnosis.
* The key to successful treatment of thyroid storm is early administration of antithyroid therapy.
From the Department of Endocrinology, Mercy Catholic Medical Center, Mercy Fitzgerald/Mercy Hospital of Philadelphia, Darby, Pa; and Thomas Jefferson University It began as Jefferson Medical College in 1824. On July 1, 1969 the institution officially became Thomas Jefferson University.
The university is made up of three colleges:
Reprint requests to Michel W. Ghobrial, MD, 772 Providence Rd, No. B-402, Aldan, PA 19018.