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 and apathy, and laboratory findings were found to be consistent with hyperthyroidism. 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.

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THYROID STORM is a relatively rare, yet potentially fatal syndrome. It can only be differentiated from uncomplicated thyrotoxicosis 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.

CASE REPORT

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, bypass surgery, congestive heart failure, hypertension, and atrial fibrillation medicated by warfarin sodium (Coumadin) and digoxin, also had a 1- to 2-month history of generalized weakness and loss of appetite. 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. Prothrombin time was 50.3 seconds (normal, 10.6 to 13.0 seconds) and international normalized ratio was 23.8 (normal, 1.0 to 1.2). Ammonia and lactate levels were normal. Liver function tests (LFTs) revealed the following values: aspartate aminotransferase 99 U/L (normal, 14 to 48 U/L), alanine aminotransferase 53 U/L (normal, 8 to 50 U/L), and total bilirubin 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 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 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 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 (TETs) revealed the following values: thyrotropin 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 of 534 ng/dL (normal, 80 to 200 ng/dL), and a thyroid hormone-binding index (TBI) of <0.2 (normal, 0.8 to 1.3). A repeat of TFTs confirmed these figures. Thyroid ultrasonography revealed an enlarged thyroid with multiple heterogeneous nodular masses b ilaterally, consistent with goiter. 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 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 abnormalities resolved in 1 to 2 weeks.

DISCUSSION

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, hypercalcemia, and LFT 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 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.

References

(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 ET, Mazzaferri EL: Thyrotoxicosis. results and risks of current therapy. Postgrad Med J 1990; 87:277-278, 281-286, 291-294

(5.) Nicoloff JT: Thyroid storm and myxedema 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 and thrombocytopenia. (Letter.) JAMA 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 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 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 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 School of Medicine, Philadelphia, Pa.

Reprint requests to Michel W. Ghobrial, MD, 772 Providence Rd, No. B-402, Aldan, PA 19018.