Hyperthyroidism affects about 1-3% of the population. The most common causes include Graves` disease, hyperactive multinodular goitre (Plummer’s disease) and autonomic, hyperactive thyroid nodules. The hypermetabolic crisis (thyroid storm) is a potentially life-threatening complication of hyperthyroidism occurring in 1-2% of patients with clinically overt hyperthyroidism [1, 2, 3]. Hyperthyroidism leads to increased metabolism and substantial oxygen consumption. The sensitization of adrenergic receptors by thyroid hormones results in circulatory hyperkinesis; prolonged adrenergic stimulation impairs the myocardial contractility and induces rhythm disorders, mainly paroxysmal atrial fibrillation [4, 5, 6, 7, 8]. The other mechanisms increasing the thyrotoxicosis-induced storm are reduced susceptibility and density of earlier strongly stimulated adrenergic receptors and relative adrenal cortex failure [9, 10]. The mortality rates associated with thyroid storm are 20-30% [1, 2, 3, 4].

We present a case of a thyrotoxicosis treated successfully in the ITU.

CASE REPORT

A 51-year-old female patient was admitted to hospital due to diturbances of consciousness and shock. The condition started suddenly with dyspnoea, precordial and abdominal pains. Physical examination showed coma with the generalized flexion reaction to pain preserved (GCS=5 pts), weakened deep tendon reflexes, core temperature of 37.6˚C, narrow, symmetric pupils not responding to light, shallow respiration accelerated to 40 min-1, with additional respiratory muscles involved. Auscultation revealed fine rales above the lung fields, weak heart sounds and heart rate of about 125 min-1. The arterial pressure was undetectable, jugular veins – overfilled. The patient was diagnosed with nodular goitre without audible vascular murmur. ECG showed accelerated sinus rhythm with ventricular extrasystole (class III according to Lown), horizontal elevation of ST (Pardee waves) by 2-4 μV in the limb leads II, III, AVF and precordial leads V2-V6. Atrial fibrillation was periodically observed with the ventricular activity of about 135-145 min-1. According to her family, the patient has been inconsistently treated due to hyperthyroidism and the disease was precipitated by emotional stress.

Laboratory tests revealed lactate acidosis (pH 7.14, lactic acid concentration 9.51 mmol L-1), PaO2 129 mm Hg (17.3 kPa) during spontaneous breathing with the mixture containing about 45% of oxygen, PaCO2 20 mm Hg (2.7 kPa), BE – 19.2 mmol L-1, levels of  HCO3 7.2 mmol L-1, K+ 6.92 mmol L-1, glucose 18.5 mmol L-1, urea 19.4 mmol L-1, creatinine 34.8 μmol L-1, CKMB 13.1 ng ml L-1, troponin I 5.1 ng mL-1, D-dimers 500 ng mL-1. Echocardiography disclosed decreased ejection fraction to 30%, impaired total heart  contractility and reduced ventricular compliance.

The patient was diagnosed with cardiogenic shock and pulmonary oedema associated with myocardial infarction and qualified for emergent invasive treatment. Coronarography was performed, which did not show functional and organic coronary stenosis. At that time, the sinus rhythm was replaced by atrial fibrillation. The patient was transfused 1000 mL of 6% HES 200/0.5; dopamine 15 μg kg-1 min-1, dobutamine 20 μg kg-1 min-1 and noradrenaline 1 μg kg-1 min-1 were started. The pulse on radial arteries was detectable, SAP/DAP was 70/50 mm Hg, yet symptoms of tissue hypoperfusion remained. Therefore, mechanical circulatory support was decided, i.e. intra-aortal counterpulsation, which increased SAP/DAP to 100/50 mm Hg; symptoms of pulmonary oedema subsided. The infusion of dopamine was withdrawn and doses of the remaining inotropic agents were gradually reduced. To diagnose the cause of coma, the concentration of carboxyhaemoglobin was additionally determined (2.2%), intoxication with methanol, glycol and salicylates was excluded; the cerebrospinal fluid was collected for tests and culture; no pathological changes were found on direct examination. Blood for culture was sampled four times (no bacteria were detected).

The diagnosis was established several hours after admission once the results of determinations of triglycerides (fT3) – 17.3 pmol L-1 (normal range 2.3-6.3 pmol L-1), thyroxin (fT4) 50.4 pmol L-1 (normal range 10.3-24.4 pmol L-1), TSH 0.009 μU mL-1 (normal range 0.4-4.0 μU mL-1) were available. The multidirectional causal and symptomatic therapy was initiated. To reduce the concentration of circulating thyroid hormones, methylthiouracil was administered through the gastric tube (intravenous forms of thyreostatics were not available) – 160 mg a day, divided into 4 portions, and 5% Lugol`s solution 100 drops a day. In order to inhibit the conversion of thyroxine into triiodothyronine the following were used: methylprednisolone 500 mg on day 1, followed by hydrocortisone 200 mg every 6 h and propranolol 120 mg per day through the gastric tube. On day 2 of hospitalization, due to weakened muscular strength, artificial lung ventilation was instituted with midazolam and fentanyl sedation. Cardioversion was repeate
d several times with no success. 

On day 4, ventricular activity was slowed down to about 100 min-1 and on day 5, sinus rhythm returned. The repeated ECG recordings showed gradual normalization of the ST segment. Intra-aortal counterpulsation was used for 72 h. On day 5, inotropic drugs were discontinued. Echocardiography was repeated which revealed an increase in the ejection fraction to 45%. Troponin I was determined (0.5 ng mL-1), laboratory indices of liver failure were observed (total bilirubin 78.8 μmol L-1, ALAT 241 U L-1, ASPAT 79 U L-1, fibrinogen 4.78 μmol L-1, INR 2.2, albumins 2.28 g dL-1). Throughout that period, the patient was on mixed feeding and glucose concentration was controlled with the infusion of insulin. The body temperature was decreased with physical methods, paracetamol and lytic mixture. Albumins and plasma were transfused. 

Hyperbilirubinemia lasted for 14 days. On day 5, the concentrations of free triiodothyronine and thyroxine increased to 30.2 pmol L-1 and 20.8 pmol L-1, respectively. On day 7, thyreostatics were discontinued and subtotal thyroidectomy was performed.  The procedure was uneventful. The controlled, followed by supported, respiration was continued for 7 days. Once the respiratory efficiency was restored, the patient, in satisfactory condition, was transferred to the surgical ward.

DISCUSSION

The thyroid storm is rarely treated in ITUs. The storm is caused by a sudden increase in serum levels of thyroid hormones or/and their decreased binding with plasma proteins, which increases the pool of free active hormones.

The range of clinical symptoms of thyrotoxicosis is extremely wide. Numerous symptoms characteristic of hypermetabolism and activation of the adrenergic system predominate. These include: hyperthermia, hyperhidrosis, muscular tremor and features of hyperkinetic circulation in the form of accelerated heart rhythm, increased arterial pressure and increased difference in the ratio of systolic to diastolic component [4, 5, 6, 7, 8]. Adrenergic stimulation results from increased number and sensitivity of adrenergic receptors with the concentration of catecholamines unchanged [9, 10]. Single cases of thyrotoxicosis without elevated body temperature and symptoms of adrenergic stimulation were also described [7]. Additionally to circulatory disorders, neurologic symptoms may develop – paralysis of ocular motor muscles, seizures, consciousness disorders, coma included, myopathy, which in extreme cases may lead to hypodynamic respiratory failure; gastrointestinal and hepatic disorders, rhabdomyolysis and secondary adre
nal cortex failure. According to the predominating pathology, thyrotoxicosis is divided into circulatory, gastrointestinal, renal, hepatic, adrenal and myasthenic. In the elderly patients, the thyroid storm may paradoxically present with the symptoms identical to those observed in hypothyroidism – the prostrative form.

The abundance of clinical symptoms makes the proper diagnosis difficult in some cases, particularly in the late period of thyrotoxicosis when hyperthermia or features of hyperkinetic circulation are no longer observed and symptoms of shock predominate [8]. 

The aetiology of shock in hyperactive thyroid storm is complex, cardiac and vascular – due to hyperhidrosis, hypovolaemia is likely to develop. In the early period, the cardiac output increases in response to increased metabolism. This phenomenon resembles the warm phase of septic shock. Myocardial damage and loss of adrenergic receptor sensitivity induce gradual circulatory failure leading to insufficient supply of oxygen to tissues and development of hypodynamic stage of shock [5].

The classical division, at present rarely used, differentiates the medical thyroid storm and surgical thyroid storm [1]. The former is most commonly caused by sudden withdrawal of antithyroid drugs, infections, stress, therapy with radioactive iodine or contrast agents containing this element in patients with thyrotoxicosis, gestosis and labour. The surgical causes include surgical procedures before euthyreosis is achieved. The prognosis in surgical thyroid storm is better than in medical storm, which is explained by the smaller size of the thyroid gland left after surgery.

Burch and Wartofsky [11] designed the classification helpful to diagnose the thyroid storm. The following are evaluated: the extent of heart action acceleration, body temperature, consciousness, gastrointestinal disorders, with possible intensified hepatitis, the extent of heart failure, presence of atrial fibrillation, predisposing factors. The score above 45 is highly suggestive of thyroid storm (Table 1). In our case, this score was 110, which makes the diagnosis of thyroid storm conclusive.

The case described is interesting for several reasons. Hyperactive multinodular goitre, unlike the Graves` disease, only exceptionally leads to thyrotoxicosis. The blood concentration of T3 and T4 in patients with thyroid storm is moderately increased and does not correlate with the severity of clinical course, which was observed in our case. A vast variety of partially atypical clinical symptoms is of interest; moderately increased temperature was particularly misleading as hyperthermia is one of the key symptoms of storm. The abundance of symptoms on admission led to diagnostic difficulties. The differential diagnosis included the diseases leading to coma, such as cerebrospinal meningitis and intoxication, or myocardial infarction, lung embolism, and sepsis manifesting in shock [8]. 

The ECG recording with persistent ST elevation was typical of acute coronary syndrome. Based on increased levels of myocardial necrosis markers, myocardial infarction was suspected and the patient was qualified for invasive treatment.

The abnormal ECG curve with normal coronary vessels evidences myocardial hypoxia related to insufficient oxygen supply. In 2000, a new definition of myocardial infarction was suggested, which, with slight corrections, was accepted for wider use in 2007 [12]. According to this definition, myocardial infarction is any myocardial necrosis, irrespective of a causative factor. The basic diagnostic parameter is elevated concentration of specific markers of myocardiocyte necrosis.

Thyrotoxicosis is one of few conditions, which may lead to myocardial necrosis without coronary atheromatosis [12, 13, 14, 15]. According to the current classification, this type of myocardial infarction is defined as type II, the essence of which is marked disproportion between the oxygen demand and supply. The cause of cardiac hypoxia is systemic and not localized in the coronary vessels in this special situation. Therefore, diffused damage to the myocardium predominates. In some cases, thyrotoxicosis results in coronary vasospasm or overcoagulation being the cause of coronary thrombosis [12, 13,14, 15]. In the case presented, the coronary angiogram was normal and cardiac hypoxia was caused by many coinciding events: hypermetabolism, hyperkinetic circulation and hypotension.

Aortal counterpulsation is the method of mechanical circulatory support, particularly useful in potentially reversible cases of cardiogenic shock. In our case, its use was also beneficial as it enabled us to reduce the doses of inotropic drugs and vasoconstricting agents minimizing their adverse arrhythmogenic and positive chronotropic effects on the heart.

Muscle weakness is the complication of thyroid storm, which may lead to respiratory failure (which was observed in our patient). The muscular dysfunction caused by hyperthyroidism presents in various, often extreme, forms – from neuromuscular stimulation manifesting as spontaneous tremor to paralysis. The cases of rhabdomyolysis and periodic hypokalemic paralysis triggered by this condition were also reported [1, 3, 4].

The liver dysfunction is induced by toxic effects of thyroid hormones on hepatocytes or, less commonly, is the complication caused by thyreostatics. It mainly presents as intrahepatic cholestasis. The post-drug dysfunction affects about 0.1% of patients treated with propylthiouracil and is associated with urticaria-like skin changes, which suggests its allergic origin [1].

The therapy of thyroid storm is to inhibit the production and release of hormones from the thyroid, to block the peripheral conversion of T4 to T3 and to reduce the adrenergic response [16, 17, 18]. The supportive activities are to normalize the body temperature, to sedate the patient, and to provide for increased caloric demand. The drugs used to reduce the production and release of thyroid hormones are thionamides (oral preparations: propylthiouracil, methimazole). The particularly strong action reducing the concentration of thyroxine is exhibited by iodine. The release of thyroid hormones from thyroglobulin is also inhibited by lithium carbonate used when thionamides are not tolerated. Another method to decrease the serum concentration of thyroid hormones is plasmapheresis. Beta-adrenolytic drugs are used to alleviate the effects of adrenergic stimulation and to inhibit the conversion of T4 into T3. To weaken the adrenergic reaction, short-acting drugs are preferable, e.g. esmolol. Their anti-arrhythmic effects are also relevant. Glycocorticosteroids inhibit the conversion of T4 into T3, decrease the iodine uptake as well as thyroid blood supply and prevent secondary adrenal cortex failure. To reduce the body temperature, methimazole is preferred; NSAIDs are not recommended as they displace proteins from thyroid hormones. In extreme cases when pharmacological therapy does dot improve the condition, strumectomy is recommended already in the acute stage of the disease [18].

The treatment in our case was carried out according to the protocol described, except for the use of catecholamines and intra-aortal counterpulsation. It was attempted to stop atrial fibrillation several times, however the procedure was ineffective under prolonging thyrotoxicosis.

The thyroid storm may cause diagnostic difficulties due to possibly complex and varied symptomology, especially when multiorgan failure develops, which is evidenced by our case.

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REFERENCES

1.    Nayak B, Burman K: Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin N Am 2006; 35: 663–686.

2.    Waldstein SS, Slodki SJ, Kaganiec GI: A clinical study of thyroid storm. Ann Intern Med 1960; 52: 626-642.

3.    Goldberg PA, Inzucchi SE: Critical issues in endocrinology. Clin Chest Med 2003; 24: 583–606.

4.    Tietgens ST, Leinung MC: Thyroid storm. Med Clin North Am 1995; 79: 169–84.

5.    Woeber KA: Thyrotoxicosis and the heart. N Engl J Med 1992; 327: 94-98.

6.    Burch WM: Nagłe stany w endokrynologii; w: Endokrynologia (Ed.: Burch W.M), Urban&Partner, Wrocław 1996, 30-32.

7.    Jiang YZ, Hutchinson KA, Bartelloni P, Manthous CA: Thyroid storm presenting as multiple organ dysfunction syndrome. Chest 2000; 118: 877-879.

8.    Pimental L, Hansen K: Thyroid disease in the emergency department: a clinical and laboratory review. J Emerg Med 2005; 28: 201–209.

9.    Landsberg L: Catecholamines and hyperthyroidism. Clin Endocrinol Metab 1977; 6: 697-718.

10.   Wilson BE, Hobbs WN: Pseudoephedrine-associated thyroid storm: thyroid hormone-catecholamine interactions. Am J Med Sci 1993; 306: 317-319.

11.    Burch HB, Wartofsky L: Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am, 1993; 22: 263–77.

12.    Dąbrowska B: Joint ESC/ACCF/AHA/WHF Task Force for the redefinition of myocardial infarction: Uniwersalna definicja zawału serca. Komentarz. Med Prakt 2008; I: 62-64.

13.    Proskey A, Saksena F, Towne W: Myocardial infarction associated with thyrotoxicosis. Chest 1997; 72: 109-111.

14.    Grabczewska Z, Białoszyński T, Kubica J: Acute myocardial infarction in a patient with iatrogenic thyrotoxicosis- a case report. Kardiol Pol 2007; 65: 280-282.

15.    Lewandowski K, Rechciński T, Krzemińska-Pakuła M, Lewiński A: Acute myocardial infarction as the first presentation of thyrotoxicosis in a 31-year old woman – case report. Thyroid Research 2010. http:/www.thyroidresearchjournal./com/conten/3/1/1

16.    Łącka K, Czyżyk A: Leczenie nadczynności tarczycy. Farmacja Współczesna 2008; 1: 69-78.

17.    Greenspan FS: The thyroid gland. Thyrotoxicosis crisis. in: Basic and Clinical Endocrinology (Ed.: Greenspan FS, Gardner DG), Lange Medical, New York, 2001.

18.    Gietka-Czernel M, Jastrzębska H, Dudek A, Szczepkowski M, Zgliczyński W: Strumektomia jako zabieg ratujący życie w ciężkiej nadczynności tarczycy. Endokrynol Pol 2007; 58: 52-56.

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Address:

*Waldemar Iwańczuk
Oddział Anestezjologii i Intensywnej Terapii
Szpitala Wojewódzkiego w Kaliszu
ul. Poznańska 79, 62-800 Kalisz
iwanczuk.waldemar@gazeta.pl

Received: 19.03.2010
Accepted: 22.06.2010