antithyroid drugs (thionamide) and corticosteroids are essentially ineffec- tive or fail to alter the dramatic course of the thyroid crisis. This limited effectiveness of ...
World J. Surg. 17, 622-627, 1993
WORLD Journal of
SURGERY 9 1993 by the Soci›233 Internationale de Chirurgie
Amiodarone-Induced Thyrotoxicosis: Is There a Place for Surgery? Michel Meurisse, M.D., Ph.D., Etienne Hamoir, M.D., Milbhor D'Silva, M.D., Jean Joris, M.D., Ph.D., and Georges Hennen, M.D., Ph.D. Departments of Endocrine Surgery, Anesthesiology, and Endocrinology, Centre Hospitalier Universitaire, Domaine du Sart-Tilman, Liege, Belgium Amiodarone-induced hyperthyroidism has on most instances been reported as mild, and thyroid functions return to normal after discontinuation of the drug. Nevertheless, life-threatening amiodarone-induced thyrotoxicosis has also been described. Conventional treatments such as antithyroid drugs (thionamide) and corticosteroids are essentially ineffective or fail to alter the dramatic course of the thyroid crisis. This limited effectiveness of medical therapy, particularly in patients with previously neglected or unknown thyroid disease, prompted us to intervene surgically. We report a series of nine patients who underwent total or near-total thyroidectomy as a first-line therapy for rive of them. Surgery resulted in rapid resolution of thyrotoxicosis with an uneventful postoperative course. This approach has the advantage of immediate effectivity, low risk of relapse, and appears to be the only treatment that permits continued therapy with amiodarone when the drug appears needed to control a life-threatening arrhythmia.
the choice therapy, as previously reported by Brennan et al. [17], Farwell et al. [18], and Blossey and Peitsch [19]. This report addresses the data obtained from nine consecutive patients who presented with amiodarone-induced severe hyperthyroidism of poor prognosis. These patients were treated by total or near-total thyroidectomy as front-line therapy in rive of them. Retrospective analysis of these data helps to define the indications of radical thyroidectomy in emergency settings such as the one described here. Patients and Methods
Patients
Amiodarone has frequently been used in Europe since 1967 for the prevention and management of refractory arrhythmias of supraventricular, junctional, and ventricular origin [1-8]. Conventional doses (300 mg daily or 5 days a week) of this iodine-containing drug yield 9 mg of free iodine daily, inflating body and thyroid iodine pools (the normal dietary requirement ranges from 0.2 to 0.8 mg/day) [9]. About 3% to 12% of patients receiving this medication can develop and present with hyperthyroidism, the pathologic process developing in normal thyroidal tissue or in pathologic thyroid tissue [10-13]. In some instances, reversal of thyrotoxicity and ultimate return to the euthyroid state by withdrawal of the drug is either not practical owing to the long half-life of the compound (22-55 days) or feasible because of the importance of this agent as the exclusive medication for controlling tachyarrhythmia [14, 15]. Though most often mild [11, 16], the evolution of the amiodaroneinduced thyrotoxicosis may be rapid and severe, particularly in "at risk" patients who have a goiter or underlying thyroid dysfunction. In these cases, because conventional treatments such as antithyroid drugs (thionamides) and steroids are ineffective or fail to stop the dramatic course of the crisis, surgery by way of a radical or near-radical thyroidectomy appeared as Offprint requests: M. Meurisse, M.D., Department of Endocrine Surgery, Centre Hospitalier Universitaire du Sart-Tilman, B35, Bd du Rectorat, B-4000 Liege, Belgium.
Our series comprises seven men and two women whose ages ranged from 50 to 84 years. Table 1 shows the indications for amiodarone prescription in the nine patients, the treatment duration until discovery of hyperthyroidism, and the duration of thyrotoxic symptoms. All these patients were admitted to our department of endocrinology and endocrine surgery for severe hyperthyroidism, rapid deterioration of their general condition, and worsening of the cardiac status. The clinical symptomatology was strikingly similar in ail patients: The most common symptoms were fatigue and intense weakness associated with rapid weight loss amounting to more than 10% to 15% of body weight over a few weeks period (2-15 weeks) (Table 1). The symptomatology, contrasting with a significant, long period of amiodarone treatment before the onset of hyperthyroidism explains that many of the patients were investigated for possible malignant process. For most of them, however, the correct diagnosis was established by the relapse or worsening of arrhythmias that had been previously well controlled by amiodarone. Patient 5 was admitted to the intensive care unit for severe congestive heart failure, asystole, and pulmonary edema with bilateral bronchopneumonia; he was considered terminal. Personal history revealed that none of these patients probably underwent endocrine baseline studies before undergoing amiodarone treatment, so there were no medical data concerning possible preexisting thyroid disease. At admission to hospital, in rive of nine cases sonography of the neck confirmed the clinical presence of a goiter, and in two of eight in whom the
Meurisse et al.: Amiodarone-Induced Thyrotoxicosis
Table 1. Amiodarone-associated
thyrotoxicosis (1991-1993): clinical
data. Duration of Age treatment Patient Sex (years) (months)
Duration of thyrotoxic Indication for symptoms amiodarone (weeks) prescription
1
M
50
48
10
2
M
55
24
15
3
M
59
36
6
4
M
69
36
6
5
M
70
24
2
6
M
73
48
14
7
F
71
3
8
8 9
F M
84 59
1 4
2 14
Premature atrial contractions Paroxysmal atrial fibrillation, premature ventricular contractions Aortic valvular replacement, atrial fibrillation Paroxysmal atrial fibrillation Mitral valvular replacement, atrial fibrillation Intractable atrial fibrillation Intractable atrial fibrillation Atrial fibrillation Potentially lethal ventricular arrhythmia
623
amiodarone administration was discontinued in ail patients, except patient 9. For the latter, this drug was considered the only medication that could be used to prevent and manage his life-threatening arrhythmia.
Surgical Intervention Anesthetic technique consisted in total intravenous anesthesia (sufentanil, propofol). Volatile anesthetics that can facilitate the development of cardiac arrhythmias in the presence of hyperthyroidism were avoided. Total or near-total thyroidectomy was conducted using standard techniques incorporating a nearly bloodless field dissection and identification and preservation of the superoexternal and recurrent laryngeal nerves and the four parathyroid glands [21]. In the event of encountering a parathyroid of questionable coloration, every attempt was made to preserve it by autotransplanting it in the sternocleidomastoid muscle.
Histopathology Operative specimens were fixed in 10% buffered neutral formalin and embedded in paraffin. They were then examined by light microscopy after hematoxylin and eosin staining. Resuits
clinical examination was negative sonography revealed a multinodular and a mediastinal goiter, respectively. Neither presented with exophthalmous or pretibial myxedema. Only patient 9 presented without clinical, sonographic, or scintigraphic evidence of preexisting thyroid disease.
Biochemical Investigations The assessment of thyroid function has been carried out with the following methods: 1. Thyrotropin and thyroglobulin determinations in serum, performed by ultrasensitive immunometric assays (Biocode S.A., Liš Belgium) 2. Free T 3 and free T4, by the Kodak diagnostic kits (Ghent, Belgium) 3. Reverse T 3 by radioimmunoassay (Biocode S.A., Liš Belgium) 4. Antithyroglobulin and antimicrosomal autoantibodies by radioimmunologic assay; anti-TSH receptor autoantibodies by a radioligand receptor assay, the three kits being from Biocode S.A.
Patients The clinical diagnosis of hyperthyroidism was substantiated and proved in all patients by confirmatory biologic testing. In the blood, free thyroxine (fT4) levels were increased more spectacularly than free triiodothyronine (fT3), with undetectable basal thyrotropin (thyroid-stimulating hormone; TSH) levels and a negative TSH response to thyroid-releasing hormone (TRH) (Table 2). Reverse T3, when assayed, was systematically in excess. Autoimmunity was not noted, if one excepts a slightly positive titer for antithyroglobulin autoantibodies (TgAb) in patient 6. Noteworthy, none exhibited autoantibodies (TRAb) against the TSH receptor. The 8.8% inhibition in the TRAb assay in patient 2 was not considered significant (cutoff value 12%) from a strict technical point of view. Patient 5 was dying of terminal cardiac failure in the intensive care unit. He presented with the greatest excess in reverse T 3 blood level. As mentioned above, eight patients probably had had neglected or overlooked preexisting thyroid disease. Sonography of the neck, when performed, revealed the presence of multinodular goiter in six patients and a single nodule in one patient. In the latter, autonomous adenoma was confirmed by 99mTc scintigraphy.
Patient Preparation Patients 2, 6, 8, and 9, before being referred to our center, had been previously treated by propylthiouracil (300-600 mg/day) for about 15 days (patient 8) to 3 months (patients 2, 6, 9) until surgery was proposed because of rapid deterioration of their condition. Thyroidectomy was front-line therapy for the other rive patients, with no specific preparation./3-Blockers were not used because of potential interactions with amiodarone (severe bradycardia) [20]. At the time of diagnosis of hyperthyroidism,
Treatment Because of initial ineffective conservative treatment of amiodarone-induced thyrotoxicosis observed in four cases, ail our patients finally underwent thyroidectomy. General anesthesia, surgery, and awakening were uneventful. Total thyroidectomy was performed in six patients, and the subtotal variant was conducted in the remainder. With the latter operation, essentially conducted for parathyroid gland preservation, the total
624
World J. Surg. Vol. 17, No. 5, Sept./Oct. 1993
Table 2. Amiodarone-associated thyrotoxicosis (1991-1993): preoperative laboratory studies.
Patient
Free T4 (8-20 pg/ml)
Free T 3 (2-6 pg/ml)
Reverse (15-35 ng/ml)
1 2 3 4 5 6 7 8 9
45 44 45 90 46 39 42 33 35
12.7 8.9 11.4 23.0 5.8 7.3 6.6 8.0 5.4
ND 54 75 ND 167 68 65 102 64
Thyroglobulin (5-55 n g / m l )
TSH Autoantibodies (0.4--4.5 Antithyroglobulin /xU/ml) (< 50 U1/ml)
Antimicrosomal (< 50 U1/ml)
Anti-TSH receptor (< 15%)
220 154 64 274 ND 58 32 9 37
< < < < < < < <
