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    Abstract
    Introduction
    Case Report
    Discussion
    References

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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 13  |  Issue : 1  |  Page : 49-52
Anesthetic management of patient with myasthenia gravis and uncontrolled hyperthyroidism for thymectomy


Department of Anesthesiology and Intensive Care and Cardiothoracic Surgery, G. B. Pant Hospital, New Delhi, India

Click here for correspondence address and email

Date of Submission01-Nov-2008
Date of Acceptance02-Apr-2009
Date of Web Publication11-Jan-2010
 

   Abstract 

The relationship between myasthenia gravis (MG) and other autoimmune disorders like hyperthyroidism is well known. It may manifest earlier, concurrently orafter the appearance of MG. The effect of treatment of hyperthyroidism on the control of MG is variable. There may be resolution or conversely, deterioration of the symptoms also. We present a patient who was diagnosed to be hyperthyroid two and half years before the appearance of myasthenic symptoms. Pharmacotherapy for three months neither improved the myasthenic symptoms nor the thyroid function tests. Thymectomy resulted in control of MG as well as hyperthyroidism. In conclusion, effective control of hyperthyroidism in the presence of MG may be difficult. The authors opine that careful peri-operative management of thymectomy is possible in a hyperthyroid state.

Keywords: General anesthesia, hyperthyroidism, myasthenia gravis, thymectomy

How to cite this article:
Datt V, Tempe DK, Singh B, Tomar AS, Banerjee A, Dutta D, Bhandari H. Anesthetic management of patient with myasthenia gravis and uncontrolled hyperthyroidism for thymectomy. Ann Card Anaesth 2010;13:49-52

How to cite this URL:
Datt V, Tempe DK, Singh B, Tomar AS, Banerjee A, Dutta D, Bhandari H. Anesthetic management of patient with myasthenia gravis and uncontrolled hyperthyroidism for thymectomy. Ann Card Anaesth [serial online] 2010 [cited 2018 Dec 17];13:49-52. Available from: http://www.annals.in/text.asp?2010/13/1/49/58835



   Introduction Top


The association of myasthenia gravis (MG) with other auto-immune disorders such as thyrotoxicosis, hypothyroidism, hypokalaemic periodic paralysis (HPP), rheumatoid arthritis, Sjögren's syndrome, systemic lupus erythmatosis, and diabetes mellitus is well known. [1],[2],[3] Among the disorders which complicate MG, hyperthyroidism is the most frequent. [4] The prevalence of hyperthyroidism in MG varies from 2-17.5%. [3],[5] Reports concerning the effect of thyroid function on MG and thymectomy on hyperthyroidism are conflicting. We report anesthetic management of a patient, with primary hyperthyroidism, MG, in whom thymectomy ameliorated both hyperthyroidism and MG.


   Case Report Top


A 25-year-old male, weighing 65 kg, presented with generalized weakness, double vision, drooping of eyelids, difficulty in chewing, reduced muscle tone, and occasional difficulty in breathing since eight months. He was a known case of primary hyperthyroidism for the last three years and was under irregular treatment. The resting heart rate was 96/min, regular and arterial blood pressure was 130/ 80 mmHg. On examination, ptosis was noted bilaterally, more on the left side. Eyeball movement was limited in all directions. He also had vertical and horizontal diplopia and paretic nystagmus in the left eye on right lateral gaze. However, motor power of the limb muscles was normal. The MG diagnosis was confirmed by injection of edrophonium (10 mg intravenous), which resulted in prompt improvement of ptosis and ocular paresis. Investigations revealed a raised acetylcholine receptor antibody titre - 1.42 nmol/L (normal less than 0.25 nmol/L). Thyroid function tests (TFT) revealed T3 - 5.64 pg/ml (normal range: 2.3 - 4.2 pg/ml), T4 - 2.03 ng/dl (normal range 0.89-1.8 ng/dl) and thyroid stimulating hormone (TSH) - 0.04 µIU/ml (normal range 0.35-5.5 µIU/ml). Anti-thyroid antibodies against thyroid peroxidase were raised to 6682.10 U/ml (normal less than 60.0 U/ml) and thyroglobulin 145.60 U/ml (normal less than 60.0 U/ml). A computerized tomography (CT) scan of the chest showed a normal size thymus. Pulmonary function tests (PFT) and echocardiography showed normal results. Pyridostigmine 60 mg qid, prednisolone 20 mg o.d., and carbimazole 5 mg t.i.d. were started. But even after 3 months of treatment, neither the myasthenic symptoms improved nor did the TFT return to normal. A thymectomy was, therefore, advised.

A total of 0.5 mg of aplprazolam was given orally the night before surgery and pyridostigmine 60 mg, prednisolone 20 mg, and carbimazole 5 mg were administered on the morning of the surgery. Fentanyl 75 mg (intravenous) and glycopyrrolate 0.2 mg (intramuscular) were given in the operating room. Anesthesia was induced with thiopentone 250 mg and tracheal intubation was facilitated using rocuronium. It was administered in two increments of 20 mg (total 40 mg) to achieve full suppression of all four responses on train of four stimulation. Hydrocortisone 200 mg was administered intravenously following induction. Anesthesia was maintained with oxygen-nitrous oxide (40:60) and isoflurane. Fentanyl 50 mg and rocuronium 10 mg bolus were given at the appearance of second response on train of four stimulation (total maintenance dose of 30 mg rocuronium). Direct arterial pressure, heart rate, electrocardiogram, temperature, airway pressure, urine output, serial arterial blood gas analysis, and neuromuscular block (by accelography) were monitored throughout the surgery. The surgery lasted two hours during which the patient lost about 300 ml of blood that was replaced with 1 L of lactated ringer. Since neuromuscular behavior is known to be unpredictable postoperatively in such patients, elective ventilation was continued overnight and trachea was extubated next morning when the standard criteria for extubation were met. Routine drug therapy was continued in the post-operative period and 2 mg of dexamethasone was given intravenously every eight hours. A histological examination of the thymus did not demonstrate hyperplasia or malignancy. Acetylcholine receptor antibody titer could not be estimated due to logistic reasons. Besides an improvement in muscle power and ophthalmoplegia, thyroid function tests returned to normal after three days. Pyridostigmine and prednisolone therapy was tapered off and carbimazole was discontinued. The remaining post-operative period was uneventful and the patient was discharged from the intensive care unit on the fourth post-operative day. At the follow-up visit six weeks later, he had no complaints and thyroid functions were normal.


   Discussion Top


Hyperthyroidism may manifest earlier, concurrently, or after the appearance of myasthenic weakness in patients where the two conditions co-exist. [4] This association of MG and hyperthyroidism is considered to be due to a common autoimmune mechanism. [6],[7] In 75% of patients, symptoms of hyperthyroidism occur before or concurrently with those of MG. Thymic hyperplasia is usually associated with hyperthyroidism. [8] There is a positive relation between the two circulating antibodies against TSH and acetylcholine receptors and they might influence the clinical manifestations of each other. [6] In our patient, hyperthyroidism was present for two-and-a-half years before myasthenic symptoms became apparent. The effect of treatment of hyperthyroidism on the control of MG is not well understood. It has been reported that pharmacologic management of hyperthyroidism results in the resolution of myasthenia-like symptoms and regression of thymic hyperplasia concomitant with normalization of thyroid functions, [9],[4],[10] but there can be deterioration also. [7],[8],[11] This paradoxical phenomenon has been described as a see-saw balance; [11] when myasthenic manifestations increase, thyrotoxic symptoms decrease, and vice-versa. A reverse see-saw relationship has also been reported. [6] The see-saw relationship occurring shortly after the beginning of treatment of hyperthyroidism with methimazole has been noted by Kuroda, et al.[12] The authors opine that worsening of MS might be caused by the immuno-modulating property of methimazole, similar to that caused by ACTH and corticosteroids. [8],[12],[13] It has also been shown that anti-cholinesterase therapy makes it difficult to achieve euthyrosis in patients in whom MG coexist with hyperthyroidism, [14] as was seen in the present patient. The association of MG and hyperthyroidism is more than a coincidence. It is opined that a clinician should look for MG in hyperthyroid patients and vice versa, especially when symptoms of MG or hyperthyroidism worsen. [5],[6] The overlapping clinical features may cause diagnostic confusion and a detailed evaluation may be necessary to distinguish the two conditions, which have differing treatment and prognosis. [6],[15] MG patients usually show normal deep tendon reflexes. Ocular involvement and history of fluctuation can be found in 75.5% and 91.2% of generalized patients with MG. [16] The presentation with fluctuations of motor weakness during the day is an important feature to distinguish it from HPP. [2] In thyrotoxicosis, the neurological manifestations can include tremors, chorea, myopathy, and periodic paralysis in susceptible Asian individuals. Preparation and peri-operative management of patients with MG and hyperthyroidism constitutes a serious problem for a surgeon as well as the anesthetist. [15] An euthyroid state should ideally be attained before thymectomy. However, it may be difficult at times. [8]

The effect of thymectomy on thyroid function is controversial. Although Ratanakorn and Vejjajiva [3] reported no benefit from thymectomy, in controlling hyperthyroidism, thymectomy has been reported to ameliorate not only myasthenic symptoms but also hyperthyroidism. [8],[17],[18] It has been shown that TSH binding inhibitory immunoglobulin and thyroid stimulating immunoglobulin values decrease after thymectomy. [17],[19] The usual management for a patient with MG with thyrotoxicosis consists of control of hyperthyroidism with neomercazole followed by thymectomy and a subtotal thyroidectomy. [20] But, it has been suggested that with proper preoperative preparation, good anesthetic management, and perioperative respiratory care both the conditions can be surgically managed at one stage. [20] This is demonstrated by the present patient and perhaps indicates that if a euthyroid state is not attained pre-operatively, a thyroidectomy can be performed with careful management. Optimization of the condition of the myasthenic patient can markedly decrease the risk of surgery and improve the outcome. [21] Anti-thyroid agents, beta blockers (to relieve adrenergic imbalance of thyrotoxicosis) and anti-cholinesterase therapy should be continued in the peri-operative period. Thiopentone, which has an anti-thyroid activity, may be considered for induction of anesthesia. Since these patients, usually, are chronically hypovolaemic and vasodilated, they are prone to developing exaggerated hypotension during induction of anesthesia. In addition, patients with MG are extremely sensitive to non depolarizing neuromuscular drugs. The effective dose of vecuronium in control patients is reported to be 250% greater than in myasthenic patients. [22] However, individual response can vary from extreme sensitivity with a small dose being effective to nearly normal relaxant requirement. In addition, the sensitivity of the non depolarising muscle relaxants in myasthenic patients might be diminished by pyridostigmine with its anticholinergic activity. [23,24] The present patient was receiving pyridostigmine and required almost a normal dose of rocuronium bromide. Thus, the use of non depolarizing agents in myasthenic patients undergoing thymectomy mandates neuromuscular monitoring and careful titration of the drug dosages for safe outcome. About one-tenth to one-fifth of ED 95 should be used as a test dose to estimate the patient ' s requirements. Different anesthetic techniques, including balanced anesthesia, with the use of neuromuscular blocking agents have been used with success in these patients undergoing a thymectomy. [25] Sevoflurane (MAC = 0.5-0.7) has been used as the sole anesthetic agent for a trans-sternal thymectomy. [26] A high epidural anesthesia with lignocaine and fentanyl has been demonstrated to be a safe and useful technique for trans-sternal thymectomy with an added advantage that the patients are able to drink and walk within one hour after operation. [27] A combined thoracic epidural anesthesia and analgesia with balanced general anesthesia has also been recommended. [28]

Peri-operative use of medicines such as benzodiazepines, beta blockers, non depolarizing muscle relaxants, and antibiotics can induce a myasthenic crisis. This may necessitate elective ventilation in the post-operative period. [7],[29]

In conclusion, effective control of hyperthyroidism in the presence of MG may be difficult. However, careful peri-operative management of a thymectomy is possible in a hyperthyroid state. A thymectomy provides control of MG as well as hyperthyroidism.

 
   References Top

1.Téllez-Zenteno JF, Cardenas G, Estañol B, Garcia-Ramos G, Weder-Cisneros N. Associated conditions in myasthenia-gravis: response to thymectomy. Eur J Neurol 2004;11:767-73.  Back to cited text no. 1      
2.Sarkar S, Mandal K. Hypokalemic periodic paralysis accompanied with myasthenia gravis: A case report. Int J Anesthesiol 2008;16:2.  Back to cited text no. 2      
3.Ratanakorn D, Vejjajiva A. Long- term follow-up of myasthenia gravis patients with hyperthyroidism. Acta Neurol Scand 2002;106:93-8.  Back to cited text no. 3      
4.Engel AG. Neuromuscular manifestations of Graves' disease. Mayo Clin Proc 1972;47:919-25.  Back to cited text no. 4      
5.Trabelsi L, Charfi N, Triki Ch, Mnif M, Rekik N, Mhiri Ch, et al. Myasthenia gravis and hyperthyroidism; two cases. Ann Endocrinol (Paris) 2006;67:265-9.  Back to cited text no. 5      
6.Sekiguchi Y, Hara Y, Takahashi M, Hirata Y. Reverse ´see-saw' relationship between Grave ' s disease and myasthenia gravis. J Med Dent Sci 2005;52:43-50.  Back to cited text no. 6      
7.Lakhal K, Blel Y, Fysekidis M, Mohammedi K, Bouadma L. Concurrent Graves disease thyrotoxicosis and myasthenia gravis: the treatment of the former may dangerously reveal the latter. Anaesthesia   Back to cited text no. 7      
8.2008;63:876-9.   Back to cited text no. 8      
9.Teoh R, Chow CC, Kay R, Cockram CS, McGuire L. Response to control of hyperthyroidism in patients with myasthenia gravis and thyrotoxicosis. Br J Clin Pract 1990;44:742-4.  Back to cited text no. 9      
10.Tsuda E, Imai T, Matsumura A, Hisahara S, Nonaka M, Shiraishi H, et al. Thymic myopathy mimicking myasthenic syndrome associated with thymic hyperplasia. Intern Med 2008;47:445-7.  Back to cited text no. 10      
11.Grob D. Myasthenia gravis: current status of pathogenesis, clinical manifestations and management. J Chronic Dis 1958;8:536-66.  Back to cited text no. 11      
12.Maclean B, Wilson JA. See-saw relationship between hyperthyroidism and myasthenia gravis. Lancet 1954;1:950-3.  Back to cited text no. 12      
13. Kuroda Y, Endo C, Neshige R, Kakigi R. Exacerbation of myasthenia gravis shortly after administration of methimazole for hyperthyroidism. Jpn J Med 1991;30:578-81.  Back to cited text no. 13      
14.Fenzi G, Hashizume K, Roudebush CP, DeGroot LJ. Changes in thyroid- stimulating immunoglobulins during antithyroid therapy. J Clin Endocrinol Metab 1979;48:572-6.  Back to cited text no. 14      
15.Mitosek-Sabbo D, Dabrowski W, Korzeniowski Z. Anaesthesia for thyroid surgery in the patient suffering from myasthenia gravis. Wiad Lek 2001;54:573-6.  Back to cited text no. 15      
16.Tanwani LK, Lohano V, Ewart R, Broadstone VL, Mokshagundam SP. Myasthenia gravis in conjunction with Graves disease: a diagnostic challenge. Endocr Pract 2001;7:275-8.  Back to cited text no. 16      
17.Tiamkao S, Tiamkao S, Chotmongkol V, Jipimol-mard S. Prevalence and clinical features of myasthenia gravis only and myasthenia gravis with hyperthyroidism. Srinagarind Med J 1994;9:8-13  Back to cited text no. 17      
18.Takanami I, Imamuma T, Yamamoto Y, Yamamoto T, Kodaira S. The rapid transformation of hyperthyroidism to hypothyroidism complicated by myasthenia gravis. J Thorac Cardiovasc Surg 1995;110:852.  Back to cited text no. 18      
19.Itoh Y, Ohuchi M, Yoshida I, Ohmi M. Surgical treatment of myasthenia gravis associated with Grave's disease. Nippon Kyobu Geka Gakkai Zasshi 1992;40:587-91.  Back to cited text no. 19      
20.Chan KH, Yang MW, Huang MH, Hseu SS, Chang CC, Lee TY, et al. A comparison between vecuronium and atracurium in myasthenia gravis. Acta Anaesthesiol Scand 1993;37:679-82.  Back to cited text no. 20      
21.Naganathan N, Nambiar R, Tan NC, Chiang SC. A case of myasthenia gravis with thyrotoxicosis treated with combined subtotal thyroidectomy and total thymectomy. Br J Surg 1977;64:817-8.  Back to cited text no. 21      
22.Toyka KV. Myasthenia gravis. In: Johnson RT editor. Current Therapy in Neurological Disease. Philadelphia; BC Deeker Inc: 1990. p. 385-91.  Back to cited text no. 22      
23.Nilsson E, Meretoja OA. Vecuronium dose-response and maintenance requirement in patients with myasthenia gravis. Anesthesiology 1990;73:28-32.  Back to cited text no. 23      
24.Naguib M, Lien CA. Pharmacology of muscle relaxants and their antagonists. In: Miller RD ed, Miller's Anesthesia 5 th edn, Philadelphia; Churchill Livingstone: 2005. p. 481-572.  Back to cited text no. 24      
25.Baraka A, Taha S, Yazbeck V, Rizkallah P. Vecuronium block in myasthenic patient. Influence of anticholinesterase therapy. Anaesthesia 1993;48:588-90.  Back to cited text no. 25      
26.Paterson IG, Hood JR, Russell SH, Weston MD, Hirsch NP. Mivacurium in the myasthenic patients. Br J Anaesth 1994;73:494-8.  Back to cited text no. 26      
27.Kiran U, Choudhury M, Saxena N, Kapoor P. Sevoflurane as a sole anaesthetic agent for thymectomy in myasthenia gravis. Acta Anaesthesiol Scand 2000;44:351-3.  Back to cited text no. 27      
28.Tsunezuka Y, Oda M, Matsumoto I, Tamura M, Watanabe G. Extended thymectomy in patients with myasthenia gravis with high thoracic epidural anaesthesia alone. World J Surg 2004;28:962-6.  Back to cited text no. 28      
29.Akpolat N, Tilgen H, Gürsoy F, Saydam S, Gürel A. Thoracic epidural anaesthesia and analgesia with bupivacaine for transsternal thymectomy for myasthenia gravis. Eur J Anaesthesiol 1997;14:220-3.  Back to cited text no. 29      

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Correspondence Address:
Vishnu Datt
Department of Anesthesiology and Intensive Care, G. B. Pant Hospital, New Delhi 110 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.58835

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