Transient Superior Vena Cava Syndrome Due to Propylthiouracil Therapy in Intrathoracic Goiter

11 Lister JW, Klotz DH, Jomain SIC, Stuckey JG, Hoffman BF. Effect of pacemaker site on cardiac output and ventricular activation in dogs with complete heart block. Am J Cardioll964; 14:494-503 12 Kersh ES, Kronfield SJ, Unger A, et al. Autonomic insufficiency in uremia as a cause of hemodialysis-induced hypotension. N Eng}J Med 290:650-53 13 Davidson DM, Brook CA, Preston TA, Judge RD. Permanent ventricular pacing: effect on long-term survival, congestive heart failure, and subsequent myocardial infarction and stroke. Ann Intern Med 1972; 77 :345-51 14 Bernstein V, Rotem CE, Peretz DI. Permanent pacemakers: 8-year follow-up study; incidence and management of congestive cardiac failure and perforations. Ann Intern Med 1971; 74:361-69

Transient Superior Vena Cava Syndrome Due to Propylthiouracil Therapy in Intrathoracic Goiter· Charles O. Hershey, M.D .; Robert C. McVeigh, M.D.; and R. Paul Miller, M.D.

Intrathoracic goiter is a rare cause of superior vena cava syndrome. We preseDt the findings in a patieDt in whom the syndrome was precipitated by therapy with propylthionracD and remitted OD withdrawal of the medicatioD. The superior vena cava syndrome did Dot recur OD medical managemeDt, suaesting that surgery is Dot always indicated ID this setting. vena cava syndrome, which is characterized Supeby riorsuffusion and dusky cyanosis of the face and

was present over the anterior superior portion of the chest, the supraclavicular fossa, and the neck. Flexion of the neck or raising the arms did not cause symptoms of obstruction of the thoracic inlet. The patient was hospitalized for investigation. The results of routine studies were normal; however, the level of thyroxine iodine was 3.~g/100 mI, and the level of thyroid" stimulating hormone was 15 IUII00 mI (normal, <10 lUI 100 ml), On the chest x-ray films, the superior mediastinal mass appeared unchanged from the evaluation in 1974. Varices in the upper thoracic portion of the esophagus were noted on barium swallow. A superior vena cavogram demonstrated that the innominate veins were obstructed bilaterally by a mass extending from the anterior portion of the neck into the superior mediastinum. Retrograde flDing of the proximal innominate veins was noted via the intracostal veins to the internal mammary veins (Fig 1 ) . Therapy with propyltln'ouracil was discontinued, and over the course of one week, the patient's obstruction of the superior vena cava gradually remitted. One month after discharge, she was frankly hyperthyroid. Her thyroid gland was half the size noted during the hospitalization. Therapy with propylthiouracil (50 mg every six hours) was reinstituted. During the next six months, following withdrawal of therapy with propylthiouracil for three days and its subsequent reinstitution, the patient received three separate doses of radioactive 131iodine, ranging between 25 and 28 mCi per dose. Eight months later, the size of the thyroid gland had dramatically decreased, and there was practically no palpable tissue in the neck. Fourteen months later, the patient died of unrelated causes, and permission for autopsy was not granted. DISCUSSION

In over 75 percent of the patients with superior vena cava syndrome, malignant tumors are the causative factors.' Rarely, intrathoracic goiters may lead to this syn-

upper extremity and a prominent venous pattern in the anterior wall of the chest, is caused by obstruction of the major veins leading to the right atrium of the heart. A malignant lesion compressing, infiltrating, or causing thrombosis is the most common cause of the syndrome." Occasionally, intrathoracic goiters may cause superior vena cava syndrome.s but to our knowledge, this syndrome as a complication of antithyroid therapy has not been previously reported.

CASE

REPoRT

A 74-year-old woman was noted to have a nontoxic multinodular goiter in 1974. A chest x-ray film demonstrated a superior mediastinal mass which was contiguous with the enlarged thyroid. In March of 1978, hyperthyroidism was documented, and propylthiouracil (200 mg orally twice daily) was prescribed. In the fall of 1978, the patient noted occasional mild swelling of the face and eyelids, most prominent in the morning. In November, on a routine office visit, her face was swollen, cyanotic, and edematous. The thyroid gland was twice its previous size. A superficial venous pattern -From the Endocrine and Metabolic Unit, St Mary's Hospital and the University of Rochester School of Medicine and Dentistry, Rochester, NY. Reprint requests: Dr. Miller, St . Mar'/a H081Jital, 89 Genesee Street, Rochester, New York 14811

356 HERSHEY, McVEIGH, MILLER

FIcmu: 1. Superior vena cavogram performed by simultaneous injection of dye into both brachial veins, demonstrating obstruction of both innominate veins by large goiter with substernal extension. Collateral circulation via intracostal veins to internal mammary veins is apparent

CHEST, 79: 3, MARCH, 1981

drorne, but their incidence as an etiologic factor is low. 2 Our patient is unusual in that the clinical presentation was caused by a substernal goiter which enlarged during treatment of hyperthyroidism with propylthiouracil and resolved on discontinuation of the antithyroid blocking agent. EfBer and Croves- reviewed the experience at the Cleveland Clinic with superior vena cava syndrome, and in two of 64 patients, the obstruction was caused by an intrathoracic goiter. These investigators 2 commented that the site of obstruction was compression of both innominate veins at the thoracic inlet. Subsequent case reports have invariably demonstrated this pattern radiographically, an unusual site of obstruction with causes other than intrathoracic goiter. 3-6 Collateral circulation around this site of obstruction is available via the internal mammary veins and the azygos vein, a more favorable pattern of drainage than with the more typical obstruction at or below the azygos vein. The collateral circulation in our patient was well developed (Fig 1), leading us to believe that the obstruction was gradual and that the intermittent complaints of facial swelling were early manifestations of impending venous obstruction. A number of symptoms, singly or in combination, such as dyspnea, cough, change in voice, stridor, or dysphagia, occur in up to 60 percent of the patients with large intrathoracic goiters.t-" Because our patient had none of the symptoms associated with a large intrathoracic goiter and because the increase in the gland's size was a prominent clinical manifestation, our initial concern was that the obstruction was caused by a carcinoma of the lung or thyroid. We were surprised when the superior vena cava syndrome resolved on withdrawal of the therapy with propylthiouracil. Although bed rest and diuretic therapy could have led to partial resolution of the syndrome, we believe that the goitrogenic effect of this medication led to enlargement of the thyroid gland and compression of the innominate veins. Propylthiouracil exerts its effects by blocking intrathyroidal organification of iodine, leading to iodine depletion and decreased synthesis of thyroid hormone." If synthesis of thyroid hormone is sufficiently depressed, the hypothalamic-pituitary axis is activated, and compensatory enlargement of the gland under the influence of thyroid-stimulating hormone will occur. Lending support that propylthiouracil, through this mechanism, led to the superior vena cava syndrome was the clinical and laboratory evidence of mild hypothyroidism at the time of hospitalization and the regression in size of the portion of the thyroid gland palpable in the patient's neck as she became hyperthyroid. The literature is unclear as to the favored therapeutic approach to superior vena cava syndrome of benign etiology. Studies by both Calkins"? and by Effier and Croves" recommend that for patients with good collateral circulation, the syndrome should be treated conservatively, reserving those with poor collateral flow for surgery. Mahajan et al11 has recently reviewed the experience at the Cleveland Clinic and reached similar

CHEST, 79: 3, MARCH, 1981

conclusions; however, they recommend surgery for the retrostemal thyroid causing superior vena cava syndrome. When thyrotoxicosis recurred in our patient, we elected to treat with 131iodine to control the hyperthyroidism and decrease the size of the gland. As multinodular goiters are resistant to conventional doses of 131iodine,12 we chose to empirically treat with three sequential doses of 131iodine, interspaced with periods of therapy with propylthiouracil. We chose to maintain therapy with propylthiouracil because the agent, by depleting the gland of iodine, would increase the efficacy of the administered 181iodine. We would like to call attention to propylthiouracil as a potential cause of superior vena cava syndrome due to its goitrogenic effect on substernal goiters. Our experience with this patient and review of the literature suggest that superior vena cava syndrome secondary to intrathoracic goiter need not necessarily be corrected surgically, that many patients do well when treated conservatively, and that large multinodular goiters can be treated safely and effectively with repetitive doses of 131iodine. In our view, emergency surgery for intrathoracic goiters should be reserved for those patients with respiratory embarrassment, and elective surgery should be considered only after a period of observation. ACKNOWLEDGMENTS: We are grateful to Ms. Bonnie DeConinck for editorial assistance and helpful criticisms during the preparation of this manuscript.

1 Lokich JJ, Goodman R. Superior vena cava syndrome. JAMA 1975; 231:58-61 2 EfBer DB, Groves LK. Superior vena cava obstruction, J Thorac Cardiovasc Surg 1962; 43:574-84 :) Silverstein GE, Burke G, Goldberg D. Superior vena cava obstmction caused by benign endothoracic goiter. Dis Chest 1969; 56:519-23 4 Siderys H, Rowe GA. Superior vena cava syndrome caused by intrathoracic goiter. Am Surg 1970; 36:446-50 5 Lindskag GE, Goldenberg IS. Differential diagnosis, pathology, and treatment of substernal goiter. JAMA 1957; 163:527-29 6 Evans JT, Vincent RG, Tahiter H. Superior vena cava obstruction with substernal thyroid. South Med J 1974; 67:3 7 Higgins CC. Intrathoracic goiter. Arch Surg 1927; 15:895912 8 Sherman PH, Shahbahrami F. Mediastinal goiter. Am Surg 1966; 32:137-42 9 Astwood EB. Thyroid and antithyroid drugs. In: Goodman LS, Gilman A. The pharmacological basis of therapeutics. 4th 00. New York: Macmillan Co, 1970:14661500 10 Calkins EA. The superior vena caval syndrome. Dis Chest 1956; 30:404-11 11 Mahajan V, Strimlan V, VanOrdstrand HS. Benign superior vena cava syndrome. Chest 1975; 68:32-35 12 Miller JM. Plummer's disease. Moo Coo North Am 1975; 59:1203-16

TRANSIENT SUPERIOR YENA CAYA SYNDROME 357