Hyperthyroidism following hypothyroidism. Data on six cases.

Hypothyroidism complicated by spontaneous hyperthyroidism is an interesting but rare occurrence in the spectrum of autoimmune thyroid disorders. We report data on six patients who had hyperthyroidism two to 20 years (mean, eight years) after the diagnosis of hypothyroidism. In three patients, triiodothyronine toxicosis accounted for the hyperthyroid symptoms. The presence of thyroid antibodies and lymphocytic infiltration in the thyroid gland points to an autoimmune mechanism. It is believed that this phenomenon occurs more often than is recognized.

Dermopathy of Graves disease (pretibial myxedema). Review of 150 cases.

Pretibial myxedema is an uncommon manifestation of Graves disease, and little information is available regarding its natural course and its relation to other manifestations of Graves disease. We reviewed 150 consecutive cases with the diagnosis of pretibial myxedema over a 20-year period in a referral center. Only 1 patient in this group did not have ophthalmopathy, whereas 88% had significant proptosis and 30% required orbital decompression surgery. Dermopathy was a late manifestation of Graves disease, and its onset usually followed the diagnosis of hyperthyroidism and ophthalmopathy. In a few patients, dermopathy preceded diagnosis of hyperthyroidism or onset of ophthalmopathy. Fourteen patients were never clinically hyperthyroid; spontaneous hypothyroidism had developed in 11 in this group. All cases involved the lower extremities, with only 1 patient having combined upper and lower extremity involvement. The most common form of thyroid dermopathy was nonpitting edema, followed by nodular and plaque forms, which occurred with equal frequency. The polypoid form occurred in 1 patient and the elephantiasic form in another; 7.3% had thyroid acropachy. Follow-up was available for 120 patients (range, 3 mo to 19 yr; mean, 3.2 yr), and complete remission was observed in only 12 patients. Topically applied corticosteroid therapy was used in 76 patients, and in this group 38% had sustained long-term partial remission, as opposed to 18% in the group receiving no corticosteroid therapy.

The glucagonoma syndrome. Clinical and pathologic features in 21 patients.

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.

Pituitary thyrotropic adenoma associated with congenital hypothyroidism. Report of two cases.

Two patients with congenital hypothyroidism and thyroid-stimulating hormone-secreting pituitary adenomas are described. Both patients had a history of long-standing, inadequately treated hypothyroidism accompanied by markedly elevated levels of serum thyroid-stimulating hormone. Pituitary tissue, obtained at autopsy in the first patient and at surgery in the second, disclosed a thyrotropic adenoma. Immunocytochemical studies with anti-thyroid-stimulating hormone antisera showed both tumors to be strongly immunoreactive. Such thyrotropic adenomas of the pituitary gland are presumed to occur as the result of protracted pituitary stimulation secondary to long-standing thyroid deficiency.

Treating the patient with differentiated thyroid cancer with thyroglobulin-positive iodine-131 diagnostic scan-negative metastases: including comments on the role of serum thyroglobulin monitoring in tumor surveillance.

Differentiated thyroid cancer (DTC) patients, especially the 10% to 15% at high risk of cancer-related death, should have long-term monitoring for detection of recurrence or metastasis. Conventional radiologic and ultrasonographic imaging is useful for localization of recurrent or persistent disease. For patients who have had ablation of residual thyroid tissue, measurement of serum thyroglobulin (Tg) levels and radioactive iodine (RAI) imaging provide highly sensitive tools for early detection. Serum Tg is reliable only in the absence of Tg autoantibodies. Sensitivity increases with TSH stimulation, either by withdrawal of thyroxine (T4) therapy, or administration of recombinant TSH (rTSH). In some patients, serum Tg levels are positive but the RAI whole body scan (WBS) is negative. In these patients, either the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between Tg synthesis and the iodine-trapping mechanism. Recent literature suggests that empiric high-dose RAI therapy of Tg-positive diagnostic scan-negative patients may result in a high rate of visualization of uptake in posttherapy scans (PTS). Evidence for subsequent improvement of parameters of disease activity has also been presented. Almost all such reported cases had micrometastases that were not visualized by conventional imaging. In our experience, aggressive macrometastases with negative diagnostic WBS do not show significant uptake after therapeutic doses of RAI. The small size of micrometastases in the first group of patients and a possible defect of the iodine-trapping mechanism in the second group may explain this apparent discrepancy. Based on presently available information, a generalized recommendation for RAI therapy of Tg-positive, diagnostic scan-negative patients should await further studies. Meanwhile, in some high-risk patients, in the absence of alternative therapies, empiric RAI therapy is justified.

Subclinical thyroid disease.

The term subclinical thyroid disease is used to describe asymptomatic thyroid abnormalities found on imaging studies or laboratory tests. Thyroid nodules not palpable on physical examination but detected on imaging studies performed for other purposes are called incidentalomas. In the absence of risk factors for thyroid cancer, nodules that are less than 1 cm in diameter do not require biopsy. Subclinical hyperthyroidism is defined as suppressed serum sensitive thyrotropin (TSH) and normal serum thyroxine and triiodothyronine levels. This condition may adversely affect the heart and the bones and should be treated, especially in patients older than 60 years. Subclinical hypothyroidism, defined as mildly elevated serum TSH and normal serum thyroxine levels, is the most common thyroid dysfunction. In patients with subclinical hypothyroidism, thyroxine therapy should be given if the serum TSH level is higher than 10 mIU/L. For TSH values between 5 and 10 mIU/L, the decision for therapy should be individualized and depends on the level of TSH, presence of antithyroid antibodies, and clinical factors.

Clinical spectrum of hyperglucagonemia associated with malignant neuroendocrine tumors.

OBJECTIVE: To review the clinical features associated with hyperglucagonemia in malignant neuroendocrine tumors. MATERIAL AND METHODS: We retrospectively reviewed the medical records of patients with hyperglucagonemia encountered at our institution from Oct. 17, 1988, through February 1993 who had a fasting serum glucagon level of at least 120 pg/mL (twice the normal value). The 71 study patients also had no evidence of a secondary cause of hyperglucagonemia and had pathologic confirmation of a neuroendocrine tumor. RESULTS: The study group consisted of 46 men and 25 women with a median age of 57 years. Two patients had multiple endocrine neoplasia. Forty-nine patients had biochemically polyfunctional tumors, and 22 had hyperglucagonemia only. The most common initial symptoms were weight loss, abdominal pain, diarrhea, nausea, peptic ulcer disease, diabetes, and necrolytic migratory erythema (NME). Diabetes eventually developed in 25 patients and was associated with NME in 11. The highest median serum glucagon values occurred in patients with the glucagonoma syndrome or insulinomas, and the lowest median values were in those with carcinoid syndrome, Zollinger-Ellison syndrome, or diabetes without NME. Fasting glucagon and glucose measurements were not correlated. The most common hormonal syndromes were the Zollinger-Ellison syndrome and the glucagonoma syndrome. All the neuroendocrine tumors were malignant. Several methods of treatment, including surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization, were used. Death occurred in 29 patients at a median of 2.79 years after diagnosis; 42 patients were alive at a median of 2.86 years after diagnosis. CONCLUSION: A mild degree of hyperglucagonemia can commonly be associated with multifunctional neuroendocrine tumors. The glucagonoma syndrome occurs in a few patients with malignant neuroendocrine tumors and hyperglucagonemia and is associated with very high serum glucagon levels. The correlation between serum glucagon levels and the development of diabetes is limited, and other factors such as insulin may be more important than hyperglucagonemia in the development of diabetes.

A practical guideline for management of hypertension in patients with diabetes.

Hypertension is common in patients with non-insulin-dependent diabetes mellitus and is also an early sign of diabetic nephropathy in those with insulin-dependent diabetes. Hypertension contributes to the progression of both macrovascular disease and nephropathy in patients with diabetes. Certain antihypertensive agents can adversely affect carbohydrate and lipid metabolism. Angiotensin-converting enzyme inhibitors and calcium channel blockers may slow the progression of renal complications in patients with diabetes. The pharmacologic approaches to treatment of hypertension in patients with diabetes potentially differ from those in nondiabetic persons. On the basis of a review of the recent literature related to antihypertensive therapy for patients with diabetes, we describe an empiric approach to treatment of hypertension in such patients. The proposed approach must be modified as new data from randomized clinical trials become available.

Hypopituitarism caused by intrasellar aneurysms.

OBJECTIVE: To determine the prevalence, clinical presentation, and outcome of hypopituitarism due to an intrasellar aneurysm. PATIENTS AND METHODS: We performed a retrospective review of Mayo Clinic, Rochester, Minn, medical records from 1950 through 1995. We calculated the prevalence of hypopituitarism, characterized the clinical presentation, and evaluated postoperative outcomes. RESULTS: Of 4087 patients with a diagnosis of hypopituitarism, 7 had hypopituitarism due to an intrasellar aneurysm, accounting for a prevalence of 0.17%. Adrenal, thyroid, and gonadal deficiencies were observed in 7, 6, and 5 patients, respectively. The prolactin level was increased in the 2 patients in whom it was measured. No patient had diabetes insipidus. All had visual impairment. In 5 patients an intrasellar aneurysm of the internal carotid artery was diagnosed preoperatively based on 1 or more imaging procedures. In the other 2 patients (1 with an internal carotid artery aneurysm and 1 with an anterior cerebral artery aneurysm), the diagnosis was made at surgical exploration. Four patients underwent a surgical procedure: 2 had direct packing of the aneurysm, and 2 had a bypass with proximal carotid occlusion or aneurysm trapping. Pituitary function remained unchanged postoperatively. CONCLUSION: An intrasellar aneurysm is a rare cause of hypopituitarism (0.17% of cases). Preoperative diagnosis is essential for successful surgical outcomes. Hypopituitarism is usually permanent.

Thyroglossal duct carcinoma: report of 12 cases.

OBJECTIVE: To report the relative frequency, natural history, and optimal treatment of thyroglossal duct (TGD) carcinoma. DESIGN: We retrospectively reviewed all cases of TGD carcinoma surgically treated during a 44-year period at a tertiary referral center. MATERIAL AND METHODS: The computerized medical records database at Mayo Clinic Rochester was searched for patients who had the diagnosis of TGD carcinoma or TGD cyst carcinoma from 1950 through 1994. Medical records and pathologic specimens of these patients were reviewed. RESULTS: Twelve patients (six male and six female patients), who were 17 to 60 years old (mean, 40), were identified. The frequency of TGD carcinoma among surgically removed TGD cysts was 0.7%. A midline upper neck mass was the initial symptom in all patients. The diagnosis of cancer was made after the Sistrunk procedure in 11 of 12 cases and preoperatively (by fine-needle aspiration biopsy) in only 1 case. All patients had papillary carcinoma. Thyroid involvement was noted in three cases. Nine patients had subtotal or near-total thyroidectomy, and three received postoperative radioactive iodine. After a mean follow-up of 13 years (range, 1 to 38), no patient had a documented local recurrence or distant metastatic involvement, and no tumor-associated mortality was observed. CONCLUSION: TGD carcinoma is a rare malignant tumor that is usually diagnosed postoperatively. Papillary carcinoma is the most common pathologic finding. The recommended treatment is the Sistrunk procedure followed by near-total or total thyroidectomy by a skilled thyroid surgeon because of the possibility of intrathyroidal foci of cancer. The prognosis is excellent in patients with papillary tumor.

Transfrontal orbital decompression after failure of transantral decompression in optic neuropathy of Graves' disease.

Transantral and transfrontal orbital decompression procedures are effective for treating optic neuropathy of Graves' disease. We studied 10 patients with Graves' disease to clarify whether transfrontal decompression is effective after prior failure of transantral orbital decompression. All patients had persistent or recurrent optic neuropathy after transantral decompression and had failed to respond to systemic corticosteroid therapy. After transfrontal decompression, visual acuity improved in 70% of the eyes, and visual field scotomas decreased in 80%. No major intraoperative or postoperative complications occurred. We conclude that in optic neuropathy of Graves' disease, transfrontal orbital decompression after failure of transantral decompression is an acceptable and beneficial salvage procedure.

Predictors of response to transantral orbital decompression in severe Graves' ophthalmopathy.

OBJECTIVE: To identify factors that may help predict the outcome after transantral orbital decompression in Graves' ophthalmopathy. DESIGN: A retrospective study was conducted of 428 patients who had undergone an initial transantral orbital decompression for severe Graves' ophthalmopathy at the Mayo Clinic between November 1969 and May 1989. MATERIAL AND METHODS: With use of logistic regression analysis, we assessed the preoperative characteristics, the early postoperative results, and the follow-up questionnaire data (obtained a median of 9.5 years postoperatively) from 304 female and 124 male patients with Graves' ophthalmopathy who had undergone transantral orbital decompression at a median age of 53 years. RESULTS: On multivariate stepwise regression analysis, young age, male sex, and long duration of eye symptoms were predictors of severe initial proptosis (P < 0.001). The only independent predictors of greater postoperative recession of proptosis were severity of initial proptosis and longer interval between operation and postoperative examination (P < 0.001). Patients with the most reduction of proptosis had the greatest improvement in visual acuity but more chance for postoperative development of continuous diplopia. Failure of prior corticosteroid or orbital radiation therapy did not affect the degree of recession of proptosis or improvement in visual acuity. On multivariate analysis for predictors of long-term overall patient satisfaction, only young age of the patient was of borderline significance (P = 0.05), and the only significant predictor of satisfaction with the postoperative eye appearance was an operation done primarily for cosmetic purposes (P = 0.012). CONCLUSION: Although various factors may influence the outcome of orbital decompression in patients with Graves' ophthalmopathy, this study showed that the more pronounced the initial proptosis, the greater the degree of recession postoperatively. A higher degree of reduction of proptosis is associated with better visual acuity but also a greater likelihood of development of continuous diplopia.

Age distribution of patients with carcinoma of the colon in a general hospital in Iran.

One hundred and eighteen consecutive patients with histologically confirmed diagnosis of carcinoma of the colon discharged during a 10 year period (1962 to 1971) from a general hospital in Tehran were studied. Twenty-five patients (21 percent) were younger than 30 years of age and six patients were under 18 years of age. None had familial polyposis or ulcerative colitis. The data are suggestive of a younger age distribution of this disease in our population as compared to that of the Western countries.

Chronology of Graves' ophthalmopathy in an incidence cohort.

PURPOSE: To determine the chronologic characteristics of Graves' ophthalmopathy in an incidence cohort of 120 patients. METHODS: We reviewed the community medical records of 120 patients residing in Olmsted County, Minnesota, in whom Graves' ophthalmopathy had been diagnosed between 1976 and 1990. RESULTS: Median age at the time of diagnosis of Graves' ophthalmopathy was 43 years; the minimum and maximum ages were 8 and 88 years, respectively. Among 108 patients with hyperthyroidism, ophthalmopathy was diagnosed in the six-month interval preceding the diagnosis of thyroid dysfunction in 20 patients (18.5%); ophthalmopathy was concurrent with the diagnosis of hyperthyroidism in 22 patients (20.3%); and ophthalmopathy developed in the six-month interval after thyroid diagnosis in 24 patients (22.2%). Ophthalmopathy was diagnosed more than six months before the diagnosis of hyperthyroidism in only four additional patients (3.7%), whereas ocular changes developed six months or more after thyroid disease in the remaining 38 patients (35.2%). There was no significant seasonal variation in the diagnosis of either thyroid dysfunction or ophthalmopathy. Treatment of hyperthyroidism with iodine-131 did not appear to influence the course of Graves' ophthalmopathy. CONCLUSIONS: There is a strong temporal relationship between the thyroid and eye manifestations of Graves' disease. The diagnosis of Graves' ophthalmopathy tends to follow the diagnosis of hyperthyroidism. Treatment with iodine-131 does not appear to influence the course of Graves' ophthalmopathy. Although both childhood Graves' disease and Graves' ophthalmopathy are uncommon, ophthalmopathy occurs at all ages.

The treatment of Graves' ophthalmopathy in an incidence cohort.

PURPOSE: To determine the frequencies of medical and surgical treatments in an incidence cohort of 120 patients with Graves' ophthalmopathy. METHODS: We reviewed the community medical records and administered a follow-up questionnaire. RESULTS: Of the 120 patients, 89 (74.2%) required either no therapy or only supportive measures. Six patients (5.0%) were treated with systemic corticosteroids. One patient had orbital radiotherapy. Twenty-four patients (20.0%) underwent one or more surgical procedures. The cumulative probabilities of undergoing ophthalmic surgery of any type were 5.0% by one year after the diagnosis of ophthalmopathy, 9.3% after two years, 15.9% after five years, and 21.8% after ten years. The need for surgery was significantly related to age (P < .01; Cox proportional hazards model) but was not significantly dependent on gender (P = .5) or the interaction of age and gender (P = .15). The overall risk of the need for surgery was 2.6 times greater in patients older than 50 years (95% confidence interval, 1.2 to 5.8) than in younger patients. There were no significant differences between tobacco smokers and nonsmokers in the cumulative probabilities of undergoing surgery. CONCLUSION: In 24 (20%) patients, one or more surgical procedures were used to treat Graves' ophthalmopathy. The probability of surgical intervention was significantly related to patient age (older than 50 years), but it was not related to gender or smoking.

Results of transantral orbital decompression in 428 patients with severe Graves' ophthalmopathy.

We reviewed records from 428 consecutive patients with severe Graves' ophthalmopathy to determine early and late results after transantral orbital decompression. Optic neuropathy was present in 217 (50.7%) patients. Post-operatively, 402 (89%) of 453 eyes with preoperative visual acuity worse than 20/20 improved or remained the same. Visual field scotomas improved or resolved in 245 (91%) of 269 eyes tested pre- and postoperatively. Preoperative papilledema resolved or improved in 99 (94%) of 105 eyes, and preoperative exposure keratitis improved or resolved in 178 (92%) of 195 eyes. Average proptosis reduction was 4.7 mm. Postoperatively, new diplopia developed in 74 (64%) of 116 patients who had no diplopia before orbital decompression, although 300 patients ultimately had strabismus surgery. At late follow-up (N = 293 patients), 226 (77%) had single vision and 44 (15%) had correction with prism. Complications included sinusitis (18 patients), lower eyelid entropion (38 patients), numb lip (23 patients), cerebrospinal fluid leaks (15 patients), and one frontal lobe hematoma (one patient). The average duration of follow-up was 8.7 years. Transantral orbital decompression effectively reduces proptosis and usually corrects optic neuropathy. In other circumstances, the benefits achieved and the side effects incurred must be carefully balanced for each patient before transantral orbital decompression is considered.

The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota.

PURPOSE: To determine the incidence of Graves' ophthalmopathy. METHODS: A population-based cohort of all Olmsted County, Minnesota, residents who had ophthalmopathy associated with autoimmune thyroid disease between Jan. 1, 1976, and Dec. 31, 1990, was identified through the medical diagnostic index of the Mayo Clinic and the Rochester Epidemiology Project. RESULTS: One hundred twenty incident patients were identified, of whom 103 (85.8%) were women (P = .00001; normal relative deviate test). The overall age-adjusted incidence rate for women was 16.0 cases per 100,000 population per year, whereas the rate for men was 2.9 cases per 100,000 population per year (standardized rate ratio, 5.5; 95% confidence interval, 3.3 to 9.3). The distribution of incidence rates by five-year age groups included peak incidence rates in the age groups 40 to 44 years and 60 to 64 years in women, and 45 to 49 years and 65 to 69 years in men. CONCLUSIONS: Incidence rates for Graves' ophthalmopathy exhibited an apparent bimodal peak for both men and women, although the peaks for men occurred approximately five years after those for women. No explanation for these trends was apparent from the data collected.

Torsional diplopia after transantral orbital decompression and extraocular muscle surgery associated with Graves' orbitopathy.

Graves' orbitopathy can be associated with horizontal, vertical, and torsional diplopia. Of 428 patients treated with transantral orbital decompression, 21 had incycloduction (mean, 12.8 degrees; range, 5 to 20 degrees) and five had excycloduction (mean, 12 degrees; range, 5 to 20 degrees). All 26 patients had had recessions of the medial or inferior rectus muscle (or both) before onset of torsional diplopia. Mean recession was 5.5 mm (range, 4 to 10 mm) and 5.3 mm (range, 2 to 10 mm) of medial rectus muscle and inferior rectus muscle, respectively. An A pattern was often associated with the condition. Superior oblique tenectomy and inferior oblique myectomy were performed most frequently for incycloduction and excycloduction, respectively. Superior oblique tenectomy induced a mean incycloduction decrease of 7.1 degrees (range, 0 to 12 degrees). Exotropia in downgaze was decreased, and a small ipsilateral hyperdeviation was induced. Bilateral inferior oblique myectomy in one patient decreased excycloduction 10 degrees without inducing new deviation. At follow-up (mean, 63.7 months) after last strabismus operation, 15 patients with incycloduction and two with excycloduction had no diplopia.

Clinical features of Graves' ophthalmopathy in an incidence cohort.

PURPOSE: To determine the clinical characteristics of an incidence cohort of patients with Graves' ophthalmopathy. METHODS: We reviewed the community medical records of 120 patients residing in Olmsted County, Minnesota, in whom Graves' ophthalmopathy was diagnosed between 1976 and 1990. RESULTS: Among 120 patients with Graves' ophthalmopathy, 108 (90%) patients had Graves' hyperthyroidism, one (1%) had primary hypothyroidism, four (3%) had Hashimoto's thyroiditis, and seven (6%) were euthyroid. At some point in their clinical course, eyelid retraction was present in 108 patients, whereas the approximate frequency of exophthalmos was 62% (73 patients); restrictive extraocular myopathy, 43% (51 patients); and optic nerve dysfunction, 6% (seven patients). Only six (5%) patients had eyelid retraction, exophthalmos, optic nerve dysfunction, extraocular muscle involvement, and hyperthyroidism. At the time of diagnosis of ophthalmopathy, upper eyelid retraction and eyelid lag were documented in 85 and 52 patients, respectively, and the most frequent ocular symptom was pain (36 patients, 30%). Diplopia was noted at the initial examination by 20 patients, lacrimation was present in 25 patients, 19 patients had photophobia, and nine patients had blurred vision. Decreased vision from optic neuropathy was present in less than 2% of eyes at the time of diagnosis. Thyroid dermopathy and acropachy accompanied Graves' ophthalmopathy in five patients (4%) and one (1%) patient, respectively. Myasthenia gravis occurred in only one patient. CONCLUSIONS: Eyelid retraction is the most common clinical sign of Graves' ophthalmopathy. The complete constellation of typical features (hyperthyroidism, eyelid retraction, exophthalmos, restrictive extraocular myopathy, and optic nerve dysfunction) occurs relatively infrequently.

Graves' disease and low-output cardiac dysfunction: implications for autoimmune disease in endomyocardial biopsy tissue from eleven patients.

Classic high-output thyrotoxic heart disease is generally considered a direct effect of thyroid hormone. In contrast, the cause of the less common low-output heart failure is generally unknown. The aim of this study was to retrospectively evaluate available endomyocardial biopsy tissue from patients with coexistent Graves' disease and idiopathic low-output heart failure and determine whether the biopsy features were consistent with an autoimmune process. The study group consisted of 11 patients whose mean age was 47 years when they were diagnosed with hyperthyroidism and 52 years when diagnosed with cardiac dysfunction. Right ventricular endomyocardial biopsy tissue revealed severe lymphocytic myocarditis in a patient with severe ophthalmopathy and showed borderline myocarditis in a patient without ophthalmopathy. Biopsy tissues from 6 other patients showed appreciable myocyte hypertrophy and interstitial fibrosis, consistent with dilated cardiomyopathy. Two patients had nondiagnostic biopsy specimens, and 1 patient had features suggestive of arrhythmogenic right ventricular dysplasia. In conclusion, for the 11 patients with Graves' disease and unexplained systolic dysfunction, only 2 (18%) had lymphocytic infiltrates consistent with an autoimmune process. Thus, among patients with Graves' disease, most cases of low-output cardiac dysfunction appear to be due to causes other than an active autoimmune inflammatory process.