Subclinical thyroid dysfunction and the heart.
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Biomedical subjects
Publications and source records attributed to V Fatourechi.
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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.
CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.
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.
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.
UNLABELLED: Posttherapy scans (PTS) with a gamma camera are typically used after therapeutic doses of 131I to visualize metastases that may not be seen with lower dose diagnostic scans. During a 16-month period, we studied 81 patients (64 with papillary thyroid cancer and 17 with follicular thyroid cancer), who had both a diagnostic whole-body scan (131I dose 3 mCi) and a PTS. A total of 117 PTS were evaluated. At the time of PTS, clinical or radiologic evidence of metastatic or residual disease was present in 68 patients (84%). The anatomic sites of known disease included, neck (63), mediastinum (23), lung (35), bone (14), trachea (16), esophagus (5), and brain (2). PTS showed focal areas of abnormal uptake not seen in diagnostic scans in 15 scans (13%). Areas with abnormal new uptake included: neck (5), lung (5), mediastinum (4), bone (2), and adrenal (1). In 7 patients (9%) the PTS results impacted future decisions regarding plans for subsequent diagnostic scanning and 131I therapy or changed the patient's risk group category. IN CONCLUSION: (1) 13% of 117 PTS demonstrated abnormal foci of 131I uptake not seen on pretherapy scans and (2) PTS changed management strategy in 9% of the studied 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.
The term "autoimmune thyroid disease" encompasses all of the autoimmune thyroid conditions, including Hashimoto's thyroiditis, Graves' disease, most cases of silent thyroiditis, and postpartum thyroiditis. Extrathyroidal manifestations (e.g., ophthalmopathy, dermopathy) can occur in Graves' disease and, less commonly, Hashimoto's thyroiditis. Spontaneous hypothyroidism is common in patients with Hashimoto's thyroiditis, and when it develops, life-long therapy with levothyroxine is needed. In the United States, most adult patients with Graves' disease are initially or eventually treated with radioiodine thyroid ablation. For transient thyroiditis involving hypothyroidism or hyperthyroidism, short-term or symptomatic therapy is adequate.
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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.
A 35-year-old woman with features of Kearns-Sayre syndrome consisting of progressive ptosis, ophthalmoparesis, mitochondrial myopathy, and pigmentary retinopathy also had autoimmune polyglandular syndrome type 11 (Addison's disease, autoimmune insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and primary ovarian failure). There was no history of similarly affected relatives. Analysis of muscle mitochondrial DNA (mtDNA) revealed a 2,532-bp deletion of the type seen in Kearns-Sayre syndrome as well as a heteroplasmic A3243G mutation in the tRNA-Leu(UUR) gene of the type seen in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The patient's blood and her mother's blood harbored the A3243G mutation but not the deletion, and the maternal grandmother's blood had neither mutation. In muscle, the species of mtDNA harboring the deletion was exclusively associated with the species harboring the A3243G mutation, suggesting that the point mutation predisposed to the large-scale deletion. The mtDNA species with both mutations accounted for 88% of total muscle mtDNA. Other and as yet unrecognized point mutations in mtDNA might also be associated with, and possible causally related to, large-scale mtDNA deletions.
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.
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.
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.
PURPOSE: To provide long-term follow-up data on patients with Graves ophthalmopathy in an incidence cohort of 120 patients. METHODS: Data were obtained from a comprehensive review of each patient's community medical record, a follow-up survey, or both. RESULTS: The median interval between the initial ophthalmic examination and most recent follow-up was 9.8 years (range, 64 days to 17.4 years). Follow-up of more than 5 years was available for 96 patients (80.0 percent), whereas follow-up exceeding 10 years was achieved for 59 patients (49.2 percent). Persistent visual loss from optic neuropathy occurred in two eyes, with final visual acuities of 20/30 and 20/60, respectively. None of the patients reported deterioration of vision attributable to Graves ophthalmopathy in the interval since their last ophthalmic examination at the authors' institution. Two patients (2.2 percent) had constant diplopia, but it was correctable with spectacles (prisms) in each case. Nearly one third of respondents had had ocular discomfort during the preceding 4 weeks; the most frequent cause in 72 percent of patients was dry eyes. Among the respondents to the survey, 60.5 percent believed that the appearance of their eyes had not returned to what it had been before the development of thyroid disease, 51.6 percent thought that their eyes appeared abnormal, and 37.9 percent were dissatisfied with the appearance of their eyes. CONCLUSIONS: Although with treatment few patients have long-term functional impairment from Graves ophthalmopathy, more than one third of patients are dissatisfied with their ultimate appearance. The psychologic, aesthetic, economic, and social sequelae of the disorder require further definition by formal outcomes studies.
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.
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.