2-Deoxy-2-[F-18]fluoro-D-glucose positron emission tomography/computed tomography in the management of melanoma.

OBJECTIVES: 2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single exam. The role of FDG-PET is proven in a variety of cancers, including melanoma, but the estimates of sensitivity and specificity are based in the majority of the published studies on dedicated PET, not PET/CT. Therefore, we were prompted to review our experience with FDG-PET/CT in the management of melanoma. METHODS: This is a retrospective study on 106 patients with melanoma (20-87 years old; average: 56.8 +/- 15.9), who had whole-body FDG-PET/CT at our institution from January 2003 to June 2005. Thirty-eight patients (35.9%) were women and 68 patients (64.1%) were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. RESULTS: All patients had the study for disease restaging. The primary tumor depth (Breslow's thickness) at initial diagnosis was available for 76 patients (71.7%) and ranged from 0.4 to 25 mm (average: 3.56 mm). The anatomic level of invasion in the skin (Clark's level) was determined for 70 patients (66%): 3, level II; 13, level III; 43, level IV; 11, level V. The administered dose of (18)F FDG ranged from 9.8 to 21.6 mCi (average: 15.4 +/- 1.8 mCi). FDG-PET/CT had a sensitivity of 89.3% [95% confidence interval (CI): 78.5-95] and a specificity of 88% (95% CI: 76.2-94.4) for melanoma detection. CONCLUSION: This study confirms the good results of FDG-PET/CT for residual/recurrent melanoma detection, as well as for distant metastases localization. PET/CT should be an integral part in evaluation of patients with high-risk melanoma, prior to selection of the most appropriate therapy.

Merkel cell carcinoma: Is there a role for 2-deoxy-2-[f-18]fluoro-D-glucose-positron emission tomography/computed tomography?

PURPOSE: 2-Deoxy-2-[F-18]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) is becoming widely available as a powerful imaging modality, combining the ability to detect active metabolic processes and their morphologic features in a single study. The role of FDG-PET/CT is proven in lymphoma, melanoma, colorectal carcinoma, and other cancers. However, there are rare malignancies such as Merkel cell carcinoma that can potentially be evaluated with PET/CT. We were therefore prompted to review our experience with FDG-PET/CT in the management of patients with Merkel cell carcinoma. PROCEDURES: This is a retrospective case series of six patients with Merkel cell carcinoma, 58-81 years old (average 69 +/- 8.3), who had whole-body PET/CT at our institution from January 1st, 2003 to August 31st, 2005. Two patients were women and four were men. Reinterpretation of the imaging studies for accuracy and data analysis from medical records were performed. RESULTS: Twelve examinations were acquired for the six patients (one patient had six PET/CT, one patient had two PET/CT, and four patients had one PET/CT). The injected FDG doses ranged 381.1-669.7 MBq (average 573.5 +/- 70.3). Four patients had the PET/CT as part of initial staging, and two patients had the exam for restaging (after surgery and XRT). A total of six Merkel lesions (pancreas, adrenal, lip, submandibular lymph nodes, cervical lymph nodes, and parapharyngeal soft tissue) were identified in three patients and confirmed on histopathological examination. The FDG uptake in these areas was intense, with maximum standardized uptake value (SUVmax) values of 5-14 (average 10.4 +/- 3.8). In one patient, the PET/CT scan identified abnormal focal distal sigmoid uptake that was biopsied and diagnosed as adenocarcinoma. Two patients had negative scans and had no clinical evidence of disease on follow-up office visits (up to one year after PET/CT). CONCLUSIONS: This case series suggests that FDG-PET/CT may have a promising role in the management of patients with Merkel cell carcinoma.

Graves' hyperthyroidism. Spontaneous occurrence after autoimmune hypothyroidism with persistent infiltrative ophthalmopathy.

The clinical course of a 39-year-old woman who exhibited uncommon features of autoimmune thyroid disease was followed. The patient's thyroid status changed from hypothyroid to hyperthyroid spontaneously. She also had severe infiltrative ophthalmopathy when she was hypothyroid. The unusual sequence of her condition raises some speculation about the pathogenesis of autoimmune hyperthyroidism and ophthalmopathy. The study also indicates that treatment of hypothyroidism may occasionally not be lifelong.

Prediction of satisfactory response to pleural sclerosis using radiopharmaceuticals: study in a patient with cirrhotic hydrothorax and LeVeen shunt.

Rapidly recurring right pleural effusion was a disabling clinical problem in a 51-year-old woman with alcoholic cirrhosis that had not been relieved by diuretic therapy or a LeVeen shunt. By injecting technetium Tc 99m albumin aggregated into the peritoneal cavity, shunt patency and rapid flow into the pleural effusion were demonstrated. In contrast, technetium Tc 99m albumin aggregated injected injected into the pleural fluid showed no movement into the abdominal cavity. These test results predicted that pleural sclerosis would help her clinical problem but would not place the abdominal contents in jeopardy. This prediction has proved to be correct.

Indium 111 WBC scan in local and systemic fungal infections.

We describe two patients-one with a systemic fungal infection and one with a localized form-who had strikingly abnormal indium 111 leukocyte (WBC) scans. The patient with systemic disease had an abnormal WBC scan before lesions became clinically apparent.

Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association.

A set of minimum clinical guidelines for use by primary care physicians in the evaluation and management of patients with thyroid nodules or thyroid cancer was developed by consensus by an 11-member Standards of Care Committee (the authors of the article) of the American Thyroid Association, New York, NY. The participants were selected by the committee chairman and by the president of the American Thyroid Association based on their clinical experience. The committee members represented different geographic areas within the United States, to reflect different practice patterns. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. Each committee participant was initially assigned to write a section of the document and to submit it to the committee chairman, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. Several of the committee members further revised and refined the document, which was then submitted to the entire membership of the American Thyroid Association for written comments and suggestions, many of which were incorporated into a final draft document, which was reviewed and approved by the Executive Council of the American Thyroid Association.

Dysthyroid ophthalmopathy: orbital evaluation with B-scan ultrasonography.

B-Scan ultrasonography was used to show muscle enlargement in all patients with Graves' disease and positive eye signs even when the clinical signs were minimal (lid lag and stare only). In addition, in cases of Graves' disease without clinical eye signs, 63% of orbital examinations showed ultrasonic evidence of muscle enlargement, often to a marked degree. This occurred more frequently in euthyroid patients after ablation of the thyroid by surgery or radiation, than in frankly thyrotoxic patients. The presence of subclinical ophthalmopathy in the fellow eye is a useful diagnostic aid in cases of uniocular proptosis.

Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.

Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.

Systemic radiation therapy with unsealed radionuclides.

Systemic unsealed radiation therapy is achieved when a radioactive substance is administered orally or parenterally and that material is concentrated in an organ or site for sufficient time to deliver a therapeutic dose of radiation. The radioactive material usually emits beta particles. In general, there is intense local radiation of the abnormal tissues, and normal organs, which do not trap the radioactive material, are exposed to a small radiation dose. The most frequent treatments involve radioiodine (131)I for hyperthyroidism and differentiated thyroid cancer. Other applications include treatment of painful skeletal metastases, polycythemia vera, malignant cysts, and neuroendocrine tumors. The treatments are usually well tolerated and not associated with long-term effects, such as cancer or infertility.

Hyperthyroxinemia in patients with acute psychiatric disorders.

Thyroid function tests were measured in 645 patients admitted to an acute psychiatric disorders unit. Thirty-three percent had elevated serum thyroxine (T4), and 18 percent had an elevated free T4 index (FTI). Serum triiodothyronine (T3) was low, normal, or minimally elevated in 77 patients, with a high initial free T4 index. Twenty-two patients with an initial elevation of their free T4 index were serially followed (study group). Serum T4, free T4 index, and free T4 fell in every patient: serum T4 from 13.95 +/- 1.93 micrograms/dl (mean +/- standard deviation: SD) to 9.33 +/- 2.4 micrograms/dl (p less than 0.001); free T4 index, from 6.15 +/- 0.83 to 3.79 +/- 1.1 (p less than 0.001); free T4, from 2.43 +/- 0.65 mg/dl to 1.38 +/- 0.35 ng/dl (p less than 0.001). Serum T3 was initially normal or low, and then fell in 17 patients, and rose in five. Serial testing of thyrotropin-releasing hormone (TRH) demonstrated both flat and normal responses in patients with a variety of psychiatric diagnoses and at varying stages of thyroid disease activity.

Thyroid abnormalities after therapeutic external radiation.

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity.

Prognostic factors in the radiotherapy of Graves' ophthalmopathy.

Between April 1968 and February 1988, 311 patients with symptomatic and progressive Graves' ophthalmopathy were treated with megavoltage orbital radiotherapy. The patients were divided into three groups: I (156 patients) treated with 20 Gy/2 weeks; II (69 patients) treated with 30 Gy/3 weeks, and III (a most recent set of 86 patients) received 20 Gy/2 weeks. The degree of eye involvement was evaluated numerically before and after therapy for each of five parameters: soft tissue signs, proptosis, eye muscle impairment, corneal involvement, and sight loss. Pre-treatment and current thyroid diagnosis and status were also noted. To evaluate the effects of radiotherapy alone, follow-up was terminated at the time any eye surgery was done; for those not treated surgically the minimum follow-up was 12 months. Because there were significant demographic differences between the patient groups, the results of each group were analyzed separately. A stepwise linear regression analysis was performed to determine if there were any significant variables affecting outcome. Based on these data formulae were derived which enable outcome to be predicted in any patient. Before therapy more than 90% of patients in all groups had soft tissue and eye muscle involvement, whereas 65-75% had proptosis and about half 50% had some degree of sight loss. Radiotherapy arrested progression of ophthalmic parameters in all but 1-6% of the patients. Objective and symptomatic improvement was noted for all parameters assessed, but there was marked individual variability. The best responses were noted for soft tissue, corneal involvement, and sight loss; however over half the patients had some improvement in eye muscle function and proptosis. Factors which resulted in less favorable outcome included male gender, advanced age, need for concurrent therapy for hyperthyroidism, and no history of hyperthyroidism. No complications have been observed. No significant differences in outcome were observed between the two dosage schedules. Following radiotherapy 29% of patients subsequently underwent some form of eye surgery, mostly eye muscle surgery to correct diplopia. After radiotherapy corticosteroid therapy was stopped without relapse in 76%. Orbital radiotherapy can result in improvement in signs and symptoms of Graves' ophthalmopathy in the majority of patients. For the remainder of patients the disease manifestations can be stabilized to allow functional surgical correction.

Radiotherapy of lymphoid diseases of the orbit.

Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. The diagnosis was made by biopsy in all patients and immunophenotyping was done in six cases, of which 5 were monoclonal. Patients were evaluated with a chest radiograph, lymphogram or abdominal CT, bone marrow biopsy and orbital CT. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. There were no relapses in those with localized disease. Two patients developed cataracts. Carefully planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma.

Long-term results of irradiation for patients with progressive Graves' ophthalmopathy.

PURPOSE: To determine the long-term outcome of radiotherapy (RT) in patients with progressively symptomatic thyroid eye disease and to evaluate the potential long-term sequelae. METHODS AND MATERIALS: Four hundred fifty-three patients provided written informed consent and received retrobulbar RT for Graves' ophthalmopathy at Stanford University Medical Center; 197 with 1 year of follow-up were retrospectively analyzed. Of the 197 patients, 189 received RT to the bilateral retrobulbar regions, and 4 received unilateral RT. The technical information was unavailable for 4 patients. Patients were assessed by chart review, telephone interview, questionnaire, and multidisciplinary physician examination. Eye impairment was scored using the SPECS system. The end point review included the before and after treatment SPECS score, surgical intervention, and patient satisfaction. Potential complications, including cataract development, retinopathy, and tumor formation, were investigated. Multivariate analyses were performed to assess the prognostic variables. RESULTS: Improvement or resolution was 89% for soft-tissue findings; 70% for proptosis; 85% for extraocular muscle dysfunction; 96% for corneal abnormalities; and 67% for sight loss. The response to RT may take >6 months to stabilize. Factors predictive of response varied in the individual SPECS categories but included the initial SPECS score, pretreatment thyroid status, female gender, a 20-Gy RT dose, and a history of hypertension. Nonpredictive factors included a history of tobacco use, diabetes mellitus, steroids, and prior cataracts. Only 16% required surgical intervention to preserve their vision or restore binocular vision. Twenty-two patients (12%) developed cataracts after irradiation (median 11 years). No patient developed a tumor within the RT field during the follow-up period (range 1-29 years). Ninety-eight percent of patients were pleased with their results, and 2% believed their symptoms progressed despite RT. CONCLUSIONS: Retrobulbar irradiation (20 Gy) is safe and effective treatment for progressive Graves' ophthalmopathy, with a 96% overall response rate, 98% patient satisfaction rate, and no irreparable long-term sequelae, with follow-up extending 29 years. The most common late effect observed was cataract development, which occurred more frequently in older patients and was reversible with extraction. Elective surgical intervention after RT should be withheld until patients have demonstrated a plateau in response.

Significance of thyroid dysfunction in human cardiac allograft procurement.

Twenty-two potential cardiac allograft donors had evaluation of thyroid function performed just prior to cardiectomy. Despite statistically significant abnormal thyroid function, no correlation to graft function or failure was observable. Multiple myocardial microinfarcts, undetected at the time of donor selection were detected in two hearts that were abandoned prior to transplantation and possibly another heart that failed as an allograft in a heart-lung transplant recipient.

Persistent fever in a patient with polycystic kidney and liver diseases and bilateral hip prostheses.

Persistent fever in a 60-yr-old man with polycystic kidney and liver diseases and bilateral hip prostheses was presented in this study. Multiple diagnostic tests failed to localize a source of infection. Subsequently, a combination of a 111In-oxine labeled WBC and 99mTc-sulfur colloid scans (and computer subtraction) demonstrated abnormally increased WBC activity in the left lobe of the liver, thus, diagnosis of an infected cyst (or cysts) was made. The patient responded to the treatment with antibiotics. This article discusses the clinical features of polycystic disease of the liver and kidneys. Infection in cysts are discussed as well as radiographic and scintigraphic investigations that can be used to diagnose and localize infection in a cyst.

Follow-up of patients with differentiated thyroid cancer using serum thyroglobulin measured by an immunoradiometric assay. Comparison with I-131 total body scans.

An immunoradiometric assay for thyroglobulin (Tg), which allows quantification of Tg in the presence of anti- Tg, has been evaluated in patients with differentiated thyroid cancer. All patients had undergone thyroidectomy plus I- 131 ablation. Three separate studies have been conducted. 1. Tg levels were compared with I- 131 whole-body scans made at 48 hr in 22 patient studies. Both tests gave similar results in 19 of the studies, but in three patients the results of the tests were discordant. 2. Tg levels were compared with clinical status in 18 patients who were free of disease; 15 had Tg values < 5 ng/ml, and three had measurable but normal Tg values. Three patients with metastatic disease had measurable Tg, and in two the values were above normal. 3. Sequential Tg measurements were made at intervals of 3 mo in 19 patients on thyroxine. Fifteen of these patients had identical results on two or more occasions.

Clinical experience with sensitive thyrotropin measurements: diagnostic and therapeutic implications.

A two-site immunoradiometric assay for serum thyrotropin (TSH) was modified to improve the analytical sensitivity. The sensitivity achieved (detection limit, approximately 0.1 microU/ml; lower limit of quantitative measurement, approximately 0.4 microU/ml) was comparable to that of the best competitive binding research assays, yet this assay can be performed routinely. Serum TSH was 1.82 +/- 0.69 (mean +/- s.d.) (range 0.4-3.4 microU/ml) in healthy individuals and 1.83 +/- 0.90 microU/ml (range 0.7-3.7 microU/ml) in patients with nonthyroidal disorders. By contrast, 97% of clinically hyperthyroid patients (Graves' disease, toxic nodular goiter) with high serum free T4 (FT4) and T3 had suppressed serum TSH values, i.e., less than 0.3 microU/ml. Among patients with euthyroid Graves' ophthalmopathy or nontoxic goiter those clinically suspected of mild hyperthyroidism had TSH values less than 0.3 microU/ml, while those judged euthyroid had normal values. A large proportion of thyroid patients on antithyroid drugs (poorly to well-controlled) had suppressed TSH. Of Graves' patients in remission (normal FT4 and T3), 75% had normal TSH, but individual levels changed significantly over time, suggesting that a progressive decline in TSH may be useful in predicting recurrences. In hypothyroid patients taking L-T4, serum TSH was subnormal in patients with elevated FT4, but TSH was also low in six patients clinically suspected to be thyrotoxic despite normal FT4 and T3 and in 32% of asymptomatic patients with normal thyroid hormone levels. Conversely, 23% of thyroid cancer patients who had undergone thyroidectomy were taking insufficient L-T4 to completely suppress TSH secretion. In 25 individuals who underwent thyrotropin releasing hormone (TRH) stimulation tests, the baseline serum TSH value correlated well with the peak serum TSH value post-TRH (r = 0.85). We conclude that sensitive TSH measurements could establish or confirm the diagnosis of hyperthyroidism in equivocal cases, replace most TRH-stimulation tests and be of value in optimizing L-T4 suppression therapy for thyroid cancer patients post-thyroidectomy.

Metastatic malignant struma ovarii presenting as paraparesis from a spinal metastasis.

A 42-yr-old woman had a solitary metastases to her spine (T2) from a malignant struma ovarii. The thyroid was excluded as the site of the primary cancer. The lesion caused paraparesis. The spinal metastasis was treated by surgery and two doses of 131I (200 mCi each time). The patient responded very well and is entirely free of symptoms and signs. Repeat whole-body 131I scan shows no abnormality.

Disparate effects of heparin on free thyroxine as measured by two radioimmunoassays: concise communication.

Free thyroxine (FT4) has been measured in two groups of patients, before and after heparin, using equilibrium dialysis (ED) and two radioimmunoassays, RIA-I and RIA-II. In Group A, nine patients were tested before and after 12-24 hr of intravenous heparin, FT4 (ED) rose from 1.9 +/- 0.5 to 2.8 +/- 3.0 ng/dl, and RIA-I from 1.37 +/- 0.37 to 1.89 +/- 1.21 ng/dl, whereas RIA-II results fell from 0.97 +/- 0.38 to 0.66 +/- 0.32 ng/dl. In Group B, ten patients were tested before and after 15 min of intravenous heparin. FT4 (ED) rose from 1.7 +/- 0.7 to 3.2 +/- 1.6 ng/dl (p less than 0.02), and RIA-I rose from 1.3 +/- 0.46 to 2.02 +/- 0.01 ng/dl (P less than 0.05), whereas RIA-II results fell from 1.07 +/- 0.38 to 0.63 +/- 0.31 ng/dl (P less than 0.02). The correlation coefficient between FT4 (ED) and RIA-I in 38 paired results was 0.96, but there was no correlation between FT4 (ED) and RIA-II results.