OBJECTIVE: To determine the accuracy of clinical palpation in the diagnosis of solitary thyroid nodule in comparison with ultrasonographic findings. METHODS: From a computerized database of 1774 patients with the diagnosis of nodular thyroid disease made from January 1990 through December 1991 at our institution, we retrieved and reviewed the medical records of the 193 patients who underwent ultrasonography of the thyroid (42 patients with multinodular glands on palpation were excluded). Nodules were categorized as "solitary" or "dominant nodule of a multinodular gland." Concordance rates were measured between results of palpation and ultrasonographic findings. RESULTS: Of 151 patients included in the study, 78 had solitary nodules on ultrasonography and 73 had multiple nodules. Of those with multiple nodules, 49 had two nodules and 24 had three or more nodules. Of clinically palpable nodules, 89% were 1 cm or greater in diameter. In 72% of the patients with multiple nodules, the other nodules not identified on palpation were less than 1 cm in diameter. The overall concordance rate between the size of the solitary nodule or the dominant nodule in a multinodular gland estimated with clinical palpation and the actual size seen on ultrasonography was 72%. The relationship between multiple nodules and malignancy was not statistically significant. CONCLUSIONS: Our results suggest that (1) a palpable solitary nodule represents a multinodular gland in about 50% of patients, (2) clinical palpation is less sensitive than thyroid ultrasonography in identifying multiple nodules, and (3) palpation is reliable only if a nodule is at least 1 cm in diameter. We recommend that small, occult (impalpable) thyroid nodules not be considered clinically important; they do not warrant further evaluation unless ultrasonographic features suggest malignancy or the nodule increases in size.

Adult↗

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Metastatic papillary cancer of the neck: a diagnostic dilemma.

The finding of papillary carcinoma in a neck mass usually leads to the presumptive diagnosis of metastatic thyroid carcinoma, with total thyroidectomy revealing the primary tumor. We report five cases of metastatic papillary carcinoma of the neck. The primary tumor in three of the cases was found to be nonthyroidal; two being discovered only after thyroidectomy failed to reveal a primary cancer. In the two thyroidal neoplasms, pathologic examination of the thyroid demonstrated only minimal tumor in one case and no detectable tumor in the other. These cases illustrate the pitfalls of diagnosis and treatment of these tumors and the utility of antithyroglobulin immunostaining in such cases.

Adenocarcinoma↗

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Relationship between vocal cord paralysis and benign thyroid disease.

BACKGROUND: Vocal cord paralysis is generally associated with advanced thyroid malignancy. It may also be present in the setting of benign thyroid disease. This association may be incidental as well as causal. METHODS: Retrospective review of cases with concurrent diagnosis of vocal cord paralysis and benign thyroid disease. RESULTS: Eight cases found, all with documented vocal cord paralysis, by laryngoscopy. Four patients had nodular thyroid disease, but in two it was contralateral to the recurrent laryngeal nerve paralysis. The remaining patients had goiters of various sizes. Six patients were euthyroid, two on thyroid hormone replacement. Two patients were thyrotoxic: one had Graves' disease and the other had subacute thyroiditis. CONCLUSIONS: Vocal cord paralysis can be the result of benign thyroid disease by such mechanisms as compression, stretching, or inflammation. Malignant thyroid disease should always be ruled out in structural thyroid abnormalities. Vocal cord paralysis can also be an incidental finding unrelated to thyroid abnormality.

Aged↗

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Familial dysalbuminemic hyperthyroxinemia: cumulative experience in 29 consecutive patients.

PURPOSE: The syndrome of familial dysalbuminemic hyperthyroxinemia (FDH), an inherited abnormality characterized by the presence of a variant serum albumin with preferential affinity for T4, is recognized with increasing frequency as a cause of elevated total and free T4 serum values in clinically euthyroid patients with normal TSH levels. Hyperthyroxinemia caused by this syndrome is occasionally confused with hyperthyroidism or thyroid hormone resistance syndromes, which may prompt unnecessary treatment. To better define the clinical and biochemical characteristics of patients with FDH, we undertook a retrospective analysis of the experience at our institution with this condition. PATIENTS: We reviewed our cumulative experience in 29 consecutive patients with FDH diagnosed between 1970 and 1991. RESULTS: FDH was diagnosed in 18 males and 11 females (mean age, 42.7 years) on the basis of clinical euthyroidism, increased total T4 and increased/normal free T4 serum values, normal T3 and TSH serum values, increased T4 binding to serum albumin, and low/normal T4 binding to T4-binding globulin and serum prealbumin. Clinical thyroid examination revealed no abnormalities except for goitre in five patients, and the results of radioiodine uptake studies were normal. Patients with subsequently documented FDH were referred for evaluation of "unusual" findings on thyroid function tests or FDH was detected on routine thyroid function tests or identified on family screening. Euthyroid hyperthyroxinemia in combination with a family history compatible with FDH correctly suggested FDH in seven patients. CONCLUSIONS: Clinical euthyroidism in conjunction with a normal basal sensitive TSH value in a hyperthyroxinemic patient differentiates euthyroid hyperthyroxinemia from thyrotoxicosis, obviating unnecessary therapy. Detection of excessive thyroxine binding to serum albumin establishes the diagnosis of FDH and allows it to be differentiated from thyroid hormone resistance syndromes. After a diagnosis of FDH has been established, family screening is advisable. Hyperthyroxinemia in clinically euthyroid patients ("euthyroid hyperthyroxinemia") is recognized with increasing frequency and should prompt a careful diagnostic evaluation. The differential diagnosis of this condition may be difficult because it includes various common and unusual syndromes, including quantitative or qualitative changes in thyroid hormone-binding proteins, circulating antibodies against thyroid hormones, resistance to thyroid hormones, influences from drugs, and acute somatic or psychiatric illness (1). The recently recognized syndrome of familial dysalbuminemic hyperthyroxinemia (FDH), an inherited abnormality with autosomal dominant transmission, is characterized by the presence of a variant serum albumin with preferential affinity for T4 (2-4). Typically, FDH is detected incidentally or patients are referred to endocrinologists on the basis of "unusual" results on routine thyroid function testing, revealing consistently elevated total T4 and elevated or normal free T4 values in a clinically euthyroid patient with normal TSH levels (1,5). Unfortunately, hyperthyroxinemia due to FDH may be confused with hyperthyroidism or thyroid hormone resistance syndromes, prompting repeated unnecessary laboratory testing and possibly even inappropriate treatment (1,3,6,7). Herein, we describe the clinical and biochemical characteristics of 29 consecutive patients with documented FDH.

Journal Article↗

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Fine-needle aspiration biopsy: use in diagnosis and management of pediatric thyroid diseases.

Fine-needle aspiration (FNA) biopsy of the thyroid is a reliable, safe, cost-effective, and widely used test. Its introduction and application have had a significant impact in the management of nodular thyroid diseases in adults. However, its utility in pediatric practice is not recognized or emphasized. During the last 12 years we performed 10,971 FNAs; 57 (0.5%) were in patients younger than age 17 years. Among 47 of these biopsies, 66% were benign, 15% were malignant, 6% were suspicious for malignancy and 13% were nondiagnostic. Biopsy was most often (96%) performed for the evaluation of diffuse or nodular goiter. The most common benign cytologic diagnosis was colloid goiter in 17 of 31 patients (55%) and Hashimoto's thyroiditis in 9 of 31 patients (29%). There were no false-positive results and there was one false-negative cytologic result. Among patients who had malignancy proved histologically, nine patients (75%) had papillary thyroid cancer. In this study, FNA biopsy was crucial in deferring surgery in 28 of 47 patients (60%). It is clear that the application of FNA biopsy prevents unnecessary surgery and improves surgical selection of patients with thyroid malignancy. On the basis of our extensive experience, we recommend FNA biopsy as the first diagnostic test for pediatric patients with nodular thyroid lesions.

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Recurrent hyperthyroidism after radioiodine-induced hypothyroidism: report of two cases and literature review.

The practice at the Mayo Clinic in treating Graves' disease with radioiodine (131 I) is to achieve a hypothyroid state. Less than 10% of the patients need more than one dose. Although cases of transient hypothyroidism have been reported after treatment with 131 I, the recurrence of hyperthyroidism is unusual after hypothyroidism has been induced with 131 I. We studied two cases seen at our institution in the past year in which the circumstances behind the recurrence have never been reported previously. The first case illustrates a recurrence of hyperthyroidism after the patient had received 38.5 mCi of 131 I. The second patient had recurrence of hyperthyroidism after 22 years of replacement therapy with levothyroxine. Both patients had increased levels of thyroid-stimulating immunoglobulin. We believe that the recurrence of the hyperthyroid state in these two patients was due to incomplete ablation of the thyroid. Apparently 131 I caused hypothyroidism, but residual cells remained viable and under continuous stimulation of thyroid-stimulating immunoglobulin produced recurrent thyrotoxicosis.

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Fine-needle aspiration biopsy of thyroid nodules.

Nodular thyroid disease is a common problem, particularly in women and the elderly population. Furthermore, 5% of thyroid nodules are likely to be malignant. Therefore, assessment for malignant potential is important, and fine-needle aspiration (FNA) biopsy is the most accurate technique. For each nodule, two to four aspirations should be attempted from different areas of the nodule. Although major complications of FNA biopsy are rare, proper cytologic interpretation necessitates special expertise. Cytologic diagnoses are usually categorized as diagnostic or nondiagnostic, and the diagnostic specimens are classified as benign, "suspicious," or malignant. Rebiopsy is indicated for enlarging nodules, recurrent cysts, and nondiagnostic cytologic findings. Because FNA biopsy is a safe, reliable, and rapid means of evaluating thyroid nodules, we recommend its routine use for diagnosis and treatment of thyroid nodular disease.

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Has fine-needle aspiration biopsy changed thyroid practice?

OBJECTIVE: To assess the influence of fine-needle aspiration (FNA) biopsy on the management of nodular thyroid disease. METHODS: We retrospectively evaluated the effect of the availability of FNA biopsy on thyroid surgical practice at our institution by comparing the data for two study periods--1975-1976 (before the introduction of FNA) and 1985-1986 (5 years after its introduction). RESULTS: The study inclusion criteria were fulfilled by 1,451 patients. In 1975-1976, 938 patients had thyroid operations at our institution. FNA biopsy was introduced into our practice in 1980. In 1985-1986, 513 patients underwent a thyroid surgical procedure. Before the FNA era, the frequency of carcinoma in patients selected for thyroidectomy was 18%, whereas after FNA became available, it increased to 25% (P< 0.0001). When patients were selected for surgical treatment because of either "suspicious" or malignant cytologic results, the yield of carcinoma increased to 40%. CONCLUSION: These data suggest that FNA biopsy has improved selectivity for operation in patients with nodular thyroid disease and has reduced the number of patients who undergo thyroidectomy for benign disease. The result is an increasing yield of malignant lesions found at surgical intervention. FNA biopsy has had a substantial cost-saving effect on thyroid practice.

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Prognostic value of suppressed thyrotropin level and positive thyrotropin-receptor antibody activity in Graves' disease with long-lasting clinical remission.

OBJECTIVE: To determine the prognostic value of suppressed thyrotropin (TSH) level and positive TSH-receptor antibodies (TSH-R Ab) in patients with Graves' disease who have long-lasting clinical remission. METHODS: We retrospectively studied patients with Graves' disease who underwent follow-up for a mean of 55 months after the withdrawal of antithyroid drug treatment. Study patients were 84 consecutive subjects in clinical remission, with normal serum free thyroxine (FT(4)) and free triiodothyronine (FT(3)) levels, regardless of serum TSH levels, a mean of 35 months (range, 6 to 135) after discontinuation of carbimazole therapy. Eighty-seven euthyroid subjects were used as control study participants. All subjects had serum determinations of FT(4) and FT(3) (radioimmunoassay), TSH (highly sensitive immunoradiometric method), TSH-R Ab (radioreceptor assay), and microsomal antibodies (M Ab, passive hemagglutination method). RESULTS: In the study patients, serum TSH was suppressed (</=0.10 mU/L) in 13 cases (15%), TSH-R Ab were positive (>/=15%) in 11 cases (13%), and M Ab were positive (>/=1:100) in 54 cases (64%). Simultaneous suppressed TSH and positive TSH-R Ab levels were present in six patients. During the follow-up, 11 patients had a relapse, demonstrated by above-normal values for serum FT(4) and FT(3) in association with clinical symptoms of hyperthyroidism. Five of them had a previously suppressed TSH level, three had a positive TSH-R Ab level, and six had a positive M Ab titer. Relapse was significantly more likely in patients with a previously suppressed TSH level (P<0.02) but not in patients with a previously positive TSH-R Ab level or positive M Ab titer. CONCLUSION: Patients with Graves' disease and long-lasting clinical remission after discontinuation of carbimazole therapy may have a suppressed TSH level, a positive TSH-R Ab level, or a positive M Ab titer (or some combination of these findings). Although positive TSH-R Ab and M Ab have no significant prognostic value, a suppressed TSH level is indicative of subclinical hyperthyroidism and higher risk of relapse.

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Increased serum carcinoembryonic antigen levels as an early sign of medullary thyroid carcinoma.

OBJECTIVE: To emphasize the potential association between increased levels of carcinoembryonic antigen (CEA) and the presence of medullary thyroid carcinoma (MTC). METHODS: We present two case reports of this association, including long-term serial measurements of CEA in one patient. RESULTS: CEA is a tumor marker often associated with colon cancer. In recent years, increased CEA in plasma has been reported in patients with other cancers. Diagnoses of MTC in two patients were preceded by increased CEA levels (for 6 years in one patient). Because CEA levels returned to normal after thyroidectomy, MTC may have been the cause of the increases. CONCLUSION: In patients with increased plasma CEA levels, MTC should be considered in the differential diagnosis even if thyroid palpation is nonrevealing and thyroid function is normal.

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