Management of thyroid nodules

Clinically apparent thyroid nodules occur in about 5 percent of the population. Because most patients with thyroid nodules present initially to their primary care physician, family physicians should have a thorough understanding of the diagnosis and treatment of thyroid nodules. The history and physical examination may be helpful in detecting thyroid nodules but are not useful in predicting malignancy. Furthermore, laboratory studies, ultrasonography and nuclear medicine scans do not reliably differentiate between benign and malignant thyroid nodules. In most cases, fine-needle aspiration biopsy can accurately identify malignant thyroid nodules. Fine-needle aspiration biopsy is safe and can be performed in an office setting.     

Thyroid palpation versus high-resolution thyroid ultrasonography in the detection of nodules

Detection of thyroid nodules by physical examination and high-resolution ultrasonography was compared using small groups of blinded, experienced physician examiners working with a sample of 2441 persons from Estonia, most of whom were Chernobyl nuclear reactor clean-up workers. A random subsample of 113 (5%) persons was subjected to triple control examinations with both physical examination and high-resolution ultrasonography. Positive high-resolution ultrasonographic findings were considerably more reproducible among different observers than were positive physical examination findings. Agreement between methods was poor. Nodules were found in 169 (6.9%) subjects by physical examination and in 249 (10.2%) subjects by high-resolution ultrasonography. Physical examination found only 53 (21%) of the 249 nodules found by high-resolution ultrasonography. High-resolution ultrasonography did not confirm the existence of 115 (68%) of the 169 nodules found by physical examination. Only 6.4% of nodules less than 0.5 cm in diameter, as based on high-resolution ultrasonographic results, were detected by physical examination. Physical examination detection improved with increasing nodule size but was still only 48.2% for nodules larger than 2 cm. Physical examination was relatively effective in detecting nodules in the isthmus of the thyroid gland but much less so for nodules in the upper pole of the gland. Clinical evaluation and epidemiologic studies of nodular thyroid disease stand to benefit from the greater sensitivity and specificity of ultrasonographic examinations.     

Thyroid cancer in pregnant women: diagnostic and therapeutic management

There is considerable literature on the effect of pregnancy on established thyroid cancer. In contrast, there are only isolated case reports of management of thyroid cancer diagnosed de novo during pregnancy. We describe four such patients. We recommend fine-needle aspiration biopsy (FNA) of solitary thyroid nodules found early in pregnancy. When the cytopathology is diagnostic of thyroid cancer, thyroidectomy under local or general anesthesia is advised. The patient should be given levothyroxine in a dose sufficient to keep serum thyroid-stimulating hormone (TSH) low. Serum thyroglobulin is a valuable noninvasive method of evaluating completeness of this therapy. The work-up of a nodule found late in pregnancy is best deferred until after delivery.     

Ultrasonic examination of the thyroid gland. Possibilities and limitations

In 440 patients with various thyroid disorders scintiphotography and ultrasonography were carried out. For ultrasonic examination both the A-mode and B-mode display technics were employed, included in the study were 324 patients with hypofunctioning solitary nodules; a histopathologic diagnosis could be obtained in 151 of these. The method proved to be especially valuable for differentiating between solid and cystic nodules. This is of practical importance because completely cystic nodules are nearly always benign and may be treated by thin needle puncture with aspiration of the cyst fluid. In addition, ultrasonography is of some value in making a better functional classification of nodules, better estimating the size of the thyroid and in the follow-up of patients with various thyroid disorders who are under treatment or untreated. Differentiating between benign and malignant solid nodules was not possible with the technic used. The examination can be safely carried out in pregnancy. The limitations of the technic are discussed.     

Utility of fine-needle aspiration cytology and frozen-section examination in the operative management of thyroid nodules

Fine-needle aspiration cytology has a high sensitivity for the diagnosis of solitary thyroid nodules. Certain diagnoses involving follicular histologies often cannot be made with needle biopsy alone. The utility of frozen-section examination of thyroid nodules, with particular regard to those lesions with follicular histologies, is also limited. We examined the correlation of fine-needle aspiration cytology and frozen-section examination in solitary thyroid nodules to determine the contribution of frozen-section examination to the operation. We reviewed the fine-needle aspiration cytology, frozen-section examination, and final pathology of 100 consecutive patients undergoing thyroidectomy for a solitary solid thyroid nodule in an 4-year period. The diagnoses were classified as indeterminant, benign, or malignant. The utility and impact of the diagnosis from fine-needle aspiration or frozen section on the operative procedure performed was analyzed. Fine-needle aspiration cytology as a diagnostic test for thyroid nodules demonstrated an indeterminant rate of 23 per cent, with a diagnostic accuracy of 77 and 92 per cent for benign and malignant disease, respectively. In all patients with inaccurate benign diagnosis on fine-needle aspiration cytology, follicular neoplasm was misinterpreted for follicular adenoma or multinodular goiter. In comparing frozen-section results, the indeterminant, benign, and malignant rates were 7, 96, and 64 per cent, respectively. Of the 23 patients with indeterminant results on fine-needle aspiration cytology, the intraoperative frozen-section diagnosis on 4 patients was deferred to permanent section; 18 received accurate cytological diagnosis; and in 1 patient, carcinoma was missed. Overall, the decision about the extent of surgical thyroid resection was changed in only 2 patients based on the frozen-section results. Preoperative evaluation with fine-needle aspiration cytology can accurately and appropriately define the extent of thyroid surgery in most patients with a diagnosis of malignant neoplasm or benign disease. Intraoperative frozen-section examination may be helpful if fine-needle aspiration cytology results are inderminant and in cases of follicular histology as an adjunct for evaluation of the thyroid nodule, but overall, frozen section does not contribute to the management of the thyroid lesion at the time of surgery.     

Manifestation of primary hyperthyroidism after pituitary adenomectomy: a case report

We report a 47-year-old Japanese man who presented with visual disturbance due to a pituitary tumor with suprasellar extension. The patient had mild secondary hypothyroidism preoperatively, and was started on administration of levothyroxine sodium immediately before transsphenoidal surgery. After the operation, levothyroxine sodium was continued for several months. Pathological examination of the surgical specimen, together with endocrinological investigation revealed that the suprasellar tumor was a FSH-producing pituitary adenoma. Since 3 months after the operation, he has developed muscle weakness and finger tremor. He was found to be thyrotoxicosis, and levothyroxine sodium was discontinued. Seven weeks after levothyroxine sodium was discontinued, thyrotoxicosis continued, with a positive thyrotropin binding inhibitory immunoglobulin (TBII) and a high diffuse 123I-uptake by the thyroid. He was started on thiamazole 30 mg/day. Although his thyroid dysfunction improved within 2 months, hyperthyroidism worsened repeatedly on attempts to discontinue thiamazole, and he required continuous treatment at 2.5 mg/day. Patients with occult autoimmune thyroiditis rarely progress to thyrotoxicosis after operations on other endocrine organs such as the adrenal or parathyroid gland. In patients with pituitary adenoma, thyroid function and thyroid-associated autoantibodies should be investigated pre- and post-operatively.     

Transition from cold to hot thyroid nodules

We report three cases of autonomously functioning thyroid nodules (AFTNs) that appeared hypofunctioning at radioactive iodine (131I) thyroid scan carried out at initial observation. Since at that time thyroid hormones and thyrotropin (TSH) were also normal, they were initially classified as "cold" nodules and treated with levothyroxine (LT4). The correct diagnosis of AFTN was made years later when a thyroid scintigraphy was repeated. In two of these patients, re-evaluation of the nodule was done because of the development of LT4 intolerance. A possible explanation is that these AFTNs had undergone hemorrhagic/cystic degeneration when they were first studied, but in subsequent years, proliferation of residual AFTN tissue caused the recurrence of a typical functioning nodule.     

Pediatric thyroid nodules: management in the era of fine needle aspiration

BACKGROUND/PURPOSE: Thyroid nodules are rare in children. The need to uncover malignancy is the most challenging dilemma in management. The aim of this report was to determine whether management of pediatric thyroid nodules has changed in the era of fine-needle aspiration (FNA) cytology. METHODS: Twenty-four children with thyroid nodules comprised the study group. Demographic characteristics, clinical manifestations, imaging results, FNA cytology results, surgical therapy, complications, and pathological reports were reviewed retrospectively. FNA cytology results were categorized as either benign, malignant, suspicious, or insufficient. RESULTS: Girls outnumbered boys (five to one) with a mean age of 14.9 years. Nineteen nodules were benign and five malignant. Malignancy was characterized by localized tenderness, multiglandular appearance, and fixation to adjacent tissues. Ultrasound scans and nuclear scans gave no clue toward management because cystic, hot, and warm nodules figured among malignant cases. FNA in 18 children achieved 80% accuracy, 60% sensitivity, 90% specificity, 75% positive, and 81% negative predictive value. Physical examination findings, persistence of the nodule, and progressive growth decided for surgery in most children. CONCLUSIONS: FNA is a safe adjunctive test that plays a minor role in the decision to withhold surgery. Its greatest strength is to resolve, in case of suspicious or malignant cytology, that a more radical procedure will be needed. Clinical judgement as determined by serial physical findings continues to be the most important factor in the management of thyroid nodules in children.     

Urethroplasty for balanitis xerotica obliterans

PURPOSE: To report a 20-month-old child with a rapidly growing dome-shaped red nodule on the left lower eyelid. The lesion was diagnosed clinically as an hemangioma, but microscopy disclosed an epithelioid Spitz nevus. METHOD: Case report. RESULT: Histopathologic examination of the excised lesion disclosed a Spitz nevus (benign juvenile melanoma) of a chiefly epithelioid cell type. CONCLUSIONS: The differential diagnosis of eyelid skin nodules in children should include Spitz nevus. This uncommon nevus has many cytologic features in common with nodular malignant melanoma. Histologically, it may be difficult to distinguish between nodular malignant melanoma and Spitz nevus.     

Thyroxine suppressive therapy in patients with nodular thyroid disease

PURPOSE: To review evidence about thyroxine suppressive therapy in patients with thyroid nodules, including the clinical importance and natural history of nodules and the effects and potential side effects of thyroxine therapy. DATA SOURCES: English-language articles published from 1986 to December 1996 were identified through searches of the MEDLINE database, selected bibliographies, and personal files. DATA EXTRACTION: Randomized, controlled trials and nonrandomized trials of thyroxine suppressive therapy for solitary and predominantly solid thyroid nodules were reviewed. In most studies, nodule cytology was evaluated by fine-needle aspiration biopsy. Therapy was considered suppressive if suppression was documented by thyroid-stimulating hormone-releasing hormone tests or sensitive thyroid-stimulating hormone assays. Response was defined as a decrease of 50% or more in nodule size or volume; most recent studies measured nodule size by ultrasonography. DATA SYNTHESIS: The evidence suggests that thyroxine suppressive therapy fails to shrink most nodules: Only 10% to 20% of nodules responded to this treatment. Fine-needle aspiration biopsy is more reliable in distinguishing benign from malignant nodules. Recent studies suggest that spontaneous decrease in size with complete disappearance of thyroid nodules is not uncommon. No data show that thyroxine therapy arrests further growth in most existing nodules or prevents the emergence of new nodules. Postoperative thyroxine therapy does not seem to prevent recurrence of thyroid nodules except in patients with a history of radiation therapy. Potential adverse effects of long-term suppressive therapy include osteoporosis and heart disease. CONCLUSIONS: Patients with cytologically benign nodules are best followed without thyroxine treatment. Most benign nodules remain stable in size and remain benign when monitored for a long time. For nodules that increase in size, biopsy should be done again or surgery should be performed.     

Significance of nondiagnostic fine-needle aspiration of the thyroid

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been shown to be rapid and cost effective in the evaluation of thyroid nodules. The significance of nondiagnostic (unsatisfactory) FNAB is uncertain, however. METHODS: We reviewed 345 consecutive thyroid FNABs and identified 59 patients with initially unsatisfactory specimens. These patients had follow-up to determine whether their thyroid nodules proved to be malignant. RESULTS: Three patients (5.1%) were found to have organ-confined papillary carcinoma of the thyroid, the largest tumor mass measuring 1.2 cm. Six patients (10.2%) had benign adenomas. CONCLUSIONS: In most cases of initially nondiagnostic FNAB of a thyroid nodule, neoplasia is not found subsequently. A minority of cases may still harbor malignancy. None of our patients in whom repeated FNA was either nondiagnostic or suggestive of benign disease were ultimately found to have a malignancy.     

Levothyroxine suppressive therapy for solitary thyroid nodule

In order to evaluate the efficacy of a TSH suppressive dose of levothyroxine to reduce the volume of a single thyroid nodule we studied 55 euthyroid patient: 45 (group A) were suppressed with LT4 (mean 1.7 +/- 0.9 micrograms/Kg/day) for 21.3 +/- 5.3 months, and 10 patients (group B) served as controls. All the nodules were "cold" at scintiscanning, solid at ultrasonography and benign by fine-needle aspiration cytology. As responders were assumed the nodules shrinked at the end of treatment of 50% in volume. Thyroid function values (TSH, T4, FT4, T3, FT3, thyroid peroxidase and thyroglobulin antibodies), clinical and ultrasonographic findings were evaluated initially and at the end of the study. A significant nodular volume decrease occurred in 8 treated patients (17.8%) while 37 (82.2%) amongst the group suppressed and all controls showed no change (A vs B = NS). In two untreated patients new nodules were noted; no new nodules were discovered in the treated group (A vs B p < 005). No side effects occurred in any treated patient, even if at the end of treatment a significant T4 and FT4 (p < 0.01) increase was observed. No one onset parameter can predict the response to the therapy. These results suggest that only a small group of patients affected by a single thyroid nodule seems to respond to a TSH suppressive therapy.     

Evaluation and management of the solid thyroid nodule

A tremendous effort has been applied to the determination of optimum management strategies in patients with solid thyroid nodules. The systematic acquisition of experience with historical and physical examination features suggestive of malignancy and the careful crafting of noninvasive techniques to assist in this determination have each contributed to improvements in the safety and cost-effectiveness of management in these patients. Despite this progress, significant difficulties await resolution, including the preponderance of patients still subjected to thyroidectomy for benign follicular lesions and the reluctance of clinicians to abandon the use of diagnostic techniques that offer little useful information, such as routine scintillation scanning and diagnostic trials of suppressive therapy. An exciting area now in its infancy is the identification of useful molecular markers for the selection of the few malignant thyroid nodules from among the multitudes of benign lesions. As is true in diagnostic evaluation, uncertainty continues to be experienced by clinicians charged with proper nonsurgical management of the solid thyroid nodule. The use of thyroid hormone suppressive therapy, once considered a cornerstone of conservative management, has been cast in a new light revealing both the limited utility and potential harm associated with this approach. These uncertainties should not be viewed as impediments, but rather, as opportunities for growth, as it is controversy rather than complacency that stimulates new investigation and fresh approaches to old problems.     

Thyroid disease among the Rongelap and Utirik population--an update

In 1954, 253 Marshallese were accidentally exposed to fallout radiation from the hydrogen bomb, BRAVO. The Marshall Islands Medical Program (MIMP) was established by the Department of Energy in 1955 to monitor and treat radiation-related disease pursuant to this accident. Medical teams from Brookhaven National Laboratory, a federal institution, regularly visit the Marshall Islands to give medical care to the exposed population. The most significant complication of the exposure has been found to be thyroid disease due to the ingestion of radioactive iodides from the fallout. In 1963 the first thyroid nodules were found in Rongelap subjects and in 1969 in Utirik. Non-neoplastic adenomatous nodules were associated with higher doses of radiation and neoplastic nodules developed in individuals receiving lower doses of radiation. Women were more susceptible to the development of palpable thyroid nodules than men. In 1994 the MIMP initiated examination of the thyroid by ultrasound to supplement the clinical examination. One hundred and sixty-four patients were evaluated. No significant differences were found in the incidence of thyroid nodules or the mean nodule count between the three groups of Rongelap and Utirik exposed and a comparison patient population. There was no significant difference in the incidence of thyroid nodules in males vs. females. Five exposed patients were referred for surgical excision of a nodule detected only by ultrasound. These ultrasound findings are unexpected in that females are known to have a higher incidence of thyroid disease than males and we expected that the incidence of ultrasound nodules would be higher in the exposed population.     

Technetium-99m tetrofosmin imaging in thyroid diseases: comparison with Tc-99m-pertechnetate, thallium-201 and Tc-99m-methoxyisobutylisonitrile scans

Technetium-99m tetrofosmin is a lipophilic phosphine used for myocardial perfusion imaging. Biodistribution studies have shown significant thyroid uptake of tetrofosmin and preliminary reports have suggested that tetrofosmin imaging may be of value in patients with thyroid cancer. In this study, tetrofosmin whole-body scintigraphy was performed in 35 patients with evidence of thyroid diseases. All patients underwent laboratory evaluation of thyroid function as well as 99mTc pertechnetate scan, thallium-201 (n=16) 99mTc-methoxyisobutylisonitrile (MIBI) (n=19) whole-body studies. Thyroid images were semi-quantitatively analysed by a 4-point score: 0=no significant uptake; 1=uptake increased as compared to background activity, but inferior to normal thyroid tissue; 2=uptake equal to normal thyroid tissue; 3=uptake superior to normal thyroid tissue. Pathology examinations were obtained. A total of 41 thyroid nodules were detected, of which 15 were goitre nodules, 13 adenomas and 13 malignant lesions. In goitre nodules, concordant results of tetrofosmin and pertechnetate uptake (score 1 or 0) were observed in the majority of lesions (87%). In function adenomas (n=10), both tetrofosmin uptake and pertechnetate uptake were score 3. In non-function adenomas (n=3), tetrofosmin uptake was score 3, while pertechnetate uptake was score 0. In six malignant lesions, tetrofosmin uptake was score 3, while pertechnetate uptake was score 0; in the other seven lesions, where a prevalence of goitre abnormalities was observed, results of tetrofosmin and pertechnetate uptake were similar (score 0 or 1). In seven (70%) of the ten patients with malignant nodules, whole-body tetrofosmin images showed increased abnormal uptake in a total of 28 extra-thyroid tumour sites, as subsequently confirmed by other techniques. When tetrofosmin images were compared to 201Tl and 99mTc-MIBI scans, concordant results were observed in all cases. In conclusion, tetrofosmin imaging may be particularly useful to characterize and stage patients with malignant thyroid nodules; it shows similar results to thallium but provides better image quality. Comparable findings were observed between tetrofosmin and MIBI studies. Thus, tetrofosmin may be an alternative to thallium and MIBI in the aforementioned patients.     

Benign thyroid oncocytomas. Outcome after more than 4 years

OBJECTIVES: Occasional malignant transformation after partial thyroidectomy for Hürthle cell tumours has led certain authors to propose total thyroidectomy in all cases. The aim of this retrospective study was to evaluate outcome 4 years after partial thyroidectomy in patients with Hürthle cell tumours. METHODS: Ten patients (9 females, 1 male; mean age 45 years; age range 21-65 years) underwent thyroid surgery for Hürthle cell tumours from 1980 to 1989. Lobectomy was performed in 7, subtotal thyroidectomy in 2 and tumourectomy in 1. The extemporaneous pathology examination reported 4 apparently benign vesicular lesions, 2 apparently benign oncocyte lesions, 2 fetal adenomas, 1 thyroiditis, 1 trabecular adenocarcinoma. Pathology examination of the surgical specimen reported isolated benign oncocyte tumours in 4 cases and benign oncocyte tumours with associated vesicular adenomas in 5. In 1 case it was not possible to confirm whether the oncocyte lesion was benign or malignant. All 10 patients were seen again 6 months later for consultation and thyroid hormone assays and thyroid echography in doubtful cases. RESULTS: All patients were seen for follow-up (mean 88 months; range 47-148 months). New thyroid nodules were observed in 2 but did not require surgery. No cervical lymph node enlargement was found. CONCLUSION: The diagnosis of Hürthle cell tumour was confirmed intraoperatively in 8 of the 10 cases. No malignant transformation was observed. These findings demonstrate that total thyroidectomy cannot be indicated intraoperatively and would not appear to be indicated after partial thyroidectomy.     

Management of cystic lesions of the tail of the pancreas

OBJECTIVE: To emphasize that although cystic pancreatic neoplasms are stated to make up only 10% of pancreatic cysts, this number may be significantly higher if patients who are misdiagnosed with pseudocysts are considered. DESIGN: A small case series. SETTING: A tertiary-care centre. PATIENTS: A consecutive sample of three patients with cystic lesions of the tail of the pancreas seen between 1992 and 1994. All three were women ranging in age from 28 to 42 years. Two had been treated previously for pancreatic pseudocysts by cystenterostomy. None had a history of pancreatitis or alcohol abuse, and gallstones were not present on ultrasonography. INTERVENTIONS: Distal pancreactectomy and splenectomy. RESULTS: The excised specimens from the two patients treated initially elsewhere revealed mucinous cystadenoma with atypia in one and mucinous cystadenocarcinoma with invasion into stomach in the other. In the third patient, a cystic neuroendocrine tumour and two other intrapancreatic nodules of neuroendocrine tumour were found on pathological examination. CONCLUSIONS: Pancreatic neoplasms may be misdiagnosed as pancreatic pseudocysts. In patients without a history or risk factors for pancreatitis, a cystic pancreatic mass is not necessarily a pseudocyst, and such patients should be considered for pancreatic resection.     

Thyroid cancer: relationship to radiation exposure and to pregnancy

Exposure to radiation results in an increased occurrence of nodularity to the thyroid and, more important, the development of cancer in a significant proportion of patients. Near-total thyroidectomy is recommended in those patients with a history of irradiation who are found on physical examination of the thyroid to have one or more nodules. Although pregnancy appears to have no effect on the course of thyroid carcinoma and the tumor has no effect on pregnancy, because of the numerous stimuli to thyroid growth during pregnancy, we feel that pregnancy is best avoided by women with known residual disease.     

Embryological considerations of thyroid surgery: developmental anatomy of the thyroid, parathyroids and the recurrent laryngeal nerve

The surgeon planning a thyroidectomy must be prepared to find variations in three important structures in the neck. He must be prepared to find ectopic thyroid nodules above, below or lateral to the normally located thyroid gland. Any unattached nodule should be considered malignant until proved otherwise. He must identify and preserve parathyroid glands that may not lie in the typical location. He must be prepared to encounter recurrent laryngeal nerves that do not recur. The surgeon who remembers the embryology of the structures in the neck may occasionally be astonished, but never surprised.     

The value of aspiration cytology within the scope of triple diagnosis of palpable breast changes

The diagnostic value of aspiration cytology and the overall diagnostic quality of the so-called triple test (aspiration cytology, mammography and physical examination) in the evaluation of palpable breast masses were investigated in a retrospective study. 608 histologically evaluated cancers and 224 benign lesions were investigated. A main purpose of the study was to find out whether the triple diagnostic test can replace surgical biopsy and thereby reduce the number of unnecessary biopsies. All lesions triple-diagnosed as malignant were histologically proved to be malignant, i.e. there were no false positive results. The rate of false negative results was found to be within the range reported for false negative results in fresh frozen sections. Based on these results we state that the dogmatic statement "every palpable mass in the breast must be excised" should be replaced by the recommendation "every palpable mass must be assessed and clarified". A great number of retrospectively unnecessary biopsies can be avoided by a systematic use of the triple diagnosis. The diagnostic safety of this method is close to that of open biopsy. In all cases where positive or negative concordant triplets are found, histological confirmation by biopsy can be avoided. Patients with benign lesions can be thoroughly followed up by repeated physical and radiological examinations. Patients with triple diagnostic malignant results can be adequately treated. Lesions for which triple diagnosis yields neither benign nor malignant, must be biopsied: This is also necessary in all cases with suspicious findings in mammography without a palpable mass, if the equipment for stereotactic or ultrasound- guided biopsies is not available.(ABSTRACT TRUNCATED AT 250 WORDS)