Palpable Thyroid Nodules Research Articles

Aspiration needle biopsy refines preoperative diagnosis of thyroid nodules defined at fine needle aspiration as microfollicular nodule

The aim of this paper was to verify the hypothesis that large needle biopsy performed preoperatively can refine preoperative fine needle aspiration (FNA) cytological diagnoses of microfollicular nodules. Since 1980 we have been using FNA and aspiration needle biopsy (ANB) (18 or 16 gauge needles) to select for surgery all euthyroid patients with palpable thyroid nodules referred to our department. From 1980 to 1994, 6,124 patients (12% male, 88% female) with thyroid nodules (71% single, 29% multiple) were examined by FNA; 29% of these patients were also examined preoperatively by ANB histology. Of all the nodule patients examined, 371 received a preoperative FNA diagnosis of microfollicular nodule. Two hundred and fifty-four of these nodules (68%) were also examined preoperatively by ANB. Unsatisfactory ANB specimens constituted 17% of cases; pure microfollicular structure was confirmed by ANB in 36% of the nodules; ANB showed the remaining 47% to contain a macrofollicular component, thus suggesting a benign hyperplastic lesion. Twelve nodules which were found to be microfollicular at FNA cytology and micro-macrofollicular at ANB were excised and were subsequently determined as benign at definitive postoperative histology. These data indicate the utility of ANB in refining the preoperative FNA diagnosis of microfollicular nodule and in preoperatively identifying benign hyperplastic mixed micro-macrofollicular lesions which can be followed by observation.

22 EARLY DETECTION OF MEDULLARY THYROID CARCINOMA (MTC) AND PREVENTIVE TOTAL THYROIDECTOMYI IN PREPUBERTAL AND PUBERTAL CASES

MTC should be screened in all children over 4y-old born from affected cases, since MTC may present as an inherited tumor. In our experience, a combined test injecting pentagastrin (Pg) 0.5 UI/Kg and calcium (Ca++) 2mg/Kg, with serum calcitonin (CT) measurements (0.2.5 and 10 min), has been proved to be a reliable screening test for occult MTC in children. In this study 12 prepubertal and pubertal individuals (M:4, F:8) were tested, they belonged to two sibs-hips with an affected pattern. Five of these cases showed CT hyperresponsiveness (>350 pg/ml) during Pg+Ca++ tests, all were females. At least two abnormal tests were detected in each case in order to establish the biochemical diagnosis of MTC and/or “C” cell hyperplasia, that preceeds the familial form of MTC. Three of the affected cases had no palpable thyroid nodules whereas it was palpable in two. Total thyroidectomy associated with preventive lymphnode resection was performed in all affected cases. Pathologycal findings confirmed the presence of MTC in all. After surgery, basal CT levels dropped to normal values and the exagerated response to Pg+Ca++ disappeared in the cases without palpable nodules. In those cases with palpable thyroid nodules, basal CT remained high despite a significant reduction after surgery, augmented CT responsiveness was also present in these latter cases. It is concluded that 1) In prepubertal and pubertal cases early detection of MTC usually leads to definitive cure after surgery. 2) cases with palpable thyroid nodules(late detection)due to MTC frequently do not achieve cure, as revealed by persistently high serum levels of the tumor marker CT.

Outcome of long standing solitary thyroid nodules.

We investigated the outcome of long standing palpable solitary thyroid nodules by surveying 441 patients and examining 140 patients who had untreated thyroid nodules for 15 +/- 4.5 years. In our clinical survey, the most common outcome was disappearance of the thyroid nodule (38.3%). Also a significant number of patients (36.3%) underwent surgery in other hospitals. Five (1.1%) patients died of thyroid cancer. When thyroid nodules were re-examined, most nodules indeed decreased in size or disappeared; however, 13% of nodules increased in size. Ultrasound of the nodules showed that most solitary nodules were multiple and partially cystic and solid. There was an increased incidence of calcification in long standing nodules. Thyroid cancer was found by fine needle aspiration biopsy in 26.3% of enlarging nodules and 6.4% of nodules without changing size. The risk of cancer decreased when the size of the nodule decreased. A total of 15 patients with suspicion of malignancy underwent surgery. Surgical procedures were lobectomy, near total thyroidectomy, or resection of nodules with or without modified neck dissection. Seven patients had papillary carcinoma and 2 patients with benign cytology had microscopically evident papillary carcinoma. In our study, the majority of palpable solitary thyroid nodules tended to decrease in size; these nodules do not require treatment. Enlarging solid nodules are a definite risk for thyroid cancer. If the size of the nodule remains the same, judicious approach with fine needle aspiration biopsy is needed.

Histologic changes in Graves' thyroid gland after 131I therapy for hyperthyroidism.

The effect of 131I therapy was examined in 13 thyroid glands affected by Graves' disease 3 to 29 years after irradiation for hyperthyroidism. All of the patients had clinically palpable thyroid nodules. Two patients were in a latent hypothyroid, 6 in a euthyroid and 5 in a hyperthyroid state. The microscopic changes in the thyroids showed a pattern of multiple adenomatous nodules with cystic changes, marked oxyphilic cell changes with nuclear atypism and various degrees of chronic thyroiditis. Immunohistochemical staining for TG and T4 was negative to mildly positive in these oxyphilic cells and entirely negative for EGF and CEA. The DNA ploidy pattern was diploid pattern in 6 cases. One papillary-type microcarcinoma occurred, but there was no evidence of a relationship between the tumor and the irradiation. The pathologic findings in Graves' thyroid gland after 131I therapy are not specific, but pathologists should differentiate this lesion from adenomatous goiter, which occurs with no apparent cause, or from thyroid carcinoma because of the marked nuclear atypism of this lesion.

Effect of nonthyroidal illness on serum thyroxine concentrations in cats: 494 cases (1988)

Summary We reviewed the medical records of 494 cats with a variety of nonthyroidal diseases in which serum thyroxine (T4) concentration was determined as part of diagnostic evaluation. The cats were grouped by category of disease (ie, renal disease, congestive heart failure, diabetes mellitus, focal neoplasia, systemic neoplasia, hepatopathy, inflammatory bowel disease, inflammatory pulmonary disease, miscellaneous diseases, or undiagnosed disease), degree of illness (ie, mild, moderate, or severe), survival (ie, lived, died, or euthanatized), and presence or absence of a palpable thyroid gland. The mean (± sd) serum T4 concentrations in all 10 groups of cats, which ranged from 10.5 ± 11.1 nmol/L in cats with diabetes mellitus to 18.7 ± 7.8 nmol/L in cats with focal neoplasia, were significantly (P < 0.001) lower than those of normal cats (27.0 ± 10.4 nmol/L). The number of ill cats with low serum T4 concentrations (<10 nmol/L) was highest in the cats with diabetes mellitus (59%), hepatopathy (54%), renal failure (48%), and systemic neoplasia (41%). When the serum T4 concentrations in cats with mild, moderate, and severe illness were compared, mean concentrations were progressively lower (21.3 ± 6.8, 14.8 ± 8.1, and 6.5 ± 5.8 nmol/L, respectively) as degree of illness increased. Severity of illness had a more significant (P < 0.001) effect in lowering serum T4 concentrations than did disease category. Mean serum T4 concentrations in the cats that died (7.8 ± 9.8 nmol/L) or were euthanatized (10.0 ± 7.0 nmol/L) were also significantly (P < 0.001) lower than those of cats that survived (15.2 ± 8.8 nmol/L). Of the 182 cats with low serum T4 concentrations, 74 (41%) died or were euthanatized. The 63 cats with palpable thyroid nodules had significantly (P < 0.001) higher mean serum T4 concentrations (21.7 ± 10.4 nmol/L) than the cats in which a thyroid nodule was not palpated (12.7 ± 8.1 nmol/L). Adenomatous hyperplasia of the thyroid gland was confirmed at necropsy in 2 cats with a palpable thyroid gland, and 4 cats that survived have subsequently developed overt hyperthyroidism. This suggests that, in some cats with early or mild hyperthyroidism, concomitant nonthyroidal disease may suppress serum T4 concentrations into the normal range.

Renal cell carcinoma metastatic to the thyroid.

Metastatic renal cell carcinoma to the thyroid is an uncommon occurrence that can cause clinical and pathologic problems in diagnosis. The authors report seven cases from the files of The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Each presented clinically as a palpable thyroid nodule months or years after the primary renal cell carcinoma had been resected. Although renal cell carcinoma is more common in men, we found a female predominance of 6:1 in this series. These lesions appear as solitary "cold" nodules on iodine 131 scans and may be misdiagnosed as primary thyroid neoplasms, especially if the renal primary is still unrecognized. A correct diagnosis is important because surgical management can be curative. The diagnosis is facilitated by the use of fat stains, electron microscopic study, and immunoperoxidase stains.

Fine-needle aspiration cytodiagnosis of the "cold" thyroid nodule.

The results of 1886 fine-needle cytoaspirations of solid, palpable thyroid nodules, "cold" on scintiscanning, performed between 1 January 1978 and 31 December 1986, were analyzed. In total 36 diagnoses of malignancy were made (1.9%). The results of cytologic and histologic examinations were compared in 114 cases to verify the diagnostic accuracy of this method; there was agreement in 98 cases and discordance in 16 consisting of 13 false negatives (11.4%) and 3 false positives (2.6%). The sensitivity was 77.9%, specificity 94.5%, positive predictive value 93.8%, negative predictive value 80% and test efficiency 86%. These values are in the range of those reported in the literature and confirm the validity of fine-needle aspiration cytology in the preoperative diagnosis of thyroid neoplasms.

Management of the thyroid nodule.

The approach to the patient with a palpable solitary thyroid nodule remains controversial. In the rare patient with signs and symptoms suggestive of malignancy, the course of action is reasonably established. However, the patient with an asymptomatic solitary thyroid nodule presents a dilemma. The therapeutic alternatives range from suppressive medical therapy with serial examinations to surgical excision; therefore, to obviate unnecessary surgery, several diagnostic techniques and approaches have evolved which attempt to predict the presence of malignancy. A multitude of articles reflects the widespread disagreement among physicians regarding these diagnostic approaches. Thus, many questions still remain as to the proper management of patients with solitary nodules. The issue is further confounded by problems in assimilating and practically applying the results of the various studies, which often differ in their results. In this report, data regarding the prevalence of the solitary thyroid nodule are reviewed, and the clinical significance of the solitary thyroid nodule is discussed. The problem of management is examined in terms of the various diagnostic approaches to the solitary thyroid nodule: history and physical examination, laboratory tests, ultrasonography, thyroid suppressive therapy, scanning techniques, and fine-needle aspiration. The efficacy of each technique is critically evaluated with an emphasis upon the ability to distinguish benign from malignant disease. The overall aim of this report is to establish a reasonable diagnostic approach to the asymptomatic patient with the solitary palpable thyroid nodule, based upon a critical review of the literature.

Morphologic changes in the thyroid after irradiation for Hodgkin's and non-Hodgkin's lymphoma.

Four cases of thyroidectomy for suspected thyroid carcinoma after previous irradiation for Hodgkin's or non-Hodgkin's lymphoma are reviewed. The patients ranged in age from 18 to 33 years at the time of thyroid surgery with an average latency period of 12 years (range, 8-20 years) from radiation therapy to thyroidectomy. All patients had a clinically palpable thyroid nodule, and pathologically showed a pattern of multiple adenomatous nodules with cytologic atypia. The microscopic changes were sufficiently striking to cause the primary pathologist to request consultation to rule out thyroid carcinoma in each case. Fine-needle aspiration was performed in one case and suggested a thyroid neoplasm. The pathologic findings are reviewed and distinction of this lesion from thyroid carcinoma is discussed.

Suppressive therapy of thyroid nodules in patients with previous radiotherapy to the head and neck

This is a prospective, randomized study of 431 patients with palpable thyroid nodules who had previous radiotherapy for benign disorders of the head and neck area to determine the response of the thyroid nodules to suppressive therapy and the incidence of thyroid cancer in patients who could not be suppressed and had surgery. A complete response was achieved within 6 months in 18.3 percent of the patients, and in an additional 26 percent of patients between 7 and 12 months postoperatively. Twenty percent of the patients showed complete disappearance of nodules after 1 to 2 years of suppressive therapy. Twenty-two percent who underwent surgery showed carcinoma. If suppressive therapy is to be used, a trial of 1 year rather than 3 or 6 months, as often recommended, may be appropriate.

Low TSH-response to TRH in a former endemic goiter area.

During 30 yr of iodine prophylaxis endemic goiter in school children had disappeared in the Savonlinna area which has been the location of continuous surveillance in the East of Finland. In adults goiter is still found to some extent especially in older people. The iodine intake has increased from about 50 to 300 micrograms per day during these yr and the thyroidal uptake of radioactive iodine has decreased from over 60% to between 20 and 30%. However, there is a significant difference in this regard between nongoitrous individuals and goiter patients. In the present study comprising only goiter patients it was found that the thyroidal uptake was significantly higher in the group of patients with a subnormal response to TRH. These patients also had larger goiters and more palpable thyroid nodules than those with a normal response to TRH. The mean age was significantly higher (60.3 yr) as compared to that in the group which had a TSH-response to TRH of greater than 20 mU/l, smaller glands and less thyroid nodules (45.1 yr). The data fit well with the reports on increasing autonomy with increasing age in nontoxic goiter.

A Comparative Study between Individuals Receiving Thymic Irradiation in Infancy and Their Nontreated Siblings: Clinical and Laboratory Thyroid Abnormalities

While impairment of thyroid function has been demonstrated for high-dose external radiation (e.g., for Hodgkin's disease), the long-term functional effects of low-dose external radiation have not been fully explored. One hundred fifty-three subjects with a past history of thymic irradiation during infancy were stratified into three dose levels and compared with 51 nonirradiated subjects from a sibling cohort with respect to previously undiagnosed clinical and laboratory thyroidal abnormalities. There was no apparent association between previous thymic irradiation and mean serum levels of T4, free T4, TSH, or antithyroid antibodies, nor was the prevalence of undetected hypothyroidism or hyperthyroidism significantly altered in the irradiated group. Serum thyroglobulin levels were elevated in subjects with palpable thyroid nodules, all of which occurred in thymic-irradiated subjects. Thus persons who have received low-level external thymic irradiation in infancy should continue to have periodic thyroid examinations, but routine serial measurement of other serum thyroidal parameters does not appear to be indicated.

Localization of abnormal parathyroid gland(s) using thallium-201/iodine-123 subtraction scintigraphy in patients with primary hyperparathyroidism.

Tl-201/I-123 subtraction scintigraphy was performed in 17 patients with clinical symptoms and biochemical measurements suggestive of primary hyperparathyroidism. Nineteen abnormal sites were identified. These results were correlated with PTH measurements and surgical findings. Three sites were considered unrelated to the parathyroid glands, two corresponding to palpable thyroid nodules and one to muscle uptake of unknown origin. One scintigram did not reveal either of two abnormal glands while two others were considered falsely positive in view of surgical failure. Fourteen sites corresponded to abnormal parathyroid gland at surgery; five glands, weighing more than 2000 mg, could be correctly located on the Tl-201 scintigraphy prior to the subtraction procedure; six glands, weighing between 500 and 2000 mg, were easily localized after the subtraction procedure; three glands, weighing between 180 and 200 mg, were correctly localized after further manipulation of the subtraction procedure. In a patient with parathyroid hyperplasia, one gland, weighing 150 mg, was not located and another was not found upon surgery. Overall sensitivity was 87.5%. A positive correlation between PTH levels, tumor weight, and ease of detection on scintigraphy was found. This correlation was particularly useful in excluding large abnormal uptake related to thyroid disorder or artifact. The results suggest that Tl-201/I-123 parathyroid scintigraphy could become an alternative to Tl-201/Tc-99m parathyroid scintigraphy, with possibly improved detection of low weight abnormal parathyroid glands.

機能性結節性甲状せんしゅの６例

Hyperfunctioning thyroid nodules are very rare in Japan. We treated six patients with hyperfunctioning thyroid nodule from 1981 to 1984. All patient were females aged 9 to 52 years. Each patient had a palpable thyroid nodule, and the scintigram showed a hot nodule without hyperthyroidism. Five patients underwent thyroid lobectomy and one thyroid lobectomy with removal of the regional lymph nodes. Pathologically, four nodules were follicular adenoma, one was adenomatous thyroid hyperplasia and one chronic thyroiditis. The resected specimen in the last case contained adenomatous thyroid hyperplasia and follicular adenocarcinoma.

Minocycline and Black Thyroid

THYROID pigmentation was discovered during surgical exploration for nodular thyroid in a patient who had been taking minocycline hydrochloride for six years. Total thyroidectomy was performed. Preoperative thyroid function studies had given results within normal limits. Report of a Case A 37-year-old woman was first seen in September 1980 for asymptomatic palpable thyroid nodule. Results of thyroid function studies—thyroxine level, triiodothyronine resin uptake, and thyroid-binding capacity—were within normal limits. Thyroid uptake scan demonstrated a right-lobe nodule of the same density as the surrounding thyroid. She was given levothyroxine sodium, 0.5 mg/day, with no subsequent change in the mass. The patient was admitted to the Baptist Medical Centers, Birmingham, Ala, in March 1981 for surgical resection. At surgery, the thyroid was noted to be uniformly black and to have a bosselated surface. A portion of the right thyroid was resected and submitted for frozen-section examination. The frozen section was interpreted as

876 MULTIPLE ENDOCRINE NEOPLASIA (MEN) TYPE III AND UROLOGIC ABNORMALITIES

The association of thyroid medullary carcinoma, pheochromocytoma, mucosal neuromas and characteristic physical features has been designated MEN III. A case is documented with previously unreported urologic abnormalities and incidental G6PD deficiency. An 11 year old girl presented with growth retardation, chronic diarrhea, enuresis, recurrent urinary tract infections, neurogenic bladder, hydroureters and hydronephrosis. She had a Marfan-like appearance, thickened eyelids and lips, tongue nodules,prominent corneal nerves, joint laxity and muscle wasting. Cervical adenopathy was present, but no palpable thyroid nodules, abdominal organomegaly or masses. Studies showed a “cold” nodule on thyroid scan, a suprarenal mass by ultrasound, multiple lytic lesions on skeletal survey and an extradural mass on myelogram. There was a markedly increased urinary VMA and plasma epinephrine, norepinephrine, CEA (380 ng/ml, normal<2.5) and calcitonin (154,500 pg/ml, normal 30-135). Biopsy of rib lesion showed infiltration by small round tumor cells filled with numerous membrane delimited secretory granules, consistent with a neural crest origin. Since the neurogenic bladder may reflect a disorder of autonomic innervation, its association with tumors of neuroectodermal origin suggests a common underlying defect of embryonal migratory neuroblastic elements.

Radiation-associated thyroid carcinoma.

Since February, 1977, 735 patients having a history of receiving radiation therapy for benign conditions of the head and neck areas during infancy and childhood were examined in a thyroid screening program, and 159 patients were found to have palpable thyroid nodules. These patients had thyroid function tests and indirect laryngoscopy and were followed closely on suppression therapy consisting of either Cytomel or thyroid extract. Thyroidectomy was advised in those in whom the nodules persisted or increased in size. This study documents the incidence of carcinoma and other benign pathological changes and postoperative complications in this group of patients. So far, 49 patients had either a lobectomy with isthmusectomy or a total thyroidectomy. Eleven patients were found to have carcinoma (six had papillary, four had mixed papillary and follicular, and one had follicular carcinoma). Three patients had a therapeutic modified neck dissection following the documentation of microscopic involvement of paratracheal lymph nodes. A high incidence of chronic nonspecific thyroiditis, postradiation fibrosis, and follicular adenomas were also found in these patients. Three patients had temporary hypocalcemia (two weeks) and none had wound infection, hematoma, or postoperative nerve palsy. Of patients who had surgical resection, 22.4% showed thyroid carcinoma.

Thyroid nodules--benign or malignant? 1. Diagnosis.

Radioisotope scanning is an invaluable aid in determining whether a palpable thyroid nodule is benign or malignant. In many cases, however, precise diagnosis is impossible without needle biopsy or surgical exploration.

Workshop on late effects of irradiation to the head and neck in infancy and childhood.

A summary statement for the Workshop on Late Effects of Irradiation to the Head and Neck in Infancy and Childhood is presented. The Workshop, conducted by the National Cancer Institute with the cooperation of several other organizations, was convened to determine the present status of knowledge about thyroid disease related to irradiation of the head and neck and to develop guidelines with respect to detection, diagnosis, treatment, and followup. It was decided that surgical exploration should be considered for all palpable thyroid nodules, particularly those that are firm and clearly demarcated and appear as a "cold" area on the scan. Persons at risk because of prior irradiation to the head or neck should have regular reexaminations every one to two years.

The single palpable thyroid nodule: evaluation by 99mTc-pertechnetate imaging.

The role of 99mTc-pertechnetate thyroid imaging in the preoperative assessment of patients with single palpable thyroid nodules was evaluated. The frequency of cancer in hypofunctional nodules was similar to that found in previous studies with 131I. The 99mTc-pertechnetate image allowed a reliable separation of pathologically uninodular thyroids from those that were multinodular, and demonstrated multiple thyroid lesions that had not been detected by physical examination in over one-third of the cases. The frequency of cancer in thyroids containing a solitary or dominant hypofunctional nodule was higher (17%) than that in thyroids with a multinodular scan appearance (less than 5%).