Biomedical subjects
J I Hamburger
Publications and source records attributed to J I Hamburger.
Thyroid nodules in pregnancy.
Thyroid nodules are common in pregnant women. Most of them are benign. Toxic autonomous nodules may be seen infrequently, and the diagnosis is supported by elevated free thyroid hormone levels and undetectable levels of TSH. The most common and most important problem is the diagnosis of thyroid cancer. FNB is the most reliable diagnostic tool. FNB findings also can be used to indicate the urgency for surgery and the appropriate extent of the operation when surgery is indicated. Best use of FNB data requires that the cytopathologist provide tissue diagnoses and that there has been enough experience to permit reasonable inferences of cancer probability for each diagnosis.
Diagnosis and management of Graves' disease in pregnancy.
Most of the hyperthyroidism seen in association with pregnancy is Graves' disease. The best treatment is prevention. For most patients there is an opportunity to treat the hyperthyroidism decisively with radioiodine or surgery before the patient becomes pregnant. Pregnancy complicated by hyperthyroidism is often a consequence of the conscious decision to treat hyperthyroidism in women in the childbearing years with antithyroid drugs. Propylthiouracil (PTU) is the preferred treatment for hyperthyroidism in pregnancy, but it does cross the placenta and can induce fetal goiter, with mental and physical retardation. Hence, the lowest possible PTU dose should be used. One should aim for high normal or slightly elevated thyroid function in the mother. Patients should be followed at 3-week intervals if progress is satisfactory, more often otherwise. Thyroid function should be monitored by the free T4 assay. PTU dosage should be reduced progressively in anticipation of the customary steady amelioration in the hyperthyroidism that occurs in later stages of pregnancy. Since pregnant hyperthyroid patients are sometimes irresponsible and continue PTU without supervision, PTU prescriptions should be limited to the amount required for the time until the next scheduled visit. For about one third of patients, PTU can be discontinued in the second half of the pregnancy. After the pregnancy is terminated, persistent or recurrent hyperthyroidism should be treated definitively to prevent another episode of pregnancy complicated by hyperthyroidism.
Clinical correlation is required to avoid erroneous thyroid image interpretations.
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Diagnosis of thyroid dysfunction in ambulatory patients: primacy of the supersensitive thyroid-stimulating hormone assay.
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Contribution of intraoperative pathology evaluation to surgical management of thyroid nodules.
With adequate experience, needle biopsy findings become as reliable or more so than frozen section diagnoses for surgical planning. Each institution must determine for itself the relative reliability of these two procedures before establishing management policies. Reduction or elimination of useless or redundant frozen section procedures reduces costs as well as anesthesia duration.
Hypothyroidism. Don't treat patients who don't have it.
An erroneous diagnosis of hypothyroidism causes unnecessary expense and inconvenience for patients, may result in needless and possibly unsafe treatment, and could delay the correct diagnosis. The erroneous diagnosis is often reversed by a second opinion, thereby causing loss of patient confidence and damage to pride and self-esteem in the initial physician. To avoid these problems, the physician should look for the cause of the hypothyroidism, which is easily and reliably established in about 95% of patients. In the rare instance that one is not evident, it may be prudent for the primary care physician to seek consultation before prescribing lifelong thyroid hormone replacement therapy.
Spontaneous degeneration of autonomously functioning thyroid nodules, potential therapeutic pitfall.
Spontaneous degeneration of an autonomously functioning thyroid nodule (AFTN) can convert the appearance of the lesion on imaging from that of a hot nodule to one that seems hypofunctional. If the patient first presents after degeneration has taken place, it may not be appreciated that whatever function persists is still autonomous. If thyroxine therapy is advised, the exogenous thyroxine will be additive to the residual autonomous secretion of the nodule, and may induce iatrogenic thyrotoxicosis. Two cases are presented, the first demonstrating the potential for the therapeutic misadventure, while the second is an actual example of this pitfall. Physicians must appreciate that any functioning component of a hypofunctional nodule may be the end result of degeneration of an AFTN. An inappropriately elevated serum T-4 (or free T-4) value during thyroxine therapy suggests the possibility. Suppression imaging will confirm the diagnosis.
Increasing the accuracy of fine-needle biopsy for thyroid nodules.
Fine-needle biopsy (FNB) is a valuable technique to use in the evaluation of thyroid nodules; however, false-negative and false-positive results do occur. At Sinai Hospital of Detroit (SHD) (Mich), a criterion was established for adequacy of an FNB specimen (ie, at least six clusters of benign cells on each of two slides prepared from separate aspirations) in an attempt to reduce the rate of false-negative diagnoses attributable to inadequate sampling. To evaluate the SHD criterion, 20 "problem" cases were selected from the SHD files and were reviewed by pathologists from three other institutions in a blind study. A total of 80 diagnoses were rendered (four institutions each reviewing 20 cases). Seven false-negative diagnoses were rendered, three of which were made in cases that did not meet the SHD criterion for adequacy. An additional three false-negative diagnoses on inadequate FNB specimens were made by a physician who asked not to be identified. Implementation of the SHD criterion may reduce the frequency of false-negative diagnoses. A separate study was undertaken to determine the number of FNB aspirations necessary to obtain satisfactory specimens. One hundred adequate FNB specimens from SHD files were reviewed. In 77% of cases the first two to four aspirations were adequate, but 23% of the time six to eight aspirations were necessary to obtain adequate material.
Fine needle biopsy diagnosis of thyroid nodules. Perspective.
Needle biopsy is the most cost-effective and reliable method for selecting thyroid nodules for observation or excision. Fine needle biopsy (FNB) is the preferred method because of safety and simplicity. FNB samples should be taken circumferentially at the periphery of the nodule to avoid the common central degeneration. The following criteria for adequate sampling reduce the potential for false negative diagnoses: e.g. a minimum of 6 aspirates, and at least 6 clusters of benign cells on each of at least 2 of the aspirates, and no malignant cells. A small rate of false positive errors is unavoidable if cancers are not to be overlooked. Study of published didactic and illustrative material permits trained and motivated cytopathologists to develop skills in FNB diagnosis quickly. FNB data may be accurate enough to supplant frozen section data for surgical planning. Patients with FNB diagnoses of benign should be followed, usually with thyroxine therapy. Nodules that do not regress after treatment for one year should be biopsied again, and observation may be safely continued if consistently benign findings are obtained. More reliable FNB diagnoses on cellular and Hurthle cell adenomas would be desirable, but it is unlikely that this will be possible in the near future.
Management of hyperthyroidism in children and adolescents.
Between 1961 and 1984, 262 patients with hyperthyroidism due to Graves' disease between the ages of 3 and 18 yr were treated in the author's clinic. This paper compares the results of different treatment methods. Initial treatment was surgery for 7 patients, radioiodine for 73, and an antithyroid drug for 182. Seven drug-treated patients subsequently had surgery. Of 14 surgically treated patients, 5 relapsed and received radioiodine, 5 became hypothyroid, 3 were lost to follow-up, and 1 remained euthyroid. Sixteen drug-treated patients were lost to follow-up; 7 are still taking drugs. Of the remaining 99 drug-treated patients not achieving remission, 92 received radioiodine, and 7 had surgery (1 later relapsed and received radioiodine). The principal reasons for abandoning drugs were toxicity, noncompliance, poor control, and failure to achieve sustained remissions. Of 61 drug-treated patients who achieved remission, 22 relapsed (21 were treated with radioiodine and 1 with drug). Remissions after antithyroid drug therapy persist in 39 patients, 2 of whom are now hypothyroid and 10 of whom have been in remission less than 2 yr. Of the 239 subjects whose treatment is complete, 191 (80%) ultimately had radioiodine. One radioiodine treatment eliminated hyperthyroidism in 163 patients, 2 treatments were effective in 17, and 3 treatments were effective in 1. The remaining 5 patients were lost to follow-up after radioiodine before the outcome of therapy could be determined. No increase in congenital abnormalities was found in 63 children of these patients, regardless of treatment. Radioiodine is a safe, simple, and economical therapy for patients with hyperthyroidism and is now considered the initial treatment of choice for such patients.
Diagnosis and management of large toxic multinodular goiters.
Toxic multinodular goiters, estimated weight 100 g or more, occurred in 35 patients between 1961 and 1984. All but two were older than 50; 32 were females. Twenty had goiters of 100-130 g; four of 140-200 g; and 11 were massive. Radioiodine uptakes were 30% or less for 22. Seven of 17 with both T4 and T3 data had T4 toxicosis. Thirty-two patients received radioiodine therapy, delivering 200 microCi per gram when possible. Doses were 25-30 mCi for 17 patients; 50-100 mCi for 12 patients, and 150-200 mCi for three patients. Hyperthyroidism was eliminated with one dose in 25 patients (78%); five patients required two doses. Twenty-two patients were euthyroid after radioiodine; 25 of 28 had persistent goiters. Two patients were treated successfully surgically. One refused surgery and radioiodine, and has been maintained on antithyroid drugs for 10 yr. Two patients died within a few months of an unsuccessful initial dose of radioiodine. Large dose radioiodine therapy is simple, safe, and effective for most patients with large toxic multinodular goiters.
Diagnosis of thyroid nodules. Use of fine-needle aspiration and needle biopsy.
The accuracy of diagnosis of 455 thyroid nodules evaluated by cytological and histological specimens obtained by fine- and large-needle biopsy, respectively, was compared with that for 1,094 nodules previously evaluated by clinical methods. The use of cytohistological data halved the number of patients with suspected cancer and doubled the number of patients to be observed. Cancers identified at operation for high and intermediate cancer-risk patients increased 75%, and operation for diagnosis of benign disease decreased 70%. Forty-two of 47 excised cancers were included in the cytohistological probable cancer group. Only 29 of these cancers were so classified clinically. Two cancers not diagnosed cytologically were suspected histologically and vice versa for one cancer. All 51 excised cytohistologically benign nodules were benign. There were more false-positive findings with cytological than with histological specimens.
Transient thyrotoxicosis associated with acute hemorrhagic infarction of autonomously functioning thyroid nodules.
Two patients with nontoxic autonomously functioning thyroid nodules had transient hyperthyroidism after acute hemorrhagic infarction. Previously solid "hot" nodules were converted to cystic "cold" nodules. Aspiration confirmed the hemorrhagic nature of the process. There was marked regression in nodule size, marked reduction of nodular autonomous secretory activity (indicated by a change from a blunted to a normal response to thyrotropin-releasing hormone), and spontaneous recovery of function in the previously suppressed extranodular thyroid tissue. Confusion of this entity with a nontoxic autonomously functioning thyroid nodule that has progressed to the toxic stage may be avoided if the loss of nodular function is noted on imaging. The possibility of granulomatous thyroiditis may be excluded by blood aspiration.
Pitfalls in the laboratory diagnosis of atypical hyperthyroidism.
When hyperthyroidism results from active thyroidal secretion, both serum hormonal levels and the radioactive iodine uptake (RAI) are elevated. Discordant results (increased serum hormone levels and a low RAI) are found either in the usual forms of hyperthyroidism when large quantities of iodide are ingested, or in atypical forms of hyperthyroidism, including spontaneously resolving hyperthyroidism of subacute thyroiditis, thyrotoxicosis factitia, toxic struma ovarii, and functioning metastatic thyroid cancer. Two patients are described who exemplify pitfalls in the interpretation of thyroid function test results in atypical hyperthyroidism. The following guidelines are helpful in avoiding these pitfalls: (1) An RAI should be performed in all thyrotoxic patients to confirm the presence of thyroidal hypersecretion, rather than atypical hyperthyroidism. (2) A positive response to thyroid-stimulating hormone stimulation is an important finding differentiating the other atypical forms of hyperthyroidism listed from subacute thyroiditis.
Hazard of high-dosage thyroid tablets.
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Letter: Intentional radioiodine ablation in Graves' disease.
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