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.
Semiquantitative criteria for fine-needle biopsy diagnosis: reduced false-negative diagnoses.
Adequate sampling is important to minimize the risk of false-negative fine-needle biopsy (FNB) diagnoses. This article reports a prospective study of the following criteria for adequacy of sampling for FNB benign diagnoses: at least six aspirates, at least two of which each contain at least six clusters of benign cells. Of 888 patients studied with FNB, 60 had FNB diagnoses of malignancy; 58 were surgically confirmed, and there was one false positive. Seven of eight nodules with diagnoses of suspected malignancy were excised; three were malignant. Fifty-seven nodules had diagnoses of cellular or Hurthle-cell adenomas; 35 were excised, and four were malignant. All 33 nodules excised after benign diagnoses (including Hashimoto's thyroiditis) were benign. Five of 23 FNBs with small numbers of benign cells were malignant, but false-negative FNB diagnoses were avoided because of adherence to the proposed criteria for adequacy of sampling.
Is expertise in cytology diagnosis on thyroid nodules transferable?
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Needle aspiration for thyroid nodules. Skip ultrasound--do initial assessment in the office.
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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.
The autonomously functioning thyroid nodule: Goetsch's disease.
The AFTN was established as a clinical entity by the 1918 report of Goetsch, correlating cellular mitochondrial content with nodular function, and showing the inverse correlation between AFTN function and extranodular tissue function. Degeneration, common in AFTNs, can preclude development of hyperthyroidism, eliminate hyperthyroidism, or even induce transient spontaneously resolving hyperthyroidism. AFTNs are nearly always benign. Most reports of malignant AFTNs are inadequately documented. Whether AFTNs are toxic can be determined by clinical evaluation, with laboratory confirmation using principally serum T3 assays and TRH testing. Whether warm nodules are AFTNs may be determined by suppression imaging. Nontoxic AFTNs are usually observed. For older patients with borderline high serum T3 levels, blunted responses to TRH, or subnormal responses on supersensitive TSH assays, prophylactic therapy may be prudent. Toxic AFTNs may be treated surgically (patients younger than 40) or with radioactive iodine (older patients). High dose radioactive iodine therapy is preferred because it more consistently ablates AFTN function.
Consistency of sequential needle biopsy findings for thyroid nodules. Management implications.
Needle biopsy can reduce unnecessary surgery for thyroid nodules. However, needle biopsy diagnoses of "benign" may be erroneous. Thyroxine may produce regression in such nodules, but usually does not. Some authorities advise surgery for nonresponding nodules; others rely on repeat needle biopsy. In 246 patients, diagnoses by repeat needle biopsy confirmed 85% of the original diagnoses by needle biopsy. Initial benign diagnoses by needle biopsy were confirmed for 187 (91%) of 205 patients. Fourteen had surgery; all nodules were benign. Changes in diagnosis from benign to suspicious by needle biopsy were made for 12 patients; five had surgery, one had a Hürthle cell carcinoma. Changes in diagnosis from benign to malignant by needle biopsy were made in six patients; five had surgery, all lesions were malignant. Reliance on repeat needle biopsy is preferable to routine surgery for nodules not responding to thyroxine.
Factitious elevation of thyrotropin in euthyroid patients, continued.
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The various presentations of thyroiditis. Diagnostic considerations.
The syndromes of thyroiditis include five disorders. Hashimoto's thyroiditis, the commonest, is an autoimmune disease whose principal manifestations are goiter and hypothyroidism. Subacute granulomatous thyroiditis is probably viral in origin and usually presents with a tender goiter. Subacute lymphocytic thyroiditis is of unknown pathogenesis, but the postpartum form may be autoimmune. Its principal manifestations are goiter and spontaneously reversible hyperthyroidism. Acute suppurative thyroiditis results from bacterial or fungal infection causing abscess. Riedel's struma, a disease of unknown cause, presents with a goiter and thoracic inlet obstruction. Thyroiditis may require differentiation from other diseases. The goiter may resemble that of Graves' disease or thyroid lymphoma. Thyroid nodules may resemble neoplasms. Hyperthyroidism may suggest Graves' disease or other hyperthyroid syndromes with low radioactive iodine uptake. Neck pain can also occur with some thyroid malignancies. Local abscess is usually infectious but may be undifferentiated thyroid carcinoma. Finally, hypothyroidism may be transient or permanent.
Fine needle biopsy of thyroid nodules: avoiding the pitfalls.
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