Manfred Blum

Adrenal insufficiency as a complication of the acquired immunodeficiency syndrome.

Excerpt Since the acquired immunodeficiency syndrome was recognized in 1980, various malignancies, infections, and immunologic defects have been found in the affected population. Recently, adrenal ...

The autonomous nodule of the thyroid: correlation of patient age, nodule size and functional status

In light of new techniques for measuring circulating thyroid hormones and for studying the thyroid gland, we present our experience with 35 patients with solitary autonomous nodules of the thyroid to define more precisely the clinical course of patients with this disorder. The patients ranged in age from 19 to 80 years and 31 of the 35 were female. Younger patients were generally euthyroid and sought attention because of a thyroid mass; virtually all older patients were hyperthyroid. Eighteen had obvious clinical features of hyperthyroidism and 5 over age 70 had apathetic hyperthyroidism; all 5 of the elderly and 13 of the 18 under age 70 had elevated thyroxine (T4) and triiodothyronine (T3) levels. Isolated elevation of T3 and elevated basal metabolic rate were observed in 5 previously untreated clinically hyperthyroid young patients. In each of these, thyroid uptake of 131I was not suppressible with exogenous T3 and BMR was elevated in those tested. Two elderly patients, who had previously been treated for conventional hyperthyroidism with radioactive iodine, had T3 toxicosis when hyperthyroidism recurred. There was a strong positive correlation between the age of the patient, the size of the nodule and the thyroid functional state. The mean area of the nodules projected on 131I rectilinear scan for euthyroid patients was 5.1 cm2. The mean area of the nodules in hyperthyroid subjects was significantly higher, 13.4 cm2 in patients with T3 toxicosis and 19.3 cm2 in subjects with conventional hyperthyroidism. Progression from a euthyroid state to hyperthyroidism was observed in four patients. One of these became thyrotoxic within days after an injection of iodinated contrast medium. Spontaneous resolution of nodules occurred in two patients.

Hyperthyroidism after iodinated contrast medium.

INORGANIC iodine administration can precipitate hyperthyroidism in susceptible patients.1 , 2 The patient with an autonomous nodule of the thyroid described below appeared clinically euthyroid desp...

Carcinoma of the thyroglossal duct

Abstract Seven patients with carcinoma in a thyroglossal duct cyst have received treatment over a 15 year period. Findings in all of these patients reflect the likelihood of carcinoma arising within thyroglossal duct tissue. In each patient there was sufficient histologic evidence of the presence of a thyroglossal duct cyst and carcinoma arising within an intimate admixture of normal thyroid tissue in the cyst wall. In the absence of a history of irradiation and with separation of the carcinoma from the pyramidal lobe of the thyroid, excision of the thyroglossal cyst alone by traditional means seems appropriate. Our experience as well as a review of reported cases to date indicate that distant metastases are extremely rare and the prognosis excellent.

I-131 SPECT/CT Elucidates Cryptic Findings on Planar Whole-Body Scans and Can Reduce Needless Therapy with I-131 in Post-Thyroidectomy Thyroid Cancer Patients

BACKGROUND Interpreting I-131 whole-body scans (WBSs) after thyroidectomy for thyroid cancer is not simple. There are scans in which interpretation is speculative because of cryptic findings (CF). Complexity is added in scans that are done a week after an ablative or therapeutic dose of I-131 because not only is I-131-labeled thyroxine (T4) distributed throughout the body, but inorganic I-131 that is derived from the de-iodination of T4 may be also detected. We present our observations regarding the analysis of CF on WBS using I-131 single-photon emission computed tomography (SPECT) in fusion with noncontrast computed tomography (CT), referred to here and elsewhere as I-131 SPECT/CT. METHODS Forty of 184 WBSs in 38 thyroidectomized thyroid cancer patients were followed up with I-131 SPECT/CTs. The SPECT/CT images were acquired after a tracer dose of I-131 (n=82) or a week after an ablative or therapeutic dose of I-131 (n=102). RESULTS Among 184 WBSs, 40 (22%) had CF. In 35 patients the WBS was negative for metastatic disease except for the CF and 5 patients had evidence of thyroid cancer in addition to the CF. There were 49 CF in the planar scans that were localized by SPECT/CT. These were characterized as physiological uptake in gingiva, thymus, gall bladder, menstrual blood, uterine fibroid, recto-sigmoid, colon, and bladder. Also observed was uptake in sites that represented nonthyroidal pathology including dental abscess, hiatal hernia, renal cyst, and struma ovarii. SPECT/CT suggested that 10 of the CF were actually of thyroid origin. In 40 SPECT/CT scans, the images contributed to interpreting the scan. In 15 of 40 patients the SPECT/CT analysis of WBS was performed with tracer doses of I-131 and was important for determining whether to administer ablative I-131 treatment. In another 25 patients, in whom SPECT/CT was performed after ablative or therapeutic doses of 131-I, information regarding the characterization of CF by SPECT/CT was useful in determining if thyroid cancer metastases or thyroid remnants were present. CONCLUSIONS I-131 SPECT/CT is a useful tool to characterize atypical or CF on WBS by differentiating thyroid remnant or cancer from physiologic activity or nonthyroid pathology. In the past, uptake on a WBS that was not explicable as physiologic activity was identified as putative or possible thyroid cancer and generally was treated with I-131. Now, by identifying activity in some possible cancer sites as not thyroid cancer, SPECT/CT can reduce inappropriate treatment with I-131. SPECT/CT of WBS performed after ablative doses of 131-I is useful in determining the nature of CF and therefore likely providing prognostic information.

HYPERTRIIODOTHYRONINÆMIA AS A PREMONITORY MANIFESTATION OF THYROTOXICOSIS

Abstract Triiodothyronine (T 3 ) levels were raised in four patients from 5 weeks to 9 months before the development of overt hyperthyroidism and before raised serum-thyroxine (T 4 ) levels were found. These observations suggest that hyperthyroid patients may pass through a stage of T 3 toxicosis before developing the usual form of thyrotoxicosis, and that serum-T 3 measurements may be helpful in the early diagnosis of the disease.

A Spectrum of Diseases of the Thyroid Gland as Imaged by Gray Scale Water Bath Sonography

A method of performing gray scale thyroid echography with a 3.5 MHz focused transducer and an open water bath is described. A preliminary echographic classification of abnormalities and representative echograms illustrating various thyroid disorders are presented.

Managing the Solitary Thyroid Nodule: Role of Needle Biopsy

Excerpt Thyroid malignancies are rare, whereas benign nodular disease is common and does not require surgical management unless there is obstruction of the thoracic inlet. The problem is to identif...

Why Do Clinicians Continue to Debate the Use of Levothyroxine in the Diagnosis and Management of Thyroid Nodules

Why do clinicians still debate whether thyroid nodule volume decreases in response to therapy with levothyroxine, given that many types of nodules do not get smaller and that the therapy could have adverse effects [1]? The reasons include the enormous number of patients with enlarged thyroids, the myriad clinical variations of the condition, insecurity about clinical findings, exceptions to current diagnostic guidelines that identify malignancy, and questions about the long-term management of benign nodules or the contralateral lobe after surgery. Suppressive therapy, in which thyroid hormone is administered to reduce the concentration of thyroid-stimulating hormone (TSH) to a level below normal (as opposed to replacement levothyroxine therapy, which normalizes the TSH level), had been used for years in the nonsurgical management of nodular thyroid disease [2-4]. However, this treatment is no longer popular: Recent studies failed to show efficacy [5, 6]; other studies showed an increased risk for osteoporosis as a consequence of thyrotoxicosis [7-9]; and fine-needle aspiration biopsy can better ascertain malignancy than can a therapeutic trial [10]. Although many patients do not need suppressive therapy, there are four main concerns about how the lack of suppressive therapy for cytologically benign disease may affect thyroid lesions or the patients prognosis: First, in the past the clinician was alerted that a nodule might be malignant if it grew during treatment with levothyroxine. Enlargement of an untreated nodule is less informative. Second, because sampling errors from fine-needle aspiration biopsy may occur and negative or inconclusive cytologic findings do not exclude malignancy, it is uncomfortably open-ended to not treat patients who have negative cytologic findings and some clinical concern about malignancy but not enough data to warrant surgery. Third, previously, the emergence of a nodule in a goiter during therapy with levothyroxine attracted attention to the possibility of neoplasm. Obtaining a biopsy of all dominant nodules in a goiter has been suggested, but a cancer could be in the nodule next to the one that was sampled. This Herculean task might be made more difficult without levothyroxine. Fourth, it is unknown which, if any, nonsuppressed nodules or lobes remaining after partial thyroidectomy for benign nodular disease will grow and cause obstruction of the thoracic inlet. I recall that 30 years ago, before suppressive therapy was common, there were relatively more patients than we see now with large, obstructive nodules and distorted, hypertrophied contralateral postoperative lobes that posed diagnostic and management problems. New reports suggest a tendency [11] or show [12] that levothyroxine can reduce the volume of some nodules. In this issue, La Rosa and colleagues [13] describe patients who had solitary cold thyroid nodules that were benign on fine-needle aspiration biopsy. As ascertained by an ultrasonographer who was blinded to treatment, nodule size decreased in 9 of 23 patients who received levothyroxine for 1 year without producing thyrotoxicosis, in 5 of 25 patients who received low-dose intermittent potassium iodine, and in none of 22 patients who received no treatment. During the 1-year study, nodules resumed growth when patients no longer received therapy, and untreated control nodules continued to grow. Unfortunately, the trial was not completely double-blinded, and the numbers, although significant, are small. Opposing, strong opinions held by well-informed people about medical matters are usually accompanied by a lack of critical data, few participants in otherwise well-designed studies, or a lack of appropriate controls. Assuming that some euthyroid nodules get smaller and that further growth of some nodules is arrested with suppressive therapy and perhaps after treatment with iodide, we need to explore several questions. 1) Are all palpable nodules similar? No. Only some palpable nodules are truly solitary masses in an otherwise normal gland. More than 90% of these are benign and belong to a pathologically heterogeneous group of disorders that includes nodular thyroid, colloid nodules, adenomas, thyroiditis, and simple cysts. Even the thyroid follicular cells are heterogeneous [14]. In many cases, a clinically palpable nodule is actually a dominant nodule in a sea of smaller nonpalpable nodules, which is called a nodular goiter. Most dominant nodules in a goiter are not separate lesions but rather are benign and part of the goiter; only a few are malignant. The likelihood of detecting a response to levothyroxine or iodide in any small study group depends on the chance mix of pathologic findings in the series and other variables. 2) Is TSH the only thyroid growth factor? No. Other growth factors include immunoglobulins, systemic and paracrine growth factors [15], and mutations in the TSH receptor [16]. 3) How do these factors affect a therapeutic trial? Nodules that have grown in response to excessive stimulation by TSH or iodine deficiency usually get smaller when TSH is suppressed or when the mineral is replenished. In contrast, autonomous nodules will not respond to suppression of TSH. Furthermore, the size of tissue that has enlarged in response to an abnormal immunologic or other growth factor will not be reduced. Finally, normal thyroid tissue is partially free of TSH control. One study showed low-level secretion of thyroid hormone that does not depend on TSH [17]; growth could also be independent of TSH. A therapeutic trial with thyroid hormone is the only way to determine whether suppression of TSH will arrest thyroid growth. 4) Does a decrease in nodule size when TSH is suppressed exclude malignancy? No. Atrophy of surrounding normal thyroid gland or reabsorption of fluid may deceive palpation, and although a few thyroid malignancies are said to respond, most do not. 5) How is reduction in size defined? We need to agree on criteria. Reduction in the size of the solid portion by 50% has been suggested. Documentation of change in size based on objective measurements such as sonography is essential [11, 18]. 6) How safe is levothyroxine? When administered in quantities sufficient to produce thyrotoxicosis, it increases risk for adverse cardiovascular effects and osteoporosis but not for bone fracture [9]. It seems prudent to avoid iatrogenic thyrotoxicosis for benign disorders. 7) How is suppressive therapy defined? A reliable third-generation assay is essential for measuring the necessary low levels of TSH. Is reducing TSH into the low-to-normal range adequate for benign disease, or must TSH be below normal? The answer is unclear. However, there seems to be no advantage to suppressing TSH below 0.1 mU/L [19] or 0.4 mU/L [20]. 8) Is iodide therapy effective? The efficacy of iodide in arresting the growth of thyroid nodules when the patients diet contains enough or too much iodide needs to be investigated further. 9) How safe is iodide? It is unsafe in pregnancy. Hypothyroidism may result when the Graves-Hashimoto diathesis is present. Thyrotoxicosis may develop with an autonomous nodule or toxic nodular goiter and poses a risk for elderly patients or those with heart disease. Supplemental iodide is essential when dietary iodine is deficient, but it may temporarily precipitate thyrotoxicosis. We must refine the answers to these questions and enhance our efforts to ascertain biochemical, cytologic, or receptor-related criteria that identify the types of thyroid tissue that are likely to enlarge if untreated but that will respond to suppression. Morita and colleagues [12] showed one such marker. Thyroglobulin levels decreased in 18 of 49 patients with cold benign nodules that responded to levothyroxine but not in the other patients whose TSH was equally suppressed. Fortunately, most nodules are benign; even the malignant ones grow slowly and rarely cause death. But some nodules do cause a problem, and a few result in death. Whether the patient has a cytologically benign solitary nodule, a nodule in a subclinical or clinical goiter, or a lobe that remains after surgery, there is a small possibility that a neoplasm will develop or that the tissue may have the propensity to grow and result in obstruction of the thoracic inlet. Life-long observation is necessary. The clinical data must be interpreted with mature judgment and an understanding of the disease process, a specific persons needs, and available resources. In many cases, suppressive therapy is not needed; in others, the patients medical condition or advanced age precludes this treatment; in still others, treatment with levothyroxine that avoids thyrotoxicosis seems a reasonable choice. The debate about suppressive therapy continues because the answers are important and clinically relevant but not yet complete.

Recurrent Hyperthyroidism Presenting as Triiodothyronine Toxicosis

Abstract Ten cases of triiodothyronine (T3) toxicosis have been identified in patients with prior histories of hyperthyroidism. In each case the recurrence came after a euthyroid interval of from 4...