Does Graves' disease or thyrotoxicosis affect the prognosis of thyroid cancer.

Twenty-one patients who underwent surgical treatment for thyrotoxicosis and who were found at operation to have thyroid cancer are presented. Sixteen had Graves' disease and 5 had toxic nodular goiter. The group with Graves' is compared with 110 euthyroid patients with thyroid cancer who underwent their initial surgery in the same time period and who were of the same age (+/- 1 yr) and sex as the patients with Graves' disease. None of the thyrotoxic patients died during follow-up of 2-24 yr or developed subsequent metastases. The 1 patient with a local lymph node metastasis has not shown evidence of recurrence. Hypoparathyroidism appeared as a complication in only 1 patient. The size of tumors in the patients with Graves' disease was significantly smaller than in the euthyroid group. The course of the disease in both the patients with Graves' disease and the thyrotoxic group as a whole was relatively benign. This series does not support the recent suggestions that thyroid cancer in patients with Graves' disease is more aggressive than in either patients with toxic nodular goiter or euthyroid subjects. Patients with Graves' disease and thyroid cancer should be treated identically to other patients with thyroid cancer. Therapy should consist of total thyroidectomy followed by a postoperative 131I scan. Residual tissue or metastases found on the scan should be ablated with 6 GBq 131I. The patient should receive a suppressive dose of T4.

A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma.

We measured lumbar spine, femoral neck, and forearm bone mineral (BMD) in 24 women (14 premenopausal and 10 postmenopausal) who had been treated with total thyroidectomy and 131 Iodine ablation therapy for nonanaplastic thyroid carcinoma and 24 case controls. At the time of the study, all patients were free of cancer (negative 131 Iodine whole body scan and serum thyroglobulin levels less than 0.3 micrograms/L) and all were receiving doses of T4 sufficiently high to prevent a rise in a serum thyroid-stimulating hormone concentration after an iv bolus of TRH. Femoral neck BMD were significantly reduced in both the premenopausal women (89 +/- 3.8% of case controls, 95% CI, 81 to 98) and postmenopausal women (77 +/- 3.9% of case controls; 95% CI, 68 to 86) receiving T4. Lumbar spine BMD and forearm BMD were unaffected in the premenopausal women, but significantly reduced in the postmenopausal women receiving T4 (lumbar spine BMD = 84 +/- 6.2% of case controls; 95% CI, 70 to 98 and forearm BMD = 89 +/- 5.6% of case controls; 95% CI, 76 to 101). Serum bone Gla-protein, a marker of bone turnover, was significantly increased in both the premenopausal and the postmenopausal women receiving T4 compared to case controls (P less than 0.001 for the difference between patient groups and controls). Whereas the cumulative dose of T4 was highly correlated with the femoral neck BMD in the premenopausal patients (r = 0.528; P less than 0.05); the presence of hypogonadism was the main determinant of the lumbar spine and forearm BMD. This data confirms that premenopausal and postmenopausal women receiving suppressive doses of T4 for thyroid carcinoma have diminished bone mineral measurements and are at risk for osteoporosis.

The effect of o,p'-DDD on adrenal steroid replacement therapy requirements.

Two patients with adrenal carcinoma treated with 2,2-bis (2-chlorophenyl-4-chlorophenyl)-1,1-dichloroethane (o,p'-DDD) as adjuvant therapy were studied. Both patients developed hypoadrenalism while on o,p'-DDD and apparently adequate dexamethasone replacement therapy. The hypoadrenalism was overcome by increasing steroid replacement therapy. Dexamethasone levels were measured in the serum by radioimmunoassay and shown to be lowered by o,p'-DDD therapy. A study of the absorption and disappearance of dexamethasone from the circulation in response to a (1 mg oral dose indicated that the steroid was absorbed normally but was cleared more rapidly from the circulation of these two patients than from normal controls. This may be due to a change in the type of metabolites excreted. It is suggested that many of the reported side-effects of o,p'-DDD may be due to hypoadrenalism and may be controlled by greatly increasing the steroid replacement dose. The adequacy of corticosteroid replacement therapy may best be assessed by monitoring the levels of ACTH.

The assay for thyroid stimulating immunoglobulins using cultured human thyroid cells.

Recent reports have shown that thyroid-stimulating immunoglobulins (TSI) may be detected by measuring cyclic AMP increases in cultures of isolated thyroid cells in response to added patient immunoglobulins (Ig). We have compared the frequency that TSI may be detected in the Ig fraction of 114 sera from 112 patients with a variety of thyroid disorders, to the presence of thyrotrophin binding inhibitor Ig (TBII). Whereas the sera of 46 out of 48 (95.6%) patients with untreated thyrotoxic Graves' disease had detectable TSI, only 26 out of 48 (54.2%) had detectable TBII. We did not find any significant correlation between TSI and TBII for these patients but there was a significant correlation between TSI and both serum T3 (r = +0.55, P less than 0.01) and T4 (r = +0.50, P less than 0.01). Twelve patients were studied at the time of relapse of thyrotoxicosis due to Graves' disease. All sera contained detectable TSI whereas only one contained detectable TBII. Of the sera from 20 patients in remission after antithyroid drug therapy three were positive for TSI. One of these samples as well as two others had detectable TBII. The two samples with TBII in the absence of TSI came from patients who had developed hypothyroidism. TSI were detected in the serum of one out of nine patients with Hashimoto's thyroiditis but not in the sera of 20 other patients with a variety of non-autoimmune thyroid disorders including five patients with thyrotoxicosis not due to Graves' disease. However TSI was found in the sera of three out of five patients with exophthalmos and no history of hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac function in acute hypothyroidism.

It has been established that chronic hypothyroidism may affect cardiac function by several mechanisms. It is not known how long the patient has to be hypothyroid for cardiac involvement to develop. This study was undertaken to assess the effect of a short period of hypothyroidism (10 days) on cardiac function. Nine patients who had had total thyroidectomy, had received ablative radioiodine for thyroid cancer and were euthyroid on replacement therapy were studied while both euthyroid and hypothyroid. Cardiac assessment was performed by X-ray, ECG, echocardiography and gated blood-pool scans. After 10 days of hypothyroidism, the left-ventricular ejection fraction failed to rise after exercise in 4 of the 9 patients studied, which was significant (P less than 0.002). No significant changes in cardiac size or function at rest were detected. This functional abnormality in the absence of any demonstrable change in cardiac size and the absence of pericardial effusion with normal basal function suggest that short periods of hypothyroidism may reduce cardiac reserve, mostly because of alterations in metabolic function.

Two cases of lymphoma of the parotid gland following ablative radioiodine therapy for thyroid carcinoma.

Two adult patients are described in whom 131I therapy thyroid carcinoma was followed by the development of non-Hodgkin's lymphoma in salivary glands. Histologically one was lymphocytic and the other histiocytic. The total doses of 131I given were 27 GBq (675 mCi) and 14GBq (350 mCi), lymphoma presenting 10 and 3 years respectively after the initial therapeutic dose of 131I. We suggest that the relationship is a causal one, because of the rarity of salivary gland lymphoma and the high dose or radiation to the salivary glands with this mode of therapy.

A comparative study of 99mTc and 131I in thyroid scanning.

Thyroid scans performed with both 99mTc pertechnetate (99mTcO4) and (131I) were compared in 46 patients with palpable thyroid nodules to determine whether 131I scanning is any longer a necessary procedure. A discrepancy between the two types of scan existed in only three cases, in one of which the thyroid nodule showed uptake of 99mTcO4 but not of 131I. Subsequent surgery revealed a thyroid malignancy in this patient. In each of the other two discrepancies a nodule "cold" on 99mTcO4 scanning was apparently functioning on 131I scanning, and was found to be benign at surgery. As the convenience and lower radiation absorbed dose of 99mTcO4 patients compared with 131I make it a better scanning agent, it is recommended that 99mTcO4 scans of the thyroid be first nodules. If these nodules prove to be functioning equally with paranodular tissue, a 131I scan should also be performed to help exclude a possible thyroid malignancy.

Thyroid stimulating immunoglobulin in Graves' disease.

There is excellent presumptive evidence that an IgG plays an aetiological role in the development of hyperthyroidism in Graves' disease but available methods for detecting thyroid stimulating immunoglobulins (TSI) are still far from satisfactory. They show considerable variation in specificity, sensitivity and precision, and comparison of the experimental data, obtained with these various methods, is difficult. A need exists for an in vitro TSI assay which is based upon the propensity of IgG molecules to stimulate the thyroid gland. Because a complex chain of biochemical events is involved, including binding to IgG to the cell membrane receptor, release of cyclic AMP, organification of iodide, hydrolysis of iodoproteins and secretion of thyroid hormones, it is not yet clear which step should be monitored to obtain the best index of thyroid stimulating activity. Although TSI and related assays appear to be of limited value in the primary diagnosis of Graves' disease, they offer some assistance to the clinician in the following situations: 1. Prediction of relapse in Graves' disease patients who have been rendered euthyroid with antithyroid drugs. 2. Identification of patients with ophthalmic Graves' disease. 3. Prediction of neonatal hyperthyroidism in thyrotoxic pregnancies.

Small cell carcinoma of the lung: primary site and hepatic metastases both detected on Tc-99m-pyrophosphate bone scan.

A case of small cell anaplastic carcinoma of the lung with hepatic secondaries has been found to accumulate Tc-99m-pyrophosphate in both lung primary and hepatic metastases and to our knowledge is the first such case reported in the literature. There was no radiographic evidence of calcification in the tumor or hepatic metastases.

Transient metastatic calcification in primary hyperparathyroidism.

Metastatic calcification has been visualised on bone scan in many hypercalcaemic states. This report illustrates the phenomenon occurring in a patient with primary hyperparathyroidism and its subsequent disappearance after therapy.

High ectopic kidney presenting as an abnormal liver-lung scan: case report.

An unusual cause for a positive liver-lung scan is presented. A cold area between the base of the right lung and the liver in a 78-year-old woman was reported as being due to a subphrenic abscess. This defect was subsequently found to be a right subphrenic kidney.