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Thyroid goiter is a common condition that is often associated with iodine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic search on a single large Canadian family with 18 cases of nontoxic multinodular goiter in which 2 individuals also had papillary lesions highly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TSHR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid cancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric methods indicates that only a very small proportion of familial NMTC (point estimate 0.001, support intervals 0-.6 under a dominant model) is attributable to MNG1.

Of 226 consecutive papillary carcinoma patients, 14 indicated that at least one other relative was similarly affected. Pathology confirmation was obtained in 8 of the 14 families. Of the eight families with documented familial papillary carcinoma, one had five members, another had four members, and yet another had three members affected. The remaining families had two members affected. In those families with two or more persons with confirmed papillary carcinomas of the thyroid, 20 first- and second-degree relatives were examined. Of those, one had a previously unidentified papillary carcinoma and 6 had a benign thyroid disease (4 primary hypothyroidism and 2 simple goiters). High-resolution chromosome studies of four patients from four different families were normal, and there was no increase in chromosome breakage in a fifth patient from yet another family. Autosomal dominant inheritance is possible. Although there was no family history of lipomas, osteomas, or intestinal polyposis to suggest Gardner syndrome, four parents of our familial papillary carcinoma patients had colon cancer. In addition, three other relatives died of unidentified intra-abdominal cancer. The apparently high frequency of colon cancer and other abdominal cancer in relatives was an additional concern. Based on our observations, three clinical recommendations can be made: obtain a family history of all patients with papillary carcinoma of the thyroid, since between 3.5 to 6.2% will have another affected relative; when two or more persons in a family have papillary carcinoma of the thyroid, all first- and second-degree relatives should have a neck palpation by an experienced examiner; and families with two or more persons with papillary carcinoma should be observed for possible colon cancer.

Plasma catecholamines, as determined by a new improved method, are increased in hypothyroidism and decreased in hyperthyroidism. In addition, plasma catecholamine values are inversely correlated with total thyroxine values in hyperthyroidism. (/ Clin Endocrinol Metab 36: 587, 1973) T HERE IS disagreement in the literature concerning the effect of abnormal thyroid function on levels of the catecholamines and their metabolites in the blood and urine (1-5). Some unconfirmed studies have suggested the blood and urine levels might be increased in hyperthyroidism and decreased in hypothyroidism (3,6). In contrast, Kuschke et al. (5) reported that urinary norepinephrine was low in 8 of 20 cases of hyperthyroidism and high in 3 cases of hypothyroidism. Wiswell et al. (7) reported slightly increased urinary norepinephrine in 20 hypothyroid patients. Levine et al. (8) reported that urinary norepinephrine and vanillylmandelic acid (VMA) appeared to be low in some cases of hyperthyroidism. Current popular thinking, a result of conflicting reports, is that abnormal thyroid function exerts little effect on the catecholamines and their metabolites in the blood and urine (1,7,(9)(10)(11).We recently began using a simple, reliable plasma catecholamine assay based on Renzini's two-column method for chromatographic purification. This assay is more sensitive and more specific than previous assays (12,23). On reviewing our initial clinical experience with this assay, we noted that several patients with hypothyroidism had increased plasma catecholamine values. Therefore, a prospective study was designed to evaluate plasma catecholamines in hypothyroidism and hyperthyroidism. The results indicate that plasma catecholamines are increased in hypothyroidism and decreased in hyperthyroidism. In addition, plasma catecholamine values are inversely correlated with total thyroxine values in hyperthyroidism. Materials and MethodsPatients with clinical hypothyroidism or hyperthyroidism and abnormal total thyroxine levels were studied. Mean ( ± SD) total thyroxine levels were 1.1 ± 0.7 jxg/100 ml (range, 0.1-2.4) in hypothyroid patients and 15.7 ±: 2.3 ng/ml (range, 12.0-19.0) in hyperthyroid patients; in our laboratory, the normal range for total thyroxine is 4-11 |xg/100 ml. Normal plasma catecholamine values were obtained from healthy normotensive (diastolic pressure < 90 mm Hg) subjects as determined by history and physical examination. The total thyroxine assay has been described (13). The plasma catecholamine assay was performed according to the method of Renzini et al. (12) with slight modification. The details of the method will be published elsewhere (23). Briefly the method involves the purification of catecholamines by alumnia and Amberlite CG-50 (Na+ form) columns. The boric acid eluate from the Amberlite CG-50 column was used for fluorimetry. Epinephrine and norepinephrine were measured collectively. Norepinephrine was used as the standard. The molar extinction coefficient of epinephrine and norepinephrine are almost identica...

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