L Hoffman

Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21.

The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. In a large Tasmanian pedigree (Tas1) with recurrence of papillary thyroid carcinoma (PTC), the most common form of NMTC, an extensive genomewide scan revealed a common haplotype on chromosome 2q21 in seven of the eight patients with PTC. To verify the significance of the 2q21 locus, we performed linkage analysis in an independent sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD score (HLOD) of 3.07 (alpha=0.42), nonparametric linkage (NPL) 3.19, (P=.001) at marker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, identified 17 such pedigrees, yielding a maximal HLOD score of 4.17 (alpha=0.80) and NPL=4.99 (P=.00002) at markers AFMa272zg9 and D2S2271, respectively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.

Somatotrophinomas in multiple endocrine neoplasia type 1: A review of clinical phenotype and insulin-like growth factor-1 levels in a large multiple endocrine neoplasia type 1 kindred

PURPOSE Within the spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN-1), widely disparate prevalence rates for somatotrophinomas have been described. Studies that combine multiple, small MEN-1 kindreds report pituitary disease in 60% to 65% of patients, somatotrophinomas accounting for 27% to 37% of total pituitary lesions. However, reports based on large MEN-1 family screening programs have produced lower prevalence rates for pituitary adenomas (9% to 40%), of which somatotrophinomas comprise up to 14%. We sought to determine the prevalence of both biochemical and clinically overt growth hormone (GH) hypersecretion in the largest reported MEN-1 genealogy, the Tasman 1 kindred. PATIENTS AND METHODS The Tasman 1 MEN-1 kindred contains 165 members with established MEN-1. We reviewed the records of 124 MEN-1 patients for evidence of acromegaly or gigantism. To determine if clinical criteria underestimate the occurrence of biochemical GH hypersecretion, a subset of 33 patients was assessed for elevated levels of serum insulin-like growth factor-1 (IGF-1). RESULTS No cases of acromegaly or gigantism were detected in the 124 patients reviewed. Of the 33 patients screened with IGF-1, 13 had previously diagnosed pituitary lesions--11 prolactinomas and 2 nonsecretory lesions. The IGF-1 levels were normal in all patients studied. There were no significant differences in mean IGF-1 values between patients with and without pituitary lesions. CONCLUSIONS This report represents the largest study of growth hormone secretion patterns thus far described in MEN-1. The apparent absence of somatotrophinomas in a kindred of this size is unexpected. These results support the existence of kindred-specific MEN-1 phenotypes. We conclude that the pathogenesis of GH-secreting adenomas in MEN-1 is influenced by secondary factors acting in synergy with the well-documented primary MEN-1 gene defect on chromosome 11q13.

Intact glucose oxidation in human fetal pancreas

1. Thomas BJ, Jarrett R J, Keen H, Ruskin HJ (1982) Relation of habitual diet to fasting plasma insulin concentration and the insulin response to oral glucose. Human Nutr Clin Nutr 36 c: 49-56 2. Arntzenius AC, Kromhout D, Barth J, Reiber JHC, Bruschke AVG, Buis B, van Gent CM, Kempen-Voogd N, Strikwerda S, van der Velde EA (1985) Diet, lipoproteins, and the progression of coronary atherosclerosis. N Engl J Med 312:805-811

CORONARY AND PERIPHERAL VASCULAR RESISTANCE IN THE ANAESTHETIZED DIABETIC SHEEP

1. To determine whether vascular resistance was altered in diabetes, the vascular resistance in both the peripheral arterial bed and the circumflex coronary artery was compared in six normal and five diabetic adult sheep, under pentobarbitone anaesthesia. Diabetes induced by alloxan significantly increased blood glucose (15.6mmol/l, s.e.m. = 2.8, vs 5.5 mmol/l, s.e.m. =0.6; P>0.001) compared with controls.