The gene for multiple endocrine neoplasia type 1 (MENi), an inherited predisposition to neuroendocrine neoplasm of the parathyroid glands, the pancreatic islet parenchyma, and the anterior pituitary gland, was recently mapped to chromosome 11q13 based on genetic linkage in families. We now show that the pathogenesis of MEN1-associated parathyroid lesions involves unmaking of a recessive mutation at the disease locus and that sporadic primary hyperparathyroidism shares the same mechanisms. MENi patients and from 24 patients with sporadic primary hyperparathyroidism were fresh-frozen and stored at -700C.The parathyroid lesions 11-3 LU-HPT and HPT-EZ were obtained from members of the LU and EZ kindreds (3). Specimens of insulinoma parenchyma from case II-1 of the LU kindred (3) were also included.Pituitary tumors from 27 cases, all but one (APA-23) with no signs of MEN1, were obtained by a trans-sphenoidal surgical approach and treated in the same manner. Four

The thyroid hormone system is rapidly down-regulated in AMI. This may be beneficial during acute ischemia. Patients with angina had higher levels of interleukin 6 and C-reactive protein and more depressed thyroid hormone system in early samples. Thyroid level depression in patients with angina may possibly have been present before the infarction process started. This novel finding needs further evaluation in large studies to sort out cause-and-effect relationships.

In two of 12 patients with clinical glucocorticoid resistance, mutant forms of GR could be found. The glucocorticoid resistance in vivo in these two patients corresponds to impaired function of the two mutated GR forms in two in vitro assays. The relevance of the conservative polymorphism for the glucocorticoid insensitivity noted in these patients remains to be clarified.

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The serum levels of the low molecular form of insulin-like growth factor binding protein (IGFBP) was determined in 56 outpatients with diabetes mellitus by a radioimmunoassay developed for amniotic 35 kDa IGFBP. The mean level of 35 kDa IGFBP was found to be threefold higher in insulin dependent diabetes mellitus (IDDM), 112 +/- 13 ng/ml, than in age matched controls, 37 +/- 2 ng/ml, while the mean level in non-insulin dependent diabetes mellitus (NIDDM), 16 +/- 2 ng/ml, was decreased. In hospitalized IDDM patients there was a significant correlation (r = 0.91, p less than 0.01) between fasting blood-glucose and 35 kDa IGFBP levels, not found in NIDDM patients. During insulin infusion the 35 kDa IGFBP levels declined with a half-life of 60-120 min. The decline in IGFBP continued even after the establishment of steady state B-glucose at 4.7 mmol/l. In conclusion, the elevated 35 kDa IGFBP levels in IDDM can be attributed to insulin deficiency and may reflect a reduced bioavailability of the IGFs at the target cells.