Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as WRN) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of the these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.

The clinical features of 20 patients from five families with multiple endocrine neoplasia syndrome type I (MEN-I) were studied. Nineteen patients (95%) had hyperparathyroidism. Five patients who had a diagnosis during surgery of adenoma and who had fewer than 3.5 glands removed had recurrence of hypercalcemia after surgery. Fourteen patients (70%) had pancreatic islet cell tumors. All had one or more elevated serum polypeptide hormones, and six had symptoms related to the hormones produced. Multiple pancreatic tumors were identified in the nine patients who underwent surgery. Three patients who died had a mean survival of 6.3 +/- 2.9 years. Eight patients had pituitary tumors; seven had macroadenomas. Of the eight patients with pituitary tumors, seven had high serum prolactin and responded to bromocriptine therapy, whereas the eighth patient had acromegaly treated with radiotherapy. It was concluded that hypercalcemia due to hyperparathyroidism in MEN-I syndrome patients should be managed by a resection of four glands and transplantation of one half gland into the forearm because none of the patients has shown evidence of a recurrence, and serum calcium levels have been normal. Pancreatic tumors, which are usually multiple, may be asymptomatic. Patients with these tumors usually have long survival rates, even with distant metastasis. Total pancreatectomy may be the method of choice, especially in patients with gastrinoma caused by the diffuse nature of the disease. Long-term follow-up is needed, however, with more patients. Pituitary tumors are primarily prolactin-producing tumors, and medical treatment is the method of choice.

A patient with hypercalcemia secondary to recurrent parathyroid carcinoma was treated for 44 days with intramuscular and intravenous injections of porcine calcitonin and on day 45 with synthetic salmon calcitonin. There was no sustained control of serum calcium during this period, but the concentration decreased transiently with intravenous administration of both types of calcitonin.No serial measurements of serum calcium were made following intramuscular administration; therefore, it is not known whether this route of administration produced similar results. Dosage and route of administration of calcitonin warrant further investigation in controlling hypercalcemia secondary to parathyroid hormone excess. No dzerence in the degree or duration of decreasing the serum calcium concentration was noted following comparable doses of intravenous infusions of porcine calcitonin and of synthetic salmon calcitonin on separate days. Parathyroid hormone levels measured during the infusion of synthetic salmon calcitonin remained elevated at essentially the same level before and after the infusion. A steady decline in urinary phosphorous excretion during the treatment period could not be explained with certainty. HE TREATMENT OF HYPERCALCEMIA PRO-T duced by hyperfunctioning parathyroid tissue, be it hyperplasia, adenoma, or carcinoma, is surgical removal of such tissue. Excision of functioning metastatic and recurrent parathyroid carcinoma is also recommended since control of hypercalcemia can be achieved.6 Multiple cervical recurrence is characteristic with this tumor, but frequently it is not possible for the surgeon to locate

A case of gonadal dysgenesis associated with unusual abnormalities is described as follows: a) enlarged pituitary fossa with clinical and laboratory manifestations of hypopituitarism; b) Hashimoto's thyroiditis and XO/X-isoX mosaicism; c) adenocarcinoma of the parotid gland. These uncommon features were present in association with renal and cardiovascular anomalies.

Twenty-four patients who had a 10-year history of hypopituitarism resulting from treated chromophobe adenoma, without known family history of diabetes, were studied during oral glucose tolerance (GTT), arginine infusion, and insulin tolerance (ITT) tests. All patients were receiving thyroid and cortisone replacement. Serum immunoreactive growth hormone (HGH) was subnormal in all patients compared with normal subjects during both arginine infusion and ITT tests (P < 0.001). Although 9 of this hypopituitary group were diabetic, all patients showed a subnormal peak immunoreactive insulin rise during an arginine infusion test and subnormal insulinogenic index during an oral glucose tolerance test, when compared with normal subjects in the same age range. Fasting plasma triglycerides were elevated in the majority of patients, serum cholesterol in 8 while free fatty acids were high in all patients. Hyperglycaemia, hypoinsulinaemia, hyperlipidaemia and low growth hormone levels were not associated with any of the clinical signs of vascular disease frequently seen in diabetic patients.