Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609→620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.

This series increases the limited knowledge of mutations and phenotypes of this rare disorder. Mutation analysis of the CaSR gene facilitates patient and family management. Low dosages of calcitriol resulted in less frequent renal calcifications.

An increased frequency of kidney stone formation is reported in patients with inflammatory bowel disease. In order to investigate its pathogenesis, the concentrations of factors known to enhance calcium oxalate stone formation (oxalate, calcium, uric acid) as well as of inhibitory factors for nephrolithiasis (magnesium, citrate) were determined in the urine of 86 patients with Crohn's disease and compared with those of 53 metabolically healthy controls. Six patients with Crohn's disease already had experienced calcium oxalate nephrolithiasis. Patients with Crohn's disease had significantly higher urinary oxalate and lower magnesium and citrate concentrations. Among all patients magnesium and citrate were significantly lower in those with a positive history of kidney stones. Our results demonstrate that the increased propensity for renal stone formation in patients with Crohn's disease is a result not only of increased urinary oxalate, but also of decreased urinary magnesium and citrate concentrations.

The long-term results of transsphenoidal adenomectomy and the incidence of possible recurrences were studied in 61 patients who had normal basal serum growth hormone (GH) levels 1 week after surgery. The patients were followed up for an average of 6.0 years (range: 1.5–14.0 years) by repeated measurements of GH, oral glucose tolerance testing (OGTT) and at the last follow-up visit also by assaying somatomedin C levels. In 4 of the patients, the basal GH levels had increased to values above 5 ng/ml. In 43 patients, a normal suppression of GH during an oral glucose load was observed shortly after surgery. In only 2 of these cases did a transiently inadequate suppression develop during the follow-up period, although clinical acromegaly did not recur and the somatomedin C levels remained normal. It is concluded that recurrence of active acromegaly is unlikely to occur in patients who achieve a normal glucose-induced suppression of GH levels shortly after adenomectomy. As such, an OGTT provides better prognostic information than basal human GH level measurements and may give a clearer and earlier indication of surgical success.

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