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Advances in cancer therapy over the last years have resulted in improved survival rates for pediatric cancer patients. However, new treatments are associated with short and long-term morbidity. The endocrine system is particularly sensitive to cancer therapies. Long-term survivors of childhood cancer are at risk for hypothalamic pituitary dysfunction, gonadal failure or disorders relating to pubertal progress, thyroid disease, obesity, disorders of lipid metabolism and disorders of bone and mineral metabolism. Long-term follow-up is indicated, as these disorders may not become apparent until adulthood.

Objective: Familial medullary thyroid carcinoma (FMTC) is caused by germ-line mutations in the RET proto-oncogene. These mutations concern mainly cysteine residues in exons 10 and 11, whereas noncysteine mutations in exons 13-16 are rare. Mutations in other exons have been reported only in isolated families. In this study we have analysed the RET gene in two FMTC families negative for mutations in the above exons., Design: We have analysed exons 7-19 and 21 in one index patient from each family using DNA sequencing., Patients: Twenty-eight subjects from both families were clinically assessed and subsequently molecularly analysed for the presence of RET gene mutations., Results: We have found the mutation c.1597G-->T (Gly533Cys) in two Greek families with FMTC. The mutation was detected in all seven MTC patients of both families as well as in 13 asymptomatic relatives in the heterozygote state, although one of the patients was also a homozygote due to consanguinity. The mutation shows a wide clinical heterogeneity, as there are carrier patients with age of diagnosis ranging from 23 to 88 years., Conclusions: It is likely that this mutation causes FMTC, as no other mutation was found in the RET gene, the mutation co-segregates with FMTC, and family members without the mutation are clinically unaffected. As the same point mutation was previously found in a large Brazilian family, it may be present in other populations as well. Therefore, exon 8 of RET should be screened in FMTC families with no identified common RET mutations.

Context: Primary hyperparathyroidism (PH) is characterized by inappropriate PTH elevation with or without hypercalcemia. Bone disease involves catabolic action at cortical sites, whereas cancellous sites and geometry might be relatively preserved., Objective: Our objective was to examine the effect of PH on quantitative and qualitative bone characteristics using peripheral quantitative computed tomography at the tibia in postmenopausal women with PH and healthy controls., Design and Setting: We conducted a cross-sectional study at a tertiary referral center., Patients: Fifty-two postmenopausal women with PH and 56 healthy controls, comparable for age and anthropometric measures, participated., Intervention: There was no intervention., Main Outcome Measure: We assessed volumetric bone mineral density (vBMD), bone mineral content (BMC), cortical thickness, cortical and trabecular area, peri- and endosteal circumference, and polar stress strength index assessed by peripheral quantitative computed tomography of the left tibia at 4% (cancellous), 14% (transition zone), and 38% (cortical) from the distal end., Results: At 4%, there was a significant decrease of trabecular BMC and vBMD (P < 0.001), effect particularly evident in hypercalcemic patients, whereas trabecular area was comparable. At 38%, cortical BMC (P < 0.01), vBMD (P < 0.01), area (P < 0.05), and thickness (P < 0.001) were reduced in the PH group, particularly in hypercalcemic patients. Endosteal circumference increased (P < 0.001), whereas periosteal circumference was comparable, indicating cancellization of cortical bone. At 14%, polar stress strength index was significantly decreased (P < 0.01) in hypercalcemic patients, indicating impairment of bone mechanical properties., Conclusions: Normocalcemic PH is characterized by catabolic actions at both cortical and cancellous sites (38 and 4%, respectively), an effect accentuated in hypercalcemic patients. Cortical geometric properties are adversely affected even in normocalcemic patients, whereas trabecular properties are generally preserved.