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Objective: In primary hyperparathyroidism (PHPT), vertebral fractures (VFx) occur regardless of bone mineral density (BMD) and may depend on decreased bone quality. Trabecular bone score (TBS) is a texture measurement acquired during a spinal dual-energy X-ray absorptiometry (DXA). Recently, TBS has been proposed as an index of bone micro-architecture. Design: We studied 92 PHPT patients (74 females, age 62.1G9.7 years) and 98 control subjects. In all patients at baseline, in 20 surgically treated patients and in 10 conservatively treated patients after 24 months, TBS, spinal (lumbar spine (LS)) and femoral (total hip (TH) and femoral neck (FN)) BMD were assessed by DXA and VFx by spinal radiograph. Results: PHPT patients had lower TBS (K2.39G1.8) and higher VFx prevalence (43.5%) than controls (K0.98G1.07 and 8.2% respectively, both P!0.0001). TBS was associated with VFx (odds ratio 1.4, 95% CI 1.1-1.9, PZ0.02), regardless of LS-BMD, age, BMI and gender, and showed a better compromise between sensitivity (75%) and specificity (61.5%) for detecting VFx than LS-BMD, TH-BMD and FN-BMD (31 and 75%, 72 and 44.2%, and 64 and 65% respectively). In surgically treated patients, TBS, LS-BMD, TH-BMD and FN-BMD increased (C47G44.8,C29.2 G34.1,C49.4G48.7 and C30.2G39.3% respectively, all P!0.0001). Among patients treated conservatively, TBS decreased significantly in those (nZ3) with incident VFx (K1.3G0.3) compared with those without (K0.01G0.9, PZ0.048), while BMD changes were not statistically different (LS 0.3G1.2 vs K0.8G0.9 respectively, PZ0.19; TH 0.4G0.8 vs K0.8G1.4 respectively, PZ0.13 and FN 0.4G0.9 vs K0.8G1.4 respectively, PZ0.14). Conclusions: In PHPT, bone quality, as measured by TBS, is reduced and associated with VFx and improves after surgery.

Mutations of the Gsalpha gene inherited from the mother lead to pseudohypoparathyroidism (PHP) type Ia (PHP Ia), in which Albright's hereditary osteodistrophy is associated to resistance to the action of different hormones, whereas the same mutations inherited from the father lead to isolated Albright's hereditary osteodistrophy [pseudo-PHP (PPHP)]. Accordingly, it has been suggested that Gsalpha is under tissue-specific imprinting control, and recent studies provided evidence for a predominant maternal origin of Gsalpha transcripts in different endocrine organs involved in the PHP Ia phenotype. To establish whether Gsalpha is imprinted also in tissues that are site of alteration both in PHP Ia and PPHP, we selected 20 bone and 10 adipose tissue samples, which were heterozygous for a known polymorphism in exon 5. Expression from both parental alleles was evaluated by RT-PCR and enzymatic digestion of the resulting fragments. By this approach, the great majority of the samples analyzed showed an equal expression of the two alleles. Our results provide evidence for the absence of Gsalpha imprinting in human bone and fat and suggest that the clinical finding of osteodystrophy and obesity in PHP Ia and PPHP patients despite the presence of a normal Gsalpha allele is likely due to Gsalpha haploinsufficiency in these tissues.

Context: Primary hyperparathyroidism (PHPT) shows a great variability in clinical course and severity. Data concerning the association between polymorphic variants of the gene encoding the calciumsensing receptor (CaSR) and clinical characteristics of PHPT are not conclusive. Objective: To evaluate the frequency of three polymorphisms; A986S, R990G, and Q1011E of CaSR in patients with PHPT and to correlate the genotypes with clinical and biochemical parameters. Patients and methods: The study included 94 consecutive unrelated patients referred to our Departments for PHPT diagnosis and management between 2000 and 2005 and 137 age and sexmatched healthy subjects. Patients and controls were genotyped according to standard procedures. Due to the rarity of 990G allele, homozygous and heterozygous subjects were grouped in R/GCG/G set. All PHPT patients were studied for calcium metabolism parameters and renal and bone complications. Results: The proportion of CaSRvariants was similar in PHPT patients and controls. In PHPT patients, only R990G polymorphism was associated with disease parameters; in comparison with R/R, R/GCG/G patients showed lower mean serum parathyroid hormone (PTH) and phosphate levels (139.9G62.2 vs 199.9G136.3 pg/ml, P!0.05 and 0.69G0.12 vs 0.81G0.18 mmol/l, PZ0.031 respectively), higher mean 24-h urine calcium concentration and calcium excretion (9.05G2.05 vs 6.77G4.31 mmol/24 h, PZ0.012 and 67G20 vs 51G26 mmol/l GF, PZ0.039), and increased prevalence of nephrolithiasis (90.0 vs 44.2%, PZ0.007). Conclusions: The study showed that patients with PHPT, bearing the 990G allele, had lower serum PTH levels and higher urinary calcium excretion in comparison with the other genotype, suggesting an increased sensitivity of the variant receptor to extracellular calcium. Since this variant was associated with increased occurrence of nephrolithiasis, analysis of this polymorphism might help to predict renal complication of the disease.European Journal of Endocrinology 155 687-692

Similar molecular alterations may lead to a broad spectrum of diseases, from isolated PTH resistance to complete PHP-Ia, and the degree of methylation alterations does not reflect or anticipate the severity and the type of different PHP/AHO manifestations.

Fetal cell microchimerism (FCM) is defined as the persistence, for decades after pregnancy, of fetal cells in maternal organs and circulation without any apparent rejection. We recently reported evidence, in papillary thyroid cancer (PTC) tissues, supporting a possible role of FCM in tumor damage and repair. To extend those data at the peripheral level, 106 women with a previous male pregnancy, comprising 57 with PTC and 49 healthy controls were enrolled. The presence of circulating male DNA was assessed by the amplification of the Y chromosome-specific gene SRY, with a sensitivity of 1 male cell per 1 million female cells. Moreover, to compare the microchimeric status in blood and in tumors, the neoplastic tissues of 19 women were studied. At the blood level, a significantly lower frequency of FCM was found in parous women with PTC with respect to controls (49.1% vs. 77.6%; p 5 0.002). By PCR, male DNA was identified in the tumor tissues of 6 patients, and FISH analyses confirmed the presence of microchimeric cells (range 2.1-6.9 cells/section). In some patients, FCM was negative in the blood, whereas microchimeric cells were identified in the tumor. In conclusion, the prevalence of FCM in peripheral blood was found to be significantly lower in patients than in healthy controls. The presence of microchimeric cells in the tumors, but not at the peripheral level, supports the hypothesis that fetal cells could reside in maternal niches and could be recruited to diseased areas, where they could differentiate to regenerate damaged tissues.During pregnancy a bi-directional exchange of cells has been observed between the fetus and the mother, starting from the 4th to 6th week of gestation, and fetal cells have been documented to persist in the maternal circulation or tissues for decades. 1,2 This cells trafficking primarily includes subsets of immune cells, including pregnancy-associated progenitor cells with the capacity for multilineage differentiation. 3 Fetal cell microchimerism (FCM) is a common event in pregnancy, being detected in the peripheral blood in 20-75% of parous women 1,4-6 and in the tissues injured by neoplastic or benign diseases in 40-100% of patients. 7-12 Different hypotheses about the role of FCM in malignancies have been proposed, 13-15 whereas scarce data on microchimerism in tissue without disease are available.The role of FCM has been first studied in autoimmune diseases, such as systemic sclerosis, primary biliary cirrhosis, Sjögren syndrome, erythematous systemic lupus, Type 1 diabetes mellitus and thyroiditis. 4,10,[16][17][18][19] More recently, studies on FCM have been extended to nonautoimmune diseases, including hepatitis C, benign and malignant thyroid diseases, cervical, breast, lung, colon, uterine, ovarian, cervical cancers, and hematological malignancies. [5][6][7][8][9][11][12][13]15 Discordant data are available about the causative relevance of FCM in both autoimmune and neoplastic diseases. Briefly, in most studies FMC has been postulated to be pathogenic in autoimmune disease...

The study provides additional evidence that prolonging therapy for more than 3 years does not reduce recurrence rate. In particular, recurrence risk was similar in micro- and macroadenomas, and higher in patients with pituitary deficits at diagnosis.