Summary: Objective   The aim of this study was to evaluate how resistin and adiponectin (ApN) are involved in maternal energy metabolism and foetal growth.Design  A cross‐sectional study.Patients and Measurements  Resistin and ApN were measured in 30 healthy nonpregnant women, 73 pregnant women [10–41 weeks of gestation; 18 with gestational diabetes mellitus (GDM), five with pregnancy‐induce hypertension (PIH), nine with pre‐eclampsia (PE), eight with chronic hypertension (CH) and 33 normal] and 40 foetal samples (20–41 weeks of gestation; 18 from GDM mothers and 22 from normal mothers).Results  Resistin levels were significantly higher in normal pregnant women than in nonpregnant controls (13·7 ± 2·1 vs. 6·3 ± 1·6 ng/ml; P < 0·005) and showed a negative correlation with gestational age (P < 0·0001, r = −0·7). Only women with PE presented resistin levels significantly lower than normotensive women of the same gestational age (8·2 ± 1·2 vs. 17·9 ± 4·3 ng/ml; P < 0·005). ApN levels, although similar in normal pregnant women to those in nonpregnant controls, were significantly lower in women with GDM (37–41 weeks; 5·2 ± 0·5 vs. 8·2 ± 0·8 mg/l; P < 0·0001) and PE (20–37 weeks; 5·0 ± 0·7 vs. 9·5 ± 0·7 mg/l; P = 0·008) than those found in normal women matched for gestational age. Resistin was detected in the umbilical venous blood in foetuses from 20 to 41 weeks of gestation. In all newborns, both resistin and ApN levels were significantly higher than those recorded in adult life and did not correlate with maternal levels (P = ns, r = 0·03 for resistin and P = ns, r = −0·3 for ApN). Foetuses from diabetic mothers had ApN significantly lower than normal foetuses (26·8 ± 2·6 vs. 37·5 ± 3·5 mg/l; P = 0·02), while resistin levels were similar (17·3 ± 3·7 vs. 18·2 ± 1·5 ng/ml; P = ns).Conclusion  The secretion pattern of ApN in normal and complicated pregnancies strongly suggests an involvement of ApN in insulin resistance during gestation, while resistin seems to have a minor role. Moreover, the detection of high levels of resistin and ApN in cord blood during gestation is consistent with a regulatory action of these adipokines on tissue differentiation and foetal growth.

Parathyroid carcinoma (PaC) is a rare cause of primary hyperparathyroidism. Though the loss of the oncosuppressor CDC73/HRPT2 gene product, parafibromin, has been involved in the hyperparathyroidism–jaw tumor syndrome and in a consistent set of sporadic PaCs, parathyroid carcinogenesis remains obscure. MicroRNAs are a new class of small, non-coding RNAs implicated in development of cancer, since their deregulation can induce aberrant expression of several target genes. The aim of the present study was to identify differentially expressed microRNAs in parathyroid cancers compared with normal tissues. We performed a TaqMan low-density array profiling of four parathyroid cancers harboring CDC73 inactivating mutations and negative for parafibromin immunostaining. Their microRNA profiling was compared with that of two normal parathyroid biopsies. Out of 362 human microRNAs assayed, 279 (77%) were successfully amplified. Fourteen and three microRNAs were significantly down- and over-expressed in parathyroid cancers respectively. Of these, miR-296 and miR-139 were down-regulated, and miR-503 and miR-222 were over-expressed with a null false discovery rate. Carcinomas could be discriminated from parathyroid adenomas by a computed score based on the expression levels of miR-296, miR-222, and miR-503 as miR-139 was similarly down-regulated in both cancers and adenomas. Finally, miR-296 and miR-222 levels negatively correlated with mRNA levels of the hepatocyte growth factor receptor-regulated tyrosine kinase substrate and p27/kip1 levels respectively. These results suggest the existence of an altered microRNA expression pattern in PaCs together with a potential role of miR-296 as novel oncosuppressor gene in these neoplasia.

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in ∼2% of PHPT cases. Lack of a family history and other specific expressions may lead to underestimated MEN1 prevalence in PHPT. The aim of this study was to identify clinical or biochemical features predictive of MEN1 and to compare the severity of the disease in MEN1‐related versus sporadic PHPT (sPHPT). We performed a 36‐mo cross‐sectional observational study in three tertiary referral centers on an outpatient basis on 469 consecutive patients with sporadic PHPT and 64 with MEN1‐related PHPT. Serum calcium, phosphate, PTH, 25(OH)D₃, and creatinine clearance were measured, and ultrasound examination of the urinary tract/urography was performed in all patients. In 432 patients, BMD was measured at the lumbar spine (LS) and femoral neck (FN). MEN1 patients showed lower BMD Z‐scores at the LS (−1.33 ± 1.23 versus −0.74 ± 1.4, p = 0.008) and FN (−1.13 ± 0.96 versus −0.6 ± 1.07, p = 0.002) and lower phosphate (2.38 ± 0.52 versus 2.56 ± 0.45 mg/dl, p = 0.003) and PTH (113.8 ± 69.5 versus 173.7 ± 135 pg/ml, p = 0.001) levels than sPHPT patients. Considering probands only, the presence of MEN1 was more frequently associated with PTH values in the normal range (OR, 3.01; 95% CI, 1.07–8.50; p = 0.037) and younger age (OR, 1.61; 95% CI, 1.28–2.02; p = 0.0001). A combination of PTH values in the normal range plus age <50 yr was strongly associated with MEN1 presence (OR, 13.51; 95% CI, 3.62–50.00; p = 0.0001). In conclusion, MEN1‐related PHPT patients show more severe bone but similar kidney involvement despite a milder biochemical presentation compared with their sPHPT counterparts. Normal PTH levels and young age are associated with MEN1 presence.

Adiponectin (ApN), an adipocytokine expressed in adipocytes with antidiabetic and antiatherogenic actions, has been detected in cord blood, suggesting a putative role in intrauterine fetal development. The aim of this study was to confirm the presence of ApN in the fetal circulation and directly investigate ApN expression in fetal tissues. The study showed high ApN levels in umbilical venous blood from fetuses [n = 44; 31.2 ± 14.1 (sd) mg/liter in umbilical vs. 8.4 ± 4.0 in maternal circulation (P < 0.0001)] that positively correlated with gestational age. By using RT-PCR, Western blotting, and immunohistochemistry, ApN was detected in several fetal tissues at mid- and late gestation (from 14 to 36 wk) but not in the placenta. ApN was expressed in tissues of mesodermic origin, i.e. brown and white adipocytes, skeletal muscle fibers of diaphragm and iliopsoas, smooth muscle cells of small intestine and arterial walls, perineurium and renal capsule, and tissues of ectodermal origin, i.e. epidermis and ocular lens. The distribution of ApN expression in nonadipose tissues showed a general decline during the progression of gestation. The unexpected pattern of ApN expression in the human fetus may account for the high ApN levels in cord blood and predicts novel roles for ApN during fetal development.

Exercise perturbs homeostasis, alters the levels of circulating mediators and hormones, and increases the demand by skeletal muscles and other vital organs for energy substrates. Exercise also affects bone and mineral metabolism, particularly calcium and phosphate, both of which are essential for muscle contraction, neuromuscular signaling, biosynthesis of adenosine triphosphate (ATP), and other energy substrates. Parathyroid hormone (PTH) is involved in the regulation of calcium and phosphate homeostasis. Understanding the effects of exercise on PTH secretion is fundamental for appreciating how the body adapts to exercise. Altered PTH metabolism underlies hyperparathyroidism and hypoparathyroidism, the complications of which affect the organs involved in calcium and phosphorous metabolism (bone and kidney) and other body systems as well. Exercise affects PTH expression and secretion by altering the circulating levels of calcium and phosphate. In turn, PTH responds directly to exercise and exercise-induced myokines. Here, we review the main concepts of the regulation of PTH expression and secretion under physiological conditions, in acute and chronic exercise, and in relation to PTH-related disorders.

A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC–MIR371–3 clusters and the molecular mechanisms presiding their modulation were investigated in a series of six normal parathyroids, 24 adenomas (Ad), 15 Ca and five matched metastases. The general expression levels of C19MC or MIR371–3 clusters in Ad lesions did not differ from normal glands, while they distinguished Ad from Ca at unsupervised hierarchical cluster analysis (P=0.0008). MIR517C showed the most significant difference in expression between Ca and Ad (P=0.0003) and it positively correlated with serum calcium, parathormone and tumour weight. In regard to the molecular mechanism determining C19MC cluster activation, we could detect C19MC copy number (CN) gain in ten Ca (67%) extending distal to the MIR371–3 cluster in almost all samples. Conversely, only four Ad (16%) showed C19MC amplification, with one case presenting distal genomic aberration to MIR371–3. Globally, CN variations of 19q13.4 loci were significantly associated with MIR517C up-regulation (P=0.006). Opposite to normal glands where C19MC promoter was methylated, hypomethylation occurred in 15 out of 30 analysed tumours. Though the epigenetic status did not correlate with C19MC miRNA expression levels, loss of C19MC promoter methylation was significantly associated with Ca and metastatic disease (P=0.01). In conclusion, C19MC cluster aberrations are a characteristic of Ca with respect to Ad. Altogether, these evidences point towards a role for 19q13.4 miRNA clusters as oncogenes in parathyroid tumourigenesis.