Endocrine Abstracts

Idiopathic central hypogonadism (ICH) is a rare and heterogeneous disease due to defects of GnRH secretion or action. Depending on the association with a normal or defective sense of smell, ICH could be respectively identified as normosmic ICH (nICH) or Kallmann’s syndrome (KS). Recent experimental evidences indicate the involvement of the new PROK2/PROKR2 pathway in GnRH neuron maturation and function and mutations affecting these two genes have been described in some IC...

ACTH resistance syndromes (ARS) are rare, severe and heterogeneous diseases that include either familial glucocorticoid deficiency (FDG) or Allgrove syndrome (AS). FDG is a rare autosomal recessive disorder resulting from mutation in genes encoding either the ACTH-receptor (ACTHR) in FDG1, or its accessory protein MRAP, in FDG2. AS is characterized by adrenal insufficiency due to ACTH resistance, alacrimia, and achalasia secondary to mutations in the AAAS gene, which ...

ICH is a rare disease characterized by a complex pathogenesis, but with a strong genetic component. ICH may be associated to several other morphogenetic or inborn defects, such as the osmic defects that identify the Kallmann syndrome (KS). The description of several pedigrees including relatives affected either with isolated osmic defects or KS or normoosmic ICH (nICH) justifies the emerging idea of ICH as a complex genetic disease characterized by variable expressivity and pe...

ICH is a rare and heterogeneous condition due to defects in the onthogenesis, migration and action of GnRH secreting neurons. Recent publications indicate that ICH, though characterized by a strong genetic component, is a disease of multifactorial origin. Indeed, digenic and oligogenic defects have been described as a possible pathogenic explanation for this disease. Among the cohort of 315 ICH patients we identified 3 KS and 7 nICH patients (7 males, 3 females) with a biallel...

Isolated central hypothyroidism (ICH) is a rare disease whose pathogenesis is so far linked to germinal mutations of TSHβ (several cases) or TRH receptor (TRHR) genes (only two cases). Here, we report the studies performed to elucidate the pathogenesis of idiopathic ICH in five cases (two men, three women) with low/normal TSH levels and low freeT4 levels (3–8 pmol/l). One male, negative at neonatal TSH screening, showed signs of severe hypothyroidism at 44...

ICH is a heterogeneous disease mainly due to functional defects of GnRH neurons. Recent studies have described the importance of prokineticin pathway in the pathogenesis of these defects. In a series of 166 ICH patients we found germline mutations affecting this pathway in about 10% of the cases. PROKR2 gene analysis revealed 3 novel (V158I, T260M, V334M) and 4 already known (L173R, R268C, V274D, V331M) mutations affecting different transmembrane and intracellular regions of t...