Search Results

You are looking at 1 - 3 of 3 items for

  • Author: Sandra Pekic x
  • All content x
Clear All Modify Search
Free access

Sandra Pekic and Vera Popovic

It has been difficult to identify factors that affect the risk of cancer, but we know that people are at higher risk as they get older, or if they have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Early population-based and case–control studies suggested that higher serum levels of IGF1 could be associated with increased cancer risk. Since GH therapy increases IGF1 levels, concern has been raised regarding its potential role as a cancer initiation factor. Experimental evidence and some clinical studies showed that when GH/IGF1 secretion or action was inhibited, a decreased incidence and rate of progression of cancers occurred. However, human populations comprise a garden variety of genotypes that respond differently to the same kind of exposures. Human population studies frequently reveal only very small effects to these exposures. So, are GH and cancer guilty by association? After more than 20 years, leukemia, a major safety issue initially believed associated with GH treatment in children with GH deficiency (GHD), has not been confirmed but the risk of second malignancies in patients previously treated with irradiation has been detected or confirmed through the National Cooperative Growth Study. Overall, this large study confirmed the favorable overall safety profile of GH therapy in children with GHD, and also highlighted specific populations at potential risk. The risk of secondary malignancy following radiotherapy is surely related to radiotherapy more than GH therapy that may increase growth but is less likely to start the oncogenic process. In GH-deficient adults treated with GH, observational studies (KIMS, HypoCCS) have shown that when IGF1 levels were targeted within normal age-related reference ranges, the occurrence of malignancies was not higher than in the general population.

Free access

Sandra Pekic and Vera Popovic

Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic–pituitary region. By far, the most common cause of hypopituitarism associated with a sellar mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditions such as other massess in the sellar and parasellar region, brain damage caused by radiation and by traumatic brain injury, vascular lesions, infiltrative/immunological/inflammatory diseases (lymphocytic hypophysitis, sarcoidosis and hemochromatosis), infectious diseases and genetic disorders. Hypopituitarism may be permanent and progressive with sequential pattern of hormone deficiencies (radiation-induced hypopituitarism) or transient after traumatic brain injury with possible recovery occurring years from the initial event. In recent years, there is increased reporting of less common and less reported causes of hypopituitarism with its delayed diagnosis. The aim of this review is to summarize the published data and to allow earlier identification of populations at risk of hypopituitarism as optimal hormonal replacement may significantly improve their quality of life and life expectancy.

Open access

Daniele Cassatella, Sasha R Howard, James S Acierno, Cheng Xu, Georgios E Papadakis, Federico A Santoni, Andrew A Dwyer, Sara Santini, Gerasimos P Sykiotis, Caroline Chambion, Jenny Meylan, Laura Marino, Lucie Favre, Jiankang Li, Xuanzhu Liu, Jianguo Zhang, Pierre-Marc Bouloux, Christian De Geyter, Anne De Paepe, Waljit S Dhillo, Jean-Marc Ferrara, Michael Hauschild, Mariarosaria Lang-Muritano, Johannes R Lemke, Christa Flück, Attila Nemeth, Franziska Phan-Hug, Duarte Pignatelli, Vera Popovic, Sandra Pekic, Richard Quinton, Gabor Szinnai, Dagmar l’Allemand, Daniel Konrad, Saba Sharif, Özlem Turhan Iyidir, Brian J Stevenson, Huanming Yang, Leo Dunkel, and Nelly Pitteloud

Objective

Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood.

Design

We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders.

Methods

Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus).

Results

Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10−11) or controls (18%, P = 5.5 × 10−12). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10−7).

Conclusions

Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty.