Noonan-like syndrome with loose anagen hair associated with growth hormone insensitivity and atypical neurological manifestations.

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721), recently related to the invariant c.4A>G missense change in SHOC2, is characterized by features reminiscent of Noonan syndrome. Ectodermal involvement, short stature associated with growth hormone (GH) deficiency (GHD), and cognitive deficits are common features. We report on a patient with molecularly confirmed NS/LAH exhibiting severe short stature associated with GH insensitivity (GHI), and chronic complex tics, a neurological feature never described before in this syndrome. IGF1 generation test revealed only a blunted increase in IGF1 after exogenous GH treatment, revealing mild GH insensitivity associated with proper STAT5 activation. Most common causes of secondary tics in childhood were excluded.

Postpartum thyroiditis is associated with fluctuations in transforming growth factor-beta1 serum levels.

Postpartum thyroiditis (PPT) is characterized by a rapid evolution and recovery of euthyroidism. Therefore, it can represent a good model to study early cytokine fluctuations in autoimmune thyroid diseases. TGFbeta1 is an immunosuppressive cytokine, as it inhibits T and B cell proliferation, natural killer cell cytotoxic activity, and the generation of T cell cytotoxicity. The aim of this study was to assess serum concentrations of TGFbeta1 during pregnancy and to study possible serum fluctuations of this cytokine during the different phases of PPT. Thyroid biochemical pattern, antithyroid autoantibodies (ATA), and total and active TGFbeta1 (aTGFbeta1) serum concentrations were evaluated in 63 pregnant women. Thirty-four of them were ATA(+), and 29 were ATA(-). Twenty of the 34 ATA(+) women were followed in the postpartum year. Nine of these 20 women developed PPT; 11 remained euthyroid. All of the PPT women became euthyroid during the follow-up. Our results showed 1) detectable serum levels of aTGFbeta1 in 50% of ATA(+) pregnant women, suggesting that the presence of autoantibodies may characterize a favorable condition for TGFbeta1 activation; and 2) decreased total TGFbeta1 and increased aTGFbeta1 serum levels during the active phase of PPT in ATA(+) women. This seems to suggest that inflammation may be responsible for TGFbeta1 activation and autoantibody increase because of antigen release. Although further studies of women with persistent hypothyroidism after the postpartum year are needed, the possibility that the enhanced activation of TGFbeta1 may contribute to resolution of thyroid inflammation postpartum cannot be excluded.

A population-based study on the frequency of additional congenital malformations in infants with congenital hypothyroidism: data from the Italian Registry for Congenital Hypothyroidism (1991-1998).

In the last decade a high frequency of other congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in the population of CH infants detected in Italy between 1991 and 1998 (n = 1420) was investigated. In Italy all of the centers in charge of screening, treatment, and follow-up of CH adhere to the Italian National Registry of infants with CH. In this study a high prevalence of additional CM (8.4%), more than 4-fold higher than that reported in the Italian population (1-2%), was found in the population of CH infants. Cardiac anomalies represented the most frequent malformations associated with CH, with a prevalence of 5.5%. However, a significant association between CH and anomalies of nervous system, eyes, and multiple CM was also observed. In conclusion, the significantly higher frequency of extrathyroidal congenital malformations reported in the CH infants than in the general population represents a further argument supporting the role of a genetic component in the etiology of CH. Investigations of the molecular mechanisms underlying developmental events of formation of thyroid and other organs represent critical steps in the knowledge of CH etiology.