IntroductionPeutz–Jeghers syndrome is an autosomal dominant disease with incomplete penetrance and variable expression caused by germline mutation of serine threonine kinase 11/liver kinase B1; it is characterized by hamartomatous polyps in the gastrointestinal tract, mucocutaneous melanin pigmentation, and increased predisposition to neoplasms. In Peutz–Jeghers syndrome, bilateral Sertoli cell testicular tumors cause endocrine manifestations including gynecomastia and feminization.This study aimed to assess the role of breast ultrasound in the evaluation of the effectiveness of an innovative surgical approach.Case presentationThis report presents a pair of European 9-year-old identical male twins with Peutz–Jeghers syndrome, bilateral prepubertal gynecomastia, and testicular multifocal calcifications. Both twins were treated with anastrozole for 2 years. After finishing treatment, both underwent subcutaneous mastectomy performed by the “modified” Webster technique. Breast examination and ultrasound were performed before and after the pharmacological and surgical treatment. A breast ultrasound scan before surgery showed bilateral gynecomastia in both patients. No solid nodular or cystic formations were present on either side. After pharmacological therapy and surgical glandular removal, a breast examination showed a significant reduction in breast volume; 1 year after surgery, a breast ultrasound scan of both patients showed a total absence of glandular parenchyma, with muscle planes well represented.ConclusionsBreast examination and ultrasound have proved to be a valid approach in the assessment of the treatment of prepubertal gynecomastia because they allow the efficacy of the pharmacological and surgical treatment to be evaluated in a multidisciplinary approach to one of the most frequent endocrine manifestations of Peutz–Jeghers syndrome.

Context: Several studies demonstrated that obese children have higher TSH than normal-weight children. The polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene showed an association with TSH. Objectives: i) To assess the effect of PDE8B on TSH in obese children; ii) to dissect the role of obesity degree in modulating this association; and iii) to stratify the individual risk to show hyperthyrotropinaemia according to PDE8B genotype. Methods: Eight hundred and sixty-seven Italian obese children were investigated. Clinical data and thyroid hormones were evaluated and the PDE8B rs4704397 was genotyped. Results: PDE8B A/A homozygous subjects showed higher TSH (PZ0.0005) compared with A/G or G/G. No differences were found for peripheral thyroid hormones. Among A/A children, 22% had hyperthyrotropinaemia, compared with 11.6% of heterozygotes and 10.8% of G/G (PZ0.0008). Consistently, A/A had an odds ratio (OR) to show abnormal TSH level of 2.25 (PZ0.0004). Body mass index (BMI) appeared correlated with TSH (PZ0.0001), but the strength of the effect of PDE8B on TSH was independent of BMI (PZ0.1). Children were subdivided into six groups according to obesity degree and genotypes. PDE8B A/A with BMI SDS above 3 had the highest OR (OR 2.6, PZ0.0015) to have hyperthyrotropinaemia, whereas G/G with BMI SDS below 3 showed the lowest possibilities (OR 0.3, PZ0.005). Conclusions: We have shown: i) in obese children, PDE8B is associated with TSH; ii) the interaction between adiposity and PDE8B on TSH is not synergistic, but follows an additive model; and iii) impact of this association in the stratification of individual risk to have hyperthyrotropinaemia.

HighlightsWe present an otherwise healthy boy of 12 years old with unilateral breast masses. No abnormalities were found on ultrasonography and on all endocrine parameters.We present a new “modified” Webster technique. The results confirmed validity of this technique in terms of esthetic and functional results, and patient satisfaction.The evaluation of unilateral gynecomastia can therefore be complex.The surgical treatment of unilateral gynecomastia requires an individual approach, based on an appropriate diagnostic algorithm.

Background: Homozygous mutations in acid-labile subunit (IGFALS) gene result in short stature, very low circulating levels of acid-labile subunit (ALS), insulin growth factor 1 (IGF1) and insulin growth factor binding protein 3 (IGFBP3) and a poor response to growth hormone (GH). The impact of IGFALS mutations heterozygosity on growth is unknown. Patient and Methods: We describe a 10-year-old girl with severe short stature (height -3.2 SDS), heterozygous for a new IGFALS mutation. Results: The girl showed low circulating IGF1, IGFBP3 and ALS levels and normal GH secretion. We found a novel heterozygous frameshift IGFALS mutation (c.1283delA, p.Gln428Argfs*14). Size-exclusion chromatography showed a reduction of the IGF1, IGFBP3 and ALS 150-kDa ternary complex (by about 55%) compared to a control. An IGF-1 generation test, with two different GH dosages, showed a good response in term of increase in IGF1 and in formation of the ternary complex at size-exclusion chromatography. Clinical response after 6 months of therapy with GH was satisfactory (height velocity increased from 3 to 8 cm/year). Conclusion: We suggest that (1) heterozygous IGFALS mutations can be responsible for a subset of patients with severe short stature (below -2.5 SDS), low IGF1 (below -2 SDS) and normal GH secretion, and (2) the identification by IGFALS molecular screening of this subset of patients could help in the administration of the appropriate therapy.