Investigation of androgen receptor gene CAG repeat length polymorphism in pubertal gynecomastia

Objectives Androgen receptor gene CAG repeat, AR (CAG)n, polymorphism is thought to have an effect on male reproductive functions and a relationship between long AR (CAG)n and decreased androgenic activity has been shown. Therefore, we hypothesized that in adolescents with long AR CAG repeat the prevalence of pubertal gynecomastia (PG) will be higher and we aimed to investigate the association between AR (CAG)n polymorphism and PG in Turkish adolescents. Methods Adolescents with PG between 11 and 19 years of age were enrolled as the study group and healthy individuals without a history of PG, who were at least 14 years of age and Tanner 4 or 5 were enrolled as the control group. The AR (CAG)n length was detected by direct DNA sequencing analysis and reproductive hormones were measured by standardized analyses. Results The mean AR (CAG)n was 22.3 ± 2.6 (mean ± SD) in the PG group (n=101) and 21.9 ± 3.1 (mean ± SD) in the control group (n=88) (p=0.276). The adolescents with short AR (CAG)n had lower body mass index standard deviation scores (BMI SDS) compared to the adolescents with intermediate and long repeat numbers (p=0.029). Conclusions The results of this study showed a lack of direct association between AR (CAG)n and PG. However, the significant relationship between the AR (CAG)n quartiles and BMI SDS suggests that long AR (CAG)n might cause PG indirectly. Further studies are needed to better clarify this relationship.

A clinical case of aromatase excess syndrome associated with 15Q21.2 duplication

Aromatase excess syndrome (SIA) is a rare autosomal dominant disease caused by increased extraglandular conversion of androgens to estrogens. SIA is characterizedby early gonadotropin-independent hyperestrogenemia, causing pre-pubertal gynecomastia in boys and premature isosexual development in girls. Adults patients have short stature, due to the early closure of epiphyses because of hyperestrogenemia. Women usually have macromastia, endometrial hyperplastic processes and the late onset of menopause. In men, there is a moderate decrease of gonadotropins, leading to secondary hypogonadism. SIA in children can be suspected on a combination of the clinical picture of an excess of estrogens, increased levels of estrogens with low levels of gonadotropins after the exclusion of an estrogen-producing tumor. The frequency of occurrence of SIA is unknown, due to the rarity of the disease and the complexity of its molecular and genetic verification. In this article, we describe a clinical case of a 10-year-old patient with a late diagnosis of aromatase overactivity syndrome caused by a 15q21.2 microduplication of the CYP19A1 gene, and conduct a brief review of the literature.

Aromatase excess syndrome in a Chinese boy due to a novel duplication at 15q21.2

Background Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by CYP19A1 overexpression. Clinical manifestations of AEXS include pre- or peri-pubertal gynecomastia, advanced bone age and compromised adult height. Case presentation Here we report an 8-year-old boy diagnosed with AEXS by chromosomal array that revealed a 1.1 Mb novel de novo duplication at 15q21.2, with a predicted final height of 157.4 cm. We prescribed letrozole and growth hormone (GH) to maximize his linear growth. Without further bone age advancement, his height increased from 137.7 cm to 144 cm after an 8-month treatment period. Conclusions We identified a novel duplication at 15q21.2 in AEXS, and found that aromatase inhibitor (AI) plus GH might provide a better growth-promoting approach for AEXS patients.

Partial androgen insensitivity syndrome presenting as pubertal gynecomastia: clinical and hormonal findings and a novel mutation in the androgen receptor gene

Summary Pubertal gynecomastia is common, can be seen in 65% of the adolescent boys and is considered physiological. It is thought to be due to transient imbalance between the ratio of testosterone and estradiol in the early stages of puberty. It resolves in 1–2 years and requires no treatment. However, more persistent and severe pubertal gynecomastia is less common and can be associated with pathological disorders. These can be due to diminished androgen production, increased estrogen production or androgen resistance. We report a case of persistent pubertal gynecomastia due to partial androgen insensitivity syndrome (PAIS), classical hormone findings and a novel mutation in the androgen receptor (AR) gene. Learning points: Laboratory testing of follicle-stimulating hormone (FSH), leutinizing hormone (LH) and testosterone for pubertal gynecomastia is most helpful in the setting of undervirization. The hormonal finding of very high testosterone, elevated LH and estradiol and relatively normal FSH are classical findings of PAIS. Gynecomastia due to PAIS will not resolve and surgery for breast reduction should be recommended.

Impaired dynamic thiol/disulfide homeostasis in pubertal gynecomastia

Background The aim of the study was to evaluate the dynamic thiol/disulfide homeostasis (TDH) with a new method in patients with pubertal gynecomastia and also to investigate the relationship between sex hormones. Methods Thiol/disulfide homeostasis, involving native thiol (SH), disulfide (SS) and total thiol (SS + SH), was evaluated between 20 adolescent boys with gynecomastia in mid-puberty and 50 healthy adolescents, who were matched for age, body mass index (BMI) and pubertal stage. The correlations of total serum testosterone (TT) and estradiol (E2) levels with the oxidative parameters were also determined. Results No significant difference was found between the total thiol, native thiol, disulfide/native thiol and disulfide/total thiol ratios of the patient and control groups. The mean disulfide concentrations, disulfide/native thiol and the disulfide/total thiol ratios were statistically significantly higher in the patient group than in the controls. A positive correlation was found between the E2 and native thiol levels, also there was a negative correlation between the E2 and disulfide levels. TT was negatively correlated with both native thiol and disulfide levels. All these did not statistically differ between the patients with unilateral and bilateral gynecomastia. Conclusions There was an impaired thiol/disulfide homeostasis in patients with pubertal gynecomastia. According to this result, we can postulate that oxidative stress may be an etiologic factor that contributes to initiation and/or progression of gynecomastia.

Oestrogen and progesterone receptors in bilateral and unilateral pubertal gynecomastia – is treatment with anti-oestrogens justified?

ABSTRAKTWstęp: Ginekomastia pokwitaniowa (GP) jest łagodnym powiększeniem gruczołów piersiowych u mężczyzn, które występuje u ponad połowy chłopców w wieku pokwitaniowym. W niejasnej etiologii ginekomastii nie ma również wyjaśnienia przyczyny przypadków jednostronnej GP. Najczęstszą metodą leczenia przetrwałych przypadków jest zabieg operacyjny, obciążony ryzykiem powikłań.Celem badania było porównanie występowania receptorów estrogenowych (ER) i progesteronowych (PR) w jednostronnej i obustronnej GP z oceną możliwego klinicznego zastosowania wyników.Materiały i metody: Przeprowadzono retrospektywną analizę dokumentacji 30 pacjentów operowanych z powodu GP z wtórną oceną immunohistochemiczną występowania ER i PR w wyciętych preparatach. Porównano przypadki jednostronne (8) z obustronnymi (22).Wyniki: Receptory estrogenowe i progesteronowe były obecne we wszystkich przebadanych preparatach. Stwierdzono statystycznie istotnie wyższy odsetek jąder komórkowych z ER i PR w materiale obustronnych GP niż w przypadkach jednostronnej patologii. Została stwierdzona dodatnia korelacja pomiędzy występowaniem obu typów receptorów. Wiek pacjentów w chwili operacji nie był istotnym czynnikiem.Wnioski: Receptory estrogenowe i progesteronowe mogą odgrywać istotną rolę w etiologii ginekomastii, szczególnie w przypadkach obustronnych. Uzyskane wyniki stanowią punkt wyjścia do dalszych badań nad różnicami pomiędzy jednostronną a obustronną ginekomastią. Randomizowane badania prospektywne oceniające skuteczność terapii GP lekami antyestrogenowymi mogłyby przyczynić się do ustalenia farmakologicznej alternatywny dla leczenia chirurgicznego.

Clinical and Etiological Aspects of Gynecomastia in Adult Males: A Multicenter Study

Objectives. To evaluate the characteristics of presentation, biochemical profile, and etiology of gynecomastia in adults. Methods. Medical records of 237 men aged 18-85 years with gynecomastia were evaluated. Results. Highest prevalence of gynecomastia was observed between 21 and 30 years (n = 74; 31.2%). The most common presenting complaints were aesthetic concerns (62.8%) and breast pain (51.2%). 25.3% of the subjects had a history of pubertal gynecomastia. 56.5% had bilateral gynecomastia. 39.9% were overweight and 22.8% were obese. The etiology could not be identified in 45.1% of the cases; the most frequent identified causes were anabolic steroids consumption (13.9%), hypogonadism (11.1%), and use of pharmaceutical drugs (7.8%). Patients with bilateral gynecomastia had a longer history of disease, higher BMI, and lower testosterone levels. Conclusions. Patients with gynecomastia presented more often with aesthetic concerns and secondarily with breast pain. The most frequent final diagnosis was idiopathic gynecomastia, whereas the most frequent identified etiologies were anabolic steroids consumption, hypogonadism, and use of pharmaceutical drugs. Despite the low frequency of etiologies such as thyroid dysfunction or adrenal carcinoma, we emphasize the importance of a thorough assessment of the patient, as gynecomastia may be the tip of the iceberg for the diagnosis of treatable diseases.