Gynecomastia Research Articles

Endocrine studies in boys with pubertal gynecomastia

25 XY boys aged 13 to 19 years with pubertal gynecomastia (breast development > 6 cm) were studied. According to their pubertal development, they were classified as 7 P2, 9 P3, 7 P4 and 2 P5. Results were compared to those established in normal boys at equivalent pubertal stages. The data demonstrated significantly increased plasma levels of testosterone (T) at stages P2 and 3 (p<0.001) and P4 (p<0.05), post HCG (3×1500 u) T at stage P2 (p<0.005), T-estradiol binding globulin at stage P2 (p<0.005), estrone and estradiol at stages P2 and 3 (p<0.005). Plasma prolactin levels and LH and FSH responses to LHRH were normal in all cases. The most striking fact is the overproduction of testosterone in the initial steps of puberty contrasting with the degree of virilization, the development of breast and the lack of decrease of TeBG. These data suggest a transient peripheral unresponsiveness to testosterone with subsequent conversion in estrogens.

Pubertal gynecomastia: Evidence for a possible role of the adrenal gland

As part of a longitudinal study of normal puberty, 14 boys who developed gynecomastia and 6 normal boys were followed at 6 month intervals from age 11 to 17 years. Serum levels of E1, E2, Δ4, T, DHEA, DHEA-S and PRL were measured at each interval. Mean age at onset of gynecomastia was 14.0±0.28 years, mean bone age 13.0±0.26 years and mean pubertal stage 2.9±0.13. Over the course of puberty there were no significant differences in mean levels of these hormones. However, ratios of E1/Δ4, E1/DHEA and E1/DHEA-S were consistently higher in the gynecomastia group between ages 12½ and 15 years. The same tendency was noted for these ratios for bone age years 12½ to 15 and pubertal stages 2 through 4. Conversely the ratio of E2/T remained essentially the same between the two groups. These results suggest that either adrenal secretions or increased peripheral conversion of Δ4 to E1 may play a role in the appearance of pubertal gynecomastia in normal boys.

ANDROGEN AROMATIZATION IN GYNECOMASTIA: IN VITRO STUDIES

The etiology of durable pubertal gynecomastia remains unexplained. Hormonal studies are controversial and receptor measurements inconclusive. A local conversion of androgens has been suggested. We have studied glandular and adipose fractions obtained from mastectomy of 3 adolescent boys. Microsomal suspension of the tissues was incubated with 14C testosterone or 3H-Δ4-androstenedione. Aromatization activity was measured by tritiated water formed during the incubation. Placental microsomes served as control. The identification of estrogen products was performed as follows: sodium partition, filtration on isomerase column, elution of the radioactivity corresponding to estrogens (E3) and finally gel chromatography of that extract. In placental microsomes, aromatase activity was: 0.66 pmoles/mg protein/min; in adipose tissues: 0.14 fmoles/mg protein/min; in glandular tissues: 0.13 fmoles/mg protein/min. We conclude that in vitro gynecomastic glandular tissue transforms androgen to the same extent as adipose tissue. An exaggerated local estrogen formation can most likely be excluded.

545 HETEROGENEITY OF CARDIAC FINDINGS IN NOONAN'S SYN-343 DROME: NINE CASES WITH A FAMILIAL EXAMPLE

Since Noonan's syndrome was described (J. Ped. 63:468, 1963), more than 200 cases have been reported. Although pulmonic stenosis is generally thought of as the classical cardiac finding, many such patients have cardiac anomalies other than pulmonic stenosis. Of the 9 cases seen by us, 5 are males and 4 are females. Hypertelorism and low-set ears were present in all, as was short stature with one exception. Three cases were mentally retarded. All males presented cryptorchidism. Pulmonic stenosis was found or suspected in 5 patients; transposition of great vessels in one. In a mother and daughter with the Noonan phenotype the mother had an atrial septal defect, but cardiological evaluation was refused in the daughter. A boy showed pseudoco-arctation of the aorta, bicuspid aortic valve and cardiomyopathy Another boy showed unusual bleeding at surgery, neonatal macro-somia and adolescent gynecomastia. An autosomal dominant mode of inheritance has been postulated. However, several examples of male to male transmission as well as phenotypic overlap with 45,X Turner's syndrome suggest the possibility of inheritance via the homologous regions of the X and Y chromosomes (partial sex-linkage).

Management of breast lesions in children and adolescents

The records of 207 patients evaluated and treated for breast abnormalities during a 10-yr period were reviewed. Patients ranged in age from 1 wk through 16 yr. Seventy-eight per cent were female. Operative procedures were performed in 134 patients (64%). Most common diagnoses were fibroadenoma, premature thelarche, and precocious puberty in the females, and pubertal gynecomastia in the males. Age and sex separate patients into natural subgroups. In females beyond the neonatal period, premature thelarche and precocious puberty are the most likely cause of breast enlargement. Breast biopsy is only rarely indicated for a distinct mass lesion in the prepubertal breast. Mass lesions in the breast of adolescent females require excisional biopsy. In the male, pubertal gynecomastia is the most common form of breast enlargement and only occasionally requires subcutaneous mastectomy for cosmetic and psychologic reasons. Careful evaluation of all children with breast enlargement is indicated to uncover underlying causes and to avoid unnecessary operative procedures.

Estrogens and the human male.

Literature on the role of estrogens in men is reviewed. The primary active estrogens in males and females are estradiol-17beta (E2), estrone (E1), and estriol (E3). The active constituents of serum E2 and testosterone (T) are those which are not bound by testosterone-estrogen binding globulin (TEBG). The concentration of TEBG is stimulated by estrogen and suppressed by androgens. Both E1 and E2 appear to be derived from the peripheral metabolism of T and androstenedione. The metabolism and physiological roles of estrogens in men are briefly discussed. The association of gynecomastia with puberty, cirrhosis of the liver, hyperthyroidism, chronic renal failure, refeeding gynecomastia, administration of digitalis and diuretics, neoplasms, and hypergonadotropic hypogonadism is reviewed. In older men, the ratio of free E2:T is increased. The relationship of andorgens, estrogens, and male sex behavior is briefly reviewed. Areas for future research include the mechanisms by which estrogens and androgens exert antagonistic effects on similar tissues, variations in the fractional conversionr ate of androgens to estrogens, the etiology of pubertal gynecomastia, the role of the free E2:T ratio in male social and sexual behavior, and the interrelation between behavior, nutrition, hormone secretion, and degenerative changes such as benign prostatic hyperplasia.

Letter: Pelvic inflammatory disease.

Letter: Pelvic inflammatory disease.

Gynecomastia with congenital virilizing adrenal hyperplasia (11-β-hydroxylase deficiency)

Gynecomastia with congenital virilizing adrenal hyperplasia (11-β-hydroxylase deficiency)

The relationship of concentrations of serum hormones to pubertal gynecomastia

Pubertal gynecomastia occurred in 20 to 29 boys who were followed for 24 or more months during puberty. Mean concentrations of LH, FSH, prolactin, testosterone, and estrone and estradiol were compared. Although levels did not differ between boys who developed gynecomastia and those who did not, when compared with the stage of puberty, changes were noted between mean concentrations from samples before and when gynecomastia was first noted. A significant increase of estradiol occurred with the onset of gynecomastia, while testosterone levels did not change; thus the testosterone-estradiol ratio decreased. Prolactin concentrations fell significantly with the onset of gynecomastia. These data indicate a difference of hormonal dynamics between boys with and without gynecomastia.

A LONGITUDINAL STUDY OF PUBERTY IN BOYS

A prospective study, designed to correlate serial measurements of tropic and end organ hormone levels with the physical changes of puberty, was carried out in 46 boys with physical examinations and blood samples every 6 months for 4 years. Serum levels of LH, FSH, prolactin, testosterone (T), andro-stenedione, dehydroepiandrosterone (DHA), DHA sulfate, progesterone (P), 17 OH-P, estrone, and estradiol were determined and correlated with genital and pubic hair staging criteria, appearance of axillary hair, facial hair, voice change, acne, pubertal gynecomastia, weight gain, and height increase.

Plasma testosterone and estrogens in pubertal gynecomastia.

Plasma levels of testosterone, estrone, and estradiol were measured in healthy males of all developmental stages and compared to the values of adolescents suffering from gynecomastia. There was no difference between normals and patients in their testosterone and estrogen levels, and no imbalance of the testosterone-estrogen ratio was observed in pubertal gynecomastia.

Correlation of serum follicular stimulating hormone (FSH) and luteinizing hormone (LH) as measured by radioimmunoassay in disorders of sexual development.

Serum FSH and LH levels in 104 patients with disorders of sexual development were determined by radioimmunoassay and compared with serum FSH and LH levels in 164 normal individuals.32 of 35 gonadal dysgenesis patients (ages 4.8-18.9 yr) had serum FSH levels which were elevated above the range of normal for chronological age, and 19 had serum LH levels similarly elevated. All patients with elevated serum LH levels were 11 yr of age or older. However, 8 of 10 gonadal dysgenesis patients, ages 4.8-10.9 yr, had serum FSH levels elevated above the normal range. In accord with these observations was the finding that in normal girls, serum FSH levels may increase at an earlier age than do serum LH levels (FSH, 5-8 yr of age; LH, 9-10 yr of age). These data indicate that serum FSH determinations may be helpful in diagnosing gonadal dysgenesis during childhood. Serum gonadotropin levels within the range of normal for chronological age were found in 2 of 18 girls with idiopathic isosexual precocity. The other 16 had serum FSH levels elevated above the range of normal for chronological age, and 8 also had serum LH levels similarly elevated. In all instances serum FSH and LH levels were in the range expected for the stage of sexual development. In 35 boys, ages 13.1-17.8 yr, with delayed adolescence, serum gonadotropin levels correlated with stage of sexual development and, therefore, were often less than those expected for age.8 patients with premature pubarche, 5 patients with premature thelarche, and 3 patients with adolescent gynecomastia had serum gonadotropin levels within the range of normal for chronological age.

HCC presenting as left breast swelling in a young patient: A case report

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths seen more in males than females. Risk factors include hepatitis B viral infection and aflatoxin contaminated food products. Metastatic lesions are common to the lungs, skull, para-aortic lymph node, bone, and adrenal glands. Breast metastasis are rare with few reported cases worldwide. We present a case of HCC with metastasis to the left breast. HCC should be considered as a differential in patients with unilateral gynaecomastia, particularly in patients with risk factors for chronic liver disease.

Determination of serum luteinizing hormone (SLH) by radioimmunoassay in disorders of adolescent sexual development.

Extract: Serum luteinizing hormone (SLH) values in children with various clinical disorders of sexual development are reported and compared with serum levels in normal people at ages. Values were determined by a double antibody radioimmunoassay method.In 51 patients aged 2–38 years with gonadal dysgenesis, 131 serial determinations revealed a singnificant increase in mean SLH at a prepubertal age of 2–9 years, as compared with the mean SLH in control patients in the same age range (fig. 1). Beyond 9 years of age, most values were greater then the normal levels for these ages. In 50% of the patients 16 years of age and older, cyclic estrogen therapy (1.25 mg/24 h) did not suppress the markedly elevated SLH values.In isosexual precocity, the mean of 48 SLH determinations in 34 females (2 3/12–12 10/12 years of age) was significantly increased for age in both menstruating and nonmenstruating patients (fig.2). The mean SLH for 13 values obtained from nine patients receiving Depo-provera (medroxyprogesterone) was significantly higher than of control patients of comparable age. SLH values for all patients with idiopathic sexual precocity were in normal range for stage of sexual development, irrespective of age.SLH in nine patients with premature pubarche and in eight with premature thelarche were in the normal range for age (fig.3). In 52 boys with constitutional delay of growth and adolescence, the mean of 95 serial determination was significantly lower the mean SLH for comparable ages (fig.4). The values increased as sexual development advaanced. SLH values for six patients with adolescent gynecomastia were in the normal range for age.Measurment of SLH by radioimmunoassay correlated weel with clinical status. Determination of SLH may help evaluate patients with clinical disorders of adolescent sexual development.Speculation: The measurment of gonadotropins using the radioimmunoassay technique can provide valuable information for base-lines studies. Such studies are preparatory and necessary to investigate and eluci-date the interrelation of the cerebral cortex, hypothalamus, pituitary, adrenals, and gonads. It is anticipated that centers of inhibition and secretion, under both hormonal and emotional control, will be found and that the physiolohy and pathophysiology of normal and abnormal adolescent development will be beter understood.

Prepubertal gynaecomastia in association with an interstitial-cell tumour of the testis.

SUMMARYA case of interstitial–cell tumour of the testis with pre–pubertal gynecomastia is described. The literature is reviewed and it is noted that only five of the 39 reported cases showed evidence of gynecomastia, although every case had features of precocious virilism. The danger of confusing bilateral testicular adrenal rests with interstitial–cell tumours of the testis and the diagnostic safeguards are mentioned. Malignancy has not been reported in any of these prepubertal tumours but can be excluded only by prolonged observation. The 17–ketosteroid and oestrogen excretions in this case are given, with reservations. It has been assumed that an excess of oestrogen is the cause of gynecomastia. The mechanisms of this excess production are mentioned. It is suggested that excess oestrogen might modify the psycho–sexual effects but not the physical effects of this virilising tumour.I wish to thank Dr W. J. Maelor Evans, Chief Medical Officer, Ministry of Health, Tanzania, for having given permission to publish this paper. I am greatly obliged to Drs P. Grech and P. J. Philip for their very considerable help and I wish to express my sincere thanks to them. My thanks also go to Drs J. Hamerton and M. T. Maletnlema for the photographs and to my House Surgeon, Dr G. A. S. Kombe for his assistance. 1 also wish to thank the laboratory staff of the Muhimbili Hospital who undertook the urinary steroid estimations whilst coping with a welter of routine work.

Gynecomastia in adolescent boys.

In an attempt to establish the incidence and duration of pubertal gynecomastia and to correlate the condition with other changes of puberty, 2,369 examinations were made of 1,890 normal boys in a Boy Scout camp. After excluding all obese boys, the data from 1,855 examinations were analyzed. The over-all incidence of gynecomastia was 38.7% (28.9% in Negroes). The peak incidence of 64.6% occurred in the 14- to 14 1/2-year-old group. In 27.1% of the cases it persisted through 2 seasons, and in 7.7% for 3 seasons. We recommend that adolescent gynecomastia should not be treated either surgically or with hormones, but that the boy and his parents should be assured that this is a normal phenomenon of puberty which will disappear within 1 or 2 years.

The Webster operation for gynecomastia.

The Webster operation for gynecomastia.

Gynecomastia in the Navy

Gynecomastia in the Navy