A case of mild partial androgen insensitivity syndrome in a juvenile boy.

Androgen insensitivity syndrome (AIS) is a rare disorder with X-linked recessive inheritance in 46 XY patients. The clinical manifestations vary between patients, especially regarding external genitalia development. Herein, the case of AIS in a 13-year-old male, who was born with hypospadias and presented to the hospital with gynaecomastia that had developed from 8 years of age, is reported. No micropenis, cryptorchidism or bifid scrotum were found. Testis volume was 12 ml on both sides. His testosterone and luteinizing hormone levels were normal compared with sex- and age-adjusted reference range. His bone age was approximately 13 years according to Greulich-Pyle assessment. Sequence analysis of the androgen receptor (AR) gene revealed a mutation (c.2041A>G) in exon 4, a novel mutation site in the AR gene. Prediction analysis suggested this to be a disease-causing variant. A milder clinical presentation and normal hormone levels in cases of partial AIS might differ from the usually reported signs and symptoms. A diagnosis of AIS should not be ignored in teenage patients who present with gynaecomastia and hypospadias, but normal hormone levels.

Unraveling the Enigma: A Rare Case of Recurrent Idiopathic Gynecomastia in an Adolescent.

Gynecomastia presents as abnormal hypertrophy of mammary tissue in males that is typically asymptomatic and usually does not require intervention. Gynecomastia responds well to medical and surgical treatment, when necessary, with low recurrence rates. The authors report an atypical case of recurrent idiopathic unilateral gynecomastia first presenting in an adolescent male. Physical examination, hormonal, and oncologic evaluations were normal. After subcutaneous mastectomy with liposuction and treatment with Tamoxifen at 19 years old, his unilateral gynecomastia recurred over the course of 3 years, requiring a second surgery. Furthermore, we review the literature for recurrent gynecomastia after surgical management to examine prevalence and risk factors.

Gynecomastia.

Enlargement of breasts among boys is termed gynecomastia. This could be due to an alteration in the androgen-estrogen ratio along with the effects of other hormones including growth hormone, insulin like growth factor 1, prolactin, and other factors affecting aromatase enzyme. The common causes of gynecomastia are pubertal gynecomastia, obesity, drugs and hypogonadism. Several other diseases including liver or renal failure, thyrotoxicosis, Klinefelter syndrome, tumors and environmental pollutants can cause gynecomastia. History and clinical examination will help formulate targeted investigations and management. The factors to be evaluated in these include examination of breasts and testes, in addition to other parts of systemic examination. Treatment of underlying disorders can improve gynecomastia, such as use of testosterone in hypogonadism. Some boys may not need any intervention as gynecomastia may resolve on its own. Medical management is useful in simple gynecomastia. Tamoxifen has been tried successfully in adolescents with gynecomastia. Other drugs including clomiphene, danazol, letrozole and anastrozole have not been consistently useful in this age group. In severe chronic gynecomastia, surgery is the treatment of choice.

Idiopathic fibroadenoma in an elderly man.

A fibroadenoma within the male breast remains a rarely diagnosed entity. Though it was once believed that a fibroadenoma could not exist within a male breast, this has now been demonstrated as incorrect by several reported cases. Most have been in individuals with gynecomastia. There are only a handful of reported cases of men with a diagnosed fibroadenoma in the absence of gynecomastia. We describe a man in his 80s with a left breast fibroadenoma and no features of gynecomastia or hormonal alterations. Based on our findings, we suggest that for men of all ages presenting with a breast lesion, a fibroadenoma remains a possible diagnosis.

Unilateral breast enlargement in males during adolescence (10-19 years): Review of current literature and personal experience.

Idiopathic unilateral breast enlargement (UBE) in males is a, commonly overlooked, diagnosis of exclusion that requires careful history, meticulous physical examination, and pertinent laboratory studies to exclude the possible pathologic causes. The aims of the present update are to review the current literature on UBE in subjects during adolescent age (10-19 years) in 18 cases, and to report the personal experience in 13 adolescents referred to our unit during the last four decades. In total, our survey and personal experience include 31 UBE cases, 10 of whom (32.2 %) being idiopathic or familial gynecomastia (GM). In 3/31 (9.6%) UBE was due to breast sarcoma/ carcinoma; one patient (11-years old) had a 5-year history of painless lump in the right breast, which increased gradually in size followed by bloody nipple discharge. In the personal cases of 13 adolescents, a moderate to marked UBE was secondary to: treatment with androgens (2 ß-thalassemic patients with hypogonadism), high estrogen/androgen ratio in 2 Klinefelter syndrome patients, peripheral aromatization of androgens in 1 patient with non-classical 21-hydroxylase deficiency (NC-21-OH-D). One patient had subareolar hematoma due to injury. In 2 patients (15,3%) marked UBE was due to cystic lymphangioma (histologically proved). Furthermore, 5 patients were characterized as idiopathic UBE In clinical practice, the persistence of UBE for long period before diagnosis necessitates attention and further evaluation. Underlying causes should be treated, when possible, while surgery can be offered to patients with persistent or atypical signs and/or symptoms of UBE. For the optimal management of this condition, better collaboration between primary care physician and specialists is mandatory.

A 14-Year-Old Saudi Boy with Gynecomastia, Cushing Syndrome, Large-Cell Calcifying Sertoli Cell Tumor of the Testis, and Carney Complex.

BACKGROUND Carney complex (CNC) is a rare multiple neoplasia syndrome with autosomal dominant inheritance. CNC is frequently misdiagnosed owing to its diverse clinical characteristics. We reported the case of a 14-year-old Saudi boy with a history of gynecomastia, Cushing syndrome, large-cell calcifying Sertoli cell tumor of the testis, and CNC. CASE REPORT The patient was referred to the pediatric endocrine clinic for evaluation of bilateral slow progressing gynecomastia for 1-year duration. His clinical examination revealed lentigenes, bilateral diffuse breast enlargement (consistent with Tanner stage III), and asymmetrical testicular enlargement, more on the left side. Other systemic examinations were unremarkable. The initial blood workup showed elevated estradiol level with unsuppressed cortisol after an overnight 1-mg dexamethasone suppression test. Breast ultrasound (US) confirmed true gynecomastia. Testicular US revealed microcalcification and the testicular biopsy confirmed diagnoses of large-cell calcifying Sertoli cell tumor (LCCSCT). A 2-step dexamethasone suppression test showed a paradoxical rise in serum and urine cortisol levels, which are characteristic for PPNAD. LCCSCT and PPNAD are 2 major criteria fulfilling a diagnosis of CNC. The gene test showed heterozygous mutation in the PRKAR1A gene, which is diagnostic for CNC. The patient underwent bilateral mastoplasty and was planned for radical left orchiectomy. CONCLUSIONS Gynecomastia and LCCSCT can be presenting features of CNC, which mandates careful, thorough clinical examination and tailored investigation to reach a diagnosis.

[Christmas article: Goose breast caused by unusual circumstances].

This case report investigate a 61-year-old healthy man who, during a Christmas goose-shooting, got repeated punches on the right breast region, owing to a defective shotgun stock. The initial suggilations and haematomas disappeared in three weeks, but after three months a tender enlargement of the periareolar area developed. Mammography and sonography showed typical right gynaecomastia. History, andrologial examination and biochemistry disclosed no explanation. It was concluded that a traumatic aetiology of the gynaecomastia was most likely. During the next year, the clinical signs regressed somewhat, but control sonography showed leftovers of ductal tissue, and the bird shooter has become reconciled with his "goose breast".

Management of Gynecomastia and Male Benign Diseases.

Gynecomastia is a common benign breast disease involving abnormally increased mammary gland tissue that can affect men of all ages. It is usually due to a hormonal imbalance without a definitive underlying cause (idiopathic), or secondary to medications/drugs, systemic disorders, or malignancy. Gynecomastia is often self-limiting, and its management is watchful waiting. Other male benign breast diseases, such as cysts, lipomas, seromas, infections, and pseudoangiomatous stromal hyperplasia, should be worked up in a similar manner and often require surgical drainage or excision.

[Gynécomastia. Management of diagnosis and therapy. Apropos of 148 cases]. / Gynécomastie : actualisation des données diagnostiques et thérapeutiques. À propos de 148 patients.

Gynecomastia is the most frequently breast lesion in males. 148 patients (mean age 24,7 years) operated in our department were reviewed with a mean follow-up of five years. Gynecomastia occurred most frequently during puberty (77,7 %), was bilateral (86,5%) and idiopathic (89,9%). The size of the enlargement was evaluated according to Simon's-classification based on breast-volume and skin-redundancy. 17 (11,5%) stage 1, 77 (52%) stage 2A, 32 (21,6%) stage 2B, 22 (14,9%) stage 3. Clinical examination and mammography determined the consistency of gynecomastia: adipose or firm. 4 different surgical managements were used: 17 (11,5%) subcutaneous mastectomies, 4 (2,7%) liposuctions, 110 (74,3%) liposuctions associated with subcutaneous mastectomy, 17 (11,5%) total mastectomy. All techniques gave good morphologic results. Nonetheless, the authors recommend the combination «liposuction and subcutaneous mastectomy¼, as this technique presents many advantages: small intraoperative blood loss, good skin redraping, short hospital stay, complete histologic examination of the material removed.

An Approach to Gynecomastia in Primary Care Clinics.

Gynecomastia is a more common finding in primary care clinics than is recognized. Because this finding can be easily overlooked, appropriate investigation and management often are missed. The workup of gynecomastia is highly individualized, based on the patient's presentation and related factors. It should be guided by thorough history taking and physical examination. Unless the patient has associated symptoms, or there is suspicion for an underlying clinical disorder causing the gynecomastia, the patient need not be investigated further. A breast ultrasound is not routinely recommended. Gynecomastia is a benign finding that will spontaneously regress in most patients; however, patients who are concerned with their physical appearance can be treated either medically or surgically. Patients who have had gynecomastia for more than 1 year tend to have fibrosis, which may be more difficult to treat. Management of gynecomastia is highly patient centered, following a detailed discussion about treatment goals and should be started early. Gynecomastia is not considered a premalignant condition; routine screening is not cost-effective, and imaging studies should be pursued only if physical examination findings suggest malignancy.

Posterior ischaemic opticus neuropathy after radical cystectomy.

In this case report, a 58-year-old male with comorbidities of BMI 41 kg/m2, hypertension and diabetes type 2 underwent radical cystectomy. The operation was performed in 30-degree Trendelenburg and lasted > 7 hours with a total blood loss of 850 ml. The patient presented with painless bilateral vision loss upon awakening. MRI, CT and CT angiography of the cerebrum was performed and revealed arteriosclerosis and hypophysis adenoma. Neurological and ophthalmic consults were performed. Three weeks post-operatively, bilateral papillary atrophy was present, and posterior ischaemic optic neuropathy was confirmed.

Assessing the impact of a gynaecomastia assessment and treatment infographic in primary care in Greater Manchester.

INTRODUCTION: Men with gynaecomastia are routinely referred to breast clinics, yet most do not require breast surgical intervention. The aim of this study was to assess the impact of a novel point-of-care gynaecomastia decision infographic in primary care on the assessment, management and referral practices to tertiary breast surgical services. METHODS: A study was carried out of male patient referrals from primary care in Greater Manchester to a tertiary breast centre between January and March in 2018-2020. Referral patterns were compared before and after the infographic went live in general practices in Greater Manchester in January 2020. Data were collected for gynaecomastia referrals, including aetiology, investigation and management. RESULTS: In total, 394 men were referred to a tertiary breast centre from 163 general practices, of which 271 (68.8%) had a diagnosis of gynaecomastia. Use of the decision infographic by primary healthcare providers was associated with a decrease in male breast referrals with gynaecomastia (79.6% to 62.0%). Fewer gynaecomastia patients were referred with a benign physiological or drug-related cause after implementation of the infographic (52.2% vs 41.8%). Only 10 (3.7%) patients with gynaecomastia underwent breast surgery during the study period. CONCLUSION: Implementation of a gynaecomastia infographic in primary care in Manchester was associated with a reduction in gynaecomastia referrals to secondary care. We hypothesise that implementation of the infographic into primary care nationally may potentially translate to hundreds of patients receiving more specialty-appropriate referrals, improving overall management of gynaecomastia. Further study is warranted to test this hypothesis.

An atypical presentation of a pathogenic STK11 gene variant in siblings not fulfilling the clinical diagnostic criteria for Peutz-Jeghers Syndrome.

OBJECTIVES: To report an atypical presentation of a pathogenic STK11 gene variant in siblings not fulfilling the clinical diagnostic criteria for Peutz-Jeghers Syndrome (PJS). CASE PRESENTATION: Two siblings presented with prepubertal gynaecomastia and bilateral macro-orchidism, without mucocutaneous pigmentation or gastrointestinal symptoms. There was no family history of PJS. Sibling 1 had unilateral gynaecomastia. Sibling 2 had bilateral gynaecomastia, advanced bone age and bilateral testicular microlithiasis, not indicative of a large-cell calcifying Sertoli cell tumour. Genetics revealed a paternally inherited heterozygous pathogenic STK11 variant (910C>T) in both siblings. The diagnosis was confirmed following the identification of multiple intestinal polyps in their father. CONCLUSIONS: Prepubertal gynaecomastia and prepubertal macro-orchidism (testicular enlargement without virilisation), always warrant endocrinological investigation, with PJS being an important differential diagnosis. Children may not fulfil the clinical criteria for a diagnosis of PJS at presentation. Genetic testing and gastroenterological investigation of parents may aid diagnosis.

Association of gynecomastia with antidiabetic medications in older adults: Data mining from different national pharmacovigilance databases.

OBJECTIVE: Gynecomastia is a benign proliferation of the glandular breast tissue in men and is generally caused by a decrease in androgen and an increase in estrogen. Diabetes has been reported to be a risk factor for lowering androgen levels. Moreover, lowered androgen levels are more common in older men. In the present study, we aimed to evaluate the signals for gynecomastia in older men on antidiabetic medications. MATERIALS AND METHODS: A disproportionality analysis was performed to detect the signals for antidiabetic drug-associated gynecomastia in the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER), using the reporting odds ratio (ROR) and information component (IC). RESULTS: Among 8 classes of medications for diabetes, a signal was detected only for dipeptidyl peptidase-4 (DPP-4) inhibitors (ROR: 1.90, 95% confidence interval (CI): 1.27 - 2.83; IC: 0.84, 95% CI: 0.26 - 1.42) in the FAERS. Regarding individual drugs, ROR and IC signals were detected for sitagliptin (ROR: 2.37, 95% CI: 1.48 - 3.79; IC: 1.12, 95% CI: 0.44 - 1.79) and vildagliptin (ROR: 3.34, 95% CI: 1.39 - 8.08; IC: 1.26, 95% CI: 0.07 - 2.44) in the FAERS and only for sitagliptin (ROR: 4.84, 95% CI: 1.92 - 12.2; IC: 1.48, 95% CI: 0.24 - 2.73) in the JADER. CONCLUSION: This study showed an association between DPP-4 inhibitor use and gynecomastia in older men with diabetes. Further pharmacoepidemiological studies are warranted to verify this finding.