Dr Ayed Alanezi Senior spescialist Pediatric endocrine Gynecomastia Dr Ayed Alanezi Senior spescialist Pediatric endocrine

Definition Gynecomastia is defined as the presence of palpable breast tissue in males It is common in normal individuals Particularly in the newborn period, at puberty, and in the elderly

Gynaecomastia Term is derived from Greek words: Gynae (female) mastos(breast)

Lobes of female breast A healthy female breast is made up of 12–20 sections called lobe

Male breast Nipple Rudimentary blind ducts Extending to short distance rarely beyond the boundary of the areola Without lobule formation Fat Fibrous tissue

Gynecomastia The benign proliferation of glandular breast tissue in males.

Gynecomastia Glandular tissue is symmetrically distributed around the areolar-nipple complex No terminal alveolar development

Gynecomastia It can generally be detected when the glandular tissue is >0.5 cm (0.2 inches) in diameter May be tender to palpation early in the course. bilateral

Pseudogynaecomastia Breast prominence due solely to Fat deposition without glandular proliferation on exam fingers will not meet any resistance until they reach the nipple  

Pathogenesis of gynecomastia

Hormones that affect the breast Estrogens Prolactin Androgens

Hormones that affect the breast Estrogens Ductal hyperplasia, elongation and branching Fibroblast proliferation Increase in vascularity

Hormones that affect the breast Source of Estrogens Peripheral conversion of androgens Aromatase enzyme Present in muscles, skin and adipose tissue

Hormones that affect the breast Prolactin:  Decrease androgen receptors Increase estrogen and progesterone receptors

Hormones that affect the breast Androgens: Inhibit breast prolofiration

Physiological gynecomastia Neonate Puberty Old age

The neonatal period In neonates, 60 to 90% have transient gynaecomastia Due to transplacental transfer of maternal estrogens Breast tissue gradually regresses over a 2 to 3 week period. It usually regresses completely by the end of first year.

Puberty Transient gynaecomastia may occur in up to 60% With a peak onset between 13 to 14 years Followed by an involution that is generally complete by 16 to 17 years

Pathological gynecomastia Occurrence outside the neonatal or pubertal age groups Rapid progression Enlargement >4 cm (1.6 inches) in diameter Persistence for more than 2 years or after age 17 years

Etiologies of gynecomastia Idiopathic : 25% Physiologic gynecomastia : 25% Medication or substance use: 10-25% Cirrhosis: 8% Hypogonadism: 10% Tumors: 3% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1%

Management The majority of cases of physiologic pubertal gynecomastia resolve spontaneously within a year of onset Most patients can be managed with reassurance and observation. Adjunctive psychotherapy may be beneficial for adolescents with psychosocial consequences

Pharmacologic therapy The US Food and Drug Administration (FDA) has not approved any drug for this indication. Accepted indications: physiologic gynecomastia > 4 cm in diameter rapidly progressive Associated with embarrassment that interferes with normal daily activities

Pharmacologic therapy Anti-estrogens Tamoxifen raloxifene Aromatase inhibitors block the estrogen receptor:

Pharmacologic therapy Neither tamoxifen nor raloxifene has been associated with significant side effects in the majority of patients. Tamoxifen has been used in doses of 10–20 mg/d Raloxifene at a dose of 60 mg/d for 3–9 months.

Aromatase inhibitors Anastrozole was successfully used to reduce the estrogen excess and breast enlargement in a patient with Familial aromatase excess Patient with a feminizing Sertoli cell tumor Hypogonadal men with gynecomastia induced by testosterone therapy.

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Approach to gynecomastia Breast enlargement  The size, timing of onset, and duration of breast enlargement Breast size ≥4 cm and rapid progression may indicate greater hormone imbalance and a pathologic cause. Beyond the neonatal period,

Approach to gynecomastia Pubertal status and age pubertal gynecomastia is most common during mid-puberty prepubertal gynecomastia is always pathologic Associated symptoms Mild pain galactorrhea Beyond the neonatal period,

Approach to gynecomastia Review of systems Family history  Medications Psychosocial effects  •Hypogonadism •Hyperthyroidism •Liver disease •Renal disease

Complete Physical Exam Body mass index (BMI) Sexual maturity rating, Testes and Genitalia Careful breast exam Stigmata of liver and kidney disease Evaluate for hyperthyroidism

Laboratory tests RFT LFT TSH LH, FSH, Estradiol, Testosterone HCG Prolactin Androstenedione, DHEAs

Imaging US and mammogram for any eccentric or discrete mass

APPROACH TO DIAGNOSIS Laboratory and imaging studies usually are not necessary in adolescents with clinical features typical of physiologic gynecomastia

Etiologies of pathological gynecomastia Idiopathic : 25% Physiologic gynecomastia : 25% Medication or substance use: 10-25% Cirrhosis: 8% Primary hypogonadism: 8% Secondary Hypogonadism: 2% Tumors: 3% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1% An increase in aromatase activity Increase in the sex hormone–binding globulin concentration

Etiologies of pathological gynecomastia Idiopathic : 25% Physiologic gynecomastia : 25% Medication or substance use: 10-25% Cirrhosis: 8% Primary hypogonadism: 8% Secondary Hypogonadism: 2% Tumors: 3% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1% Medications used in disease management Declining nutrition Chronic illness

Etiologies of pathological gynecomastia Idiopathic : 25% Physiologic gynecomastia : 25% Medication or substance use: 10-25% Cirrhosis: 8% Increase in the sex hormone–binding globulin concentration Reduced clearance of estrogens Primary hypogonadism: 8% Secondary Hypogonadism: 2% Tumors: 3% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1% )

Etiologies of pathological gynecomastia Idiopathic : 25% Physiologic gynecomastia : 25% Medication or substance use: 10-25% Cirrhosis: 8% Primary hypogonadism: 8% Secondary Hypogonadism: 2% Tumors: 3% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1% Klinefelter syndrome Cryptorchidism Anorchia Enzyme defects of testosterone production Infections Trauma

Approach to gynecomastia Review of systems Family history  Medications Psychosocial effects  •Hypogonadism •Hyperthyroidism •Liver disease •Renal disease

Etiologies of pathological gynecomastia Idiopathic : 25% Physiologic gynecomastia : 25% Medication or substance use: 10-25% Cirrhosis: 8% Primary hypogonadism: 8% Secondary Hypogonadism: 2% Tumors: 3% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1% Testicular Leydig-cell or Sertoli-cell tumor. (hCG)–secreting tumor Adrenal tumor Androstenedione DHEAs

Etiologies of pathological gynecomastia Idiopathic : 25% Physiologic gynecomastia : 25% Medication or substance use: 10-25% Cirrhosis: 8% Primary hypogonadism: 8% Secondary Hypogonadism: 2% Tumors: 3% Hyperthyroidism: 1.5% Chronic renal insufficiency: 1% Congenital Gonadotropin-releasing hormone deficiency Acquired Pituitary tumor (hyperprolactinemia)