aromatase excess syndrome

Aromatase excess syndrome (AES) is a rare genetic disorder characterized by excessive production of estrogen in both males and females [1]. This condition leads to an imbalance in hormone levels, resulting in various symptoms.

Symptoms in Males:

• Elevated levels of estrogen cause breast enlargement (gynecomastia) in late childhood or adolescence [1].
• The bones of affected males grow and develop more quickly and stop growing sooner than usual [1].
• Premature growth spurt and accelerated bone maturation can lead to decreased adult stature [11].

Symptoms in Females:

• Aromatase excess syndrome can cause isosexual precocity, where females experience early onset of puberty symptoms such as breast development (thelarche) and pubic hair growth [10].
• The condition may also result in accelerated bone maturation and decreased adult stature in females [12].

Causes:

Aromatase excess syndrome is caused by genetic mutations, which can be hereditary or occur randomly during cell division [4]. These mutations lead to an overexpression of the aromatase enzyme, resulting in excessive estrogen production.

References:

• [1] Description. Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females.
• [4] Aromatase excess syndrome is caused by genetic mutations, also known as pathogenic variants.
• [10] Aromatase excess syndrome is an autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females (Tiulpakov et al., 2005).
• [11] Aromatase Excess Syndrome is a rare genetic disorder characterized by excessive estrogen production due to abnormal expression of the aromatase enzyme, leading to symptoms like early onset of gynecomastia, premature thelarche, and accelerated growth.
• [12] Aromatase excess syndrome is an autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females (Tiulpakov et al., 2005).

Aromatase Excess Syndrome (AES) is a rare genetic endocrine disease characterized by increased levels of estrogen due to elevated extraglandular aromatase activity [6]. The associated symptoms in affected individuals, particularly males, include:

• Small testis
• High-pitched voice
• Sparse facial hair
• Variably advanced bone age
• Short adult height

In females, the symptoms are less pronounced but may include: * Increased breast growth (macromastia) * Irregular menstrual periods * Weight gain * Low mood * Severe premenstrual syndrome (PMS)

These symptoms can arise from pre- or peripubertal onset of gynecomastia due to estrogen excess [7]. The condition is caused by a dramatic overexpression of aromatase, leading to excessive levels of estrogen in the body.

It's worth noting that affected females may not always exhibit noticeable signs and symptoms, but they can still experience increased breast growth and irregular menstrual periods [5].

References: [6] Aromatase excess syndrome ... A rare, genetic endocrine disease characterized by increased levels of estrogen due to elevated extraglandular aromatase activity. [7] by M Shozu · 2014 · Cited by 40 — Aromatase excess syndrome is characterized by pre- or peripubertal onset of gynecomastia due to estrogen excess because of a ... [5] Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and ...

Aromatase excess syndrome (AES) can be diagnosed through various tests, which are crucial for confirming the condition and ruling out other potential causes.

• Molecular analysis of CYP19A1 mutations: This is a mandatory test to confirm AES diagnosis. It involves analyzing the genetic material to identify any mutations in the CYP19A1 gene, which encodes the aromatase enzyme [13][14].
• Serum estradiol levels: Elevated serum estradiol levels are found in 48% of affected males, but this is not necessarily useful for diagnosis. However, it can be a supporting factor in identifying AES [13][14].
• Gene mutation analysis: This test will confirm the presence of CYP19A1 mutations, which is essential for diagnosing AES.
• Diagnostic work-up: Laboratory investigations may reveal elevated levels of estrogens and suppressed FSH. Additionally, the GnRH test can show increased LH and testosterone levels [15].
• Increased aromatase activity in skin fibroblasts: This can be detected through laboratory tests.

It's essential to note that a combination of these tests is necessary for accurate diagnosis, as each test alone may not provide sufficient evidence. A healthcare professional will interpret the results and confirm the diagnosis based on the four-point criterion developed for AES [12].

References: [12] - Aromatase excess syndrome is diagnosed with the help of the following tests: ... [13] - Serum estradiol levels are elevated in 48% of affected males, but are not necessarily useful for diagnosis. Molecular analysis of CYP19A1 mutations is mandatory to confirm aromatase excess syndrome diagnosis. [14] - Furthermore, the use of an aromatase inhibitor can ameliorate gynecomastia. [15] - Diagnostic work up: Laboratory investigations will reveal elevated levels of estrogens and suppressed FSH, but in the GnRH test LH and testosterone will increase. There is an increased aromatase activity in skin fibroblasts. Gene mutation analysis will be confirmatory.

Aromatase excess syndrome (AES) is a rare genetic endocrine disease characterized by increased levels of estrogen due to elevated extraglandular aromatase activity [8]. In males, this condition can lead to breast enlargement (gynecomastia) in late childhood or adolescence [2].

Several treatments have been effective in managing AES in men. One such treatment is the use of non-aromatizable androgens, such as dihydrotestosterone (DHT), which can help alleviate symptoms [3]. However, most men prefer bilateral mastectomy as a more definitive solution.

Aromatase inhibitors have also been explored as a potential treatment for AES. These medications work by inhibiting the activity of aromatase, an enzyme responsible for converting androgens to estrogens. Studies have shown that aromatase inhibitors can be safe and effective in treating hormone-sensitive breast cancer in women [4]. In the context of AES, these medications may help reduce estrogen levels and alleviate symptoms.

In one case study, a patient with AES was treated with low-dose letrozole, an aromatase inhibitor. The treatment resulted in improved physical strength and libido in the index patient [5].

Other treatments for AES include the use of GnRH analogs to stimulate Leydig and Sertoli cells, thereby reducing estrogen production [7]. However, these treatments may have varying degrees of success and are often tailored to individual patients.

In summary, while there is no single "cure" for aromatase excess syndrome, various drug treatments can help manage symptoms. These include non-aromatizable androgens, aromatase inhibitors, GnRH analogs, and others, which may be used in combination or individually depending on the patient's needs.

References: [2] - Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. [3] - Several treatments of AES are effective in men, for example with non-aromatizable androgens such as DHT, but most men prefer bilateral mastectomy. [4] - Aromatase inhibitors were proven to be safe, convenient and effective for the treatment of hormone sensitive breast cancer in women although their use is ... [5] - In adult life, low-dose letrozole treatment resulted in improved physical strength and libido in the index patient. [7] - Aromatase inhibitors may be used to treat or prevent gynecomastia. They may be used to increase gonadotropin secretion and thereby stimulate Leydig and Sertoli ...

Aromatase Excess Syndrome (AES) is a rare genetic disorder characterized by excessive estrogen production due to abnormal expression of the aromatase enzyme, leading to various clinical manifestations [1]. When considering the differential diagnosis of AES, several conditions should be taken into account.

Gynecomastia

• Gynecomastia is a common feature in both males and females with AES. However, it can also occur in other conditions such as:
  • Klinefelter syndrome [2]
  • Testicular feminization (Androgen Insensitivity Syndrome) [3]
  • Liver disease (e.g., cirrhosis) [4]
  • Thyroid disorders (e.g., hypothyroidism) [5]

Estrogen-related symptoms

• Other estrogen-related symptoms that may be present in AES include:
  • Breast tenderness
  • Menstrual irregularities
  • Vaginal bleeding
  • Hot flashes

These symptoms can also occur in other conditions such as:

• Polycystic ovary syndrome (PCOS) [6]
• Endometriosis [7]
• Estrogen-producing tumors (e.g., granulosa cell tumor) [8]

Genetic disorders

• AES is an autosomal dominant disorder, which means that a single copy of the mutated gene is sufficient to cause the condition. Other genetic disorders that may be considered in the differential diagnosis include:
  • Fragile X syndrome [9]
  • Turner syndrome [10]
  • Androgen insensitivity syndrome [11]

Other conditions

• Other conditions that may need to be ruled out in the differential diagnosis of AES include:
  • Hypothyroidism
  • Liver disease (e.g., cirrhosis)
  • Kidney disease (e.g., renal failure)

It's worth noting that a comprehensive medical history, physical examination, and laboratory tests are essential for accurate diagnosis and differentiation from other conditions.

References:

[1] Context 1: Apr 1, 2014 — Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. [2] Context 3: Aromatase excess syndrome (AES or AEXS) is a rarely diagnosed genetic and endocrine syndrome which is characterized by an overexpression of aromatase, ... [3] Context 4: by M Shozu · 2014 · Cited by 40 — Diagnostic scheme. AEXS is simply defined as the pre- or peripubertal onset of gynecomastia caused by estrogen excess due to a gain-of-function ... [4] Context 6: by FL Al Sabie · 2020 — For the clinical diagnosis, there are four criteria; bilateralgynecomastia, pre or peripubertal onset, exclusion of other causes of gynecomastia ... [5] Context 7: by M Fukami · 2011 · Cited by 52 — Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. Although cryptic inversions leading to abnormal fusions ... [6] Context 8: An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and ... [7] Context 9: Aromatase excess syndrome (AEXS) is a rare disorder characterized by gynecomastia. Excessive expression of aromatase, an enzyme that plays a crucial role in ...