report aromatase deficiency in a male patient

Aromatase deficient males experience a normal growth into adulthood. With a very low level of circulating estrogen (<7pg/mL), resulting in a higher level of FSH and LH in the blood. Elevated level of androgens do not contribute to harmonic skeletal muscle growth like estrogen, thus, patients exhibits eunuchoid body habitus.

Full Answer

What is aromatase deficiency in men?

Human aromatase deficiency is a very rare syndrome characterized by congenital estrogen deprivation that is caused by loss-of-function mutations in CYP19A1, which encodes aromatase. Here, we review the presentation, diagnosis and treatment of aromatase deficiency in men to provide useful advice for …

What are key laboratory findings in aromatase deficiency?

Key Laboratory Findings in Aromatase Deficiency Mother (pregnant woman): Severely low maternal serum estradiol and estriol Remarkably elevated maternal serum testosterone Infancy/Early Childhood (girls): Elevated FSH and undetectable serum estradiol Multi-cystic ovaries (ultrasound) Puberty (girls): Multi-cystic ovaries (ultrasound)

What are the phenotypic features of aromatase mutations in females?

These mutations in the aromatasegene in females have given rise to certain common phenotypic features, e.g., congenital genital ambiguity, pubertal failure, hypergonadotropic hypogonadism and multicystic ovaries.

How does aromatase deficiency affect follicular growth?

Aromatase deficiency or estrogen resistance, however, do not prevent uncontrolled follicular growth, which seems to be mediated primarily by gonadotropins.(29, 30)

How do you know if you have aromatase deficiency?

In adulthood, symptoms include virilisation, absent of breast development, primary amenorrhea and infertility, and multicystic ovaries. Other symptoms include hypergonadotropic hypogonadism, polycystic ovaries, hypoplastic ovaries and tall stature.

What is aromatase deficiency?

Aromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of the male sex hormone testosterone.

What does aromatase do to males?

Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty.

What causes aromatase deficiency?

Aromatase deficiency results from autosomal recessive inheritance of mutations in the CYP19A1 gene. It gives rise to ambiguous genitalia in 46,XX fetuses. At puberty, affected girls have hypergonadotropic hypogonadism, do not develop secondary sexual characteristics, and exhibit progressive virilization.

How is aromatase deficiency treated?

Adult men should be treated immediately upon diagnosis: daily transdermal administration of up to 50 µg of estradiol (serum estradiol at 40 pg/ml) for 6-9 months to complete skeletal maturation. Upon epiphyseal closure, estradiol replacement may be reduced to 25 µg daily.

Where is aromatase found in males?

Gonad. The gonad is the chief source of aromatase in adults of both sexes. In men, the source of androgens is the Leydig cells that are outside of the seminiferous tubules cells. The sertoli cells express aromatase and convert testicular androgens to estrogens (40).

Do men need aromatase?

In males, the main source of estrogen comes from the conversion of testosterone to estradiol (E2) by the enzyme aromatase, which indicates the crucial role of this enzyme in defining sex hormone levels in men.

How can men increase aromatase?

Get Enough Zinc: In addition to strengthening your immune system, zinc plays an important role in controlling the action of aromatase on your testosterone. Zinc can be found in some foods like pumpkin seeds, but a supplement is typically the best way to increase your zinc intake.

Is there a blood test for aromatase?

A blood test that is able to detect mutations in the estrogen receptor (ER) gene ESR1 in circulating cancer DNA and thus provide early warning of resistance to aromatase inhibitors has been developed by investigators at The Institute of Cancer Research (London,UK).

What is the role of aromatase?

Aromatase is an enzyme involved in the conversion of androgen (such as testosterone) to estrogen (such as 17β-estradiol). It is also a very effective therapeutic target for the treatment of endocrine-responsive breast cancer.

What is the function of aromatase enzyme?

Aromatase is the enzyme responsible for the conversion of androgens to estrogen in many tissues, including the gonads and adipocytes.

Where is aromatase found?

In both sexes, aromatase is found in a number of extragonadal sites, including bone, breast, adipose tissue and brain. This tissue-specific expression of aromatase maintains tight local control over the synthesis and action of oestrogens.

What is aromatase enzyme?

Aromatase, or CYP19A1, is a type II cytochrome CYP450 enzyme that catalyzes the conversion of C19 androgens to C18 estrogens. Its crucial role in both female and male physiology has been deduced from human and animal studies using aromatase inhibitors, genetically altered mice, and patients with aromatase deficiency. The latter is an extremely rare disorder. Its diagnosis is particularly difficult in males, who go through puberty normally and therefore usually present as adults with elevated testosterone, bone abnormalities (e.g., delayed bone age and low bone mass), and metabolic syndrome. In this report, we describe a new case of a male patient with aromatase deficiency harboring a known mutation who presented with less severe clinical and biochemical features.

Where is aromatase located?

Aromatase, or CYP19A1, is a type II cytochrome P450 enzyme located in the endoplasmic reticulum [1]. It catalyzes the conversion of C19 steroids testosterone, 16alpha-hydroxytestosterone, and androstenedione to C18 steroids 17beta-estradiol, estriol, and estrone respectively [1]. The CYP19A1 gene is located on chromosome 15q21.2 and encodes a roughly 500 amino acid long protein that is expressed throughout the body, including the placenta, gonads, adipose tissue, bone, cartilage, skin, brain and vascular smooth muscle [1], [2]. The distinct phenotypes of patients with aromatase deficiency as well as aromatase knockout mice have confirmed a crucial role of aromatase in both female but also male physiology. While the first publications of aromatase expression and its regulation date back to the 1970s, the first case of a patient with aromatase deficiency was only reported in 1991 in a female infant who exhibited signs of a 46, XX disorder of sexual development. In addition, the patient's mother showed increased signs of virilization, elevated androgen levels, and low serum and urinary estrogen levels during the third trimester of her pregnancy [3].

What is the specific nature of mutation c.628G > A?

We conclude that the specific nature of mutation c.628G > A, which can potentially result in several different forms of the aromatase enzyme, may lend an explanation to the variable phenotypes associated with this particular genotype.

Abstract

Human aromatase deficiency is a very rare syndrome characterized by congenital estrogen deprivation that is caused by loss-of-function mutations in CYP19A1, which encodes aromatase. Here, we review the presentation, diagnosis and treatment of aromatase deficiency in men to provide useful advice for clinical management of the condition.

Key Points

Aromatase deficiency in men often remains undiagnosed until adulthood, which results in delayed and insufficient treatment

Introduction

Human aromatase deficiency is a very rare syndrome that is caused by naturally occurring loss-of-function mutations in CYP19A1, which encodes aromatase. These mutations lead to abnormal protein products that result in the dysfunction of the aromatase enzyme and, consequently, in a complete lack of estrogen synthesis.

Clinical presentation

Clinical manifestations of aromatase deficiency ( Box 1) are believed to occur at puberty—mainly during late adolescence—when the effects of estrogen deprivation on bone become evident ( Box 2 ).

Diagnosis

Aromatase deficiency has few symptoms during childhood and/or adolescence ( Box 2) and is characterized by a slow progression during adulthood; therefore, the condition usually remains overlooked until adulthood, 20 which often results in a delayed diagnosis ( Box 2 ).

Treatment

Estrogen replacement therapy should be started as soon as the clinical diagnosis of aromatase deficiency has been reached in an adult man; the genetic diagnosis provides further information that is useful to choose appropriate treatment. The treatment approach should take into account the known effects of estrogen in men.

Follow-up

The most useful parameters for monitoring the adequacy of estrogen treatment are BMD and serum levels of estradiol, gonadotropins (especially LH) and testosterone. 12, 16, 17 The estrogen dosage can be considered optimal when all these parameters remain within the normal range. 16

What is aromatase enzyme?

Aromatase, or CYP19A1, is a type II cytochrome CYP450 enzyme that catalyzes the conversion of C19 androgens to C18 estrogens. Its crucial role in both female and male physiology has been deduced from human and animal studies using aromatase inhibitors, genetically altered mice, and patients with aromatase deficiency. The latter is an extremely rare disorder. Its diagnosis is particularly difficult in males, who go through puberty normally and therefore usually present as adults with elevated testosterone, bone abnormalities (e.g., delayed bone age and low bone mass), and metabolic syndrome. In this report, we describe a new case of a male patient with aromatase deficiency harboring a known mutation who presented with less severe clinical and biochemical features.

What is the specific nature of mutation c.628G > A?

We conclude that the specific nature of mutation c.628G > A, which can potentially result in several different forms of the aromatase enzyme, may lend an explanation to the variable phenotypes associated with this particular genotype.

What happens if you don't have aromatase?

A shortage of functional aromatase results in an inability to convert androgens to estrogens before birth and throughout life. As a result, there is a decrease in estrogen production and an increase in the levels of androgens, including testosterone. In affected individuals, these abnormal hormone levels lead to impaired female sexual development, ...

What is the role of aromatase in fetal development?

This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth and blood sugar levels. During fetal development, aromatase converts androgens to estrogens in the placenta, which is the link between the mother's blood supply and the fetus. This conversion in the placenta prevents androgens from directing sexual development in female fetuses. After birth, the conversion of androgens to estrogens takes place in multiple tissues.

Why are men abnormally tall?

Affected individuals are abnormally tall because of excessive growth of long bones in the arms and legs.

What is autosomal recessive gene?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Can aromatase deficiency cause high blood sugar?

Males and females with aromatase deficiency can have abnormally high blood sugar (hyperglycemia) because the body does not respond correctly to ...