What is female pseudohermaphroditism? If it is a hermaphroditism, why is “she” or “he” defined as “female”? In female pseudohermaphroditism, the sex chromosomes are XX, the sex chromatin is positive, and the gonads are ovarian, so what are the deformities? Usually, the malformation is in different degrees, especially in the vulva, that is, the essence is female, but there are different degrees of masculinity in various parts of the body. There are various causes of female pseudohermaphroditism, and 21-hydroxylase deficiency is one of the most common types. In the following, we will introduce the situation of this female pseudohermaphroditism in detail. In the human body, there is a class of hormones called steroid hormones, including aldosterone, progesterone, cortisol, estrogen, androgen, etc. All these hormones have a common “ancestor”, which is cholesterol. Yes, it is the substance that raises your blood lipids, but it is essential to the human body. Cholesterol undergoes a series of changes to become the above-mentioned steroid hormones, but how is the cholesterol change achieved? It takes some specific enzymes to help. There is an enzyme called 21-hydroxylase, which is necessary to help convert cholesterol into aldosterone and cortisol. Originally there were three major paths for the conversion of cholesterol to go to —- aldosterone, cortisol, and androgens. However, the decrease or lack of 21-hydroxylase makes the conversion of cholesterol to aldosterone and cortisol obstructed, so cholesterol has only one way to go, and that is to be converted to androgens. But what if the body lacks aldosterone and cortisol? Usually, when the human body has less of these hormones, our body will report to the brain, and the brain will give orders to increase the production of aldosterone and cortisol, and the human body will immediately increase the production of these lacking substances, but now the assembly line for manufacturing aldosterone and cortisol is broken, and the brain does not know that the raw materials for producing aldosterone and cortisol are still piling up, and too many precursors are crowding to another path – the conversion to androgens. The excess precursors flock to another path – to be converted into androgens, resulting in increased production of androgens and causing a series of physical changes: for example, the reproductive system has ovaries, but the uterus and vagina are dysplastic, and the external genitalia have different degrees of masculinity and other manifestations of gender dysphoria. Second, the type of the disease To talk about the typology, we should first introduce a substance mentioned earlier —- aldosterone. This substance helps the body retain water and salt and exclude potassium ions. The disease is divided into two types according to the degree of aldosterone deficiency in the body. 1, simple masculinization type compensatory type This type of patient has a mild degree of 21-hydroxylase deficiency, no obvious aldosterone deficiency, no clinical manifestations of salt loss, and androgen increase is the main manifestation. Specific clinical manifestations: 1. Abnormalities of external genitalia and secondary sexual characteristics. Female patients are born with an enlarged clitoris resembling a male penis, and abnormal openings of the urethra and vagina, both of which often merge into a common opening urogenital sinus, presenting different degrees of hypospadias similar to that of males, and in severe cases, completely resembling the opening of the male urethra, with the fusion of the labia majora on both sides resembling the male scrotum. Due to the action of large amounts of androgens, pubic hair can appear in female children at the age of 2-5 years; axillary hair and gradually growing body hair can be seen at the age of 4-7 years, and pubic hair is distributed in a male rhombus shape, reaching the umbilicus, the lower anal circumference, and the outer groin on both sides, with rough skin and even acne; laryngeal nodes appear at the age of 8-10 years, and the voice is low. In primary amenorrhea, the secondary sexual characteristics of women do not develop, they have a male physique with well-developed bones and muscles, a strong and powerful body, and undeveloped breasts, often with short limbs and a short and stout “Little Rex” physique, which some people jokingly refer to as just like a “lightweight weightlifter”. The company’s main goal is to provide a comprehensive range of products and services to the public. The effect of early androgens accelerates protein synthesis and bone development, so that children with this condition grow faster than their peers before the age of 10, often developing earlier than children of the same age and having a higher stature, but after the age of 10, due to the early healing of the epiphysis, growth is slow, and finally the stature will be shorter than normal. 3. Low resistance. Due to the lack of cortisol, a product of another pathway of cortisol cholesterol, the stress capacity is reduced and the resistance is low. 4. Skin pigmentation. The deficiency of aldosterone and cortisol prompts the brain to compensate for the secretion of ACTH, a hormone that stimulates the body to produce aldosterone and cortisol, and another role of this hormone is to promote the secretion of melanocytes, making the patient’s skin color black or mucous membrane pigmentation. The more severe the deficiency, the more obvious the pigmentation.5 High androgens also lead to reduced fertility.6 High concentrations of androgens in the blood lead to hypoplasia of the gonads, that is, the ovaries and uterus, which are commonly seen under ultrasound: unilateral ovaries or poorly displayed, an absent or infantile uterus, and a narrow vagina with an abnormal opening. The vagina is narrow and has an abnormal opening, often covering or co-opting the urethra in the form of a “genitourinary sinus”.7 The secretion of aldosterone and cortisol is insufficient, and the brain gives instructions to increase the secretion of aldosterone and cortisol, so that the adrenal glands, the main organ producing these two hormones, often show functional enlargement and need to be distinguished from pheochromocytoma. Laboratory indicators: abnormally high testosterone, which can reach the level of adult men, significantly increased urinary 17-ketosteroids and urinary triol excretion in 24 hours, increased FSH, and normal or decreased cortisol concentration. 2, masculinization with salt loss type of loss of compensation This type of patient has a more severe 21-hydroxylase deficiency and an obvious lack of aldosterone, clinically, in addition to the compensatory type of androgen increase, but also accompanied by aldosterone reduction caused by salt loss and electrolyte disorders, salt loss and electrolyte disorders to maintain the internal composition and concentration of various ions changes, and beyond the scope of the body’s own regulation This type of disorder is usually seen in the first two years of life. The most common symptoms are refusal to eat, restlessness, vomiting, diarrhea, lethargy, and even shock, often leading to the death of the child due to electrolyte disorders. The incidence of the disease is not low, but few survive. Survivors tend to prefer salt and this electrolyte disorder gradually disappears after the age of 3 years. In addition, the patient has the same signs as the purely masculine form, with slow growth within the first 1-2 years, rapid growth and late onset of early healing of the epiphysis compared to the purely masculine form. Laboratory examination: basically the same as the simple type, urinary 17-ketosteroid and urinary triol excretion is obviously increased, but 17-hydroxysteroid excretion is decreased, accompanied by the manifestation of low blood sodium and high blood potassium. 3.Atypical Also known as late-onset, insidious or mild, it is due to slight deficiency of 21-hydroxylase. The clinical manifestations of this disease vary, and the age of onset varies. Masculine manifestations do not appear until childhood or adolescence. Patients may present with delayed age at menarche, primary amenorrhea, hirsutism and infertility. Treatment 1. Cortisol therapy, with cortisol hormone treatment, feedback inhibits the increased production of compensatory androgens due to the lack of cortisol and aldosterone. 2. Further endocrine therapy, monitors and adjusts the hormone imbalance to achieve optimal growth and puberty. Proper medication can gradually transform the patient’s deformed body into a normal female, with coordinated proportions, fine skin, reduced hair, female secondary sexual characteristics, and feminized body. 3.Surgical treatment. In early stage, clitoral reduction surgery is feasible, and in adulthood, hair removal, facial contouring, laryngeal node surgery, vaginal external orifice surgery, vaginal enlargement and vaginoplasty are feasible.