Is There a Connection Between Corticosteroids and Weight Gain?

Congenital adrenal hyperplasia (CAH) is a more common autosomal recessive disease caused by a congenital defect in the enzymes required during the synthesis of corticosteroids. Insufficient cortisol synthesis reduces blood concentration. Due to the negative feedback effect, the pituitary gland secretes an increase in adrenocorticotropic hormone (ACTH), which leads to hyperplasia of the adrenal cortex and excessive secretion of cortisol precursor substances such as 11-deoxycortisol and adrenal androsterone . A series of clinical symptoms occurred. There are many differences in the incidence of CAH among different races.

Basic Information

English name

congenital adrenal cortical hyperplasia

Visiting department

Pediatrics

Common causes

Congenital deficiency of corticosteroid synthase

Common symptoms

Virilization, loss of salt manifestation (poor appetite, vomiting, lethargy and slow weight gain)

Causes of congenital adrenal hyperplasia

Due to a congenital defect in the enzymes required for corticosteroid synthesis. Six types currently recognized are: 21-hydroxylase deficiency, 11-hydroxylase deficiency, 17-hydroxylase deficiency, 3-hydroxydehydrogenase deficiency, corticosterone methyloxidase deficiency, and congenital lipid Qualitative adrenal hyperplasia.

Clinical manifestations of congenital adrenal hyperplasia

21-hydroxylase deficiency and 3-hydroxydehydrogenase deficiency are virilizing and salt-losing. The emergence of hyponatremia, hyperkalemia, circulatory failure, and salt loss crisis can occur within weeks after birth and are life-threatening. According to the severity of clinical manifestations, it is divided into typical and atypical. Typical include (lost salt, simple virilization). It reflects the general law of 21-hydroxylase deficiency to varying degrees.

Loss of salt

It is the type with the most severe clinical manifestations. In addition to virilization caused by excessive androgen, there is a clear manifestation of salt loss. Due to the complete lack of 21-hydroxylase activity, the 21-hydroxylation process of progesterone was severely impaired, resulting in insufficient aldosterone secretion. Deficiency of aldosterone causes sodium loss in the kidneys, colon and sweat glands. Insufficient cortisol secretion caused by 21-hydroxylase deficiency also aggravates the effect of aldosterone deficiency. Simultaneous defects in mineralocorticoid and glucocorticoid are more likely to cause shock and severe hyponatremia.

In addition, the accumulation of steroid precursors will directly antagonize the mineralocorticoid receptor, aggravating the manifestation of mineralocorticoid deficiency, especially in patients who are not receiving treatment. Progesterone is known to have a clear anti-mineral corticosteroid effect. There is no evidence that 17-hydroxyprogesterone has a direct or indirect effect on mineralocorticoids.

The clinical manifestations of salt loss can be nonspecific symptoms such as poor appetite, vomiting, lethargy, and slow weight gain. Severe patients usually develop adrenal crisis manifestations such as hyponatremia, hyperkalemia, hyperreninemia, and hypovolemic shock within 1 to 4 weeks after birth. Without proper and timely diagnosis and treatment, adrenal crisis can lead to death. The problem is particularly acute for males who are desalinated, because they do not have genital hermaphroditism in female infants, and doctors are not alert to the diagnosis of CAH until dehydration and shock occur in these children. With the increase of age, the sodium balance ability of CAH cases with severe salt loss in infants and young children will be improved, and aldosterone synthesis will be more effective.

2. Purely masculine

Compared with the salt-loss type, with the exception of no severe salt-loss, the clinical manifestations of other androgen excess are roughly the same. It accounts for 1/4 of classic cases.

3. Non-classical

Previously known as late-onset 21-hydroxylase deficiency, patients had only clinical manifestations of mild androgen excess. Female patients were born with normal or mild clitoral hypertrophy of the external genitalia and no genital hermaphroditism. Adrenal steroid precursors are only slightly elevated, and 17-hydroxyprogesterone levels are between heterozygous carriers and classic cases. After the ACTH1 ~ 24 excitement test (at 60 minutes), 17-hydroxyprogesterone is generally above 10ng / ml. If only the basic serum 17-hydroxyprogesterone level is measured, the patient will be missed. Symptoms and signs of mild androgen vary widely, and many affected individuals will be asymptomatic. The most common symptoms are early onset of pubic hair in children, or severe cystic acne, hirsutism, polycystic ovary, thin menstruation, and even amenorrhea in young women. Female patients with non-classical 21-hydroxylase deficiency also have reduced fertility, to a lesser extent than classic patients.

Congenital adrenal hyperplasia

1.ACTH1-24 Excitation Test

For patients with classic 21-hydroxylase deficiency, the diagnosis is generally clear based on clinical manifestations and basic 17-OHP (17-hydroxyprogesterone). When the serum 17-OHP basal value does not provide sufficient diagnostic evidence, it is necessary to perform an ACTH (Adrenocorticotropic Hormone) 1-24 Excitation Test. In general, the diagnosis of non-classical 21 hydroxylase deficiency is considered when the 17-OHP level is above 10 ng / ml at 60 minutes. Each laboratory should determine its own diagnostic criteria based on 21 hydroxylase deficiency heterozygous carriers and normal people.

2. Check for loss of salt

An increase in PRA (plasmin renin activity) values, especially an increase in the ratio of PRA to 24-hour urinary aldosterone, indicates a disorder in aldosterone synthesis. In circulating blood, ACTH, 17-0HP, and progesterone levels are high, but these indicators are also elevated in cases with normal aldosterone levels, so that the biochemical performance of purely virilized patients who are not well controlled may be confused with the salt-loss type. Mineralocorticoid therapy can inhibit the adrenal glands in these patients and help distinguish between the two. Ideally, plasma and urinary aldosterone levels should be related to PRA and sodium balance, which can help to accurately determine the clinical type. When analyzing the significance of renin levels, it is important to note that normal neonates are higher than older children.

3. Sex chromosome examination

Women's nuclear chromatin is positive, men's are negative, women's chromosome counts are XX, and men's are XY, which can determine their true sex.

4. Type B ultrasound

The female genitalia of pseudohermaphroditism with congenital adrenal hyperplasia is normal, and ultrasound and intubation X-ray can show the uterus and fallopian tubes. B-ultrasound, CT, and MRI are helpful in identifying adrenal hyperplasia or tumor. Congenital hyperplasia is bilateral adrenal enlargement, while tumors are mostly unilateral isolated masses, which may have calcification. Liquefaction chambers can be formed due to bleeding and necrosis.

5. Other

Female with adrenal cortical hyperplasia and pseudohermaphroditism, the genitourinary sinus can be examined with urethroscopy, and the vaginal opening can be seen in the cervix. If the family has 21-hydroxylase deficiency, polymerase chain reaction (PCR) and amniotic membrane HLA Typing and DNA analysis.

Diagnosis of congenital adrenal hyperplasia

Non-classical male cases diagnosed after puberty usually show acne or infertility. But most are diagnosed in family screenings without any symptoms. In rare cases, cases of non-classical 21-hydroxylase deficiency in men present with unilateral testicular enlargement. In boys, it is difficult to clearly define the line between classic virilized cases and non-classical cases. Because the level of 17-hydroxyprogesterone is a continuous process between mild and severe cases, the clinical manifestations of androgen excess in men are less pronounced than in women.

Treatment of congenital adrenal hyperplasia

Glucocorticoids should be applied early after early diagnosis.

1. Timely correct water and electrolyte disorders (for children with salt loss)

For intravenous rehydration, physiological saline can be used. For metabolic acidosis, 0.45% sodium chloride and sodium bicarbonate solution can be used. Avoid using potassium-containing solutions. Severe salt loss type requires intravenous infusion of hydrocortisone. If low sodium and dehydration are not easy to correct, intramuscular injection of deoxycorticosterone acetate (DOCA) or oral hydrocortisone can be used. After dehydration is corrected, glucocorticoids are changed to oral And long-term maintenance, while oral sodium chloride. The amount can be adjusted appropriately according to the condition.

2. Long-term treatment

(1) Glucocorticoids Glucocorticoid treatment can on the one hand compensate for the lack of cortisol secreted by the adrenal glands, on the other hand can inhibit the release of too much ACTH, thereby reducing the excessive production of androgens, so it can improve symptoms such as virilization and precocious puberty To ensure the normal growth and development of children.

(2) Mineralocorticoids Mineralocorticoids can cooperate with glucocorticoids to further reduce the secretion of ACTH. Can be taken orally with fludrocortisone. After the symptoms improve, the dose is gradually reduced and the drug is discontinued. Can cause hypertension due to long-term application. 0.1mg fludrocortisone is equivalent to 1.5mg hydrocortisone, and its amount should be calculated in the amount of cortisol to avoid excessive cortisol.

During the course of corticosteroid treatment, blood 17-hydroxyprogesterone or urine 17-ketosteroids should be monitored. Salt-loss type should also monitor blood potassium, sodium, and chlorine. Regulate the dosage of hormones. In children under stress (such as: infection, overwork, surgery, etc.) or adolescence, the dose of glucocorticoids should be increased by 1.5 to 2 times than usual.

3. Surgical treatment

Male patients do not need surgery. Partial clitoris or orthopedics should be performed at 6 months to 1 year of age for female bisexual children.