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The Merck Manual of Medical Information--Home Edition
Section 23. Children's Health Issues
Chapter 268

Hormonal Disorders

The endocrine system consists of a group of glands and organs that secrete hormones into the bloodstream. (see illustration, page 694) The major glands are the pituitary gland (controlled by the hypothalamus), the thyroid gland, the parathyroid glands, the islets of the pancreas (which produce insulin), the adrenal glands, the testes in males, and the ovaries in females. Hormones secreted by these glands control physical growth, sexual function, metabolism, and other functions. Many of the endocrine disorders that affect adults also affect children but may produce different symptoms.

Pituitary Gland Disorders

The pituitary gland, a pea-sized gland at the base of the brain, produces a number of hormones. (see illustration, page 697) Several of these hormones, such as corticotropin, thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone, control the function of other endocrine glands and stimulate these glands to produce other hormones. Growth hormone, another pituitary hormone, ensures growth during childhood.

Inadequate pituitary function is called hypopituitarism. In children, hypopituitarism may be caused by a noncancerous pituitary tumor (craniopharyngioma), an injury, or an infection, or it may have no identifiable cause (idiopathic hypopituitarism). Rarely, hypopituitarism (and diabetes insipidus [see page 703 in Chapter 144, Pituitary Gland Disorders]) occurs as part of Hand-Schüller-Christian disease, (see page 191 in Chapter 40, Infiltrative Lung Diseases) which affects small areas of bone and lungs and the function of the pituitary gland.

If the pituitary gland malfunctions before puberty, growth is delayed, sexual characteristics do not develop, and the thyroid and adrenal glands function inadequately. After puberty, pituitary malfunction can cause decreased sex drive, impotence, and shrinking of the testes.

In panhypopituitarism, the production of all pituitary hormones decreases or stops. This disorder can result when the entire pituitary gland is damaged.

Sometimes only one pituitary hormone is missing. For example, if only luteinizing hormone is missing (isolated luteinizing hormone deficiency), the testes develop and produce sperm, because these functions are controlled by follicle-stimulating hormone, but the testes do not produce enough testosterone. Testosterone is the hormone that stimulates the development of male secondary sexual characteristics, such as deepening of the voice, growth of facial hair, and maturation of the penis. Consequently, boys who have isolated luteinizing hormone deficiency do not develop these characteristics. Abnormally long arms and legs may be another symptom of this deficiency.

Growth hormone may also be deficient. In pituitary dwarfism, the pituitary gland produces inadequate amounts of growth hormone, which cause abnormally slow growth and short stature with normal proportions. Most short children, however, have normally functioning pituitary glands and are short because their growth spurt is late or their parents are relatively short.

Symptoms and Diagnosis

The symptoms of inadequate pituitary function vary depending on which hormone is deficient. For example, growth may be impaired and mental development may be poor in children who lack thyroid-stimulating hormone.

The age at which the deficiencies start also influences which symptoms develop. The effects on a fetus are different from those on a newborn or an older child.

If inadequate pituitary function seems likely, a doctor orders blood tests to measure hormone levels. Measuring the level of growth hormone is not always useful or indicative of a deficiency because the body produces the hormone in short bursts that cause its level to rise and fall quickly. To look for a deficiency of growth hormone, a doctor can measure the level of insulin-like growth factor I (IGF-I). Some pituitary hormones are measured directly; others are measured repeatedly over 1 to 2 hours after a specific stimulus is given by mouth or by injection. X-rays of the hand may be performed to determine bone age, which indicates whether the bones are still growing and how much longer they are likely to grow. A computed tomography (CT) scan or magnetic resonance imaging (MRI) of the head may detect a tumor or other structural abnormality in or near the pituitary gland.

Treatment

Children deficient in a particular pituitary hormone can be given an identical synthetic hormone as replacement. For instance, children who are short because of a deficiency of growth hormone can be given synthetic growth hormone. They may grow 4 to 6 inches in the first year of treatment; subsequent growth is slower. Growth hormone replacement is not appropriate for short children who have normal levels of growth hormone. New treatments that stimulate the body's natural production of growth hormone are being investigated.

Either the missing pituitary hormone or the hormone that is dependent on the pituitary hormone can be replaced. The latter approach is generally preferred. For example, a child who cannot produce thyroid-stimulating hormone is given thyroid hormone. Testosterone is given to a boy who cannot produce follicle-stimulating hormone and luteinizing hormone, and estrogen is given to a girl who cannot produce these two hormones.

Thyroid Gland Disorders

The thyroid gland is located in the front of the neck. It produces thyroid hormone, which controls the speed at which the body's chemical functions proceed (metabolic rate).

click on thumbnail to see full-size imageSome problems that affect the thyroid gland may also cause the gland to enlarge--a condition called goiter. A goiter may exist if the thyroid gland is underactive (producing too little thyroid hormone) or overactive (producing too much). An enlarged thyroid gland that is present at birth is called congenital goiter. Some children have Pendred's syndrome, a hereditary condition that combines deaf-mutism and congenital goiter.

Hypothyroidism results when the thyroid gland cannot produce adequate amounts of thyroid hormone for the body's needs. Symptoms of hypothyroidism in children and adolescents differ from those in adults. (see page 708 in Chapter 145, Thyroid Gland Disorders) In newborns, hypothyroidism causes cretinism (neonatal hypothyroidism), which is characterized by jaundice, poor appetite, constipation, a hoarse cry, outpouching of the navel (umbilical hernia), and slowed bone growth. If not diagnosed and treated within a few months of birth, hypothyroidism results in mental retardation. Hypothyroidism that begins in childhood (juvenile hypothyroidism) slows growth, sometimes resulting in disproportionately short limbs. Tooth development is delayed. Hypothyroidism that begins in adolescence (adolescent hypothyroidism) is similar to that in adults, except that it may delay puberty. Symptoms include a hoarse voice, slowed speech, droopy eyelids, a puffy face, hair loss, dry skin, a slow pulse, and weight gain.

In all newborns, the thyroid hormone level in the blood is routinely measured within 2 days of birth. A newborn who has hypothyroidism is promptly given thyroid hormone as replacement. This treatment prevents brain damage. Hypothyroidism that begins in childhood or adolescence is also treated with a replacement hormone.

Hyperthyroidism results from overactivity of the thyroid gland. (see page 705 in Chapter 145, Thyroid Gland Disorders) In newborns, the most common cause of hyperthyroidism is neonatal Graves' disease, a potentially life-threatening illness that can occur in infants whose mothers have or have had Graves' disease. Graves' disease, a form of hyperthyroidism, is an autoimmune disorder in which the body produces antibodies that stimulate the thyroid gland. In pregnant women, these antibodies cross the placenta and stimulate the fetus' thyroid gland. Graves' disease in the mother may result in stillbirth, miscarriage, or premature birth. In a newborn, symptoms of an overactive thyroid gland--poor weight gain, fast heart rate, high blood pressure, nervousness or irritability, vomiting, and diarrhea--may start within several days after birth. The enlarged thyroid gland (goiter) can press on the windpipe and interfere with breathing. The high thyroid hormone levels cause the fast heart rate, which can lead to heart failure. Bulging eyes, common in the adult form of the disorder, also occur in newborns. Graves' disease is potentially fatal if not recognized and treated appropriately.

Infants who receive treatment recover within weeks, although they may remain at risk of recurring illness for 6 months to a year. Persistently high levels of the thyroid-stimulating antibodies can also lead to premature closure of the bones of the skull (fontanelles), mental retardation, hyperactivity later in childhood, and slowed growth.

Hyperthyroidism is treated with a drug, such as propylthiouracil, that blocks the formation of thyroid hormones. Infants may also need treatment for heart failure. For severely affected newborns who have very high blood levels of thyroid-stimulating antibodies, an exchange blood transfusion (in which some of the newborn's blood is removed and exchanged with donated blood) may be needed to decrease the antibody levels.

Adrenal Gland Disorders

The two adrenal glands, located above the kidneys in the lower back, (see illustration, page 713) produce several types of hormones. The inner part (medulla) of each gland produces epinephrine and norepinephrine, which are responsible for the fight-or-flight reaction to danger and emotional stress. The outer part (cortex) produces aldosterone, which regulates the salt balance in the body; cortisol, which is essential for processing protein, fat, and carbohydrate; and certain male sex hormones (androgens).

In some adrenal gland disorders, cortisol and aldosterone cannot be produced, most commonly because enzymes needed for their production are missing. The hypothalamus detects the low levels of these hormones and stimulates the pituitary gland, which then tries to stimulate the adrenal glands to produce enough cortisol and aldosterone. The adrenal glands enlarge by as much as 10 to 20 times their normal weight because of the constant stimulation by the hypothalamus and pituitary gland, yet they remain unable to produce cortisol and aldosterone. However, they may produce large amounts of other hormones, such as androgens, which lead to masculinization.

Symptoms and Diagnosis

A deficiency of adrenal hormones causes various symptoms, depending on which hormone is deficient. If aldosterone production is low, too much sodium is excreted in the urine, resulting in low blood pressure and increased blood levels of potassium. If cortisol production is severely deficient, especially if aldosterone production is blocked, life-threatening adrenal failure can occur within days to weeks of birth, along with low blood pressure, a rapid heartbeat, and malfunction of many organs.

A deficiency of androgens before birth leads to inadequate growth of the genitals in male infants--an abnormal urethral opening, a small penis, and small testes--a condition called male pseudohermaphroditism. (see page 1237 in Chapter 254, Birth Defects) Girls who are deficient in adrenal hormones appear normal at birth but do not undergo puberty or menstruate.

An overabundance of adrenal hormones also produces symptoms. When a female fetus is exposed to high levels of androgens early in pregnancy, the genitals develop abnormally. The external genitals are masculinized (female pseudohermaphroditism). (see page 1237 in Chapter 254, Birth Defects) If a female fetus is exposed to high androgen levels before the 12th week of pregnancy, the labia may fuse, and a single opening for the urethra and vagina develops. After the 12th week of pregnancy, the main effect is enlargement of the clitoris, giving the appearance of a penis. The ovaries, uterus, and other internal reproductive organs develop normally. Male fetuses are essentially unaffected by high androgen levels.

In young boys, high androgen levels cause accelerated growth. However, because the bones mature faster than normal and stop growing too soon, final height is shorter than normal.

Adrenal gland disorders can be diagnosed by measuring levels of adrenal hormones in blood or urine samples.

Treatment

Treatment requires giving a synthetic hormone to replace the one the adrenal glands cannot produce. Once the deficient hormone is replaced, the hypothalamus and pituitary gland stop stimulating the adrenal glands, which then stop producing excessive amounts of other hormones. Cortisol deficiency is treated with a corticosteroid, such as hydrocortisone or prednisone; for a severe deficiency, which is an emergency, treatment with fluids, sodium, and other minerals may also be required. Aldosterone is used to treat aldosterone deficiency, and testosterone is used to treat androgen deficiency. Blood pressure is measured frequently because if the levels of these hormones are too high or too low, they can disrupt salt and water regulation in the body and thus affect blood pressure. Growth is checked twice a year, and bone age is determined every year by taking an x-ray of the hand. With sufficient amounts of hydrocortisone, growth is normal. Girls who have been exposed to high androgen levels often need to have surgical reconstruction of the external genitals to create a normal vaginal opening for functional and cosmetic reasons.

Testicular Disorders

The testes have two main functions: synthesizing testosterone, the primary male sex hormone (androgen), and producing sperm. The testes may be underactive--a condition called male hypogonadism--because the pituitary gland does not secrete the hormones that stimulate the testes or because there is a problem within the testes. When the testes are underactive, androgen production is deficient. Growth and sexual development may be retarded, sperm production is low, and the penis may be small.

Symptoms

The symptoms vary depending on the age at which the androgen deficiency begins. In a male fetus, an androgen deficiency before the 12th week of pregnancy causes incomplete development of the genitals. The urethra may open on the underside of the penis instead of at its end, or a male infant may develop female genitals (male pseudohermaphroditism). (see page 1237 in Chapter 254, Birth Defects) If an androgen deficiency develops later in pregnancy, a male fetus may have an abnormally small penis (microphallus) or testes that do not descend fully into the scrotum.

Androgen deficiency in childhood results in incomplete sexual development. An affected boy retains a high-pitched voice and has poor muscle development for his age. The penis, testes, and scrotum are underdeveloped. Pubic and underarm hair is sparse, and the arms and legs are abnormally long.

Androgen deficiency after puberty can cause a weak sex drive, impotence, and subnormal strength in boys. The testes may be shriveled, the skin around the eyes and lips may be finely wrinkled, body hair may be sparse, and bones may be weak. If the androgen deficiency is caused by a problem within the testes, breasts may develop (gynecomastia).

Klinefelter's syndrome occurs in about 1 out of 700 male births. It is caused by a chromosomal abnormality. Boys with Klinefelter's syndrome usually have two X chromosomes and one Y chromosome (XXY instead of the normal XY), although some have even more copies of the X chromosome. Generally, this syndrome is not detected until puberty, when an affected child does not undergo normal sexual maturation.

Boys with Klinefelter's syndrome have small testes (less than ¾ inch across the scrotum) that are firm and filled with fibrous tissue. The breasts are usually somewhat enlarged, and the skeletal proportions are abnormal, with the legs longer than the torso and head. Antisocial behavior may occur. Also, the risk of diabetes mellitus, chronic lung disease, varicose veins, hypothyroidism, and breast cancer is increased. The diagnosis is made by analyzing chromosomes in cells from a blood sample.

The vanishing testes syndrome (bilateral anorchia) occurs in about 1 out of 20,000 males. The testes are presumably present during early development but are resorbed by the body before or after birth. Without testes, these children cannot produce testosterone or sperm and therefore do not develop male secondary sexual characteristics at puberty and are infertile.

Congenital absence of Leydig's cells (cells in the testes that normally produce testosterone) leads to the development of ambiguous genitals (male pseudohermaphroditism), because not enough testosterone is produced to stimulate the fetus to develop normal male genitals. Affected children are genetically male.

click on thumbnail to see full-size imageCryptorchidism is a condition in which one or both testes remain in the abdomen, where they are formed in the fetus. Usually, the testes descend into the scrotum shortly before birth. At birth, about 3 percent of boys have cryptorchidism, but in most of them, the testes descend on their own by 1 year of age. If the testes do not descend, surgery is necessary to reposition the testes in the scrotum to prevent infertility or torsion (painful twisting of the testis on its spermatic cord) (see page 1062 in Chapter 229, Disorders of the Penis, Prostate, and Testes) and to reduce the risk of testicular cancer. This surgery should be performed before a boy is 5 years old.

Noonan's syndrome results in small testes that produce too little testosterone. Other symptoms may include webbing of the neck, low-set ears, droopy eyelids, short stature, shortened fourth (ring) fingers, a high-arched palate, and heart and blood vessel abnormalities. Blood tests detect low levels of testosterone and high levels of two pituitary hormones, luteinizing hormone and follicle-stimulating hormone.

Myotonic dystrophy is a muscle disease that includes testicular failure in 80 percent of the cases. The testes are replaced by fibrous tissue and usually do not produce sperm. Other symptoms are muscle weakness and wasting, balding, mental retardation, cataracts, diabetes mellitus, hypothyroidism, and abnormally thick skull bones.

Diagnosis

Various tests are used to identify which testicular disorder is present. First, a doctor examines the boy's penis and testes to see if they are normally developed for his age. Blood levels of testosterone are measured. Because the function of the testes is regulated by the pituitary gland and hypothalamus, levels of luteinizing hormone and follicle-stimulating hormone also may be measured. In boys who have gone through puberty, a sample of semen is analyzed to determine its volume and sperm count.

A small tissue sample of the testis is rarely needed to diagnose hypogonadism. However, such a sample is generally analyzed if a boy has normal-sized testes but no sperm, as determined by a semen analysis.

Chromosomal analysis may be needed, especially when Klinefelter's syndrome is suspected. Generally, chromosomes in cells from a blood sample are analyzed.

Treatment

If the pituitary gland is not producing luteinizing hormone and follicle-stimulating hormone, which stimulate the testes, testosterone supplementation is given. If a boy has psychologic adjustment problems because a delay in puberty has resulted in incomplete sexual development, he can be given testosterone injections for 3 months. This treatment causes some masculinization without stunting growth.

Testosterone deficiency can be treated with injections of testosterone once or twice a month. The hormone is given by injection because this method is safer than taking it by mouth and fewer doses are needed. Testosterone can also be given in a skin patch applied daily. Treatment with testosterone restores the balance in the body and stimulates growth, sexual development, and fertility. Major side effects include fluid retention, acne, and, occasionally, temporary breast development (gynecomastia).

No cure is available for chromosomal abnormalities, but testosterone may be helpful in treating the symptoms.

Surgery to repair an abnormally developed penis is often possible. Artificial testes can be inserted into the scrotum for cosmetic purposes, but they do not produce sperm or hormones. Surgery to move undescended testes into the scrotum usually enables the testes to function normally.

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