Pituitary Dwarfism

Overview

Dwarfism refers to a number of conditions that cause delayed growth and results in short adult stature. Pituitary dwarfism is caused by growth hormone underproduction in childhood due to the malfunction of the pituitary gland. Children with pituitary dwarfism grow slowly and their growth pattern doesn't follow the normal growth curve.

Symptoms

Common symptoms of pituitary dwarfism may include:

• Slow growth before the age of 5
• Slowed or absent growth after the age of 5
• Short stature (with height less than the fifth percentile for their chronologic age)
• Absent or delayed puberty
• Headaches
• Excessive thirst and urination

Causes

Pituitary dwarfism runs in families. The condition may also be caused by genetic (inherited) mutations, or an injured or missing pituitary gland. The greater the damage to the pituitary gland, the less able it is to produce hormones.

Diagnosis

A child suspected of pituitary dwarfism is given a complete medical history and physical examination. The child's height and weight are then compared to the standardized growth chart for children of his or her age and sex.

Common tests for pituitary dwarfism include:

• Growth hormone stimulation test.
• Insulin-like growth factors (IGF-I and IGFBP-3) test, as well as tests for other possibly related hormone levels.
• Hand X-rays or DEXA (Dual Energy X-ray Absorptiometry) determine the child's bone age and growth potential.
• Head X-rays or MRI identifies possible skull irregularities.
  

Treatment

The primary treatment for pituitary dwarfism is synthetic (recombinant) growth hormone. Untreated children have extremely short stature as adults and delayed puberty. The growth rate improves for most treated children but it begins to slow down as their bones start to fuse in adolescence. Children will not grow if their growth hormone treatment does not start until after their bones fuse. Additional hormone replacement therapy is provided for other pituitary hormone deficiencies.

Achondroplasia is the most common type of short-limbed dwarfism. It is a genetic condition that results in short stature with disproportionately short limbs. Unlike pituitary dwarfism, children have normal growth hormone levels. Achondroplasia is evident at birth and diagnosed using genetic testing. Although growth hormone treatment studies for achondroplasia suggest growth improvement, the studies are ongoing and their results won't be final until the children reach their adult heights.

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Small-for-Gestational Age (SGA)

Overview

A newborn whose weight is below the 10th percentile for its estimated gestational age is considered small-for-gestational-age (or intrauterine growth retardation). Most small newborns experience catch-up growth on their own by the age of 2 years. Children who remain small by age 2 should be evaluated for growth hormone deficiency.

Symptoms

Common SGA symptoms include:

• Low birth length and/or weight (less than the 10th percentile for estimated gestational age)
• Insufficient catch-up growth in first 2 years
• Lack of muscle mass and/or poor muscle tone

Causes

The common causes of SGA may include:

• Chronic placental insufficiency (inadequate oxygen and nutrient supply)
• Genetic (inherited) factors due to short-stature parents
• Infections (cytomegalovirus, rubella virus, or toxoplasmosis)
• Maternal illegal drug, alcohol, or tobacco use
• Environmental factors
• Unidentified cause

Diagnosis

A newborn's height and weight are compared to the standardized growth chart for children of his or her age. Those newborns whose weight falls below the 10th percentile are diagnosed as small-for-gestational age. Ultrasound is also used for developing fetuses showing signs of poor fetal growth to identify intrauterine growth restriction.

Common tests for SGA include:

• Growth hormone stimulation test.
• Insulin growth factor-I (IGF-1) test.
  

Treatment

Most infants whose SGA is due to chronic placental insufficiency undergo rapid catch-up growth without treatment by age 2. This is not the case for infants whose SGA is due to genetic factors, infections, or maternal drug or alcohol use.

The Food and Drug Administration (FDA) has approved growth hormone treatment for children diagnosed with SGA even if they have normally functioning pituitary glands and normal levels of growth hormone.

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Idiopathic Short Stature (ISS)

Overview

Sometimes the cause of a child's short stature is unknown (idiopathic).

Symptoms

Although children with ISS are normal physically, their only symptom is their short stature

Causes

The cause of ISS cannot be identified or remains unknown despite extensive testing.

Diagnosis

Some parents become concerned if their child's height is below the norm for its age and search for a cause. Children with short stature are given a complete medical history and physical examination. A diagnosis of idiopathic short stature is given after other causes of growth failure are rejected, such as:

• Bone trauma
• Chronic illnesses (such as heart or kidney disease)
• Delayed puberty
• Genetic (inherited) factors due to short-stature parents
• Growth hormone deficiency (using the growth hormone stimulation and supression tests)
• Known genetic conditions (such as Turner syndrome and Prader-Willi syndrome)
• Medications that slow growth (such as corticosteroids or Ritalin)

Treatment

Although children with idiopathic short stature do not have a growth hormone deficiency, studies have shown that these children can benefit from growth hormone treatment before their bones fuse. In 2003, the FDA approved growth hormone treatment for children with idiopathic short stature whose heights are more than 2.25 standard deviations below the mean for their age and sex. The FDA based its definition of short stature on the definitions used by the American Association of Clinical Endocrinologists and the Growth Hormone Research Society.

These children comprise the shortest 2.3 percent of all children. Because children with ISS are healthy, some people question the justification of their treatment with growth hormones.

It's recently been discovered that some ISS children with normal-to-high levels of growth hormone have low levels of insulin-like growth factor 1 (IGF-1) and that the low level of IGF-1 is the cause of their short stature. In 2005, the FDA approved treating primary insulin-like growth factor deficiency children with the drugs mecasermin (brand name: Increlex, Iplex) and mecasermin rinfbate (Iplex).

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Noonan Syndrome (NS)

Overview

Noonan syndrome is a rare genetic (inherited) condition that causes symptoms similar to those of Turner syndrome. Unlike Turner syndrome, Noonan syndrome occurs in both males and females, and the chromosomes are normal. Because Noonan syndrome resembles Turner syndrome but is not unique to females, it is occasionally referred to as:

• Female Pseudo-Turner syndrome
• Male Turner syndrome
• Turner-like syndrome.

Symptoms

Common Noonan syndrome symptoms may include:

• Short stature
• Short, webbed neck
• Unusual facial characteristics (such as low-set or abnormally shaped ears, sagging eyelids, small jaw)
• Heart defects
• Mental retardation
• Hypogonadism (inadequate function of the testes and ovaries)
• Delayed puberty

Causes

Noonan syndrome is an inherited condition caused by mutations in the KRAS and PTPN11 genes. The condition affects at least 1 in 2,500 children of both sexes.

Diagnosis

Children with the distinct characteristics of Noonan syndrome are given a complete physical examination. Genetic testing is used to check for the typical gene mutations. Additional tests help identify less obvious medical conditions associated with the condition, such as heart defects. Females are also tested for Turner syndrome to exclude this condition as a possible cause of their symptoms.

Treatment

The FDA approved the use of growth hormone to treat Noonan syndrome in November 2007.

Additional treatments may include:

• Testosterone or estrogen treatment to help stimulate sexual maturation
• Correction of any visual problems
• Special education classes to help improve mental faculties
• Treatment for any medical problems that may be present (such as heart defects)

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Turner Syndrome (TS)

Overview

Females normally have two X chromosomes. Females with Turner syndrome are born with only one functioning X chromosome and develop a group of symptoms associated with the condition.

Symptoms

Common symptoms of Turner syndrome may include:

• Short stature
• Swelling on the backs of their hands and tops of their feet.
• Swelling or loose folds of skin on the back of the neck
• Skin connecting the neck and shoulders
• Low hairline at the back of the neck
• Broad chest with wide-spaced nipples
• Poorly developed nails
• Lack of secondary sexual characteristics and amenorrhea (irregular or missing menstrual periods)
• Obesity
• Medical problems, such as heart and kidney defects, diabetes mellitus, and thyroid diseases
• Visual problems
• Low mathematical ability

Causes

Females with Turner syndrome are born partially or completely missing one of their X chromosomes. The condition occurs in 1 of every 2000 female births.

Diagnosis

Female children with the distinct characteristics of Turner syndrome are given a complete physical examination. The final diagnosis is reached after testing their X chromosomes. Because the physical symptoms may be subtle for some children, the chromosome test may not be given until they become teenagers and fail to mature sexually. Additional tests help identify any additional medical symptoms associated with the condition, such as heart and kidney defects.

Treatment

The FDA approved growth hormone treatment for children with Turner syndrome. Growth hormone is used successfully to stimulate the growth of children with Turner syndrome before their bones fuse. Additional treatments may include:

• Estrogen treatment to help stimulate sexual maturation
• Correction of any visual problems.
• Special education classes to help improve mental faculties
• Treatment for any medical problems that may be present (such as heart defects and thyroid diseases)

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Prader-Willi Syndrome (PWS)

Overview

Prader-Willi syndrome is an inherited condition that causes a group of symptoms that include short stature. Although PWS is a genetic (inherited) cause of obesity, infants with PWS typically have difficulty feeding without assistance. Their appetites start increasing at age one and becomes increasingly difficult to control. Sometimes the uncontrolled eating and resulting obesity may become serious enough to require gastric bypass surgery.

Symptoms

Common symptoms of Prader-Willi syndrome may include:

• Short stature
• Small hands and feet
• Characteristic facial features (almond-shaped eyes, crossed eyes, narrowed temples, thin upper lip)
• Compulsive overeating
• Childhood onset obesity
• Decreased mental capacity
• Decreased muscle tone
• Developmental delay
• Hypogonadism (inadequate function of the testes and ovaries)

Causes

Prader-Willi syndrome is caused by inherited defects on chromosome 15. The condition occurs in 1 of every 20,000 to 25,000 births.

Diagnosis

Genetic testing can accurately diagnose Prader-Willi syndrome. Infants who have difficulty feeding, poor muscle tone, developmental delay, or the characteristic facial features of PWS should be given a complete physical examination and genetic testing. Children and adults who exhibit the symptoms of PWS should also be tested.

Treatment

Treatment during infancy includes therapies to improve muscle tone. Infants with difficulty feeding may require special feeding devices.

Starting at childhood, treatment includes the following:

• Growth hormone therapy to improve short stature and decreased muscle tone
• Reduced-calorie diets and exercise to help prevent obesity
• Specialized education to help improve language, motor skills, and speech

Maintaining a healthy weight is essential to avoid the health conditions associated with obesity.

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Hypopituitarism

Overview

People with hypopituitarism are deficient in one or more hormones of the anterior (front) lobe of the pituitary gland. These hormones influence growth, metabolism, and maturation. If there is a deficiency of all anterior pituitary hormones, the condition is called panhypopituitarism. (Diabetes insipidus, a condition of excessive thirst and urine production, is a deficiency of the posterior pituitary hormones.)

Symptoms

The symptoms of hypopituitarism usually start slowly and vary depending on the impacted pituitary hormones. If a growth hormone deficiency occurs during childhood, it causes slow growth and short stature. If the growth hormone deficiency occurs in adulthood, it causes reduced muscle mass, osteoporosis, energy, and strength.

Causes

Common causes of hypopituitarism may include:

• Autoimmune condition
• Infection
• Inflammation
• Low blood supply
• Surgery
• Tumor

Diagnosis

Common tests for hypopituitarism to include:

• Blood tests measure the various hormones produced by the pituitary gland. In addition to growth hormone tests, insulin-like growth factor 1 (IGF-1) is also tested because the level of IGF-1 tends to change slowly in proportion to the overall amount of growth hormone produced by the pituitary.
• Computed tomography (CT) or magnetic resonance imaging (MRI) scans identify abnormal tissue growth, as well as growth or shrinkage of the pituitary gland.
• Cerebral angiography examines the blood vessel supply to the pituitary gland.
  

Treatment

Common treatments for hypopituitarism include:

• Hormone replacement is used when the cause of the hormone deficiency cannot be corrected by surgery or irradiation.
• Radiation therapy helps normalize growth hormone levels and may be used after surgery for tumors that cannot be removed totally. Due to its side effects, radiation is used as a last resort. Because radiation therapy may impact the function of the pituitary gland, regular functional testing is needed afterwards.
• Pituitary tumors are removed surgically. Removal of tumors with well-defined borders has an 80% cure rate. Sometimes the surgery is combined with radiation therapy or hormone replacement.

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Chronic Renal Insufficiency

Overview

Chronic renal insufficiency (chronic renal failure) occurs when a person's kidneys fail to function properly. The function of the kidneys is to balance the body's water and electrolytes (acids, bases, and salts). The kidneys also filter metabolic wastes from the blood, which are then excreted as urine. Children with chronic renal insufficiency develop several metabolic conditions, which may slow their bone growth and result in their short stature.

Symptoms

The symptoms of chronic renal insufficiency develop slowly due to the kidneys growing inability to excrete wastes and store electrolytes. Common symptoms may include:

• Fatigue
• Fluid retention
• Generalized itching
• Increased or decreased urine output
• Nausea, vomiting, weight loss
• Short stature

Short stature occurs when people develop chronic renal insufficiency as children.

Causes

Common causes of short stature due to chronic renal insufficiency may include:

• Abnormal increase in the acidity of the body's fluids
• Low levels of insulin growth factor-I (IGF-1)
• Malnutrition
• Secondary hyperparathyroidism (increased functioning of the parathyroid glands)
• Zinc deficiency
• Long-tem use of corticosteroids
• Kidney dialysis

Diagnosis

Common tests for chronic renal insufficiency include:

• Abdominal CT scan, MRI, ultrasound, or X-ray
• Kidney X-ray
• Urinalysis

Treatment

The Food and Drug Administration (FDA) approved growth hormone treatment for children with chronic renal insufficiency whose height is less than the third percentile for their chronologic age. Children should have their height measured regularly and compared to the standardized growth chart to determine whether they fit within the FDA's guidelines for growth hormone treatment. Any metabolic problems need to be corrected before starting growth hormone treatment.

Growth hormone treatment is not FDA approved after kidney transplantation surgery unless it is given as part of a research study.

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Adult Growth Hormone Deficiency

Overview

Although the pituitary gland normally produces less growth hormone as people age, the typical cause of adult growth hormone deficiency results from damage to a malfunctioning pituitary gland. In 1996 the Food and Drug Administration (FDA) approved growth hormone treatment for adults with a proven case of growth hormone deficiency.

Symptoms

The symptoms of adult growth hormone underproduction include:

• Decreased energy and endurance
• Decreased muscle mass
• Increased body fat
• Increased combined blood cholesterol level
• Osteoporosis

Causes

The most common causes of adult growth hormone underproduction include:

• Pituitary tumor (most common)
• Surgery
• Irradiation
• Trauma
• Hypothalamic disease
• Reconfirmed childhood growth hormone deficiency

Diagnosis

Common tests for adult growth hormone deficiency include:

• Growth hormone stimulation test
• Insulin growth factor-I (IGF-1) test

Treatment

The FDA requires adults to have a proven growth hormone deficiency before they can receive growth hormone treatment.  Although growth hormone treatment has not been shown to extend a person's lifespan of adults with growth hormone deficiency, the benefits may include:

• Increased energy and endurance
• Increased muscle mass
• Decreased body fat
• Decreased combined blood cholesterol levels
• Increased bone density

The long-term effects of growth hormone treatment are unknown. Long-term treatment needs to be evaluated and adjusted regularly. Continued monitoring is needed for possible side effects and irregular hormone levels.

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AIDS Wasting

Overview

Growth hormone helps maintain muscle mass in the wasting associated with HIV (human immunodeficiency virus) or AIDS (acquired immunodeficiency syndrome).

Symptoms

The wasting that people with HIV and AIDS experience is actually the loss of muscle mass and fat. Patients with AIDS may lose more than 10% of their body weight, which can lead to disease progression and death.

Causes

The causes of AIDS wasting syndrome may include:

• Altered hormone levels causing the body to produce less protein, and more fats and sugars
• Decreased appetite due to drug side effects, digestive system infections, and a lack of energy needed to prepare meals
• Increased metabolism due to the immune system fighting the disease
• Poor nutrient absorption due to disease-related intestinal infections and drug side effects (diarrhea)

Diagnosis

HIV is diagnosed by testing a person's blood or oral mucus for the presence of antibodies to the virus. Common tests include:

• Standard blood test: The ELISA (enzyme-linked immunosorbent assay) test result is then confirmed with the Western Blot test to avoid false positives.
• Oral mucosal transudate test: A specially treated pad is rubbed between a person's lower cheek and gum to collect an oral fluid called oral mucosal transudate (not saliva).
• Urine HIV antibody test (eliminates accidental needle sticks).
• Rapid HIV antibody tests: Take less than an hour. The standard blood tests can take as long as two weeks. The test result is then confirmed with an additional specific test.

Unfortunately HIV antibodies usually take 12 weeks to develop (in rare cases as long as six months). As a result, HIV test results aren't accurate immediately after infection. Home testing kits are available, which people can use to collect blood and send it to a lab for testing.

Treatment

Treatments for AIDS wasting include:

• Medications to reduce nausea and vomiting.
• Appetite stimulants to help increase food intake.
• Medications to reduce diarrhea and opportunistic intestinal infections improve poor nutrient absorption.
• Growth hormone, testosterone, anabolic (muscle building) steroids, and thalidomide to treat changes in metabolism.
• Progressive resistance training (PRT) using small weights to increase lean body mass.

The Food and Drug Administration (FDA) has approved recombinant human growth hormone to treat people with wasting due to HIV or AIDS. Higher doses of human growth hormone are required to increase their muscle mass and weight. Growth hormone treatment increases weight and lean body mass, and decreases fat mass. The treatment for AIDS wasting requires higher doses of growth hormone and the treatment costs can exceed $40,000 per year.

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Short Bowel Syndrome

Overview

Short bowel syndrome (small intestine insufficiency) is a malabsorption condition caused by either the surgical removal or disease of the small intestine. The small intestine is usually about 20 feet long. Short bowel syndrome usually appears when there is less than 1.8 meters (6 feet) of the small intestine left to absorb sufficient nutrients.

Symptoms

The initial symptoms of short bowel syndrome may include:

• Abdominal pain
• Diarrhea
• Fatigue
• Fluid retention
• Pale, greasy, foul-smelling stools
• Pernicious anemia
• Weight loss and malnutrition

Causes

When portions of the small intestine are removed surgically, the remaining bowel may not have sufficient surface area to sufficiently absorb nutrients from consumed food. Short bowel syndrome due to surgery may improve over time. Diseases of the small intestine that may require surgery include:

• Regional enteritis (inflamed small intestine)
• Crohn's disease (inflammatory disease of the digestive tract)
• Volvulus (twisted small intestine that leads to tissue death)
• Cancer, injury, or trauma

Diagnosis

Tests for short bowel syndrome include:

• Chem 20 identifies malabsorption
• CBC identifies anemia
• Fecal fat test

Treatment

Human clinical studies have shown that growth hormone enhances the transport of water, electrolytes, and nutrients through the wall of the small intestine. In 2003, the Food and Drug Administration (FDA) approved recombinant human growth hormone for short bowel syndrome.

Additional treatment designed to relieve symptoms include:

• A high-calorie, low-residue diet
• Antidiarrheal medicine
• Medications to extend the time nutrients spend in the small intestine
• Surgery (including intestinal lengthening or organ transplant)
• Tube feeding (through a vein or stomach tube)
• Vitamin and mineral supplements (A, B12, E, folic acid, D, calcium, iron, magnesium, and zinc)

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Pituitary Gigantism

Overview

Pituitary gigantism is a condition of excessive height that occurs when the pituitary gland overproduces growth hormone before a child's growth plates have closed.

Symtoms

Symptoms of pituitary gigantism may include:

• Long arms and legs
• Large hands and feet
• Prominent forehead and jaw
• Thick facial features
• Delayed onset of puberty
• Headaches
• Increased perspiration
• Vision problems
• Weakness
• Women: irregular menstrual cycles

Causes

Pituitary gigantism is usually caused by the overproduction of growth hormone due to a benign (noncancerous) pituitary gland tumor. Pituitary tumors are never malignant (cancerous) but may disrupt the release of other pituitary hormones. Certain rare tumors of the pancreas, lungs, adrenal glands, thyroid, and intestine may produce hormones that stimulate the pituitary to overproduce growth hormone.

Gigantism may also be caused by an underlying medical condition that alters hormone levels (such as multiple endocrine neoplasia type, McCune-Albright syndrome, neurofibromatosis, or Carney complex).

Diagnosis

A child suspected of pituitary gigantism is given a complete medical history and physical examination. The child's height and weight are then compared to the standardized growth chart for children of his or her age.

Common tests for pituitary gigantism include:

• Growth hormone suppression test
• Insulin growth factor-I (IGF-1) test
• Computerized tomography (CT) or magnetic resonance imaging (MRI) scan of the head that shows a pituitary tumor
• Prolactin (pituitary hormone) test

Treatment

Several approaches are used individually or in combination to reduce growth hormone levels.

Surgery

Radiation

Medication

• somatostatin analogs
  octreotide (brand name: Sandostatin) inhibits growth hormone and insulin-like growth factor (IGF) secretion.
• growth hormone antagonists
  pegvisomant (Somavert) blocks the effects of growth hormone.
• dopamine-receptor agonists
  cabergoline (cabergoline) decreases growth hormone secretion.

Although successful, some of the treatments for gigantism can lead to deficiencies in other pituitary hormones. Radiation therapy takes years to reduce growth hormone levels, and can cause learning and emotional problems in children. Yearly evaluations are recommended to check that the pituitary gland is functioning normally.

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Acromegaly

Acromegaly is a chronic (lifelong) hormonal disorder caused by the pituitary gland producing too much growth hormone during adulthood. The condition occurs in approximately 6 of every 100,000 adults.

Symptoms

Acromegaly symptoms develop slowly at first. The symptoms may include:

• Enlarged facial bones
• Enlarged hands and feet
• Thickened skin
• Enlarged jaw and tongue
• Deep, hoarse voice
• Headaches
• Joint swelling and pain
• Muscle weakness
• Diabetes mellitus
• Excessive sweating and body odor
• Polyps of the colon that may lead to cancer
• Vision problems
• Men: erectile dysfunction
• Women: irregular menstrual cycles

Causes

Acromegaly is usually caused by an overproduction of growth hormone due to a benign (noncancerous) pituitary gland tumor. Pituitary tumors are never malignant (cancerous) but may disrupt the release of other pituitary hormones. Certain rare tumors of the pancreas, lungs, pancreas, adrenal glands, thyroid, and intestine may produce hormones that stimulate the pituitary to overproduce growth hormone.

Diagnosis

A person suspected of acromegaly is given a complete medical history and physical examination. The person's height is then compared to adult height tables.

Common tests for acromegaly include:

• Growth hormone suppression test
• Insulin growth factor-I (IGF-1) test
• Cranial MRI (magnetic resonance imaging) or CT (computerized tomography) to locate a pituitary tumor
• Echocardiogram to locate a leaky heart valve
• Spinal X-ray to identify abnormal bone growth

Treatment

Several approaches are used individually or in combination to reduce growth hormone levels.

Surgery

Radiation

Medication

• somatostatin analogs
  octreotide (brand name: Sandostatin) inhibits growth hormone and insulin-like growth factor (IGF) secretion.
• growth hormone antagonists
  pegvisomant (Somavert) blocks the effects of growth hormone.
• dopamine-receptor agonists
  cabergoline (cabergoline) decreases growth hormone secretion.

Although successful, some of the treatments for acromegaly can lead to deficiencies in other pituitary hormones. Radiation therapy takes years to reduce growth hormone levels, and can cause learning and emotional problems in children. Yearly evaluations are recommended to check that the pituitary gland is functioning normally.

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