Deficiency of GH produces significantly different problems at various ages. In newborn infants the primary manifestations may be hypoglycemia or micropenis. In later infancy and childhood, growth failure may be the major effect.
Growth hormone deficiency in adults is rare, but may feature diminished lean body mass and poor bone density and a number of physical and psychological symptoms, including poor memory, social withdrawal, and even depression. Abnormally low growth hormone levels in adults typically result in diminished quality of life and can even be disabling. Physical symptoms include loss of strength, stamina, and musculature. Adults suffering from these symptoms should seek laboratory testing by an endocrinologist. Other hormonal or glandular disorders frequently coincide with diminished growth hormone production.
GH deficiency can be congenital or acquired in childhood or adult life. It can be partial or complete. It is usually permanent, but sometimes transient. It may be an isolated deficiency or occur in association with deficiencies of other pituitary hormones.
GH deficiency is treated by growth hormone replacement.
Many cases of isolated growth hormone deficiency (IGHD) recognized in childhood are idiopathic. IGHD has been reported to affect about 1 in 4000 children, but IGHD is difficult to distinguish from other causes of shortness such as constitutional delay, and the true incidence is unsettled.
Severe prenatal deficiency of GH, as occurs in congenital hypopituitarism, has little effect on fetal growth. However, prenatal and congenital deficiency can reduce the size of a male's penis, especially when gonadotropins are also deficient. Besides micropenis, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyperbilirubinemia). Female infants will lack the microphallus of course but may suffer from hypoglycemia and jaundice.
Even congenital GH deficiency does not usually impair length growth until after the first few months of life. From late in the first year until mid teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency is present from birth and never treated, adult heights can be as short as 48-58 inches (122-147 cm).
Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone, muscle, and fat) is affected in many children with severe deficiency, so that mild to moderate chubbiness is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence (said to resemble a kewpie doll).
Reported effects of severe GH deficiency in adults have included:
As an adult ages, diminishing amounts of GH are produced by the pituitary. This is characteristic of other hormones (especially the sex steroids) as well, and most physicians distinguish between the "naturally" reduced (age-related slowing) secretion of aging and the lower levels of real deficiency (idiopathic GH deficiency). Genuine deficiency in adulthood without a definable cause ("idiopathic GH deficiency") is extremely rare.
GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion. Where indicated, lower doses are called for in the elderly, to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-I.
Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians therefore use a combination of indirect and direct criteria.
Several types of evidence are used to ascertain GH sufficiency or deficiency.
"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15 minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine, levodopa, clonidine, epinephrine and propranolol, glucagon and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults, and so is the test of choice.
Severe GH deficiency in childhood has the following measurable characteristics:
Severe GH deficiency in adults has the following measurable characteristics:
When these features are accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary, the diagnosis is confirmed and presumed to be lifelong. When these corroborative features are not present, further testing is needed to establish the diagnosis.
For GH deficiency, as for many other diseases, the practical purpose and effect of these diagnostic criteria is to determine who is to be treated with it. GH deficiency accounts for only a minority of short stature among children. GH deficiency accounts for an even smaller proportion of fatigability, excessive fat, osteopenic bones, and underdeveloped muscles in adults. An ideal diagnostic test cleanly separates people who would benefit from a treatment from those who would not. Unfortunately, none of the criteria listed above do so, not even in various combinations.
There are almost no significant side effects of this type of physiologic replacement. Rare risks and unsettled issues are discussed in the article on GH treatment, but GH deficient children receiving replacement doses are at the lowest risk for problems and receive the greatest benefit.
Nevertheless, costs of treatment in terms of money, effort, and perhaps quality of life, are substantial. Treatment usually involves daily injections of growth hormone for children. Most pediatric endocrinologists monitor growth and adjust dose every 3-4 months and many of these visits involve blood tests. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes, pen injectors, or a needle-free delivery system reduce the discomfort. Most children and families are enthusiastic once the benefits begin to be seen. Treatment is expensive - as much as $US 10,000 to 40,000 a year is common.
Little except the cost of treating severely deficient children is controversial, and it is likely that the majority of children with severe growth hormone deficiency in North America, Japan, and much of Europe and the rest of the developed world are offered treatment, and most accept. The story is very different for adult deficiency.
It has been shown repeatedly in research studies that GH treatment can confer a number of measurable benefits to severely GH-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. Blood lipid levels improve, but long term mortality benefit has not yet been demonstrated.
GH for severe adult deficiency is usually prescribed as three injections per week at a weekly dose about 25% of children's doses and comparably lower cost. Despite the demonstrated benefits, most adults with GH deficiency are not being treated due to a combination of factors such as unwillingness of young adults to seek medical care, unacceptability of injections, inadequate insurance coverage, and significantly lower rates of diagnosis and treatment offer by internist endocrinologists.
Perhaps the most famous person who exemplified the appearance of untreated congenital growth hormone deficiency was Charles Sherwood Stratton (1838-1883), who was exhibited by P.T. Barnum as General Tom Thumb, and married Lavinia Warren. Pictures of the couple appear to show the typical adult features of untreated severe growth hormone deficiency. Despite the severe shortness, limbs and trunk are proportional.
Like many other 19th century medical terms which lost precise meaning as they gained wider currency, “midget” as a term for someone with severe proportional shortness acquired pejorative connotations and is no longer used in a medical context.
The traditional term for this condition is Laron dwarfism, but over the last 15 years many different types of GH resistance have been identified, primarily involving mutations of the GH binding protein or receptors. Trials of treatment with IGF1 were not successful enough to warrant adoption as standard use.
The two major United States support organizations for childhood and adult GH deficiency (as well as other growth problems).
Many good links related to GH deficency.
Links written for physicians:
Practice guidelines and recommendations for diagnosis and treatment of GH deficiency, reflecting standard practice among U.S. endocrinologists.
Online journal primarily written for pediatric endocrinologists that has been publishing brief reviews and research synopses related to growth hormone and growth issues for many years.
Online textbook of endocrinology with chapters on growth and pituitary disorders.
Non-profit advocacy group for adults of short stature.