GROWTH HORMONE DISORDERS
Growth hormone deficiency (GHD) is a medical condition, caused by problems arising in the pituitary gland, in which the body does not produce enough growth hormone (GH). Growth hormone, also called somatropin, is a polypeptide hormone which stimulates growth and cell reproduction.
Growth hormone deficiency has a variety of different negative effects at different ages; for example, in newborn infants, the primary manifestations may be hypoglycemia or micropenis, while in later infancy and childhood, growth failure is more likely. Deficiency in adults is rare, but may feature diminished lean body mass, poor bone density, and a number of physical and psychological symptoms. Psychological symptoms include poor memory, social withdrawal, and depression, while physical symptoms may include loss of strength, stamina, and musculature. Other hormonal or glandular disorders frequently coincide with diminished growth hormone production.
The most common cause of GHD (representing two-thirds of cases) are pituitary and parasellar tumors. The origin of adult GHD may be congenital or acquired. Of those adult GHD that are acquired, roughly 15% are idiopathic, 50% are from pituitary tumors, 20% from extrapituitary tumors, and 5% from infiltrative or inflammatory lesions.
The incidence of idiopathic GHD in infants is about 1 in every 3800 live births, and rates in older children are rising as more children survive childhood cancers which are treated with radiotherapy, although exact rates are hard to obtain.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 in males, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyperbilirubinemia).
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 48-65 inches (122–165 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).
Other side effects in children include sparse hair growth and frontal recession, and pili torti and trichorrhexis nodosa are also sometimes present.
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 in assessing GHD, including:
Auxologic criteria (defined by body measurements)
Indirect hormonal criteria (IGF levels from a single blood sample)
Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:
Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours
Subnormal GH secretion in response to at least two provocative stimuli
Increased IGF1 levels after a few days of GH treatment
Response to GH treatment
Corroborative evidence of pituitary dysfunction
Severe GH deficiency in childhood additionally has the following measurable characteristics:
Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency
Below-normal velocity of growth
Delayed physical maturation
Delayed bone age
Low levels of IGF1, IGF2, IGF binding protein 3
Increased growth velocity after a few months of GH treatment
In childhood and adulthood, the diagnosing doctor will look for these features 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. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be