Growth failure is a major concern for families who have children with inflammatory Bowel Disease. In response to requests for more precise information relative to the growth process, the Pediatric Crohn’s & Colitis Association engaged Dr. Stuart Brink, Senior Physician at New England Diabetes & Endocrinology Center, Chestnut Hill, MA, to speak with families and respond to their questions. The following article, submitted by Dr. Brink, summarizes his presentation. PCCA hopes this material will benefit our readers and those persons who have expressed disappointment at having missed our evening referencing growth and the IBD child.
Abnormalities of growth are commonly seen in infants, children and adolescents who also have gastrointestinal disorders (see Table 1). In youngsters with these problems, weight is generally less than expected but height may be abnormal as well. One of the vital tools available to the health care provider who works with children and adolescents is the ability to use knowledge about growth as a signal that all is either well or not well developmentally. Typically, because gastrointestinal disorders often involve some degree of malnutrition, weight is much further below the norm than height. Length of illness combined with effects of prescribed medication can also decelerate growth. It is therefore extremely important to make sure that all youngsters followed for any kind of gastrointestinal problem have accurate records kept not only for height and weight, but for rate of change in height and weight compared with others their own age and sex. Standard male and female growth charts must be utilized. Abnormalities of growth are defined as being underweight, being short, or not gaining weight or height at the proper rate. Sometimes the astute pediatrician or family physician will suspect a medical problem in the absence of other symptoms merely because weight, height or velocity of growth are abnormal.
In patients with gastrointestinal problems whose height is relatively normal but whose weight is markedly abnormal, treatment of growth abnormalities often focuses on supplying sufficient calories. As with any case of inadequate caloric intake, the treatment goal is to supply the patient with enough calories to permit growth to resume. (This is known as “catch-up” growth.) Sometimes, gastrointestinal problems involve motility disorders where the musculature of the stomach and intestinal tract is unable to coordinate movement of nutrients through the gastrointestinal system; treatment then involves medications to stimulate more normal motility or else attempts at surgical correction.
Other GI problems include those where certain areas of the gut are unable to allow for proper absorption of particular nutrients. Specifically, iron, calcium, vitamin B 12 and folic acid deficiencies may sometimes be corrected by attacking the primary disease process itself and, at other times, by supplying additional amounts of such nutrients. Subtle mineral and vitamin deficiencies may be extremely difficult to diagnose, however, since measurements of blood and urine levels do not always correlate with tissue levels of such micronutrients.
Other malabsorptive problems reflect an inability to break down and process protein, carbohydrate or fat substances in the normal diet, as when pancreatic enzymes are deficient or when the enzymes normally available at the brush border of the intestinal tract are either not made properly or the surface has been irritated and/or destroyed by some other process. Simple sugars or amino acids as well as simple fat substances may be used to promote better absorption in cases where the gut surface is damaged. An alternative strategy is to deliver smaller amounts of nutrients through nasogastric feedings overnight. This solves the problem of overworking the gastrointestinal tract at any given time. When such feedings are utilized, patients with a variety of inflammatory bowel diseases have not only felt and functioned better but also have improved stamina and increases in both height and weight.
If macronutrient and micronutrient deficiencies are detected, treatment focuses on replacing these substances in sufficient amounts to promote catch-up growth and eliminate other indicators of their deficiency. As stated earlier, with most of these problems weight is compromised in advance of also linear growth. If such deficiencies are not identified and corrected within a short period, linear growth may also be compromised.
The gastroenterologist, working in close conjunction with the primary care physician may outline a treatment plan that provides adequate calories intravenously by hyperalimentation, using specially designed nutrients permitting the affected gastrointestinal tract a period of rest. By resting the damaged area and providing essential nutrients, growth is allowed to take place (anabolism). In some cases, surgery produces the best treatment outcome while in others, a variety of medications alone or surgery in combination with medication may be the approach of choice. While anti-inflammatory medications may, as a side effect, retard growth, others may cause stomach discomfort, nausea or vomiting. Some, such as prednisone and Decadron, while very effective in counteracting inflammation, may interfere with long bone growth. An added drawback is that when high doses of cortisone-like medicines are prescribed, certain parts of the body increase their deposits of fat, resulting in a round “moon” face and generalized excess body fat (called “Cushingoid”).
Hormone disturbances are frequently suggested as possible causes of growth disturbances in youngsters. Most of the growth problems that occur in patients with gastrointestinal diseases, however, are not related to classical hormone deficiencies. Making this subtle distinction may be a very complex process involving a series of both general and hormonal assessments. Diagnostic difficulties arise because of the association of specific hormone abnormalities with specific types of GI disorders. For example, patients with celiac disease are more likely to also have insulin dependent Type 1 diabetes mellitus (IDDM), or thyroid problems (thyroiditis with or without thyroid enlargement, called a goiter). Another group of patients with nonspecific malabsorption syndromes also have abnormal levels of immunglobulins as well as an increased prevalence of IDDM, thyroid, parathyroid and adrenal diseases. A common feature of such problems is an autoimmune attack on different body systems, including the gut’s absorptive surfaces and hormone-producing glands. In more recent studies, patients with IDDM have been shown to have an increased incidence of peptic ulcer disease.
Whenever any kind of chronic illness is present, delays in growth and the onset of puberty may occur. Some youngsters merely need reassurance that normal adolescent development will occur, only more slowly than usual. This allows for a longer period of continued slow but steady growth to take place before the final adolescent growth spurt and ultimate closure of the long bones. Patterns of delayed growth and delayed puberty are common place in certain families, so that a detailed knowledge of family growth patterns is essential to understand growth variability in the individual. Calculation of mid-parent height allows for prediction of the young patient’s expected final adult height coupled with a detailed family growth history.
Plotting height and weight data and tracking the patterns may result in the identification of the problem. However, when available data fail to point to a specific cause of growth failure, additional tests may be carried out (see Table 2), all of which need to be repeated on several occasions to make sure that random measurements accurately reflect the hormonal state of affairs. Consultation with pediatric endocrinologists may be most helpful at this point of evaluation.
A single X ray of the left wrist and hand is used to determine current bone development and to predict onset of puberty as well as how much additional growth is possible. Once the bones begin to close, the amount of time left for further growth is limited. Yearly bone age determinations provide an excellent way to monitor growth progress as well as treatment effects.
Endocrine evaluations have become possible with the development of very sensitive radioimmunoassays (RIAs) of small amounts of blood. Somatomedin-C or IGF-1 blood measurements provide information about overall nutrition as well as the ability of the liver to respond to growth hormones produced in the pituitary gland. Prior to puberty, IGF-1 values are relatively low so that distinguishing between normal and low values is difficult; once there is evidence that adolescence has begun, the distinction between normal and abnormal IGF-1 levels is easier to make so that the diagnostic value of IGF-1 determinations increases. In order for Somatomedin-C or IGF-1 to be generated by the liver, growth hormone must be produced in the right proportions and at the appropriate time of the day or night. The growth hormone production system is under the control of the brain which sends signals to the hypothalamus (the area of the brain above the pituitary gland.) The hypothalamus is known to secrete a variety of substances which in turn coordinate the release of many hormones. One such hypothalamic hormone is called GHRH (growth hormone releasing hormone). GHRH’s job is to stimulate GH from the pituitary. GH then travels to the liver to stimulate IGF-1 production. IGF-1 then promotes long bone growth.
Special growth stimulation tests are needed in order to determine how the body responds under specific circumstances. In the case of very young children, these tests are done in a hospital setting, whereas older children and adolescents who have larger veins as well as the capacity to understand the purpose of the procedures are usually tested in the endocrinologist’s office. Knowledge about interpreting such stimulation or overnight tests has increased in recent years.
Individuals can produce GH but do not do so in adequate increments. Or they can produce some GH but without sufficient overnight bursts (neurosecretory OH deficiency.) Food itself seems to dampen GH bursts, while achieving deep sleep is associated with significant GH surges. Overnight monitoring may be useful to detect such abnormalities.
Classical or complete growth hormone deficiency as a reflection of hypothalamic or pituitary disorders is not commonly seen and is certainly not related to most GI disorders that interfere with growth. How well or how frequently partial neurosecretory growth hormone deficiency occurs in patients being treated for GI disturbances is not known either, nor is it known how such patients would respond to the provision of supplemental growth hormone. Some researchers are now looking at the capacity of hormones- e.g. growth hormone- to promote protein deposition (an anabolic effect) so that healing of damaged tissue may occur. Burn patients and patients recovering from surgery have undergone such studies but more research is still needed to prove that use of growth hormone is beneficial in all these circumstances. Whether or not growth hormone could be used to counteract the growth-retardant catabolic effects of medications like prednisone is not yet known, but studies looking at the possibility of using growth hormone for patients with unexplained growth abnormalities are about to be undertaken by our office.
Growth hormone treatment is unlikely to be a panacea for growth problems in patients with GI disorders but may assist in treatment. Problems secondary to GH use have been minor and easily monitored. It is expensive, and it must be injected nightly. Special injector devices help a great deal as do the use of very fine needles. Other ways of delivering GH remain in experimental stages.
In summary, then, optimal treatment to promote normal growth and pubertal development involves treatment of the normal primary gastrointestinal disorders; this, in combination with caloric supplementation, frequently results in catch-up leading to normal growth. In other cases surgery, a combination of medications, or surgery combined with such medications may bring the primary GI problems under control. Providing sufficient calories to allow for healing to take place is often burdensome. When it succeeds with overnight nasogastric feedings or hyperalimentation protocols, decreased inflammation, a sense of improved well-being, decreased fatigue, and weight gain and height acceleration may all follow. If these measures are not working will enough, endocrinologic evaluation and specific hormone treatment should be considered.