Failure to Thrive in Older People

In the present issue, Fox et al. describe the occurrence of failure to thrive following hip fracture.1 They used a functional definition of failure to thrive: decreasing ability to walk one block. They concluded that this progressive decline occurred in about 10% of patients following hip fracture and that it was associated with physical and cognitive impairment and increased health care utilization. Whereas some metabolic predictors could be inferred from their data, they concluded that the failure to thrive syndrome, as observed in their subjects, appeared to be a “complex and multifaceted condition,” with “multiple causes and influences.” People don't die of old age any more. Not that they ever did die of old age. At one time, however, “old age” was an acceptable cause of death. In the present era, older people die of specific diagnoses or, at least, failure of a specific organ system. Nonetheless, old age is associated with general and nearly universal changes in organs and metabolism that impair the response to physiological, metabolic, psychological, or other stress that precedes death. This state of impaired homeostatic reserve is the condition called “frailty.” The course from robust health to frailty is called “failure to thrive.” Failure to thrive is related to other age-associated changes that presage death. The change most commonly recognized is weight loss. An article published last year in the Journal of the American Geriatrics Society by Wallace et al. focused on weight loss in outpatients.2 Similar to the 10% incidence of failure to thrive found by Fox et al., Wallace et al. found that the incidence of unexplained weight loss was about 13% in outpatients. Because the amount of weight loss was 4%, it must have come primarily from fat or muscle. Loss of fat and muscle is commonly called malnutrition, and loss of muscle alone is called sarcopenia. Because muscle loss, with or without concomitant fat loss results in loss of strength, endurance, and ability to walk, these conditions and syndromes are interrelated: failure to thrive, malnutrition, sarcopenia, and frailty. See also p 371 We do not have a clear picture still of the natural history of failure to thrive. Data from Fox et al., Wallace et al., and others cited by these investigators suggest that 10 to 25% of people older than 65 years of age have failure to thrive, associated with loss of fat, muscle, and ability to walk and perform other functions. Fox et al. noted that it can occur after a hip fracture; Wallace et al. noted that it can occur in an outpatient setting without any clear antecedent problem. Because the study by Fox et al. was an uncontrolled epidemiological study, focused on loss of function that occurred from 6 to 12 months after hip fracture, the failure to thrive that they observed may have developed independent of the hip fracture. Alternatively, some hip fractures may have occurred in people with pre-existing failure to thrive because of antecedent loss of bone mass and protective muscle strength. Further observational studies of natural history are needed to clarify these and similar possibilities. Further studies of risk factors are needed. Fox et al. observed high glucose and CO2 and low creatinine and SGPT in their subjects with failure to thrive. Although statistically significant, these findings may not be the best or the most important risk factors. Future observational studies should be coupled with cross-sectional studies of associated metabolic, physiological, psychological, functional, and/or social variables to develop a list of risk factors. Such a list can be expected to lead to strong inferences about potential mechanisms. In addition, autopsies are needed. Fox et al. did not report the causes of deaths occurring in their subjects, and Wallace et al. found that, of 15 people with outpatient weight loss who died, six died of heart disease, six died of cancer, and three died of infection. This small number of observations needs to be increased. People with chronic diseases who die at extreme old age are seldom autopsied. One easily can hypothesize that most of them would be found to have cancer if it was looked for with enough care. Alternatively, it might be hypothesized that a group of patients will be found without clear indication of the underlying process leading to death, apart from the involutional changes seen in the bodies of all older people. Such observation would point to the likelihood that previously unrecognized conditions cause death in extreme old age and need to be studied further if only to understand the nature of aging, itself. Intervention studies are needed. Too few studies have tried to stop failure to thrive or to reverse malnutrition, sarcopenia, or loss of physical function. The role of energy and protein supplementation remains controversial. Physical exercise is useful for some people, but it has limited efficacy, too. The value of hormonal supplementation, particularly growth hormone or IGF-1 replacement in treating this syndrome, is unknown. Also, there is a large collection of hormones and other nutritional and metabolic modifiers; these are of interest to the general public, but they have not been studied systematically by the scientific community. Animal models are needed because animals, too, fail to thrive at the end of life. An animal model would make it possible to test hypotheses about both mechanisms and interventions. If failure to thrive is one manifestation of loss of physiological homeostasis, animal models would make it possible to study this end-of-life phenomenon at a cellular and molecular level. What is the practical implication of such studies? How should a geriatrician approach an individual with failure to thrive, unexplained weight loss, progressive functional disability, malnutrition, and/or sarcopenia? Is failure to thrive merely an academic concern? The late Dr. Daniel Rudman, in introductory remarks at a workshop on failure to thrive held in Tucson, noted that it is potentially dangerous to consider failure to thrive as a diagnosis because failure to thrive is actually just a syndrome. Diagnosing someone with failure to thrive should never be used as justification to stop diagnostic workups because most failure to thrive is secondary failure to thrive, to use Dr. Rudman's nomenclature. Secondary failure to thrive is attributable to diagnosable and potentially treatable diseases, including diabetes, tuberculosis, other chronic infections, thyroid disease, cancer, heart failure, and inflammatory conditions such as temporal arteritis. Nonetheless some people, including those carefully studied by Fox et al., have primary failure to thrive. The term is useful particularly where the cause of the progressive decline is obscure. Certainly it can be used descriptively to separate healthy “thriving” older people from those who are following a course of progressively worsening disability leading to death. Although the syndrome may go to the heart of what it means to die of old age, and may raise important scientific questions, the bottom line for the geriatrician is that failure to thrive has its own ICD-9 number, 783.4. Usually used for children, this diagnosis also is used for older adults, sometimes as a principal diagnosis, even though it must be a diagnosis of exclusion. There is nothing particularly unusual about workup for failure to thrive. All organ systems need to be evaluated by medical history, physical examination, and appropriate laboratory testing. Diseases causing wasting need to be excluded; psychosocial and functional causes of starvation must be eliminated; and starvation, itself, must be excluded by a trial of nutritional intervention. Treatment options are limited at present. We can only expect that, with sufficient interest and research support, it will, in the future, be possible to identify both underlying causes and the potential for treatment. In addition, we may be able to identify those people who are coming inexorably to the end of life and to understand the physiological and metabolic causes underlying this process.