Hormone levels and fuel flow in patients with weight loss and lung cancer. Evidence for excessive metabolic expenditure and for an adaptive response mediated by a reduced level of 3,5,3′-triiodothyronine

Abstract

Hormone levels, fuel flow, and basal metabolic rate were studied in five men with weight loss and non-oat cell carcinoma of the lung and eight normal men during a brief fast (96 hours). The patients with cancer had lost approximately 11.0 ± 3.3 kg (16.6 ± 5.1% of ideal body weight) before participation in the study (mean ± SEM). They exhibited many of the characteristic clinical and laboratory features of this syndrome but, at 94.2 ± 6.9% of ideal body weight at the onset of the fast, were not wasted. Their estimated mean daily caloric intake before admission was 1832 ± 408 kcal. All subjects received a balanced weight maintenance diet for 62 hours before fasting. Compared with the normal subjects, the patients with weight loss and cancer demonstrated a diminished increase in the plasma free fatty acid level during the fast, a decreased blood alanine level at all times before and during the fast, a decreased total urine nitrogen excretion rate before and during the fast (in grams per 24 hours and grams per square meter of body surface area, but not in grams per gram of creatinine), and a decreased serum 3,5,3′-triiodothyronine (total T 3) level before and during the fast. The urine total ketone excretion rate was low in three of the five cancer patients. A comparison of the circulating levels of glucose, ketones, lactate, pyruvate, insulin, glucagon, 3,3′,5′-triiodothyronine (reverse T 3), norepinephrine, epinephrine, cortisol, and growth hormone in the cancer patients with those of the normal subjects before and during the fast revealed no important difference. The basal metabolic rate was significantly higher in the cancer patients than in the normal subjects on the last day of the fast, despite the reduced total T 3 level and the normal catecholamine levels. Our findings indicate that patients with weight loss and non-oat cell carcinoma of the lung exhibit excessive metabolic expenditure. In addition, they respond adaptively to total caloric deprivation, to the maladaptive elevation in metabolic expenditure, or to both, by conserving lipid and nitrogen stores; they do not waste nitrogen. This adaptive conservation of fuels may be mediated by the reduced total T 3 level, which can account for the decrease in lipolysis and which appears to decrease alanine release from the periphery. These findings cannot be attributed to recent deprivation of calories or carbohydrate, in view of the daily intake before admission and while on a balanced weight-maintenance diet before fasting. The pathogenesis of the reduced total T 3 level is unknown; it may reflect the loss of weight before the study or chronic illness. In cancer patients, the rate of weight loss reflects the level of caloric intake, the extent of excessive metabolic expenditure, and the effectiveness of the adaptive conservation of fuels mediated by the reduced total T 3 level.