Abstract
OBJECTIVE: Fatigue is a prominent symptom among patients with GH excess and acromegaly. Identifying the physiological basis of such complaints and obtaining objective measures to quantify their severity remains an ongoing challenge. We investigated whether submaximal measures of aerobic performance can be used to assess GH excess-associated fatigue objectively. DESIGN AND PATIENTS: To investigate this possibility we examined the relation between physical function and physical capacity in 12 patients with active acromegaly and persistent fatigue before and after 3 and 6 months of treatment with the long-acting somatostatin analogue octreotide (LAR®). MEASUREMENTS: Heart rate (HR) and rating of perceived exertion (RPE using Borg's 10-point scale) were measured during a 160-metre self-paced walk test (SPW). Maximum oxygen uptake (VO2max) and ventilation threshold (VeT: a measure of work rate when breathlessness develops) were measured during a progressive treadmill test to fatigue or symptom-limited maximum. The Profile Of Mood States questionnaire (POMS) was used to quantify subjective feelings of fatigue and vigour. Morning fasting levels of GH and IGF-I were measured using immunoassay of serum samples. RESULTS: SPW speed at a fast pace of 1.69 ± 0.18 m/s was achieved with higher than normal HR (112 ± 15/min; normal = 102) and RPE (2.4 ± 1.2). Similar to GH-deficient adults, VO2max (22.6 ± 6.4 ml.kg-1.min-1; normal ∼30 ml.kg-1.min-1) and VeT (13.1 ±2.9 ml.kg-1.min-1; predicted normal ∼16 ml.kg-1(min-1) were low. However, VeT occurred at a normal fraction of VO2max (VeT/V02max = 0.58). VeT was significantly increased and plasma IGF-I levels reduced following 3 and 6 months of octreotide LAR® treatment. Reduction in circulating IGF-I levels was correlated with improvement in reported vigour (r = 0.85) and VeT (r = 0.65) (P < 0.05). CONCLUSIONS: Our findings demonstrate impairment in physical function and physical capacity consistent with the perception of increased fatigue among acromegalic patients. These objective measures of compromised physical function are similar to the changes that we have reported previously in adults with GH deficiency. Taken together, these data suggest that a narrow window for GH/IGF-I levels is required to maintain optimal physical function.