Neuromuscular dysfunction in adult growth hormone deficiency

Adult growth hormone deficiency (AGHD) is associated with fatigue, tiredness and myalgias, which improve after initiating recombinant human GH (rhGH) therapy.To conduct an extensive neuromuscular investigation of patients with AGHD in an attempt to explain their neuromuscular symptoms.Twenty adult patients (11 males) with untreated GHD of whom 10 were childhood-onset (CO) underwent a prospective neurological protocol, including physical examination and a neurophysiological study that comprised sensory and motor neurography, repetitive stimulation, electromyogram (EMG) and interference pattern analysis (IPA). In the first seven patients (four CO), a biceps muscle biopsy was also performed for histochemical analysis and Western blot, and investigation of signal transducers and activators of transcription (STATs)-1 and -3 and the two isoforms STAT-5a and -5b.Neuromuscular examination, sensory and motor neurography and repetitive stimulation were normal in 20/20 patients. Fourteen [seven CO and seven adult-onset (AO)] of the 20 patients had abnormal EMG and/or IPA suggestive of a neurogenic involvement. In those seven patients with initially abnormal results, who also remained on regular rhGH for at least 1 year, repeated IPA was normal in six and improved in the remaining patient (P=0.004). The biceps muscle biopsy disclosed abnormal groupings in the seven cases tested, indicative of a neurogenic pattern. No changes in skeletal muscle STAT-1 and -3 were seen compared to controls, but a marked increase in both STAT-5 isoforms was observed in all seven patients.Skeletal muscle of patients with both adult-onset and childhood-onset adult GH deficiency shows a neuromuscular dysfunction, indicated by the muscle biopsy and the neurophysiological study, which in the subgroup of treated patients responds positively to rhGH therapy. The results obtained suggest that the STAT-5 signal transduction pathway in muscle is abnormal in adult GH deficiency.