Clinical Endocrinology. 2000;52(2):187-195.
OBJECTIVE Insulin-like growth factor binding-protein-1 (IGFBP-1) has a role in glucose
homeostasis and is present at high concentrations in hyperthyroidism. We have investigated
the relationship between IGFBP-1 concentration and glucose homeostasis in hyperthyroidism.
DESIGN Patients and controls had intravenous glucose tolerance tests (IVGTT) and/or
oral glucose tolerance tests (OGTT). Patients were tested when hyperthyroid and when
euthyroid whilst the controls were tested once. The IVGTT was used to assess insulin
sensitivity and the OGTT to establish that the study group had abnormal glucose tolerance.
The hyperthyroid patients were treated with methimazole to restore euthyroidism. PATIENTS
Ten patients (9 females) and 13 healthy controls (9 females) consented to the study.
Ten patients and nine controls (7 females) had IVGTT. Six patients (5 females) and
six controls (4 females) had OGTT. MEASUREMENTS Glucose, insulin, glucagon, GH and
IGFBP-1 were measured during GTT. IGF-I, free thyroid hormones, and TSH concentrations
were measured basally. RESULTS Hyperthyroid subjects were insulin resistant and 67%
had impaired glucose tolerance. Fasting IGFBP-1 levels were doubled in hyperthyroid
subjects compared to healthy controls and correlated positively with free T4 (r =
0.84, P < 0.0001), with peak glucose during the OGTT (r = 0.68, P < 0.005) with peak
insulin during the IVGTT (r = 0.51, P < 0.005) and negatively with glucose disappearance
constant (r = - 0.52, P < 0.005). IGFBP-1 was highly phosphorylated in hyperthyroid
and control subjects. Fasting insulin and IGFBP-1 levels were unrelated but IGFBP-1
suppressed acutely during GTT in all groups. GH levels fell less in patients with
hyperthyroidism than in normals during GTTs. CONCLUSIONS We conclude that in hyperthyroidism
thyroid hormones directly increase fasting IGFBP-1 concentration but acute regulation
of IGFBP-1 by insulin is normal and that elevated fasting phosphorylated IGFBP-1 concentration
is associated with insulin resistance.