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Overdosage of IGF-I can lead to androgenization, a previously undescribed undesirable effect of IGF-I. Long-term IGF-I treatment necessitates progressive adjustment of the IGF-I dose to avoid overtreatment.

Z. Effect of insulin-like growth factor I on the thyroid axis in patients withLaron-typedwarfism and healthy subjects.We have evaluated the effect of exogenous administration of IGF-I on the thyroid axis in four separate studies: (1) iv bolus injection; (2) single sc injection; (3) seven days' sc treatment, and (4) four months' treatment. Thirteen patients with Laron-type dwarfism (LTD) participated in the investigations. In studies 1 and 2,10 healthy subjects were also included. Before and during long-term treatment (study 4) six LTD patients underwent a TRH test. IGF-I was administered in a dose of 75 \ g=m\ g\ m=. \ kg\ m=-\ 1 iv or 120\p=n-\ 150 \ g=m\ g\ m= . \ kg\m=-\ 1 sc. Single injections of IGF-I caused significant decreases of serum TSH in LTD patients (iv: 1.7\m=+-\0.2 to 1 . 1 \ m = + -\ 0 . 1 mU/l; sc: from 2.1\m=+-\0.4to 1.1 \m=+-\0.2;p<0.0005). In controls the decrease was for iv from 1.2\m=+-\0.2to 0.8\m=+-\0.2mU/l (p<0.02) and for sc from 2.0\m=+-\0.5to 0.8\m=+-\0.2mU/l (p<0.05). Long-term administration of IGF-I induces a transitory decrease of both serum TSH and fT4, followed by a spontaneous rise to pretreatment or even higher values. No changes in T3 were observed. TSH stimulation by TRH was significantly augmented after four months of IGF-I treatment (p<0.005). The effects of IGF-I can be explained by an early stimulation of somatostatin release causing a decrease in TSH and followed by the development of compensatory mechanisms. All changes were within the normal ranges, not causing abnormal thyroid function. As the clinical use of recombinant IGF-I extends for longer periods than those described, it is recommended that thyroid function is followed. Z Laron, Recent reports have documented that exogenously administered growth hormone (GH) affects thyroid function in both normal individuals ( 1 ) and GH deficient adults (2), as well as in children with either GH deficiency (3) or hypothyroidism (4). All the reports describe suppression of the thyroid function during GH administration, but the expression of the results varied.Thus, some reported a lowering of serum T4 and an increase of serum T3 (2-4), decrease in 151I thyroidal uptake (5), or decrease in serum TSH (6). The avail¬ ability of recombinant IGF-I, the effector hormone of hGH and its introduction into clinical use made it possible to test whether the GH effect on the thyroid function is a direct one or is mediated by IGF-I.We report the effect on thyroid function of a single intravenous or subcutaneous injection of IGF-I and short and long-treatment of IGF-I in Laron-type dwarfism (LTD) patients. Subjects and methodsThe effect of rIGF-I on the thyroid function was investi¬ gated during four separate studies. Study 1 comprised 10 patinets with LTD (5M, 5F) aged 8 to 35 years and a control group of 8 healthy subjects (5M, 3F)aged8 to 39 years. Thyroid function was studied before and after an iv bolus of rIGF-I (75 jUg.kg-1). The study was performed after an overnight fast and blood samples for TSH determinations were drawn at 0, 2, ...