Table 2. Classification of the causes of IGF-1 deficiency, from (e16).

Classification	Secondary IGF-1 deficiency	Primary IGF-1 deficiency	Primary IGF-1 deficiency	Functional IGF-1 deficiency
Pathogenesis	Defects in growth hormone production	Defects in growth hormone action	Defects in IGF production	Defects in IGF action
GH secretion	Low	High/normal	High/normal	High/normal
Level of disruption	GH production:	Binding to GHR;	IGF-1 gene:	Lack of binding protein:
	GHRH/GHRIH defect	Anti-GH-antibodies	Mutation/deletion	IGFBP-3
	GHRH receptor defect	GHBP excess	Other	ALS
	GH gene defects			Other
	Functional (aging)
	Other
Level of disruption	Hypophyseal development:	GH receptor:	Cofactors:	Excess of binding proteins:
	Cellular structures	GHR antibodies	Thyroid hormones	IGF-1 antibodies
	Other	GHR gene defects	Insulin	Renal failure
			Nutrition	Other
			Liver function
			Other
Level of disruption	Hypophyseal destruction	Post-GHR:		IGF-1 receptor:
		JAK-STAT		IGF-1-R
		Other		Post receptor

IGF-1, insulin-like growth factor 1; GH, growth hormone; GHRH, growth hormone releasing hormone; GHRIH, growth hormone release inhibiting hormone; GHR, growth hormone receptor; GHPB, growth hormone binding protein; ALS, acid-labile subunit; IGF-1-R, IGF-1 receptor; JAK/STAT, “Janus kinases/signal transducers and activators of transcription”