The precise cause of hyperparathyroidism (HPT) is uncertain. Alteration of growth factors (epidermal growth factor, fibroblast growth factor) and genetic mutations (parathyroid hormone (PTH) gene (11p15), PRAD1 oncogene (11q13) and multiple endocrine neoplasia type 1 (MEN1) gene (11q13)) are implicated in the pathogenesis. The escape of secretory function from physiological control and excess growth is still incompletely understood. The insulin-like growth factor (IGF) axis is a ubiquitous growth and regulatory system (IGF-1 and -II, IGF receptors (IGFRs) and binding proteins (IGFBPs)). Hormonal/endocrine signals (e.g. androgens, thyroid-stimulating hormone) and tumour supressor genes (e.g. Wilms' tumour suppressor gene (WT-1) (11p13) and p53) modulate the IGF axis. Expression of the WT-1 gene is tissue specific (kidney, mesothelium, prostate). Wild-type WT-1 governs normal kidney development and mutation results in Wilm's tumour. Loss of transcriptional repression of WT-1 and IGF control can lead to mitogenesis. A mutation (chromosome 11) appears to be the key event in the evolution of primary HPT. This mutation may increase IGFR expression, IGF production giving rise to unregulated autocrine growth. In polyclonal hyperplasia (secondary HPT and MEN1) a serum factor initiates polyclonal growth, thereby increasing the susceptibility to mutation and resulting in nodular hyperplasia.