Endocrine disease is characterized by irregulated hormone release (a productive pituitary adenoma), inappropriate response to signalling (hypothyroidism), lack of a gland (diabetes mellitus type 1, diminished erythropoiesis in chronic kidney failure), or structural enlargement in a critical site such as the thyroid (toxic multinodular goitre). Hypofunction of endocrine glands can occur as a result of the loss of reserve, hyposecretion, agenesis, atrophy, or active destruction. Hyperfunction can occur as a result of hypersecretion, loss of suppression, hyperplastic, or neoplastic change, or hyperstimulation.