Dst, Acth, or Trh Stim: What’s New with Ppid Testing & Treatment?

Pituitary pars intermedia dysfunction (PPID), also known as equine Cushing’s disease, is the most common endocrinopathy of older horses, affecting 20-30% of horses over the age of 20. It develops as a consequence of degeneration of hypothalamic dopaminergic neurons that regulate (by tonic inhibition) the pituitary gland, specifically the pars intermedia (PI) that is entirely composed of a single cell type – the melanotrope. Similar to Parkinson’s Disease, progressive loss of dopaminergic innervation over many years leads to unregulated enlargement of the PI, initially by melanotrope hyperplasia and progressing to microand macroadenoma formation within the PI. Dopamine concentrations in the PI of horses with PPID have been shown to be one-tenth those of normal horses and tyrosine hydroxylase activity, the rate limiting enzyme for production of dopamine, is also markedly reduced in equids with PPID. Another consequence of loss of PI dopaminergic innervation is excess production of the prohormone proopiomelanocortin (POMC, 241 amino acids). Processing of POMC by prohormone convertase 1 and prohormone convertase 2 leads to increased amounts of many POMC-derived peptides, including ACTH1-39 (POMC138-176) and α-MSH (ACTH1-13) in jugular venous plasma. Excess amounts of POMC peptides are thought to be responsible for development of clinical signs of PPID, including a long hair coat that fails to shed, loss of muscle mass, increased drinking and urination, recurrent infections, and chronic laminitis.