The role of the hypothalamus in pituitary neoplasia

Although the role of the hypothalamus in the genesis of pituitary tumours has emerged to be one of promotion rather than of initiation, it remains of utmost clinical importance. The epidemiological finding that occult pituitary tumours are very frequent, but only very seldom progress towards clinical evidence and exceptionally to malignancy suggests that their aggressive potential is kept under control by a host of factors and that only the disruption of this complex mechanism can allow occult tumours to grow. Most of these factors are hypothalamic in origin, although the stimulatory action of releasing hormones can be enhanced and the inhibitory action of inhibiting hormones reduced by receptor/post-receptor alterations occurring in pituitary tumours. If in the case of oncogenic mutations the clone expansion might be sustained only by the constitutive activation of proliferative signals and not require the intervention of other promoting factors, in other circumstances promoting factors (such as an excess of stimulatory or lack of inhibitory factors) may be necessary for the expansion of the tumoral clone. The development of pituitary somatotrophinomas or corticotrophinomas in patients with GHRH or CRH hyperproduction, respectively, gives clinical evidence to the role of releasing hormones. The shrinking effect of dopamine or SRIH agonists on the tumour mass of prolactinomas and somatotrophinomas, respectively, and, conversely, the rapid tumour expansion of corticotrophinomas after the removal of the cortisol negative feedback by bilateral adrenalectomy are clinical proofs of the importance of inhibitory signals on tumour growth.