DYNAMICS OF PROLACTIN SECRETION IN PATIENTS WITH HYPOPITUITARISM AND PITUITARY MACROADENOMAS

Mild hyperprolactinemia frequently accompanies the hypopituitarism see n in patients with pituitary macroadenomas that do not secrete PRL. We postulated that hypopituitarism in this setting, is primarily caused by compression of the portal vessels and/or pituitary stalk. If this w ere the case, the dynamics of PRL secretion in this instance would be similar to those in patients with stalk section, dopamine deficiency, or hypothalamic disease. Furthermore, as hypopituitarism in this setti ng is largely reversible, we postulate that PRL dynamics should also n ormalize after adenomectomy as a result of the resumption of hypothala mic regulation of pituitary hormone secretion. To test these hypothese s, we examined PRL responsiveness to TRH and the dopamine antagonist, perphenazine (PZ), in patients with pituitary macroadenomas who had hy popituitarism and others with intact pituitary function (controls). Dy namic studies were performed before and 2-3 months after total or subt otal adenomectomy, and the results were correlated with alterations in other pituitary function. In addition, plasma ACTH, cortisol, and PRL levels were measured hours to days after surgery to investigate immed iate alterations in pituitary function following surgical decompressio n. Before surgery, hypopituitary patients had higher serum PRL level t han controls (25.5 +/- 12 vs. 11 +/- 3 mu g/L; P < 0.001). Preoperativ e dynamic testing of PRL secretion in hypopituitary patients demonstra ted an increase in PRL levels after TRH, but not after PZ, administrat ion. In contrast, PRL levels increased appropriately when either stimu lus was given to controls. Hours after adenomectomy, PRL levels decrea sed by 50% in hypopituitary patients (P < 0.0001) and remained so unti l discharge. In contrast, controls had a transient increase in serum P RL levels after adenomectomy. After surgery, 25 of 43 previously hypop ituitary patients recovered part or all pituitary function. Serum PRL levels in the latter subgroup became normal and increased appropriatel y after stimulation with either TRH or PZ. In contrast, patients who d id not recover pituitary function had lower PRL levels that increased minimally after TRH or PZ. The mild increase in serum PRL levels in hy popituitary patients and the discordant responses to stimulation with TRH and PZ suggest dopamine deficiency as a cause of hyperprolactinemi a. The drop in serum PRL levels immediately after surgery, at a time w hen other pituitary hormones (e.g. ACTH), were documented to rise sugg ests restoration of hypothalamic control over pituitary hormone secret ion. The pattern of PRL responses to stimulation in patients recoverin g function postoperatively was similar to that in controls, although t he incremental rise was subnormal. The data support the hypothesis tha t hypopituitarism in this setting is reversible and largely caused by compression of the portal vessels and associated interruption of the d elivery of hypothalamic hormones to the anterior pituitary. The persis tence of hypopituitarism in some patients and the subnormal PRL respon ses to stimulation in patients recovering function suggest that prolon ged compression of the normal pituitary might, in addition, result in ischemic necrosis that could limit the potential recovery of function.