ASSESSMENT OF PITUITARY-FUNCTION AFTER TRANSSPHENOIDAL HYPOPHYSECTOMYIN BEAGLE DOGS

Pituitary function was assessed in healthy adult beagle dogs before an d after hypophysectomy. Anterior pituitary function was tested by use of the combined anterior pituitary (CAP) function test, which consiste d of sequential 30-sec intravenous injections of four hypothalamic rel easing hormones, in the following order and doses: 1 mu g of corticotr opin-releasing hormone (CRH)/kg, 1 mu g of growth hormone-releasing ho rmone (GHRH)/kg, 10 mu g of gonadotropin-releasing hormone (GnRH)/kg, and 10 mu g of thyrotropin-releasing hormone (TRH)/kg. Plasma samples were assayed for adrenocorticotropin (ACTH), cortisol, GH, luteinizing hormone (LH), and prolactin (PRL) at multiple times for 120 min after injection. Pars intermedia function was assessed by the alpha-melanot ropin (alpha-MSH) response to the intravenous injection of the dopamin e antagonist haloperidol in a dosage of 0.2 mg/kg. Posterior pituitary function was assessed by the plasma vasopressin (AVP) response to the intravenous infusion of 20% saline. Basal plasma ACTH, cortisol, thyr oxine, LH, PRL, and AVP concentrations were significantly lower at 10 wk after hypophysectomy than before hypophysectomy. In the CAP test an d the haloperidol test, the peaks for the plasma concentrations of ACT H, cortisol, GH, LH, PRL, and alpha-MSH occurred within 45 min after i njection. At 2 and 10 wk after hypophysectomy, there were no responses of plasma GH, LH, PRL, and alpha-MSH to stimulation. In four of eight hypophysectomized dogs, there were also no plasma ACTH and cortisol r esponses, whereas in the other four dogs, plasma ACTH and cortisol res ponses were significantly attenuated. The basal plasma ACTH and cortis ol concentrations were significantly lower in the corticotropic nonres ponders than in the responders. Plasma AVP responses were completely a bolished by hypophysectomy, although water intake by the dogs was norm al. Histopathological examinations at 10 wk after hypophysectomy revea led that adrenocortical atrophy was much more pronounced in the cortic otropic nonresponders than in the responders. No residual pituitary ti ssue was found along the ventral hypothalamic diencephalon. However, i n all hypophysectomized dogs that were investigated, islets of pituita ry cells were found embedded in fibrous tissue in the sella turcica. A significant positive correlation was found between the number of ACTH -immunopositive cells and the ACTH increment in the CAP test at 10 wk after hypophysectomy. It is concluded that 1) stimulation of the anter ior pituitary with multiple hypophysiotropic hormones, stimulation of the pars intermedia with a dopamine antagonist, and stimulation of the neurohypophysis with hypertonic saline do not cause side effects that would prohibit routine use, 2) in the routine stimulation of the ante rior pituitary and the pars intermedia, blood sampling can be confined to the first 45 min, 3) the ACTH and cortisol responses to hypophysio tropic stimulation are the most sensitive indicators for residual pitu itary function after hypophysectomy, 4) small islets of pituitary cell s in the sella turcica, containing corticotropic cells, are the most l ikely source of the attenuated corticotropic response that may occur a fter hypophysectomy, and 5) residual AVP release from the hypothalamus after hypophysectomy is sufficient to prevent diabetes insipidus, des pite the fact that the AVP response to hypertonic saline infusion is c ompletely abolished. (C) Elsevier Science Inc. 1997.