The renin-angiotensin system in panhypopituitarism: dynamic studies and therapeutic effects in Sheehan's syndrome.

To gain insight in the influence of the pituitary gland on the renin-angiotensin system plasma renin substrate (PRS) and the response of PRA to stimulation were studied in a homogeneous group of 20 female patients with the same etiology and degree of pituitary failure, before treatment (group P), after hydrocortisone substitution (group F), and after hydrocortisone and thyroid hormone treatment (group F + T). All patients were studied before and after each treatment by response to two stimulatory tests, acting through two different pathways; orthostasis test (O-T) and the furosemide test (Furo-T). Results were compared between groups, each patient serving as her own control, and with those obtained in a 12 healthy women control group (group C). The diet contained about 85 meq Na/day. Compared to group C (O-T response, 5.97 +/- 0.54 ng ml-1 h-1; Furo-T response, 6.71 +/- 0.82 ng ml-1 h-1; mean +/- SEM), PRA response to both tests was blunted in group P (O-T: 2.48 +/- 0.46, P less than 0.001; Furo-T: 3.02 +/- 0.53, P less than 0.001) and remained so in F (O-T: 2.18 +/- 0.40, P less than 0.001; Furo-T: 2.52 +/- 0.28, P less than 0.001), In group F + T, the response to both tests was greater than in P and F (O-T, 6.61 +/- 1.19; Furo-T, 4.36 +/- 0.44; 0.001 less than P less than 0.05). However, whereas the response to orthostasis is entirely normalized, the response to a diuretic remained significantly smaller than in group C (P less than 0.01). These improvements were observed without significant change in PRS concentration which remained low. We conclude that panhypopituitarism is accompanied by an altered renin angiotensin system. Basal levels of PRS and PRA are low and unresponsive to adequate stimulation. Whereas glucocorticoid therapy alone is without effect on this hyporeninism, addition of thyroid hormones completely normalized the response to orthostasis and significantly improved furosemide response.