Natural killer (NK) cell activity was assessed in the peripheral blood of 20 patients with growth hormone (GH) deficiency due to a hypothalamic deficit of GH-releasing hormone (GHRH). All patients failed to respond to at least two provocative tests of GH secretion (GH below 7 ng/ml) but responded to a single GHRH iv bolus injection (1 microgram/kg body wt). In 14 of the 20 patients (20 determinations), lymphocyte subsets were also measured; in all patients the distribution of lymphocyte subsets was within the normal range. More importantly, NK cell activity in the 20 patients was significantly lower than in controls (P less than 0.01). To assess the in vivo effect of GH and GHRH on NK activity and lymphocyte subset distribution, immunologic tests were performed (i) before and after a single iv bolus injection of GHRH (1 microgram/kg body wt) in six patients; (ii) before and after 3 weeks of GHRH treatment (3-9 micrograms/kg body wt, one to four times daily) in five patients; and (iii) after 6 weeks of GH treatment (5 IU sc every alternate day) in one patient. Neither NK activity nor the distribution of lymphocyte subsets was altered during short-term GHRH administration. In conclusion, low NK activity is found in GH-deficient patients, and short-term administration of GH or GHRH fails to restore this immunological abnormality. This result suggests that the hypothalamus may be a regulator of NK activity in the human and that patients with hypothalamic deficiencies should be monitored for the development of discrete immunodeficiencies.

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