A nine-year-old girl, who presented with a severe hypoglycemic coma, proved to have isolated ACTH deficiency, a finding previously reported in only two children. On the initial evaluation, before any treatment, GH did not respond to provocative stimuli. On replacement therapy with hydrocortisone, normal linear growth was observed. Repeated testing while on glucocorticoids replacement four years after the initial attack revealed normal GH response to stimulation test. It is suggested that cortisol deficiency was responsible for the severe hypoglycemic coma and subnormal GH response. A similar mechanism is speculated for the normal growth observed in some patients with apparent deficiency of anterior pituitary hormones, including GH. The possibility of permanent ACTH deficiency and transitory GH deficiency following hypophysitis is discussed.
Recently, abnormalities of cell-mediated immunity were found in hemophiliac patients receiving factor VIII concentrate therapy. Contradictory results were reported concerning cellular immune functions in hemophiliacs treated only with cryoprecipitate or fresh frozen plasma. Therefore, we evaluated the immunological status of 15 Israeli patients with severe classic hemophilia-A who were treated only with cryoprecipitate and never exposed to factor VIII concentrate whether of commercial source or blood bank prepared. As a group, only mildly depressed cellular immune functions and slight reduction in the helper to suppressor cell ratio were found. However, when patients treated more than 15 years were analyzed separately, a significant reduction in proportion of T cells, T-helper cells, helper to suppressor ratio, and proliferative response to phytohemaglutinin and pokeweed mitogen were observed compared to patients treated for less than 15 years and normal controls. Proportion of T-suppressor cells, Con A-activated suppressor activity, and IgG and IgA levels were significantly elevated in patients treated for more than 15 years. These results may support the view that derangement of immune function in hemophiliacs results from infusion of foreign proteins or an ubiquitous virus rather than contracting AIDS infectious agent.
Despite many years of clinical use in Hodgkin lymphoma, no previous studies have evaluated the relationship between doxorubicin pharmacokinetics and clinical response. In a pilot study, we associated the area under the curve of doxorubicin with successful remission. Patients with successful remission (n = 14) had a trend toward a higher median area under the curve than those who failed remission (n = 4; 36,390 versus 19,350 ng/mL x minute, P = 0.08, respectively). Median peak serum concentrations were 73 ng/mL among failures and 280 ng/mL in those who achieved remission (P = 0.06). The 2 groups did not differ regarding demographic and clinical parameters or doxorubicin dose. If corroborated by further studies, therapeutic drug monitoring of doxorubicin may be warranted in patients with Hodgkin lymphoma.
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