Hormonal changes and pituitary histological and immunocytochemical studies of patients with multiple organ failure

OBJECTIVE: We investigated the correlation between the endogenous hormonal changes of pituitary-adrenal and pituitary-thyroid hormones and the prognosis of patients in multiple organ failure, and elucidated the mechanism of blunted thyrotropin (TSH) secretion by histological and immunocytochemical studies of anterior pituitary glands. PATIENTS: Forty-three patients were studied who had been admitted to the intensive care unit of Sapporo Medical University Hospital and had been diagnosed as having multiple organ failure. MEASUREMENTS: Pituitary adrenal hormones [corticotropin (ACTH), cortisol] and pituitary thyroid hormones [TSH, triiodothyronin (T3), free-T3, thyroxine (T4), free-T4, thyroxine-binding globulin (TBG)] were measured, and TSH and prolactin (PRL) responses thyrotropin-releasing hormone (TRH) were examined within 24 hours of admission to the ICU. Individual variables were compared between survivors (n = 19) and nonsurvivors (n = 24). Thirteen patients (five survivors, eight nonsurvivors) were investigated again before discharge from the ICU or death. Morphology was examined by hematoxilin-eosin staining, and avidin-biotin-peroxidase complex immunostaining was used to demonstrate the spectrum of TSH in 14 nonsurvivors. RESULTS: (1) ACTH levels remained within the normal range, while cortisol levels increased to above normal levels. Neither hormone showed significant differences between survivors and nonsurvivors. In nonsurvivors, cortisol levels decreased before death despite the increased ACTH levels. (2) T3 and free-T3 levels decreased markedly to below normal values, and reverse-T3 levels increased markedly to above normal values. Nonsurvivors showed significant differences in TSH, T4 and reverse-T3 levels compared with survivors. (3) TSH response to TRH was blunted in both groups but PRL response to TRH was normal. Nonsurvivors showed severely depressed TSH response. Nonsurvivors continued to show blunted TSH response to TRH, while this improved in survivors. (4) The histological study did not show very serious damages to anterior pituitary glands as TSH secretion was depressed. Many TSH immunoreactive cells were also observed by immunocytochemical study. CONCLUSION: Decreased cortisol, low T4 levels and blunted TSH response to TRH correlated with mortality in MOF patients. Histological and immunocytological studies suggest that blunted TSH secretion is not caused by pituitary damages or TSH exhaustion but by disturbances in TSH secretion. This blunted TSH secretion is reversible and its improvement is an indicator of survival.