Occurrence of pituitary dysfunction following traumatic brain injury.
ABSTRACT Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.
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ABSTRACT: There is growing evidence to suggest that growth hormone plays a role in the growth and development of the CNS. Specifically, growth hormone has been implicated in promoting brain growth, myelination, neuronal arborisation, glial differentiation and cognitive function. Here we investigate if growth hormone has a role in the recovery from an unilateral hypoxic-ischaemic brain injury. Using moderate (15 min hypoxia) and severe (60 min hypoxia) models of hypoxic-ischaemia in juvenile rats and standard immunohistochemical techniques, we found intense growth hormone-like immunoreactivity present within regions of cell loss by 3 days (P<0.05). Growth hormone-like immunoreactivity was observed on injured neurones, myelinated axons, glial cells within and surrounding infarcted tissue and on the choroid plexus plus ependymal cells within the injured hemisphere. The pattern of immunoreactivity suggests that (a) growth hormone (or a growth hormone-like substance) is transported via the cerebrospinal fluid and (b) that growth hormone (or a growth hormone-like substance) is acting in a neurotrophic manner specifically targeted to injured neurones and glia. To test this hypothesis we treated a moderate hypoxic-ischaemic brain injury with 20 microg of rat growth hormone by intracerebroventricular infusion starting 2 h after injury (n=12/group). After 3 days the animals were killed and the extent of neuronal loss quantified. Growth hormone treatment reduced neuronal loss in the frontoparietal cortex (P<0.001), hippocampus (P<0.01) and dorsolateral thalamus (P<0.01) but not in the striatum. This spatial distribution of the neuroprotection conveyed by growth hormone correlates with the spatial distribution of the constitutive neural growth hormone receptor, but not with the neuroprotection offered by insulin-like growth factor-I treatment in this model. These results suggest that some of the neuroprotective effects of growth hormone are mediated directly through the growth hormone receptor and do not involve insulin-like growth factor-I induction.In summary, we have found that a growth hormone-like factor increased in the brain in the days after injury. In addition, treatment with growth hormone soon after an hypoxic-ischaemic injury reduced the extent of neuronal loss. These results further suggest that a neural growth hormone axis is activated during recovery from injury and that this may act to restrict the extent of neuronal death.Neuroscience 02/2001; 104(3):677-87. · 3.12 Impact Factor
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ABSTRACT: During the past decade studies have shown that growth hormone (GH) may exert profound effects on the central nervous system (CNS). For instance, GH replacement therapy was found to improve the psychological capabilities in adult GH deficient (GHD) patients. Furthermore, beneficial effects of the hormone on certain functions, including memory, mental alertness, motivation, and working capacity, have been reported. Likewise, GH treatment of GHD children has been observed to produce significant improvement in many behavioral problems seen in these individuals. Studies also indicated that GH therapy affects the cerebrospinal fluid levels of various hormones and neurotransmitters. Further support that the CNS is a target for GH emerges from observations indicating that the hormone may cross the blood-brain barrier (BBB) and from studies confirming the presence of GH receptors in the brain. It was previously shown that specific binding sites for GH are present in discrete areas in the CNS of both humans and rats. Among these regions are the choroid plexus, hippocampus, hypothalamus, and spinal cord. The density of GH binding in the various brain regions was found to decline with increasing age. More recently, we were able to clone and determine the structure of several GH receptors in the rat and human brain. Although the brain receptor proteins for the hormone were shown to differ in molecular size compared to those present in peripheral tissues the corresponding transcripts did not seem to differ from their peripheral congeners. GH receptors in the hypothalamus are likely to be involved in the regulatory mechanism for hormone secretion and those located in the choroid plexus have been suggested to have a role in the receptor-mediated transport of GH across the BBB. The functions mediated by the GH receptors identified in the hippocampus are not yet known but recently it was speculated that they may be involved in the hormone's action on memory and cognitive functions.Frontiers in Neuroendocrinology 11/2000; 21(4):330-48. · 7.99 Impact Factor
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ABSTRACT: To study the impact of severe head injury on both basal pituitary hormone secretion and the response to exogenous synthetic hypothalamic releasing factors (TRH and GHRH) in order to evaluate sequential changes in the central control of hypophyseal secretion in the days following head injury. Prospective clinical study 21 comatose male patients with head injuries, each intubated and ventilated, intensively monitored and having no previous endocrine problems. AND RESULTS The GH and PRL responses to TRH (200 microg iv), and the GH and PRL responses to GHRH (50 microg iv) were evaluated, respectively, on the days 1 and 16 and on days 2, 7and 15 after admission. Daily blood samples were also collected for GH, PRL, TSH, T3 and T4 evaluation. In the basal samples taken on days 2, 7 and 15, IGF-I and cortisol were also determined. Nitrogen balance was assessed daily. On the day 1, TRH increased GH levels from 9.8 +/- 2.2 to 22.4 +/- 6.5 mU/l but failed to induce GH release on day 16. The PRL response to TRH was normal. The GH peak response to GHRH was normal on the day 2 (35.7 +/- 13.9 mU/l), but was increased on days 7 and 15 (68.3 +/- 10.7 mU/l on day 7; 73.8 +/- 9.2 mU/l on day 15, P < 0.01 vs. day 2). We found a significant PRL response to GHRH during the whole period of observation. In the daily evaluation, nitrogen balance was negative in all patients from the day 1 to 5. On average, all patients reached a positive nitrogen balance on the day 8. Compared to the day 2, a statistical increase in IGF-I concentration was observed on days 7 and 15. The evaluation of pituitary dynamics in the acute phase of a severe injury demonstrates an alteration of GH and PRL secretion, which correlate with the aminergic and/or peptidergic derangements. Taken together, our data suggest augmented tone of both GHRH and somatostatin in the very acute phase, while an imbalance of releasing factors is hypothesized in the following days. The metabolic consequences of this neuroendocrine pattern could be advantageous in the rapid recovery from the cascade of events produced by the trauma, as documented by the increase in IGF-1 levels and the positive nitrogen balance.Clinical Endocrinology 06/1999; 50(6):741-7. · 3.40 Impact Factor