Perspectives Commentary on: High Prevalence of Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage: A Long-Term Prospective Study Using Dynamic Endocrine Testing by Kronvall et al. World Neurosurg 83:574-582, 2015
Subarachnoid Hemorrhage and the Pituitary Adriana G. Ioachimescu and Daniel L. Barrow
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ronvall et al. (10) investigated pituitary gland function in 44 patients after treatment for aneurysmal subarachnoid hemorrhage (SAH) at Lund University. In this prospective study the authors evaluated and reported basal hormone evaluation 6e12 months after SAH and dynamic hormonal testing after 12e24 months. The authors found a significant proportion of patients with growth hormone (GH) and adrenocorticotroph hormone (ACTH) deficiency at the end of the study period (25% and 20%, respectively). These results demonstrate a significant long-term risk of hypopituitarism after recovery from SAH and provide an opportunity for improving outcomes. Many patients with SAH experience fatigue, cognitive deficits, mood changes, and decreased quality of life despite neurologic recovery (3, 4, 12). These symptoms may persist many months after SAH and hamper patients’ rehabilitation. Such clinical manifestations, also reported in patients with traumatic brain injury (TBI), resemble those of hypopituitarism and may improve with hormonereplacement therapy. Therefore, investigation of pituitary hormones has been evaluated in several clinical studies. On the basis of results of cross-sectional and a few prospective cohort studies, the 2007 Consensus Conference on GH deficiency recommended that TBI and SAH patients undergo neuroendocrine dynamic testing (2). The mechanism of hypopituitarism after SAH has not been clarified and may be the result of increased intracranial pressure, ischemic lesions of the hypothalamus, stalk or pituitary gland, as well the surgical procedure. In the TBI literature, autoimmunity, neuroinflammation and genetic predisposition have been implicated. These mechanisms may also apply to SAH but have not been investigated in this patient population.
Key words Growth hormone deficiency - Hypopituitarism - Outcome - Pituitary deficiency - Subarachnoid hemorrhage -
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Abbreviations and Acronyms ACTH: Adrenocorticotroph hormone GH: Growth hormone ITT: Insulin tolerance test SAH: Subarachnoid hemorrhage TBI: Traumatic brain injury
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Most studies have shown that isolated GH deficiency is the most frequent abnormality encountered a few months after SAH. GH deficiency is also the most frequent hormone abnormality that occurs in patients with TBI (1, 5). The prevalence of GH deficiency approximately 12 months after SAH is in the range of 20%e36% (1, 6, 7, 9, 10, 13). In contrast, a 2010 Danish study had discrepant results showing no hormone deficiency (8). These authors acknowledged that a group of patients with SAH were allocated to an ongoing intervention study that may have resulted in a selection bias. Otherwise, the wide prevalence range is explained by different endocrine tests and thresholds to define deficiency in each study, different time intervals elapsed since SAH, and different patient populations (Table 1). For example, use of basal GH and insulin-like growth factor I levels without GH stimulation has a low sensitivity to detect GH deficiency. Several GH stimulation tests currently are used in adults, including the insulin tolerance test (ITT), GHRH-arginine, and glucagon administration. For some of the tests, the thresholds to define GH deficiency should be adjusted on the basis of patient’s body mass index (ie, lower threshold for patients with greater body mass index). ITT is considered the gold standard for diagnosis of GH deficiency but implies achieving significant hypoglycemia. In the study by Kronvall et al., ITT was performed in 30 patients and 25% of them had a peak
Subarachnoid Hemorrhage and the Pituitary Adriana G. Ioachimescu and Daniel L. Barrow
K
ronvall et al. (10) investigated pituitary gland function in 44 patients after treatment for aneurysmal subarachnoid hemorrhage (SAH) at Lund University. In this prospective study the authors evaluated and reported basal hormone evaluation 6e12 months after SAH and dynamic hormonal testing after 12e24 months. The authors found a significant proportion of patients with growth hormone (GH) and adrenocorticotroph hormone (ACTH) deficiency at the end of the study period (25% and 20%, respectively). These results demonstrate a significant long-term risk of hypopituitarism after recovery from SAH and provide an opportunity for improving outcomes. Many patients with SAH experience fatigue, cognitive deficits, mood changes, and decreased quality of life despite neurologic recovery (3, 4, 12). These symptoms may persist many months after SAH and hamper patients’ rehabilitation. Such clinical manifestations, also reported in patients with traumatic brain injury (TBI), resemble those of hypopituitarism and may improve with hormonereplacement therapy. Therefore, investigation of pituitary hormones has been evaluated in several clinical studies. On the basis of results of cross-sectional and a few prospective cohort studies, the 2007 Consensus Conference on GH deficiency recommended that TBI and SAH patients undergo neuroendocrine dynamic testing (2). The mechanism of hypopituitarism after SAH has not been clarified and may be the result of increased intracranial pressure, ischemic lesions of the hypothalamus, stalk or pituitary gland, as well the surgical procedure. In the TBI literature, autoimmunity, neuroinflammation and genetic predisposition have been implicated. These mechanisms may also apply to SAH but have not been investigated in this patient population.
Key words Growth hormone deficiency - Hypopituitarism - Outcome - Pituitary deficiency - Subarachnoid hemorrhage -
1026
Abbreviations and Acronyms ACTH: Adrenocorticotroph hormone GH: Growth hormone ITT: Insulin tolerance test SAH: Subarachnoid hemorrhage TBI: Traumatic brain injury
www.SCIENCEDIRECT.com
Most studies have shown that isolated GH deficiency is the most frequent abnormality encountered a few months after SAH. GH deficiency is also the most frequent hormone abnormality that occurs in patients with TBI (1, 5). The prevalence of GH deficiency approximately 12 months after SAH is in the range of 20%e36% (1, 6, 7, 9, 10, 13). In contrast, a 2010 Danish study had discrepant results showing no hormone deficiency (8). These authors acknowledged that a group of patients with SAH were allocated to an ongoing intervention study that may have resulted in a selection bias. Otherwise, the wide prevalence range is explained by different endocrine tests and thresholds to define deficiency in each study, different time intervals elapsed since SAH, and different patient populations (Table 1). For example, use of basal GH and insulin-like growth factor I levels without GH stimulation has a low sensitivity to detect GH deficiency. Several GH stimulation tests currently are used in adults, including the insulin tolerance test (ITT), GHRH-arginine, and glucagon administration. For some of the tests, the thresholds to define GH deficiency should be adjusted on the basis of patient’s body mass index (ie, lower threshold for patients with greater body mass index). ITT is considered the gold standard for diagnosis of GH deficiency but implies achieving significant hypoglycemia. In the study by Kronvall et al., ITT was performed in 30 patients and 25% of them had a peak
