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Subarachnoid Hemorrhage and the Pituitary
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
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 -
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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 <3 ng/mL. For 14 patients in whom ITT was contraindicated, GHRH-arginine tests yielded a smaller prevalence of GH deficiency of 14%. These findings make overestimation of GH deficiency in this study unlikely. The prevalence of ACTH/cortisol deficiency after aneurysmal SAH is a subject of debate in the literature. Some studies suggest
From Emory University School of Medicine, Atlanta, Georgia, USA To whom correspondence should be addressed: Daniel L. Barrow, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 83, 6:1026-1028. http://dx.doi.org/10.1016/j.wneu.2015.01.044
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.01.044
PERSPECTIVES
Table 1. Prospective Studies Investigating Hypopituitarism After Aneurysmal SAH No. Patients (No. Men)
Time After SAH, months
Kreitschmann-Andermahr 44 7 et al., 2004 (9)
40 (14)
12e66
55%
Aimaretti et al., 2005 (1) 52 2
32 (12) 32(12)
3 12
46.8% 37.5%
48 3
22 (11)
Day of admission 12
Klose et al., 2010 (8)
46 (22e64)
26 (7) 62 (14)
Karaca et al., 2013 (6)
47 13
Khajeh et al., 2014 (7)*
56 12
Age
Tanriverdi et al., 2007 (13)
Kronvall et al., 2014 (10) 55 (28e75)
Hypopituitarism ACTH GH TSH FSH/LH GH Dynamic (One or More Axes) Deficiency Deficiency Deficiency Deficiency Testing 40%
20%
2.5%
None
ITT
3.1% 6.25%
25% 21.8%
9.3% 9.3%
9.3% 6.25%
GHRH-Arg GHRH-Arg
63.6% 36%
22.7% 13.6%
22.7% 36.4%
None None
31.8% None
None GHRH-Arg
<0.5 12
93% None
12% None
15% None
None None
93% None
None ITT/other
20 (12) 20 (12)
12 36
25% 20%
5% None
25% 20%
None None
None None
Glucagon Glucagon
84 (28)
<1 6 14
39% 26% 7%
2% None None
31% 10% 6%
1% 1% None
34% 20% 5%
Ghrelin GHRH-Arg GHRH-Arg
44 (1)
6e12 12e24
34% 43%
20% 20%
13% 25%
None None
2% 12%
None ITT or GHRH-Arg
Age (years) is shown as mean SD or median (range), as reported in original article. SAH, subarachnoid hemorrhage; ACTH, adrenocorticotroph hormone; GH, growth hormone; TSH, thyroid-stimulating hormone; FSH/LH, follicle-stimulating hormone/luteinizing hormone; ITT, insulin tolerance test; GHRH-Arg, growth hormoneereleasing hormone-arginine. *In the study by Khajeh et al. (7), only patients with previous ACTH and GH abnormalities were retested at 14 months.
prevalence as high as 40% when dynamic testing is performed more than 12 months after SAH (9). Other authors suggest that ACTH/cortisol deficiency is rare (<6.25%) (1, 6-8, 11), and one study indicated a prevalence of 13.6% at 12 months (13). The wide spectrum occurs in the context of different testing methods in each study, which included basal early morning cortisol determination, ACTH stimulation test (1 or 250 mg) or ITT, the latter considered the gold standard. Kronvall et al. (10) reported that central adrenal insufficiency occurs in 20% of patients both in the first and second year after SAH. The study authors used basal hormone measurements in the first year and ITT in the second year with a widely accepted cutoff of 18 mg/ dL. Of note, ACTH/cortisol insufficiency is rare in patients with a history of TBI (1, 5). Somatotroph cells are located on the wings of the anterior pituitary gland and receive blood supply from the hypothalamic-portal vessels. They are more susceptible to ischemia than corticotroph cells that have a central location and receive blood supply from the portal vessels as well as the anterior pituitary artery branches. The discordance between literature on TBI and SAH regarding central adrenal insufficiency has mechanistic implications that point towards a hypothalamic (rather than pituitary) dysfunction in SAH. This finding also has important therapeutic implications, because hypocortisolemia with onset in the early phase after aneurysmal rupture could lead to immediate complications and excess mortality. This issue cannot be readily ascertained from the literature, because dynamic endocrine studies usually are not performed in the neurointensive care setting. Also, patients with a poor neurologic outcome after SAH were not included in prospective trials. Studies agree that gonadotropin and thyrotropin deficiency are rare in patients evaluated 6 months or more after SAH
WORLD NEUROSURGERY 83 [6]: 1026-1028, JUNE 2015
(1, 6-10, 13). These results are based on basal hormone evaluation, which is the standard for adult endocrinology today. Although gonadotroph and gonadal hormone levels are low immediately after SAH, they almost always recover during follow-up (Table 1). Responses of the gonadotroph and thyrotroph axes to the acute phase of SAH reflect adaptation to critical illness, as previously shown in patients with septic shock. In contrast, the expected ACTH/cortisol response to acute illness consists of increased levels. A mild degree of hyperprolactinemia may occur immediately after SAH but usually resolves after a few months. Dysfunction of the posterior pituitary with diabetes insipidus is rare after SAH. In accordance with previous data, Kronvall et al. (10) found a small proportion of patients with gonadotroph deficiency and no patients with central hypothyroidism. Several studies have investigated predictors of neuroendocrine abnormalities after SAH. In the acute phase, one study identified an association between the severity of bleeding on computed tomography scan (Fisher scale) and hormone levels, i.e., a direct correlation with serum cortisol and ACTH levels and an inverse correlation with testosterone levels. These likely reflected adaptation to acute illness as they were not found 12 months after SAH (13). Three previous studies did not find an association between parameters that illustrate SAH severity and presence of hypopituitarism during follow-up (1, 9, 13). Authors used Hunt and Hess grade, the Fisher computed tomography scale, or Glasgow Outcome Scale. Only in 1 study did authors find that initial hydrocephalus was associated with hypopituitarism 6 months after SAH (7). Aneurysm location or type of neurosurgical intervention (clipping versus coiling) was not a significant factor. In accordance with previous literature, Kronvall et al. (10) did not
www.WORLDNEUROSURGERY.org
1027
PERSPECTIVES
identify an association between hypopituitarism and Fisher scale, Hunt and Hess grade, or neurosurgical treatment type. Sex seems to play a role is some studies: women were more predisposed to central adrenal insufficiency in one study (9), and men developed more GH deficiency in another (7). This was not investigated in Krovall et al.’s study (10) that included only 1 male subject. Further research is needed to understand the consequences of neuroendocrine impairment on neurocognitive, emotional, and quality of life parameters. Correction of potential hormone deficiencies may favorably impact the outcome of patients with SAH. Thus far, no intervention studies were performed in patients with hypopituitarism after SAH, whereas studies in patients with TBI are ongoing. Randomized-controlled studies are needed to determine whether GH replacement is beneficial.
REFERENCES 1. Aimaretti G, Ambrosio MR, Di Somma C, Gasperi M, Cannavò S, Scaroni C, Fusco A, Del Monte P, De Menis E, Faustini-Fustini M, Grimaldi F, Logoluso F, Razzore P, Rovere S, Benvenga S, Degli Uberti EC, De Marinis L, Lombardi G, Mantero F, Martino E, Giordano G, Ghigo E: Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12month study. J Clin Endocrinol Metab 90:6085-6092, 2005. 2. Ho KK: Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol 157:695-700, 2007. 3. Hutter BO, Gilsbach JM, Kreitschmann I: Quality of life and cognitive deficits after subarachnoid haemorrhage. Br J Neurosurg 9:465-475, 1995. 4. Hutter BO, Kreitschmann-Andermahr I, Mayfrank L, Rohde V, Spetzger U, Gilsbach JM: Functional outcome after aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl 72:157-174, 1999. 5. Ioachimescu AG, Hampstead BM, Moore A, Burgess E, Phillips LS: Growth hormone defi-
Because many clinical manifestations of hypopituitarism are nonspecific, a thorough correlation with the degree of laboratory abnormalities is required. Detection of adrenal insufficiency in the acute SAH setting should be promptly treated as it may impact early outcome. In the subsequent months after SAH, neuroendocrine evaluation is recommended but treatment should be individualized. If cortisol and thyroid hormones deficits are found, treatment is recommended as these hormones are essential for stress adaptation, cardiovascular and metabolic regulation. Growth hormone testing should be performed in the appropriate clinical scenario after cortisol and thyroid deficiencies are appropriately replaced. Close monitoring and retesting is necessary, because pituitary function may improve over time in some patients, and a few patients with initially normal levels may develop new neuroendocrine deficits during follow-up (1, 6-8, 10, 13).
ciency after mild combat-related traumatic brain injury. Pituitary Sep 30 2014 [epub ahead of print].
prospective study using dynamic endocrine testing. World Neurosug 83:574-582, 2015.
6. Karaca Z, Tanriverdi F, Dagli AT, Selcuklu A, Casanueva FF, Unluhizarci K, Kelestimur F: Three years prospective investigation of pituitary functions following subarachnoid haemorrhage. Pituitary 16:76-82, 2013.
11. Lammert A, Bode H, Hammes HP, Birck R, Fatar M, Zohsel K, Schmieder K, Schubert GA, Thomé C, Seiz M: Aneurysmal subarachnoid hemorrhage (aSAH) results in low prevalence of neuro-endocrine dysfunction and NOT deficiency. Pituitary 15:505-512, 2012.
7. Khajeh L, Blijdorp K, Heijenbrok-Kal MH, Sneekes EM, van den Berg-Emons HJ, van der Lely AJ, Dippel DW, Neggers SJ, Ribbers GM, van Kooten F: Pituitary dysfunction after aneurysmal subarachnoid haemorrhage: course and clinical predictors—the HIPS study. J Neurol Neurosurg Psychiatry 2014 Nov 6 [epub ahead of print].
12. Powell J, Kitchen N, Heslin J, Greenwood R: Psychosocial outcomes at three and nine months after good neurological recovery from aneurysmal subarachnoid haemorrhage: predictors and prognosis. J Neurol Neurosurg Psychiatry 72:772-781, 2002.
8. Klose M, Brennum J, Poulsgaard L, Kosteljanetz M, Wagner A, Feldt-Rasmussen U: Hypopituitarism is uncommon after aneurysmal subarachnoid haemorrhage. Clin Endocrinol 73: 95-101, 2010. 9. Kreitschmann-Andermahr I, Hoff C, Saller B, Niggemeier S, Pruemper S, Hütter BO, Rohde V, Gressner A, Matern S, Gilsbach JM: Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage. J Clin Endocrinol Metab 89:4986-4992, 2004.
13. Tanriverdi F, Dagli AT, Karaca Z, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F: High risk of pituitary dysfunction due to aneurysmal subarachnoid haemorrhage: a prospective investigation of anterior pituitary function in the acute phase and 12 months after the event. Clin Endocrinol 67:931-937, 2007.
Citation: World Neurosurg. (2015) 83, 6:1026-1028. http://dx.doi.org/10.1016/j.wneu.2015.01.044 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
10. Kronvall E, Valdemarsson S, Saveland H, Nilsson OG: High prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a long-term
1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
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www.SCIENCEDIRECT.com
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.01.044
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 <3 ng/mL. For 14 patients in whom ITT was contraindicated, GHRH-arginine tests yielded a smaller prevalence of GH deficiency of 14%. These findings make overestimation of GH deficiency in this study unlikely. The prevalence of ACTH/cortisol deficiency after aneurysmal SAH is a subject of debate in the literature. Some studies suggest
From Emory University School of Medicine, Atlanta, Georgia, USA To whom correspondence should be addressed: Daniel L. Barrow, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 83, 6:1026-1028. http://dx.doi.org/10.1016/j.wneu.2015.01.044
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.01.044
PERSPECTIVES
Table 1. Prospective Studies Investigating Hypopituitarism After Aneurysmal SAH No. Patients (No. Men)
Time After SAH, months
Kreitschmann-Andermahr 44 7 et al., 2004 (9)
40 (14)
12e66
55%
Aimaretti et al., 2005 (1) 52 2
32 (12) 32(12)
3 12
46.8% 37.5%
48 3
22 (11)
Day of admission 12
Klose et al., 2010 (8)
46 (22e64)
26 (7) 62 (14)
Karaca et al., 2013 (6)
47 13
Khajeh et al., 2014 (7)*
56 12
Age
Tanriverdi et al., 2007 (13)
Kronvall et al., 2014 (10) 55 (28e75)
Hypopituitarism ACTH GH TSH FSH/LH GH Dynamic (One or More Axes) Deficiency Deficiency Deficiency Deficiency Testing 40%
20%
2.5%
None
ITT
3.1% 6.25%
25% 21.8%
9.3% 9.3%
9.3% 6.25%
GHRH-Arg GHRH-Arg
63.6% 36%
22.7% 13.6%
22.7% 36.4%
None None
31.8% None
None GHRH-Arg
<0.5 12
93% None
12% None
15% None
None None
93% None
None ITT/other
20 (12) 20 (12)
12 36
25% 20%
5% None
25% 20%
None None
None None
Glucagon Glucagon
84 (28)
<1 6 14
39% 26% 7%
2% None None
31% 10% 6%
1% 1% None
34% 20% 5%
Ghrelin GHRH-Arg GHRH-Arg
44 (1)
6e12 12e24
34% 43%
20% 20%
13% 25%
None None
2% 12%
None ITT or GHRH-Arg
Age (years) is shown as mean SD or median (range), as reported in original article. SAH, subarachnoid hemorrhage; ACTH, adrenocorticotroph hormone; GH, growth hormone; TSH, thyroid-stimulating hormone; FSH/LH, follicle-stimulating hormone/luteinizing hormone; ITT, insulin tolerance test; GHRH-Arg, growth hormoneereleasing hormone-arginine. *In the study by Khajeh et al. (7), only patients with previous ACTH and GH abnormalities were retested at 14 months.
prevalence as high as 40% when dynamic testing is performed more than 12 months after SAH (9). Other authors suggest that ACTH/cortisol deficiency is rare (<6.25%) (1, 6-8, 11), and one study indicated a prevalence of 13.6% at 12 months (13). The wide spectrum occurs in the context of different testing methods in each study, which included basal early morning cortisol determination, ACTH stimulation test (1 or 250 mg) or ITT, the latter considered the gold standard. Kronvall et al. (10) reported that central adrenal insufficiency occurs in 20% of patients both in the first and second year after SAH. The study authors used basal hormone measurements in the first year and ITT in the second year with a widely accepted cutoff of 18 mg/ dL. Of note, ACTH/cortisol insufficiency is rare in patients with a history of TBI (1, 5). Somatotroph cells are located on the wings of the anterior pituitary gland and receive blood supply from the hypothalamic-portal vessels. They are more susceptible to ischemia than corticotroph cells that have a central location and receive blood supply from the portal vessels as well as the anterior pituitary artery branches. The discordance between literature on TBI and SAH regarding central adrenal insufficiency has mechanistic implications that point towards a hypothalamic (rather than pituitary) dysfunction in SAH. This finding also has important therapeutic implications, because hypocortisolemia with onset in the early phase after aneurysmal rupture could lead to immediate complications and excess mortality. This issue cannot be readily ascertained from the literature, because dynamic endocrine studies usually are not performed in the neurointensive care setting. Also, patients with a poor neurologic outcome after SAH were not included in prospective trials. Studies agree that gonadotropin and thyrotropin deficiency are rare in patients evaluated 6 months or more after SAH
WORLD NEUROSURGERY 83 [6]: 1026-1028, JUNE 2015
(1, 6-10, 13). These results are based on basal hormone evaluation, which is the standard for adult endocrinology today. Although gonadotroph and gonadal hormone levels are low immediately after SAH, they almost always recover during follow-up (Table 1). Responses of the gonadotroph and thyrotroph axes to the acute phase of SAH reflect adaptation to critical illness, as previously shown in patients with septic shock. In contrast, the expected ACTH/cortisol response to acute illness consists of increased levels. A mild degree of hyperprolactinemia may occur immediately after SAH but usually resolves after a few months. Dysfunction of the posterior pituitary with diabetes insipidus is rare after SAH. In accordance with previous data, Kronvall et al. (10) found a small proportion of patients with gonadotroph deficiency and no patients with central hypothyroidism. Several studies have investigated predictors of neuroendocrine abnormalities after SAH. In the acute phase, one study identified an association between the severity of bleeding on computed tomography scan (Fisher scale) and hormone levels, i.e., a direct correlation with serum cortisol and ACTH levels and an inverse correlation with testosterone levels. These likely reflected adaptation to acute illness as they were not found 12 months after SAH (13). Three previous studies did not find an association between parameters that illustrate SAH severity and presence of hypopituitarism during follow-up (1, 9, 13). Authors used Hunt and Hess grade, the Fisher computed tomography scale, or Glasgow Outcome Scale. Only in 1 study did authors find that initial hydrocephalus was associated with hypopituitarism 6 months after SAH (7). Aneurysm location or type of neurosurgical intervention (clipping versus coiling) was not a significant factor. In accordance with previous literature, Kronvall et al. (10) did not
www.WORLDNEUROSURGERY.org
1027
PERSPECTIVES
identify an association between hypopituitarism and Fisher scale, Hunt and Hess grade, or neurosurgical treatment type. Sex seems to play a role is some studies: women were more predisposed to central adrenal insufficiency in one study (9), and men developed more GH deficiency in another (7). This was not investigated in Krovall et al.’s study (10) that included only 1 male subject. Further research is needed to understand the consequences of neuroendocrine impairment on neurocognitive, emotional, and quality of life parameters. Correction of potential hormone deficiencies may favorably impact the outcome of patients with SAH. Thus far, no intervention studies were performed in patients with hypopituitarism after SAH, whereas studies in patients with TBI are ongoing. Randomized-controlled studies are needed to determine whether GH replacement is beneficial.
REFERENCES 1. Aimaretti G, Ambrosio MR, Di Somma C, Gasperi M, Cannavò S, Scaroni C, Fusco A, Del Monte P, De Menis E, Faustini-Fustini M, Grimaldi F, Logoluso F, Razzore P, Rovere S, Benvenga S, Degli Uberti EC, De Marinis L, Lombardi G, Mantero F, Martino E, Giordano G, Ghigo E: Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12month study. J Clin Endocrinol Metab 90:6085-6092, 2005. 2. Ho KK: Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol 157:695-700, 2007. 3. Hutter BO, Gilsbach JM, Kreitschmann I: Quality of life and cognitive deficits after subarachnoid haemorrhage. Br J Neurosurg 9:465-475, 1995. 4. Hutter BO, Kreitschmann-Andermahr I, Mayfrank L, Rohde V, Spetzger U, Gilsbach JM: Functional outcome after aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl 72:157-174, 1999. 5. Ioachimescu AG, Hampstead BM, Moore A, Burgess E, Phillips LS: Growth hormone defi-
Because many clinical manifestations of hypopituitarism are nonspecific, a thorough correlation with the degree of laboratory abnormalities is required. Detection of adrenal insufficiency in the acute SAH setting should be promptly treated as it may impact early outcome. In the subsequent months after SAH, neuroendocrine evaluation is recommended but treatment should be individualized. If cortisol and thyroid hormones deficits are found, treatment is recommended as these hormones are essential for stress adaptation, cardiovascular and metabolic regulation. Growth hormone testing should be performed in the appropriate clinical scenario after cortisol and thyroid deficiencies are appropriately replaced. Close monitoring and retesting is necessary, because pituitary function may improve over time in some patients, and a few patients with initially normal levels may develop new neuroendocrine deficits during follow-up (1, 6-8, 10, 13).
ciency after mild combat-related traumatic brain injury. Pituitary Sep 30 2014 [epub ahead of print].
prospective study using dynamic endocrine testing. World Neurosug 83:574-582, 2015.
6. Karaca Z, Tanriverdi F, Dagli AT, Selcuklu A, Casanueva FF, Unluhizarci K, Kelestimur F: Three years prospective investigation of pituitary functions following subarachnoid haemorrhage. Pituitary 16:76-82, 2013.
11. Lammert A, Bode H, Hammes HP, Birck R, Fatar M, Zohsel K, Schmieder K, Schubert GA, Thomé C, Seiz M: Aneurysmal subarachnoid hemorrhage (aSAH) results in low prevalence of neuro-endocrine dysfunction and NOT deficiency. Pituitary 15:505-512, 2012.
7. Khajeh L, Blijdorp K, Heijenbrok-Kal MH, Sneekes EM, van den Berg-Emons HJ, van der Lely AJ, Dippel DW, Neggers SJ, Ribbers GM, van Kooten F: Pituitary dysfunction after aneurysmal subarachnoid haemorrhage: course and clinical predictors—the HIPS study. J Neurol Neurosurg Psychiatry 2014 Nov 6 [epub ahead of print].
12. Powell J, Kitchen N, Heslin J, Greenwood R: Psychosocial outcomes at three and nine months after good neurological recovery from aneurysmal subarachnoid haemorrhage: predictors and prognosis. J Neurol Neurosurg Psychiatry 72:772-781, 2002.
8. Klose M, Brennum J, Poulsgaard L, Kosteljanetz M, Wagner A, Feldt-Rasmussen U: Hypopituitarism is uncommon after aneurysmal subarachnoid haemorrhage. Clin Endocrinol 73: 95-101, 2010. 9. Kreitschmann-Andermahr I, Hoff C, Saller B, Niggemeier S, Pruemper S, Hütter BO, Rohde V, Gressner A, Matern S, Gilsbach JM: Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage. J Clin Endocrinol Metab 89:4986-4992, 2004.
13. Tanriverdi F, Dagli AT, Karaca Z, Unluhizarci K, Selcuklu A, Casanueva FF, Kelestimur F: High risk of pituitary dysfunction due to aneurysmal subarachnoid haemorrhage: a prospective investigation of anterior pituitary function in the acute phase and 12 months after the event. Clin Endocrinol 67:931-937, 2007.
Citation: World Neurosurg. (2015) 83, 6:1026-1028. http://dx.doi.org/10.1016/j.wneu.2015.01.044 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
10. Kronvall E, Valdemarsson S, Saveland H, Nilsson OG: High prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a long-term
1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
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WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.01.044