| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Division of Endocrinology and Metabolism (G.A., S.R., E.G.), Department of Internal Medicine, University of Turin, 10126 Turin, Italy; Department of Biomedical Sciences and Advanced Therapies (M.R.A., E.C.d.U.), Section of Endocrinology, University of Ferrara, 44100 Ferrara, Italy; Departments of Molecular and Clinical Endocrinology and Oncology (C.D.S., G.L.), University of Naples Federico IIø, 80138 Naples, Italy; Department of Endocrinology and Metabolism (M.G., E.M.), University of Pisa, 56127 Pisa, Italy; Department of Medicine and Pharmacology (S.C., S.B.), Section of Endocrinology, University of Messina, 98100 Messina, Italy; Division of Endocrinology (C.S., F.M.), Department of Surgical and Medical Sciences, University of Padua, 35122 Padua, Italy; Division of Endocrinology (A.F., L.D.M.), Catholic University, 00168 Rome, Italy; Division of Endocrinology (P.D.M.), Galliera Hospital, 16128 Genova, Italy; Service of Endocrinology (E.D.M.), Treviso Hospital, 31100 Treviso, Italy; Division of Endocrinology (M.F.-F.), Bellaria Hospital, 40139 Bologna, Italy; Division of Endocrinology (F.G.), S. Maria della Misericordia Hospital, 33100 Udine, Italy; Division of Endocrinology (F.L.), University of Bari, 70126 Bari, Italy; Division of Endocrinology (P.R.), S. Croce e Carle Hospital, 12100 Cuneo, Italy; and Italian Society of Endocrinology (G.G.), Chairman of the Study Group on Physiopathology of GH Secretion
Address all correspondence and requests for reprints to: Ezio Ghigo, M.D., Division of Endocrinology and Metabolic Diseases, Department of Internal Medicine, University of Turin, C.so Dogliotti, 14, 10126 Turin, Italy. E-mail: ezio.ghigo{at}unito.it.
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Objective: The objective of the study was to clarify whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury.
Design and Patients: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32).
Results: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency.
Conclusion: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The pathogenesis of brain injury-induced hypopituitarism is still to be elucidated. However, very old studies in patients who had had fatal TBI demonstrated that various degrees of pituitary hemorrhagic infarction were present in more than 70% of patients (1, 23, 24), whereas hypothalamic microhemorrages were present in at least 40% of patients (25). It is noteworthy that hypopituitarism is not associated with the severity of the neurological status after the brain injury (6, 15, 18). However, clear posttraumatic hypothalamus-pituitary lesions well explain the high incidence of hypopituitarism. This kind of lesion leaves open the possibility that neuroendocrine abnormalities recorded early after brain injury would further progress or, alternatively, that would be transient allowing recovery of pituitary function.
The high risk for brain-induced hypopituitarism also was clear in our previous study in which we tested the pituitary function 3 months after the pathological event (18). That study had been planned as a prospective one aiming to define pituitary function over 1 yr after brain injuries such as head trauma (TBI) or SAH. In fact, we would like to clarify variations in pituitary function over time after the brain injury. To this goal, in a multicenter study under the auspices of the Italian Society of Endocrinology, in a considerable number of patients who suffered TBI (n = 70) or SAH (n = 32), pituitary function was tested at 3 and again at 12 months.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In collaboration with neurosurgeons and neurologists of various Italian centers, we tested pituitary function in brain-injured patients at 3 and 12 months after the pathological event (Tables 1
and 2).
|
|
8)]. The GCS represents a summary of the TBI patient’s level of consciousness as indicated by scores of eye opening, motor responses, and verbal responses. Severity of injury is indicated by the total score: 3–8, severe; 9–13, moderate; and 14–15, mild (26).
SAH (from rupture of an aneurysm). There was a total of 32 patients: 12 males and 20 females aged 51.9 ± 2.2 yr with a BMI of 24.7 ± 0.6 kg/m2 (Fisher’s scale 1–4).
The Fisher’s computerized tomography (CT) Scale is used to estimate the density of subarachnoid blood shown by CT scanning. A Fisher score is usually obtained at the time of admission (26).
No patient had had known neuroendocrine disease before the pathological event. No patient was receiving glucocorticoid treatment during the prospective study. Patients who had been treated with glucocorticoid during their stay in the intensive care unit had stopped glucocorticoid administration at least 2 months before hormonal testing at 3 months. In this prospective study, all patients who were diagnosed as hypopituitaric at 3 months were treated accordingly with international guidelines and the most important textbook of Endocrinology (3, 27, 28, 29) as follows: 1) 1-desamino-8-D-arginine vasopressin (0.1 mg tablet orally) as appropriate for replacement of diabetes insipidus; 2) hydrocortisone or cortisone acetate as appropriate (15–20 and 25–37.5 mg, respectively) for replacement in secondary hypoadrenalism; and 3) L-thyroxine as appropriate for replacement in secondary hypothyroidism.
Secondary hypogonadism at 3 months was not replaced, waiting for reconfirmation at 12 months. GH deficiency (GHD) was never replaced after demonstration at 3 months. It had been planned to replace severe GHD with recombinant human GH only after appropriate replacement of other pituitary deficits when present and after retesting confirming the defect at 12 months.
The hormonal replacement was eventually withdrawn at least 7 d before retesting for 1-desamino-8-D-arginine vasopressin and hydrocortisone or cortisone acetate and at least 30 d before for L-thyroxine replacement.
Data analysis
In each clinical center, the internal standard reference ranges were used to discriminate abnormal from normal results.
Specifically, diabetes insipidus was demonstrated by the presence of massive dilute urine volume (>2.5–3 liters per 24 h) with low urine osmolality (<300 mmol/kg) (3, 27, 28, 29). Second, moderate and severe secondary adrenal insufficiency was demonstrated by early-morning (at 0900 h) cortisol concentrations less than 80 µg/liter. Low 24-h urinary free cortisol levels (<30 µg/24 h) were also taken into account, although urinary free cortisol measurement is not generally considered a reliable parameter for the diagnosis of adrenal insufficiency (27). Third, secondary hypothyroidism was demonstrated by low free T4 (<8 ng/liter) concentrations with normal or low normal TSH levels (3, 27, 28, 29). And fourth, secondary hypogonadism was demonstrated by, in premenopausal women by menstrual disturbances, low estradiol levels (<20 pg/ml) with normal or low FSH and LH levels, and, in men, by low testosterone levels (<3 µg/liter) with low or normal FSH and LH levels (3, 27, 28, 29).
GHD was demonstrated by peak GH response to GHRH + arginine less than 16.5 µg/liter (third centile limit of normal GH response). Peak GH response less than 9.0 µg/liter (first centile limit) indicated severe GHD; the latter cut-off represents the limit below which severe GHD is demonstrated by the GHRH + arginine test that is a provocative test approximately 3 times more potent than insulin tolerance test (ITT) (30, 31). That the diagnostic accuracy of GHRH + arginine test with a cut-off of 9 µg/liter is the same one of ITT with a cut-off of 3 µg/liter has been already demonstrated (31).
IGF-I levels were considered with respect to the 25th centile age-related normal limits (30, 31, 32, 33). It is widely accepted that normal IGF-I levels do not rule out severe GHD, although low levels strongly suggest the presence of GHD. Because the concordance between GH peak after provocative test and IGF-I levels markedly increases by adopting the 25th centile of normal IGF-I limits (32), in the present study, IGF-I levels below this arbitrary cut-off were considered.
The results are expressed as mean ± SEM and percentage of abnormal response with respect to normative cut-off levels. The statistical analysis was carried out using the SPSS, Inc. (Cary, NC) package. The correlation between variables was sought calculating the Pearson coefficient. The risk to develop hypopituitarism was calculated by logistic regression analysis. The percentages were compared using 
2 test, with Fisher correction when appropriate. A two-tailed P < 0.05 was taken as showing statistical significance.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
and Fig. 1)In TBI patients, the 3-month evaluation had shown some degree of hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively.
|
|
Severe GHD (peak GH below the first centile, i.e. <9 µg/liter) (30, 31) was recorded in 16 of 70 patients (22.8% of the total TBI; isolated in nine and associated with other deficits in seven). Another 11 of 70 patients had GH peak in between the first and third centile limit; this subnormal GH response to a provocative test as potent as GHRH + arginine could be assumed as partial GHD (pGHD). IGF-I levels below the 25th centile of the age-related normal limits were present in 12.8% of patients always associated with GHD either severe or partial. Mild hyperprolactinemia was demonstrated in 4.2% of TBI patients and associated to pituitary deficits in two of three TBI patients.
The 12-month retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH recorded at 3 months was confirmed in nearly 25% only. Conversely, in 5.5% of TBI with normal pituitary function at 3 months (two of 36), IH deficits were recorded at 12 months. Moreover, in 13.3% (two of 15) of TBI with IH at 3 months, MH was demonstrated at 12-month retesting.
Diabetes insipidus was present in 2.8% of the patients. Secondary adrenal, thyroid, and gonadal deficit was present in 7.1, 5.7, and 11.4%, respectively. Specifically, four of 70 patients had secondary adrenal insufficiency, 5 of 70 patients had secondary hypothyroidism, and eight patients had secondary hypogonadism (three women and five men). Secondary hypothyroidism was always associated with other pituitary deficits. Secondary hypoadrenalism was always associated with other pituitary deficits in all but one of the patients.
Severe GHD (peak GH below the first centile, i.e. <9 µg/liter) (30, 31) was recorded in 14 of 70 patients (20% of the total TBI; isolated in seven and associated with other deficits in seven). Another 13 of 70 patients had GH peak in between the first and third centile limit; this subnormal GH response to a provocative test as potent as GHRH + arginine could be assumed as pGHD.
IGF-I levels below the 25th centile of the age-related normal limits were present in 15.7% of patients, always associated with GHD either severe or partial. Mild hyperprolactinemia was demonstrated in 5.7% of TBI patients and never associated with severe pituitary deficits.
SAH patients (Table 3
and Fig. 2)
In SAH patients, the 3-month evaluation had shown some degree of H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively.
|
Specifically, one of 32 patients had secondary adrenal insufficiency, three of 32 patients had secondary hypothyroidism, and three of 32 patients had secondary hypogonadism (one women and two men). Secondary hypothyroidism was associated with other pituitary deficits in two of three patients; in one patient it was isolated. Secondary hypoadrenalism was diagnosed as isolated.
Severe GHD (peak GH below the first centile, i.e. <9 µg/liter) (30, 31) was recorded in eight of 32 patients (25% of the total TBI; isolated in seven and associated with other deficits in one). Another four of 32 patients (12.5%) had GH peak between the first and third centile limit; this subnormal GH response to a provocative test as potent as GHRH + arginine could be assumed as pGHD. No patient showed IGF-I levels below the 25th centile of the age-related normal limits.
Mild hyperprolactinemia was demonstrated in only one patient after SAH and associated with severe pituitary deficit.
The 12-month retesting demonstrated some degree of H in 37.5%.
MH and IH were present in 6.2 and 31.3%, respectively. However, whereas no MH recorded at 3 months was confirmed at 12 months, two patients with IH at 3 months showed MH at 12-month retesting. On the other hand, four patients who had shown IH deficit at 3 months displayed normal pituitary function at 12 months.
In SAH patients, normal pituitary function at 3 months was always confirmed at 12 months.
No patient showed diabetes insipidus. Secondary adrenal, thyroid, and gonadal deficit was present in 6.25, 9.3, and 6.25%, respectively. Specifically, two of 32 patients had secondary adrenal insufficiency, three of 32 patients had secondary hypothyroidism, and two of 32 patients had secondary hypogonadism (one woman and one man). Secondary hypothyroidism was associated with other pituitary deficits in one of three patients; in two patients it was isolated. Secondary hypoadrenalism was always associated with other deficits.
Severe GHD (peak GH below the first centile, i.e. <9 µg/liter) (30, 31) was recorded in seven of 32 patients (21.8% of the total TBI; isolated in six and associated with other deficits in one). Another five of 32 patients (15.6%) had GH peak between the first and third centile limit; this subnormal GH response to a provocative test as potent as GHRH + arginine could be assumed as pGHD.
IGF-I levels less than the 25th centile of the age-related normal limits were present in 3.1% of patients always associated with GHD.
Mild hyperprolactinemia was reconfirmed in the patient already diagnosed as hyperprolactinemic at 3-month testing.
Comparison between TBI and SAH patients
The frequency of hypopituitarism was comparable between TBI and SAH patients population (2 = 1.295 and 1.686, P = NS, respectively), both at 3- and 12-month testing. Moreover, at both 3 and 12 months in each patient population were seen any difference in the occurrence of hypopituitarism.
The occurrence of hypopituitarism was not associated with the GCS (odds ratio 1.08, 95% confidence interval 0.92–1.19) or the Fisher’s scale (odds ratio 0.95, 95% confidence interval 0.47–1.71) in TBI and SAH, respectively. These scores did not associate with the GH responses too (TBI: r = 0.1, P = 0.6; SAH: r = 0.09, P = 0.68) (Table 4).
|
There was no gender-related difference in both patient populations at either 3- or 12-month follow-up.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Several studies had demonstrated that brain injuries such as head trauma (TBI) or SAH are often the cause of hypopituitarism. Indeed the risk for hypopituitarism after brain injuries is much greater than previously suspected, i.e. from 20 to 50% of brain-injured patients (4, 5). Given the very high incidence of TBI (annual incidence 
230 in 300,000 in the United States and 300 in 100,000 in Italy), the high percentage of hypopituitarism induced by TBI represents a relevant problem (7, 8, 9, 10, 11, 12). Hormonal replacement of hypopituitarism is always mandatory, but appropriate hormonal replacement would also provide peculiar benefit to brain-injured patients improving the postinjury syndrome (4, 5, 6, 15, 18).
Interest about this topic had been awakened by some case reports published in early 2000 (4, 5, 6). Kelly et al. (5) and Lieberman et al. (6) first found high prevalence of neuroendocrine dysfunction in patients who had had previous moderate and severe TBI. Kelly et al. also emphasized how SAH is at high risk for hypopituitarism (5). This picture was more recently confirmed by other studies in both TBI and SAH (14, 15, 16, 17, 18, 19).
As anticipated, the percentage of hypopituitaric patients after TBI or SAH generally varied between 20 and 50%. The studies were generally retrospective ones, some testing patients who had had brain injury more than a year ago (4, 6), others testing patients early after TBI or SAH (13, 14, 20, 21, 22). The existence of clear posttraumatic hypothalamus-pituitary lesions well explain the high incidence of hypopituitarism (1, 23, 24, 25). In fact, old studies in patients who had had fatal TBI demonstrated that various degrees of pituitary hemorrhagic infarction was present in more than 70% of patients (1, 23, 24), whereas hypothalamic microhemorrages were present in at least 40% of patients (25). This kind of lesion leaves open the possibility that neuroendocrine abnormalities recorded early after brain injury would further progress or, alternatively, would be transient, allowing recovery of pituitary function over time. To clarify this point, we planned a prospective study aiming to define pituitary function over 1 yr after brain injuries such as TBI or SAH.
In agreement with our previous study (18), the results show that 3 months after the TBI or SAH, 50 and 40% of patients show fully normal pituitary function. Another 12–15% are likely to be normal, although there is slight impairment of somatotroph function that would represent partial GHD, given some significant reduction of the GH response to a maximal provocative test such as GHRH + arginine test. Besides this percentage, 3 months after the brain injury, 5.7% of patients show panhypopituitarism (only in TBI group), 5.7 and 6.25% multiple pituitary deficits (TBI and SAH, respectively) and 21.4 and 40% isolated pituitary deficit (TBI and SAH, respectively). In all, 32.8–46.8% of patients has some degree of pituitary impairment, whereas 11.4–6.25% were from multiple to total pituitary deficits. This picture is impressive and fits well with observation made by others (5, 6, 15).
The follow-up at 12 months after TBI or SAH demonstrated some significant change. Twelve months after the injuries, nearly 60 and 50% (for TBI and SAH) show fully normal pituitary function. Another 18.6 and 15.6% of patients are likely to be normal, although present with slight impairment of somatotroph function that would represent partial GHD. Thus, the follow-up shows some significant increase in the percentage of preserved pituitary function. Nevertheless, 22.2 and 37.5% of patients (TBI and SAH) has some degree of pituitary impairment, whereas 9.9 and 6.25% had from multiple to total pituitary deficits. Interestingly, total hypopituitarism is always confirmed by the follow-up. Conversely, isolated and even multiple pituitary insufficiencies recorded in the short term seem transient, no longer being recorded at 12 months. Thus, pituitary function in brain-injured patients may improve over time, and this transient hypopituitarism would reflect effective repair of the hypothalamus-pituitary damages induced by the brain injury (1, 13, 23). However, although rarely, in brain-injured patients, pituitary function may worsen over time as indicated by the worsening of some isolated deficits to multiple pituitary insufficiencies or the appearance of isolated deficits in subjects who had been normal at 3 months. This worsening over time after brain injuries would agree with the possibility that injury-induced hypothalamus-pituitary damage may become functionally apparent only in the long term.
Evidence that the high risk of brain injury-induced hypopituitarism is subject to variations as function of the time in which pituitary function is tested indicates that brain-injured patients must always undergo neuroendocrine follow-up over time. This appears of major importance to monitoring pituitary function and eventually providing appropriate hormonal replacement.
In agreement with some (5, 6, 17) but not with others (4, 15), it is confirmed that severe GHD is the most common brain injury-induced pituitary deficit either isolated or associated with other pituitary deficit at 12 as well as 3 months after the pathological event. Because somatotropic cells are located in the wings of the pituitary and the vascular supply and oxygen they receive come out of the hypothalamopituitary portal vessels, brain injury-induced damage can well impair blood and oxygen supply resulting in cell death and frequent GHD (23). In contrast, ACTH- and TSH-secreting cells are located ventrally in the medial pituitary portion in which they receive blood from the portal vessels and the anterior pituitary artery branch; this vasculature more easily provides any way for nutrients and oxygen to cells in this area as well as the subcapsular part (23).
Severe GHD as well as hypopituitarism in general does not appear to be correlated to the severity of brain injury (6, 15, 17, 18, 22). Moreover, the low GH response to the provocative test is not under negative association to BMI (18). Although GHD is the most common brain injury-induced pituitary deficit, it appears transient in 2% of the TBI patients and 4% in SAH patients, in whom it had been found at 3 months. This low frequency of transitory GHD would also reflect that retesting was performed under appropriate hormonal replacement of other deficits in patients with multiple or total hypopituitarism recorded at 3 months. In any case, the incidence of severe GHD at 12 months as either an isolated deficit or within multiple or total hypopituitarism remains very remarkable, being present in approximately 20%. As anticipated, the pathogenesis of brain injury-induced hypopituitarism might often reflect hypothalamic damage (1, 23, 24, 25). Taking into account that a GHRH + arginine test would underestimate GHD due to hypothalamic origin early after cranial radiation (34), it might be that this provocative test underestimated a bit the number of GHD patients in the first year after TBI or SAH. It remains that ITT is contraindicated after brain injuries.
The second most frequent pituitary deficit after brain injury is secondary hypogonadism. It is found in approximately 14% of brain-injured patients at 3 months and in approximately 7% after 12 months. Thus, secondary hypogonadism is frequently transient; the full recovery of gonadal function over time would also suggest that transient hypogonadism was functional eventually reflecting stressful condition more intense in the short term after brain injury (14, 35, 36).
Evidence that severe GHD and secondary hypogonadism more often seem a transient pituitary deficit in the context of brain injury-induced hypopituitarism support our choice to wait for hormonal replacement of these functions when demonstrated in the short term (3 months) after TBI or SAH. On the other hand, early hormonal replacement of other more critical pituitary functions such as antidiuretic hormone, corticotroph, and thyrotrophic secretion seems the best choice. In our hands, other pituitary deficits such as diabetes insipidus, secondary hypothyroidism, and/or hypoadrenalism were less frequent but generally stable and confirmed at 12 months. Regarding the diagnosis of secondary adrenal insufficiency, the evaluation of the adrenal reserve by dynamic test would increase its reliability; Dimopoulou et al. (37, 38) already showed that secondary adrenal insufficiency after TBI is more appropriately diagnosed by ACTH test. However, as anticipated, the adrenal alterations recorded in our present study were generally stable over time and associated with other pituitary deficits.
Our picture about the most common pituitary deficits agree with some (5, 6, 17) but not others (4, 15) who found secondary hypoadrenalism or hypogonadism as the most frequent defects. It is not easy to explain these discrepancies; however, it should be taken into account that a clear picture of what pituitary function exactly is just after the brain injury is a piece of information not yet available. How many and how much pituitary functions can be impaired in the acute phase afterbrain injury and how much this impairment has role in the probabilities of survival and recovery are questions awaiting answers. The current criteria by which pituitary deficits are defined would also have a role in different frequencies of various pituitary functions (26, 29).
In all, this prospective study confirms the high risk for hypopituitarism in TBI and SAH patients. Early diagnosis of panhypopituitarism is always confirmed in the long term after the brain injury, whereas partial impairment of pituitary function (isolated and even multiple deficits) recorded just after brain injures may improve over time. Conversely, normal pituitary function in the short term, although rare, becomes impaired later on. Thus, brain-injured patients must always undergo neuroendocrine follow-up over time to monitor pituitary function and eventually provide appropriate hormonal replacement.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
First Published Online September 6, 2005
Abbreviations: BMI, Body mass index; CT, computerized tomography; GCS, Glasgow Coma Scale; GHD, GH deficiency; H, hypopituitarism; IH, isolated H; ITT, insulin tolerance test; MH, multiple H; pGHD, partial GHD; PH, panhypopituitarism; SAH, subarachnoid hemorrhage; TBI, traumatic brain injury.
Received March 8, 2005.
Accepted August 18, 2005.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  L A Behan, J Phillips, C J Thompson, and A Agha Neuroendocrine disorders after traumatic brain injury J. Neurol. Neurosurg. Psychiatry, July 1, 2008; 79(7): 753 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Tanriverdi, A. De Bellis, A. Bizzarro, A. A. Sinisi, G. Bellastella, E. Pane, A. Bellastella, K. Unluhizarci, A. Selcuklu, F. F Casanueva, et al. Antipituitary antibodies after traumatic brain injury: is head trauma-induced pituitary dysfunction associated with autoimmunity? Eur. J. Endocrinol., July 1, 2008; 159(1): 7 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Mossberg, B. E. Masel, C. R. Gilkison, and R. J. Urban Aerobic Capacity and Growth Hormone Deficiency after Traumatic Brain Injury J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2581 - 2587. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Tanriverdi, K. Unluhizarci, I. Kocyigit, I. S. Tuna, Z. Karaca, A. C. Durak, A. Selcuklu, F. F. Casanueva, and F. Kelestimur Brief Communication: Pituitary Volume and Function in Competing and Retired Male Boxers Ann Intern Med, June 3, 2008; 148(11): 827 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Xydakis, A. S. Robbins, G. A. Grant, R. R. Das, L. D. Stonesifer, R. L. Ruff, C. W. Hoge, C. C. Engel, and C. A. Castro Mild traumatic brain injury in U.S. soldiers returning from Iraq. N. Engl. J. Med., May 15, 2008; 358(20): 2177 - 2178. [Full Text] [PDF]
|
|
|
|
 |
|
 P Poomthavorn, W Maixner, and M Zacharin Pituitary function in paediatric survivors of severe traumatic brain injury Arch. Dis. Child., February 1, 2008; 93(2): 133 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Rothman, D. B. Arciniegas, C. M. Filley, and M. E. Wierman The Neuroendocrine Effects of Traumatic Brain Injury J Neuropsychiatry Clin Neurosci, November 1, 2007; 19(4): 363 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Schneider, I. Kreitschmann-Andermahr, E. Ghigo, G. K. Stalla, and A. Agha Hypothalamopituitary Dysfunction Following Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: A Systematic Review JAMA, September 26, 2007; 298(12): 1429 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Manetti, I. Lupi, L. L. Morselli, S. Albertini, M. Cosottini, L. Grasso, M. Genovesi, G. Pinna, S. Mariotti, F. Bogazzi, et al. Prevalence and Functional Significance of Antipituitary Antibodies in Patients with Autoimmune and Non-Autoimmune Thyroid Diseases J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2176 - 2181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L Acerini, R. C Tasker, S. Bellone, G. Bona, C. J Thompson, and M. O Savage Hypopituitarism in childhood and adolescence following traumatic brain injury: the case for prospective endocrine investigation. Eur. J. Endocrinol., November 1, 2006; 155(5): 663 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H J Schneider, S Rovere, G Corneli, C G Croce, V Gasco, R Ruda, S Grottoli, G K Stalla, R Soffietti, E Ghigo, et al. Endocrine dysfunction in patients operated on for non-pituitary intracranial tumors. Eur. J. Endocrinol., October 1, 2006; 155(4): 559 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Tanriverdi, H. Senyurek, K. Unluhizarci, A. Selcuklu, F. F. Casanueva, and F. Kelestimur High Risk of Hypopituitarism after Traumatic Brain Injury: A Prospective Investigation of Anterior Pituitary Function in the Acute Phase and 12 Months after Trauma J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2105 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Molitch, D. R. Clemmons, S. Malozowski, G. R. Merriam, S. M. Shalet, M. L. Vance, and for The Endocrine Society's Clinical Guidelines Su Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1621 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H J Schneider, M Schneider, B Saller, S Petersenn, M Uhr, B Husemann, F von Rosen, and G K Stalla Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury Eur. J. Endocrinol., February 1, 2006; 154(2): 259 - 265. [Abstract] [Full Text] [PDF]
|
|
Read all eLetters
| |||||||||||||||||||||||||||||||||||||||||||||||||||
