High risk of hypopituitarism after traumatic brain injury: a prospective investigation of anterior pituitary function in the acute phase and 12 months after trauma

CONTEXT: Recent data have demonstrated that traumatic brain injury (TBI)-mediated hypopituitarism could be more frequent than previously known. However, most previous data were obtained from retrospective studies. OBJECTIVES: The aim of this study was to determine 1) the prevalence of anterior pituitary hormone deficiencies in the acute phase of TBI and after 12 months, 2) whether severity of trauma correlated with basal hormone levels, and 3) whether initial hormone deficiencies predicted medium-term hormonal status. DESIGN AND PATIENTS: Fifty-two TBI patients (43 men and nine women) were included in the prospective study. Pituitary function was evaluated within 24 h of admission and after 1 yr. RESULTS: Some 5.8% of the patients had TSH deficiency, 41.6% had gonadotropin deficiency, 9.8% had ACTH deficiency, and 20.4% had GH deficiency (GHD). Twelve months after TBI, 5.8% had TSH deficiency, 7.7% had gonadotropin deficiency, 19.2% had ACTH deficiency, and 37.7% had GHD. Twenty-six patients (50.9%) had at least one anterior pituitary hormone deficiency, 21 patients (41.2%) had isolated hormone deficiencies, and five patients (9.7%) had combined hormone deficiencies. Overall, the pituitary hormone deficiencies recovered in 30 (57.7%) patients after 1 yr, and new pituitary hormone deficiencies were present in 27 (51.9%) patients after 1 yr. CONCLUSIONS: GHD is the most common pituitary deficit 12 months after TBI, and 50.9% of the patients had at least one anterior pituitary hormone deficiency. Pituitary function may improve or worsen in a considerable number of patients over 12 months.     

Three years prospective investigation of anterior pituitary function after traumatic brain injury: a pilot study

Objective It has been recently demonstrated that traumatic brain injury (TBI)‐mediated hypopituitarism could be more frequent than previously known. However, most of the previous data were obtained from retrospective studies, and the natural history of the hypopituitarism due to TBI is still unclear. So far no study has been reported in which the pituitary function of the same patients has been investigated more than 1 year after TBI. Therefore, we report the results of 3 years prospective follow‐up of anterior pituitary function in patients with mild, moderate and severe TBI. Patients and design Thirty patients (25 males, 5 females; age 37·2 ± 2·4 years) with TBI were included in the study. Pituitary function was evaluated at 1 and 3 years after TBI. Results After individual evaluation of GH deficiency from 1 year to 3 years after TBI, 7 of 13 (53·8%) GH‐deficient patients at 1st year recovered after 3 years of TBI, and GH deficiency detected at 3 years in one patient was new onset. Additionally, five of six (83·3%) ACTH‐deficient patients at 1st year recovered after 3 years of TBI, and ACTH deficiency detected at 3 years in one patient was new onset. Conclusions GH deficiency is the most common pituitary deficit 1 and 3 years after TBI. In patients with mild and moderate TBI, pituitary function improves over time in a considerable number of patients, but it may also worsen rarely over the 3‐year period. In patients with severe TBI, ACTH and GH deficiencies at 1st year evaluation persist at 3rd year.     

Manifesto for the current understanding and management of traumatic brain injury-induced hypopituitarism

Traumatic brain injury (TBI)-induced hypopituitarism remains a relevant medical problem, because it may affect a significant proportion of the population. In the last decade important studies have been published investigating pituitary dysfunction after TBI. Recently, a group of experts gathered and revisited the topic of TBI-induced hypopituitarism. During the 2-day meeting, the main issues of this topic were presented and discussed, and current understanding and management of TBI-induced hypopituitarism are summarized here.     

Epidemiology of community-acquired and nosocomial bloodstream infections in tropical Australia: a 12-month prospective study

OBJECTIVES: To define the relative incidence of organisms causing blood stream infections in a tropical setting with a very low prevalence of human immunodeficiency virus infection (<1%). METHODS: A 12-month prospective study of blood stream infections in 2000 at Royal Darwin Hospital in the tropical north of Australia. RESULTS: Significant isolates were grown from 257 sets of blood cultures. Staphylococcus aureus was the most common isolate overall (28%); 26% of these were methicillin-resistant (MRSA). Escherichia coli was the most common cause of community-acquired bacteraemia. Burkholderia pseudomallei caused 32% of community acquired, bacteraemic pneumonia; 6% of bacteraemias overall. Vancomycin-resistant enterococci were not isolated. Crude mortality rates (13% overall; 9% attributable mortality) were lower than in most comparable studies. CONCLUSIONS: The major difference between these findings and surveys performed elsewhere is the presence of B. pseudomallei as a significant cause of bacteraemic community-acquired pneumonia. Our results demonstrate the effects of local environmental and patient characteristics on the range of organisms causing blood stream infections, and emphasize the important role of local microbiology laboratories in guiding empiric antibiotic therapy.     

Hypothalamic hypopituitarism after pituitary apoplexy in acromegaly.

Pituitary apoplexy in acromegaly is an uncommon event having been recorded approximately 30 times in the English literature.This report records two additional cases that included growth hormone measurements and an assessment of pituitary function. The apoplectic event developed spontaneously in one, and in the other it developed within two weeks of completing a course of radiotherapy to the pituitary gland. Autocure of the acromegaly was apparent. Basal levels of growth hormone were in the normal range but failed to change with provocative stimuli. Luteinizing hormone and follicle-stimulating hormone titers, although detectable, were inappropriately low for the degree of hypogonadism. Pituitary insufficiency was associated with a significant thyroid-stimulating hormone response to protirelin in one patient tested. It is suggested that these experiments of nature lend credence to the proposal that the hypothalamus may play a critical role in the perpetuation of growth hormone hypersecretion in some patients with acromegaly.     

Acute and long-term pituitary insufficiency in traumatic brain injury: a prospective single-centre study

OBJECTIVE: To assess the prevalence of hypopituitarism following traumatic brain injury (TBI), describe the time-course and assess the association with trauma-related parameters and early post-traumatic hormone alterations. DESIGN: A 12-month prospective study. PATIENTS: Forty-six consecutive patients with TBI (mild: N = 22; moderate: N = 9; severe: N = 15). MEASUREMENTS: Baseline and stimulated hormone concentrations were assessed in the early phase (0-12 days post-traumatically), and at 3, 6 and 12 months postinjury. Pituitary tests included the Synacthen-test (acute +6 months) and the insulin tolerance test (ITT) or the GHRH + arginine test if the ITT was contraindicated (3 + 12 months). Insufficiencies were confirmed by retesting. RESULTS: Early post-traumatic hormone alterations mimicking central hypogonadism or hypothyroidism were present in 35 of the 46 (76%) patients. Three months post-traumatically, 6 of the 46 patients failed anterior pituitary testing. At 12 months, one patient had recovered, whereas none developed new insufficiencies. All insufficient patients had GH deficiency (5 out of 46), followed by ACTH- (3 out of 46), TSH- (1 out of 46), LH/FSH- (1 out of 46) and ADH deficiency (1 out of 46). Hypopituitary patients had more frequently been exposed to severe TBI (4 out of 15) than to mild or moderate TBI (1 out of 31) (P = 0.02). Early endocrine alterations including lowered thyroid and gonadal hormones, and increased total cortisol, free cortisol and copeptin were positively associated to TBI severity (P < 0.05), but not to long-term development of hypopituitarism (P > 0.1), although it was indicative in some. CONCLUSION: Long-term hypopituitarism was frequent only in severe TBI. During the 3-12 months follow-up, recovery but no new insufficiencies were recorded, indicating manifest hypothalamic or pituitary damage already a few months postinjury. Very early hormone alterations were not associated to long-term post-traumatic hypopituitarism. Clinicians should, nonetheless, be aware of potential ACTH deficiency in the early post-traumatic period.     

Modest reversal of metabolic syndrome manifestations with vitamin D status correction: a 12-month prospective study

Numerous cross-sectional studies have noted significant negative associations between circulating levels of 25-hydroxyvitamin D and cardiometabolic risk factors, highlighting potential extraskeletal functions of this sterol hormone. Prospective studies, however, have been limited; and hence, no cause-and-effect relations can be inferred. This study aims to determine whether vitamin D status correction can reverse already established manifestations of the metabolic syndrome (MetS). A total of 59 adult nondiabetic, overweight, and obese Saudis (31 male, 28 female) were prospectively enrolled in this 1-year interventional study. Anthropometry and biochemical evaluation were performed, including determination of serum 25-hydroxyvitamin D, calcium, and phosphorous concentrations, as well as fasting blood glucose and lipid profile. Subjects were advised to regularly expose themselves to sunlight and increase intake of vitamin D-rich foods. All measurements were repeated 6 and 12 months later. At the initial baseline visit, the prevalence of both low high-density lipoprotein cholesterol and hypertension was significantly increased among patients with 25-vitamin D deficiency (P < .05), even after adjusting for sex and body mass index. Overall prevalence of MetS patients by the modified National Health and Nutrition Examination Survey Adult Treatment Panel III definition decreased from 25.2% to 13.0%; and this was largely due to a parallel decrease in the prevalence of low high-density lipoprotein cholesterol, triglycerides, and hypertension. Optimization of vitamin D status through sun exposure and increased intake of a vitamin D-rich diet can lead to an improved cardiometabolic profile, offering a promising nonpharmacologic approach in the prevention of MetS manifestations.     

A clinical and pathophysiological approach to traumatic brain injury-induced pituitary dysfunction

Pituitary - This review aimed to evaluate the data underlying the pathophysiology of TBI-induced hypothalamo-pituitary dysfunction. Recent literature about the pathophysiology of TBI-induced...     

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

Objective Recent investigations have provided evidence for a high prevalence of pituitary dysfunction in patients with subarachnoid haemorrhage (SAH). However, apart from one study, all of the previous data were obtained from retrospective studies. To our knowledge there is no previously reported study in which pituitary function was investigated in the same patients immediately after SAH and 12 months later. The aim of this study was to understand the prevalence and progression of anterior pituitary hormone deficiencies both in the acute phase of SAH and 12 months after the event. Patients and design Twenty‐two SAH patients (11 men, 11 women) were included in the study. Pituitary function was evaluated in the early acute phase (within 24 h of admission) and after 12 months. Results Pituitary hormone deficiencies in the acute phase were as follows: 31·8% had gonadotrophin, 22·7% had ACTH and 22·7% had GH deficiencies. At 12 months after SAH: 0·0% had gonadotrophin, 13·6% had ACTH and 36·4% had GH deficiencies. Overall, after 12 months, pituitary hormone deficiencies recovered in 15 (68·2%) patients and new‐onset pituitary hormone deficiencies were present in nine (40·9%) patients. Conclusions GH deficiency (GHD) was the most common pituitary deficit at 12 months after SAH and the majority of the patients (87·5%) had isolated GHD. During the 12‐month follow‐up, pituitary function was found to either improve or worsen in a considerable number of patients.     

Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas.

Surgery is the treatment of choice for many pituitary tumors; pituitary function may suffer after operation, but relief of pressure on the normal pituitary may also favor postoperative recovery of hypopituitarism. The aim of this study was to investigate the frequency of new appearance and recovery of hypopituitarism after neurosurgery and try to identify features associated with it. Pre- and postoperative anterior pituitary functions were investigated in 234 patients with pituitary adenomas (56 nonfunctioning, 71 PRL-secreting, 66 GH-secreting, 39 ACTH-secreting, 1 LH/FSH-secreting, and 1 TSH-secreting tumors). Eighty-eight new postoperative pituitary hypofunctions appeared in 52 patients (12 NF, 14 PRL-secreting, 15 GH-secreting, 10 ACTH-secreting, and 1 LH/FSH-secreting adenomas). They corresponded to 27% ACTH deficiencies (in 29 of the 107 patients with normal preoperative ACTH in whom postoperative evaluation was complete), 14.5% (15 of 103) new GH deficiencies, 10.5% (15 of 143; P < 0.0005, significantly less than ACTH deficiency) new TSH deficiencies, 16.5% (20 of 121) new gonadotropin deficiencies, and 13% (9 of 71) new PRL deficiencies. Preoperatively, 93 were deficient in at least 1 pituitary hormone; after surgery, 45 (48%) recovered between 1 and 3 hormones. The 2 patients with LH/FSH- and TSH-secreting macroadenomas did not recover pituitary function. Factors associated with a higher probability of postoperative pituitary function recovery were: no tumor rests on postoperative pituitary imaging (P = 0.001) and no neurosurgical (P = 0.001) or pathological evidence (P = 0.049) of an invasive nature. Tumor size did not differ significantly between those who did and those who did not recover pituitary function after surgery. Even if clear hypofunction is observed at initial work-up, patients should be reassessed after surgery without substitution therapy, because practically half the preoperative pituitary hormone deficiencies recover postoperatively, eliminating the need for life-long substitution therapy.     

垂体前叶功能减退患者经皮冠状动脉介入治疗后诱发垂体功能急性失代偿一例

患者男性,42岁。主因“突发全身酸痛伴恶心、呕吐、胸闷3天”于2006年11月27日入院。患者10天前曾于我院住院,行冠状动脉造影提示左主干开口70％狭窄,前降支近段50％～60％狭窄,右冠状动脉近段50％狭窄,于左主干置入Endeavor4．0mm×15mm支架1枚（美敦力公司）。并给予辛伐他汀（商品名：京必舒新）20mg每晚1次（连续10天）及其他抗冠心病治疗出院。2006年11月24日患者出现感冒,体温最高37．5℃左右,对症治疗后体温正常,但持续恶心、呕吐,呕吐物为胃内容物,连续3天未能进食,并感全身酸痛不适。11月26日再次转入我院,入院诊断：冠心病,自发性心绞痛,PTCA加支架术后,心包积液原因待查,怀疑横纹肌溶解症;颅咽管瘤术后、放疗后,低钠血症收住病房。1997年曾于外院行颅咽管瘤切除术。     

The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study

Increased cardiovascular morbidity and mortality were reported in GH deficiency (GHD), and GH replacement can ameliorate cardiac abnormalities of adult GHD patients. To test the potential progression of untreated GHD on the cardiovascular risk and cardiac function, cardiovascular risk factors, cardiac size, and performance were prospectively evaluated in 15 GHD patients (age, 18-56 yr) who were treated with recombinant GH at the dose of 0.15-1.0 mg/d, 15 GHD patients (age, 18-56 yr) who refused GH replacement, and 30 healthy subjects (age, 18-53 yr). Electrocardiogram, systolic and diastolic blood pressure, and heart rate measurement, serum IGF-I, total cholesterol, low- and high-density lipoprotein (LDL, HDL) cholesterol, triglycerides, and fibrinogen level assay, echocardiography, and equilibrium radionuclide angiography were performed basally and after 12 months. At study entry, low IGF-I levels, unfavorable lipid profile, and inadequate cardiac and physical performance were found in GHD patients compared with controls. After 12 months of GH treatment, IGF-I levels normalized; HDL-cholesterol levels, left ventricular (LV) mass index (LVMi), left ventricular ejection fraction (LVEF) at peak exercise, peak filling rate, exercise duration and capacity significantly increased; total- and LDL-cholesterol levels significantly decreased. After 12 months in GH-untreated GHD patients, IGF-I levels remained stable, and HDL-cholesterol levels, LVEF both at rest and at peak exercise, and exercise capacity were further reduced; total- and LDL-cholesterol levels increased slightly. LVEF at rest and its response at peak exercise normalized in 60 and 53.3%, respectively, of GH-treated patients and in none of the GH-untreated patients. In conclusion, 12 months of GH replacement normalized IGF-I and improved lipid profile and cardiac performance in adult GHD patients. A similar period of GH deprivation induced a further impairment of lipid profile and cardiac performance. This finding strongly supports the need of GH replacement in adult GHD patients.     

Evaluation of pituitary function after traumatic brain injury in childhood

Objectives Post‐traumatic hypopituitarism is well described amongst adult traumatic brain injury (TBI) survivors. We aimed to determine the prevalence and clinical significance of pituitary dysfunction after head injury in childhood. Design Retrospective exploratory study. Patients: 33 survivors of accidental head injury (27 boys). Mean (range) age at study was 13·4 years (5·4–21·7 years) and median (range) interval since injury 4·3 years (1·4–7·8 years). Functional outcome at study: 15 good recovery, 16 moderate disability, two severe disability. Measurements Early morning urine osmolality and basal hormone evaluation were followed by the gonadotrophin releasing hormone (GnRH) and insulin tolerance (n = 25) or glucagon tests (if previous seizures, n = 8). Subjects were not primed. Head injury details were extracted from patient records. Results No subject had short stature (mean height SD score +0·50, range −1·57 to +3·00). Suboptimal GH responses (<5 μg/l) occurred in six peri‐pubertal boys (one with slow growth on follow‐up) and one postpubertal adolescent (peak GH 3·2 μg/l). Median peak cortisol responses to insulin tolerance or glucagon tests were 538 and 562 nm . Nine of twenty‐five and two of eight subjects had suboptimal responses, respectively, two with high basal cortisol levels. None required routine glucocorticoid replacement. In three, steroid cover was recommended for moderate/severe illness or injury. One boy was prolactin deficient. Other basal endocrine results and GnRH‐stimulated LH and FSH were appropriate for age, sex and pubertal stage. Abnormal endocrine findings were unrelated to the severity or other characteristics of TBI or functional outcome. Conclusions No clinically significant endocrinopathy was identified amongst survivors of accidental childhood TBI, although minor pituitary hormone abnormalities were observed.     

Delirium in elderly home-treated patients: a prospective study with 6-month follow-up

Delirium usually occurs during hospitalisation. The aims of this study were to evaluate the incidence of delirium in “hospital-at-home” compared to a traditional hospital ward and to assess mortality, hospital readmissions and institutionalisation rates at 6-month follow-up in elderly patients with intermediate/high risk for delirium at baseline according to the criteria of Inouye. We performed a prospective, non-randomised, observational study with 6-month follow-up on 144 subjects aged 75 years and older consecutively admitted to the hospital for an acute illness and followed in a geriatric hospital ward (GHW) or in a geriatric home hospitalisation service (GHHS). Baseline socio-demographic information, clinical data, functional, cognitive, nutritional status, mood, quality of life, and caregiver’s stress scores were collected. Of the 144 participants, 14 (9.7%) had delirium during their initial hospitalisation: 4 were treated by GHHS and 10 in a GHW. The incidence of delirium was 16.6% in GHW and 4.7% in GHHS. All delirious patients were very old, with a high risk for delirium at baseline of 60%, according to the criteria of Inouye. In GHW, the onset of delirium occurred significantly earlier and the mean duration of the episode was significantly longer. The severity of delirium tended to be higher in GHW compared to GHHS. At 6-month follow-up, mortality was significantly higher among patients who suffered from an episode of delirium. Moreover, they showed a trend towards a greater institutionalisation rate. GHHS may represent a protective environment for delirium onset in acutely ill elderly patients.     

Effects of GH on cognitive function in elderly patients with adult-onset GH deficiency: a placebo-controlled 12-month study

OBJECTIVE: Young adults with childhood-onset GH deficiency (GHD) have reduced memory and attention, which can be improved by treatment with GH. Little information is available on cognitive function in elderly GHD patients. DESIGN: Single center, double-blind, randomized, placebo-controlled study of 52-week duration. METHODS: Elderly GH therapy na?ve GHD patients (n=34; age range 60-77 years) were enrolled and randomized to receive placebo or GH therapy which was titrated to achieve a target IGF-I level of +1 to +2 s.d. of the normal mean for age. Cognitive function was assessed at baseline and after 24 and 52 weeks, using a computerized psychometric test package (Neurobehavioral Examination System-2). RESULTS: The mean GH dose was 0.16+/-0.06 mg/day; mean IGF-I increased from 135+/-59 ng/ml at baseline to 213+/-77 ng/ml during active treatment. The GH-treated group had better mean serial digit learning scores compared with placebo group (P<0.05). Assessment of effect sizes showed that improvements in memory occurred with GH after 24 weeks. The overall adverse event rates were similar in the GH and the placebo group. CONCLUSION: This study indicates that GH replacement may be accompanied by improvement in certain measures of cognitive function in elderly patients with GHD.     

Improvement in OMERACT domains and renal function with regular treatment for gout: a 12-month follow-up cohort study

OMERACT proposed a set of mandatory and discretionary domains to evaluate the effect of treatment in patients with gout. To determine the percentage of improvement and the effect size 6 and 12 months after starting a proper treatment in patients with gout from our cohort (GRESGO) based on the OMERACT proposal for chronic gout. GRESGO is a cohort of consecutive, new patients with gout attending either of two dedicated clinics. This report includes 141 patients evaluated at baseline and 6 months plus 101 of them completing a 12-month follow-up in 2012. Clinical data including the OMERACT domains for chronic gout were collected at baseline and every 6 months. Treatment was prescribed by their attending physician with the purpose of getting <?6 mg/dL of seric uric acid (sUA). Most patients were males (96%) with inappropriate treatment (95%); 66% had tophi, 30% metabolic syndrome, and 32% low renal function. Mean dose of allopurinol at baseline and throughout the study went from 344?±?168 mg/day to 453?±?198 at 12 months. Most OMERACT domains and renal function improved significantly; 73% improved >?20% from 6 to 12 months. Greater improvement was observed in the domains: flares, index tophus size, pain, general health assessment, and HAQ score, all of them associated to lower sUA values. Chronic gout patients improve significantly in most OMERACT domains when conventional and regular treatment is indicated. sUA <?6 mg/dL is associated with greater improvement.     

Transient diabetes insipidus and hypopituitarism after pituitary apoplexy: a rare association with pericardial effusion and painless thyroiditis

Pituitary apoplexy in a 38-year-old male patient with acromegaly who presented with pericardial effusion, anterior pituitary dysfunction, and diabetes insipidus is described. With corticosteroid therapy, there was good initial recovery of pituitary function and regression of pericardial effusion. On withdrawal of corticosteroids, he developed painless thyroiditis, with transient thyrotoxicosis. Subsequently, the pituitary function tests remained normal for a year, but later he gradually developed hypogonadotropic hypogonadism, hypocortisolism, growth hormone deficiency, and progressive pituitary atrophy, resulting in empty sella syndrome.     

Pulmonary function after autologous bone marrow transplantation in children: a long-term prospective study

We performed serial pulmonary function tests (PFTs) consisting of spirometry and diffusing capacity in 26 children after BMT. The median follow-up was 10 years. The influence of total body irradiation (TBI) on long-term pulmonary function was of particular interest. In the 20 children who had received TBI, after an initial decrease the PFTs showed recovery, but the mean lung volumes were still significantly decreased 5 years after BMT at 10% below baseline. The proportions of children with restrictive impairment 5 and 10 years after BMT were 20 and 21%, respectively. Only one child was diagnosed with obstructive impairment. The proportions of children with isolated diffusing impairment at 5 and 10 years were 7/20 (35%) and 7/13 (54%), respectively. Six children had received chemotherapy only and showed isolated diffusing impairment as the only long-term sequela in 4/5 and 1/3 at 5 and 10 years. Our main finding was that there was little change in PFTs 1-10 years after BMT. TBI was associated with persistently decreased lung volumes in a proportion of patients, whereas chemotherapy also might have been of importance for the development of impaired gas exchange.