Self-reported Gastrointestinal Side Effects of Antifibrotic Drugs in Dutch Idiopathic Pulmonary Fibrosis patients.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is an inexorably progressive disease, which has a great impact on patients' lives. Pirfenidone and nintedanib are approved and recommended antifibrotic drugs for patients with IPF. The aim of this study was to evaluate self-reported gastrointestinal side effects of antifibrotic drugs in 176 Dutch IPF patients. METHODS: A cross-sectional web-based anonymous survey about complaints and side effects was conducted among IPF patients in the Netherlands. Logistic regression was used to quantify whether pirfenidone and nintedanib caused complaints of nausea, vomiting, diarrhoea, appetite loss, weight loss or loss of taste or smell perception. RESULTS: The questionnaire was completed by 176 IPF patients, 71 of whom used pirfenidone and 85 nintedanib, while 20 patients did not use any antifibrotic drugs. Nintedanib users reported complaints of diarrhoea, vomiting, weight loss and loss of appetite (p < 0.01). Nausea was a significant adverse reaction (p < 0.05). Pirfenidone caused increased appetite loss (p < 0.01) and the risk of weight loss (p < 0.05). The increase in loss of appetite and weight loss did not differ significantly between the two drugs. CONCLUSION: The current study showed that nintedanib causes a significant increase in diarrhoea, vomiting, weight loss and loss of appetite, while pirfenidone led to loss of appetite. Our results suggest new avenues regarding dietary recommendations for IPF patients.

DNA methylation profiling in MEN1-related pancreatic neuroendocrine tumors reveals a potential epigenetic target for treatment.

OBJECTIVE: Epigenetic changes contribute to pancreatic neuroendocrine tumor (PanNET) development. Hypermethylation of promoter DNA as a cause of tumor suppressor gene silencing is a well-established oncogenic mechanism that is potentially reversible and therefore an interesting therapeutic target. Multiple endocrine neoplasia type 1 (MEN1) is the most frequent cause of inherited PanNETs. The aim of this study was to determine promoter methylation profiles in MEN1-related PanNETs. DESIGN AND METHODS: Methylation-specific multiplex ligation-dependent probe amplification was used to assess promoter methylation of 56 tumor suppressor genes in MEN1-related (n = 61) and sporadic (n = 34) PanNETs. Differences in cumulative methylation index (CMI), individual methylation percentages and frequency of promoter hypermethylation between subgroups were analyzed. RESULTS: We found promoter methylation of a large number of potential tumor suppressor genes. CMI (median CMI: 912 vs 876, P = 0.207) was the same in MEN1-related and sporadic PanNETs. We found higher methylation percentages of CASP8 in MEN1-related PanNETs (median: 59% vs 16.5%, P = 0.002). In MEN1-related non-functioning PanNETs, the CMI was higher in larger PanNETs (>2 cm) (median: 969.5 vs 838.5; P = 0.021) and in PanNETs with liver metastases (median: 1036 vs 869; P = 0.013). Hypermethylation of MGMT2 was more frequent in non-functioning PanNETs compared to insulinomas (median: 44.7% vs 8.3%; P = 0.022). Hypermethylation of the Von Hippel-Lindau gene promoter was observed in one MEN1-related PanNET and was associated with loss of protein expression. CONCLUSION: Promoter hypermethylation is a frequent event in MEN1-related and sporadic PanNETs. Targeting DNA methylation could be of therapeutic value in MEN1 patients with advanced PanNETs.

Expression of p27Kip1 and p18Ink4c in human multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors.

PURPOSE: Pancreatic neuroendocrine tumors are a major manifestation of multiple endocrine neoplasia type 1 (MEN1). This tumor syndrome is caused by germline mutations in MEN1, encoding menin. Insight into pathogenesis of these tumors might lead to new biomarkers and therapeutic targets for these patients. Several lines of evidence point towards a role for p27Kip1 and p18Ink4c in MEN1-related tumor development in animal models for MEN1, but their contribution to human MEN1-related pancreatic neuroendocrine tumor development is not known. METHODS: In this study, we characterized protein expression of p27Kip1 and p18Ink4c in human MEN1-related PanNETs by immunohistochemistry. From the nationwide DutchMEN1 Study Group database including > 90% of the Dutch MEN1 population, MEN1-patients, who underwent pancreatic surgery, were selected. A tissue micro-array was constructed with available paraffin tissue blocks, and PanNETs from 61 MEN1 patients were eligible for analysis. RESULTS: Expression of p27Kip1 was high in 57 (93%) PanNETs and 67% of the tumors showed low expression of p18Ink4c (67.3%). No association was found between expression of either p27Kip1 or p18Ink4c and clinic-pathological characteristics. CONCLUSIONS: These findings indicate that loss of p18Ink4c, but not p27Kip1, is a common event in the development of MEN1-related PanNETs. Restoration of p18Ink4c function through CDK4/6 inhibitors could be a therapeutic option for MEN1-related PanNETs.

The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin.

Idiopathic pulmonary fibrosis (IPF) is characterized by a disturbed pulmonary redox balance associated with inflammation. To restore this balance, antioxidants are often suggested as therapy for IPF but previous clinical trials with these compounds and their precursors have not been successful in the clinic. The exogenous antioxidant quercetin, which has a versatile antioxidant profile and is effective in restoring a disturbed redox balance, might be a better candidate. The aim of this study was to evaluate the protective effect of quercetin on oxidative and inflammatory markers in IPF. Here, we demonstrate that IPF patients have a significantly reduced endogenous antioxidant defense, shown by a reduced total antioxidant capacity and lowered glutathione and uric acid levels compared to healthy controls. This confirms that the redox balance is disturbed in IPF. Ex vivo incubation with quercetin in blood of both IPF patients and healthy controls reduces LPS-induced production of the pro-inflammatory cytokines IL-8 and TNFα. This anti-inflammatory effect was more pronounced in the blood of the patients. Our pro-fibrotic in vitro model, consisting of bleomycin-triggered BEAS-2B cells, shows that quercetin boosts the antioxidant response, by increasing Nrf2 activity, and decreases pro-inflammatory cytokine production in a concentration-dependent manner. Collectively, our findings implicate that IPF patients may benefit from the use of quercetin to restore the disturbed redox balance and reduce inflammation.

Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults.

PURPOSE: The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing's disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). METHODS: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. RESULTS: At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. CONCLUSIONS: During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.

Oestrogens are Not Related to Emotional Processing: a Study of Regional Brain Activity in Female-to-Male Transsexuals Under Gonadal Suppression.

Although the prevailing opinion is that emotional processes are influenced by sex hormones, the literature is still inconclusive. The aim of the current study was to examine the effects of gonadal suppression on brain activity during affective picture processing. Twenty-one female-to-male (FtM) transsexuals and 19 control women were recruited and underwent functional magnetic resonance imaging scanning while rating emotional pictures adapted from the International Affective Picture System. The gonadal hormone production of the FtMs was suppressed for 8 weeks, the control group did not receive any treatment before scanning. Under gonadal suppression, FtMs showed less brain activation in the superior temporal lobe compared with female controls during perception of positive affective pictures. Regression analysis showed that during processing of positive affective images, brain activity within the right superior temporal lobe was not correlated with levels of estradiol, luteinizing hormone, and follicle-stimulating hormone. In the absence of associations with hormonal levels, the difference in activation in the superior temporal lobe during positive emotional stimuli between FtMs and control women may be attributed to a priori differences between the 2 groups. Future studies should clarify if these differences are a result of atypical sexual differentiation of the brain in FtMs.

Tumor Recurrence or Regrowth in Adults With Nonfunctioning Pituitary Adenomas Using GH Replacement Therapy.

CONTEXT: GH replacement therapy (GH-RT) is a widely accepted treatment in GH-deficient adults with nonfunctioning pituitary adenoma (NFPAs). However, some concerns have been raised about the safety of GH-RT because of its potentially stimulating effect on tumor growth. OBJECTIVE: The aim of this study was to evaluate tumor progression in NFPA patients using GH-RT. DESIGN, SETTING, AND PATIENTS: From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severely GH-deficient adults (1998-2009), all NFPA patients with ≥ 30 days of GH-RT were selected (n = 783). Data were retrospectively collected from the start of GH-RT in adulthood (baseline). MAIN OUTCOME MEASURE: Tumor progression, including tumor recurrence after complete remission at baseline and regrowth of residual tumor. RESULTS: Tumor progression developed in 12.1% of the patients after a median (range) time of 2.2 (0.1-14.9) years. Prior radiotherapy decreased tumor progression risk compared to no radiotherapy (hazard ratio = 0.16; 95% confidence interval, 0.09-0.26). Analysis in 577 patients with available baseline imaging data showed that residual tumor at baseline increased tumor progression risk compared to no residual tumor (hazard ratio = 4.5; 95% confidence interval, 2.4-8.2). CONCLUSIONS: The findings in this large study were in line with those reported in literature and provide further evidence that GH-RT does not appear to increase tumor progression risk in NFPA patients. Although only long-term randomized controlled trials will be able to draw firm conclusions, our data support the current view that GH-RT is safe in NFPA patients.

Cerebrovascular events, secondary intracranial tumors, and mortality after radiotherapy for nonfunctioning pituitary adenomas: a subanalysis from the Dutch National Registry of Growth Hormone Treatment in Adults.

CONTEXT: Radiotherapy is frequently administered as adjuvant treatment in patients with clinically nonfunctioning pituitary adenomas (NFPAs). However, concerns have been raised about potential long-term side effects, including cerebrovascular events (CVEs) and secondary intracranial tumors. OBJECTIVE: The aim of this study was to analyze the risk of CVEs, secondary intracranial tumors, and mortality in irradiated (IRR) NFPA patients, compared with NFPA patients who were not irradiated (non-IRR). DESIGN, SETTING, AND PATIENTS: The study cohort included 806 patients with a NFPA from the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide long-term surveillance study in severe GH-deficient adult patients. IRR patients (n = 456) were compared with non-IRR patients (n = 350). MAIN OUTCOME MEASURES: CVEs, secondary intracranial tumors, and mortality were measured. RESULTS: Sixty-nine subjects developed a CVE. In men, but not in women, the incidence of a CVE was significantly higher in IRR patients than in non-IRR patients (hazard ratio 2.99, 95% confidence interval 1.31-6.79). A secondary intracranial tumor developed in five IRR patients and two non-IRR patients. After adjustment for age, radiotherapy was not associated with mortality. CONCLUSIONS: The incidence of secondary intracranial tumors and mortality did not differ between IRR and non-IRR patients. However, a CVE was found significantly more frequently in IRR men but not in women. Further research into the long-term effects of cranial radiotherapy seems mandatory. The potential risks of radiotherapy have to be taken into account when radiotherapy is considered in NFPA patients, and long-term follow-up is recommended.

Mimivirus is not a frequent cause of ventilator-associated pneumonia in critically ill patients.

Acanthamoeba polyphaga mimivirus (APMV) belongs to the amoebae-associated microorganisms. Antibodies to APMV have been found in patients with pneumonia suggesting a potential role as a respiratory pathogen. In addition, positive serology for APMV was associated with an increased duration of mechanical ventilation and intensive care unit stay in patients with ventilator-associated pneumonia. The aim of the present study was to assess the presence of APMV in bronchoalveolar lavage fluid samples of critically ill patients suspected of ventilator-associated pneumonia. The study was conducted in the intensive care unit of the Maastricht University Medical Centre. All consecutive bronchoalveolar lavage fluid samples obtained between January 2005 and October 2009 from patients suspected of ventilator-associated pneumonia were eligible for inclusion. All samples were analyzed by real-time PCR targeting the APMV. A total of 260 bronchoalveolar lavage fluid samples from 214 patients (139 male, 75 female) were included. Bacterial ventilator-associated pneumonia was confirmed microbiologically in 105 out of 260 (40%) suspected episodes of ventilator-associated pneumonia (86 patients). The presence of APMV DNA could not be demonstrated in the bacterial ventilator-associated pneumonia positive or in the bacterial ventilator-associated pneumonia negative bronchoalveolar lavage fluid samples. Although suspected, APMV appeared not to be present in critically ill patients suspected of ventilator-associated pneumonia, and APMV does not seem to be a frequent cause of ventilator-associated pneumonia.

Reduced growth hormone secretion after cranial irradiation contributes to neurocognitive dysfunction.

The objective of this study was to investigate the relation between growth hormone (GH) and attentional electro-cortical responses to task-relevant stimuli (N2b), target detections, speed of responding, P300 latencies, and performance on neuropsychological tests in 19 patients who received external beam radiation therapy for brain tumors in adulthood. In addition, we studied the association between IGF-I and activation of the motor cortex responses (lateralized readiness potential, LRP). Brain function was assessed using event-related potentials (ERPs) during a go/no go selective-attention task, including N2b, P300 and selective motor preparation as reflected in the LRP. Correlations were calculated between peak GH levels after a standardized growth hormone-releasing hormone (GHRH)-arginine test, plasma IGF-I, and cognitive functions. We separately studied four patients who were diagnosed with GHD according to the GHRH-arginine test. Performance on WAIS digit span backward and the Rey-Osterrieth complex figure test correlated positively with GH peak. GHD patients performed worse than non-GHD patients on Stroop interference, trail making B/A attentional shifting and Rey-Osterrieth complex figure test. At trend-level significance, trails A performance was better in patients with lower GH levels and higher radiation doses, and GHD participants detected fewer targets in the go/no go selective attention task. N2b was not significantly altered by GH status. Furthermore, plasma IGF-I was positively correlated with the sum of digit span forward and backward. No relations with P300 were observed. In this study only 21% (4/19) of the patients who received fractionated radiotherapy for a non-endocrine brain tumor were diagnosed with GHD. GHD in these patients was associated with impaired interference control, attentional shifting, and visual long-term memory. The results for interference control and attentional shifting suggest an additional effect of the radiation history.

Endpoints for clinical trials of sarcoidosis.

Over the past few years an increasing number of prospective controlled sarcoidosis treatment trials have been completed. Unfortunately, these studies utilize different endpoints making comparisons between studies difficult. At the recent World Association of Sarcoidosis and other Granulomatous disease (WASOG) meeting, a session was dedicated to the evaluation of clinical endpoints for various disease manifestations. These included pulmonary, pulmonary hypertension, fatigue, cutaneous, and a classification of clinical disease phenotypes. Based on the available literature and our current understanding of the disease, recommendations for clinical evaluation were proposed for each disease category. For example, it was recommended that pulmonary studies should include changes in the forced vital capacity. Additionally, it was recommended that all trials should incorporate measurement of quality of life.

Adalimumab successful in sarcoidosis patients with refractory chronic non-infectious uveitis.

INTRODUCTION: Adalimumab, a humanized monoclonal antibody targeted against TNF-α, has proved to be successful in the treatment of uveitis. Another anti-TNF-α agent, i.e., infliximab, has been reported of benefit in the treatment of refractory sarcoidosis. The aim of this prospective case series was to evaluate the effect of adalimumab on intraocular inflammatory signs and other relevant clinical manifestations (lung function, serological inflammatory parameters, and fatigue) of sarcoidosis. METHODS: Sarcoidosis patients with refractory posterior uveitis (n = 26, 17 females, 41 eyes in total) were systematically followed for 12 months after initiation of adalimumab 40 mg sc once a week. Inclusion criteria were non-responsiveness to prednisone and methotrexate (MTX) or intolerance to these drugs. Adjunctive therapy with prednisone and MTX was tapered during treatment with adalimumab. Localization and improvement, stabilization or deterioration of intraocular inflammatory signs was scored. Pulmonary function- and laboratory testing were performed and Fatigue Assessment Scale was completed. Results at baseline, 6 months, and 12 months were compared. RESULTS: Choroidal involvement resolved in 10/15 patients, five had partial improvement; vasculitis resolved in 1/1 patient; papillitis resolved in 7/8 patients, one had partial response; macular edema resolved in 5/8 patients, three had partial response; vitreous cleared completely in 5/5 patients. Overall outcome regarding intraocular inflammatory signs showed improvement in 22 patients (85%) and stabilization in four patients (15%). At 12 months, no recurrences were reported in those successfully treated. Laboratory parameters of inflammatory activity (C-reactive protein; serum angiotensin-converting enzyme and soluble interleukin-2 Receptor) improved (p < 0.01). Moreover, fatigue improved in 14/21 (67%) of the patients suffering from fatigue and the diffusion capacity for carbon monoxide (DLCO) improved in 7/8 (88%) of patients with a decreased DLCO (p < 0.01). The dosage of both prednisone and MTX could be tapered down significantly (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Adalimumab appeared successful in sarcoidosis patients with refractory chronic non-infectious uveitis showing improvement in intraocular inflammatory signs as well as in other relevant clinical indicators of disease activity. Future randomized studies are needed to determine the optimal dosage, dose interval and duration of therapy in refractory multisystemic sarcoidosis.

Lung cancer in idiopathic pulmonary fibrosis patients diagnosed during or after lung transplantation.

Lung transplantation is an accepted therapy for patients with end-stage lung disease and offers a major survival benefit in selected patients. The most important indications are chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis besides cystic fibrosis and pulmonary arterial hypertension. The incidence of lung cancer in patients after Ltx is 20-25 times higher than in the general population. Diagnosis is often difficult in IPF patients because of the diffuse lung abnormalities due to the underlying fibrosis. Moreover, the lung cancer may mimic a pulmonary infection. Symptoms are often aspecific, diagnosis is difficult, and prognosis is extremely poor. We describe three patients who were transplanted for idiopathic pulmonary fibrosis and who developed a primary lung cancer.

Incidence of venous thromboembolism in patients with Cushing's syndrome: a multicenter cohort study.

CONTEXT: Venous thrombosis has frequently been reported in patients with endogenous Cushing's syndrome (CS). OBJECTIVE: The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with CS prior to treatment and after surgery. DESIGN AND SETTING: We conducted a multicenter cohort study at all university medical centers in The Netherlands. PATIENTS: Consecutive patients diagnosed with endogenous CS of benign origin between January 1990 and June 2010 were eligible for inclusion. Patients surgically treated for nonfunctioning pituitary adenoma served as controls for the incidence of postoperative VTE in ACTH-dependent CS. MAIN OUTCOME MEASURES: We documented all objectively confirmed VTE during 3 yr prior to, and 3 yr after treatment onset. The incidences of VTE were expressed as incidence rates. RESULTS: A total of 473 patients (mean age 42 yr, 363 women) were included (360 ACTH-dependent pituitary CS). The total number of person-years was 2526. Thirty-seven patients experienced VTE during the study period, resulting in an incidence rate of 14.6 [95% confidence interval (CI) 10.3-20.1] per 1000 person-years. The incidence rate for first-ever VTE prior to treatment was 12.9 (95% CI 7.5-12.6) per 1000 person-years (17 events). The risk of postoperative VTE, defined as risk within 3 months after surgery, was 0% for ACTH-independent and 3.4% (95% CI 2.0-5.9) for ACTH-dependent CS (12 events in 350 patients); most events occurred between 1 wk and 2 months after surgery. Compared with the controls, the risk of postoperative VTE in patients undergoing transsphenoidal surgery was significantly greater (P = 0.01). CONCLUSIONS: Patients with CS are at high risk of VTE, especially during active disease and after pituitary surgery. Guidelines on thromboprophylaxis are urgently needed.

Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force.

The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.

Type D or 'distressed' personality in sarcoidosis and idiopathic pulmonary fibrosis.

BACKGROUND: Personality factors have shown to be related to mortality, morbidity, and psychological aspects in chronic disorders. Little is known about the effect of personality on disease severity in sarcoidosis and idiopathic pulmonary fibrosis (IPF). The aim of this study was to assess the prevalence of Type D personality and its relation with relevant clinical characteristics in sarcoidosis and IPF patients. METHODS: The study included 441 sarcoidosis and 49 IPF patients from the outpatient clinic of the ild care team of the MUMC, the Netherlands. They completed the DS14 (Type D questionnaire), the fatigue assessment scale (FAS), the WHO quality of life-BREF (WHOQOL-BREF) and the Centre for Epidemiological Studies-Depression Scale (CES-D). Moreover, relevant clinical data were collected. The control group consisted of 3678 subjects from a general population. RESULTS: Type D personality was found in 25.6% of the sarcoidosis patients compared to 21% in the controls, but only in 18.8% of the IPF patients. No relation with disease severity was found in either of these disorders. Fatigue was a substantial problem in both populations. Depressive symptoms but not Type D personality predicted fatigue and poorer QOL in sarcoidosis and IPF. CONCLUSION: Prevalence of Type D personality is not higher in sarcoidosis and IPF patients than in the general population and does not explain QOL impairment. Depressive symptoms explain QOL impairment and fatigue substantially. Therefore, in the multidisciplinary management of sarcoidosis and IPF psychological screening and psychological counselling concerning adequate coping strategies should be incorporated.

Dutch National Registry of GH Treatment in Adults: patient characteristics and diagnostic test procedures.

OBJECTIVE: The Dutch National Registry of GH Treatment in Adults was established in 1998 as an initiative of the Ministry of Health. The main goals were to gain more insight into long-term efficacy, safety, and costs of GH therapy (GHT) in adult GH-deficient (GHD) patients in The Netherlands. METHODS: Baseline patient characteristics and diagnostic test procedures were evaluated. RESULTS: Until January 2009 in roughly 10 years, 2891 patients (1475 men and 1416 women, mean age 43.5±16.5 years) were registered. GHD was of childhood-onset (CO) in over 20% of the patients and of isolated in 11%. The most common causes of GHD were pituitary tumors and/or their treatment, craniopharyngiomas, and idiopathic GHD. In 85% of the patients, a GH stimulation test was performed, in the majority an insulin tolerance test (ITT) (49%) or a combined GHRH-arginine test (25%). In 12% of the patients, IGF1 levels were ≤-2 s.d. combined with two or more additional pituitary hormone deficits, and in 2%, it concerned patients with CO-GHD continuing GHT in adulthood. Over the years, the test of first choice shifted from ITT toward GHRH-arginine test. CONCLUSION: Nearly, 2900 patients were included in the nationwide surveillance database of the Dutch National Registry of GH Treatment in Adults until January 2009. Baseline patient characteristics are comparable to that reported previously. In 85% of these patients, the diagnosis of GHD was established by provocative testing, particularly an ITT or a combined GHRH-arginine test, with an evident increase in the percentage of GHRH-arginine tests being performed in the last years.

Self-reported loss of consciousness after head trauma does not predispose to hypopituitarism in an older population.

OBJECTIVE: This population study examines the prevalence of hypopituitarism and low bone mineral density (BMD) in older persons reporting loss of consciousness after head trauma (HT). METHODS: Data from the Longitudinal Aging Study Amsterdam were used pertaining to 630 women (53 HT) and 533 men (63 HT). Subjects were asked whether they had ever had an HT with loss of consciousness. Linear regression analysis (adjusted for age, body mass index, chronic diseases, smoking, alcohol use, and gender) was performed to examine the association between HT and serum anteriory pituitary hormone levels, BMD, and quantative ultrasound measurements. RESULTS: Serum follicle stimulating hormone was significantly higher in males in the HT group (P = .05) than in the non-HT group. This difference was not found in women (P = .25). No other differences were observed in serum hormone levels between subjects with and without HT (P > .30). Also, no significant differences between the HT and non-HT group were found in BMD and quantitative ultrasound measurements. CONCLUSION: A self-reported history of HT with loss of consciousness does not seem to increase the risk of hypopituitarism and lower BMD in an aging population.

Treating prolactinoma and psychosis: medication and cognitive behavioural therapy.

The patient in this case report had two severe medical conditions that require oppositional treatment: prolactinoma and psychosis. A prolactinoma is a benign tumour of the pituitary gland that produces prolactin. Dopamine agonist medication is the first-line treatment in patients with prolactinoma. The psychotic symptoms started after a dosage increase of a dopamine D2-receptor agonist. Several antipsychotic medications were tried with and without the dopamine D2-receptor agonist, but severe command hallucinations remained. Cognitive behavioural therapy (CBT) was added which reduced the impact of the hallucinations to a great extent, indicating that CBT can have an additional positive effect in prolactinoma patients with psychosis that shows incomplete recovery after antipsychotic medication. Future research should be aimed at the severe and prolonged side effects of dopamine agonists in the treatment of prolactinoma patients with multiple risk factors for a psychotic decompensation.