The effect of coping strategies on health-related quality of life in acromegaly patients.

PURPOSE: Patients with acromegaly oftentimes exhibit a reduced physical and psychological health-related quality of life (HRQoL). Maladaptive coping styles are associated with poor HRQoL in a number of diseases and patients with pituitary adenomas in general exhibit less effective coping styles than healthy controls. This study aimed to assess coping strategies in acromegaly patients in order to explore leverage points for the improvement of HRQoL. METHODS: In this cross-sectional study, we administered self-report surveys for coping strategies and HRQoL (Short Form SF-36, Freiburg questionnaire on coping with illness, FKV-LIS) in patients with acromegaly. These were set into relation with a variety of health variables. RESULTS: About half of the 106 patients (44.3% female) with a mean age of 56.4 ± 1.3 years showed impaired physical and psychological HRQoL on average 11.2 years after the initial diagnosis. Body mass index, age at survey date and concomitant radiotherapy explained 27.8% of the variance of physical HRQoL, while depressive coping added an additional 9.2%. Depressive coping style and trivialization and wishful thinking were pivotal predictors of an impaired psychological HRQoL with a total explained variance of 51.6%, whereas patient health variables did not affect psychological HRQoL. CONCLUSION: Our results show that maladaptive coping styles have a substantial negative impact on psychological HRQoL in patients with acromegaly, whereas physical HRQoL is influenced to a lesser extent. Specialized training programs aimed at improving coping strategies could reduce long-term disease burden and increase HRQoL in the affected patients.

Transition from Paediatric to Adult Care in CAH: 20 Years of Experience at a Tertiary Referral Center.

Transition medicine aims at the coordinated transfer of young patients with a chronic disease from paediatric to adult care. The present study reflects 20 years of experience in transitioning patients with congenital adrenal hyperplasia (CAH) in a single center setting. Our endocrine transition-clinic was established in 2002 and offers joint paediatric and adult consultations. Data were evaluated retrospectively from 2002 to 2005 and 2008 to present. Fifty-nine patients (29 males) were transferred. Median age was 18.4 years (17.6-23.6). Ninety percent of the patients presented with 21-hydroxlase-deficiency (21-OHD), 38 patients (23 m) with salt-wasting (sw), 7 (1 m) with simple-virilising (sv) and 8 (3 m) with the non-classic (nc) form. Rarer enzyme deficiencies were found in 6 cases: 17α-OHD (2 sisters), P450-oxidoreductase-deficiency (2 siblings), 3ß-hydroxysteroid-dehydrogenase-deficiency (1 m) and 11ß-OHD (1 female). Thirty-four patients (57.6%, 20 m) are presently still attending the adult clinic, 1 patient (1.7%, m) moved away and 24 (40.7%, 8 m) were lost to follow-up (13 sw-21-OHD, 6 sv-21-OHD, 5 nc-21-OHD). Thirty-seven patients (62.7%) attended the adult clinic for >2 years after transfer, 17 (28.8%) for >10 years. In the lost to follow-up group, median time of attendance was 16.3 months (0-195.2). Defining a successful transfer as two or more visits in the adult department after initial consultation in the transition clinic, transfer was efficient in 84.7% of the cases. A seamless transfer to adult care is essential for adolescents with CAH. It requires a continuous joint support during the transition period, remains challenging, and necessitates adequate funding.

Efficacy and Safety of 124I-MIBG Dosimetry-Guided High-Activity 131I-MIBG Therapy of Advanced Pheochromocytoma or Neuroblastoma.

We aim to evaluate the efficacy and safety of 124I-metaiodobenzylguanidine (MIBG) dosimetry-guided high-activity 131I-MIBG therapy of advanced pheochromocytoma or neuroblastoma. Methods: Fourteen patients with advanced pheochromocytoma or neuroblastoma, age 9-69 y, underwent 124I-MIBG PET scans and whole-body retention measurements to assess the whole-body dose as a surrogate of bone marrow toxicity and tumor (absorbed) dose per unit of administered activity. Dosimetry results together with individual patient characteristics were combined to guide a single therapeutic activity to achieve a high tumor dose without exceeding toxicity threshold. Toxicity was assessed for hematologic, hepatic, and renal function. Response was evaluated by RECIST, International Society of Pediatric Oncology Europe Neuroblastoma-like score, change in PET uptake, and quantitative PET parameters (SUVmax, SUVpeak, metabolic tumor volume, total lesion glycolysis), as well as visual decrease in number or in visual intensity of lesions on baseline to follow-up 124I-MIBG PET/CT. Results: The average therapeutic activity was 14 GBq. Eleven of 14 patients (79%) received each more than 10 GBq. One male patient was treated with a single activity of 50 GBq. Three patients were treated with lower activities between 3.5 and 7.0 GBq. Median overall survival was 85 mo (95% CI), and median progression-free survival was 25 mo (95% CI). Four (29%) and 5 (36%) patients demonstrated response (complete response or partial response) by RECIST and functional imaging, respectively. One patient exceeded whole-body dose of 2 Gy and demonstrated grade 3 hematologic toxicity, which resolved spontaneously within 12 mo after the therapy without the need for further treatment. Three patients (21%) demonstrated transient grade 1 renal toxicity. Conclusion: 124I-MIBG dosimetry-guided high-activity 131I-MIBG therapy in patients with advanced pheochromocytoma or neuroblastoma resulted in durable responses with a low rate of manageable adverse events. Efficacy of 124I-MIBG-guided activity escalation should further be assessed in a prospective setting.

Analysis of the GPR17 receptor in NG2-glia under physiological conditions unravels a new subset of oligodendrocyte progenitor cells with distinct functions.

NG2-glia comprise a heterogeneous population of cycling cells that give rise to mature, myelinating oligodendrocytes. The mechanisms that regulate the process of differentiation from NG2-glia into oligodendrocytes are still not fully understood but over the last years the G Protein-coupled Receptor 17 (GPR17) has been on the spotlight as a possible key regulator. Interestingly, GPR17-expressing NG2-glia show under physiological conditions a slower and lower level of differentiation compared to NG2-glia without GPR17. In contrast, after a CNS insult these react with proliferation and differentiation in a high rate, pointing towards a role in repair processes. However, the role of GPR17+ NG2-glia under healthy conditions in adulthood has not been addressed yet. Therefore, we aimed here to characterize the GPR17-expressing NG2-glia. Using transgenic mouse models, we showed restricted GPR17 expression in only some NG2-glia. Furthermore, we found that these cells constitute a distinct subset within the NG2-glia population, which shows a different gene expression profile and behavior when compared to the total NG2-glia population. Genetic depletion of GPR17+ cells showed that these are not contributing to the dynamic and continuous generation of new oligodendrocytes in the adult brain. Taken together, GPR17+ NG2-glia seem to play a distinct role under physiological conditions that goes beyond their classic differentiation control, that needs to be further elucidated. These results open new avenues for using the GPR17 receptor as a target to change oligodendrogenesis under physiological and pathological conditions, highlighting the importance of further characterization of this protein for future pharmacological studies.

Pituitary enlargement in patients with cerebrospinal fluid drainage due to ventricular shunt insertion: know the condition and do not mistake for adenoma.

OBJECTIVE: Childhood hydrocephalus patients treated by ventriculo-peritoneal (v.-p.) shunting are sometimes referred years after this therapy for evaluation of suspicious pituitary enlargement. Since pituitary size has been shown to depend on cerebrospinal fluid (CSF) pressure, we assume this phenomenon to be caused by shunt overdrainage. Therefore, we studied pituitary size and morphology in shunted hydrocephalus patients with radiological signs of high CSF drainage. PATIENTS AND METHODS: Retrospective study of pituitary size and morphology in 15 shunted patients with non-tumoral hydrocephalus and 7 shunted hydrocephalus patients due to childhood brain tumor compared to a population mean. In five brain tumor patients also pre- and postsurgical comparisons were performed. RESULTS: Pituitary mid-sagittal size and pituitary volume were significantly higher in both hydrocephalus groups, compared to the population mean (midsagittal size t = 5.91; p < 0.001; pituitary volume, t = 3.03; p = 0.006). In patients available for pre- and postoperative comparison, there was also a significant increase in pituitary size and volume postoperatively (mean preoperative midsagittal height 2.54 ± 1.0 mm vs. 6.6 ± 0.7 mm post-surgery; mean pre-operative pituitary volume 120.5 ± 69.2 mm3 vs. 368.9 ± 57.9 mm3 post-surgery). CONCLUSION: Our results confirmed a significant increase in pituitary size and volume, mimicking pituitary pathology, after v.-p. shunt insertion. This phenomenon can be explained by the Monro-Kellie doctrine, stating that intracranial depletion of CSF-as caused by v.p. shunting-leads to compensatory intracranial hyperemia, especially in the venous system, with the consequence of engorged venous sinuses, most likely responsible for enlargement of the pituitary gland.

Pre-Surgery Patient Health Contributes to Aggravated Sino-Nasal Outcome and Quality of Life after Pituitary Adenomectomy.

Objectives: The transphenoidal bi-nostril endoscopic resection of pituitary adenomas is regarded as a minimally invasive treatment nowadays. However, sino-nasal outcome and health-related quality of life (HRQoL) might still be impaired after the adenomectomy, depending on patients' prior medical history and health status. A systematic postoperative comparison is required to assess differences in perceived sino-nasal outcome and HRQoL. Methods: In this single-center observational study, we collected data from 81 patients, operated between August 2016 and August 2021, at a 3-6-month follow-up after adenomectomy. We employed the sino-nasal outcome test for neurosurgery (SNOT-NC) and the HRQoL inventory Short Form (SF)-36 to compare sino-nasal and HRQoL outcome in patients with or without allergies, previous nose surgeries, presence of pain, snoring, sleep apnea, usage of continuous positive airway pressure (cpap), and nose drop usage. Results: At the 3-6-month follow-up, patients with previous nasal surgery showed overall reduced subjective sino-nasal health, increased nasal and ear/head discomfort, increased visual impairment, and decreased psychological HRQoL (all p ≤ 0.026) after pituitary adenomectomy. Patients with pain before surgery showed a trend-level aggravated physical HRQoL (p = 0.084). Conclusion: Our data show that patients with previous nasal surgery have an increased risk of an aggravated sino-nasal and HRQoL outcome after pituitary adenomectomy. These patients should be thoroughly informed about potential consequences to induce realistic patient expectations. Moreover, the study shows that patients with moderately severe allergies, snoring, and sleep apnea (± cpap) usually do not have to expect a worsened sino-nasal health and HRQoL outcome.

Clonidine suppression test for a reliable diagnosis of pheochromocytoma: When to use.

OBJECTIVE: In clinical practice, false-positive results in biochemical testing for suspected pheochromocytoma/paraganglioma (PPGL) are not infrequent and may lead to unnecessary examinations. We aimed to evaluate the role of the clonidine suppression test (CST) in the era of analyses of plasma-free metanephrines for the diagnosis or exclusion of PPGL in patients with adrenal tumours and/or arterial hypertension. DESIGN AND METHODS: This single-centre, prospective trial investigated the use of CST in 60 patients with suspected PPGL associated with out-patient elevations of plasma normetanephrine (NMN) and/or metanephrine (MN), in most cases accompanied with hypertension or an adrenal mass. Measurements of plasma catecholamines and free metanephrines were performed by liquid chromatography with electrochemical detection and tandem mass spectrometry, respectively. RESULTS: Forty-six patients entered final analysis (n = 20 with PPGL and n = 26 with a nonfunctional adrenal mass and/or hypertension). CST reliably excluded false-positive baseline NMN results with a specificity of 100%. The sensitivity of CST improved from 85% to 94% when tumours with isolated MN increase (n = 3) were not considered. In patients with elevated baseline NMN (n = 24), CST correctly identified all patients without PPGL. Patients with falsely elevated baseline NMN results (n = 7, 26.9%) exhibited increases of baseline NMN up to 1.7-fold above the upper reference limit. CONCLUSION: CST qualifies as a useful diagnostic tool for differential diagnosis of borderline elevated plasma-free NMN in patients with suspected PPGL. In this context, CST helps to correctly identify all false-positive NMN screening results.

Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe.

Objective: To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Design and methods: A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN. Results: Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4-5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France. Conclusions: This study reveals a high international variability and discrepancy in the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence-based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH.

Diagnostic Performance of 124I-Metaiodobenzylguanidine PET/CT in Patients with Pheochromocytoma.

123/131I-metaiodobenzylguanidine (MIBG) scintigraphy has shown a high specificity for imaging pheochromocytoma and paraganglioma, but with low sensitivity because of low spatial resolution. 124I-MIBG PET may be able to overcome this limitation and improve the staging of patients with (suspected) pheochromocytoma. Methods: We analyzed the sensitivity, specificity, and positive and negative predictive values of 124I-MIBG PET in 43 consecutive patients with suspected (recurrence of) pheochromocytoma using histopathologic (n = 25) and clinical validation (n = 18) as the standard of truth. Furthermore, we compared the detection rate of 124I-MIBG PET versus contrast-enhanced (CE) CT on a per-patient and per-lesion basis in 13 additional patients with known metastatic malignant pheochromocytoma. Results:124I-MIBG PET/CT was positive in 19 (44%) of 43 patients with suspected pheochromocytoma. The presence of pheochromocytoma was confirmed in 22 (51%) of 43. 124I-MIBG PET/CT sensitivity, specificity, and positive and negative predictive values were 86%, 100%, 100%, and 88%, respectively. 124I-MIBG PET was positive in 11 (85%) of 13 patients with malignant pheochromocytoma. Combined 124I-MIBG PET and CE CT detected 173 lesions, of which 166 (96%) and 118 (68%) were visible on 124I-MIBG PET and CE CT, respectively. Conclusion:124I-MIBG PET detects pheochromocytoma with high accuracy at initial staging and a high detection rate at restaging. Future assessment of 124I-MIBG PET for treatment guidance, including personalized 131I-MIBG therapy, is warranted.

Streptozocin/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy.

PURPOSE: The role of streptozocin-based chemotherapy (STZ CTx) in advanced, well-differentiated pancreatic neuroendocrine tumours (PanNET) and the best sequence of treatments in advanced PanNET are unclear. We examined the outcomes after STZ CTx in patients who had been selected according to the current therapeutic guidelines. METHODS: Data from 50 PanNET patients consecutively treated with STZ CTx between 2010 and 2018 were analysed. The endpoints of the study were the objective-response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: STZ CTx was the first-line treatment in 54% of patients. The PanNET grades were as follows: 6% G1, 88% G2, and 6% well-differentiated G3. The ORR was 38%. Stable disease was the best response in 38% of patients and 24% showed progressive disease. Treatment was discontinued because of toxicity in one patient. Median PFS and OS were 12 (95% confidence interval (CI), 8.5-15.5) and 38 months (95% CI, 20.4-55.6), respectively. In the Kaplan-Meier analysis, the median OS was 89 months (95% CI, 34.9-143.1) for STZ CTx as first-line therapy compared with 22 months (95% CI, 19.3-24.7; p = 0.001, log-rank test) for subsequent lines. Bone metastases negatively impacted survival (HR, 2.71, p = 0.009, univariate analysis, HR, 2.64, p = 0.015, multivariate analysis, and Cox regression). CONCLUSIONS: In patients selected according to current guidelines, PFS, and OS after STZ CTx were lower than previously reported, whereas ORR was unchanged. First-line treatment was positively associated with OS and the presence of bone metastases was negatively associated with OS. Pre-treatment with targeted or peptide-receptor radionuclide therapy did not alter ORR, PFS, or OS.

Distinct Late-Night Salivary Cortisol Cut-Off Values for the Diagnosis of Hypercortisolism.

Due to high morbidity and mortality of untreated hypercortisolism, a prompt diagnosis is essential. Measurement of late-night salivary cortisol provides a simple and non-invasive method. However, thresholds and reference ranges differ among studies. The goal of this study was to define a threshold of late-night salivary cortisol for the diagnosis of hypercortisolism based on the used assay. Moreover, the influence of different aetiologies of hypercortisolism and individual comorbidities were investigated. Prospective analyses of 217 patients, including 36 patients with proven hypercortisolism were carried out. A sum of 149 patients with suspicion of hypercortisolism but negative endocrine testing and 32 patients with hypercortisolism in remission served as control group. Late-night salivary cortisol was measured using an automated chemiluminescence immunoassay. Cut-off values were calculated by ROC analysis. The calculated cut-off value for the diagnosis of hypercortisolism was 10.1 nmol/l (sensitivity 94%; specificity 84%). Only slightly lower thresholds were obtained in patients with suspected hypercortisolism due to weight gain/obesity (9.1 nmol/l), hypertension or adrenal tumours (both 9.8 nmol/l) or pituitary adenomas (9.5 nmol/l). The late-night salivary cortisol threshold to distinguish between Cushing's disease and Cushing's disease in remission was 9.2 nmol/l. The cut-off value for the diagnosis of ectopic ACTH-production was 109.0 nmol/l (sensitivity 50%, specificity 92%). Late-night salivary cortisol is a convenient and reliable parameter for the diagnosis of hypercortisolism. Except for ectopic ACTH-production, thresholds considering different indications for evaluation of hypercortisolism were only slightly different. Therefore, they might only be useful if late-night salivary cortisol results near the established cut-off value are present.

Illness-related burden, personal resources and need for support in patients with acromegaly: Results of a focus group analysis.

OBJECTIVE: It was the aim of this study to evaluate illness-related burdens and support needs of patients with acromegaly to identify hitherto unadressed research questions and to open up avenues for improvements in patient care. This was done by using the focus group approach as a qualitative research method. DESIGN: Seven patients with acromegaly took part in a focus group moderated by an external medical communication specialist. The discourse focused on topics such as impact of the illness on everyday life, support needs and personal resources. The discussion was recorded and transcribed and analyzed by qualitative content analysis. RESULTS: Participants reported a huge impact of acromegaly on daily life, ranging from time expenditure for managing their illness, to bodily and mental sequelae and strain caused by physical disfigurement. Patients' coping strategies included family support, physical activities and humor. The participants wished for a sound patient-doctor relationship, more interdisciplinary and holistic treatment, medical rehabilitation services with special knowledge on acromegaly-related morbidity, a stable contact person in the medical process and reliable information material for themselves and their relatives. CONCLUSIONS: The results provide multi-facetted impressions of the overwhelming impact of acromegaly and unmet support needs of the afflicted patients. Further quantitative research is necessary to examine the generalisibility of the present results in order to implement tailored support measures. We suggest to develop standardized questionnaires to explore the prevalence and severity of the addressed problems in a large patient sample and to establish screening instruments to monitor disease burden in clinical practice.

Adults' Adherence to Growth Hormone Replacement in Relation to Medication-Related Beliefs, Coping and Quality of Life - An Exploratory Analysis.

Introduction: Little is known about psychological reasons associated with adherence to growth hormone (GH) replacement therapy (GHRx) in adults. As in other chronic diseases, medication-related beliefs, coping strategies and disease impact on quality of life (QoL) might play an important role. We thus explored these psychological factors in relation to adherence in patients with GH deficiency (GHD) in order to find leverage points for the improvement of adherence. Patients and Methods: Cross-sectional analysis including 107 adult GHD patients on GHRx who completed self-assessment inventories on health-related QoL (Short-Form SF-36), coping style (Freiburg questionnaire on coping with illness, FKV-LIS) and medication beliefs (Beliefs about Medicine questionnaire, BMQ). Results were correlated to general and GH-specific adherence to medication. Results: In the BMQ, 92.5% of the patients (n=99) reported a strong belief in the need for their medication, which correlated significantly with general adherence (rs = 0.325). Active coping was significantly related to general (rs = 0.307) and GH-specific adherence (rs = 0.226). Better mental QoL (rs = 0.210) but worse physical QoL (rs = -0.198; all p < 0.05) were related to higher GH-specific adherence. Older age was associated with a higher degree of active coping, a higher belief in the necessity of medication and worse physical QoL. Conclusion: We provide preliminary data that most GHD patients on GHRx are strongly convinced of their need for medication and that adherence to GHRx is influenced by coping strategies and QoL. Patients with impaired psychological QoL are less able to translate their convictions into good adherence, a phenomenon to be addressed in future research.

Prevalence of Osteopathologies in Children and Adolescents After Diagnosis of Acute Lymphoblastic Leukemia.

Background: Impaired bone health is a late effect of childhood malignancies which can be difficult to detect in juvenile survivors. It may, however, lead to compromised quality of life, or even permanent disability later in life due to osteoporosis, pain or fractures if left untreated. Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy with an over 85% five-year survival. ALL and its treatment cause bone alterations in adults, but little information on the bone health status in juvenile survivors is available. Objective: To report data on skeletal late effects in juvenile survivors of childhood ALL based on a comprehensive assessment of bone health and to assess the influence of a vitamin D deficiency on bone health in this cohort. Methods: In a single center cross sectional study 128 pediatric patients (11.9 ± 4.76 years) with a mean follow up of 5.88 ± 3.75 years after diagnosis of ALL were recruited. The bone health status of the survivors was assessed based on clinical examination, review of medical records, biochemical and radiographic analyses, by clinical experts. A score which utilized 8 different parameters was formed and used to assess the effect of a vitamin D deficiency on bone health. Results: In this cohort, 18% of survivors displayed overt osteopathologies as defined by clinical expert assessment. Impaired bone health, defined by at least one pathological screening parameter, was detected in 77%. Despite recommendations for adequate vitamin D supplementation, 15% displayed a vitamin D deficiency associated with hyperparathyroidism. The applied score identified survivors with osteopathologies with high sensitivity and specificity. The median score did not differ between patients without and with severe vitamin D deficiency. Conclusion: Our findings suggest that impaired bone health and osteopathologies are common skeletal late effects following treatment of childhood ALL. Major contributing factors are BMT, irradiation and older age at diagnosis. Vitamin D deficiency likely accounts for hyperparathyroidism in some patients but does not seem to further affect bone health in this cohort. Survivors of ALL need thorough surveillance to investigate bone health, since bone morbidity is common and still poorly understood. Early detection and appropriate intervention may improve bone health.

Motivation for and adherence to growth hormone replacement therapy in adults with hypopituitarism: the patients' perspective.

INTRODUCTION: While reasons for non-adherence in children requiring growth hormone (GH) replacement (GH-Rx) are well researched, few studies have investigated adherence in adult GH deficient patients. Against the background of the adverse medical sequelae of untreated severe GH deficiency (GHD) in adults, we explored adherence to GH-Rx and associated factors in this patient group. METHOD: Cross-sectional analysis including 107 adult patients with severe GHD on GH-Rx, 15 untreated GDH patients and 19 who had discontinued therapy. Patients completed self-developed ad hoc surveys on adherence to medication and GH-Rx, specific beliefs about GH-Rx, side effects and burden of injection, reasons for never receiving or dropping out of therapy, respectively. RESULTS: Adherence to GH-Rx was high (mean 15.8/18 points on the self-developed adherence score) and significantly correlated with general medication adherence. Higher age was significantly associated with better adherence to GH-Rx, while injection side effects, duration of treatment or device used were not. The most frequent reasons for not being on GH-Rx apart from medical reasons included fear of side effects, lack of belief in treatment effects and dislike of injections. In patients not on GH-Rx, the proportion of patients in employment was significantly smaller than in the treatment group, despite similar age and comorbidities. CONCLUSIONS: Adherence to GH-Rx was high for those patients on therapy. Instead of focusing on improving adherence in those adults already on GH-Rx, efforts should be undertaken to ally fear of side effects and provide education on positive treatment effects for those eligible but not receiving therapy.

Efficacy of Temozolomide Therapy in Patients With Aggressive Pituitary Adenomas and Carcinomas-A German Survey.

CONTEXT: Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging. OBJECTIVE: We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness. DESIGN AND SUBJECTS: Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients. RESULTS: Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated. CONCLUSION: We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.

Resistance to GHRH but Not to PTH in a 15-Year-Old Boy With Pseudohypoparathyroidism 1A.

Pseudohypoparathyroidism 1A (PHP1A) consists of signs of Albright hereditary osteodystrophy (AHO) and multiple, variable hormonal resistances. Elevated PTH levels are the biochemical hallmark of the disease. Short stature in PHP1A may be caused by a form of accelerated chondrocyte differentiation leading to premature growth plate closure, possibly in combination with GH deficiency in some patients. Treatment of short stature with recombinant growth hormone (rhGH) in pediatric patients may improve final height if started during childhood. The 10 11/12-year-old boy with clinical signs of AHO presented for evaluation of short stature [height standard deviation score (SDS) -2.72]. Clinically his mother was affected by AHO as well. A heterozygous mutation c.505G>A (p.E169K) in exon 6 of the GNAS gene confirmed a diagnosis of PHP1A in the boy. However, hormonal assessment was unremarkable except for low serum IGF-1 (SDS -2.67). On follow-up, GH deficiency due to GHRH resistance was suspected and confirmed by clonidine and arginine stimulation tests. Treatment with rhGH (0.035 mg/kg) for 2 years resulted in catch-up growth (height SDS -1.52). At age 15 years the PTH levels and bone age of the patient remain within the normal range. In patients with PHP1A, short stature is caused by the effects of Gs-α deficiency on the growth plate. However, resistance to GHRH and the resulting GH deficiency might also contribute. Recombinant GH treatment increases growth in these patients. Diagnostic workup for GH deficiency as a factor contributing to short stature is recommended even in the absence of other hormonal resistances.

Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood.

Whereas microglia involvement in virtually all brain diseases is well accepted their role in the control of homeostasis in the central nervous system (CNS) is mainly thought to be the maintenance of neuronal function through the formation, refinement, and monitoring of synapses in both the developing and adult brain. Although the prenatal origin as well as the neuron-centered function of cortical microglia has recently been elucidated, much less is known about a distinct amoeboid microglia population formerly described as the "fountain of microglia" that appears only postnatally in myelinated regions such as corpus callosum and cerebellum. Using large-scale transcriptional profiling, fate mapping, and genetic targeting approaches, we identified a unique molecular signature of this microglia subset that arose from a CNS endogenous microglia pool independent from circulating myeloid cells. Microglia depletion experiments revealed an essential role of postnatal microglia for the proper development and homeostasis of oligodendrocytes and their progenitors. Our data provide new cellular and molecular insights into the myelin-supporting function of microglia in the normal CNS.