Cardiometabolic outcomes in children and adolescents following discontinuation of long-term risperidone treatment

Objective: Second-generation antipsychotics (SGAs) cause weight gain and cardiometabolic abnormalities in children and adolescents. Less well-investigated is the outcome of these adverse events following SGA discontinuation, which we examined. Methods: Medically healthy 7 to 17-year-old patients treated with risperidone for ≥6 months were enrolled and returned for follow-up, 1.5 years later. Treatment history was extracted from the medical and pharmacy records. Anthropometric and laboratory measurements were obtained at each research visit. Multivariable linear regression analysis and Fisher's exact test were used to compare participants who remained on risperidone at follow-up (Risp Cont Group) with those who had discontinued SGA treatment (SGA Disc Group) and those who had switched to another SGA (SGA Cont Group). Correlational analyses examined the association between change in age-sex specific body mass index (BMI) z score between study entry and follow-up and change in cardiometabolic outcomes. Results: The sample consisted of 101 participants (93% male) with a mean age of 11.7±2.6 years at study entry. The majority had an externalizing disorder and received 0.03±0.02 mg/kg/day of risperidone, for 2.5±1.6 years. At follow-up, 18% (n=18) were in the SGA Disc Group and 9% (n=9) were in the SGA Cont Group. BMI z score decreased in the SGA Disc Group, remained unchanged in the Risp Cont Group (n=74), and increased in the SGA Cont Group. Importantly, the change in BMI z score between study entry and follow-up was significantly correlated with the change in systolic and diastolic blood pressure z scores, heart rate, waist circumference, percent body fat, inflammatory markers, fasting total insulin, homeostatic model assessment insulin resistance index (HOMA-IR), C-peptide, total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, triglycerides, triglycerides/HDL ratio, and leptin. Conclusions: Following several years of treatment, risperidone discontinuation is associated with a reversal of the excessive weight gain, mediated by a negative energy balance, and a corresponding improvement in cardiometabolic parameters

Crystallographic disorder and electron scattering on structural two-level systems in ZrAs1.4Se0.5

Single crystals of ZrAs1.4Se0.5 (PbFCl type structure) were grown by chemical vapour transport. While their thermodynamic and transport properties are typical for ordinary metals, the electrical resistivity exhibits a shallow minimum at low temperatures. Application of strong magnetic fields does not influence this anomaly. The minimum of the resistivity in ZrAs1.4Se0.5 apparently originates from interaction between the conduction electrons and structural two-level systems. Significant disorder in the As-Se substructure is inferred from X-ray diffraction and electron microprobe studies

The risk for breast cancer is not evidently increased in women with hyperprolactinemia

The question has been raised whether hyperprolactinemia in humans is associated with an excess risk for breast cancer. We aimed to assess the risk of breast cancer in a previously defined large cohort of patients treated for idiopathic hyperprolactinemia or prolactinomas. Based on the pattern of drug prescriptions we identified 11,314 subjects in the PHARMO network with at least one dispensing of dopamine agonists between 1996 and 2006. Of these, 1,607 subjects were considered to have dopamine agonist—treated hyperprolactinemia based on the prescribing pattern. For the present analysis, we included only women (n = 1,342). Patients with breast cancer were identified by hospital discharge codes. Data on breast cancer incidence in the Netherlands were derived from the Dutch cancer registry. Standardized mortality ratio (SMR) was the measure of outcome to assess the association between hyperprolactinemia and breast cancer. The 1,342 patients accounted for a total of 6,576 person years. Eight patients with breast cancer during follow-up were identified. Indirect standardization with incidence proportions from the general Dutch population revealed a 7.47 expected cases. The calculated SMR for breast cancer risk in patients treated hyperprolactinemia was 1.07 (95% confidence interval 0.50–2.03). In conclusion, there is no clear evidence for increased breast cancer risk in female patients treated for either idiopathic hyperprolactinemia or prolactinomas. The uncertainty about the exact risk that is due to the relatively low number of breast cancer cases, should be overcome by pooling results in a future meta-analysis

Guidelines for acromegaly management: An update

"Objective: The Acromegaly Consensus Group reconvened in November 2007 to update guidelines for acromegaly management. Participants: The meeting participants comprised 68 pituitary specialists, including neurosurgeons and endocrinologists with extensive experience treating patients with acromegaly. Evidence/Consensus Process: Goals of treatment and the appropriate imaging and biochemical and clinical monitoring of patients with acromegaly were enunciated, based on the available published evidence. Conclusions: The group developed a consensus on the approach to managing acromegaly including appropriate roles for neurosurgery, medical therapy, and radiation therapy in the management of these patients.

Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists

Despite the fact that consensus guidelines recommend long-term dopamine agonist (DA) therapy as a first-line approach to the treatment of small prolactinoma, some patients continue to prefer a primary surgical approach. Concerns over potential adverse effects of long-term medical therapy and/or the desire to become pregnant and avoid long-term medication are often mentioned as reasons to pursue surgical removal. In this retrospective study, 34 consecutive patients (30 female, 4 male) preferably underwent primary pituitary surgery without prior DA treatment for small prolactinomas (microprolactinoma 1–10 mm, macroprolactinoma 11–20 mm) at the Department of Neurosurgery, University of Bern, Switzerland. At the time of diagnosis, 31 of 34 patients (91%) presented with symptoms. Patients with microprolactinomas had significantly lower preoperative prolactin (PRL) levels compared to patients with macroprolactinomas (median 143 μg/l vs. 340 μg/l). Ninety percent of symptomatic patients experienced significant improvement of their signs and symptoms upon surgery. The postoperative PRL levels (median 3.45 μg/l) returned to normal in 94% of patients with small prolactinomas. There was no mortality and no major morbidities. One patient suffered from hypogonadotropic hypogonadism after surgery despite postoperative normal PRL levels. Long-term remission was achieved in 22 of 24 patients (91%) with microprolactinomas, and in 8 of 10 patients (80%) with macroprolactinomas after a median follow-up period of 33.5 months. Patients with small prolactinomas can safely consider pituitary surgery in a specialized centre with good chance of long-term remission as an alternative to long-term DA therapy

Medical treatment of prolactinomas.

Prolactinomas, the most prevalent type of neuroendocrine disease, account for approximately 40% of all pituitary adenomas. The most important clinical problems associated with prolactinomas are hypogonadism, infertility and hyposexuality. In patients with macroprolactinomas, mass effects, including visual field defects, headaches and neurological disturbances, can also occur. The objectives of therapy are normalization of prolactin levels, to restore eugonadism, and reduction of tumor mass, both of which can be achieved in the majority of patients by treatment with dopamine agonists. Given their association with minimal morbidity, these drugs currently represent the mainstay of treatment for prolactinomas. Novel data indicate that these agents can be successfully withdrawn in a subset of patients after normalization of prolactin levels and tumor disappearance, which suggests the possibility that medical therapy may not be required throughout life. Nevertheless, multimodal therapy that involves surgery, radiotherapy or both may be necessary in some cases, such as patients who are resistant to the effects of dopamine agonists or for those with atypical prolactinomas. This Review reports on efficacy and safety of pharmacotherapy in patients with prolactinomas

Bone mass in schizophrenia and normal populations across different decades of life

<p>Abstract</p> <p>Background</p> <p>Chronic schizophrenic patients have been reported as having higher osteoporosis prevalence. Survey the bone mass among schizophrenic patients and compare with that of the local community population and reported data of the same country to figure out the distribution of bone mass among schizophrenic patients.</p> <p>Methods</p> <p>965 schizophrenic patients aged 20 years and over in Yuli Veterans Hospital and 405 members aged 20 and over of the community living in the same town as the institute received bone mass examination by a heel qualitative ultrasound (QUS) device. Bone mass distribution was stratified to analyzed and compared with community population.</p> <p>Results</p> <p>Schizophrenic patients have lower bone mass while they are young. But aging effect on bone mass cannot be seen. Accelerated bone mass loss during menopausal transition was not observed in the female schizophrenic patients as in the subjects of the community female population.</p> <p>Conclusion</p> <p>Schizophrenic patients have lower bone mass than community population since they are young. Further study to investigate the pathophysiological process is necessary to delay or avoid the lower bone mass in schizophrenia patients.</p

Effects of plasma magnesium and prolactin on quantitative ultrasound measurements of heel bone among schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Osteoporosis is a bone disease that can reduce both bone mass and bone strength. It can cause serious fractures of bones, along with causing significant and even devastating physical, psychological and financial consequences for patients and their family members. Many reports have revealed that the prevalence of decreased bone density is higher in schizophrenic patients than in the non-psychological diseased population. The previous report of our group revealed that chronic schizophrenia patients have poorer BUA levels since they were young as compared to the general community population. Hyperprolactinemia and antipsychotics are reported to be among the risk factors for osteoporosis in chronic schizophrenic patients.</p> <p>Methods</p> <p>93 schizophrenic patients with severely poor adjusted BUA values and 93 age and gender matched patients with normal adjusted BUA values from a previous survey study were selected. Data were collected via questionnaires and via reviews of antipsychotic medications. Blood samples were drawn, and serum levels of prolactin, estradiol, testosterone, magnesium, calcium, phosphate, osteocalcin, Cross-linked N-teleopeptide of type I collagen (NTX), thyroid hormone and parathyroid hormone were checked. The association between BUA levels and serum levels of the above items, along with the type of received antipsychotic medication, was evaluated.</p> <p>Results</p> <p>There was no significant association found between reduced BUA levels and serum prolactin, calcium, phosphate, osteocalcin, NTX, thyroid stimulating hormone and parathyroid hormone levels. There was also no association between BUA levels and types of currently received antipsychotics. There was no association between BUA levels and menstruation condition in female patients. Hypermagnesemia had a borderline association with classical and combined (classical and atypical) antipsychotic medications in male patients. Nevertheless, hypermagnesemia is a significant protective factor of reduced BUA levels in female patients. Hyperprolactinemia had a significant association with classical and combined antipsychotic medications in female patients. Hyperprolactinemia, however, provides a protective effect on reduced BUA levels in male patients. There was no significant association found between serum prolactin level and the type of antipsychotic medication received.</p> <p>Conclusions</p> <p>The results of this study are in contrast with literature that has reported an association between bone mass and serum prolactin levels, serum magnesium levels and type of received antipsychotics. Further study to investigate the pathophysiological process and the association between bone mass and serum prolactin level, serum magnesium level and specific antipsychotics is necessary.</p

Prolactinomas, Cushing's disease and acromegaly: debating the role of medical therapy for secretory pituitary adenomas

Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients