Treatment of Pasireotide LAR-Associated Hyperglycemia In A Patient With Acromegaly

Objective: Hyperglycemia was noted in pasireotide long-acting release (PAS LAR}-treated patients with acromegaly during clinical trials. We describe a clinical approach to hyperglycemia in a patient with acromegaly and diabetes mellitus type 2 (DM2) during PAS LAR initiation and treatment. Methods: Clinical response to PAS LAR, including self­ monitored blood glucose (SMBG) levels, HbA1c, IGF-1, and adverse effects, was reported. Case Presentation: A 44-year-old male was referred for consultation in 2007 owing to uncontrolled DM2 despite maximum metformin (MET) dose. Testing led to a biochemical diagnosis of acromegaly. An 8-mm pituitary adenoma was seen on MRI. Transsphenoidal pituitary adenoma resection was performed, but residual tumor remained. Postoperative IGF-1 levels were 394 ng/mL (age-normalized range, 75-216 ng/mL). Octreotide (OCT) therapy was initiated, switched to OCT LAR 20 mg monthly, increased to 40 mg monthly, and twice­ weekly cabergoline (CAB) 0.5 mg was added; none of these treatments normalized IGF-1 or resolved symptoms. Change to either lanreotide or pegvisomant (PEG), combined with CAB, was also unsuccessful; IGF-1 levels were 364 ng/mL (age-normalized range, 61-200 ng/mL), FPG 174 mg/dL, and HbA1c 7.3%. Metformin was initially decreased postoperatively then re-optimized. Before switching from PEG to PAS LAR, SMBG frequency increased. Within 24 hours of PAS LAR initiation (and continuation of CAB), glucose levels increased to 200 to 300 mg/dL. Liraglutide (LIRA) was added, although severe nausea slowed titration, and glimepiride (GLIM) was added. After 6 weeks of PAS LAR, LIRA, GLIM, and MET, IGF-1 levels were reduced to 239 ng/mL, whereas glucose and HbA1c increased to 265 mg/dL and 7.9%, respectively. Frequency of SMBG remained consistent. Severe nausea improved upon increase to GLIM 8 mg daily and switch from LIRA to dulaglutide. Glucose levels slowly dropped to 150 to 160 mg/dL. Three months after PAS LAR initiation, IGF-1, glucose, and HbA1c were 274 ng/mL, 172 mg/dL, and 7.9%, respectively. Discussion: PAS LAR resulted in IGF-1 reduction. Significant hyperglycemia occurred immediately after initiation and required rapid changes to DM2 medication. Following recommendations to increase SMBG, frequent medication adjustment, and addition of GLP-1 analogue in response to hyperglycemia returned SMBG levels to baseline, although HbA1c was predictably unchanged at 3 months. Conclusion: Hyperglycemia is an expected adverse effect of PAS LAR. Vigilant SMBG and rapid response to hyperglycemia using GLP-1 analogues can be an effective option for treating patients with acromegaly and DM2 who are receiving PAS LAR, although more study is warranted

Cognitive Effects of Aromatase and Possible Role in Memory Disorders

Diverse cognitive functions in many vertebrate species are influenced by local conversion of androgens to 17β-estradiol (E2) by aromatase. This enzyme is highly expressed in various brain regions across species, with some inter-species variation in terms of regional brain expression. Since women with breast cancer and men and women with other disorders are often treated with aromatase inhibitors (AI), these populations might be especially vulnerable to cognitive deficits due to low neuroE2 synthesis, i.e., synthesis of E2 directly within the brain. Animal models have been useful in deciphering aromatase effects on cognitive functions. Consequences of AI administration at various life cycle stages have been assessed on auditory, song processing, and spatial memory in birds and various aspects of cognition in rodent models. Additionally, cognitive deficits have been described in aromatase knockout (ArKO) mice that systemically lack this gene throughout their lifespan. This review will consider evidence to date that AI treatment in male and female rodent models, birds, and humans results in cognitive impairments. How brain aromatase regulates cognitive function throughout the lifespan, and gaps in current knowledge will be considered, along with future directions to better define how aromatase might guide learning and memory from early development through the geriatric period. Better understanding the importance of E2 synthesis on neurobehavioral responses at various ages will likely aid in the discovery of therapeutic strategies to prevent potential cognitive deficits, including Alzheimer's Disease, in individuals treated with AI or those possessing CYP19 gene polymorphisms, as well as cognitive effects of normal aging that may be related to changes in brain aromatase activity

Diffuse Sclerosing Papillary Carcinoma In A Pediatric Patient With Intrauterine Diagnostic Xray Exposure

Objective: The relationship between occurrence of childhood cancer and intrauterine exposure to radiation is well known. We describe a case of diffuse sclerosing papillary carcinoma (PTC) in a pediatric patient exposed to diagnostic radiation in utero. Methods: Clinical presentation, including radiation history and outcome, was reported. Case Presentation: A 14 year old male was referred for a thyroid cancer consultation in 2008. His history was notable for a rapidly growing thyroid mass during the preceding 3 months and in utero exposure to radiation, in the form of multiple xrays and CT scans, at 12 weeks gestation as a result of maternal multiple trauma due to a car accident. A total thyroidectomy with bilateral central, level 7 and right modified neck dissection for a rapidly growing thyroid mass was performed. Pathology revealed multifocal, bilateral, moderately differentiated, diffuse sclerosing PTC 8.6 em in greatest dimension. The tumor was not encapsulated, with vascular invasion and extensive extrathyroidal extension. Metastases were positive in 32 of 36 lymph nodes sampled. Post-operative unstimulated thyroglobulin (Tg) by RIA and Tg antibody (TgAb) were 137 (0-39 ng/mL) and 4183 (0- 100 IU/mL), respectively. Ultrasound (US), PET/CT and post I-131 treatment scan revealed abnormal nodes but no distant metastases. To date, he has had an additional right neck dissection for poorly differentiated PTC lymph node metastases, a total of 340 mCi ofl-131, and has persistently positive unstimulated Tg and TgAb at 9.2 (/mL) and 36 ( Discussion: Diffuse sclerosing PTC occurred in this pediatric patient exposed to diagnostic radiation in utero. His clinical course was notable for locally aggressive behavior of the PTC and biochemically persistent disease. A causal relationship between the timing and quantity of the radiation exposure and the development of a rare variant of PTC in this patient was suspected. Conclusion: The relationship between radiation exposure and PTC is well known. Case control studies have documented an increased risk of childhood cancer in those exposed to radiation over 10mSv in utero. Although radiation exposure to the developing fetus rarely occurs, consideration should be given for close monitoring of in utero radiation exposed patients for the development of PTC

Corticosteroid Weaning in Stable Heart Transplant Patients: Guidance by Serum Cortisol Level

Background: Despite earlier studies describing the feasibility of steroid weaning in heart transplant patients, the majority of patients are maintained on steroid therapy for life. We examined a strategy based on a single morning serum cortisol measurement. Methods: We assigned stable posttransplant patients, who were maintained on tacrolimus, mycophenolate mofetil, and corticosteroids, into one of two groups based on a screening morning cortisol level. Patients with a cortisol \u3c 8 micrograms/deciliter were assigned to a maintenance group and the others were assigned to the weaning group and steroids were tapered off over 4-6 weeks. Patients were monitored on subsequent office visits for adrenal insufficiency and allograft rejection. Results: Thirty-one patients were enrolled (6 patients in the maintenance group and 25 in the steroid-weaning group). Mean follow-up was 10.2 ± 4 years for the weaning group and 9.0 ± 4.9 years in the maintenance group (p = 0.6). No cases of rejection were noted, nor did any patient resume steroid treatment following discontinuation. Conclusion: Steroids can be safely discontinued in stable heart transplant patients with an AM serum cortisol ≥ 8 micrograms/deciliter with appropriate outpatient follow-up. In this study, no patient suffered late rejection or clinically noted adrenal insufficiency

Recital: Continuum: Sheila Schonbrun, Soprano; Jayn Rosenfeld, Flutist; Cheryl Seltzer, Piano; Joel Sachs, Piano; February 17, 1977

Centennial East Recital HallThursday EveningFebruary 17, 19778:00 p.m

Offspring sex ratio varies with maternal condition in mice

Abstract only availableField and laboratory animal studies have demonstrated that maternal body condition can directly cause adjustments in offspring sex ratio. A mother's condition is affected by a variety of environmental and endogenous factors, but in particular food availability plays a major determining role. During famine conditions, the females should theoretically bias their offspring's sex ratio towards the sex with the lower reproductive value, e.g. daughters in most species. When resources become more plentiful, however, the dams should bias their offspring towards the sex with the greater reproductive value e.g sons in most species. In our experiment, we have chosen to examine the effects of diet manipulation in NIH Swiss and CF1 mice housed under standard laboratory conditions. This experiment was a follow-up to an initial study performed by this laboratory that indicated mouse mothers fed a very high fat diet (VHF) before conception gave birth to more male offspring. However, female mice fed on the low fat (LF) diet produced more daughters. The aim of our current study is to determine when during gestation the shift in offspring sex ratio is occurring in the females provisioned with the two diets. We are focusing initially on two time periods, at fertilization and post-implantation or day 8 phase of pregnancy. To determine the sex of these early stage embryos, two approaches are being employed: 1) PCR analysis of sex chromosome DNA and 2) Fluorescence in Situ Hybridization (FISH) with X and Y chromosome probes. In the course of our experiments, we have met and are currently working to overcome several problems that have occurred. We are close to optimizing both procedures, and in the next few months, we anticipate having more data and a better understanding of when the shift in offspring sex ratio is occurring in the females fed the LF and VHF diets.Life Sciences Undergraduate Research Opportunity Progra

Karyotype analysis and sex determination in Australian Brush-turkeys (Alectura lathami)

Sexual differentiation across taxa may be due to genetic sex determination (GSD) and/or temperature sex determination (TSD). In many mammals, males are heterogametic (XY); whereas females are homogametic (XX). In most birds, the opposite is the case with females being heterogametic (ZW) and males the homogametic sex (ZZ). Many reptile spe- cies lack sex chromosomes, and instead, sexual differentiation is influenced by temperature with specific temperatures promoting males or females varying across species possessing this form of sexual differentiation, although TSD has recently been shown to override GSD in Australian central beaded dragons (Pogona vitticeps). There has been speculation that Australian Brush-turkeys (Alectura lathami) exhibit TSD alone and/or in combination with GSD. Thus, we sought to determine if this species possesses sex chromosomes. Blood was collected from one sexually mature female and two sexually mature males residing at Sylvan Heights Bird Park (SHBP) and shipped for karyotype analysis. Karyotype analysis revealed that contrary to speculation, Australian Brush-turkeys possess the classic avian ZW/ZZ sex chromosomes. It remains a possibility that a biased primary sex ratio of Austra- lian Brush-turkeys might be influenced by maternal condition prior to ovulation that result in her laying predominantly Z- or W-bearing eggs and/or sex-biased mortality due to higher sensitivity of one sex in environmental conditions. A better understanding of how maternal and extrinsic factors might differentially modulate ovulation of Z- or W-bearing eggs and hatching of developing chicks possessing ZW or ZZ sex chromosomes could be essential in conservation strategies used to save endangered members of Megapodiidae

How do women prepare for pregnancy? Preconception experiences of women attending antenatal services and views of health professionals

Copyright: © 2014 Stephenson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Main objective - To determine the extent to which women plan and prepare for pregnancy. Methods - Cross-sectional questionnaire survey of pregnant women attending three maternity services in London about knowledge and uptake of preconception care; including a robust measure of pregnancy planning, and phone interviews with a range of health care professionals. Main results - We recruited 1173/1288 (90%) women, median age of 32 years. 73% had clearly planned their pregnancy, 24% were ambivalent and only 3% of pregnancies were unplanned. 51% of all women and 63% of those with a planned pregnancy took folic acid before pregnancy. 21% of all women reported smoking and 61% reported drinking alcohol in the 3 months before pregnancy; 48% of smokers and 41% of drinkers reduced or stopped before pregnancy. The 51% of all women who reported advice from a health professional before becoming pregnant were more likely to adopt healthier behaviours before pregnancy [adjusted odds ratios for greatest health professional input compared with none were 2.34 (95% confidence interval 1.54–3.54) for taking folic acid and 2.18 (95% CI 1.42–3.36) for adopting a healthier diet before pregnancy]. Interviews with 20 health professionals indicated low awareness of preconception health issues, missed opportunities and confusion about responsibility for delivery of preconception care. Significance of the findings - Despite a high level of pregnancy planning, awareness of preconception health among women and health professionals is low, and responsibility for providing preconception care is unclear. However, many women are motivated to adopt healthier behaviours in the preconception period, as indicated by halving of reported smoking rates in this study. The link between health professional input and healthy behaviour change before pregnancy is a new finding that should invigorate strategies to improve awareness and uptake of pre-pregnancy health care, and bring wider benefits for public health.Department of Healt