Pregnancy-associated Cushing’s disease? An exploratory retrospective study

Purpose

In most clinical series of Cushing’s disease (CD), over 80% of patients are women, many of whom are of reproductive age. The year following pregnancy may be a common time to develop CD. We sought to establish the incidence of CD onset associated with pregnancy.

Methods

A retrospective review was conducted for patients with biochemically-proven CD. Demographics, clinical history, biochemistry, imaging, pathology, and outcomes were reviewed. Pregnancy-associated CD was defined as symptom onset within 1 year of childbirth.

Results

Over 10 years, 77 patients including 64 women (84%), with CD underwent endonasal surgery. Of the 64 women, 64% were of reproductive age (15–45 years) at the time of diagnosis, and 11 (27%) met criteria for pregnancy-associated CD. Of these 11 women, median number of pregnancies prior to onset of CD was 2 (range 1–4) compared to zero (range 0–7) for 30 other women with CD onset during reproductive age (p?=?0.0024). With an average follow-up of 47?±?34 months, sustained surgical remission rates for woman with pregnancy-associated CD, other women of reproductive age, and women not of reproductive age were 91%, 80% and 83%, respectively. The average lag-time from symptom onset to diagnosis for women with pregnancy-associated CD was 4?±?2 years.

Conclusions

In this exploratory study, over one quarter of women of reproductive age with CD appeared to have symptomatic disease onset within 1 year of childbirth. This relatively high rate of pregnancy-associated CD suggests a possible causal relationship related to the stress of pregnancy and pituitary corticotroph hyperactivity in the peripartum period. This possible association suggests a heightened degree of clinical suspicion and biochemical testing for CD may be warranted after childbirth. Further study of this possible link between pregnancy and CD is warranted.

     

Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: analysis of histopathology and outcome

To examine the histopathologic effect of neoadjuvant therapy and its impact on survival in patients with carcinoma of the pancreas, we retrospectively reviewed the records of 116 patients who underwent resections for pancreatic cancer from 1987 to 2000. Median follow-up of surviving patients was 19 mo(range 4-150 mo). Preoperative chemotherapy was administered in 61 patients (53%) and consisted of 5-fluorouracil/mitomycin C in 35 patients and gemcitabine in 26 patients, given concurrently with external beam radiation (5040 cGy). All resections were performed with curative intent (98 Whipples, 11 total, 6 distal, and 1 central pancreatectomy). Histopathologic examination included an estimation of the amount of fibrosis present in the tumor specimen (expressed as the percentage of fibrosis identified relative to the amount of neoplastic cells present). The mean fibrosis level for the series was 56% (range 5% to 100%). The administration of neoadjuvant therapy resulted in greater fibrosis (73%) than no preoperative treatment (38%) (p = 0.0001). Higher mean fibrosis levels were observed in patients with negative lymph nodes (p = 0.0006) and negative margins (p = 0.05). Factors associated with improved survival(log rank test) included: negative margins (p = 0.001), negative lymph nodes (p = 0.03), and use of neoadjuvant therapy (p = 0.03). Median survival in the neoadjuvant group was 23 mo vs 16 mo without preoperative therapy (p = 0.03). In conclusion, the use of neoadjuvant therapy resulted in a greater degree of fibrosis in the specimen. Patients with negative margins and negative lymph nodes had a greater amount of fibrosis present, and these were significant predictors of improved outcome. Although retrospective,this series suggests an improvement in survival in patients treated with neoadjuvant therapy.     

Medical cannabis: A forward vision for the clinician

Medical cannabis has entered mainstream medicine and is here to stay. Propelled by public advocacy, the media and mostly anecdote rather than sound scientific study, patients worldwide are exploring marijuana use for a vast array of medical conditions including management of chronic pain. Contrary to the usual path of drug approval, medical cannabis has bypassed traditional evidence‐based study and has been legalized as a therapeutic product by legislative bodies in various countries. While there is a wealth of basic science and preclinical studies demonstrating effects of cannabinoids in neurobiological systems, especially those pertaining to pain and inflammation, clinical study remains limited. Cannabinoids may hold promise for relief of symptoms in a vast array of conditions, but with many questions as yet unanswered. Rigorous study is needed to examine the true evidence for benefits and risks for various conditions and in various patient populations, the specific molecular effects, ideal methods of administration, and interaction with other medications and substances. In the context of prevalent use, there is an urgency to gather pertinent clinical information about the therapeutic effects as well as risks. Even with considerable uncertainties, the health care community must adhere to the guiding principle of clinical care ‘primum non nocere’ and continue to provide empathetic patient care while exercising prudence and caution. The health care community must strongly advocate for sound scientific evidence regarding cannabis as a therapy.

Significance

Legalization of medical cannabis has bypassed usual drug regulatory procedures in jurisdictions worldwide. Pending sound evidence for effect in many conditions, physicians must continue to provide competent empathetic care with attention to harm reduction. A vision to navigate the current challenges of medical cannabis is outlined.     

Disparities in Weight and Weight Behaviors by Sexual Orientation in College Students

Objectives. We assessed disparities in weight and weight-related behaviors among college students by sexual orientation and gender.Methods. We performed cross-sectional analyses of pooled annual data (2007–2011; n = 33 907) from students participating in a Minnesota state-based survey of 40 two- and four-year colleges and universities. Sexual orientation included heterosexual, gay or lesbian, bisexual, unsure, and discordant heterosexual (heterosexuals engaging in same-sex sexual experiences). Dependent variables included weight status (derived from self-reported weight and height), diet (fruits, vegetables, soda, fast food, restaurant meals, breakfast), physical activity, screen time, unhealthy weight control, and body satisfaction.Results. Bisexual and lesbian women were more likely to be obese than heterosexual and discordant heterosexual women. Bisexual women were at high risk for unhealthy weight, diet, physical activity, and weight control behaviors. Gay and bisexual men exhibited poor activity patterns, though gay men consumed significantly less regular soda (and significantly more diet soda) than heterosexual men.Conclusions. We observed disparities in weight-, diet-, and physical activity–related factors across sexual orientation among college youths. Additional research is needed to better understand these disparities and the most appropriate intervention strategies to address them.In 2011, the Institute of Medicine highlighted the significant lack of research on the health of lesbian, gay, and bisexual (LGB) groups.1 Research has indicated that LGB adults experience worse health outcomes than their heterosexual peers.2–11 These disparities may be attributable to an array of factors, including stigmatization, stress, and limited access to and use of health services.1,12,13 Specific areas of potential disparities among LGB groups lacking substantial research evidence include obesity, diet, physical activity patterns, unhealthy weight control behaviors, and body image. With two thirds of US adults now overweight or obese,14 obesity prevention is a national health priority. Findings from studies examining adult weight disparities by sexual orientation have consistently indicated that lesbian women are more likely to be overweight than heterosexual women.2,11,15–19 Several recent population-based studies have suggested that gay men may be less likely to be overweight than heterosexual men,2,18,20 and additional studies have highlighted concerns regarding body image and unhealthy weight control behaviors among gay men.21–24 Disparities in other behaviors, such as dietary intake and physical activity patterns, have not been studied extensively using population-based samples and, when studied, have yielded inconsistent findings.11,25,26Furthermore, much of the work in this area to date has not focused on the college years. Because nearly half of US high school graduates up to age 24 years are enrolled in postsecondary education,27 colleges and universities offer unique environments for addressing health disparities among young people, including those of LGB students. For many, the college years represent a time during which health disparities emerge28,29 and adverse changes occur in weight, dietary quality, physical activity, and other behaviors.30–38 For LGB people, this age is commonly when sexual identity is declared and assimilation into the LGB community occurs.39 Important postsecondary institutions that could act as platforms for intervention delivery include not only traditional 4-year universities but also 2-year community and technical colleges, which serve millions of students, particularly those from lower income and minority backgrounds.40,41The objective of this study was to characterize gender-specific weight-related disparities among college students by sexual orientation. We analyzed state survey data of nearly 34 000 students attending a wide array of 2- and 4-year colleges and universities in 2007 to 2011, including a subsample of more than 2000 LGB-identified and LGB-questioning participants. This research was intended to fill several gaps in the literature. For example, although a recent wave of studies11,19,22–25 were published after the release of the Institute of Medicine report,1 most of these studies used data from 1999 to 2007 and thus were not able to characterize disparities during the past 5 to 8 years (when important societal shifts in weight-related factors42,43 and social shifts regarding LGB issues occurred). Moreover, a majority of these studies focused not on the college years but rather on adulthood overall (e.g., 18–74 years) or on adolescence (e.g., 9th–12th grade). Finally, only a small number of studies have examined population-level LGB disparities in dietary intake or physical activity,11,20,25,26 which are critical factors to address in weight-related intervention strategies. Among the few population-based studies that have addressed diet and activity, unidimensional indicators have been used to assess fruit and vegetable consumption or moderate to vigorous intensity physical activity, but these studies have generally lacked characterization of other important dietary factors (e.g., frequency of soda, fast food, away-from-home eating, or breakfast consumption) or activities (e.g., strengthening activities, screen time).     

Single oral high-dose vitamin D3 prophylaxis in the elderly

A poor vitamin D status is common in the elderly during the winter months. Because it is possible that hypovitaminosis D may be a cause of senile osteopenia, a simple method of prophylaxis would be useful. The single, oral, high-dose method was tested in two old-age homes, and the efficacy of vitamin D3 was compared with that of 25-hydroxyvitamin D3 (25-OHD3). The trials showed that 25-OHD3 caused a higher peak value in the serum 25-OHD levels in the second week than did vitamin D3. However, follow-up after four to five months showed that in those patients who received a single, oral dose of 25-OHD3, the serum 25-OHD levels had returned to the baseline low values, whereas in those patients who had had oral vitamin D3, the serum 25-OHD levels still remained significantly raised compared with the baseline values and were within normal limits. It is concluded that the single, oral, high-dose method using vitamin D3 is a safe and simple method of prophylaxis and could be used easily in large populations of elderly persons.     

Effects of lovastatin therapy on LDL receptor activity in circulating monocytes and on structure and composition of plasma lipoproteins

The effect of lovastatin therapy on LDL-receptor activity in fresh monocytes and on the structure and composition of lipoproteins was determined in 9 patients with familial hypercholesterolemia (FH) and 8 patients with non-familial hypercholesterolemia (NFH). Lovastatin reduced LDL-cholesterol levels by 34.8 and 47.5%, respectively, in the 2 groups of patients, and plasma apo B levels by 33.3 and 42.5%. LDL receptor activity in fresh monocytes increased by 53% and 86% respectively. HDL-cholesterol and plasma apo A-I levels increased only in the NFH group, by 10.2 and 7.1%. Lipoproteins were separated by centrifugation on a zonal rotor. Except for the intermediate density lipoprotein (IDL) fraction, no changes were observed in the structure and composition of the various lipoproteins. The investigations thus demonstrated that lovastatin therapy is associated with a measurable and significant increase of LDL-receptor activity in circulating monocytes that may contribute to the lipid lowering action of the drug.