By Shyama Ghosh, PhD, and
Predictors of morbidity and
mortality in acromegaly
In the first large-scale epidemiological study on acromegaly in Italy, data were presented on a large population of patients followed up for more than 10 years. The survey described the demographic, clinical, and hormonal characteristics of this well-defined acromegalic population; evaluated the kind of therapies preferred by Italian endocrinologists and their effectiveness; and assessed the long-term outcome of the disease and what factors were predictive of morbidity and mortality.
All the major endocrinological centers in Italy were invited to participate in the survey that was endorsed by the Italian Society of Endocrinology. Inclusion criteria were age at diagnosis older than 18 years, Italian residence and diagnosis of acromegaly made between 1 January 1980 and 31 December 2002 according to standard biochemical criteria at the time of enrollment, with at least 1-year follow-up after diagnosis.
The final study cohort included 1,512 patients, 624 (41.2%) men and 888 (58.8%) women. The mean age at the time of diagnosis was 45 years. Male patients were significantly younger than female patients (43 vs 47 years). About 70% of patients were diagnosed between 1990 and 2002. Estimated duration of the disease prior to diagnosis was 74 months.
Clinicopathology: Radiological imaging revealed a microadenoma in 30% and a macroadenoma in 70% of available cases, respectively. The latter was intrasellar in 44% of cases. Tumor size and extension were missing in 7.6% of cases. The mean growth hormone (GH) concentration at diagnosis was 31.1 mcg/l. Insulin-like growth factor 1 (IGF1) serum levels were available at diagnosis in 1,004 patients (66.4%). The mean value was 744 ng/ml. The median IGF1 as age-specific standard deviation score (SDS) was 8.53.
Hyperprolactinemia was reported in 250/1,310 patients (19%). It was observed more frequently in women than in men (65.7% vs 34.3%) and in macro- than in microadenomas (80.5% vs 19.5%). 9 patients had associated thyroid stimulating hormone (TSH) hypersecretion and central hyperthyroidism. At diagnosis, 392 (26%) patients had one or more pituitary deficiencies: 4.1% hypoadrenalism, 8.1% hypothyroidism, 16.4% hypogonadism, and 0.6% diabetes insipidus. All were adequately treated. Pituitary deficiencies were equally distributed between the two genders except for hypogonadism that was more frequent in men (24.2% vs 10.9%).
Outcomes: At the last follow-up, IGF1 serum levels were available in 1321 patients (87% of the overall cohort). The mean value was 293 ng/ml and 802 patients (60.7%) achieved IGF1 levels within the normal range. The median IGF1 SDS was 1.34; it was significantly higher in men than in women (1.95 vs 1.11). A univariate model considering age, gender, GH, and IGF1 (expressed either as SDS or absolute value) at diagnosis, extension and size of the adenoma, delay of diagnosis, diabetes, hypertension, and hyperprolactinemia showed that male gender, extrasellar extension of the adenoma, highest GH levels at diagnosis, and diabetes were significant independent predictors of disease activity.
Mortality: By the end of 2002, 61 patients had died: 4.1% of men and 3.9% of women. The average age was 64 years without differences between genders. Older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and conventional radiotherapy were independent predictors of mortality.
This study included nearly 45% of all the Italian acromegalic cases of that period, considering an Italian population of 57 million inhabitants in 2002 and an estimated prevalence of acromegaly of 60 per million. Diabetes mellitus and hypertension were more frequent and peaked much earlier in acromegaly than in the background population. Male patients with extrasellar adenomas, high GH levels at diagnosis, and diabetes mellitus had the lowest probability of achieving control of their disease. Modern management of the disease is associated with an almost normal life span. This study has shown for the first time the importance of IGF1 levels at diagnosis in causing morbidity and long-term mortality.
Melatonin and MS
A team from Brigham and Women's Hospital (Boston) and the Argentinian Raul Carrea Institute for Neurological Research has linked melatonin levels to the seasonal variation in multiple sclerosis risk. Multiple sclerosis is a relapsing remitting disorder, with relapses more likely in summer and remission more likely in winter. In their work, the authors linked this pattern to seasonal variations in melatonin levels, which are higher in autumn and winter. They furthermore showed that melatonin directly affected T cells, increasing the relative proportion of inhibitory T cells and decreasing proinflammatory TH17 cells. Treatment with melatonin improved the symptoms of animal models of multiple sclerosis, and directly affected the differentiation of T cells. The authors said their results demonstrate that "melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis." The findings appeared in the Sept. 10, 2015, issue of Cell.
Stroke of insight into addiction
Researchers from the University of Rochester Medical Center have identified a brain region called the insular cortex as being involved in nicotine addiction. Pharmacological drugs that are meant to help smokers quit target the mesolimbic reward pathway, but are relatively ineffective. Recent work had implicated the insula cortex as a possible seat of addiction, and in their study, the authors looked at individuals who had sustained damage to the insular cortex during stokes. They found that compared to other brain regions, strokes that damaged the insular cortex left individuals significantly more likely to quit smoking, and with fewer withdrawal symptoms if they did quit. The insula may thus be a novel target for smoking cessation interventions. The researchers published their findings in two papers in the Sept. 8, 2015, online issue of Addiction and the July 6, 2015, online issue of Addictive Behaviors, respectively.
Boston Sci gets CE mark for the Vercise Primary Cell DBS
Boston Scientific (Marlborough, Mass.) has received the CE mark for the Vercise Primary Cell (PC) deep brain stimulation (DBS) system. The Vercise PC system is intended to provide precise neural targeting to address the varying needs of patients suffering from Parkinson's disease (PD), primary and secondary dystonia, and essential tremor. The system is a non-rechargeable treatment option that also powers the Vercise DBS directional lead.
The Vercise platform is a DBS solution that controls the size and shape of stimulation with multiple independent current control technology. The directional lead with MICC produces multi-directional stimulation which increases target efficiency.
DBS therapy involves the placement of a device that stimulates specific areas in the brain using electrical signals. The Vercise PC System supplements the company's rechargeable DBS device, a system with an unparalleled 25-year battery life.