Prevalence of pituitary deficiency in patients after aneurysmal subarachnoid hemorrhage

After aneurysmal subarachnoid hemorrhage (SAH), patients frequently present with persistent bodily, psychosocial, and cognitive impairments that resemble those of patients with untreated partial or complete pituitary insufficiency. Because of these similarities, the authors hypothesized that aneurysmal SAH may cause pituitary dysfunction. Pituitary function testing was performed in 40 aneurysmal SAH patients between 12 and 72 months after the SAH. A combined TRH-LHRH-arginine test and the insulin tolerance test were performed on two separate days. Only 18 of 40 (45%) of the tested patients had normal pituitary function. Five of 40 exhibited isolated severe GH deficiency (GHD), and an additional three of 40 had severe GHD plus corticotroph deficiency. Isolated corticotroph deficiency was seen in 13 of 40 patients, and one patient showed isolated thyrotroph deficiency. All but one patient with corticotroph insufficiency were female. Patients with severe GHD had gained significantly more weight since their SAH than patients without GHD and exhibited a significantly higher body mass index. None of the clinical parameters indicative of a poor neurological outcome in aneurysmal SAH were related to pituitary insufficiency. In summary, neuroendocrine dysfunction was identified in a substantial portion of patients with previous aneurysmal SAH and should be borne in mind as a potential long-term sequel of the illness.     

Variants in the neuronal nitric oxide synthase (nNOS,NOS1) gene are associated with restless legs syndrome

Sixty percent of the patients with restless legs syndrome (RLS) report a positive family history. To date five loci have been mapped on chromosome 12q, 14q, 9p, 2q, and 20p (RLS1‐5) but no gene has been identified so far. To identify genes related to RLS, we performed a three‐stage association study (explorative study, replication study, high‐density mapping) in two Caucasian RLS case‐control samples of altogether 918 independent cases and controls. In the explorative study (367 cases and controls, respectively), we screened 1536 SNPs in 366 genes in a 21 Mb region encompassing the RLS1 critical region on chromosome 12. Armitage trend test revealed three genomic regions that were significant (P < 0.05). In the replication study (551 cases and controls, respectively) we genotyped the most significant SNPs of Stage 1. After correction for multiple testing, association was observed with SNP rs7977109 (P_nominal = 0.00175, P_{Westfall‐Young} = 0.04895, OR = 0.76228, 95% CI = 0.64310–0.90355), which is in the neuronal nitric oxide synthase (NOS1) gene. High‐density mapping using altogether 34 tagging and coding SNPs of the NOS1 gene in both case‐control samples further confirmed the significant association results to NOS1. Ten more SNPs revealed significance with nominal P‐values from 0.0001 to 0.0482 (genotypic test and Armitage test). Altogether, this study provides evidence for an association of variants in the NOS1 gene and RLS, and suggests the involvement of the NO/arginine pathway in the pathogenesis of RLS. Potential usage of NO modulating agents as new treatment options for RLS have become a challenging aspect for future research of this disorder. © 2007 Movement Disorder Society     

Polymorphisms in genes involved in sex hormone metabolism, estrogen plus progestin hormone therapy use, and risk of postmenopausal breast cancer.

Hormone therapy, estrogen plus progestin (E+P) particularly, is associated with increased risk of breast cancer. Functionally relevant polymorphisms in genes involved in sex hormone metabolism may alter exposure to exogenous sex hormones and affect risk of postmenopausal breast cancer. We evaluated associations of common polymorphisms in genes involved in estrogen and/or progesterone metabolism, E+P use, and their interactions with breast cancer risk in a case-control study of postmenopausal women (324 cases; 651 controls) nested within the VITAL cohort. None of the polymorphisms studied was, by itself, statistically significantly associated with breast cancer risk. E+P use was significantly associated with increased breast cancer risk (> or =10 years versus never; odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P(trend) = 0.0002). Statistically significant interactions between CYP1A1 Ile(462)Val (P(interaction) = 0.04), CYP1A1 MspI (P(interaction) = 0.003), CYP1B1 Val(432)Leu (P(interaction) = 0.007), CYP1B1 Asn(453)Ser (P(interaction) = 0.04) and PGR Val(660)Leu (P(interaction) = 0.01), and E+P use were observed. The increased risk of breast cancer associated with E+P use was greater among women with at least one rare allele of the CYP1A1 Ile(462)Val, CYP1A1 MspI, CYP1B1 Asn(453)Ser, and PGR Val(660)Leu polymorphisms than among women homozygous for the common allele of these polymorphisms. Risk of breast cancer increased little with increasing years of E+P use among women with at least one CYP1B1 Val(432) allele; a large increase in risk was seen among women homozygous for CYP1B1 Leu(432). Our results support the hypothesis that specific polymorphisms in genes involved in sex hormone metabolism may modify the effect of E+P use on breast cancer risk.     

Diagnosis and management of acromegaly: the patient’s perspective

Purpose

Early diagnosis is a success factor for the prevention of long-term comorbidity and premature death in patients with acromegaly, but large-scale data on the diagnostic process and disease management are scarce. Therefore, we aimed to evaluate the diagnostic process, implementation of treatment and changes in life situation in patients with acromegaly, focusing on sex-specific differences.

Methods

Non-interventional patient-reported outcome study. 165 patients with clinically and biochemically proven acromegaly were questioned about the diagnostic process and utilization of health care by means of a self-developed standardized postal survey including questions on acromegaly symptoms experienced before diagnosis, number and specialty of consulted doctors, time to diagnosis and aftercare.

Results

The diagnostic process took 2.9 (SD 4.53) years, during which 3.4 (SD 2.99) physicians were consulted. Women waited longer [4.1 (SD 5.53) years] than men [1.6 (SD 2.69) years; p = 0.001] for the correct diagnosis, and consulted more doctors in the process [4.0 (SD 2.99) vs. 2.7 (SD 2.84) doctors, p < 0.001, respectively]. In 48.5 % of patients, acromegaly was diagnosed by an endocrinologist (men: 45.1 %; women: 52.4 %). Overall disease duration from symptom onset until last surgery was 5.5 (SD 6.85) years, with no sex differences. A change in employment status was the most commonly reported event after diagnosis and a quarter of the patients stated that the illness had changed their lives.

Conclusions

Our findings confirm the urgent need to increase awareness of the clinical manifestation of acromegaly to facilitate an earlier diagnosis of the disease and to provide diagnostic equality across the sexes.

     

Source localization of MEG sleep spindles and the relation to sources of alpha band rhythms.

OBJECTIVE: First, to determine the distribution of the estimated sources of sleep spindles, and alpha and mu rhythms based on whole-head magnetoencephalogram (MEG) recordings; second, to scrutinize the physiological relevance of the dipole fit algorithm in localizing on-going normal rhythmic activities. METHODS: One hundred and fifty-one channels were used to record spontaneous MEG activity during wakefulness and superficial sleep in 4 normal subjects. The equivalent dipolar sources were estimated by a new 'dipole fit algorithm' and projected on the corresponding magnetic resonance images. RESULTS: Equivalent dipoles of MEG spindles were distributed over the centro-parietal region. Those of alpha rhythms were concentrated around the occipito-parietal sulcus and those of mu rhythms were confined to the area around the central sulcus. CONCLUSIONS: MEG sleep spindles, and alpha and mu rhythms have distinct spatial distributions of their equivalent dipolar sources. This demonstrates that various cortical regions that oscillate within the same frequency band have different spatial organizations and different functional aspects.