Hypopituitarism and pregnancy: clinical characteristics, management and pregnancy outcome.

PURPOSE: To describe the clinical characteristics, management and pregnancy outcome of women with prepregnancy hypopituitarism (HYPO) that received care at our center. METHODS: Retrospective study describing 12 pregnancies in women with prepregnancy HYPO (two or more pituitary hormonal deficiencies under replacement treatment) that received care during pregnancy at Hospital Santa Creu i Sant Pau. Clinical characteristics, management and pregnancy outcome were systematically collected. RESULTS: Average patients' age was 35 years and HYPO duration at the beginning of pregnancy was 19 years. The most frequent cause of HYPO was surgical treatment of a sellar mass (8 pregnancies). Eight pregnancies were in primigravid women and 10 required assisted reproductive techniques. The hormonal deficits before pregnancy were as follows: GH in 12 women, TSH in 10, gonadotropin in 9, ACTH in 5 and ADH in 2. All deficits were under hormonal substitution except for GH deficit in 4 pregnancies. During pregnancy, 4 new deficits were diagnosed. The dosage of replacement treatment for TSH, ACTH and ADH deficits was increased and GH was stopped. Average gestational age at birth was 40 weeks, gestational weight gain was excessive in 9 women, 8 patients required induction/elective delivery and cesarean section was performed in 6. Average birthweight was 3227 g. No major complications were observed. Five women were breastfeeding at discharge. CONCLUSIONS: In this group of women with long-standing HYPO, with careful clinical management (including treatment of new-onset hormonal deficits) pregnancy outcome was satisfactory but with a high rate of excessive gestational weight gain and cesarean section.

Defective involuntary attention to novelty in type 1 diabetes and impaired awareness of hypoglycaemia.

AIM: To determine if there are differences in terms of neurophysiology and neurocognitive functioning in a group of type 1 diabetes (T1D) patients regarding hypoglycaemia awareness. METHODS: 27 patients with T1D were classified according to Clarke score as having impaired awareness of hypoglycaemia (IAH; n = 11) or normal awareness to hypoglycaemia (NAH; n = 16). We measured several clinical and sociodemographic variables and cognitive performance using neuropsychological tests. Electroencephalography was assessed during an auditory oddball task. We compared the groups in terms of clinical/sociodemographic variables as well as two event-related brain potentials (ERPs): The P3a which is associated with automatic orientation of attention to novelty, and the P3b which is associated with target detection and processing. RESULTS: The IAH group performed significantly worse on the Trail Making Test part A (TMT-A) (p = 0.05). Compared to the NAH group, P3a and P3b amplitudes in the frontal-central sites were significantly lower in the IAH group (p < 0.05). The P3a was strongly associated with worse performance on the TMT-A in the IAH group (r = 0.540; p < 0.005) CONCLUSION: IAH is accompanied by decreased neurophysiological activity in ERPs associated with information processing and with the automatic orientation of attention to novelty and environmental changes. These findings suggest a possible framework to better understand the cognitive origin of IAH in this patient population.

Effectiveness of Bariatric Surgery in Patients with the Metabolically Healthy Obese Phenotype.

BACKGROUND: To evaluate the effectiveness and safety of bariatric surgery in metabolically healthy obese (MHO) patients. METHODS: In this retrospective, observational study, we reviewed the medical records of patients who underwent bariatric surgery at a tertiary care hospital between January 2007 and March 2015. Patients who underwent revisional surgery and patients with type 1 diabetes were excluded from the analysis. MHO patients were defined as those without a previous diagnosis of diabetes or atherogenic dyslipidemia and absence of hypoglycemic treatment or treatment with fibrates. RESULTS: A total of 188 patients were included (mean age 48.97 ± 10.32 years, 68.6% of women). Sleeve gastrectomy was performed in 121 patients (64%) and a gastric bypass in 67 patients (36%). Prior to surgery, 36 patients (19%) were MHO. In the second- and third-year post-surgery, MHO patients presented a higher percentage of total weight loss (%TWL) (35.16% vs. 30.34%; p = 0.02 and 33.97% vs. 27.78%; p = 0.013 respectively). Multiple regression analysis showed that MHO was associated with a higher weight loss irrespective of age, sex, baseline BMI, and type of surgery. We did not detect any differences in acute complications between patients with and without MHO after bariatric surgery. CONCLUSIONS: Bariatric surgery in MHO patients in our study was associated with higher weight loss than that in MUHO patients. There were no differences between the two groups in respect to acute complications following surgery.

Structural Gray and White Matter Differences in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.

CONTEXT: Type 1 diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycemia (SH) and impaired awareness of hypoglycemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI). OBJECTIVE: To investigate whether there are structural brain differences in a group of T1D patients with IAH compared with normal awareness of hypoglycemia (NAH). DESIGN: General practice, population-based, cross-sectional study (July 2018 to July 2019). SETTING: Endocrinology Department, Hospital Santa Creu i Sant Pau. PARTICIPANTS: A total of 40 T1D patients (20 each with IAH and NAH) matched for age, sex, T1D duration, and education level. MAIN OUTCOME MEASURES: Using different neuroimaging techniques, we compared whole-brain gray matter (GM) and white matter (WM) differences. We used voxel-based morphometry and cortical surface area analysis methods to assess GM differences, and fractional anisotropy (FA) to assess WM differences. RESULTS: Compared with patients with T1D-NAH, patients with T1D-IAH had reduced GM volumes and cortical surface areas, especially in frontal and parietal regions (P < 0.05 corrected), and also showed reduced FA values in major WM tracts. The observed MRI differences correlated with both SH frequency and IAH severity. CONCLUSIONS: MRI for patients with T1D show that IAH is associated with brain changes involving both GM and WM. Further research is needed to elucidate whether the observed differences are a consequence of increased SH episode frequency and increased IAH severity.

Increased cerebral FDG-PET uptake in type 1 diabetes patients with impaired awareness of hypoglycaemia.

Approximately 20% of type 1 diabetes (T1D) patients have an impaired awareness of hypoglyceamia (IAH). IAH represents a risk factor for severe and recurrent hypoglycaemic events, which can lead to brain damage. Because no effective treatments are currently available to prevent IAH in this population, characterising the set of brain alterations associated with IAH may reveal novel preclinical diagnostic or therapeutic strategies. Using state-of-the art neuroimaging techniques, we compared 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake at rest between 10 T1D patients with IAH and nine patients with normal awareness of hypoglycaemia (NAH). T1D-IAH patients showed a pattern of increased FDG-PET uptake with respect to NAH patients (P < .05 corrected). Topographically, glucose metabolism was increased in the frontal and precuneus regions. Importantly, within the IAH group, this abnormal hypermetabolism correlated with IAH severity. This hypermetabolic state appeared to be unrelated to compensatory mechanisms as a result of reduced grey matter density or a neuroinflammatory state. We observed an abnormal increase in FDG-uptake in T1D patients with IAH in brain regions strongly related to cognition. Because this hypermetabolic state correlated with IAH severity, its biological characterisation could reveal new preventive or therapeutic strategies. A possible mechanism could be that glucose transport is increased in hypoglycaemia unawareness to compensate for recurrent hypoglycaemia, although this need to be confirmed in further research.

Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia.

INTRODUCTION: Impaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences and cerebral damage. Non-invasive, cost-effective, and logistically efficient biomarkers for this condition have not been validated. Here, we propose plasma neurofilament light chain (NfL) levels as a biomarker of neuroaxonal damage in patients with T1D-IAH. RESEARCH DESIGN AND METHODS: 54 patients were included into the study (18 T1D-IAH, 18 T1D with normal awareness of hypoglycemia (NAH) and 18 healthy controls). We measured plasma NfL levels and studied cerebral gray matter alterations on MRI. RESULTS: We found that NfL levels were increased in patients with T1D-IAH compared with patients with T1D-NAH and healthy controls. Importantly, increased NfL levels correlated with reduced cerebral gray matter volume and increased IAH severity in patients with T1D-IAH. CONCLUSION: Overall, our findings identify plasma NfL levels as a potential biomarker of cerebral damage in this population, motivating further confirmatory studies with potential implications in clinical trials.