Nonalcoholic Fatty Liver Disease, Bone and Muscle Quality in Prolactinoma: A Pilot Study.

OBJECTIVE: Hyperprolactinemia has negative impacts on metabolism and musculoskeletal health. In this study, individuals with active prolactinoma were evaluated for nonalcoholic fatty liver disease (NAFLD) and musculoskeletal health, which are underemphasized in the literature. METHODS: Twelve active prolactinoma patients and twelve healthy controls matched by age, gender, and BMI were included. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was used to evaluate hepatic steatosis and magnetic resonance elastography (MRE) to evaluate liver stiffness measurement (LSM). Abdominal muscle mass, and vertebral MRI-PDFF was also evaluated with MRI. Body compositions were evaluated by dual energy X-ray absorptiometry (DXA). The skeletal muscle quality (SMQ) was classified as normal, low and weak by using "handgrip strength/appendicular skeletal muscle mass (HGS/ASM)" ratio based on the cut-off values previously stated in the literature. RESULTS: Prolactin, HbA1c and CRP levels were higher in prolactinoma patients (p<0.001, p=0.033 and p=0.035, respectively). The median MRI-PDFF and MRE-LSM were 3.0% (2.01-15.20) and 2.22 kPa (2.0-2.5) in the prolactinoma group and 2.5% (1.65-10.00) and 2.19 kPa (1.92-2.54) in the control group, respectively and similiar between groups. In prolactinoma patients, liver MRI-PDFF showed a positive and strong correlation with the duration of disease and traditional risk factors for NAFLD. Total, vertebral and pelvic bone mineral density was similar between groups, while vertebral MRI-PDFF tended to be higher in prolactinoma patients (p=0.075). Muscle mass and strength parameters were similar between groups, but HGS/ASM tended to be higher in prolactinoma patients (p=0.057). Muscle mass was low in 33.3% of prolactinoma patients and 66.6 of controls. According to SMQ, all prolactinoma patients had normal SMQ, whereas 66.6% of the controls had normal SMQ. CONCLUSION: Prolactinoma patients demonstrated similar liver MRI-PDFF and MRE-LSM to controls despite their impaired metabolic profile and lower gonadal hormone levels. Hyperprolactinemia may improve muscle quality in prolactinoma patients despite hypogonadism.

Nonfunctioning Pituitary Microadenomas: Should Imaging Interval be Extended? A Large Single-center Cohort Study.

CONTEXT: Characterization of the clinical features and natural history of nonfunctioning pituitary microadenomas (NFPmAs) is limited by heterogeneous and small-scale studies. OBJECTIVE: To characterize the clinical presentation and natural history of NFPmAs and evaluate if imaging follow-up interval can be extended. METHODS: Retrospective single-center cohort study (years 2006-2021) of conservatively managed patients with NFPmAs. Initial symptoms, pituitary function, and tumor size were assessed. A change in NFPmA size ≥2 mm, as determined by pituitary or brain magnetic resonance imaging (MRI), was considered significant. RESULTS: There were 347 patients in the study cohort. Headache (78.4%) and fatigue (70.0%) were commonly reported despite no evidence of mass effect or significant pituitary hypofunction. Pituitary deficiencies at baseline were rare, with hypogonadism being most common (5.1%). During a median imaging follow-up period of 29 months (range 3-154), 8.1% of NFPmAs grew. Growth incidence was 2.1 per 100 person-years with a mean and median time to growth of 38.1 (SD ± 36.4) and 24.5 (interquartile range 12.0-70.8) months, respectively. Tumor growth was mild and not associated with new pituitary deficiencies or visual deficits. CONCLUSION: These data indicate that the natural history of NFPmAs is overall benign. Consequently, we propose that the initial MRI follow-up timeline for NFPmAs can be extended up to 3 years unless a lesion is close to the optic chiasm, there are worrisome mass effect symptoms, or new pituitary deficiencies.

Altered endocannabinoid-dynamics in craniopharyngioma patients and their association with HPA-axis disturbances.

OBJECTIVE: Patients with craniopharyngioma (CP) frequently suffer from morbid obesity. Endocannabinoids (ECs) are involved in weight gain and rewarding behavior but have not been investigated in this context. DESIGN: Cross-sectional single-center study. METHODS: Eighteen patients with CP and 16 age- and sex-matched controls were included. Differences in endocannabinoids (2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)) and endocannabinoid-like molecules (oleoyl ethanolamide (OEA), palmitoylethanolamide (PEA), and arachidonic acid (AA) were measured at baseline and following endurance exercise. We further explored ECs-dynamics in relation to markers of HPA-axis activity (ACTH, cortisol, copeptin) and hypothalamic damage. RESULTS: Under resting conditions, independent of differences in BMI, 2-AG levels were more than twice as high in CP patients compared to controls. In contrast, 2-AG and OEA level increased in response to exercise in controls but not in CP patients, while AEA levels decreased in controls. As expected, exercise increased ACTH and copeptin levels in controls only. In a mixed model analysis across time and group, HPA measures did not provide additional information for explaining differences in 2-AG levels. However, AEA levels were negatively influenced by ACTH and copeptin levels, while OEA levels were negatively predicted by copeptin levels only. There were no significant differences in endocannabinoids depending on hypothalamic involvement. CONCLUSION: Patients with CP show signs of a dysregulated endocannabinoid system under resting conditions as well as following exercise in comparison to healthy controls. Increased 2-AG levels under resting conditions and the missing response to physical activity could contribute to the metabolic phenotype of CP patients.

ENDOCRINE TUMOURS: Thyrotropin-secreting pituitary adenoma: a structured review of 535 adult cases.

BACKGROUND AND AIMS: Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare entity, occurring in one per million people. We performed a systematic review of 535 adult cases summarizing the clinical, biochemical, hormonal and radiological characteristics of TSHoma. Furthermore, we discussed the current guidelines for diagnosis and treatment. METHODS: A structured research was conducted using Pubmed and Web of Science with the following MeSH terms: 'thyrotropin secreting pituitary adenoma' OR 'TSHoma' OR 'thyrotropinoma.' RESULTS: Our analysis included 535 cases originating from 18 case series, 5 cohort studies and 91 case reports. The mean age at diagnosis was 46 years. At presentation, 75% had symptoms of hyperthyroidism, 55.5% presented with a goitre and 24.9% had visual field defects. The median TSH at diagnosis was 5.16 (3.20-7.43) mU/L with a mean FT4 of 41.5 ± 15.3 pmol/L. The majority (76.9%) of the TSHomas were macroadenoma. Plurihormonality was seen in 37.4% of the adenoma with a higher incidence in macroadenoma. Surgical resection of the adenoma was performed in 87.7% of patients of which 33.5% had residual pituitary adenoma. Post-operative treatment with a somatostatin analogue (SSA) led to a stable disease in 81.3% of the cases with residual tumour. We noticed a significant correlation between the diameter of the adenoma and residual pituitary adenoma (r = 0.490, P < 0.001). However, in patients preoperatively treated with an SSA, this correlation was absent. CONCLUSION: TSHomas are a rare cause of hyperthyroidism and are frequently misdiagnosed. Based on our structured analysis of case series, cohort studies and case reports, we conclude that the majority of TSHomas are macroadenoma being diagnosed in the fifth to sixth decade of life and presenting with symptoms of hyperthyroidism. Plurihormonalitiy is observed in one-third of TSHomas. Treatment consists of neurosurgical resection and SSA in case of surgical failure.

Case Report: SARS-CoV-2 Infection in a Child With Suprasellar Tumor and Hypothalamic-Pituitary Failure.

In early 2020, a novel coronavirus leading to potentially death was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread to become a worldwide pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the endocrinological impact that COVID-19 may have, especially in vulnerable individuals with pre-existing endocrinological health conditions. To date new information is emerging regarding severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) in children but the literature is still scarce concerning this infection in patients with intracranial malignant neoplasms. We report a 9-year-old child infected with SARS-CoV-2 and recent diagnosis of suprasellar non-germinomatous germ cell tumor also suffering from diabetes insipidus and hypothalamic-pituitary failure (hypothyroidism, adrenal insufficiency, hypothalamic obesity and growth hormone deficiency) and its clinical course. The patient remained asymptomatic for the duration of the infection without requiring any change in the replacement therapeutic dosages taken before the infection. We then discuss the proposed approach to treat a pediatric patient with SARS-CoV-2 infection and hypothalamic-pituitary failure and we include a review of the literature. Our report suggests that SARS-CoV-2 infection is usually mild and self-limiting in children even those immunocompromised and with multiple endocrinological deficits. Patients are advised to keep any scheduled appointments unless informed otherwise.

Complications and Comorbidities of Acromegaly-Retrospective Study in Polish Center.

Introduction: In acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them. Materials and Methods: It was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis. Results: The study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20-78) and 46 for men (range 24-76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent. Conclusions: In our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups.

Anterior pituitary function in Rathke's cleft cysts versus nonfunctioning pituitary adenomas.

Although Rathke's cleft cysts (RCCs) are common sellar/parasellar lesions, studies examining pituitary function in patients with nonsurgical RCC are limited. This study aimed to clarify the importance of RCCs, including small nonsurgical ones, as a cause of hypopituitarism by determining the prevalence of pituitary hormone secretion impairment and its relationship to cyst/tumor size in patients with RCC and in those with nonfunctioning pituitary adenoma (NFA). We retrospectively investigated the basal levels of each anterior pituitary hormone, its responses in the stimulation test(s), and cyst/tumor size in patients with RCC (n = 67) and NFA (n = 111) who were consecutively admitted to our hospital for endocrinological evaluation. RCCs were much smaller than NFAs (median height, 12 vs. 26 mm). The prevalence of gonadotropin, PRL, and GH secretion impairment in RCC was lower in comparison to NFA (19% vs. 44%, 34% vs. 61%, and 24% vs. 46%, respectively), whereas the prevalence of TSH and ACTH secretion impairment was comparable (21-27% and 17-24%, respectively). A significant positive relationship between cyst/tumor size and number of impaired hormones was observed in both groups, but smaller cysts could cause hormone secretion impairment in RCC. Stimulation tests suggested that most hormone secretion impairment was attributable to the interrupted hypothalamic-pituitary axis in both groups. Therefore, RCC, even small ones, can cause pituitary dysfunction. Different mechanisms may underlie hypothalamic-pituitary interruption in RCC and NFA.

An overview of thyroid function tests in subjects with resistance to thyroid hormone and related disorders.

Confirmation of sustained syndrome of inappropriate secretion of thyrotropin (SITSH) is a milestone in diagnosis of ß type of resistance to thyroid hormone (RTHß). The differential diagnoses of RTHß include TSH-producing pituitary adenoma (TSHoma) and familial dysalbuminemic hyperthyroxinemia (FDH), which also present SITSH. Recently, patients with RTHα caused by a mutation in thyroid hormone receptor α were reported and they did not present SITSH but a decline in the serum T4/T3 ratio. This review was aimed to overview thyroid function tests in RTH and related disorders. First, the characteristics of the thyroid function in RTHß, TSHoma, and FDH obtained from a Japanese database are summarized. Second, the degrees of SITSH in patients with truncations and frameshifts were compared with those in patients with single amino acid deletions and single amino acid substitutions obtained from the literature. Third, the degrees of SITSH in homozygous patients were compared with those in heterozygous patients with cognate mutations. Finally, the FT3/FT4 ratios in RTHα are summarized. In principle, the TSH values in FDH were within the normal range and apparent FT4 values in FDH were much higher than in RTHß and TSHoma. The FT3/FT4 values in RTHß were significantly lower than in TSHoma. The degrees of SITSH in patients with truncations and frameshifts were more severe than those in patients with single amino acid deletions and single amino acid substitutions, and those in homozygous patients were more severe than those in heterozygous patients with cognate mutations. The FT3/FT4 ratios in RTHα were higher than 1.0.

The "Double-Peak" Pattern of Pituitary Adenoma Intrasellar Pressure and Its Effects on the Microvascular Structure.

OBJECTIVE: The purpose of the present study was to investigate the relationship between the intrasellar pressure (ISP) and the microvascular structure of pituitary adenomas. METHODS: We retrospectively analyzed the ISP in 66 patients with pituitary adenomas. The corresponding microvascular structure was obtained using immunohistochemistry and analyzed for its correlation with the ISP. RESULTS: The average ISP was 25.89 ± 8.27 mm Hg, and the ISP was not related to the size of the adenoma (Pearson correlation coefficient, 0.103; P = 0.415). The ISPs of adenomas with different Knosp grades were significantly different (P < 0.05). From grade 0 to grade 4, at first, the ISP increased with the Knosp grade and reached the first peak at grade 2. It then decreased at grade 3 and increased again at grade 4, showing a "double-peak" pattern. The minimal diameter and perimeter of the microvessels and the vessel-covered area percentage were positively related to the ISP. When these parameters were compared among the adenomas of different Knosp grades, they also exhibited a "double-peak" pattern. CONCLUSIONS: In the present study, we found that with the increase in pituitary adenoma size and invasion of the surrounding tissues, the ISP of pituitary adenomas showed a "double-peak" pattern. The ISP and certain parameters of the microvascular structure are related, because the microvasculature adaptively changes its structure in response to the changing ISP to ensure a sufficient blood supply to the adenoma. The specific mechanism of this phenomenon requires further study.

Impact of sleep, neuroendocrine, and executive function on health-related quality of life in young people with craniopharyngioma.

AIM: To examine the impact of clinical factors, cognitive deficits, and sleepiness on health-related quality of life (HRQoL) among young people with craniopharyngioma. METHOD: Seventy-eight patients (67% White; 41 males, 37 females; mean age 10y 8mo, SD 3y 11mo, range 6-20y) with craniopharyngioma were assessed for tumor extent and diabetes insipidus. All patients underwent overnight polysomnography and multiple sleep latency tests after surgical resection. Executive functioning was assessed using parent-reported measures. Patients and their parents completed measures of HRQoL. None had a history of previous radiation therapy. RESULTS: Path analysis was used to test hypothesized relations while controlling for demographic and disease characteristics. Analyses revealed poorer parent-reported HRQoL among young people with greater executive functioning symptoms (estimate -0.83; p<0.001). Direct and indirect effects were found among diabetes insipidus, executive functioning, and parent-reported HRQoL. Diabetes insipidus directly predicted greater global executive functioning impairment (estimate 5.15; p=0.04) and indirectly predicted lower HRQoL through executive functioning impairment (estimate -4.25; p=0.049). No significant effects were found between excessive daytime sleepiness, tumor hypothalamic involvement, diabetes insipidus, executive functioning, and patient-reported HRQoL. INTERPRETATION: These findings suggest that young people with craniopharyngioma presenting with diabetes insipidus may benefit from targeted neurocognitive and psychosocial screening to inform interventions. What this paper adds Children with craniopharyngioma and executive functioning impairment are more likely to have poorer health-related quality of life (HRQoL). Diabetes insipidus, a complication associated with surgery, predicted greater executive functioning impairment. Diabetes insipidus indirectly predicted lower parent-reported HRQoL through executive functioning impairment.

Lactate-induced M2 polarization of tumor-associated macrophages promotes the invasion of pituitary adenoma by secreting CCL17.

Background: Lactate greatly contributes to the regulation of intracellular communication within the tumor microenvironment (TME). However, the role of lactate in pituitary adenoma (PA) invasion is unclear. In this study, we aimed to clarify the effects of lactate on the TME and the effects of TME on PA invasion. Methods: To explore the correlation between TME acidosis and tumor invasion, LDHA and LAMP2 expression levels were quantified in invasive (n = 32) and noninvasive (n = 32) PA samples. The correlation between immune cell infiltration and tumor invasion was evaluated in 64 PAs. Critical chemokine and key signaling pathway components were detected by qPCR, Western blotting, siRNA knockdown, and specific inhibitors. The functional consequences of CCR4 signaling inhibition were evaluated in vitro and in vivo. Results: Lactate was positively associated with PA invasion. Of the 64 PA tissues, invasive PAs were related to high infiltration of M2-like tumor-associated macrophages (TAMs) (P < 0.05). Moreover, lactate secreted from PA cells facilitated M2 polarization via the mTORC2 and ERK signaling pathways, while activated TAMs secreted CCL17 to promote PA invasion via the CCL17/CCR4/mTORC1 axis. According to univariate analysis of clinical data, high CCL17 expression was associated with larger tumor size (P = 0.0438), greater invasion (P = 0.0334), and higher susceptibility to postoperative recurrence (P = 0.0195) in human PAs. Conclusion: This study illustrates the dynamics between PA cells and immune TME in promoting PA invasion via M2 polarization. CCL17 levels in the TME are related to the PA invasiveness and clinical prognosis, and the CCL17/CCR4/mTOCR1 axis may serve as potential therapeutic targets for Pas.

Gonadotroph Pituitary Adenoma Causing Treatable Infertility and Ovarian Hyperstimulation Syndrome in Female Patients: Neurosurgical, Endocrinologic, Gynecologic, and Reproductive Outcomes.

BACKGROUND: Gonadotroph pituitary adenoma (Gn-PA) may rarely cause ovarian hyperstimulation syndrome, leading to infertility in women, although this remains poorly described. METHODS: We present a quantitative systematic review including 2 patients from our institutional and 48 from the literature with Gn-PA causing ovarian hyperstimulation syndrome to thoroughly describe the clinical features and therapeutic outcomes from multidisciplinary aspects. RESULTS: The patients had a mean age of 31.5 years and a mean follicle-stimulating hormone level of 14.4 IU/L. Estradiol level was high in 82% of patients, at >350 pg/mL. The mean maximal adenoma diameter was 22 mm, with a Knosp grade ≥3 in 10 patients. Abdominal surgery preceded adenoma resection in 24 patients (48%). Among 25 patients for whom extent of resection was recorded, total adenoma resection was achieved in 12. Through a mean follow-up of 25 months, adenoma recurrence was observed in 5 patients, who were treated with re-resection (n = 2), radiation (n = 2), and medical therapy followed by bilateral oophorectomy (n = 1). Medical therapies were partially effective or ineffective, and adenoma shrinkage did not follow; gonadotropin-releasing hormone agonists/antagonists were partially effective in 20% of patients (2/10), dopamine agonists in 44% (8/18), and somatostatin analogues in 50% (1/2). Four experienced swelling of tumor/ovaries after gonadotropin-releasing hormone agonists/antagonists administration. Overall, chemical remission was obtained in 26 of 28 patients, normalization of ovaries in 25 of 27, and successful pregnancy in 12 of 14. CONCLUSIONS: Adenoma resection is the main treatment, leading to reduction in ovarian size and biochemical remission, with a high likelihood of subsequent spontaneous pregnancy. Increased awareness of this rare condition may help avoid unnecessary abdominal procedures.

Endoscopic Endonasal Approach to Giant Pituitary Adenomas: Surgical Outcomes and Review of the Literature.

OBJECTIVE: To present the outcomes of endoscopic endonasal surgery for giant pituitary adenomas and discuss the extent of resection to minimize morbidity and mortality. METHODS: We retrospectively reviewed medical records of 44 patients with giant pituitary adenomas who underwent endoscopic endonasal surgery. Clinical presentation, laboratory results, imaging studies, clinical outcomes, extent of resection, and complications were collected and analyzed. Factors affecting long-term outcome according to surgical technique were identified and analyzed. RESULTS: Radical resection (RR) was defined as either gross total resection or near-total resection (90%-100% of the tumor). There were 28 patients (63.6%) who underwent RR, 10 patients (22.7%) who underwent subtotal resection, and 6 patients (13.6%) who underwent partial resection. Visual improvement was achieved in 27 patients (81.8%). Thirteen patients (72.2%) with pituitary dysfunction had improvement in at least 1 preoperative endocrinological dysfunction. RR rates for dumbbell and multilobular tumors were 44.4% and 28.6%, respectively. Surgical complications were observed in 14 (31.8%) patients. Major vascular injury occurred in 3 patients (6.8%). Mean follow-up period was 38.5 months (range, 1-70 months). No patients with RR had recurrence or residual tumor progression. Ten patients (22.7%) received adjuvant radiation therapy after resection. Two patients were reoperated on for tumor regrowth, and 3 patients (including the 2 patients with tumor regrowth) were lost to follow-up. CONCLUSIONS: Long-term follow-up results and low recurrence rate of tumors indicate that RR is effective to decrease morbidity and mortality.

Early Experience of Endoscopic Endonasal Transphenoidal Surgery for Pituitary Adenoma: Preliminary Report of 56 Cases Operated in a West African Institution.

BACKGROUND: Although endoscopic endonasal approach (EEA) has been popularized worldwide for pituitary adenoma surgery, in sub-Saharan Africa, neurosurgeons are still only starting their experience with it. This study was designed to assess the early results of EEA for pituitary adenoma from an under-equipped environment, namely, the Department of Neurosurgery of the Teaching Hospital of Yopougon Abidjan and Bouaké in Ivory Coast. METHODS: The data of 56 cases of EEA for pituitary adenoma surgery performed between 2016 and March 2019 at the Teaching Hospital of Yopougon-Abidjan and Bouaké were retrospectively assessed. Pre- and postoperative neuro-ophthalmologic and hormonal status were analyzed. Moreover, the quality of tumor removal, and pre- and postoperative complications were also evaluated. RESULTS: In this study, there were nonfunctional adenomas (20), prolactinoma (18), Cushing disease (9), and acromegaly (3). A reduced visual acuity and/or visual field defect was observed in 49 cases. The mean operation time was 225 ± 94.7 minutes. The tumor removals were complete in 57.14%, subtotal in 35.71%, and partial in 7.14%. These led to a visual improvement in 69.64%. Postoperative complications were cerebrospinal fluid leaks (19.64%), diabetes insipidus (12.50%), visual worsening (7.14%), meningitis (3.57%), and carotid injury (3.57%) that led to death. CONCLUSIONS: This study represents the early surgical experience using EEA for treating pituitary adenoma in an under-equipped environment. Although the postoperative complication rate was relatively high, refinements of local surgeons' technique would lead to a better patient outcome.

Cardiac autonomic dysfunction is associated with hypothalamic damage in patients with childhood-onset craniopharyngioma.

BACKGROUND: Autonomic nervous system dysfunction is implicated in the development of hypothalamic obesity. We investigated the relationship between hypothalamic involvement (HI), central obesity, and cardiac autonomic dysfunction by assessing heart rate variability (HRV) indices in patients with childhood-onset craniopharyngioma. METHODS: A cross-sectional study of 48 patients (28 males, 10-30 years old) with hypothalamic damage after childhood-onset craniopharyngioma was performed. Postoperative HI was graded as mild (n = 19) or extensive (n = 29) on magnetic resonance imaging. Anthropometry, body composition and HRV indices including the standard deviation of all normal R-R intervals (SDNN) and total power (TP) as overall variability markers, root-mean square differences of successive R-R intervals (RMSSD) and high frequency (HF) as parasympathetic modulation markers, and low frequency (LF) as a sympathetic/sympathovagal modulation marker were measured. RESULTS: Patients with extensive HI had increased means of body mass index, waist circumference, and fat mass than those with mild HI (P < 0.05, for all). Centrally obese patients had a lower mean HF, a parasympathetic modulation marker, than centrally non-obese patients (P < 0.05). The extensive HI group had lower means of overall variability (SDNN and TP), parasympathetic modulation (HF), and sympathetic/sympathovagal modulation (LF) than the mild HI group (P < 0.05, for all). The interaction effect of HI and central obesity on HRV indices was not significant. In models adjusted for age, sex, and family history of cardiometabolic disease, the means of the overall variability indices (P < 0.05 for both SDNN and TP) and a sympathetic/sympathovagal modulation index (P < 0.05 for LF) were lower with extensive HI, without differences according to central obesity. CONCLUSIONS: The reduced HRV indices with extensive HI suggests that hypothalamic damage may contribute to cardiac autonomic dysfunction, underscoring the importance of minimizing hypothalamic damage in patients with childhood-onset craniopharyngioma.

Body Habitus Across the Lifespan and Risk of Pituitary Adenoma.

CONTEXT: No studies have examined the association between body habitus and incidence of pituitary adenoma. OBJECTIVE: To determine if body mass index (BMI), waist circumference, body somatotype, or height are associated with risk of pituitary adenoma. DESIGN: Pooled analysis of 3 prospective cohort studies. SETTING: Population-based study. PARTICIPANTS: Participants of the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and the Health Professionals Follow-Up Study (HPFS), totaling 284 946 American health professionals. EXPOSURES: BMI, waist circumference, body somatotype, and height. OUTCOME MEASURES: Self-reported incident pituitary adenoma. Multivariable (MV)-adjusted hazard ratios (HRs) of pituitary adenoma were estimated using Cox proportional hazards models. RESULTS: During 7 350 156 person-years of follow-up, 387 incident pituitary adenomas were reported. Comparing BMI of ≥30 to <25 kg/m2, higher adult BMI was associated with higher risk of pituitary adenoma (MV HR = 1.74; 95% CI, 1.33-2.28), as was higher maximum adult BMI (MV HR = 1.76; 95% CI, 1.34-2.30), higher waist circumference (MV HR = 1.06; 95% CI, 1.04-1.09 per inch), and higher BMI during early adulthood (at age 18 to 21, MV HR = 2.65; 95% CI, 1.56-4.49). Taller adult height was associated with pituitary adenoma (MV HR = 1.05; 95% CI, 1.01-1.09 per inch). Overall findings were similar in women and men, although power was limited in men (n = 62 cases). Sensitivity analyses demonstrated that the association between adult BMI and pituitary adenoma extended to at least 14 years prior to diagnosis and that the results were not affected when analyses were restricted to participants with similar healthcare utilization. CONCLUSION: Higher BMI and waist circumference, from early adulthood to the time of diagnosis, were associated with higher risk of pituitary adenoma.

Nuchal Skinfold Thickness in Pediatric Brain Tumor Patients.

Background: Severe obesity and tumor relapse/progression have impact on long-term prognosis in pediatric brain tumor patients. Methods: In a cross-sectional study, we analyzed nuchal skinfold thickness (NST) on magnetic-resonance imaging (MRI) follow-up monitoring as a parameter for assessment of nuchal adipose tissue in 177 brain tumor patients (40 World Health Organization (WHO) grade 1-2 brain tumor; 31 grade 3-4 brain tumor; 106 craniopharyngioma), and 53 healthy controls. Furthermore, body mass index (BMI), waist-to-height ratio, caliper-measured skinfold thickness, and blood pressure were analyzed for association with NST. Results: Craniopharyngioma patients showed higher NST, BMI, waist-to-height ratio, and caliper-measured skinfold thickness when compared to other brain tumors and healthy controls. WHO grade 1-2 brain tumor patients were observed with higher BMI, waist circumference and triceps caliper-measured skinfold thickness when compared to WHO grade 3-4 brain tumor patients. NST correlated with BMI, waist-to-height ratio, and caliper-measured skinfold thickness. NST, BMI and waist-to-height ratio were associated with increased blood pressure. In craniopharyngioma patients with hypothalamic involvement/lesion or gross-total resection, rate and degree of obesity were increased. Conclusions: NST could serve as a novel useful marker for regional nuchal adipose tissue. NST is highly associated with body mass and waist-to-height ratio, and easily measurable in routine MRI monitoring of brain tumor patients.

Is there any gender difference in epidemiology, clinical presentation and co-morbidities of non-functioning pituitary adenomas? A prospective survey of a National Referral Center and review of the literature.

PURPOSE: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy. METHODS: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated. RESULTS: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ2 = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ2 = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R2 = 0.060; IC 1.00-1.10). Headache (62.8% vs. 31.6%; χ2 = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ2 = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ2 = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI. CONCLUSIONS: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA.

Diffusion Tensor Imaging-Based Analysis of Baseline Neurocognitive Function and Posttreatment White Matter Changes in Pediatric Patients With Craniopharyngioma Treated With Surgery and Proton Therapy.

PURPOSE: To determine the preirradiation baseline association of white matter integrity with neurocognitive function and to assess posttreatment changes in pediatric patients with craniopharyngioma treated with proton therapy. METHODS AND MATERIALS: Ninety children and adolescents (2-20 years old) with craniopharyngioma were treated with proton therapy (54 Gy[RBE]) in a prospective therapeutic trial. Neurocognitive performance at the postoperative baseline before proton therapy and diffusion tensor imaging (DTI) data acquired at baseline and at annual follow-up were analyzed. Tract-based spatial statistics and structural connectomics were used to derive global and local white matter features from DTI. Baseline DTI features were compared for patients with average and below-average neurocognitive performance. Longitudinal DTI data were analyzed to determine the proton dose effect on white matter structures in relation to the irradiated brain volume and baseline age. RESULTS: Before proton therapy, patients with below-average working memory, processing speed, verbal fluency, verbal learning, or fine motor dexterity exhibited more globally degraded white matter structures compared with their counterparts with average performance, as indicated by lower mean fractional anisotropy, decreased global efficiency, or higher modularity. Surgery, obstructive hydrocephalus, and preoperative hypothalamic involvement appeared to be related to this degradation. In local analyses, tract-based spatial statistics revealed left-lateralized associations with verbal and motor functions, which supported surgical approaches to midline tumors via the right hemisphere. The mean fractional anisotropy of the brain and the global efficiency derived from DTI increased over the 5 years after proton therapy. The rate of increase was lower with larger irradiated brain volumes and in older children. CONCLUSIONS: Below-average baseline neurocognitive performance in patients with craniopharyngioma before proton therapy appeared to be related to structural degradation of white matter tracts. Posttherapy longitudinal DTI showed improving trends in global integrity and efficiency measures, particularly in children in whom a smaller brain volume was irradiated.