Endocrinological Data Research Articles

Effect of Post-Activation Potentiation on Weightlifting Performance and Endocrinological Responses

Purpose: This study examined the acute performance-enhancing effects and endocrinological responses of a supramaximal clean pull performed at 120% of clean and jerk, one repetition maximum, on clean performance. Methods: Eight (n = 8) ranked collegiate level weightlifters attended two days of testing in a randomised order. A control session was used to identify a baseline measure of kinetic and kinematic clean performance and endocrinological status following three cleans interspersed with one-minute recovery between repetitions. The experimental condition required participants to perform a single clean pull at 120% of clean and jerk, one repetition maximum, followed by three minutes recovery, prior to executing three cleans with one-minute recovery between repetitions. All cleans were performed on a dual force plate set up, synchronised with a 3D motion capture system to simultaneously record barbell and ground reaction force data. All endocrinological data were measured prior to the participant warming up and also following each testing protocol. Results: The results indicated that no significant differences were found between the control and PAP condition (p = 0.140–0.902); however, effect sizes from group analysis identified moderately negative to trivial effects across kinetic, kinematic and endocrinological variables (d = −0.30–0.14). Further analysis on an individual level demonstrated values, both negative and positive, ranging from extremely large (d = −4.10) to trivial (d = 0.04). Conclusions: The findings suggest a potentially negative affect of PAP on kinetic and kinematic measures of clean performance. However, individual responses varied, and thus some weightlifters may find this useful.

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord-stromal tumors. Results of the TGM13 National Registry.

Sex cord-stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes. Patients (<19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected. Sixty-three ovarian SCST (juvenile granulosa tumor (JGT) n=34, Sertoli-Leydig cell tumor (SLCT) n=17, other SCST n=12) were included. Median age was 13.1 years (0.4-17.4). Germline DICER1 pathogenic variant was present in 9/17 SLCT. Sixty-one were FIGO stage I (IC n=14). Adjuvant chemotherapy was administered for 15. Seven had recurrence (FIGO IA n=3, IX n=2, III n=2), leading to one death. With a median follow-up of 42 months (2.5-92), the 3-year progression-free survival (PFS) was 89% (95% CI 76%-95%). Median age was 6.4 years (0.1-12.9) among the 15 testicular SCST (Leydig cell tumor n=6, JGT n=5, Sertoli cell tumor n=3, mixed SCST n=1). Tumor-nodes-metastases (TNM) stage was pSI in 14. Eight underwent a tumorectomy, 7 an orchiectomy. None experienced recurrence. Endocrinological data were reviewed for 41 patients (18 prepubescent). Endocrine symptoms were present at diagnosis in 29/34 females and 2/7 males (gynecomastia). After a median follow-up of 11 months, 15 patients had persistent endocrine abnormalities: gynecomastia/breast growth (2 males, 1 prepubescent female), precocious/advanced puberty (4 prepubescent females), and hirsutism/menstruation disorders/voice hoarseness/hot flashes (8 pubescent females). The mean height at the last follow-up was within normal ranges (+0.3 standard deviation). SCSTs have a favorable prognosis. Tumorectomy appears safe with testicular primary. Endocrinological disorders, common at diagnosis, may persist warranting endocrinological follow-up.

Clinical and therapeutic outcomes of pediatric pituitary adenomas: a single pituitary center experience.

Pediatric pituitary adenomas (PPA) are rare. Although PPAs are mostly benign, they can be challenging to manage. Most studies evaluating PPA are based on surgical series. We aimed to present the clinical features, hormonal status and treatment outcomes of children with PPA managed in a joint neuroendocrine setting. In this single-center study, demographic, clinical and endocrinological data of patients under 19 years old who were followed up with the diagnosis of PPA between 2002-2022 were retrospectively reviewed. A total of 21 studies published in the past 20 years were also systematically reviewed. There were 79 patients (52 girls, 27 boys) with a median age of 15.8 years. Median follow-up time was 30 months. The most common adenoma subtype was non-functioning adenoma (NFA) (35.5%), followed by prolactinoma (29.1%), corticotropinoma (21.5%), and somatotropinoma (13.9%), respectively. The frequency of micro and macroadenomas was almost equal while 38% of all adenomas were invasive. Headache, visual impairment and menstrual irregularity were the most common complaints, while the most common hormonal deficiency at diagnosis was central hypothyroidism (31.6%), followed by hypogonadotropic hypogonadism (22.7%), growth hormone deficiency (15.2%) and central adrenal insufficiency (11.4%), respectively. Fifty patients (63.2%) underwent endoscopic endonasal transsphenoidal surgery (EETS). Following the surgery, impaired endocrine functions recovered at a rate of 62% while permanent central diabetes insipidus was observed in 6%, and new onset hypopituitarism developed in 4%. NFA was more common in this cohort than in previous reports, which is one of the largest PPA series in the literature. Hormonal disorders, which were common at the time of diagnosis, were largely resolved with appropriate endocrinological and surgical approaches, while the rate of pituitary hormonal deficiencies after EETS was relatively low. Therefore, we recommend that children with PPA be managed in the setting of a high-volume pituitary center to provide long-term low morbidity.

Nuclear translocation of beta catenin in patients with Rathke cleft cysts—clinical and imaging characteristics and risk of recurrence

PurposeAlthough Rathke cleft cysts (RCC) are benign lesions of the sellar region, recurrence is frequent after surgical treatment. Nuclear translocation of ß-catenin (NTßC), a key effector of the wnt-signaling pathway that is responsible for cell renewal, has been shown to act as a proto-oncogene and is considered to be a potential risk factor for increased recurrence in RCC. In this study, we analyzed a surgically treated cohort into patients with and without NTßC expression in order to identify clinical and imaging differences and further evaluate the risk of recurrence.MethodsPatients with resection of RCC between 04/2001 and 11/2020 were included. Histological specimens were immunohistochemically stained for ß-catenin. Study endpoints were time to cyst recurrence (TTR) and functional outcome. Functional outcome included ophthalmological and endocrinological data. Furthermore, MRI data were assessed.ResultsSeventy-three patients (median age 42.3 years) with RCC underwent mainly transsphenoidal cyst resection (95.9%), 4.1% via transcranial approach. Immunohistochemical staining for ß-catenin was feasible in 61/73 (83.6%) patients, with nuclear translocation detected in 13/61 cases (21.3%). Patients with and without NTßC were equally likely to present with endocrine dysfunction before surgery (p = 0.49). Postoperative new hypopituitarism occurred in 14/73 (19.2%) patients. Preoperative visual impairment was equal in both groups (p = 0.52). Vision improved in 8/21 (33.3%) patients and visual field deficits in 22/34 (64.7%) after surgery. There was no difference in visual and perimetric outcome between patients with and without NTßC (p = 0.45 and p = 0.23, respectively). On preoperative MRI, cyst volume (9.9 vs. 8.2 cm3; p = 0.4) and evidence of hemorrhage (30.8% vs. 35.4%; p = 0.99) were equal and postoperative cyst volume decreased significantly in both groups (0.7 vs. 0.5 cm3; p < 0.0001 each). Cyst progression occurred in 13/73 (17.8%) patients after 39.3 ± 60.3 months. Cyst drainage with partial removal of the cyst wall resulted in improved recurrence-free survival without increasing the risk of complications compared with cyst fenestration alone. Patients with postoperative diabetes insipidus had an increased risk for recurrence according to multivariate analysis (p = 0.005). NTßC was evident in 4/15 patients (26.7%) and was not associated with a higher risk for recurrence (p = 0.67).ConclusionTransnasal transsphenoidal cyst drainage with partial removal of the cyst wall reduces the risk of recurrence without increasing the risk of complications compared with fenestration of the cyst alone. Patients with postoperative diabetes insipidus seem to have an increased risk for recurrence. In contrast, NTßC was not associated with a higher risk of recurrence and did not provide stratification for clinically distinct patients.

Low serum zinc concentration is associated with low serum testosterone but not erectile function.

To investigate the relation between serum zinc concentration and several factors, including serum testosterone concentration and the score of questionnaires on sexual function in patients with sexual problems. This study comprised 720 men (age, 46.3 [21-83] years) with some kind of sexual problem. Age, scores of the Sexual Health Inventory for Men and the Erection Hardness Score, and endocrinologic data including serum concentrations of testosterone, prostate-specific antigen, and zinc were included in this study. After serum zinc concentration of the men was classified into 5 groups (<70, 70≤ <80, 80≤ <90, 90≤ <100, ≤100 μg/dl), the relation of each parameter with serum zinc concentration was assessed for a trend analysis. Finally, the relation between serum concentrations of zinc and testosterone as well sexual function evaluated by the scores of the questionnaires was investigated. Only serum testosterone concentration (ptrend=0.028) and serum cortisol concentration (ptrend=0.003) showed a statistically significant relation to serum zinc concentration by trend analysis. Interestingly, trend analysis between serum concentrations of testosterone and zinc still showed a significant association after adjustment for serum cortisol concentration (ptrend=0.032). However, no significant association was found in the relation between serum zinc concentration and the scores of the questionnaires after adjustment for serum concentrations of testosterone and cortisol. We clearly showed that after adjustment for serum cortisol concentration by trend analysis, serum testosterone concentration decreased as serum zinc concentration decreased, although sexual symptoms were not associated with this decrease.

PS-R03-10: CASE REPORT: CUSHING SYNDROME IN A YOUNG MALE

A 27-year-old male without any significant past medical history was advised to visit a hospital for elevated blood pressure, elevated liver enzymes, and dyslipidemia in a workplace health checkup. His body weight had increased by more than 10 kg in the last two years. He presented to our department and underwent laboratory work-up. He had bilateral lower limb pitting edema, hypokalemia, and elevation of low-density lipoprotein. No sign of dysthyroidism, renin-angiotensin-aldosterone system disorder, or increased catecholamine secretion was found. Diet and exercise therapy and calcium channel blocker did not improve his hypertension, and he suffered from lumber vertebral fracture, refractory hypokalemia, and lower leg cellulitis. He was admitted to our department for detailed examination of worsening lower limb edema. On admission, he had striae on his abdomen and legs as well as edema of both lower extremities. The endocrinological data showed high levels of adrenocorticotropic hormone (ACTH) and cortisol. Overnight 1 mg dexamethasone suppression test resulted in a non-suppression response, and his circadian rhythm of cortisol was absent. Urine cortisol level was high. These findings confirmed the diagnosis of ACTH-dependent Cushing syndrome. A contrasted magnetic resonance imaging (MRI) scan demonstrated enlargement of the pituitary gland more than 1 cm in length. Taking into account drug-resistant hypokalemia and vulnerability to infection, he was administered with metyrapone 500 mg per day until he underwent transsphenoidal hypophysectomy. The pathological findings were consistent with that of a pituitary adenoma. Postoperative MRI scan showed remnant lesions which stretch to the bilateral cavernous sinuses and the right middle cranial fossa. Although a decrease in urine cortisol was observed, the absence of a circadian rhythm of cortisol, hypertension, and hypokalemia persisted. He is now treated with somatostatin analog and craniotomy followed by gamma knife surgery is planned. Cushing syndrome should be suspected in cases of early-onset hypertension with symptoms including weight gain, hypokalemia, and bone fracture.

The Endoscopic Endonasal Transsphenoidal Approach for Thyrotropin-Secreting Pituitary Adenomas: Single-Center Experience and Clinical Outcomes of 49 Patients

To analyze surgical outcomes and tumor characteristics of 49 patients with thyrotropin-secreting pituitary adenoma, a rare functional pituitary adenoma subtype with challenging surgery, who underwent endoscopic endonasal transsphenoidal surgery. In this single-center study, clinical, radiological, surgical, and endocrinological data of 49 patients diagnosed with thyrotropin-secreting pituitary adenoma were retrospectively reviewed. Mean tumor size was 21.12 mm (6 microadenomas, 41 macroadenomas, 2 giant adenomas). Cavernous sinus invasion was present in 12 (24.48%) patients. Tumor consistency was firm in 23 (46.93%) patients. Plurihormonal secretion characteristics were present in 9 patients (5 growth hormone+ thyrotropin and 4 growth hormone+ prolactin+ thyrotropin). Mean follow-up duration was 51.73 months. Of the cases with firm tumors, 14 patients had a history of antithyroid drug use; there was no statistically significant correlation between the antithyroid medication and the firmness of the tumor. Gross total resection was achieved in 32 (65.30%) cases, near-total resection was achieved in 14 (28.57%) cases, and subtotal resection was achieved in 3 (6.12%) cases. The analysis showed that the negative effect of >2 cm tumor size and cavernous sinus invasion on resection rate was statistically significant (P < 0.001). Although early remission was achieved in 33 (67.34%) patients, 44 (89.79%) patients were in euthyroid state at >3 months' follow-up. Complications were 4 new-onset pituitary deficiencies, 3 cases of permanent diabetes insipidus, 1 thyrotoxic crisis, and 1 cerebrospinal fluid leak. Endoscopic endonasal transsphenoidal surgery is the first-line treatment in thyrotropin-secreting pituitary adenoma and should be performed in a tertiary center. Gross total resection is the goal, and early diagnosis is essential for surgical success.

Hepatic glycogen storage diseases type 0, VI and IX: description of an italian cohort

BackgroundGlycogen storage disease (GSD) type 0, VI and IX are inborn errors of metabolism involving hepatic glycogen synthesis and degradation. We performed a characterization of a large Italian cohort of 30 patients with GSD type 0a, VI, IXa, IXb and IXc. A retrospective evaluation of genetical, auxological and endocrinological data, biochemical tests, and nutritional intakes was assessed. Eventual findings of overweight/obesity and insulin-resistance were correlated with diet composition.ResultsSix GSD-0a, 1 GSD-VI, and 23 GSD-IX patients were enrolled, with an age of presentation from 0 to 72 months (median 14 months). Diagnosis was made at a median age of 30 months, with a median diagnostic delay of 11 months and a median follow-up of 66 months. From first to last visit, patients gained a median height of 0.6 SDS (from − 1.1 to 2.1 SDS) and a median weight of 0.5 SDS (from − 2.5 to 3.3 SDS); mean and minimal glucose values significant improved (p < 0.05). With respect to dietary intakes, protein intake (g/kg) and protein intake (g/kg)/RDA ratio directly correlated with the glucose/insulin ratio (p < 0.05) and inversely correlated with HOMA-IR (Homeostasis model assessment of insulin resistance, p < 0.05), BMI SDS (p < 0.05) and %ibw (ideal body weight percentage, p < 0.01).ConclusionA prompt establishment of specific nutritional therapy allowed to preserve growth, improve glycemic control and prevent liver complication, during childhood. Remarkably, the administration of a high protein diet appeared to have a protective effect against overweight/obesity and insulin-resistance.

Central precocious puberty in children after COVID-19 outbreak: a single-center retrospective study.

Central precocious puberty (CPP) was an unexplored issue during COVID-19 pandemic and an important disease in the adolescence life. Our aim was to evaluate the incidence of the new cases of central precocious puberty (CPP) during COVID-19 pandemic, comparing these results with the data for the same period over the previous three years. The secondary objective was to analyze the rate of pubertal progression in children during COVID-19 outbreak. We performed a retrospective study of all children presented at our hospital for suspected CPP during COVID-19 outbreak, comparing their clinical and endocrinological data to the same over the previous three years. Secondary, endocrinological data of some patients in follow-up, with at least two visits 6 months apart during the COVID-19 period, are compared to evaluate the rate of pubertal progression. We enrolled 90 suspected enrolled CPP cases, 26 (28.9%) referred to our hospital during the COVID-19 outbreak and 64 (71.1%) in the previous 3 years. During COVID-19 outbreak 12 girls (42.9%) were at stage T3 compared to 14 (23%) of the 3 previous years (p=0.01). New CPP diagnosis were found in 11 (39.3%) children during pandemic, while 15 (24.2%) in the previous 3 years. A accelerated pubertal progression rate was observed in 22/45 (48.9%) patients, with a greater number of children at stages T3 and T4-5. Our data showed a progressive increase of newly diagnosed CPP and a significantly accelerated rate of pubertal progression in children during COVID-19 outbreak. We hypothesize that the increase in the weight and BMI during the lockdown and the psychological effects of the COVID-19 outbreak were involved in triggering and progression of puberty.

Fall Patterns Are Independent Risk Factors for Mortality After Hip Fracture in Older Adults

Abstract Hip fracture is becoming a major health problem with high mortality and morbidity in older adults. However, whether specific fall patterns could act as independent risk factors for predicting mortality after hip fracture remains unknown. We aimed to investigate whether fall patterns can serve as an independent risk factor for mortality after hip fracture. Electronic medical records (EMR) of individuals who visited emergency room or admitted to the Severance hospital, Seoul, Korea, between January 2005 to December 2019 were reviewed to categorize fall patterns. Fall patterns were categorized upon review of explanatory description in EMR, using modified classification based on motion analysis of video-captured falls in a prior study. Among 1,991 study subjects (mean age 77 years, 71% women), 211 patients died (10.6%; median survival 296 days). Fall location was divided into home (67.4%) and outdoor (32.6%) with mortality rate of 11.9% and 8.0% (p=0.009), respectively. Fall patterns were specified by “cause of fall” (6 categories; slip [29.6%], trip or stumble [17.5%], etc.) and by “activity at time of fall” (6 categories; walking [54.8%], getting up or rising [14.1%], etc). Among the combinations of both causes and activities, individuals who sustained hip fracture during “incorrect weight shift while sitting down or lowering”(hazard ratio [HR] 3.35, p=0.003), “collapsed during unclassified activity”(HR 2.37, p=0.006), “incorrect weight shift while getting up or rising”(HR 2.13, p=0.003), and “slipped while walking”(HR 1.83, p=0.004) had increased mortality after hip fracture compared to those with outdoor falls, after adjustment for age, sex, and Charlson comorbidity index. Specific fall patterns in individuals who sustained hip fracture predicted excess mortality in older adults, independent of age, sex, and comorbidities. Acknowledgement: We thank Doori Cho of the the SENTINEL (Severance ENdocrinology daTa scIeNcE pLatform) team (4-2018-1215) for the data acquisition process. Conflict of Interest: SB, NH, and YR have nothing to declare.

Cushing Syndrome in the Setting of Chronic Dilated Cardiomyopathy: Can Treatment Improve Chronic Dilated Cardiomyopathy?

Background: Cushing syndrome (CS) is well known to be associated with metabolic syndrome, venous thromboembolism, hypertension, left ventricular hypertrophy, and rarely dilated cardiomyopathy. The pathophysiological effects of hypercortisolism on the myocardium results in cardiomyocyte hypertrophy, myofibrillolysis, myocardial fibrosis, global longitudinal and circumferential strain. Our patient presents an example of CS in the setting of chronic heart failure with reduced ejection fraction, multiple thromboembolic events, and diabetes mellitus in a young adult.Clinical Case: A 34-year male with a past medical history of dilated cardiomyopathy with biventricular failure and left ventricle ejection fraction of 10%, pulmonary embolism, diabetes mellitus, and gout presented with shortness of breath. On physical exam he presented with symptoms of CS: moon facies, supraclavicular fat pads, dorsal fat pads, purple striae of abdominal skin, truncal obesity, ecchymosis, and skin atrophy. Labs showed elevated morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 8.6 mcg/dl, n< 5 mcg/dl), repeat morning cortisol after overnight 1 mg dexamethasone suppression test (cortisol 5.7 mcg/dl, n< 5 mcg/dl), and ACTH-concentrations <5 pg/ml. CT-scan was insignificant for adrenal hyperplasia. He was admitted and treated for acute congestive heart failure exacerbation with plans for definitive treatment of CS outpatient with further imaging studies.Conclusion: The occurrence of CS induced heart failure results in increased mortality. There have been numerous accounts of resolution of cardiomyopathy after surgical treatment for CS secondary to adrenal adenoma. Our patient had a 10-year history of chronic dilated cardiomyopathy prior to cushingoid symptoms and confirmatory endocrinological data. The definitive treatment for CS syndrome in our patient would eventually be surgery targeting the source of hypercortisolism, however his cardiovascular risk factors would make him a poor surgical candidate. Severely reduced ejection fraction is a contraindication for generalized anesthesia needed for surgery. When surgery is contraindicated in CS medical management is recommended according to guidelines that target pituitary-directed medical treatments for Cushing’s disease and targeted therapies to treat ectopic ACTH syndrome. To our knowledge there have been few studies that demonstrate the effects of CS treatment on chronic conditions such as dilated cardiomyopathy. Studies have shown that surgical treatment for CS have reversed cardiomyopathy caused by CS but it still remains to be answered whether this same effect is achieved to some degree in chronic dilated cardiomyopathy.

Time-Varying Risk of Atrial Fibrillation in Patient With Medically and Surgically Treated Primary Aldosteronism: A Nationwide Cohort Study

Evidence of increased cardiovascular risk, especially atrial fibrillation, has been accumulating among patients with primary aldosteronism (PA), but there is still limited information about long-term prognosis related to different treatment strategy. The aim of this study was not only to investigate the incidence of atrial fibrillation, but also to evaluate their time-dependent changes after adrenalectomy (surgery group) or mineralocorticoid receptor antagonists (drug group) for patients with PA compared to those with essential hypertension (EH). From a nationwide cohort in Korea (2003–2017), PA were individually matched for sex, age (±10 years), and index year in a 1:5 ratio with EH. The primary end point was the time-varying risk of new-onset atrial fibrillation (NOAF) among PA according to treatment mode compared to EH. The secondary end points were the risks of major adverse cardiovascular events (composite of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular causes), hospitalization for heart failure, and all-cause mortality. Cox proportional-hazards analysis or time-dependent Cox analysis based on the Schoenfeld residuals testing were performed. We enrolled 1,418 PA patients (755 in PA surgery group and 663 in PA drug group), and matched theses with 7,090 EH controls with a median of 5 years. The risk of incident NOAF was statistically higher in patients with PA (both surgery and drug groups) within the three years after diagnosis (adjusted hazard ratio, 3.02; p<0.001), whereas there was no statistically significance after the three years compared to EH (adjusted hazard ratio, 0.50; p=0.053). Patients in the PA drug group had higher risk of non-fatal stroke during the total followed up period (adjusted hazard ratio, 1.53, p=0.031), although the PA surgery group didn’t. In contrast, patients with PA had no statistically significant difference in risks for other secondary cardiovascular outcomes. In conclusion, this propensity cohort study of adults with PA demonstrated the changeable risk of NOAF over time possibly due to the residual effect of inappropriate aldosterone levels. These findings can provide clinically relevant guidance in the monitoring the cardiovascular complications, especially NOAF and non-fatal stroke, even after treatment among patients with PA. Acknowledgements: This study was supported by Collaborative Research Project of Korean Endocrine Society and National Health Insurance Sharing Service (NHIS-2019-4-005). We also thank Minheui Yu and Doori Cho, the members of the SENTINEL (Severance ENdocrinology daTa scIeNcE pLatform) team for technical assistance in searching and summarizing the relevant literature (4-2018-1215).

High levels of physical activity in female adolescents with anorexia nervosa: medical and psychopathological correlates.

While overexercise is commonly described in patients who experience anorexia nervosa (AN), it represents a condition still underestimated, especially in the paediatric population. The present study aims at assessing the possible associations between levels of physical activity (PA) and clinical features, endocrinological data and psychopathological traits in a sample of 244 female adolescents hospitalised for AN subdivided into two groups according to PA levels (high PA vs. no/low PA). The two groups were compared through multivariate analyses, while multiple regression analysis was conducted to determine whether physical activity predict specific outcomes. No significant differences were found between the two groups in terms of last Body Mass Index (BMI) before illness, BMI at admission and disease duration, while a difference emerged in delta BMI(rapidity of weight loss), significantly higher in high-PA group (p = 0.021). Significant differences were observed in Free triiodothyronine- (p < 0.001), Free thyroxine (p = 0.046), Follicle-stimulating hormone (p = 0.019), Luteinising hormone (p = 0.002) levels, with values remarkably lower in high-PA group. Concerning psychopathological scales, the high-PA group showed worst Children's Global Assessment Scale (CGAS) scores (p = 0.035). Regression analyses revealed that higher PA predicts higher delta BMI (p = 0.021), presence of amenorrhea (p = 0.003), lower heart rate (p = 0.012), lower thyroid (Free triiodothyronine p < 0.001, Free thyroxine p = 0.029) and gynaecological hormones' levels (Follicle-stimulating hormone p = 0.023, Luteinising hormone p = 0.003, 17-Beta estradiol p = 0.041). Concerning psychiatric measures, HPA predicts worst scores at CGAS (p = 0.019), and at scales for evaluation of alexithymia (p = 0.028) and depression (p = 0.004). Results suggest that high levels of physical activity in acute AN associate with worst clinical conditions at admission, especially in terms of endocrinological and medical features. Level III.

Treatment with endoscopic transnasal resection of hypothalamic pilocytic astrocytomas: a single-center experience

BackgroundsPilocytic astrocytomas (PAs) are World Health Organization (WHO) grade I tumors, which are relatively common, and are benign lesions in children. PAs could originate from the cerebellum, optic pathways, and third ventricular/hypothalamic region. Traditional various transcranial routes are used for hypothalamic PAs (HPAs). However, there are few studies on hypothalamic PAs treated through the endoscopic endonasal approach (EEA). This study reports the preliminary experience of the investigators and results with HPAs via expanded EEAs.MethodsAll patients with HPAs, undergone EEA in our hospital from 2017 to 2019, were retrospectively reviewed. The demographic data, clinical symptoms, complications, skull base reconstruction, prognosis, and endocrinological data were all recorded and analyzed in detail.ResultsFinally, five female patients were enrolled. The average age of patients was 28.6 ± 14.0. All patients had complaints about their menstrual disorder. One patient had severe bilateral visual impairment. Furthermore, only one patient suffered from severe headache due to acute hydrocephalus, although there were four patients with headache or dizziness. Four cases achieved gross-total resection, and one patient achieved subtotal resection. Furthermore, there was visual improvement in one patient (case 5), and postoperative worsening of vision in one patient (case 4). However, only one patient had postoperative intracranial infection. None of the patients experienced a postoperative CSF leak, and in situ bone flap (ISBF) techniques were used for two cases for skull base repair. In particular, ISBF combined with free middle turbinate mucosal flap was used for case 5. After three years of follow-up, three patients are still alive, two patients had no neurological or visual symptoms, or tumor recurrence, and one patient had severe hypothalamic dysfunction. Unfortunately, one patient died of severe postoperative hypothalamus reaction, which presented with coma, high fever, diabetes insipidus, hypernatremia and intracranial infection. The other patient died of recurrent severe pancreatitis at one year after the operation.ConclusionAlthough the data is still very limited and preliminary, EEA provides a direct approach to HPAs with acceptable prognosis in terms of tumor resection, endocrinological and visual outcomes. ISBF technique is safe and reliable for skull base reconstruction.

Genome-wide association study for age at puberty and resumption of cyclicity in a crossbred dairy cattle population

Fertility is of primary economic importance in dairy cattle and the most common reason for involuntary culling. However, standard fertility traits have very low heritability that renders genetic selection slow and difficult. In this study, we explored fertility from an endocrine standpoint. A total of 1,163 crossbred Holstein-Normande females in a 3-generation familial design were studied for progesterone level measured every 10 d to determine age at puberty (PUB) and commencement of postpartum luteal activity (CPLA). Genetic parameters were estimated using REML with WOMBAT software. The heritability estimates were 0.38 ± 0.10 and 0.16 ± 0.07 for PUB and CPLA, respectively. Moreover, the 2 traits were genetically correlated (0.45 ± 0.23), suggesting a partially common determinism. Because of the family structure, a linkage disequilibrium and linkage analysis approach was preferred over standard genome-wide association study to map genomic regions associated with these traits. Ten quantitative trait loci (QTL) were detected for PUB on chromosomes 1, 3, 11, 13, 14, 21, and 29, whereas 3 QTL were associated with CPLA on chromosomes 21 and 26. Only the QTL on chromosome 21 was common to both traits. Four functional candidate genes (NCOA2, GAS2, OVOL1, and FOSL1) were identified in the detected regions. These findings will contribute to a clearer understanding of fertility determinism and enhance the value of introducing endocrinological data in fertility studies.

MON-905 A Case of Cushing’s Disease with Glucocorticoid Positive-Feedback

Background: Although paradoxical response of cortisol (F) during high dose dexamethasone (Dex) suppression test (DST) is observed in a part of ectopic ACTH syndrome, few reports have been shown in Cushing’s disease (CD). It suggests a presence of glucocorticoid (GC)-driven positive-feedback loop. However, the underlying mechanism remains elusive. Here we present a case of CD showing clear clinical and pathophysiological evidences of GC positive-feedback using ex vivo 3-dimensional (D) culture method. Case: A 62-year-old woman manifested typical Cushing’s symptoms, including moon face, central obesity, hypertension, hypokalemia, and vertebral fractures. Endocrinological data were consistent with a diagnosis of CD; morning plasma ACTH 299 pg/mL, serum F 28 μg/dL, midnight serum F 43 μg/dL, and 24hr urinary free cortisol 988 μg/day. CRH test showed a slight increase in plasma ACTH levels (1.4 fold), and pituitary MRI revealed a 14 mm macroadenoma invading into the left cavernous sinus. Interestingly, both 1 mg and 8 mg DST showed a paradoxical increase in serum cortisol levels (27.7→64.7μg/dL and 17.17→35.68μg/dL, respectively). These data indicated a presence of positive-feedback response to GC in the tumor. Indeed, after the initiation of metyrapone (1,000 mg/day) administration for the treatment of hypercortisolemia, plasma ACTH levels were decreased to 147.5 pg/mL accompanied with the decrease in serum F levels to 4.12 μg/dL. Moreover, pituitary tumor obviously shrank during the metyrapone treatment. Thereafter, we undertook transsphenoidal surgery and plasma ACTH and serum F levels decreased to 35.8 pg/mL and 7.6μg/dL, respectively. ex vivo studies: To prove the presence of the positive feedback response and explore the underlying mechanisms, we performed a primary culture experiment using the tumor and applied 3D culture method. The resected tumor tissue was enzymatically digested, dispersed and embedded into the Matrigel. Then cells were treated with Dex (0.1-10 nM), and ACTH concentrations were measured after 72 hrs. Interestingly, ACTH levels significantly increased by 10 nM Dex treatment at 72 h (129 %, p <0.01), indicating a paradoxical response to Dex in the tumor ex vivo. Conclusions: To our knowledge, this is the first case of CD who showed clinically obvious GC positive-feedback that was proved by ex vivo 3D primary culture cell models. Notably, tumor shrinkage was observed during the metyrapone treatment, suggesting that GC positive-feedback mechanisms also involve tumor proliferation. Further investigation is required for elucidating the underlying mechanisms.

Thyroid-Stimulating Hormone-Secreting Pituitary Adenomas : Single Institutional Experience of 14 Consecutive Cases.

ObjectiveThyroid-stimulating hormone (TSH)-secreting pituitary adenoma (PA) is an extremely rare functioning form of PA that accounts for 0.7–2% of all such cases. The previously reported outcomes of the surgical removal of TSH-PA are poor. Owing to its extremely low incidence, most available reports on TSH-PA are case reports or small case series. Thus, we investigated the clinical and endocrinological outcomes of surgically treated TSH-PA through our institutional series. MethodsWe retrospectively reviewed 14 consecutive cases of surgically treated TSH-PA, focusing on the clinical, radiological, surgical, and endocrinological data. ResultsThere were seven male (50%) and seven female (50%) patients. The mean age was 42.5 years (range, 19–63). The mean tumor size was 16.6 mm (range, 4–30). Optic chiasm compression was noted in six patients (42.9%), and no patient showed cavernous sinus invasion. Thirteen of 14 patients (92.8%) underwent transnasal transsphenoidal approach (TSA), and one patient underwent TSA followed by transcranial approach for residual tumor removal. Thirteen of 14 patients (92.8%) showed endocrinological remission; all patients who experienced remission showed subnormal levels of TSH (<0.4 μU/mL) on postoperative day 2. Recurrence occurred in two patients (14.2%). One patient underwent subsequent revision transnasal TSA for recurrent tumor removal, and the other patient underwent gamma knife radiosurgery for recurrence. ConclusionSurgical treatment showed excellent surgical outcomes. The TSH level in the immediate postoperative period may be a predictor for endocrinological remission.

What’s in a whisker? High-throughput analysis of twenty-eight C19 and C21 steroids in mammalian whiskers by ultra-performance convergence chromatography-tandem mass spectrometry

Obtaining longitudinal endocrinological data from free-ranging animals remains challenging. Steroid hormones can be extracted sequentially from non-invasively sampled biologically inert keratinous tissues, such as feathers, nails, hair and whiskers. However, uncertainty regarding the type and levels of steroids incorporated into such tissues complicates their utility in wildlife studies. Here, we developed a novel, comprehensive method to analyze fourteen C19 and fourteen C21 steroids deposited chronologically along the length of seal whiskers in a single, 6-minute chromatographic step, using ultra-performance convergence chromatography-tandem mass spectrometry. The limits of detection and quantification ranged from 0.01 to 2 ng/mL and from 0.1 to 10 ng/mL, respectively. The accuracy and precision were within acceptable limits for steroids at concentrations ≥2 ng/mL. The recovery (mean = 107.5% at 200 ng/mL), matrix effect and process efficiency of steroids evaluated, using blanked whisker matrix samples, were acceptable. The method was applied to the analysis of steroid hormone levels in adult female whisker segments obtained from southern elephant seals (Mirounga leonina), n = 10, and two fur seal species, Antarctic fur seals (Arctocephalus gazella; n = 5) and subantarctic fur seals (Arctocephalus tropicalis; n = 5), sampled between 2012 and 2017. In the whisker subsamples analyzed (n = 71), the median concentration of steroid hormones detected above the LOQ ranged from 2.0 to 273.7 pg/mg. This was the first extraction of multiple C19 and C21 steroids, including their C11-oxy metabolites, from the whiskers of mammals. Measuring hormones sequentially along the whisker lengths can contribute to our understanding of the impact of stress associated with environmental/climate changes that affect the health, survival of organisms, as well as to delineate the reproductive cycles of free-living mammals with cryptic life stages.

The Impact of Parental Role Distributions, Work Participation, and Stress Factors on Family Health-Related Outcomes: Study Protocol of the Prospective Multi-Method Cohort "Dresden Study on Parenting, Work, and Mental Health" (DREAM).

The Dresden Study on Parenting, Work, and Mental Health (“DResdner Studie zu Elternschaft, Arbeit, und Mentaler Gesundheit”, DREAM) aims to prospectively investigate the relationship between parental work participation, role distribution, stress factors, and their effects on perinatal outcomes and long-term family mental and somatic health in a community sample targeting N = 4,000 individuals, i.e., 2,000 couples, expecting a child and residing in Dresden, Germany (interim sample of N = 1,410 participants, recruitment ongoing). Various questionnaires are completed at four measurement points from pregnancy to 2 years postpartum (prolongation into middle childhood planned). Applying a multi-method approach, long-term endocrinological data (analyses of hair cortisol concentrations and other endogenous hormones, “DREAMHAIR”) and qualitative interview data (regarding gender role attitudes and distribution of domestic work, child care, and paid employment; “DREAMTALK”) are obtained. In this study protocol, the theoretical background, methods, and preliminary results considering sociodemographic characteristics during pregnancy and birth-related factors at 8 weeks postpartum are presented. Additionally, there is a focus on our endocrinological sub-study DREAMHAIR. In this sub-study currently comprising N = 152 participants, i.e., 88 families (recruitment ongoing), we want to gain knowledge on the transgenerational processes of stress regulation and psychopathology in the whole family by analyzing hair cortisol concentrations in both parents and children during the course from pregnancy (or after birth regarding children) to at least 2 years postpartum. By comparing data of the community sample to a clinical sample of mothers with postpartum mental disorders, their children, and their partners during the period between admission and discharge from a mother-baby unit and post-treatment (“DREAMMBU”), the course of mothers' psychopathology, parent-infant interaction, and infant regulation disorders with special regard to long-term endocrine correlates will be examined. With previous studies neglecting the fathers or partners involved, a major advantage of DREAM is the use of a multi-method and multi-level approach by examining the whole family in a longitudinal design. Therefore, the DREAM study will contribute to a better understanding of the role of social, work, and stress factors for mental and somatic health and its long-term endocrine correlates in the natural course of becoming a family.

Delayed Remission of Growth Hormone-Secreting Pituitary Adenoma After Transsphenoidal Adenectomy

To investigate the clinical characteristics of delayed remission (DR) of growth hormone (GH)-secreting pituitary adenoma after transsphenoidal adenectomy and inform follow-up treatments. We retrospectively reviewed 87 patients who had undergone transsphenoidal surgery for acromegaly. Demographic, radiological, and endocrinological data were reviewed before, immediately after, 3 months after, and in the long term (2.4 ± 1.1 years) after surgery. The definition of DR was that patients did not achieve GH remission immediately, 3 months, or later after surgery, but did so in the long term without any additional postoperative treatment. Fifty-one patients (58.6%) achieved long-term GH remission. There were 24 (27.6%) DR patients immediately postoperatively and 9 (10.3%) DR patients 3 months postoperatively. On average, the 24 DR patients achieved remission at 10.2 (range, 3-32) months. Immediate postoperative random and nadir GH after an oral glucose load were significantly lower in the DR group than in the nonremission group (2.73 ± 3.17 and 2.03 ± 2.59 vs. 8.05 ± 10.35 and 5.55 ± 5.91 μg/L, respectively). Three-month postoperative nadir GH was significantly lower in the DR group than in the nonremission group (1.63 ± 2.82 vs. 3.48 ± 4.25 μg/L, P= 0.007). Immediate postoperative random GHeffectively predicted long-term remission (Spearman's ρ= 0.513, area under the curve= 0.905 > 0.90). However, the best predictor of long-term remission was 3-month postoperative nadir GH (Spearman's ρ= 0.728, area under the curve= 0.944 > 0.90), with 76.5% sensitivity and 97.2% specificity. For certain groups of patients likely to achieve DR, additional treatments should not be performed early after surgery. Prolonged follow-up and close observation could help determine the therapeutic effect of surgery and guide postoperative treatments.