Serum Metabolomic and Lipidomic Profiling Reveals the Signature for Postoperative Obesity among Adult-Onset Craniopharyngioma.

Craniopharyngioma patients often suffer from a diminished quality of life after surgery, which is usually associated with metabolic disorders and hypothalamic obesity. However, the precise etiology of these conditions remains elusive. To identify the metabolic changes after surgery, we conducted a cross-sectional study using metabolomic and lipidomic analysis to profile metabolic alterations in adult-onset craniopharyngioma patients with postoperative obesity. A cohort of 120 craniopharyngioma patients who had undergone surgery were examined. Differential analyses, including clinical characteristics, serum metabolome, and lipidome, were conducted across distinct body mass index (BMI) groups. Our findings indicated no statistically significant differences in age, sex, and fasting blood glucose among postoperative craniopharyngioma patients when stratified by BMI. However, a noteworthy difference was observed in uric acid and blood lipid levels. Further investigation revealed that alterations in metabolites and lipids were evidently correlated with increased BMI, indicating that postoperative obesity of craniopharyngioma patients affected their whole-body metabolism. Additionally, the multi-omics analysis identified specific metabolites and lipids, including uric acid and DG(18:2/20:4), as contributors to the metabolic disorders associated with postoperative obesity of craniopharyngioma patients. This work provides valuable insight into the involvement of metabolites and lipids in metabolic disorders subsequent to craniopharyngioma surgery.

Germline AIP variants in sporadic young acromegaly and pituitary gigantism: clinical and genetic insights from a Han Chinese cohort.

PURPOSE: Variants in the Aryl hydrocarbon receptor-interacting protein (AIP) gene have been identified in sporadic acromegaly and pituitary gigantism, especially in young patients, with a predisposition to aggressive clinical phenotype and poor treatment efficacy. The clinical characteristics of patients with sporadic acromegaly and pituitary gigantism as well as AIP variants in Han Chinese have been rarely reported. We aimed to identify AIP gene variants and analyze the clinical characteristics of patients with sporadic acromegaly and pituitary gigantism in Han Chinese. METHODS: The study included 181 sporadic acromegaly (N = 163) and pituitary gigantism (N = 18) patients with an onset age of no more than 45 years old, who were diagnosed, treated, and followed up in Huashan Hospital. All 6 exons and their flanking regions of the AIP gene were analyzed with Sanger sequencing or NGS. The clinical characteristics were compared between groups with and without AIP variants. RESULTS: Germline AIP variants were found in 15/181 (8.29%) cases. In patients with an onset age ≤30 years old, AIP variants were identified in 12/133 (9.02%). Overall, 13 variants were detected. The pathogenic (P) variants p.R304X and p.R81X were identified in four cases, with two instances of each variant. Six exon variants (p.C254R, p.K103fs, p.Q228fs, p.Y38X, p.Q213*, and p.1115 fs) have not been reported before, which were likely pathogenic (LP). Patients with P/LP variants had younger onset ages, a higher prevalence of pituitary gigantism, larger tumor volumes, and a higher percentage of Ki-67-positive cells in tumors. In addition, the group with P/LP variants showed a less significant reduction of GH levels in an acute octreotide suppression test (OST) [17.7% (0, 65.0%) vs. 80.5% (63.9%, 90.2%), P = 0.001], and a trend of less GH decrease after the 3-month treatment with long-acting somatostatin analogs (SSAs). CONCLUSION: Germline AIP variants existed in sporadic Chinese Han acromegaly and pituitary gigantism patients and were more likely to be detected in young patients. AIP variants were associated with more aggressive tumor phenotypes and less response to SSA treatment.

Early identification of postoperative remission for thyrotropin-secreting adenomas.

OBJECTIVE: Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. RESULTS: The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. CONCLUSIONS: Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.

Clinical Characteristics of Adipsic Diabetes Insipidus.

OBJECTIVE: Adipsic diabetes insipidus (ADI) is a life-threatening disease. It is characterized by arginine vasopressin deficiency and thirst absence. Data about clinical characteristics of ADI were scarce. This study investigated the clinical features of hospitalized ADI patients. METHODS: A retrospective study was conducted of hospitalized ADI patients admitted to the Endocrinology Department of Huashan Hospital between January 2014 and December 2021, and compared with central diabetes insipidus (CDI) patients with normal thirst. RESULTS: During the study period, there were a total of 507 hospitalized CDI patients, among which 50 cases were ADI, accounting for 9.9%. Forty percent of ADI patients were admitted due to hypernatremia, but there were no admissions due to hypernatremia in the control group. The lesions of ADI patients were more likely to be located in the suprasellar area (100% vs 66%, P < .05). Higher prevalence of hypothalamic dysfunction (76% vs 8%, P < .001), central hypothyroidism (100% vs 90%, P = .031), hyperglycemia (66% vs 32%, P < .001), dyslipidemia (92% vs 71%, P = .006), and hyperuricemia (64% vs 37%, P = .003) was found in the ADI group than in the control group. The proportions of hypernatremia were higher in the ADI group both at admission and at discharge (90% vs 8%, 68% vs 8%, respectively, both with P < .001), contributing to higher prevalence of complications, such as renal insufficiency, venous thrombosis, and infection. CONCLUSION: ADI patients were found with higher prevalence of hypernatremia, hypopituitarism, hypothalamic dysfunction, metabolic disorders, and complications, posing a great challenge for comprehensive management.

Successful Diagnoses and Remarkable Metabolic Disorders in Patients With Solitary Hypothalamic Mass: A Case Series Report.

Background: Solitary intracranial hypothalamic mass occurs rarely. The etiological diagnosis of solitary hypothalamus lesion is challenging and often unachievable. Although previous studies indicated that lesions affecting the hypothalamus often cause significant metabolic disorders, few reports about the metabolic disturbances of patients with solitary hypothalamic mass have been reported. Method: Twenty-five patients with solitary hypothalamus lesions who had been evaluated and treated in Huashan Hospital from January 2010 to December 2020 were retrospectively enrolled. The clinical manifestations, radiological features, endocrine and metabolic disorders, and pathology were analyzed. Results: The male to female ratio was 5/20. The median age of onset was 22 (19, 35) years old. The most common initial symptom was polydipsia/polyuria (19/25, 76.0%) and amenorrhea (9/20, 45.0%). A high prevalence of hypopituitarism of different axes was found, with almost all no less than 80%. Central hypogonadism (21/22, 95.5%) and central diabetes insipidus (19/21, 90.5%) were the top two pituitary dysfunctions. Conclusive diagnoses were achieved by intracranial surgical biopsy/resection or stereotactic biopsy in 16 cases and by examining extracranial lesions in 3 cases. The pathological results were various, and the most common diagnoses were Langerhans cell histiocytosis (7/19) and hypothalamitis (5/19). The mean timespan from onset to diagnosis in the 19 cases was 34 ± 26 months. Metabolic evaluations revealed remarkable metabolic disorders, including hyperlipidemia (13/16, 81.3%), hyperglycemia (10/16, 62.5%), hyperuricemia (12/20, 60%), overweight/obesity (13/20, 65.0%), and hepatic adipose infiltration (10/13, 76.6%). Conclusion: Either surgical or stereotactic biopsy will be a reliable and relatively safe procedure to help to confirm the pathological diagnosis of solitary hypothalamic mass. Metabolic disorders were severe in patients with solitary hypothalamic mass. The management of such cases should cover both the treatment of the primary disease, as well as the endocrine and metabolic disorders.

Risk Factors for Hypothalamic Obesity in Patients With Adult-Onset Craniopharyngioma: A Consecutive Series of 120 Cases.

Context: Hypothalamic obesity (HO) is a severe complication following craniopharyngioma, but studies regarding the sequelae in adult-onset patients with craniopharyngioma are sparse. Objective: The objective of the study was to describe weight changes after surgical treatment in adult-onset craniopharyngioma patients and to analyze risk factors for postoperative weight gain and HO. Subjects and Method: A retrospective analysis was conducted of 120 adult-onset patients who underwent surgery for craniopharyngioma and follow-up at the institution of the authors between January 2018 and September 2020. Clinical characteristics, anthropometric data, image features, treatment modalities, and endocrine indices were collected. Multivariable logistic regression analysis was used to identify independent risk factors for postoperative weight gain and HO. Results: Forty-nine (40.8%) patients had clinically meaningful weight gain (≥5%) in a median follow-up time of 12.0 months (range 1.0-41.0 months) after surgery. The mean postoperative weight gain in this subgroup was 17.59 ± 12.28 (%). Weight gain continued in the first year following surgery. Patients with lower preoperative BMI [OR 0.78, 95% CI (0.67-0.90), P = 0.001] and the adamantinomatous subtype [OR 3.46, 95% CI (1.02-11.76), P = 0.047] were more likely to experience postoperative weight gain ≥5%. The prevalence of HO was 19.2% preoperatively and increased to 29.2% at last follow-up postoperatively. Only preoperative BMI [OR 2.51, 95% CI (1.64-3.85), P < 0.001] was identified as an independent risk factor for postoperative HO. Conclusions: HO is a common complication in patients with adult-onset craniopharyngioma. Patients with higher preoperative BMI had a greater risk for developing HO postoperatively.

Neuropeptide Y Plays an Important Role in the Relationship Between Brain Glucose Metabolism and Brown Adipose Tissue Activity in Healthy Adults: A PET/CT Study.

Introduction: Brown adipose tissue (BAT) becomes the favorite target for preventing and treating metabolic diseases because the activated BAT can produce heat and consume energy. The brain, especially the hypothalamus, which secretes Neuropeptide Y (NPY), is speculated to regulate BAT activity. However, whether NPY is involved in BAT activity's central regulation in humans remains unclear. Thus, it's essential to explore the relationship between brain glucose metabolism and human BAT activity. Methods: A controlled study with a large sample of healthy adults used Positron emission tomography/computed tomography (PET/CT) to noninvasively investigate BAT's activity and brain glucose metabolism in vivo. Eighty healthy adults with activated BAT according to the PET/CT scan volunteered to be the BAT positive group, while 80 healthy adults without activated BAT but with the same gender, similar age, and BMI, scanning on the same day, were recruited as the control (BAT negative). We use Statistical parametric mapping (SPM) to analyze the brain image data, Picture Archiving & Communication System (PACS), and PET/CT Viewer software to calculate the semi-quantitative values of brain glucose metabolism and BAT activity. ELISA tested the levels of fasting plasma NPY. The multiple linear regression models were used to analyze the correlation between brain glucose metabolism, the level of NPY, and the BAT activity in the BAT positive group. Results: (1) Compared with controls, BAT positive group showed significant metabolic decreases mainly in the right Insula (BA13a, BA13b) and the right claustrum (uncorrected P <0.01, adjusted BMI). (2) The three brain regions' semi-quantitative values in the BAT positive group were significantly lower than the negative group (all P values < 0.05). (3) After adjusting for age, gender, BMI, and outside temperature, there was a negative correlation between brain metabolic values and BAT activity (all P values < 0.05). However, after further adjusting for NPY level, there were no significant differences between the BA13b metabolic values and BAT activity (P>0.05), while the correlation between the BA13a metabolic values and BAT activity still was significant (P< 0.05). Conclusions: Regional brain glucose metabolism is closely related to healthy adults' BAT activity, which may be mediated by NPY.

Pituitary Dysfunction in Patients with Intracranial Germ Cell Tumors Treated with Radiotherapy.

OBJECTIVE: To evaluate the endocrine abnormalities in intracranial germ cell tumors (iGCTs) treated with radio-therapy (RT), and to discuss the effects of RT on pituitary functions. METHODS: Seventy-seven patients diagnosed with iGCTs who had received RT and endocrine follow-up in Huashan Hospital between January 2010 and July 2017 were retrospectively analyzed, consisting of 49 germinomas and 28 NGGCTs. The median follow-up period was 50.0 months. Fifty-one patients had radiologically proved suprasellar/sellar lesions. RESULTS: The male to female ratio was 62/15. The median endocrine follow-up period was 19 (4, 42) months. The median age at the last endocrine visit was 18 (16, 20) years old. The 5-year overall and recurrence-free survival were both 98.7%. The overall prevalence of central adrenal insufficiency (CAI), central hypothyroidism (CHT), central hypogonadism (CHG), hyperprolactinemia, and central diabetes insipidus (CDI) was 57.3%, 56%, 56.6%, 35.3%, and 52.1%, respectively, after RT. Patients having suprasellar/sellar lesions showed significantly higher post-therapeutic prevalence of hypopituitarism than those who didn't. Compared to that before RT, CAI, CHT, and CHG weren't significantly improved while the levels of prolactin and the prevalence of CDI declined significantly (P =.03 and.001). The radiation doses to pituitary and hypothalamus between those with and without CAI, CHT, and CHG weren't significantly different. CONCLUSION: The prevalence of hypopituitarism was high in iGCTs, especially in those with suprasellar/sellar involvement. The levels of prolactin and the prevalence of CDI declined significantly after RT. The hypopituitarism in iGCTs was mainly induced by tumor effects, and RT showed no additional damage to pituitary functions in our study. ABBREVIATIONS: AFP = alpha-fetoprotein; CAI = central adrenal insufficiency; CDI = central diabetes insipidus; CHG = central hypogonadism; CHT = central hypothyroidism; CT = computed tomography; DA = dopamine; GH = growth hormone; ßHCG = beta-human chorionic gonadotropin; HPA = hypothalamus-pituitary-adrenal; HPG = hypothalamus-pituitary-gonadal; HPL = hyperprolactinemia; HPT = hypothalamus-pituitary-thyroid; iGCT = intracranial germ cell tumor; IGF-1 = insulin-like growth factor 1; NGGCT = nongerminomatous germ cell tumors; OS = overall survival; PFS = progression-free survival; PRL = hypothalamus-pituitary-prolactin; RT = radiotherapy.

Association of hypokalemia with cortisol and ACTH levels in Cushing's disease.

Hypokalemia is a common feature in patients with Cushing's syndrome (CS). Whether the occurrence of hypokalemia is associated with cortisol and adrenocorticotropic hormone (ACTH) levels is still unclear. Approximately 80% of cases of endogenous CS are due to Cushing's disease (CD). The purpose of this study was to determine the association of hypokalemia with cortisol and ACTH levels in patients with CD. The retrospective study included 195 patients with CD referred to our medical center from January 2011 to December 2017. The results show that 25.64% (50/195) of the patients had hypokalemia. The 24-h urinary free cortisol (UFC) and plasma cortisol levels were significantly higher in patients with hypokalemia than those with normokalemia (P < 0.05). Plasma ACTH levels were similar between the patients with hypokalemia and normokalemia (P > 0.05). Cortisol levels were negatively correlated with plasma potassium levels (08:00: r = -0.344 (P < 0.01), 00:00: r = -0.435 (P < 0.01); 24-h UFC: r = -0.281 (P < 0.05)). There was no significant correlation between the plasma ACTH and potassium (08:00: r = -0.093 (P > 0.05), 00:00: r = -0.184 (P > 0.050)). Our current data suggest that cortisol level, instead of ACTH level, is correlated with plasma potassium level. A high cortisol level may be the principal cause of hypokalemia.

A study of thyroid functions in patients with Cushing's syndrome: a single-center experience.

OBJECTIVE: The aim of this study was to evaluate thyroid functions in Cushing's syndrome (CS), the dynamic changes of thyroid hormones and antithyroid antibodies in Cushing's disease (CD) pre- and postoperatively. DESIGN AND METHODS: This is a retrospective study enrolling 118 patients with CS (102 CD, 10 adrenal CS and 6 ectopic adrenocorticotropic syndrome (EAS)). Thyroid functions (thyroid-stimulation hormone (TSH), T3, free T3 (FT3), T4 and free T4 (FT4)) were measured in all CS at the time of diagnosis and in all CD 3 months after transsphenoidal pituitary tumor resection. Postoperative hormone monitoring within 3 months was conducted in 9 CD patients completing remission. Twenty-eight remitted CD patients experienced hormone and antithyroid antibody evaluation preoperatively and on the 3rd, 6th and 12th month after surgery. RESULTS: TSH, T3 and FT3 were below the reference range in 31%, 69% and 44% of the 118 CS patients. Remitted CD patients (81/102) had significantly higher TSH (P = 0.000), T3 (P = 0.000) and FT3 (P = 0.000) than those in the non-remission group (21/102). After remission of CD, TSH, T3 and FT3 showed a significant increase, with a few cases above the reference range. By 12 months, most CD patients' thyroid functions returned to normal. Thyroid hormones (including TSH, T3 and FT3) were negatively associated with serum cortisol levels both before and after surgery. No significant changes of antithyroid autoantibodies were observed. CONCLUSIONS: TSH, T3 and FT3 are suppressed in endogenous hypercortisolemia. After remission of CD, TSH, T3 and FT3 increased significantly, even above the reference range, but returned to normal 1 year after surgery in most cases. Antithyroid antibodies did not change significantly after remission of CD.