Clinical characteristics and predictive factors of delayed diagnosis in patients with sellar germ cell tumors.

PURPOSE: To investigate the clinical characteristics and predictive factors associated with delayed diagnosis in patients with sellar germ cell tumors (GCTs), aiming for early diagnosis. METHODS: A total of 345 patients with sellar GCTs were retrospectively collected. Patients were classified into a delayed diagnosis group (> 6 months from onset to diagnosis) and a non-delayed diagnosis group (≤ 6 months). We compared general characteristics, clinical symptoms, diagnostic methods, treatment strategies, tumor prognosis, and pituitary function between the two groups. Predictive factors for delayed diagnosis were explored using multivariate logistic regression analysis. RESULTS: 225 patients (65.2%) experienced delayed diagnosis. Although there was no association between delayed diagnosis and survival rates or tumor recurrence rates, the delayed diagnosis group had a higher incidence of central diabetes insipidus, central adrenal insufficiency, central hypothyroidism, central hypogonadism, and growth hormone deficiency. Moreover, polyuria/polydipsia (OR 5.46; 95% CI 2.33-12.81), slow growth (OR 5.86; 95% CI 2.61-13.14), amenorrhea (OR 6.82; 95% CI 2.68-17.37), and germinoma (OR 4.99; 95% CI 1.08-3.61) were associated with a higher risk of delayed diagnosis, while older age of onset (OR 0.88; 95% CI 0.84-0.94) and nausea/vomiting (OR 0.31; 95% CI 0.15-0.63) contributed to earlier diagnosis. CONCLUSION: In patients with sellar GCTs, delayed diagnosis is common and linked to increased pituitary dysfunction. The initial symptoms of slow growth, polyuria/polydipsia, and amenorrhea, as well as germinoma with negative tumor markers, predict the possibility of a delayed diagnosis. Early diagnosis is crucial to minimize the impact of sellar GCTs on pituitary function.

Clinical Characteristics and Management of Cosecreting Thyroid Stimulating Hormone or Prolactin Pituitary Growth Hormone Adenomas: A Case-Control Study.

OBJECTIVE: Cosecreting thyroid stimulating hormone (TSH) or prolactin (PRL) in patients with pituitary growth hormone (GH) adenomas has been rarely reported. Our study aimed to elucidate their clinical characteristics. METHODS: We retrospectively collected data of 22 cases of cosecreting GH and TSH pituitary adenomas [(GH+TSH)oma] and 10 cases of cosecreting GH and PRL pituitary adenomas [(GH+PRL)oma] from Beijing Tiantan Hospital, Capital Medical University between January 2009 and January 2023. The clinical manifestation, preoperative hormone levels, imaging features, pathologic characteristics, and biochemical remission rates were compared among 335 patients with solo-secreting GH adenomas (GHoma) and 49 patients with solo-secreting TSH adenoma (TSHoma). Patients with (GH+TSH)oma and (GH+PRL)oma were grouped according to biochemical remission to explore the risk factors leading to biochemical nonremission. RESULTS: Cosecreting pituitary GH adenomas had various clinical manifestations and a larger tumor volume and were more likely to invade the cavernous sinus bilaterally and compress the optic chiasm. GH and TSH levels were lower in (GH+TSH)oma than in GHoma or TSHoma. Solo part remission was observed both in (GH+TSH)oma and (GH+PRL)oma. Cavernous sinus invasion was an independent risk factor for biochemical nonremission in patients with (GH+TSH)oma and (GH+PRL)oma. CONCLUSIONS: The clinical manifestation of (GH+TSH)oma and (GH+PRL)oma may be atypical. When screening for pituitary adenomas, a comprehensive evaluation of all pituitary target gland hormones is needed. Cosecreting pituitary GH adenomas are more aggressive and surgery is often unable to completely remove the tumor, requiring pharmacologic or radiological treatment if necessary. Clinicians should give high priority to biochemical remission, although solo part remission may occur.

Clinical Characteristics of Childhood-Onset Craniopharyngioma.

Objective: Craniopharyngioma (CP) is an intracranial congenital epithelial tumor that can occur at any age. CP tumors are histologically benign (WHO grade I), and childhood­onset CP (CO-CP) patients have a high rate of survival. The major concern for CO-CP patients is delayed diagnosis. Delayed diagnosis can further lead to serious adverse consequences such as acute and chronic complications, thereby endangering the life of the patient.We evaluated the early-stage clinical characteristics of CO-CP patients to provide clues for making rapid and accurate diagnoses. Methods: This was a retrospective, single-center study. We retrospectively reviewed all pediatric patients (<18 years of age) undergoing CP surgery between 2012 and 2019 at a single institution. Data including demographic data, clinical presentation, neuroendocrine dysfunction, and tumor imaging characteristics at diagnosis were analyzed. Results: The average age of the 192 children in this study was 7.32±3.94 (0-16) years, 91.0% were diagnosed when under 14 years old, and 92.7% of patients had at least one clinical symptom, and 90.7% of tumors have a diameter greater than 2cm, and 95.9% of tumor consistency was mixed or cystic, and 89.0% of tumors found calcification. The patients with hydrocephalus had higher BMI values than those without hydrocephalus (P = .006), and the incidence of calcification of tumors significantly decreased with age (P = .027). Conclusions: For pediatric patients with calcification, >2 cm, cystic or mixed intracranial mass lesions, CP tumors should be considered, and early neuroendocrine function evaluation and further surgical treatment should be performed to avoid delayed diagnosis.

Central precocious puberty secondary to peripheral precocious puberty due to a pineal germ cell tumor: a case and review of literature.

BACKGROUND: The pineal lesion affecting melatonin is a rare cause of central precocious puberty by decreasing the inhibition of hypothalamic-pituitary-gonadal axis. Germ cell tumor secreting human chorionic gonadotropin is a rare cause of peripheral puberty. CASE PRESENTATION: A 5.8-year-old male presented facial hair and phallic growth, deepened voice, and accelerated growth velocity for 6 months. The elevated human chorionic gonadotropin level with undetectable gonadotropin levels indicated peripheral precocious puberty. Brain imaging revealed a pineal mass and further pathology indicated the diagnosis of teratoma. During chemoradiotherapy with operation, the elevated human chorionic gonadotropin level reduced to normal range, while the levels of gonadotropins and testosterone increased. Subsequently, progressing precocious puberty was arrested with gonadotrophin-releasing hormone analog therapy. Previous cases of transition from peripheral precocious puberty to central precocious puberty were reviewed. The transitions were caused by the suddenly reduced feedback inhibition of sex steroid hormones on gonadotropin releasing hormone and gonadotropins. CONCLUSIONS: For patients with human chorionic gonadotropin-secreting tumors, gonadotropin levels increase prior to sex steroid decrease, seems a sign of melatonin-related central PP related to melatonin.

The Effect and Potential Mechanism Analysis of Growth Hormone-Secreting Pituitary Adenomas on Thyroid Function.

OBJECTIVE: Current studies on the effect of high growth hormone (GH)/insulin-like growth factor (IGF)-1 on thyroid function are inconsistent. The aim was to explore the effect and potential mechanism of high GH/IGF-1 on thyroid function by analyzing the changes of thyroid function in patients with growth hormone-secreting pituitary adenoma (GHPA). METHODS: This was a retrospective cross-sectional study. Demographic and clinical data of 351 patients with GHPA who were first admitted to Beijing Tiantan Hospital, Capital Medical University, from 2015 to 2022 were collected to analyze the relationship between high GH/IGF-1 levels and thyroid function. RESULTS: GH was negatively correlated with total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH). IGF-1 was positively correlated with total triiodothyronine (TT3), free triiodothyronine (FT3), and FT4 and negatively correlated with TSH. Insulin-like growth factor-binding protein (IGFBP)-3 was positively correlated with TT3, FT3, and FT3:FT4 ratio. The FT3, TT3, TSH, and FT3:FT4 ratio of patients with GHPA and diabetes mellitus (DM) were significantly lower than those with GHPA but without DM. With the increase of tumor volume, thyroid function gradually decreased. GH and IGF-1 were correlated negatively with age in patients with GHPA. CONCLUSION: The study emphasized the complex interaction between the GH and the thyroid axes in patients with GHPA and highlighted the potential effect of glycemic status and tumor volume on thyroid function.

The effect of acromegaly on thyroid disease.

Long-term stimulation of thyroid follicular epithelium by high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly can lead to thyroid dysfunction, goiter, thyroid nodules, and even thyroid cancer and thyroid-associated ophthalmopathy (TAO). Excessive GH/IGF-1 promotes goiter and thyroid nodule formation, which can be reversed by normalizing the IGF-1 levels with surgery or medical treatment. Whether patients with acromegaly have an increased risk of thyroid cancer remains controversial, and routine thyroid ultrasonography and regular cancer screening are recommended in such cases, especially when the nodules possess malignant propensity. TAO is an autoimmune disease and newer treatments are being discovered against it. Recent studies have reported that the IGF-1 receptor (IGF-1R) plays an important role in the pathogenesis of TAO, and the IGF-1R inhibitor teprotumumab involves significantly improved disease endpoints in patients with active TAO. Thyroid-stimulating hormone (TSH) receptor (TSHR) and IGF-1R co-immunoprecipitate in orbital and thyroid tissues to form a functional complex; thus, combined therapy targeting TSHR and IGF-1R may be more effective than single therapy.

Diabetes mellitus and the risk of gastrointestinal cancer in women compared with men: a meta-analysis of cohort studies.

BACKGROUND: The increasing epidemic proportions of diabetes mellitus (DM) are a major cause of premature illness and death. However, whether DM confers the same excess risk of gastrointestinal cancer for women as it does for men remains controversial. The purpose of this study was to estimate the relation between DM and gastrointestinal cancer in women compared with men after accounting for other major risk factors based on cohort studies. METHODS: We performed a meta-analysis of cohort studies published through May 2017 from PubMed, Embase, and the Cochrane Library. Studies with cohort designs were stratified by sex and reported the relation between DM and esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), hepatocellular carcinoma (HCC), or pancreatic cancer (PC) risk. The ratio of relative risk (RRR) between men and women was employed to measure the sex differences in the relation between DM and gastrointestinal cancer with a random effects model with inverse variance weighting. RESULTS: We included 38 cohort studies reporting data on 18,060,698 individuals. The pooled RRR indicated DM women was associated with an increased risk of GC (RRR: 1.14; 95%CI: 1.06-1.22; p < 0.001), while the risk of HCC was lower (RRR: 0.88; 95%CI: 0.79-0.99; p = 0.031) as compared with DM men. Further, there was no evidence of sex differences in the RRR between participants who had DM compared with those without DM for EC (p = 0.068), CRC (p = 0.618), and PC (p = 0.976). In addition, the pooled RRR showed a statistically significant association between DM and the risk of CC in women compared with men (RRR: 0.93; 95%CI: 0.86-1.00; p = 0.050), and there was no evidence of sex differences for RC among participants with DM compared to those without DM (p = 0.648). Finally, the sex differences of the comparison between DM and non-DM for gastrointestinal cancer risk at different sites were variable after stratification for different effect estimates. CONCLUSIONS: The findings of this study suggested female-to-male RRR of DM was increased for GC, while reduced for HCC and CC. However, there were no sex differences for the relation between DM and the risk of EC, CRC, PC, and RC.

Comparison of central diabetes insipidus (antidiuretic hormone deficiency) and stalk effect in patients with adamantinomatous and papillary craniopharyngioma.

Craniopharyngioma (CP), a rare benign intracranial tumor, is still a major clinical challenge. There are two major histologic phenotypes: papillary CP (PCP) and adamantinomatous CP (ACP). This research aimed to assess the occurrence of central diabetes insipidus (antidiuretic hormone deficiency), the level of prolactin, and the stalk effect between PCP and ACP subtypes prior to and after surgery. Clinical data of CP patients before and after surgical resection of the tumor were analyzed retrospectively. These patients were divided into PCP and ACP groups, in accordance with the pathologic classification. The data of prolactin level, 24-h urinary volume, urine specific gravity and electrolyte status before and after surgery were evaluated in these two CP subtypes. A total of 86 CP patients were included, among which 28 patients were PCP and 58 were ACP. Compared to those prior to surgery, 24-h urine volume, serum sodium and serum chlorine concentrations were obviously increased, while prolactin and urine specific gravity were remarkably decreased in all the CP patients after surgery. Compared to those before operation, prolactin level and urine specific gravity were decreased, and 24-h urine volume, serum sodium and serum chlorine were elevated after operation in ACP patients. Moreover, after surgery, 24-h urine volume in PCP patients was higher than that in ACP group. The central diabetes insipidus in patients with CP was aggravated after surgical resection, especially in ACP patients. Moreover, the central diabetes insipidus of PCP subtype was more serious than that of ACP subtype.

Growth hormone-secreting pituitary adenoma combined with Graves' disease: retrospective case series and literature review.

Purpose: The coexistence of growth hormone-secreting pituitary adenoma (GHPA) and Graves' disease (GD) is rare. This study aimed to investigate the relationship between growth hormone (GH)/insulin-like growth factor 1 (IGF-1) levels and thyroid function in patients with GHPA combined with GD and to explore the underlying mechanisms. Methods: Eleven patients with GHPA combined with GD during 2015-2022 were collected by searching the medical record system of Beijing Tiantan Hospital, Capital Medical University. Changes in GH/IGF-1 levels and thyroid function were compared before and after the application of antithyroid drugs (ATD) and before and after transsphenoidal surgery (TSS) or somatostatin analog (SSA) treatment, respectively. Results: After the application of ATD, with the decrease of thyroid hormone levels, GH/IGF-1 levels also decreased gradually. In patients without ATD application, after surgery or SSA treatment, thyroid hormone levels decreased as GH/IGF-1 decreased. Conclusion: Hyperthyroidism due to GD promotes the secretion of GH/IGF-1, and when thyroid hormone levels were decreased by the use of ATD, GH and IGF-1 levels were also decreased, suggesting that thyroid hormones may influence the synthesis and secretion of GH/IGF-1. The use of ATD to control thyrotoxicosis before TSS is not only beneficial in reducing the risk of anesthesia but may help to promote biochemical control of GHPA. On the other hand, high levels of GH/IGF-1 in patients with GHPA also exacerbate GD hyperthyroidism, which is ameliorated by a decrease in GH/IGF-1 levels by TSS or SSA treatment, suggesting that the GH-IGF-1 axis promotes growth, thyroid function, and thyroid hormone metabolism.

Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes.

OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.

Feasibility study on individualized management of postoperative patients with differentiated thyroid cancer based on internet and programming technology.

PURPOSE: To explore the feasibility of individualized management of postoperative patients with differentiated thyroid cancer by a mode based on internet and programming technology. METHODS: The enrolled patients were randomly divided into the study group and the control group. The study group used a mobile application to collect patient information, evaluate the risk of thyroid cancer recurrence and levothyroxine medication risk, develop individual thyrotropin control targets, and push levothyroxine adjustment recommendations to patients. In the control group, the traditional outpatient follow-up mode was used. RESULTS: Two hundred patients were randomly divided into the study group and the control group at a 1:1 ratio. There was no significant difference in the physical and chemical indices between the two groups at baseline. During the 1-year follow-up, there was no significant difference in the thyrotropin attainment rate, heart rate or bone mineral density between the study group and the control group. During the 2-year follow-up, the thyrotropin attainment rate of the study group was better than that of the control group. The total score of Symptom Checklist 90 of the study group was lower than the control group, and satisfaction with the treatment was significantly higher than that of the control group. CONCLUSION: The management based on the internet and programming technology is not inferior to the traditional outpatient follow-up mode, and is beneficial to improve patients' quality of life, promote the implementation of the national graded diagnosis and treatment system and the grassroots management of chronic diseases.

Intracranial germ cell tumors: a view of the endocrinologist.

Intracranial germ cell tumors (iGCTs) are rare malignant neoplasms that mainly affect children and adolescents. The incidence, clinical presentation, and prognosis of iGCTs exhibit high heterogeneity. Previous studies have primarily focused on eliminating tumors, reducing tumor recurrence, and improving survival rates, while neglecting the impact of the tumors and their treatment on neuroendocrine function. Throughout the entire course of the disease, neuroendocrine dysfunction may occur and is frequently overlooked by oncologists, neurosurgeons, and radiologists. Endocrinologists, however, are more interested in this issue and have varying priorities at different stages of the disease. From onset to the diagnostic phase, most patients with iGCTs may present with symptoms related to impaired neuroendocrine function, or even experience these symptoms as their first indication of the condition. Particularly, a minority of patients with sellar/suprasellar lesions may exhibit typical imaging features and elevated tumor markers long after the onset of initial symptoms. This can further complicate the diagnosis process. During the peritumor treatment phase, the neuroendocrine function shows dynamic changes and needs to be evaluated dynamically. Once diabetes insipidus and dysfunction of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes occur, hormone replacement therapy should be administered promptly to ensure successful tumor treatment for the patient. Subsequently, during the long-term management phase after the completion of tumor treatment, the evaluation of growth and development as well as corresponding hormone replacement therapy are the most concerning and complex issues. Thus, this paper reviews the interest of endocrinologists in iGCTs at different stages.

Comparison of different predominant lesions in intracranial bifocal germ cell tumors to predict neuroendocrine outcomes.

Purpose: Intracranial germ cell tumors frequently arise from the midline of the brain, occasionally presenting as bifocal diseases. The predominant lesion might affect clinical characteristics and neuroendocrine outcomes. Method: A retrospective cohort study involving 38 patients with intracranial bifocal germ cell tumors was performed. Result: Twenty-one patients were assigned to the sellar-predominant group, while the other 17 patients were assigned to the non-sellar-predominant group. Differences in gender ratio, age, manifestation, the incidence of metastasis, the incidence of elevated tumor markers, human chorionic gonadotropin levels in serum and in cerebrospinal fluid, diagnostic method, and tumor type were not significant between the sellar-predominant group and the non-sellar-predominant group. Before treatment, the sellar-predominant group had a higher incidence of adenohypophysis hormone deficiencies and central diabetes insipidus than those of the non-sellar-predominant group, without significant differences. After multidisciplinary therapy, the sellar-predominant group also had a higher incidence of adenohypophysis hormone deficiencies and central diabetes insipidus than those of the non-sellar-predominant group. The differences in the hypothalamic-pituitary-adrenal (HPA) axis impairment (P = 0.008), hypothalamic-pituitary-thyroid (HPT) axis impairment (P = 0.048), and hypothalamic-pituitary-gonad (HPG) axis impairment (P = 0.029) were significant between sellar-predominant group and non-sellar-predominant group, while the others were not. At median 6 (3, 43) months of follow-up visit, sellar-predominant group had a higher incidence of adenohypophysis hormone deficiencies than those of non-sellar-predominant group. The differences in the HPA impairment (P = 0.002), HPT impairment (P = 0.024), and HPG impairment (P < 0.000) were significant, while the others were not. Further comparison of the neuroendocrine function between different subtypes of sellar-predominant patients indicated that the differences in adenohypophysis hormone deficiencies and central diabetes insipidus were not significant between the two subtype groups. Conclusion: Bifocal patients with different predominant lesions present similar manifestations and neuroendocrine disorders before treatment. Non-sellar-predominant patients would have better neuroendocrine outcomes after tumor treatment. The distinction of the predominant lesion in patients with bifocal intracranial germ cell tumor plays a valuable role in predicting neuroendocrine outcomes, as well as in optimizing long-term neuroendocrine management during survival time.

Central hyperthyroidism combined with Graves' disease: case series and review of the literature.

Background: Central hyperthyroidism is characterized by elevated free thyroid hormone and unsuppressed thyroid-stimulating hormone (TSH), and this laboratory feature includes TSH-secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone ß (RTHß). Central hyperthyroidism combined with Graves' disease (GD) has been rarely reported. Case Report: We describe three patients with TSHoma combined with GD and one patient with GD combined with RTHß and pituitary adenoma. These three patients with TSHoma combined with GD showed elevated thyroid hormone, while TSH level was normal or elevated, and TSH receptor antibodies were positive. After thyrotoxicosis was controlled, they all underwent transsphenoidal surgery. We also describe a patient with an initial presentation of GD who developed hypothyroidism after anti-hyperthyroidism treatment and TSH was inappropriately significantly increased. His head magnetic resonance imaging revealed a pituitary adenoma. Genetic testing confirmed a heterozygous mutation in the thyroid hormone receptor ß gene c.1148G>A (p.R383H). After levothyroxine and desiccated thyroid tablet treatment, the TSH level decreased to normal. Conclusion: These four cases highlight the need to consider the diagnosis of GD combined with central hyperthyroidism when faced with inconsistent thyroid function test results, illuminating the specific diagnostic and therapeutic challenges of coexisting primary and central hyperthyroidism. Finally, we propose clinical management for central hyperthyroidism combined with GD.

Benefits and risks evaluation of recombinant human growth hormone replacement therapy in children with GHD after craniopharyngioma surgery.

OBJECTIVES: Childhood-onset craniopharyngiomas (CPs) have a high incidence of growth hormone deficiency (GHD) leading to growth failure and metabolic disorders. We aim to evaluate the benefits and risks of recombinant human growth hormone replacement therapy (GHRT) in postoperative children. METHODS: We retrospectively analyzed auxological and metabolic parameters and adverse events before and after GHRT of 44 children after CP surgery. RESULTS: The median duration of GHRT was 24 months (IQR, 12.5-36). Growth velocity (GV) increased significantly after different treatment duration (TD) compared with baseline (p<0.001) and attained the greatest GV of 12.06 ± 4.16 cm/year at TD6. The mean height standard deviation score (HtSDS) from -3.20 ± 1.16 at baseline improved significantly to -1.51 ± 1.32 at TD36 (p<0.001). There were significant increases in insulin-like growth factor-1 SDS (IGF-1SDS), insulin-like growth factor binding protein 3 SDS (IGFBP-3SDS), bone age (BA), and BA/chronological age (CA) (p<0.05). There was a significant reduction in waist-to-hip ratio (WHR), but there were no significant changes in weight SDS (WtSDS) or BMISDS. Low-density lipoprotein-cholesterol (LDL-C) levels and the incidence of hypercholesterolemia decreased (p<0.05). Three patients (6.8%) had tumor recurrence after 15, 30, and 42 months, respectively. A patient had residual tumor enlargement after 3 months. There was no adverse influence on glucose metabolism or any severe adverse events. CONCLUSIONS: GHRT effectively accelerates GV, increases HtSDS, and improves lipid profiles without unfavorable effects on glucose metabolism. The benefits are clear and the risks of adverse events are low.

Uric acid levels correlate with disease activity in growth hormone-secreting pituitary adenoma patients.

Objective: Few studies reported the effects of growth hormone-secreting pituitary adenoma (GHPA) on uric acid (UA) metabolism and the relationship between growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels and UA are controversial. This study aimed to evaluate the relationship between IGF-1 and UA in patients with GHPA and to further clarify whether UA levels are associated with GHPA disease activity by follow-up. Methods: A longitudinal study of 424 GHPA patients presenting to Beijing Tiantan Hospital, Capital Medical University between January 2015 and January 2023 was conducted. Spearman's correlation tests were performed to examine the relationship between IGF-1 and UA at baseline. Univariate and multivariate linear regression analysis was conducted to investigate the independent association between UA and IGF-1. Changes in postoperative IGF-1 and UA levels were followed prospectively, and the differences in UA levels between the biochemical remission and nonremission groups were compared. Results: At baseline, male patients, the lower the age, the higher the IGF-1 and body mass index (BMI), and the higher the UA levels. IGF-1 was significantly associated with UA after controlling for sex, age, and BMI (r = 0.122, P = 0.012). In adjusted multiple linear regression analysis, IGF-1 was independently associated with UA, and UA levels increased significantly with increasing IGF-1. During postoperative follow-up, UA decreased gradually as IGF-1 levels decreased. At 12 months postoperatively, UA levels were significantly lower in the biochemical remission group than in the nonremission group (P = 0.038). Conclusions: In patients with GHPA, UA levels are associated with disease activity. Changes in UA levels should be taken into account in the comprehensive treatment of GHPA, patients presenting with HUA should be given lifestyle guidance and appropriate urate-lowering treatment according to their condition to better improve their prognosis.

Characteristics and factors influencing hypothalamic pituitary dysfunction in patients with craniopharyngioma.

Background: Craniopharyngioma is a benign tumor originating from the sellar region. Damages in this area caused by the tumor itself, surgery, or radiotherapy may result in severe hypothalamic-pituitary dysfunction (HPD) and eventually lead to a significant impairment in the long-term quality of life of patients. This study aimed to investigate the characteristics of HPD in patients with adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) and to identify the factors affecting HPD after surgery. Methods: In this single-center retrospective study, a total of 742 patients with craniopharyngioma were included. The neuroendocrine function of these patients before and after surgery was investigated. The differences in hypothalamic-pituitary function between the ACP and PCP groups were compared. The factors influencing the aggravation of HPD after surgery were identified. Results: The median follow-up after surgery was 15 months. Before surgery, the proportion of patients with diabetes insipidus (DI) and hyperprolactinemia in the PCP group was significantly higher than that in the ACP group (P<0.01), and the proportion of patients with adrenocortical hypofunction in the PCP group was significantly lower than that in the ACP group (P=0.03). Most cases of ACP originated in the sellar region, while most cases of PCP originated in the suprasellar region (P<0.01). More patients experienced adenohypophyseal hypofunction, DI, and hypothalamic obesity at postoperative follow-up than at onset in both the ACP and PCP groups (both P<0.01), with a higher increase observed in the ACP group (P<0.01). Older age at CP onset, tumor recurrence or progression, and ACP type were risk factors for postoperative aggravation of HPD in CP patients. Conclusion: Surgical treatment significantly aggravated HPD in both the ACP and PCP groups, but the specific characteristics and risk factors leading to aggravation were different between the two groups.

Prevalence and Clinical Characteristics of PDX1 Variant Induced Diabetes in Chinese Early-Onset Type 2 Diabetes.

CONTEXT: Maturity-onset diabetes of the young 4 (MODY4) is caused by mutations of PDX1; its prevalence and clinical features are not well known. OBJECTIVE: This study aimed to investigate the prevalence and clinical characteristics of MODY4 in Chinese people clinically diagnosed with early-onset type 2 diabetes (EOD), and to evaluate the relationship between the PDX1 genotype and the clinical phenotype. METHOD: The study cohort consisted of 679 patients with EOD. PDX1 mutations were screened by DNA sequencing, and their pathogenicity was evaluated by functional experiments and American College of Medical Genetics and Genomics guidelines. MODY4 was diagnosed in individuals with diabetes who carry a pathogenic or likely pathogenic PDX1 variant. All reported cases were reviewed for analyzing the genotype-phenotype relationship. RESULT: 4 patients with MODY4 were identified, representing 0.59% of this Chinese EOD cohort. All the patients were diagnosed before 35 years old, either obese or not obese. Combined with previously reported cases, the analysis revealed that the carriers of homeodomain variants were diagnosed earlier than those with transactivation domain variants (26.10 ± 11.00 vs 41.85 ± 14.66 years old, P < .001), and the proportions of overweight and obese individuals with missense mutation were higher than those with nonsense or frameshift mutations (27/34 [79.4%] vs 3/8 [37.5%], P = .031). CONCLUSION: Our study suggested that MODY4 was prevalent in 0.59% of patients with EOD in a Chinese population. It was more difficult to identify clinically than other MODY subtypes owning to its clinical similarity to EOD. Also, this study revealed that there is some relationship between genotype and phenotype.

Abnormal glucose regulation in patients with acute stroke across China: prevalence and baseline patient characteristics.

BACKGROUND AND PURPOSE: The prevalence of diabetes is high among patients with ischemic stroke. However, the prevalence of abnormal glucose regulation and clinical characteristics among patients with stroke in the Chinese population is uncertain. We investigated the prevalence of prediabetes and diabetes in Chinese patients after stroke onset in a nationwide cohort study and investigated abnormal glucose regulation in patients with acute stroke across China (ACROSS-China). METHODS: The ACROSS-China study consecutively recruited patients hospitalized for acute stroke in 2008 to 2009 and investigated the prevalence of impaired glucose tolerance and diabetes among the patients on day 14 after stroke onset. Oral glucose tolerance test was performed in the diagnosis of abnormal glucose regulation. RESULTS: The prevalence of abnormal glucose regulation was 68.7% among all the patients with stroke. Diabetes was identified in 42.3% of all the patients (45.8% for patients with ischemic stroke, 31.2% for patients with intracerebral hemorrhage, and 26.4% for patients with subarachnoid hemorrhage, respectively). Prediabetes (impaired fasting glucose and impaired glucose tolerance) was identified in 26.4% of all the patients with stroke. The prevalence of diabetes and impaired glucose tolerance was the highest in the patients with atherothrombotic infarction (73.4%). CONCLUSIONS: The prevalence of abnormal glucose regulation was high in Chinese patients with acute stroke, especially in patients with atherothrombotic infarction. Oral glucose tolerance test identified a large percentage of patients with newly diagnosed diabetes or impaired glucose tolerance after stroke onset.

Pituitary Stalk Germ Cell Tumors: Retrospective Case Series and Literature Review.

Objective: Intracranial germ cell tumors with isolated pituitary stalk involvement are rare. Early recognition and long-term monitoring deserve further exploration. Methods: A retrospective study reviewing eleven intracranial germ cell tumor patients with isolated pituitary stalk involvement was performed. Results: Seven boys and four girls who presented with a hyperintense pituitary stalk on postcontrast T1-weighted magnetic resonance imaging without a posterior pituitary signal were included. The average maximum width of the pituitary stalk was 5.2 ± 1.6 mm. Polydipsia and polyuria occurred in all patients, followed by growth retardation, fatigue, and amenorrhoea. Eight patients (72%) had concomitant partial anterior pituitary hormone deficiency. Seven patients initially had elevated human chorionic gonadotropin levels. After chemoradiotherapy, ten patients attended follow-up. Central diabetes insipidus remained in all survivors, and four (40%) of them had concomitant partial anterior pituitary hormone deficiency, primarily of growth hormone and insulin-like growth factor-1. The causes of the delayed diagnosis of previous studies were mainly negative tumor markers and the initial pathological diagnosis of autoimmune diseases. Conclusion: Isolated pituitary stalk lesions could be a signal of intracranial germ cell tumors, especially coexisting with diabetes insipidus, hypopituitarism, and a worse response to glucocorticoid therapy. Negative results of tumor markers and pathology could not exclude the diagnosis. Chemoradiotherapy is an effective therapy, leaving mild-t-moderate hypothalamus-pituitary dysfunction. This rare neuroimaging feature may be used as a factor to predict long-term neuroendocrine outcomes.