OBJECTIVE: We aimed to elucidate the clinical features of pituitary immune-related adverse events (irAEs) induced by PD-1 inhibitors in a Chinese cohort and the previous literatures.
UNASSIGNED: We retrospectively analysed the clinical manifestations, laboratory examination findings, imaging features and treatments of 14 patients with pituitary irAEs caused by PD-1 inhibitors in our cohort. In addition, we searched PubMed for all English articles on pituitary irAEs induced by PD-1 inhibitors published from 1950 to 2023. A total of 47 articles were included, and the clinical characteristics of 94 patients with pituitary irAEs induced by PD-1 inhibitors in these literatures were compared to the characteristics of our cohort.
RESULTS: Among the 14 patients in our cohort with pituitary irAEs induced by PD-1 inhibitors, 12 patients (85.71%, 12/14) exhibited isolated ACTH deficiency (IAD), 100.0% (14/14) of the central adrenocortical insufficiency, and 2 patients showed more than one hypothalamic-pituitary axis injury (14.29%, 2/14). Pituitary magnetic resonance imaging in all the 14 patients showed no pituitary enlargement. In previous studies we reviewed, 82.98% of the total (78/94) presented with pituitary irAEs as IAD, 100.0% (94/94) of the central adrenocortical insufficiency, and 78.33% of the patients showed no abnormality of the pituitary gland (47/60). The pituitary irAEs caused by PD-1 inhibitors did not involve typical manifestations of hypophysitis, such as pituitary enlargement, headache, visual field defects, and multiple pituitary function impairments in our cohort and the previous literatures.
CONCLUSIONS: In our study, pituitary immune-related adverse reactions induced by PD-1 inhibitors mainly manifested isolated ACTH deficiency rather than hypophysitis.

OBJECTIVE: Pituitary abscess (PA) accounts for only 0.3-0.5% of sellar masses, and the lack of specific clinical symptoms makes diagnosing PA difficult without a surgical biopsy. In clinical practice, PA is often mistaken for cystic pituitary adenoma, craniopharyngioma, and Rathke\'s cyst. Thus, this study aims to investigate challenges in diagnosing PA and evaluate the importance of combining intraoperative surgery with postoperative antibiotic treatment.
METHODS: We conducted a retrospective analysis of 19 patients diagnosed with PA through histopathology. All patients underwent transsphenoidal surgery (TSS) for pituitary adenomas after undergoing comprehensive preoperative evaluations, including routine tests, endocrine assay, and imaging examination. Furthermore, we compared different treatments for pituitary abscess (PA) to determine the most effective approach for achieving a favorable prognosis.
RESULTS: The most prevalent symptom of PA was headache, especially in the frontal-temporal and vertex regions, ranging from mild to moderate severity. Hypopituitarism-related symptoms were also frequently observed, including hypaphrodisia, cold sensitivity, fatigue, weight loss, polyuria, and amenorrhea. Twelve patients exhibited abnormalities in endocrinology examinations. Diagnosing PA correctly is challenging. In our study, none of the patients were correctly diagnosed with PA prior to surgery, and many sellar lesions were misdiagnosed. The favorable prognosis was largely attributed to surgical intervention and active postoperative antibiotic therapy.
CONCLUSIONS: Given the lack of clarity in preoperative diagnosis, typical intraoperative findings and effective antibiotics treatment are more indicative of the correct diagnosis than other tests. In terms of therapy, optimal surgical intervention and active postoperative antibiotic treatment contribute to resolving the challenges posed by PA.

Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.
We systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.
Our study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.
Based on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.

More and more clinical evidence confirms that hypopituitary dysfunction can lead to liver cirrhosis. The causes of hypopituitary dysfunction include sellarneoplastic diseases, hereditary diseases, perinatal adverse events, etc. Clinically, growth hormone deficiency (GHD) often the first cause in hypopituitary dysfunction.Hypopituitary dysfunction, especially GHD, can lead to liver cirrhosis, which in turn can result in damage to multiple organs such as the secondary lungs, spleen, and heart.Therefore, its clinical manifestations are complex, and the patients are first diagnosed in various departments.Reliable clinical observations have shown that GH replacement therapy at the early stage of the disease can effectively prevent and reverse the progression of cirrhosis, or even avoid inappropriate or unnecessary combined transplantation of liver or liver-related organs.Multidisciplinary collaboration and attention to the new findings that hypopituitary dysfunction can lead to liver cirrhosis will help to improve the accurate diagnosis and treatment of liver cirrhosis.
越来越多的临床证据证实垂体前叶功能减退可导致肝硬化。垂体前叶功能减退病因包括鞍区肿瘤性疾病、遗传性疾病和围产期不良事件等。临床上，发生垂体前叶功能减退时，生长激素缺乏（GHD）常首当其冲。垂体前叶功能减退尤其是GHD，可导致肝硬化，随之而来又会次生肺、脾和心脏等多种器官功能受损。因此，其临床表现往往复杂多样，患者首诊科室各异。已有可靠的临床观察表明，在垂体前叶功能减退所致肝硬化早期阶段应用生长激素替代治疗可有效阻止和逆转肝硬化进程，甚或避免不恰当或不必要的肝脏或与肝脏相关器官的联合移植手术。多学科联动，知晓并重视垂体前叶功能减退可导致肝硬化的新发现，将有助于提高临床对肝硬化的精准诊治。.

Pituitary stalk interruption syndrome (PSIS) is a congenital disease commonly found in patients with combined pituitary hormone deficiency (CPHD). Most PSIS patients manifest growth retardation and delayed puberty. We report a rare case of PSIS with tall stature, liver cirrhosis and diabetes, possibly caused by an inactivating KCNJ11 gene mutation.
A 37-year-old female patient initially presented with liver cirrhosis and diabetes, without any secondary sexual characteristics. Endocrine investigation indicated CPHD. Small anterior pituitary, invisible pituitary stalk and no eutopic posterior lobe hypersignal in the sella turcica viewed in magnetic resonance imaging (MRI) confirmed the diagnosis of PSIS. Despite receiving no growth hormone or sex hormone therapy, she reached a final height of 186 cm. Liver histopathology revealed nonalcoholic fatty cirrhosis. Genetic testing identified a heterozygous p.Arg301Cys mutation in the KCNJ11 gene.
This is a rare case of PSIS with liver cirrhosis and diabetes associated with an inactivating KCNJ11 gene mutation. It\'s supposed that early hyperinsulinism caused by the KCNJ11 gene mutation, as well as delayed epiphyseal closure due to estrogen deficiency, contributed to the patient\'s exceptionally tall stature. Untreated growth hormone deficiency (GHD) resulted in increased visceral fat, leading to nonalcoholic fatty liver disease (NAFLD) and cirrhosis. The decline in β cell function with age, combined with NAFLD, may have played a role in the development of diabetes.

OBJECTIVE: To compare the effects of combined gonadotropin and pulsatile gonadotropin-releasing hormone (GnRH) therapy on spermatogenesis in patients with pituitary stalk interruption syndrome (PSIS).
METHODS: Male patients with PSIS (N = 119) were retrospectively studied. Patients received pulsatile GnRH therapy (N = 59) were divided into response and poor-response groups based on luteinizing hormone (LH) levels after 1-month treatment with a cutoff value of 1 or 2 IU/L. Participants with gonadotropin therapy were divided into human menopausal gonadotropin (hMG)/human chorionic gonadotropin (hCG) group (N = 60), and patients with pulsatile GnRH therapy were classified into GnRH group (N = 28) with treatment duration ≥6 months.
RESULTS: The overall success rates of spermatogenesis for hMG/hCG and GnRH therapy were 51.67% (31/60) vs 33.90% (20/59), respectively. GnRH group required a shorter period to induce spermatogenesis (8 vs 15 months, P = .019). hMG/hCG group had higher median total testosterone than GnRH group [2.16, interquartile range(IQR) 1.06-4.89 vs 1.31, IQR 0.21-2.26 ng/mL, P = .004]. GnRH therapy had a beneficial effect on spermatogenesis compared to hMG/hCG therapy (hazard ratio 1.97, 95% confidence interval 1.08-3.57, P = .026). In patients with pulsatile GnRH therapy, compared with the poor-response group, the response group had a higher successful spermatogenesis rate (5.00% vs 48.72%, P = .002) and higher median basal total testosterone (0.00, IQR 0.00-0.03 vs 0.04, IQR 0.00-0.16 ng/mL, P = .026) with LH = 1 IU/L as the cutoff value after 1-month pulsatile GnRH therapy.
CONCLUSIONS: Pulsatile GnRH therapy was superior to hMG/hCG therapy for spermatogenesis in patients with PSIS. Earlier spermatogenesis and higher concentrations of sperm could be obtained in the GnRH group if patients received therapy over 6 months.

Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively.
Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children\'s Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate.
The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%.
This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

BACKGROUND: Magnetic resonance imaging (MRI) has become the most important radiological procedure for diagnosing and following pituitary tumors. But previous MRI studies on pituitary adenomas are mainly focused on the posterior pituitary. Few research has been done on residual normal pituitary tissue before and after transsphenoidal surgery. This retrospective cohort study investigates the pre- and postoperative magnetic resonance imaging characteristics of normal pituitary tissues regarding transsphenoidal resection of pituitary macroadenomas.
METHODS: Pre- and postoperative magnetic resonance imaging scanning of 112 consecutive pituitary macroadenoma patients who underwent tumor resection via transsphenoidal approach was performed, and their medical records were studied.
RESULTS: On preoperative MRI, 66 cases of pituitary stalks were identifiable, 9 of them were roughly in the middle, and 57 cases showed left or right deviation, with the angle between pituitary stalks and the sagittal plane was 5.32°-64.05° (average 21.65°). Among the 57 patients with preoperative pituitary stalk deviation, 55 of the pituitary stalk deviations improved in 1 week after surgery, and 30 cases were almost in the middle in 4-6 months after operation, with the other cases get better in varying degrees. The diameter of pituitary stalk was 1.08-3.89 mm (mean 2.36 mm) in pre-operation, and 1.29-3.43 mm (mean 2.30 mm) in 4-6 months after operation. The length of pituitary stalk was 1.41-11.74 mm (mean 6.12 mm) preoperatively, 3.61-11.63 mm (mean 6.93 mm) early postoperatively, and 5.37-17.57 mm (mean 8.83 mm) in 4-6 months after operation. Pituitary stalk was thickened or compressed on preoperative MR images, and gradually recovered to normal during postoperative period. It tended to be in the middle position and its length increased gradually until 4-6 months after operation. On preoperative MRI, 69 out of 112 patients showed residual pituitary tissues (RPT)(+) on enhanced MRI. RPT were likely located above the adenomas in somatotroph adenoma patients. Morphological restitution of postoperative normal pituitary tissues was better in lateral displacement than in superior or superolateral patterns on preoperative magnetic resonance imaging. Postoperative normal pituitary tissues usually subsided directly in superior displacement pattern on preoperative MRI, while were likely to be confined in the lateral side in lateral and superolateral displacement patients. Postoperative morphologic remodeling grade of RPT was positively correlated with the maximum diameter of pituitary adenoma (p = 0.000), but not with age.
CONCLUSIONS: The larger the tumor diameter, the worse the pituitary morphological recovery after tumor resection. Relative locations of normal pituitary and adenoma tissues may be related to adenoma type and may affect postoperative reconstruction of residual normal pituitary tissues. These findings enable surgeons to distinguish pituitary tissue from residual or recurring tumor tissue on postoperative magnetic resonance imaging.

In humans and mice, loss-of-function mutations in growth hormone-releasing hormone receptor (GHRHR) cause isolated GH deficiency. The mutant GHRHR mouse model, GhrhrLit/Lit (LIT), exhibits loss of serum GH, but also fewer somatotropes. However, how loss of GHRH signaling affects expansion of stem and progenitor cells giving rise to GH-producing cells is unknown. LIT mice and wild-type littermates were examined for differences in proliferation and gene expression of pituitary lineage markers by quantitative reverse transcription polymerase chain reaction and immunohistochemistry at postnatal day 5 (p5) and 5 weeks. At p5, the LIT mouse shows a global decrease in pituitary proliferation measured by proliferation marker Ki67 and phospho-histone H3. This proliferative defect is seen in a pituitary cell expressing POU1F1 with or without GH. SOX9-positive progenitors show no changes in proliferation in p5 LIT mice. Additionally, the other POU1F1 lineage cells are not decreased in number; rather, we observe an increase in lactotrope cell population as well as messenger RNA for Tshb and Prl. In the 5-week LIT pituitary, the proliferative deficit in POU1F1-expressing cells observed neonatally persists, while the number and proliferative proportion of SOX9 cells do not appear changed. Treatment of cultured pituitary explants with GHRH promotes proliferation of POU1F1-expressing cells, but not GH-positive cells, in a mitogen-activated protein kinase-dependent manner. These findings indicate that hypothalamic GHRH targets proliferation of a POU1F1-positive cell, targeted to the somatotrope lineage, to fine tune their numbers.

The invasive behavior of nonfunctioning pituitary neuroendocrine tumors (NF-PitNEts) affects complete resection and indicates a poor prognosis. Cancer immunotherapy has been experimentally used for the treatment of many tumors, including pituitary tumors. The current study aimed to screen the key immune-related genes in NF-PitNEts with invasion.
We used two cohorts to explore novel biomarkers in NF-PitNEts. The immune infiltration-associated differentially expressed genes (DEGs) were obtained based on high/low immune scores, which were calculated through the ESTIMATE algorithm. The abundance of immune cells was predicted using the ImmuCellAI database. WGCNA was used to construct a coexpression network of immune cell-related genes. Random forest analysis was used to select the candidate genes associated with invasion. The expression of key genes was verified in external validation set using quantitative real-time polymerase chain reaction (qRT‒PCR).
The immune and invasion related DEGs was obtained based on the first dataset of NF-PitNEts (n=112). The immune cell-associated modules in NF-PitNEts were calculate by WGCNA. Random forest analysis was performed on 81 common genes intersected by immune-related genes, invasion-related genes, and module genes. Then, 20 of these genes with the highest RF score were selected to construct the invasion and immune-associated classification model. We found that this model had high prediction accuracy for tumor invasion, which had the largest area under the receiver operating characteristic curve (AUC) value in the training dataset from the first dataset (n=78), the self-test dataset from the first dataset (n=34), and the independent test dataset (n=73) (AUC=0.732/0.653/0.619). Functional enrichment analysis revealed that 8 out of the 20 genes were enriched in multiple signaling pathways. Subsequently, the 8-gene (BMP6, CIB2, FABP5, HOMER2, MAML3, NIN, PRKG2 and SIDT2) classification model was constructed and showed good efficiency in the first dataset (AUC=0.671). In addition, the expression levels of these 8 genes were verified by qRT‒PCR.
We identified eight key genes associated with invasion and immunity in NF-PitNEts that may play a fundamental role in invasive progression and may provide novel potential immunotherapy targets for NF-PitNEts.