UNASSIGNED: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1.
UNASSIGNED: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation.
UNASSIGNED: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease\'s manifestations.

Pituitary carcinoma is a condition defined by metastasis of a pituitary tumor to a distant location, and it is a very rare type of adenohypophyseal tumor. We present a case of a 29-year-old female who was followed up in our Endocrinology Department. Past medical history included the diagnosis of Cushing disease and transsphenoidal tumor resection at 12 years of age, followed by transcranial resection two years later because of persistently elevated adrenocorticotropic hormone (ACTH). Despite the surgical management, the patient persisted with increased ACTH and hypercortisolism, and, thus, bilateral adrenalectomy was performed a year later. Two years after the procedure, the patient presented with a newly diagnosed pituitary macroadenoma, and the diagnosis of Nelson syndrome was made. Linear accelerator radiotherapy was given, which reduced the size of the tumor. Later, several imaging studies showed multiple lesions on the falx cerebri, posterior clinoid process, retroclival region, cerebellopontine angle, pterygopalatine fossa, infratentorial region, and posterior ethmoidal cells. Biopsy and immunohistochemistry of the falx cerebri lesions described ACTH-producing pituitary adenocarcinoma. Treatment was given with intramuscular octreotide, dabrafenib, and trametinib. Despite persistently elevated ACTH levels, the patient has since remained clinically stable, without new development or worsening of symptoms. There are three unique aspects of our case. First, we reported an unusual presentation of this disease, since the patient in our case was a female with an early age of onset. Second, this is the first reported case demonstrating pituitary carcinoma in the falx cerebri. Third, the prognosis of pituitary carcinoma is usually very poor, and mortality is extremely high; however, the patient in our case has been followed up for seven years since the diagnosis of the metastatic lesions and has remained clinically stable.

Objective: To investigate the value of serum dehydroepiandrosterone sulfate (DHEAS) in the differential diagnosis of primary bilateral macronodular adrenal hyperplasia (PBMAH) from nonfunctional adenoma tumors (NFA), adrenocortical adenoma (ADA) and Cushing\'s disease (CD). Methods: A cross-sectional study. The clinical data of 302 patients with PBMAH, NFA, ADA and CD diagnosed and treated in the First Medical Center of PLA General Hospital from January 2010 to June 2021 were retrospectively analyzed. Among them, 97 were males and 205 were females, aged (45.7±7.2) years. The area under receiver operating characteristic (ROC) curve was used to evaluate the DHEAS ratio (serum DHEAS value divided by the lower limit of normal reference range for the corresponding age and sex) and the 8∶00 adrenocorticotropic hormone (ACTH) level in the differential diagnosis of PBMAH from NFA, ADA and CD. The maximum value of Youden index was cut-off value. Results: Among the 302 patients, 33 were in PBMAH group, 125 were in NFA group, 67 were in ADA group, and 77 were in CD group. The DHEAS ratio in CD group, NFA group, PBMAH group and ADA group decreased successively, with values of 6.34(4.44, 9.93), 3.37(2.24, 4.79), 1.14(1.04, 2.40) and 0.58(0.27, 1.05), respectively. There was statistical significance among all groups (all P<0.01). The area under the ROC curve for distinguishing PBMAH from NFA, ADA and CD were 0.803, 0.741 and 0.930, and the cut-off value were 2.59, 0.99 and 2.92, respectively. The sensitivity was 66.1%, 64.2% and 87.9%, respectively. The specificity was 81.8%, 81.2% and 85.7%. According to the level of 8∶00 ACTH, PBMAH was divided into ACTH-inhibited group (ACTH<2.2 pmol/L,n=18) and ACTH-non-inhibited group (ACTH≥2.2 pmol/L, n=15).The DHEAS ratio in ACTH-non-inhibited PBMAH group was higher than that in ACTH-inhibited PBMAH group(P<0.01).The area under ROC curve of DHEAS ratio for identifying ACTH-non-inhibited PBMAH and CD was 0.877, the cut-off value was 4.55, the sensitivity was 93.3%, and the specificity was 75.3%. If the DHEAS ratio combined with 8∶00 ACTH was used as a differential diagnostic indicator, the area under the ROC curve for distinguishing ACTH-non-inhibitory PBMAH from CD can reach 0.967, with the sensitivity of 100.0% and the specificity of 81.8%. Conclusions: DHEAS ratios is different in PBMAH, NFA, ADA and CD patients, which can assist in the differential diagnosis of PBMAH from NFA、ADA and CD patients, especially in the differential diagnosis of ACTH-non-inhibited PBMAH patients and CD patients.
目的： 探讨血清硫酸脱氢表雄酮（DHEAS）在原发性双侧肾上腺大结节样增生（PBMAH）与肾上腺无功能腺瘤（NFA）、肾上腺皮质腺瘤（ADA）、库欣病（CD）鉴别诊断中的价值。 方法： 横断面研究。回顾性分析解放军总医院第一医学中心2010年1月至2021年6月诊治的302例PBMAH、NFA、ADA、CD患者的临床资料，其中男97例，女205例，年龄（45.7±7.2）岁。采用受试者工作特征（ROC）曲线下面积评估DHEAS比值（血清DHEAS除以其相应年龄及性别正常参考值范围下限）及8点促肾上腺皮质激素（ACTH）水平鉴别诊断PBMAH与NFA、ADA、CD的效能，取约登指数最大值为cut-off值。 结果： 302例患者中PBMAH组33例，NFA组125例、ADA组67例和CD组77例。DHEAS比值在CD组、NFA组、PBMAH组及ADA组依次降低，分别为6.34（4.44，9.93）、3.37（2.24，4.79）、1.14（1.04，2.40）和0.58（0.27，1.05），各组间差异均有统计学意义（均P<0.01）。DHEAS比值将PBMAH与NFA、ADA、CD相鉴别的ROC曲线下面积分别为0.803、0.741、0.930，cut-off值分别为2.59、0.99、2.92，灵敏度分别为66.1%、64.2%、87.9%，特异度分别为81.8%、81.2%、85.7%。根据8点ACTH水平，将PBMAH分为ACTH抑制组（ACTH<2.2 pmol/L，n=18）和ACTH非抑制组（ACTH≥2.2 pmol/L，n=15），ACTH非抑制组DHEAS比值高于ACTH抑制组（P<0.01）。DHEAS比值鉴别ACTH非抑制PBMAH与CD的ROC曲线下面积为0.877，cut-off值为4.55，灵敏度93.3%，特异度75.3%。若DHEAS比值联合8点ACTH水平作为鉴别诊断指标，鉴别ACTH非抑制PBMAH与CD的ROC曲线下面积可达0.967，灵敏度100.0%，特异度81.8%。 结论： DHEAS比值在PBMAH、NFA、ADA、CD患者中存在差异，可协助PBMAH与NFA、ADA及CD的鉴别诊断，特别是在ACTH非抑制PBMAH与CD的鉴别诊断中更具有优势。.

Endogenous hypercorticism (EH) is a severe symptom complex caused by hypercortisolemia; according to the etiology, ACTH-dependent and ACTH-independent variants are distinguished, which, according to the literature, occur in 70-80% and 20-30% of cases, respectively. A rare cause of ACTH-dependent endogenous hypercorticism is ACTH-ectopic syndrome (ACTH-ES) (about 15-20% of cases). ACTH-ES is a syndrome of adrenocorticotropic hormone (ACTH) hyperproduction by neuroendocrine tumors of extrahypophyseal origin. Various tumors can secrete ACTH: bronchopulmonary carcinoid, small cell lung cancer, less frequently, thymus carcinoid, islet cell tumors and pancreatic carcinoid, medullary thyroid cancer, carcinoid tumors of the intestine, ovaries, as well as pheochromocytoma (PCC).This publication presents a clinical case of rarely detected paraneoplastic ACTH production by pheochromocytoma. The patient had clinical manifestations of hypercorticism, therefore, she applied to the Russian National Research Center of Endocrinology of the Ministry of Health of Russia. During the examination Cushing\'s syndrome (CS) was confirmed, multispiral computed tomography (MSCT) of the abdominal cavity revealed a voluminous formation of the left adrenal gland. Additional examination recorded a multiple increase in urinary catecholamine levels. Subsequently, the patient underwent left-sided adrenalectomy. The diagnosis of pheochromocytoma was confirmed morphologically, immunohistochemical study demonstrated intensive expression of chromogranin A and ACTH by tumor cells.

In this article, we will review common pituitary disorders. There are 6 hormones secreted by the anterior pituitary gland: thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, growth hormone, and prolactin. The posterior pituitary gland stores and releases the hormones made in the hypothalamus, oxytocin and antidiuretic hormone, based on the body\'s needs. This article will discuss the role of these hormones, conditions and symptoms that occur with elevated or reduced hormone levels, as well as the evaluation and treatment of these pituitary disorders.

Cushing disease is a life-threatening disorder caused by autonomous secretion of ACTH from pituitary neuroendocrine tumors (PitNETs). Few drugs are indicated for inoperative Cushing disease, in particular that due to aggressive PitNETs. To explore agents that regulate ACTH-secreting PitNETs, we conducted high-throughput screening (HTS) using AtT-20, a murine pituitary tumor cell line characterized by ACTH secretion. For the HTS, we constructed a live cell-based ACTH reporter assay for high-throughput evaluation of ACTH changes. This assay was based on HEK293T cells overexpressing components of the ACTH receptor and a fluorescent cAMP biosensor, with high-throughput acquisition of fluorescence images. We treated AtT-20 cells with compounds and assessed ACTH concentrations in the conditioned media using the reporter assay. Of 2480 screened bioactive compounds, over 50% inhibition of ACTH secreted from AtT-20 cells was seen with 84 compounds at 10 μM and 20 compounds at 1 μM. Among these hit compounds, we focused on thiostrepton (TS) and determined its antitumor effects in both in vitro and in vivo xenograft models of Cushing disease. Transcriptome and flow cytometry analyses revealed that TS administration induced AtT-20 cell cycle arrest at the G2/M phase, which was mediated by FOXM1-independent mechanisms including downregulation of cyclins. Simultaneous TS administration with a cyclin-dependent kinase 4/6 inhibitor that affected the cell cycle at the G0/1 phase showed cooperative antitumor effects. Thus, TS is a promising therapeutic agent for Cushing disease. Our list of hit compounds and new mechanistic insights into TS effects serve as a valuable foundation for future research.

UNASSIGNED: This research aims to investigate the levels of lymphocytes, immunoglobulins, and cytokines in children with infantile spasms (IS) before and after adrenocorticotropic hormone (ACTH) therapy and to explore the application of these markers in evaluating the therapeutic effects of ACTH on infantile spasms.
UNASSIGNED: From May to November 2022, 35 children initially diagnosed with IS and treated at our hospital were regarded as the observation group, and 35 healthy children who underwent physical examination at our hospital during the same period were regarded as the control group. Children in the observation group received intramuscular injections of ACTH for 2 weeks. Fasting venous blood was collected from the control group and the observation group before and after ACTH therapy. Serum levels of immunoglobulins IgG, IgA, and IgM in serum were detected by immunoturbidimetry. T-cell subsets (CD3+, CD3+CD4+, and CD3+CD8+) and B-cell subsets [CD3-CD19+ and CD3-CD16+CD56+ natural killer (NK) cells] were detected by flow cytometry, and the ratio of CD3+CD4+/CD3+CD8+ was calculated. Serum levels of interleukin-1β (IL-1β), interleukin-2R (IL-2R), and interleukin-6 (IL-6) cytokines were detected by the enzyme-linked immunosorbent assay, and changes in serum cytokine and immunoglobulin levels in the two groups were compared before therapy, whereas in observation group one, these comparisons were made both before and after ACTH therapy.
UNASSIGNED: Compared to the control group, the observation group showed significantly increased serum levels of immunoglobulins IgG and IgM before therapy, while the level of IgA was significantly decreased (p < 0.05). Also, the percentage of CD3-CD19+ B cells was significantly increased, while the percentages of CD3+ T cells and CD3+CD4+ T cells were significantly decreased (p < 0.05). The percentages of CD3+CD8+ T cells, CD3-CD16+CD56+ NK cells, and CD3+CD4+/CD3+CD8+ cells did not change significantly (p > 0.05); the levels of cytokines IL-1 β, IL-2R, and IL-6 were significantly increased (p < 0.05). Compared to levels before treatment, the serum level of immunoglobulin IgG in the observation group after ACTH therapy was significantly reduced (p < 0.05), while the IgA and IgM levels did not change significantly (p > 0.05). The percentages of CD3+ T cells and CD3+CD4+ T cells were significantly increased, while the percentages of CD3-CD16+CD56+ NK cells and CD3-CD19+ B cells were significantly decreased (p < 0.05); however, the percentages of CD3+CD8+ T cells and the CD3+CD4+/CD3+CD8+ ratio did not change significantly (p > 0.05). Furthermore, the levels of cytokines IL-1 β, IL-2R, and IL-6 were significantly reduced (p < 0.05).
UNASSIGNED: Children with IS exhibit immune dysfunction, and the changes in serological immune indices after ACTH treatment indicate that ACTH may control seizures in IS children by regulating and improving immune dysfunction. Therefore, the therapeutic effects of ACTH on IS can be evaluated by detecting the levels of cytokines and immunoglobulins.

UNASSIGNED: Infection with SARS-CoV-2 virus may result in long COVID, a syndrome characterized by symptoms such as dyspnea, cardiac abnormalities, cognitive impairment, and fatigue. One potential explanation for these symptoms is hypocortisolism.
UNASSIGNED: To evaluate the prevalence of hypocortisolism in patients with a history of COVID-19 pneumonia.
UNASSIGNED: Cross-sectional study of patients who were aged ≥18 years and had a 3-month history of radiography-confirmed COVID-19 pneumonia. Exclusion criteria included current or previous treatment with glucocorticoids and use of an oral contraceptive. Adrenal function was evaluated using a low dose (1ug) corticotropin stimulation test (CST). Serum cortisol levels were measured at 0, 30, and 60 minutes, and baseline plasma ACTH was also measured.
UNASSIGNED: Of the 41 patients enrolled, the median age was 62 years, 17 (42%) were female, and all 41 (100%) had severe pneumonia at baseline. Eleven patients (27%) had hypocortisolism, as evidenced by peak cortisol of less than 402.81 nmol/l after low dose (1 µg) CST. Of these 11 patients, 10 (91%) had secondary hypocortisolism (median ACTH 6.27 pmol/L, range 4.98-9.95 pmol/L) and one had primary hypocortisolism (mean ACTH 32.78 pmol/L). Six of the 11 patients with hypocortisolism (54.5%) reported symptoms of persistent fatigue and 5 (45.5%) required regular glucocorticoid replacement.
UNASSIGNED: Our results suggest that hypocortisolism, predominantly caused by pituitary disruption, may emerge after SARS-CoV-2 infection and should be considered in patients with a history of COVID-19 pneumonia with or without clinical hypocortisolism.

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype-a gene-by-environment interaction that leaves a lasting developmental signature.

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