OBJECTIVE

This study determined the incidence of perioperative complications associated with routine preoperative glucocorticoid use in patients undergoing pituitary surgery with normal preoperative hypothalamo-pituitary-adrenal axis (HPA axis).

From 2011-2021 retrospective chart review, 243 patients undergoing pituitary surgery with normal preoperative HPA axis were analyzed into 2 groups: 1) with preoperative steroids and 2) without preoperative steroids.  Development of postoperative complications was subsequently evaluated.

Incidence of primary composite postoperative complications of in-hospital mortality, postoperative infection and postoperative diabetes insipidus (DI) was significantly increased among those who had preoperative steroids compared to those without (58.33% versus 33.33%, p-value 0.004)  with an adjusted odds ratio of 2.90 (CI 1.29 to 6.53, p-value 0.010). Among the components of the composite outcome, post-operative DI was statistically higher among those who were given preoperative steroids (52.45% versus 28.21%, p-value 0.006) with an adjusted OR of 3.31 (CI 1.43 to 7.67, p-value 0.005). The incidence of postoperative adrenal insufficiency was similar between the 2 groups (20.15% with steroids versus 8.70% without steroids, p-value 0.258).

Among patients with normal preoperative HPA axis, the routine use of preoperative steroids is associated with an increased risk of composite postoperative complications (in-hospital mortality, postoperative infection and postoperative DI). Steroid-sparing protocol is not associated with an increased risk of postoperative AI. The findings will encourage more rational use of steroids and minimize preventable complications.

OBJECTIVES: To investigate the therapeutic effect of recombinant human growth hormone (rhGH) on children with growth hormone deficiency (GHD) and different pituitary developmental conditions. METHODS: A prospective study was performed on 90 children with GHD who were admitted to Xuchang Maternity and Child Health Hospital from June 2020 to December 2021. According to pituitary height on the median sagittal plane, they were divided into three groups: pituitary dysplasia group (n=45), normal pituitary group (n=31), and enlarged pituitary growth group (n=14). The changes in body height, growth velocity, height standard deviation score and serum levels of insulin-like growth factor binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) were examined after treatment in the above three groups, and the differences of the above indices before and after treatment were compared among the three groups. RESULTS: After treatment, all three groups had significant increases in body height, growth velocity, height standard deviation score, and the serum levels of IGFBP-3 and IGF-1 (P<0.05). Compared with the normal pituitary group, the pituitary dysplasia group and the enlarged pituitary growth group had significantly higher values in terms of the differences in body height, growth velocity, height standard deviation score, IGF-1, and IGFBP-3 before and after treatment (P<0.05). There was no significant difference in the incidence rate of adverse reactions among the three groups (P>0.05). CONCLUSIONS In GHD children with different pituitary developmental conditions, rhGH can promote bone growth and increase body height, especially in children with pituitary dysplasia and pituitary hyperplasia, with good safety.
Child ; Female ; Humans ; Pregnancy ; Body Height ; Human Growth Hormone/therapeutic use* ; Hyperplasia ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Prospective Studies ; Pituitary Gland/pathology* ; Recombinant Proteins/therapeutic use*

OBJECTIVE: To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs. METHODS: Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05). CONCLUSION JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.
Guinea Pigs ; Male ; Animals ; Glucocorticoids ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Myopia/metabolism* ; Body Weight ; RNA, Messenger ; Disease Models, Animal

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.
Humans ; Pituitary Hormones/metabolism* ; Luteinizing Hormone ; Follicle Stimulating Hormone ; Prolactin ; Pituitary Gland/metabolism*

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.
Adenocarcinoma of Lung/drug therapy* ; Adrenocorticotropic Hormone/therapeutic use* ; Aged ; B7-H1 Antigen/therapeutic use* ; Humans ; Hydrocortisone/therapeutic use* ; Hyponatremia/drug therapy* ; Hypopituitarism/drug therapy* ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Male ; Methylprednisolone/therapeutic use* ; Middle Aged ; Nausea/drug therapy* ; Pituitary Gland/pathology* ; Pneumonia ; Prednisone/therapeutic use* ; Programmed Cell Death 1 Receptor/therapeutic use* ; Prolactin/therapeutic use*

Suanzaoren Decoction(SZRD) is a classical formula for the clinical treatment of insomnia. This study analyzed the effect of SZRD on endogenous metabolites in insomnia rats based on metabonomics and thereby explored the anti-insomnia mechanism of SZRD. To be specific, DL-4-chlorophenylalanine(PCPA) was used to induce insomnia in rats. Then pathological changes of the liver and brain were observed and biochemical indexes such as 5-hydroxytryptamine(5-HT), dopamine(DA), glutamate(Glu), γ-aminobutyric acid(GABA), and norepinephrine(NE) in the hippocampus and prostaglandin D2(PGD2), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and IL-6 in the serum of rats were detected. On this basis, the effect of SZRD on PCPA-induced insomnia rats was preliminarily assessed. The metabolic profile of rat serum samples was further analyzed by ultra-performance liquid chromatography-quadrupole-time of flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS). Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined with t-test and variable importance in projection(VIP) to identify differential metabolites, and MetaboAnalyst 5.0 was employed for pathway analysis. The results showed that SZRD could improve the pathological changes of brain and liver tissues, increase the levels of neurotransmitters 5-HT, DA, and GABA in hippocampus and the level of PGD2 in hypothalamic-pituitary-adrenal axis(HPA axis), and reduce the levels of IL-1β and TNF-α in serum of insomnia rats. Metabonomics analysis yielded 12 significantly changed potential metabolites: 5-aminovaleric acid, N-acetylvaline, L-proline, L-glutamate, L-valine, DL-norvaline, D(-)-arginine, pyroglutamic acid, 1-methylguanine, L-isoleucine, 7-ethoxy-4-methylcoumarin, and phthalic acid mono-2-ethylhexyl ester(MEHP), which were related with multiple biochemical processes including metabolism of D-glutamine and D-glutamate, metabolism of alanine, aspartate, and glutamate, metabolism of arginine and proline, arginine biosynthesis, glutathione metabolism. These metabolic changes indicated that SZRD can improve the metabolism in insomnia rats by regulating amino acid metabolism.
Animals ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal ; Hypothalamo-Hypophyseal System ; Metabolomics/methods* ; Pituitary-Adrenal System ; Rats ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Tandem Mass Spectrometry

Animals ; Brain Diseases/pathology* ; Cell Cycle ; Interneurons/pathology* ; Median Eminence/pathology* ; Mice

Sleep deprivation (SD) has many deleterious health effects and occurs in more than 70% of pregnant women. However, the changes in sex hormones and relevant mechanisms after SD have not been well clarified. The aim of the present study was to explore the effects of SD on the secretion of sex hormones and the underlying mechanisms. Twelve pregnant Wistar rats were divided into control (CON, n = 6) and SD (n = 6) groups. Pregnant rats in the SD group were deprived of sleep for 18 h, and allowed free rest for 6 h, and then the above procedures were repeated until delivery. The CON group lived in a 12 h light/dark light cycle environment. Estradiol (E2) and progesterone (P4) levels were detected by enzyme-linked immunosorbent assay (ELISA), and the expression of circadian clock genes, Bmal1, Clock and Per2, in hypothalamus and pituitary gland tissues were evaluated by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The PI3K and Akt phosphorylation levels in the hypothalamic and pituitary tissues were determined by Western blot. The results showed that, compared with the CON group, the SD group exhibited significantly reduced serum E2 and P4 levels, down-regulated Bmal1, Clock and Per2 expression, as well as decreased phosphorylation levels of PI3K and Akt. But there was no significant difference of the total PI3K and Akt protein expression levels between the two groups. These results suggest that SD might affect the expression of the circadian clock genes in the hypothalamus and pituitary via PI3K/Akt pathway, and subsequently regulate the secretion of sex hormones in the pregnant rats, which hints the important roles of SD-induced changes of serum sex hormone levels in the pregnant rats.
ARNTL Transcription Factors/metabolism* ; Animals ; Circadian Clocks/physiology* ; Circadian Rhythm/genetics* ; Female ; Gene Expression Regulation/genetics* ; Gonadal Steroid Hormones/metabolism* ; Hypothalamus/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Pituitary Gland/metabolism* ; Pregnancy ; Progesterone ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Wistar ; Signal Transduction ; Sleep Deprivation/metabolism*

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive impairment. The pathogenesis of AD is complex, and its susceptibility and development process are affected by age, genetic and epigenetic factors. Recent studies confirmed that gut microbiota (GM) might contribute to AD through a variety of pathways including hypothalamic pituitary adrenal axis and inflflammatory and immune processes. CM formula, herbs, and monomer enjoy unique advantages to treat and prevent AD. Hence, the purpose of this review is to outline the roles of GM and its core metabolites in the pathogenesis of AD. Research progress of CMs regarding the mechanisms of how they regulate GM to improve cognitive impairment of AD is also reviewed. The authors tried to explore new therapeutic strategies to AD based on the regulation of GM using CM.
Humans ; Alzheimer Disease/drug therapy* ; Gastrointestinal Microbiome ; Hypothalamo-Hypophyseal System ; Medicine, Chinese Traditional ; Neurodegenerative Diseases ; Pituitary-Adrenal System ; Brain/pathology*

BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.
Animals ; Biomarkers ; Endocrine Disruptors/toxicity* ; Environmental Exposure/adverse effects* ; Environmental Pollutants/toxicity* ; Hypothalamo-Hypophyseal System/physiopathology* ; Infertility, Male/physiopathology* ; Male ; Phenols/toxicity* ; Rats ; Rats, Sprague-Dawley ; Sulfones/toxicity* ; Testis/physiopathology* ; Toxicity Tests, Chronic