1.Comparison of coagulation function between adrenocorticotropic hormone independent Cushing syndrome and nonfunctional adrenal adenoma and its influence factors.
Wei WANG ; Jia Ning WANG ; Wei YU ; Sai Nan ZHU ; Ying GAO ; Jun Qing ZHANG
Journal of Peking University(Health Sciences) 2023;55(6):1062-1067
OBJECTIVE:
To investigate the coagulation function indicators and identify influence factors of hypercoagulability in patients with adrenocorticotropic hormone (ACTH) independent Cushing syndrome (CS).
METHODS:
In our retrospective study, the electronic medical records system of Peking University First Hospital was searched for the patients diagnosed with ACTH independent CS on discharge from January 2014 to June 2019. Nonfunctional adrenal adenoma patients were chosen as control group and matched 1 ∶1 by body mass index (BMI), gender, and discharge date. Clinical features and coagulation function indicators were compared between the two groups.
RESULTS:
In the study, 171 patients were included in each group. Compared with control group, activated partial thromboplastin time (APTT), and prothrombin time (PT) in ACTH independent CS group were significantly lower [(29.22±3.39) s vs. (31.86±3.63) s, P < 0.001; (29.22±3.39) s vs. (31.86±3.63) s, P < 0.001], and both D-dimer and fibrin degradation products (FDP) levels were significantly higher (P < 0.05). Percentage of APTT levels under the lower limit of reference range in the CS patients was significantly higher than that in nonfunctional group (21.6% vs. 3.5%, P < 0.001). Percentage of D-dimer levels over the upper limit of reference range in the CS patients was significantly higher than that in nonfunctional group (13.5% vs. 6.6%, P=0.041). There were three patients with deep venous thrombosis and one patient with pulmonary embolism in CS group, however none was in control group. The area under curve (AUC) of serum cortisol rhythm (8:00, 16:00 and 24:00) levels was negatively associated with the levels of PT (r=-0.315, P < 0.001) and APTT (r=-0.410, P < 0.001), and positively associated with FDP (r=0.303, P < 0.001) and D-dimer levels (r=0.258, P < 0.001). There were no differences in coagulation function indicators among different histopathologic subgroups (adrenocortical adenoma, adrenocortical hyperplasia, oncocytic adenoma, adrenocortical carcinoma). With Logistic regression analysis, the AUC of cortisol and glycosylated hemoglobin A1c (HbA1c) levels were independent risk factors for hypercoagulability in the ACTH independent CS patients (P < 0.05).
CONCLUSION
ACTH independent CS patients were more likely in hypercoagulable state compared with nonfunctional adrenal adenoma, especially in ACTH independent CS patients with higher levels of cortisol AUC and HbA1c. These patients should be paid attention to for the hypercoagulability and thrombosis risk.
Humans
;
Cushing Syndrome/complications*
;
Adrenocortical Adenoma/complications*
;
Adrenocorticotropic Hormone
;
Hydrocortisone
;
Retrospective Studies
;
Glycated Hemoglobin
;
Adrenal Cortex Neoplasms/diagnosis*
;
Adenoma/diagnosis*
;
Thrombophilia/complications*
2.Hypothalamic-Pituitary-Adrenal axis activity in SARS-CoV-2 infected noncritically ill hospitalized patients
Hurjahan Banu ; Nusrat Sultana ; Md Shahed Morshed ; MA Hasanat ; Ahmed Abu Saleh ; Shohael Mahmud Arafat
Journal of the ASEAN Federation of Endocrine Societies 2023;38(2):65-70
Objectives:
This study determined the baseline hormonal levels of the hypothalamic-pituitary-adrenal axis and their associated factors in noncritically ill hospitalized patients with coronavirus disease 2019 (COVID-19).
Methodology:
This cross-sectional observational study was carried out in 91 noncritical RT-PCR-confirmed COVID-19 patients (18-65 years) recruited consecutively from the COVID unit, of two tertiary care hospitals over a period of six months. After screening for exclusion criteria relevant history and physical examinations were done, and blood was drawn between 07:00 am to 09:00 am in a fasting state to measure serum cortisol and plasma adrenocorticotropic hormone (ACTH) by chemiluminescent microparticle immunoassay.
Result:
Of 91 patients, 54, 26, and 11 had mild, moderate, and severe disease respectively. Median values of serum cortisol (p=0.057) and plasma ACTH (p=0.910) were statistically similar among the severity groups. Considering cortisol cut-off of 276 nmol/L (<10 μg/dL), the highest percent of adrenal insufficiency was present in severe (27.3%), followed by mild (25.9%) and least in moderate (3.8%) COVID-19 cases. Using the cortisol/ACTH ratio >15, only 6.6% had enough reserve.
Conclusions
The adrenocortical response was compromised in a significant percentage of noncritically ill hospitalized patients with COVID-19, which is unrelated to infection severity, with greater percentages present in severely infected cases.
Hydrocortisone
;
Adrenocorticotropic Hormone
;
SARS-CoV-2
;
COVID-19
3.Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension.
Zhen Cheng YAN ; Nan JIANG ; He Xuan ZHANG ; Qing ZHOU ; Xiao Li LIU ; Fang SUN ; Ruo Mei YANG ; Hong Bo HE ; Zhi Gang ZHAO ; Zhi Ming ZHU
Chinese Journal of Cardiology 2023;51(11):1152-1159
Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.
Male
;
Humans
;
Cushing Syndrome/complications*
;
Hydrocortisone
;
Adrenal Gland Neoplasms/surgery*
;
Feasibility Studies
;
Blood Glucose
;
Hyperplasia/complications*
;
Hypertension/complications*
;
Adenoma/complications*
;
Body Weight
;
Catheters/adverse effects*
4.Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension.
Zhen Cheng YAN ; Nan JIANG ; He Xuan ZHANG ; Qing ZHOU ; Xiao Li LIU ; Fang SUN ; Ruo Mei YANG ; Hong Bo HE ; Zhi Gang ZHAO ; Zhi Ming ZHU
Chinese Journal of Cardiology 2023;51(11):1152-1159
Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.
Male
;
Humans
;
Cushing Syndrome/complications*
;
Hydrocortisone
;
Adrenal Gland Neoplasms/surgery*
;
Feasibility Studies
;
Blood Glucose
;
Hyperplasia/complications*
;
Hypertension/complications*
;
Adenoma/complications*
;
Body Weight
;
Catheters/adverse effects*
5.Effects of comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome.
Shun Tang LI ; Yuan LIN ; Bin Xian OU ; Da En LIU ; De Hui LI ; Qing Wen NONG ; Ya Jun WU ; Shu Mei QIU ; Zhen Xing HUANG
Chinese Journal of Burns 2022;38(6):512-519
Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.
Adrenocorticotropic Hormone
;
China
;
Cushing Syndrome/surgery*
;
Female
;
Gout
;
Humans
;
Hydrocortisone
;
Iatrogenic Disease
;
Male
;
Skin, Artificial
;
Wound Infection
6.The Development of a Protocol for Critical Illness-Related Corticosteroid Insufficiency (CIRCI) at a Tertiary Hospital
Anna Elvira Arcellana ; Kenneth Wilson Lim ; Marlon Arcegono ; Cecilia Jimeno
Journal of the ASEAN Federation of Endocrine Societies 2022;37(1):14-23
Objectives:
The diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) remains a challenge. This initiative aimed to develop a protocol for the diagnosis and management of CIRCI which will facilitate informed decision-making among clinicians through consensus-building among a multi-disciplinary team.
Methodology:
This was a single-center, qualitative study which utilized the modified Delphi method, consisting of a sequential iterative process with two rounds of voting. A cut-off value of 70% was set as the threshold for reaching consensus.
Results:
The protocol on the diagnosis and management of CIRCI was approved after two rounds of voting, with all the components reaching 83.3%-100% agreement. This protocol on CIRCI provided a framework for the clinical approach to refractory shock. It was advocated that all cases of probable CIRCI should immediately be started on hydrocortisone at 200 mg/day. The definitive diagnosis of CIRCI is established through a random serum cortisol <10 mcg/dL or increase in cortisol of <9 mcg/dL at 60 minutes after a 250 mcg ACTH stimulation test in patients with indeterminate random cortisol levels
Conclusion
The presence of refractory shock unresponsive to fluid resuscitation and vasopressors should warrant the clinical suspicion for the existence of CIRCI and should trigger a cascade of management strategies.
Shock
;
Adrenal Cortex Hormones
;
Hydrocortisone
7.Factors associated with dietary behaviour among patients With Type 2 Diabetes Mellitus in rural Indonesia
Anggraini Dwi Kurnia ; Nur Lailatul Masruroh ; Nur Melizza ; Yoyok Bekti Prasetyo ; Herdianti Nur Hidayani
Journal of the ASEAN Federation of Endocrine Societies 2022;37(2):60-64
Background:
Type 2 Diabetes Mellitus (T2DM) is one of the fastest-growing diseases and most serious major health problems worldwide. Few studies have focused on the association of social support with diabetes-related dietary behaviour.
Objective:
To examine the relationship between social support and dietary behaviour among patients with diabetes in a rural area of Indonesia.
Methodology:
This was a descriptive cross-sectional study that included 120 physically healthy patients above 18 years old with T2DM for at least 6 months. Data analysis was done using a stepwise regression model.
Results:
The mean age was 61.97 years (SD = 7.85, range = 52-74); 86.7% of the participants were females. Social support (β = 0.272, p = <0.001), diabetes medications (β = 0.169, p = 0.003), duration of diabetes (β = 0.118, p = 0.0047), and presence of diabetes complications (β = 0.197, p = 0.008) were significant predictors of dietary behaviour and accounted for 34.2% of the variance.
Conclusions
Social support, diabetes medications, presence of diabetes complications, and duration of diabetes were associated with improved dietary behaviour. Therefore, social support should be considered when designing dietary interventions for patients with type 2 diabetes mellitus.
Shock
;
Adrenal Cortex Hormones
;
Hydrocortisone
8.Chronic psychological stress exacerbates aortic medial calcification via glucocorticoids.
Yan-Qing LI ; Pan-Na HUANG ; Hao-Zhe ZHANG ; Lu-Yu HAN ; Ruo-Xiang MIAO ; Wan-Yun FENG ; Hua PAN ; Lin FENG ; Xin-Hua WU ; Juan HE ; Xu TENG ; Xiao-Ning WANG
Acta Physiologica Sinica 2022;74(6):927-938
Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D3 (VitD3) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD3, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD3, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.
Rats
;
Animals
;
Glucocorticoids/metabolism*
;
Rats, Sprague-Dawley
;
Nicotine/metabolism*
;
Hydrocortisone/metabolism*
;
Muscle, Smooth, Vascular
;
Dexamethasone/metabolism*
;
Vascular Calcification/metabolism*
;
Myocytes, Smooth Muscle/metabolism*
;
Cells, Cultured
9.Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases.
Yang Chun GU ; Ying LIU ; Chao XIE ; Bao Shan CAO
Journal of Peking University(Health Sciences) 2022;54(2):369-375
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*
10.Effect of wheat-grain moxibustion on the expression of 5-HT and cortisol in the serum, and MR and GR in the hippocampus in rats with hypothyroidism complicated with depression.
Ji-Yu ZHAO ; Jing YAN ; Hong-Yang WANG ; Qing-Qing LIU ; Tian-Sheng ZHANG ; Chong-Yao HAO
Chinese Acupuncture & Moxibustion 2022;42(5):525-532
OBJECTIVE:
To observe the effect of wheat-grain moxibustion on behavior, 5-hydroxytryptamine (5-HT) and cortisol in the serum, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus in rats with hypothyroidism complicated with depression, and to explore the possible mechanism of wheat-grain moxibustion on improving depression in rats with hypothyroidism.
METHODS:
A total of 32 SPF SD rats were randomly divided into a blank group, a model group, a medication group and a wheat-grain moxibustion group, 8 rats in each group. Except for the blank group, the rats in the remaining groups were treated with intragastric administration of 0.1% propylthiouracil (PTU) suspension at 1 mL/100 g, once a day for 4 weeks to establish the rat model of hypothyroidism, and whether the rats were accompanied with depression-like behavior determined through behavioristics evaluation. The rats in the medication group were intervened with euthyrox at 0.9 mL/100 g, once a day, for 4 weeks; the rats in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Mingmen" (GV 4), "Shenshu" (BL 23) and "Pishu" (BL 20), 7 cones each acupoint, once a day, six times a week for 4 weeks. After the intervention, the depression status was observed by behavioristics test; the contents of thyroid stimulating hormone (TSH), total thyroxine (TT4), 5-HT and cortisol in the serum were detected by ELISA; the protein expressions of MR and GR in hippocampus were detected by Western blot; the expressions of MR mRNA and GR mRNA in the hippocampus were detected by real-time PCR.
RESULTS:
Before the intervention, compared with the blank group, the scores of open field test (OFT) were decreased and the immobility time of tail suspension test (TST) was prolonged (P<0.05); the serum TSH contents were increased and TT4 contents were decreased (P<0.01) in the other three groups. After the intervention, compared with the model group, the vertical score of OFT was increased and the immobility time of forced swimming test (FST) was prolonged in the medication group (P<0.05), while the scores of three items of OFT were increased (P<0.05, P<0.01), and the immobility time of FST and TST was shortened in the wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the medication group, the immobility time of TST and FST in the wheat-grain moxibustion group was shorter (P<0.05, P<0.01). Compared with the blank group, in the model group, the contents of serum TSH and cortisol were increased (P<0.01, P<0.001), while the contents of serum TT4 and 5-HT were decreased (P<0.01, P<0.001). Compared with the model group, the contents of serum TT4 and 5-HT were increased, while the contents of serum TSH and cortisol were decreased in the medication group and wheat-grain moxibustion group (P<0.01, P<0.05). Compared with the blank group, the protein and mRNA expression of MR, GR in the hippocampus in the model group was decreased (P<0.01, P<0.05, P<0.001); compared with the model group, the protein and mRNA expression of MR in the hippocampus in the medication group were increased (P<0.05), and the protein expression of MR, GR and mRNA expression of MR in the hippocampus in the wheat-grain moxibustion group were increased (P<0.05, P<0.01). Compared with the medication group, the expression of MR mRNA in the wheat-grain moxibustion group was increased (P<0.05).
CONCLUSION
Wheat-grain moxibustion could significantly improve thyroid function and depression in rats with hypothyroidism. Its mechanism may be related to up-regulating the protein and mRNA expression of MR and GR in the hippocampus, and then affecting the expression of serum cortisol and 5-HT.
Acupuncture Points
;
Animals
;
Depression/therapy*
;
Hippocampus/metabolism*
;
Hydrocortisone/metabolism*
;
Hypothyroidism/therapy*
;
Moxibustion
;
RNA, Messenger/metabolism*
;
Rats
;
Rats, Sprague-Dawley
;
Receptors, Glucocorticoid/metabolism*
;
Receptors, Mineralocorticoid/metabolism*
;
Serotonin
;
Thyrotropin/metabolism*
;
Triticum/metabolism*


Result Analysis
Print
Save
E-mail