Secondary adrenocortical insufficiency after treatment with retifanlimab: a case report.

With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.

Hypopituitarism with secondary adrenocortical insufficiency and arginine vasopressin deficiency due to hypophysitis after COVID-19 vaccination: a case report.

BACKGROUND: Although vaccination against coronavirus disease (COVID-19) has several side effects, hypopituitarism due to hypophysitis has rarely been reported. CASE PRESENTATION: An 83-year-old healthy woman, who had received her fourth COVID-19 vaccine dose 2 days before admission, presented to the emergency department with difficulty moving. On examination, impaired consciousness (Glasgow Coma Scale: 14) and fever were observed. Computed tomography and magnetic resonance imaging of the head revealed swelling from the sella turcica to the suprasellar region. Her morning serum cortisol level was low (4.4 µg/dL) and adrenocorticotropic hormone level was normal (21.6 pg/mL). Central hypothyroidism was also suspected (thyroid stimulating hormone, 0.46 µIU/mL; free triiodothyronine, 1.86 pg/mL; free thyroxine, 0.48 ng/dL). Secondary adrenocortical insufficiency, growth hormone deficiency, delayed gonadotropin response, and elevated prolactin levels were also observed. After administration of prednisolone and levothyroxine, her consciousness recovered. On the 7th day of admission, the patient developed polyuria, and arginine vasopressin deficiency was diagnosed using a hypertonic saline test. On the 15th day, the posterior pituitary gland showed a loss of high signal intensity and the polyuria resolved spontaneously. On the 134th day, the corticotropin-releasing hormone loading test showed a normal response; however, the thyrotropin-releasing hormone stimulation test showed a low response. The patient's disease course was stable with continued thyroid and adrenal corticosteroid supplementation. CONCLUSIONS: Herein, we report a rare case of anterior hypopituitarism and arginine vasopressin deficiency secondary to hypophysitis following COVID-19 vaccination.

Alkindi Sprinkle for Pediatric Patients With Primary Adrenocortical Insufficiency: A Narrative Review.

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.

A rare case report of reversible glucose counterregulation in an insulinoma patient with type 2 diabetes.

CONTEXT: Insulinoma is a neuroendocrine tumor derived from pancreatic ß -cells whose clinical manifestation is recurrent hypoglycemia. Insulinoma in a patient with preexisting diabetes is extraordinarily rare, and the unmasking of type 2 diabetes (T2DM) after insulinoma surgery is even rarer. CASE REPORT: This article reports a 49-year-old male patient with insulinoma that masked the diagnosis of T2DM. The patient was admitted to the hospital with symptoms of hypoglycemia, such as repeated sweating, palpitations, and asthenia for over 4 years. The patient was diagnosed with insulinoma after completing relevant examinations. The emergence of hyperglycemia after the removal of insulinoma is attributable to the coexistence of T2DM. Surprisingly, a reversible decrease in cortisol levels was observed during the diagnostic process. We searched the previously published reports of this type of case from PubMed to determine why type 2 diabetes was covered by insulinoma and why glucocorticoids decreased. CONCLUSIONS: The diagnosis of T2DM in the patient after surgery may be related to increased food intake and insulin resistance induced by hyperinsulinemia caused by long-term hypoglycemia. The reversible decrease in cortisol levels, not adrenocortical insufficiency during the diagnostic process, may be caused by a transient abnormality in glucose counterregulation.

Impact of the severity of brain injury on secondary adrenal insufficiency in traumatic brain injury patients and the influence of HPA axis dysfunction on prognosis.

OBJECTIVE: To investigate secondary adrenal insufficiency post varying traumatic brain injuries' and its impact on prognosis. METHODS: 120 traumatic brain injury patients were categorized into mild, moderate and severe groups based on Glasgow Coma Scale. Adrenal function was evaluated through testing. RESULTS: Secondary adrenal insufficiency rates were 0% (mild), 22.85% (moderate) and 44.82% (severe). Hypothalamus-pituitary-adrenal axis dysfunction rates were 14.81% (mild), 42.85% (moderate) and 63.79% (severe). Differences among groups were significant (p < .05). Patients with intact hypothalamus-pituitary-adrenal axis had shorter hospital stays and higher Glasgow Coma Scale scores. Receiver operating characteristic analysis of 24-h urinary free cortisol showed an area of 0.846, with a 17.62 µg/24h cutoff, 98.32% sensitivity and 52.37% specificity. In the low-dose adrenocorticotropic hormone test, with an 18 µg/dL cutoff, the receiver operating characteristic area was 0.546, with 46.28% sensitivity and 89.39% specificity. CONCLUSION: As traumatic brain injury severity increases, secondary adrenal insufficiency incidence rises. The low-dose adrenocorticotropic hormone test is promising for hypothalamus-pituitary-adrenal axis evaluation. Patients with hypothalamus-pituitary-adrenal dysfunction experience prolonged hospitalization and worse prognosis.

A case of central adrenocortical insufficiency with alexithymia and alexisomia.

The patient was a 27-year-old woman. Following physical examination for unconscious hypoglycemia, the patient was diagnosed with central adrenocortical insufficiency. She also had alexithymia and alexisomia. Alexisomia is the inability to recognize or describe bodily sensations. Alexithymia is the difficulty of expressing one's feelings adequately. Alexisomia can be described as impaired interoceptive awareness. She had been maltreated and emotionally abused by her parents; thus, her upbringing may have influenced the development of alexithymia and alexisomia. In addition, her upbringing may have influenced the reduced hypothalamus-pituitary-adrenal axis activity. Her failure to perceive hypoglycemic symptoms as hypoglycemia was thought to have been influenced by her alexisomia. Interestingly, her alexisomia improved with steroid replacement therapy; however, the underlying mechanism remains unclear. However, exogenous steroids can also affect interoception. The patient was diagnosed with central adrenocortical insufficiency, an endocrine disorder, suggesting that psychosomatic factors may have been related to the patient's growth history.

Pituitary Stalk Morphology as a Predictor of New-Onset Adrenocortical Insufficiency and Arginine Vasopressin Deficiency after Transsphenoidal Resections of Pituitary Macroadenomas: A Retrospective Single-Center Study with a Focus on iMRI.

BACKGROUND: A new-onset adrenocortical insufficiency (NAI) is the most critical postoperative endocrinological complication after transsphenoidal surgery for macroadenomas. Because of increased mortality risk, arginine vasopressin deficiency (AVP-D) is also a relevant postoperative complication. This study aimed to identify easy-to-acquire magnet resonance imaging (MRI) aspects of the pituitary stalk to predict these insufficiencies after transsphenoidal surgery. METHODS: Pituitary stalk morphology was reviewed intraoperatively and three months postoperatively in the MRIs of 48 transsphenoidal surgeries for macroadenomas. NAI was validated in endocrinological follow-up controls 10-14 months post-surgery. RESULTS: Intraoperative pituitary stalk diameters were 0.5 mm larger in patients who developed NAI and AVP-D. The odds ratio was 29 for NAI and 6 for AVP-D in binary regression analysis. A value of 2.9 mm was identified as the optimal cut-off for the minimal pituitary stalk diameter regarding NAI, with a high specificity of 89%. There was no difference in pituitary stalk diameter regarding these insufficiencies three months post-surgery. CONCLUSIONS: We identified an increased pituitary stalk diameter in intraoperative MRIs as a predictive factor of NAI and AVP-D after transsphenoidal surgery. These findings might improve the early detection of NAI and, thus, optimal management. However, validating these retrospective findings in prospective studies is obligatory.

Partial Sheehan's syndrome with abdominal tuberculosis presented with pancytopenia and fluctuating thyroid profile: a case report.

Sheehan's syndrome is a well-recognized cause of panhypopituitarism secondary to pituitary apoplexy, followed by postpartum hemorrhage. Depending upon the degree of ischemic injury, it can be either partial or complete. Case presentation: We report an interesting case of a 35-year-old woman admitted to our hospital with complaints of abdominal distension, which was later presumed to be due to disseminated tuberculosis (TB) after excluding the possible differentials. During the treatment course, she was going through repeated attacks of hypovolemic shock and hypoglycemia due to adrenocortical insufficiency. This, along with the history of prolonged amenorrhea 4 years back due to severe postpartum hemorrhage in her last pregnancy, has led us to our diagnosis of partial Sheehan's syndrome. After 1 month of starting steroid and anti-TB therapy, it was quite surprising when she presented with features of pancytopenia and antitubercular drug-induced hepatitis. Discussion: Sheehan's syndrome may have a varying degree of presentation depending upon the degree of damage to the pituitary gland, which includes amenorrhea, lactation failure, adrenocortical insufficiency, hyponatremia, hypoglycemia, as well as pancytopenia in some rare instances The hormone panel especially the thyroid profile should be monitored carefully. Such cases are often challenging to deal with because of their varying degrees of presentation and the delay in diagnosis due to a lack of clinical suspicion. Conclusion: Therefore, we believe that this rare presentation of pancytopenia in Sheehan's syndrome with fluctuating thyroid profile and abdominal TB in the background will let clinicians approach such a rare disease differently.

Strongyloidiasis infection in a borderline lepromatous leprosy patient with adrenocorticoid insufficiency undergoing corticosteroid treatment: a case report.

BACKGROUND: Strongyloidiasis is a soil-transmitted helminthiasis mainly caused by Strongyloides stercoralis. It is endemic to the tropics and subtropics. Sri Lanka has a 0-1.6% prevalence rate. S. stercoralis infection was identified in a 33-year-old Sri Lankan male patient treated with corticosteroids for borderline lepromatous leprosy with adrenocortical dysfunction. CASE PRESENTATION: In March 2020, a 33-year-old Sri Lankan (Sinhalese) male patient presented with watery diarrhea, lower abdominal pain, and post-prandial abdominal fullness. Previously, he was diagnosed with borderline lepromatous leprosy and was treated with rifampicin, clofazimine, and prednisolone 60 mg daily since July 2019. After developing gastrointestinal symptoms, he had defaulted leprosy treatment including the prednisolone for 3 months. Duodenal biopsy revealed numerous intraepithelial nematodes within the lumina of glands in the duodenum whose appearance favored Strongyloides. Fecal wet smear revealed numerous Strongyloidis stercoralis L1 rhabditiform larvae. Larval tracks were seen in the agar plate culture. L3 filariform larvae of Strongyloidis stercoralis were seen in the Harada-Mori culture. In addition, the short synacthen test revealed adrenocortical insufficiency, and oral hydrocortisone and fludrocortisone were started with albendazole treatment against strongyloidiasis. Fecal wet smear and culture repeated after treatment with albendazole were negative for Strongyloidis stercoralis. The patient was discharged in July 2020 on oral hydrocortisone. One month later his condition was reviewed and the repeated fecal wet smear and agar plate culture was normal. He is being followed up every 3 months. CONCLUSION: This is the first case of strongyloidiasis diagnosed in a patient with borderline lepromatous leprosy from Sri Lanka. The patient manifested symptoms of strongyloidiasis while on high-dose steroid therapy for his lepromatous reaction. Subsequently, the patient not only discontinued his steroid therapy, but also developed adrenocortical insufficiency as a complication of leprosy. Therefore, although diagnosis of strongyloidiasis was delayed, his subsequent low steroid levels probably protected him from disseminated disease. This is an interesting case where symptomatic strongyloidiasis was diagnosed in a patient who was initially treated with high-dose steroids but subsequently developed adrenocortical insufficiency. We emphasize the need to screen all patients prior to the commencement of immunosuppressive therapy.

Differentiating Immune-Related Adrenal Insufficiency From Low Cardiac Output Syndrome: A Case Report.

We report a case of a 58-year-old woman with secondary adrenocortical insufficiency due to adrenocorticotropic hormone (ACTH) deficiency after pembrolizumab treatment that required differentiation from low cardiac output syndrome. The patient had chronic heart failure due to radiation cardiomyopathy and underwent implantation of cardiac resynchronization therapy defibrillator (CRT-D). One year ago, she was diagnosed with squamous cell lung cancer and started combination therapy with carboplatin, paclitaxel, and pembrolizumab. She was hospitalized for anorexia, nausea, and hypotension. A diagnosis of secondary hypoadrenocorticism due to isolated ACTH deficiency was made, and from the course of the disease, it was diagnosed as a side effect of immune checkpoint inhibitors (ICIs). As the indications for ICIs continue to expand, it is necessary to understand the screening and management of their side effects.

Chinese primary adrenal lymphoma complicated with adrenal crisis: A case report and literature review.

Primary adrenal lymphoma (PAL) is an extremely rare malignancy, and it accounts for approximately 1% of non-Hodgkin's lymphoma (NHL). The growth of adrenal lymphoma is characterized by rapid infiltration in the adrenal gland and further involvement and metastasis in other tissues and organs. This report describes the case of a 67-year-old man with fatigue, poor appetite, and weight loss. Positron emission tomography and computed tomography (PET-CT) scan showed irregular mass-like soft tissue density shadows were noted in the bilateral adrenal glands and immunohistochemical (IHC) studies confirmed the diagnosis of PAL with multiple metastases throughout the body. This report characterizes the clinical manifestations in patients with PAL. When the disease progresses to bilateral adrenal involvement, it may be accompanied by adrenal insufficiency or even adrenal crisis occurred.

Long-acting Porcine Sequence ACTH (Acton Prolongatum) Stimulation Test is a Reliable Alternative Test as Compared to the Gold Standard Insulin Tolerance Test for the Diagnosis of Adrenal Insufficiency.

Context: As synacthen use is not licensed in India and there are concerns about the safety of the insulin tolerance test (ITT), an alternative dynamic test to diagnose adrenal insufficiency (AI) is required. Objective: The study aimed to evaluate the diagnostic performance of the Acton Prolongatum stimulation test (APST) with a standard ITT for the diagnosis of AI. Design: Prospective study comparing two diagnostic tests. Participants: Six healthy volunteers and 53 suspected or known AI patients. Measurements: Serum cortisol response to ITT and APST. Results: The median (95% confidence interval [CI]) peak cortisol levels among healthy volunteers in ITT and APST were 17 (14.58-19.08) and 30.5 (22.57-34.5) µg/dL. Of the 53 patients (age: 39.6 ± 9.38 years; females: 38 [71.1%]), 34 had AI (peak ITT serum cortisol < 14.5 µg/dL) whereas 19 had a normal hypothalamic-pituitary-adrenocortical (HPA) axis. In the receiver operator characteristic curve analysis, 60-min APST cortisol had an area under the curve of 0.984 (95% CI: 0.904-1.00, P < 0.0001). The best accuracy was obtained at a cut-off of 16.42 µg/dL (sensitivity: 97.7% [95% CI: 87.7-99.9%]; specificity: 100% [69.2-100%]). Forty-three of the 53 patients with suspected AI had hypoglycemic symptoms during ITT and two of them required intravenous dextrose, whereas, none had adverse events during APST. The ITT was incomplete in two patients whereas all completed APST. Conclusions: APST is a simple, safe, and reliable alternative to ITT for the diagnosis of AI; 60-min serum cortisol of 16.42 µg/dL in APST best distinguishes the AI patients from those with adequate cortisol response.

Hipocortisolismo hipofisario por sobrecarga férrica en un paciente conAnemia de Blackfan-Diamond / Pituitary hypocortisolism due to iron overload in a patient with Blackfan-Diamond anemia

Iron overload in the context of a Blackfan-Diamond anemia is a extremely uncommon cause of central adrenal insufficiency. We report apatient with Blackfan-Diamond anemia diagnosis during his childhood.Ten years later, as a consequence of iron overload caused by repeatedtransfusions, he developed central hypocortisolism. Blackfan-Diamondanemia is a hereditary syndrome characterized by erythroid aplasia,predisposition to hematologic and solid organ malignancies and congenital abnormalities.Endocrine complications of Blackfan-Diamond anemia are reported inthe literature and highly variable. Hypocortisolism is considered as anuncommon complication (0.7-4 %). Therefore, in a patient with repeated transfusions, we must considerer in a possible ACTH deficiency inthe context of hemochromatosis due to iron overload. (AU)

Las causas de insuficiencia adrenal de origen central son múltiples,siendo la sobrecarga férrica en el seno de una anemia de Blackfan-Diamond extremadamente infrecuente. Se presenta el caso de un pacientede 15 años diagnosticado de anemia de Blackfan-Diamond en la infancia que desarrolla hipocortisolismo de origen central como consecuencia de la sobrecarga férrica por transfusiones de repetición comotratamiento de soporte de la anemia. La anemia de Blackfan-Diamondes un síndrome hereditario caracterizado por una aplasia eritroide queconlleva un recuento reducido de glóbulos rojos, anomalías congénitasy predisposición a neoplasias hematológicas y de órganos sólidos. Laprevalencia de las complicaciones endocrinas reportadas en la literatura secundarias a esta patología es muy variable siendo el hipocortisolismo muy poco frecuente (0,7-4 %).Por ello, ante un paciente contransfusiones de repetición, debemos tener en cuenta el posible déficitde ACTH en en el contexto de una hemocromatosis por sobrecarga férrica. (AU)

A case of secondary adrenocortical insufficiency due to isolated adrenocorticotropic hormone deficiency with empty sella syndrome after pembrolizumab treatment in a patient with metastatic renal pelvic cancer.

Pembrolizumab, an anti-programmed death-1 specific monoclonal antibody is a second-line treatment for metastatic urothelial carcinoma. Physicians should be aware of adverse immune-related events associated with the use of immune checkpoint inhibitors, particularly adrenocortical insufficiency, which poses a risk of death. We report a case of secondary adrenocortical insufficiency due to isolated adrenocorticotropic hormone deficiency with empty sella syndrome after pembrolizumab treatment in a patient with metastatic renal pelvic cancer. Fortunately, a therapeutic effect was observed 4 months after discontinuation of pembrolizumab, and a durable antitumor response has persisted for 5 months.

Risk factors and predictive model of adrenocortical insufficiency in patients with traumatic brain injury.

BACKGROUND: Neuroendocrine dysfunction after traumatic brain injury (TBI) has received increased attention due to its impact on the recovery of neural function. The purpose of this study is to investigate the incidence and risk factors of adrenocortical insufficiency (AI) after TBI to reveal independent predictors and build a prediction model of AI after TBI. METHODS: Enrolled patients were grouped into the AI and non-AI groups. Fourteen preset impact factors were recorded. Patients were regrouped according to each impact factor as a categorical variable. Univariate and multiple logistic regression analyses were performed to screen the related independent risk factors of AI after TBI and develop the predictive model. RESULTS: A total of 108 patients were recruited, of whom 34 (31.5%) patients had AI. Nine factors (age, Glasgow Coma Scale [GCS] score on admission, mean arterial pressure [MAP], urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, diffuse axonal injury [DAI], and skull base fracture) were probably related to AI after TBI. Three factors (urinary volume [X 4], serum sodium level [X 5], and DAI [X 8]) were independent variables, based on which a prediction model was developed (logit P= -3.552+2.583X 4+2.235X 5+2.269X 8). CONCLUSIONS: The incidence of AI after TBI is high. Factors such as age, GCS score, MAP, urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, DAI, and skull base fracture are probably related to AI after TBI. Urinary volume, serum sodium level, and DAI are the independent predictors of AI after TBI.

Nivolumab-induced Vogt-Koyanagi-Harada-like Syndrome and Adrenocortical Insufficiency with Long-term Survival in a Patient with Non-small-cell Lung Cancer.

A 58-year-old man was diagnosed with lung adenocarcinoma with a tumor proportion score of 10%. After six cycles of second-line chemotherapy with nivolumab, he achieved a complete response (CR) but developed uveitis and sensorineural hearing disorder, which were consistent with Vogt-Koyanagi-Harada (VKH)-like syndrome. Simultaneously, pituitary adrenocortical insufficiency was identified. Nivolumab discontinuation and systemic corticosteroid administration resolved these immune-related adverse events (irAEs). The patient has maintained a CR without any chemotherapy for approximately two years. We herein report a patient with a long-term progression-free survival despite chemotherapy discontinuation due to irAEs, including VKH-like syndrome, which were appropriately managed.

Occult Adrenal Insufficiency in Renal Amyloidosis Patients.

OBJECTIVE: Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. METHODS: Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 µg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. RESULTS: Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients' stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). CONCLUSION: ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.

Adrenocortical Crisis Triggered by Levothyroxine in an Unrecognized Autoimmune Polyglandular Syndrome Type-2: A Case Report with Review of the Literature.

BACKGROUND: Autoimmune polyglandular syndrometype-2 (APS-2) is an uncommon endocrine disorder of Addison's disease with an autoimmune thyroid disorder and/or type 1 diabetes mellitus. The diagnosis is more challenging when a patient presents with nonspecific neuropsychiatric features with hypothyroidism in the setting of unrecognized Addison's disease. CASE REPORT: We report a case of subclinical autoimmune hypothyroidism presented with nonspecific neuropsychiatric symptoms precipitated by stress. Despite levothyroxine treatment, her symptoms deteriorated and she was admitted with persistent vomiting and hypovolemic shock. Clinical features and laboratory parameters were suggestive of underlying adrenocortical insufficiency. Preexisting autoimmune hypothyroidism combined with Addison's disease confirmed the diagnosis of unrecognized APS-2. She remarkably improved and her thyroid function tests also normalized with the treatment of corticosteroids only. REVIEW OF THE LITERATURE: We identified only five published case reports of our title by searching the database. Neufeld and Betterle have reported their data of APS-2 and concluded that a full- blown clinical picture of two or more components of the syndrome is like the tip of the iceberg. CONCLUSION: The patients of one major component of APS-2 should be screened for other components of the disease to pick up latent cases. Addison's disease should be ruled out in patients of hypothyroidism who are intolerant to levothyroxine.

Analysis of Drug Use in a Lung Squamous Carcinoma Patient with Immune Checkpoint Inhibitors Associated Adrenocortical Insufficiency / 中国药房

OBJECTIVE：To explore the role of clinical pharmacists in the diagnosis and tre atment of immune checkpoint inhibitor related adrenocortical insufficiency ，so as to provide reference for the diagnosis and treatment of similar cases. METHODS：A lung squamous carcinoma patient with tumor immunotherapy ，who received long-term intravenous infusion of Pembrolizumab injection ，was hospitalized for more than 10 days due to fatigue and poor appetite. The clinical pharmacists consulted the literature and evaluated the correlation of ADR on the basis of patient ’s physical examination results （plasma cortisol 16.41 nmol/L at 8：00 in the morning on the second day of admission ，adrenocorticotropic hormone 8.39 pg/mL，serum electrolyte sodium 126.00 mmol/L，chlorine 88.00 mmol/L，etc.）and medication history （receiving the treatment with immune checkpoint inhibitors）. The clinical pharmacists assisted the doctor to confirm that the patient was adrenocortical insufficiency ，and the correlation with pembrolizumab was “very likely ”. On the basis of discontinuation of pembrolizumab ，it was recommended to take Hydrocortisone tablets orally （20 mg at 8：00 in the morning and 10 mg at 4：00 in the afternoon ）for glucocorticoid physiological dose substitution therapy. Before treatment ，the patient and his families should be educated on the use of drugs ，pharmaceutical care should be implemented to evaluate the glucocorticoid doseand efficacy during treatment ，and medication education was carried out at discharge. RESULTS ：The doctor adopted theli_xyan suggestions of the clinical pharmacist. On the 5th day after @126.com administration，the symptoms of adrenocortical insufficiency were significantly impro ved，and the patient was discharged with medicine. CONCLUSIONS ：During the treatment of the patient ， the clinical pharmacist gave full play to his pharmaceutical expertise ，assisted the doctor to formulate an appropriate medication plan，and carried out medication education for the patient and his family members ，so as to ensure the effectiveness and safety of the patient ’s medication. It is suggested that the baseline examination of patients should be improved before immune checkpoint inhibitor treatment ，including physical examination and plasma cortisol level at 8：00 in the morning ；the frequency of monitoring plasma cortisol level and serum electrolyte level at 8：00 in the morning. should be increased during medication ；the patients should be followed up for at least 1 year after withdrawal ，so as to early detect and treat immune checkpoint inhibitor related adrenocortical dysfunction.

Risk factors and predictive model of adrenocortical insufficiency in patients with traumatic brain injury / 世界急诊医学杂志（英文）

@#BACKGROUND: Neuroendocrine dysfunction after traumatic brain injury (TBI) has received increased attention due to its impact on the recovery of neural function. The purpose of this study is to investigate the incidence and risk factors of adrenocortical insufficiency (AI) after TBI to reveal independent predictors and build a prediction model of AI after TBI. METHODS: Enrolled patients were grouped into the AI and non-AI groups. Fourteen preset impact factors were recorded. Patients were regrouped according to each impact factor as a categorical variable. Univariate and multiple logistic regression analyses were performed to screen the related independent risk factors of AI after TBI and develop the predictive model. RESULTS: A total of 108 patients were recruited, of whom 34 (31.5%) patients had AI. Nine factors (age, Glasgow Coma Scale [GCS] score on admission, mean arterial pressure [MAP], urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, diffuse axonal injury [DAI], and skull base fracture) were probably related to AI after TBI. Three factors (urinary volume [X4], serum sodium level [X5], and DAI [X8]) were independent variables, based on which a prediction model was developed (logit P= -3.552+2.583X4+2.235X5+2.269X8). CONCLUSIONS: The incidence of AI after TBI is high. Factors such as age, GCS score, MAP, urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, DAI, and skull base fracture are probably related to AI after TBI. Urinary volume, serum sodium level, and DAI are the independent predictors of AI after TBI.