Introduction: Adrenal insufficiency (AI) is a life-threatening condition that frequently presents with non-specific symptoms, complicating early diagnosis. Morning serum cortisol serves as an effective initial screening tool for assessing the hypothalamic-pituitary-adrenal (HPA) axis, potentially reducing the necessity for dynamic investigations such as the Short Synacthen Test (SST). This study aims to assess the clinical indications for morning cortisol testing and evaluate institutional compliance with guideline-based cortisol cut-offs, the initiation of hydrocortisone therapy, and the provision of “sick day” education. Methodology: A retrospective cross-sectional study was conducted among inpatients at a tertiary hospital in Central Pahang who underwent morning cortisol evaluation between March and August 2025. Data regarding demographics, indications, biochemical results, and clinical management were analyzed using SPSS version 26.0. Results: Among the 111 patients included (mean age: 54.96 ± 15.88 years), the primary indications for testing were hyponatremia (54.1%), hypotension (27.9%), and a history of traditional medication use (26.1%). Based on Endocrine Society guidelines: <150 nmol/L (AI likely): 16.2%, 150–300 nmol/L (Borderline): 26.1%, and >300 nmol/L (AI unlikely): 57.7%. Notably, only 10 of the 18 patients with cortisol levels <150 nmol/L were formally diagnosed and initiated on appropriate therapy. In the borderline group, only two patients underwent an SST. Although 12 patients overall were treated for AI, only eight received documented “sick day” education. Low cortisol levels were significantly associated with hyponatremia, hypotension, and traditional medication use, and demonstrated a negative correlation with serum sodium and albumin levels. Conclusion Morning serum cortisol is a valuable screening tool for AI, particularly in patients presenting with hyponatremia or hypotension. However, significant gaps persist in follow-up management, confirmatory testing, and patient education. Implementing standardized protocols and enhancing clinician education are essential to optimize care.
Hydrocortisone ; Adrenal Insufficiency ; Tertiary Care Centers

Introduction: RENI syndrome (renal, endocrine, neurologic, and immune syndrome), also known as sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS), is a rare autosomal recessive disorder caused by pathogenic variants in the SGPL1 gene. This gene encodes sphingosine-1- phosphate lyase, an enzyme responsible for the final step in sphingolipid degradation. Impaired enzyme activity results in the accumulation of sphingolipid intermediates, leading to multisystem involvement affecting the kidneys, adrenal glands, skin, immune system, and nervous system. Frequently reported manifestations include steroid-resistant nephrotic syndrome, primary adrenal insufficiency, ichthyosis, and neurological abnormalities. Case: We report a 15-year-old male with a history of primary adrenal insufficiency diagnosed at age three after presenting with recurrent vomiting and abdominal pain. He was started on steroid replacement therapy and remained stable without episodes of adrenal crisis. He also had ichthyosis requiring dermatological follow-up. During routine surveillance, persistent proteinuria was detected, and urinary protein excretion increased over time. Ultrasound showed renal parenchymal changes despite preserved renal function. Whole-exome sequencing identified a homozygous variant of uncertain significance in the SGPL1 gene, consistent with RENI syndrome. He was started on enalapril for his proteinuria and continues to undergo multidisciplinary follow-ups. Both parents are consanguineous, but were not screened. Mutations in SGPL1 have increasingly been recognized as a monogenic cause of syndromic steroid-resistant nephrotic syndrome, associated with endocrine and dermatological features. Renal histopathology in cases reported often shows focal segmental glomerulosclerosis, reflecting podocyte injury due to disruption of sphingolipid signaling pathways. Early recognition is crucial, as patients need multidisciplinary care. Conclusion This case highlights the importance of considering RENI syndrome in patients presenting with early-onset primary adrenal insufficiency accompanied by renal and dermatological symptoms. Increased clinical awareness and prompt genetic testing can enable earlier diagnosis, guide long-term monitoring, and support appropriate genetic counseling.
Adrenal Insufficiency ; Proteinuria ; Ichthyosis

OBJECTIVE: To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene. METHODS: Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed. RESULTS: Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously. CONCLUSION FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.
Humans ; Child ; Glucocorticoids/therapeutic use* ; Receptor, Melanocortin, Type 2/genetics* ; Retrospective Studies ; Adrenal Insufficiency/genetics* ; Mutation

Objectives: Among critically ill patients, there is usually impairment of the hypothalamic-pituitary- adrenal axis, leading to a condition known as critical illness-related corticosteroid insufficiency (CIRCI). The aims of this investigation are to determine the incidence of and characterize CIRCI among patients with COVID-19 as well as to analyze the outcomes of these critically ill patients. Methodology: This is a single-center, retrospective, cohort study that investigated the occurrence of CIRCI among critically ill patients infected with COVID-19. Results: In this cohort, there were 145 COVID-19 positive patients with refractory shock included, which reflects that 22.94% of the COVID-19 admissions have probable CIRCI. Patients who were given corticosteroids were found to have statistically significant longer median days on ventilator (p= 0.001). However, those on the corticosteroid arm were at higher risk of morbidity and mortality and a greater proportion of patients with organ dysfunction. Multivariable logistic regression analysis revealed that SOFA score was a significant predictor of mortality in CIRCI (p=0.013). Conclusion CIRCI has a unique presentation among COVID-19 patients because of the presence of a high level of inflammation in this life-threatening infection. It possibly is a harbinger of markedly increased risk of mortality in these patients.
adrenal insufficiency ; COVID-19 ; critical illness ; shock

Addison's disease is a rare disease caused by insufficient production of glucocorticoids, mineralocorticoids, and androgens in the adrenal cortex. It occurs more frequently in women and develops most often between the ages of 30 and 50. About two-thirds of patients with Addison's disease may develop other autoimmune disorders in the context of autoimmune polyglandular syndrome (APS), including autoimmune thyroid disease (ATD), autoimmune gastritis, type 1 diabetes, premature ovarian failure (POF), vitiligo, or celiac disease. We reported a case of 51-year-old woman with complaints of weakness, nausea, vomiting, weight loss, frequent bowel movements, and hyperpigmentation. Laboratory examinations showed decreased level of morning cortisol, increased ACTH, increased FT4, decreased TSH, increased thyrotropin receptor antibody (TRab), and positive glutamic acid decarboxylase (GAD) 65. Patient was diagnosed with Addison's disease accompanied by autoimmune thyroid disease-causing' disease and type 1 diabetes mellitus, leading to autoimmune polyglandular syndrome (APS) type 2. After being given steroid, insulin, and anti-thyroid drugs therapy, the patient's condition improved.
Addison Disease

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
Adrenal Hyperplasia, Congenital/genetics* ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hydrocortisone ; Hydroxyprogesterones ; Hyperplasia ; Infant ; Male ; Mutation ; Phosphoproteins/genetics* ; Retrospective Studies

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with congenital isolated adrenocorticotropic hormone deficiency (IAD). METHODS: Clinical characteristics of the patient was reviewed. Genomic DNA of the child was subjected to whole exome sequencing. RESULTS: Genetic testing has confirmed the diagnosis of congenital IAD by identification of compound heterozygous variants of the TBX19 gene, which included a pathogenic nonsense c.535C>T (p.R179X) variant inherited from his father and a novel missense c.298C>T (p.R100C) variant inherited from his mother. CONCLUSION Congenital IAD due to variants of the TBX19 gene is a rare autosomal recessive disease. It is characterized by low plasma adrenocorticotropic hormone and cortisol levels but normal levels of other pituitary hormones. Delayed diagnosis may lead to severe early-onset adrenal failure and wrong treatment which may result in neonatal mortality. Hydrocortisone replacement is effective. Detection of pathogenic variant of TBX19 gene is the key to diagnosis.
Adrenal Insufficiency/genetics* ; Child ; Homeodomain Proteins/genetics* ; Humans ; T-Box Domain Proteins/genetics*

We report one case of estimated glomerular filtration rate (eGFR) decline after taking unilateral adrenalectomy due to aldosterone adenoma. A 60-year-old male with 23-year history of hypertension was reported to the endocrinologist due to hypokalemia (serum potassium 3.01 mmol/L). Urine microalbumin/creatinine (ALB/CR) was 70.15 mg/g, serum creatinine was 82 μmol/L and eGFR was 89.79 mL/(min·1.73 m²). Random serum aldosterone was 172.2-203.5 ng/L, and random plasma rennin activity was 0-0.17 μg/(L·h). His captopril challenge test suggested that his aldosterone le-vels were suppressed by 8% (< 30%) and the adrenal enhanced computed tomography scan revealed a left adrenal tumor. The patient was diagnosed with primary hyperaldosteronism (PA), aldosterone adenoma and underwent left laparoscopic adrenalectomy. Histological examination confirmed adrenal cortical adenoma. One week after the operation, his serum creatinine was increased to 127 μmol/L compared with preoperative level; eGFR was 32.34 mL/(min·1.73 m²). His systolic blood pressure (SBP) was 110 mmHg and diastolic blood pressure (DBP) was 60 mmHg (hypotensive drugs discontinued), and serum potassium level was 5.22 mmol/L. At the end of the 2-year follow up, the serum creatinine of this patient remained at 109-158 μmol/L and eGFR fluctuated from 63.28-40.12 mL/(min·1.73 m²). PA is one of the most common causes of secondary hypertension. Several studies have reported renal function deterioration of PA patients after unilateral adrenalectomy, like the patient in this article. Age, preoperative plasma aldosterone concentration, albuminuria and preoperative potassium level might be significant predictors of a decrease in the eGFR. Growing evidence suggests that aldosterone could contribute to structural kidney damage, arterial injury and hemodynamic disorder. At the same time, patients with PA exhibit glomerular hyperfiltration and glomerular vascular hypertension, leading to the misinterpretation of renal function in PA patients as subtle kidney damage may be masked by the glomerular hyperfiltration before treatment. After a unilateral adrenalectomy, glomerular hyperfiltration by aldosterone excess is resolved and renal damage can be unmasked. In conclusion, kidney function deterioration after adrenalectomy can be detected in some patients with PA. Thus, accurate evaluation of kidney function in patients with PA may be essential, especially for those with preoperative risk factors for postoperative renal impairment. After unilateral adrenalectomy, close monitoring of renal function and adequate management are required for PA patients.
Adrenal Gland Neoplasms/surgery* ; Adrenalectomy ; Glomerular Filtration Rate ; Humans ; Hyperaldosteronism/surgery* ; Male ; Middle Aged ; Renal Insufficiency, Chronic

OBJECTIVE: To summarize clinical manifestations, inheritance pattern and mutations of NR0B1 gene in 7 children with X-linked adrenal dysplasia congenita (XL-AHC). METHODS: Clinical data of the 7 children was collected. Next-generation sequencing was carried out to detect potential mutations in the coding regions of adrenal gland-related genes. Suspected mutations were verified with Sanger sequencing. RESULTS: In all of the children, the initial symptom was adrenocortical insufficiency. Five cases had neonatal onset, while the remaining two developed it at the age of 2. Three cases (42.9%) had a short stature and 1 showed growth retardation (14.3%). Of the 7 cases, 6 (85.7%) had mutations occurring in exon 1, and 1 (14.3%) had it occurring in exon 2. Four cases (57.1%) were frameshift mutations, 2 cases (28.6%) were nonsense mutations and 1 case (14.3%) was missense mutation. Two mutations were known to be pathogenic, and 5 had not been reported previously. Maternal inheritance was found in 6 cases. Three children had a maternal uncle died of unexplained causes. The mothers of 2 children had a history of spontaneous abortions. One child had a brother died of unexplained reason. CONCLUSION Male children with primary adrenal insufficiency should be routinely checked for NR0B1 mutations, especially those with a family history. mutations of NR0B1 gene occur mostly in exon 1, with frameshift mutations being the most common type. The development of all patients with XL-AHC should be closely monitored during follow-up.
Adrenal Insufficiency ; Child ; DAX-1 Orphan Nuclear Receptor ; DNA Mutational Analysis ; Genes, X-Linked ; Humans ; Hypoadrenocorticism, Familial ; Male ; Mutation

OBJECTIVE: To report on the clinical pictures of 7 patients from a pedigree affected with X-linked adrenal hypoplasia congenita (XL-AHC) and hypogonadotropic hypogonadism (HH) and the underlying mutations. METHODS: Seven patients were identified from a four-generation pedigree affected with XL-AHC and HH. Their clinical features, endocrinological changes, treatment and drug response were recorded. The patients were subjected to next-generation sequencing, and the result was verified by Sanger sequencing. PolyPhen-2 was used for predicting the influence of the mutation on protein production. RESULTS: Three deceased patients had manifested adrenal insufficiency (AI) within one year after birth. Two died at 6 and one died at 12. The four survivors presented with salient clinical and endocrinological features of AHC and HH, adrenal and testicular atrophy, and renin-angiotensin compensation. Two adult patients had testicular micro-stone detected by ultrasound.One of them also had remarkable seminiferous tubule degeneration by biopsy. The patients were followed up for 0.5 to 10 years. All required hyper-physiological dose of hydrocortisone to stabilize their clinical condition. In three patients, gonadotropic or androgen replacement induced cardinal masculine development but with unsatisfactory testis growth and sperm production.Genetic analysis revealed a novel missense c.827A>C (p.Q276P) mutation in a hotspot region within a highly conserved domain. PolyPhen-2 predicted the mutation to be highly hazardous. CONCLUSION The novel p.Q276P mutation of the DAX1 gene probably underlies the XL-AHC and HH in this pedigree with variable clinical presentations in the patients.
Adrenal Insufficiency ; DAX-1 Orphan Nuclear Receptor ; genetics ; Humans ; Hypoadrenocorticism, Familial ; genetics ; Male ; Mutation ; Mutation, Missense ; Pedigree ; Repressor Proteins