This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency (PAI), a severe and potentially life-threatening condition characterized by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids. The guideline is developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. **Key Recommendations:** 1. **Diagnosis:** - Diagnostic testing should be conducted in all patients with indicative clinical symptoms or signs, especially in acutely ill patients and those with predisposing factors. - The corticotropin stimulation test is the "gold standard" for diagnosis, with a standard dose (250 μg) of corticotropin. - If the corticotropin test is not feasible, a low-dose (1 μg) corticotropin test or a morning cortisol level <140 nmol/L (5 μg/dL) combined with ACTH measurement can be used as preliminary tests. - Plasma ACTH measurement is recommended to establish PAI, with a value >2-fold the upper limit of the reference range indicating PAI. - Mineralocorticoid deficiency should be determined through plasma renin and aldosterone measurements. 2. **Treatment:** - Glucocorticoid therapy is recommended for all patients with confirmed PAI, with hydrocortisone or cortisone acetate as preferred options. - Hydrocortisone is suggested for pregnant women with unexplained persistent nausea, fatigue, and hypotension. - Mineralocorticoid replacement with fludrocortisone is recommended for all patients with confirmed aldosterone deficiency. - DHEA replacement may be considered for women with PAI and low libido, depressive symptoms, and/or low energy levels. - Treatment during pregnancy should be monitored closely, with adjustments based on clinical symptoms and signs. - In children, hydrocortisone is recommended at a starting dose of 8 mg/m²/day, with adjustments as needed. - Genetic counseling is recommended for patients with PAI due to monogenic disorders. 3. **Management and Prevention:** - Immediate treatment with hydrocortisone is recommended in severe cases or adrenal crisis. - Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for emergency use. - Annual endocrinologist visits and monitoring for over- and under-replacement are recommended. - Periodic screening for autoimmune diseases is suggested, especially in patients with unexplained PAI. The guideline emphasizes the importance of early diagnosis and prompt treatment to prevent severe morbidity and mortality associated with PAI.This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency (PAI), a severe and potentially life-threatening condition characterized by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids. The guideline is developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. **Key Recommendations:** 1. **Diagnosis:** - Diagnostic testing should be conducted in all patients with indicative clinical symptoms or signs, especially in acutely ill patients and those with predisposing factors. - The corticotropin stimulation test is the "gold standard" for diagnosis, with a standard dose (250 μg) of corticotropin. - If the corticotropin test is not feasible, a low-dose (1 μg) corticotropin test or a morning cortisol level <140 nmol/L (5 μg/dL) combined with ACTH measurement can be used as preliminary tests. - Plasma ACTH measurement is recommended to establish PAI, with a value >2-fold the upper limit of the reference range indicating PAI. - Mineralocorticoid deficiency should be determined through plasma renin and aldosterone measurements. 2. **Treatment:** - Glucocorticoid therapy is recommended for all patients with confirmed PAI, with hydrocortisone or cortisone acetate as preferred options. - Hydrocortisone is suggested for pregnant women with unexplained persistent nausea, fatigue, and hypotension. - Mineralocorticoid replacement with fludrocortisone is recommended for all patients with confirmed aldosterone deficiency. - DHEA replacement may be considered for women with PAI and low libido, depressive symptoms, and/or low energy levels. - Treatment during pregnancy should be monitored closely, with adjustments based on clinical symptoms and signs. - In children, hydrocortisone is recommended at a starting dose of 8 mg/m²/day, with adjustments as needed. - Genetic counseling is recommended for patients with PAI due to monogenic disorders. 3. **Management and Prevention:** - Immediate treatment with hydrocortisone is recommended in severe cases or adrenal crisis. - Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for emergency use. - Annual endocrinologist visits and monitoring for over- and under-replacement are recommended. - Periodic screening for autoimmune diseases is suggested, especially in patients with unexplained PAI. The guideline emphasizes the importance of early diagnosis and prompt treatment to prevent severe morbidity and mortality associated with PAI.