Condition
Hypoadrenalism
Hypoadrenalism, or adrenal insufficiency, happens when the adrenal glands make too little cortisol, because they are damaged (Addison's disease) or because the pituitary sends too little ACTH to switch them on. Among supplements, DHEA and salt have the strongest support, both moderate, though one small DHEA trial found no clear difference in body fat. Diagnosis stands on firmer ground: a cosyntropin test detected primary cases with about 97% sensitivity.
Sources: PMID 20122035; PMID 27270475
- Supplements studied
- 1
- Medicines and peptides
- 1
- Graded outcomes
- 5
- Trials
- 1
- People studied
- 20
Evidence by supplement
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Body Fat No effect | NoneNo effect | 20 people | ||||
| Testosterone | Improves (the measure goes up) | 3 studies | 40 people | |||
Studies that measured testosterone
| ||||||
| Serum DHEA | Improves (the measure goes up) | 2 studies | 20 people | |||
| Growth Hormone | Improves (the measure goes up) | 1 study | 20 people | |||
Studies that measured growth hormone | ||||||
| IGF-1 | Improves (the measure goes up) | 1 study | 20 people | |||
| Glycemic Control | Improves (the measure goes up) | 20 people | ||||
| High-density lipoprotein (HDL) | Improves (the measure goes up) | 20 people | ||||
| Low-density lipoprotein (LDL) | Improves (the measure goes down) | 20 people | ||||
| Serum T3 | Improves (the measure goes up) | 20 people | ||||
| Total cholesterol | Improves (the measure goes down) | 20 people | ||||
Prescription medicines and peptides studied, for context
Cosyntropin (Cortrosyn/Synacthen)
- Cortisol Stimulation: changes; see studies
- Safety Profile: improves
- Diagnostic Sensitivity (Primary AI): improves
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Cortisol Stimulation Normal response: cortisol ≥18 mcg/dL (500 nmol/L) at 30-60 minutes. Reliable stimulation of adrenal cortex in healthy individuals. | Changes; see studies | Large effect | 20 studies | |||
| Safety Profile Less immunogenic than natural ACTH. Rare hypersensitivity reactions. Well-tolerated diagnostic procedure used for decades. | Improves (the measure goes up) | Large effect | 11 studies | |||
| Diagnostic Sensitivity (Primary AI) 97% sensitivity at 95% specificity for primary adrenal insufficiency. Meta-analysis of multiple studies confirms high diagnostic accuracy. | Improves (the measure goes up) | Large effect | 10 studies | |||
| Diagnostic Accuracy (Secondary AI) 57-61% sensitivity for secondary AI. Better for ruling in than ruling out. Low-dose (1mcg) may be superior (AUC 0.94 vs 0.85). | Improves (the measure goes up) | Moderate effect | 10 studies |
Key findings
- Body Fat
The Hypoadrenalism (Adrenal Insufficiency) Supportive Care protocol
2 primary supplements · 6 supporting supplements
- Vitamin C500–1,000 mg daily in divided doses
- Vitamin B5 (Pantothenic Acid)500–1,000 mg daily
Studies cited
60 studies from PubMed
- Examining aldosterone plasma concentration alterations post-ACTH stimulation in healthy subjects: a systematic literature review and meta-analysis on ACTH's role in aldosterone secretion.
- Salivary corticosterone measurement in large-billed crows by enzyme-linked immunosorbent assay.
- New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol Assays
- Cortisol levels in blood and hair of unanesthetized grizzly bears (Ursus arctos) following intravenous cosyntropin injection.
- Cosyntropin for the Treatment of Refractory Postdural Puncture Headache in Pediatric Patients: A Retrospective Review.
- Pitfalls in the interpretation of the cosyntropin stimulation test for the diagnosis of adrenal insufficiency
- Diagnostic accuracy of basal cortisol level to predict adrenal insufficiency in cosyntropin testing: results from an observational cohort study with 804 patients
- Total and free cortisol levels during 1 μg, 25 μg, and 250 μg cosyntropin stimulation tests compared to insulin tolerance test: results of a randomized, prospective, pilot study.
- ACTH Stimulation Tests for the Diagnosis of Adrenal Insufficiency: Systematic Review and Meta-Analysis
- Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline
- Cosyntropin as a diagnostic agent in the screening of patients for adrenocortical insufficiency
- Normal hypothalamic-pituitary-adrenal axis by high-dose cosyntropin testing in patients with abnormal response to low-dose cosyntropin stimulation: a retrospective review.
- Is the cosyntropin test redundant in the acutely ill patient suspected of adrenal insufficiency? A case report and literature review.
- H.P. Acthar Gel and Cosyntropin Review: Clinical and Financial Implications
- Hypothalamic-pituitary-adrenal axis assessment in healthy term neonatal foals utilizing a paired low dose/high dose ACTH stimulation test.
- Performance of low-dose ACTH stimulation test in patients suspected of secondary adrenal insufficiency
- Autoimmune polyglandular syndrome, type II.
- Can 1 microg of cosyntropin be used to evaluate adrenal insufficiency in critically ill patients?
- Adrenal function in critically ill patients: how to test? When to treat?
- The short corticotropin stimulation test revisited: new normal reference range using Immulite 2000
- High-dose and low-dose cosyntropin stimulation tests for diagnosis of adrenal insufficiency.
- Serum concentrations of cortisol, sex hormones of adrenal origin, and adrenocortical steroid intermediates in healthy dogs following stimulation with two doses of cosyntropin.
- Comparison of low and high dose corticotropin stimulation tests in patients with pituitary disease
- Diagnosis of adrenal insufficiency.
- Prevalence of abnormal adrenocortical function in human immunodeficiency virus infection by low-dose cosyntropin test.
- Comparison between low-dose and high-dose ACTH stimulation tests for adrenal insufficiency
- A low dose ACTH test for assessment of hypothalamic-pituitary-adrenal function
- Severe hyperkalemia in two patients with diabetes after cosyntropin administration.
- Enhanced adrenal sensitivity to exogenous cosyntropin (ACTH alpha 1-24) stimulation in major depression. Relationship to dexamethasone suppression test results.
- Cosyntropin stimulation in adrenal vein testing for aldosteronoma.
- The use of a cosyntropin stimulation test to predict adrenal suppression in renal transplant patients being withdrawn from prednisone.
- Combined dexamethasone suppression and cosyntropin (synthetic ACTH) stimulation test in the dog: new approach to testing of adrenal gland function.
- Effects of dehydroepiandrosterone and atamestane supplementation on frailty in elderly men
- Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women
- Effect of 1-year oral administration of dehydroepiandrosterone to 60- to 80-year-old individuals on muscle function and cross-sectional area: a double-blind placebo-controlled trial
- Dehydroepiandrosterone replacement in healthy men with age-related decline of DHEA-S: effects on fat distribution, insulin sensitivity and lipid metabolism
- Effects of dehydroepiandrosterone vs androstenedione supplementation in men
- Oral dehydroepiandrosterone replacement in older adults: effects on central adiposity, glucose metabolism and blood lipids
- Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial
- Short-term dehydroepiandrosterone treatment increases platelet cGMP production in elderly male subjects
- Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men
- Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids
- Lack of dehydroepiandrosterone effect on a combined endurance and resistance exercise program in postmenopausal women
- Impact of DHEA supplementation on testosterone and estradiol levels in postmenopausal women: a meta-analysis of randomized controlled trials assessing dose and duration effects.
- Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men
- Effects of short-term dehydroepiandrosterone supplementation on body composition in young athletes
- Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training
- Dehydroepiandrosterone supplementation and bone turnover in middle-aged to elderly men
- Dehydroepiandrosterone replacement therapy in older adults: 1- and 2-y effects on bone
- A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA supplementation of bone mineral density in healthy adults.
- Effects of dehydroepiandrosterone supplementation on cognitive function and activities of daily living in older women with mild to moderate cognitive impairment
- Effects of dehydroepiandrosterone supplementation on cognitive function and quality of life: the DHEA and Well-Ness (DAWN) Trial
- Dhea supplementation and cognition in postmenopausal women
- Effects of dehydroepiandrosterone (DHEA) supplementation on hormonal, metabolic and behavioral status in patients with hypoadrenalism
- Androgens and sexual function: a placebo-controlled, randomized, double-blind study of testosterone vs. dehydroepiandrosterone in men with sexual dysfunction and androgen deficiency
- A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgia
- Dehydroepiandrosterone (DHEA) effects on HIV replication and host immunity: a randomized placebo-controlled study
- Effects of dehydroepiandrosterone supplementation during stressful military training: a randomized, controlled, double-blind field study
- Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study
- A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials.