11β-Hydroxysteroid Dehydrogenase Type 2 (11β-HSD2) Deficiency

11β-HSD2 deficiency is a rare genetic condition in which the body cannot properly switch the hormone cortisol into its inactive form, cortisone, inside certain kidney cells. When this “switch” does not work, cortisol wrongly turns on the mineralocorticoid receptor (the same receptor that aldosterone uses). This makes the kidneys keep too much salt and water, lose potassium, and create an imbalance that raises blood pressure even in children. Doctors call this overall picture “apparent mineralocorticoid excess (AME)” because the body looks as if it has too much aldosterone—even though aldosterone levels are actually low. 11β-HSD2 deficiency happens when both copies of the HSD11B2 gene carry harmful variants. It is inherited in an autosomal recessive way. Key lab clues are high blood pressure with low renin, low aldosterone, hypokalemia, and a high ratio of cortisol-to-cortisone metabolites in urine. BioMed Central+2Orpha+2

11β-HSD2 deficiency, also called apparent mineralocorticoid excess (AME), is a rare inherited condition. In this condition the kidney enzyme 11β-HSD2 does not work well. This enzyme normally changes cortisol into cortisone, which is inactive at the mineralocorticoid receptor. When 11β-HSD2 is weak, cortisol stays active and acts like aldosterone. This makes the body keep too much salt and water and lose potassium. The result is early, hard-to-control high blood pressure, low potassium, metabolic alkalosis, and often nephrocalcinosis in children. It is usually due to mutations in the HSD11B2 gene and passes in an autosomal recessive way. Licorice and some azole antifungals can “mimic” this by blocking the same enzyme. PMC+2PubMed+2

In healthy kidneys, the 11β-HSD2 enzyme protects the mineralocorticoid receptor by converting active cortisol to inactive cortisone. In 11β-HSD2 deficiency, this protection is lost. Active cortisol is present in far higher amounts than aldosterone and now “hijacks” the receptor. The kidney tubules then reabsorb more salt and water, dump potassium, and the body becomes volume-expanded and alkalotic. The renin-angiotensin-aldosterone system shuts down, so renin and aldosterone are low even though blood pressure is high. Over time, patients may develop growth problems, kidney calcium issues, and heart changes from long-standing hypertension. BioMed Central+2Frontiers+2

Other names

This condition is also called: Apparent mineralocorticoid excess (AME), AME syndrome, Ulick syndrome, 11β-HSD2 deficiency, and HSD11B2-related AME. Orpha+1

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Types (clinical patterns you may see)

1. Classic (severe, early-onset) AME – Presents in infancy/early childhood with severe hypertension, marked hypokalemia, failure to thrive, and very high urine cortisol/cortisone metabolite ratios. Usually caused by variants that almost abolish enzyme activity. ScienceDirect+1

2. Non-classic or mild (late-onset) AME – Presents later with milder hypertension and potassium loss; urine steroid profiles are abnormal but less extreme; often due to partial-function variants. AHA Journals+1

3. Acquired AME phenotype from enzyme inhibitors – Not genetic deficiency, but looks similar because certain substances block 11β-HSD2 (for example, natural licorice [glycyrrhizin/glycyrrhetinic acid] or the drug carbenoxolone). Stopping the trigger usually improves findings. PubMed+2PubMed+2

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Causes

Genetic (true 11β-HSD2 deficiency)

1. Biallelic HSD11B2 missense variants that reduce enzyme activity. PubMed

2. Nonsense variants leading to truncated, non-functional enzyme. PNAS

3. Frameshift/indel variants disrupting the enzyme’s catalytic domain. PNAS

4. Splice-site variants causing abnormal mRNA and reduced enzyme. PubMed

5. Promoter or regulatory variants lowering 11β-HSD2 expression. Oxford Academic

6. Compound heterozygosity (two different pathogenic variants, one on each allele). PubMed

7. Homozygosity due to consanguinity increasing risk of recessive disease. Orpha

8. Copy-number changes (rare gene deletions/duplications affecting HSD11B2). NCBI

9. Post-zygotic/variable residual activity producing milder, later-onset disease. AHA Journals

10. Genetic modifiers in pathways of cortisol metabolism that worsen phenotype (research/observational). BioMed Central

Acquired 11β-HSD2 inhibition or AME phenocopies

11. Licorice (glycyrrhizin/glycyrrhetinic acid) intake—tea, candies, herbal products. PubMed+1

12. Carbenoxolone (a glycyrrhetinic acid derivative; research/legacy drug) inhibiting 11β-HSD enzymes. PNAS

13. Other 11β-HSD inhibitors in foods or supplements (rare; case-based). MDPI

14. Heavy salt intake aggravating salt-sensitive hypertension in partial deficiency. Nature

15. Low birth weight/prematurity exposure to maternal 11β-HSD inhibitors (animal/human data suggest programming of salt-sensitive BP). AHA Journals

16. Drug interactions that reduce 11β-HSD2 activity (reported with some experimental or off-target agents). Nature

17. Epigenetic suppression (promoter methylation lowering HSD11B2 expression). Oxford Academic

18. Renal disease stressors that unmask partial deficiency (clinical observation across monogenic hypertension). Frontiers

19. Endocrine stress with high cortisol exposure that overwhelms limited 11β-HSD2 capacity in mild cases. BioMed Central

20. Unknown or novel HSD11B2 variants not yet cataloged that present with AME features. PubMed

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Symptoms and signs

1. High blood pressure, often at a young age and hard to control. BioMed Central

2. Muscle weakness or cramps from low potassium. BioMed Central

3. Headache due to hypertension. Frontiers

4. Tiredness and low energy from potassium loss and alkalosis. BioMed Central

5. Excess thirst (polydipsia) because kidneys lose too much water. ScienceDirect

6. Frequent urination (polyuria) for the same reason. ScienceDirect

7. Poor weight gain/failure to thrive in infants and young children. ScienceDirect

8. Irritability or sleep troubles linked to hypertension/electrolyte imbalance. BioMed Central

9. Constipation from hypokalemia. BioMed Central

10. Tingling or numbness (paresthesias) due to alkalosis/hypokalemia. BioMed Central

11. Palpitations or irregular heartbeat (arrhythmia) when potassium is very low. Frontiers

12. Short stature or growth delay if long-standing disease. ScienceDirect

13. Kidney stones or nephrocalcinosis from calcium handling changes. BioMed Central

14. Vision complaints (e.g., from severe hypertension; may show retinal changes). Frontiers

15. Shortness of breath or chest discomfort if blood pressure is very high or there is cardiac strain. Frontiers

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Diagnostic tests

A) Physical examination

1. Blood pressure measurement in both arms – Persistently high readings suggest AME, especially in children; measure seated and, when possible, standing to check for any postural changes. Frontiers

2. Growth assessment – Plot height/weight for age; many children with classic AME show growth failure if untreated. ScienceDirect

3. Volume status check – Signs of fluid overload (e.g., mild edema is uncommon but volume expansion is physiologic); helps interpret renin-aldosterone suppression. BioMed Central

4. Neuromuscular exam – Weakness, reduced reflexes, or cramps point to hypokalemia. BioMed Central

5. Funduscopic (eye) exam – Hypertensive retinopathy can appear with severe, sustained pediatric hypertension. Frontiers

B) Manual/bedside tests

6. Standardized blood pressure protocols (proper cuff size, repeat readings, home or ambulatory monitoring) to confirm true hypertension and its severity. Frontiers

7. Dietary/medication history focused on licorice (candies, teas, herbal mixes) or carbenoxolone exposure that can mimic AME; stopping the trigger can correct findings. PubMed+1

8. Salt intake review – High salt worsens the phenotype; counseling may be a first step while diagnostic labs are pending. Nature

C) Laboratory & pathological tests

9. Serum electrolytes and bicarbonate – Hypokalemia and metabolic alkalosis are typical. BioMed Central

10. Plasma renin activity (or direct renin) – Suppressed/low for the degree of hypertension. BioMed Central

11. Plasma aldosterone – Low or inappropriately normal despite hypertension and hypokalemia. BioMed Central

12. 24-hour urine steroid profile – High ratio of cortisol metabolites (THF + allo-THF) to cortisone metabolite (THE) confirms 11β-HSD2 dysfunction; this is a cornerstone test. Yonsei Medical Journal

13. Spot urine cortisol/cortisone ratio – A practical screen when 24-hour collection is difficult; often elevated in AME. BioMed Central

14. Genetic testing of HSD11B2 – Sequencing detects biallelic pathogenic variants; confirms diagnosis and guides family counseling. NCBI

15. Functional studies (research settings) – Enzyme activity assays or in-vitro expression to characterize variant impact in unclear cases. PNAS

16. Urine sodium and potassium – Help quantify renal potassium wasting and salt handling. BioMed Central

17. Screen for other monogenic hypertension causes if the pattern is atypical (for example, GRA, Liddle syndrome); ensures correct therapy. PMC

D) Electrodiagnostic tests

18. Electrocardiogram (ECG) – Looks for hypokalemia changes (e.g., U waves), arrhythmias, and left ventricular strain from hypertension. Frontiers

19. Echocardiogram – Not electrical, but cardiac testing is essential to assess hypertensive heart effects (left ventricular hypertrophy). Some centers also evaluate ambulatory BP load with device-stored tracings. Frontiers

E) Imaging tests

20. Renal ultrasound – Screens for nephrocalcinosis or stones and assesses kidney size/structure in long-standing disease. In severe cases, clinicians may add vascular ultrasound or MRI if secondary anatomical causes of hypertension are also considered. BioMed Central

Non-pharmacological treatments

1. Strict sodium restriction: Aim for a low-salt diet to reduce volume and BP; this directly counters MR overstimulation. Wiley Online Library

2. Stop licorice in any form (foods, teas, herbal mixes). Even small daily amounts can sustain the problem. PMC

3. Medication review: Avoid or replace itraconazole/posaconazole when possible; monitor if unavoidable. PMC+1

4. Adequate dietary potassium (food sources under medical guidance) to support K⁺ levels. PMC

5. Hydration optimization to protect kidneys and reduce stone risk when hypercalciuria is present. ScienceDirect

6. Weight management and physical activity appropriate for BP control and cardiovascular risk. MDPI

7. Home BP monitoring with a validated cuff; track readings and symptoms. PMC

8. Dietary calcium/oxalate balance if nephrocalcinosis/hypercalciuria; dietitian input helps. ScienceDirect

9. Avoid high-dose NSAIDs (can worsen BP and kidney function). MDPI

10. Limit alcohol and caffeine that may elevate BP; emphasize sleep and stress control. MDPI

11. Family screening/genetic counseling for siblings in recessive disease. PMC

12. Sick-day rules (keep fluids, check BP, seek care early for weakness or palpitations). PMC

13. Salt-label literacy: learn to spot hidden sodium in packaged foods. Wiley Online Library

14. Avoid potassium-wasting laxatives if possible; they can aggravate hypokalemia. MDPI

15. Dietitian-led low-salt meal plan tailored to culture and preferences. Wiley Online Library

16. Educate about herbal products (Kampo/others) frequently containing licorice. Frontiers

17. Medication adherence coaching for chronic MR antagonists/ENaC blockers. PMC

18. Regular kidney ultrasound follow-up if nephrocalcinosis is present. Oxford Academic

19. Cardiovascular risk reduction (lipids, glucose, exercise). MDPI

20. School/work safety plan for symptoms of hypokalemia (muscle cramps, palpitations). PMC

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Drug treatments

Mineralocorticoid receptor antagonists (MRAs)
Spironolactone blocks the MR so cortisol cannot cause salt retention. It lowers BP and helps potassium. Typical start: 25–50 mg daily, titrate to effect; watch for hyperkalemia, gynecomastia, menstrual changes. In resistant hypertension and AME physiology, MRAs are effective even when aldosterone is low because they block the final receptor. PMC+1

Eplerenone is a more selective MRA. Dose often 25–50 mg twice daily; fewer sex-hormone side effects than spironolactone but still monitor potassium and kidney function. Useful if spironolactone is not tolerated. AHA Journals

ENaC blockers
Amiloride directly blocks the epithelial sodium channel activated downstream of MR. Start commonly 5–10 mg/day, can go to 20 mg/day; watch for hyperkalemia, especially with MRAs or CKD. Works very well in mineralocorticoid-type hypertension with hypokalemia. Triamterene is an alternative (e.g., 50–100 mg/day). Frontiers

Adjunct antihypertensives
ACE inhibitors or ARBs, and long-acting dihydropyridine calcium-channel blockers (like amlodipine), are often added to reach BP targets; they help protect the heart and kidneys. Dosing follows standard hypertension guidance; monitor kidney function and potassium. MDPI

Potassium supplementation
Oral potassium chloride can be used short-term to correct hypokalemia while MRAs/amiloride take effect. Dose is individualized; monitor ECG and serum potassium to avoid rebound high potassium. PMC

Glucocorticoids (selected cases only)
Low-dose dexamethasone has been tried to suppress endogenous cortisol production in difficult cases, but benefits are variable and side-effects can be significant; this is specialist-directed and not routine first-line. PMC

When azoles cause a “pseudo-AME”
If hypertension/hypokalemia appears on posaconazole/itraconazole, the best “treatment” is dose reduction or switching agents; MRAs/amiloride help while the drug is tapered. Close monitoring is required because posaconazole can also disturb other adrenal enzymes. PMC+1

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Dietary molecular supplements

There is no supplement that fixes the enzyme defect. But nutrition can support BP and potassium. Food-first strategies are safest.

• Potassium-rich foods (bananas, oranges, tomatoes) can help, if kidney function allows; avoid if on high-dose MRA without monitoring. PMC
• DASH-style eating (vegetables, fruits, low-fat dairy, whole grains) helps lower BP naturally. MDPI
• Magnesium-adequate diet may help muscle symptoms and BP modestly; supplements only under supervision. MDPI
• Avoid licorice-containing products in any “supplement” form (including teas and powders). PMC

(If you want detailed 10-item supplement monographs with dosing and mechanisms, I can draft them—bearing in mind evidence is supportive rather than curative.)

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Immunity booster / regenerative / stem-cell drugs

There are no proven immune-booster or stem-cell drugs for AME. Management focuses on blocking MR/ENaC, fixing potassium, and stopping enzyme inhibitors. Experimental or regenerative therapies are not established for this enzyme defect. PMC

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Surgery

1. Kidney stone procedures (e.g., ureteroscopy) if stones form due to long-standing hypercalciuria. This treats the complication, not the cause. ScienceDirect

2. Percutaneous nephrostomy or stenting (rare) for obstructing stones. ScienceDirect

3. Arteriovenous fistula creation (only if dialysis becomes necessary from chronic kidney damage, which is uncommon with modern care). PMC

4. Kidney transplant (very rare end-stage scenario). PMC

5. Cardiac procedures for hypertension sequelae (e.g., management of severe LVH/heart failure) when indicated by cardiology. PMC

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Prevention tips

1. Keep salt intake low every day. Wiley Online Library

2. Never use licorice products (check labels; avoid “natural sweeteners” with glycyrrhizin). PMC

3. Review medicines for azoles or other inhibitors with your clinician. PMC

4. Take MRAs/amiloride exactly as prescribed. PMC

5. Check BP at home and keep a log. PMC

6. Stay hydrated; ask about calcium/stone prevention if needed. ScienceDirect

7. Regular labs (potassium, creatinine) while on MRAs/ENaC blockers. PMC

8. Family counseling/testing for siblings in inherited cases. NCBI

9. Heart-healthy lifestyle (activity, weight, sleep). MDPI

10. Carry a medication/allergy list noting “NO LICORICE / caution with azoles.” Frontiers

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When to see a doctor

Seek urgent care now for severe headache, chest pain, shortness of breath, confusion, fainting, or muscle paralysis—these can be hypertensive crisis or dangerously low potassium. Schedule prompt care for new or worsening high BP, persistent cramps, palpitations, extreme thirst/urination, or if you start any azole antifungal. Children with poor growth or high BP need specialist assessment quickly. PMC

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What to eat / what to avoid

Eat more: fresh vegetables and fruits; whole grains; lean proteins; unsalted nuts and legumes; low-fat dairy; foods naturally rich in potassium if your doctor says it is safe. Flavor with herbs, lemon, garlic, not salt. MDPI

Avoid: added salt, salty snacks, instant noodles, pickles, processed meats; anything with licorice (candies, teas, herbal mixes, cough syrups); energy or protein products listing glycyrrhizin/glycyrrhetinic acid; and non-prescribed azole-containing supplements. PMC

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FAQs

1) Is AME the same as high aldosterone?
No. AME looks like aldosterone excess, but renin and aldosterone are low. Cortisol is acting on the MR because 11β-HSD2 is weak. PMC

2) Is it inherited?
Yes—most true AME is autosomal recessive due to HSD11B2 mutations. NCBI

3) Can foods trigger it?
Yes. Licorice strongly blocks 11β-HSD2 and can cause or worsen AME-like states. PMC

4) Which medicines can worsen it?
Itraconazole and posaconazole can cause pseudo-AME. Review all meds with your doctor. PMC+1

5) What test confirms it?
Urine steroid profile showing a high THF+alloTHF/THE ratio, plus HSD11B2 gene testing. PubMed+1

6) What is first-line treatment?
Low-salt diet plus MRAs (spironolactone/eplerenone) and/or amiloride; stop licorice/azole triggers. PMC+1

7) Do I need steroids like dexamethasone?
Only in select specialist-managed cases; benefits vary and side effects can be high. PMC

8) Will I always need medicines?
Many people need long-term blockers to protect heart and kidneys; dose may change over time. PMC

9) Can children grow normally?
With early diagnosis, salt restriction, and proper medicines, growth and BP control can improve. PMC

10) Are potassium tablets safe?
They help when potassium is low, but must be monitored—especially with MRAs/amiloride. PMC

11) Is surgery needed?
Not to fix AME. Surgery is only for complications like stones or severe kidney disease. ScienceDirect

12) Can pregnancy be managed?
Yes, but requires careful specialist care and avoidance of licorice/azole triggers; BP and potassium must be watched closely. PMC

13) What happens if untreated?
Long-term severe hypertension can damage the heart, brain, and kidneys. PMC

14) Does licorice in small amounts matter?
Even modest daily intake can raise BP and lower potassium in sensitive people—avoid entirely. PMC

15) What should my family do?
Relatives may consider genetic counseling/testing and should avoid licorice; measure BP regularly. NCBI

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: September 20, 2025.