Adrenal Insufficiency
Cushings syndrome
Adrenal Incidenteloma
  • Adrenal Adenoma
    • Hyperaldosteronism / Cunn's Syndrome
  • Pheochromocytoma
Questions to answer from this page. 

1. Identify the causes of Adrenal Insufficiency related to normal aldosterone production?
2. What are the 8 symptoms, 5 signs, and 7 biochemical findings in adrenal insufficiency and their prevalence?
3. Identify the differences in the management of acute adrenal insufficiency vs chronic adrenal insufficiency?
4. What is adrenal escape mechanism?
5. What are the screening and confirmatory tests for conn's syndrome?
6. What are the precautions one should take in interpreting PRA tests results?
7. What are the 6 tests for Pheo, and what is the sensitivity and specificity of each tests and how to decide Possible, likely, unlikely pheo based on lab values?
8. Name drugs that interfere with Pheo assays and in what ways?
9. What is the typical radiological findings of Pheo?
10. Name 3 Pheo syndromes?

Adrenal Insufficiency:
(Ref: UptoDate)
  • Reduced aldosterone production
    • Hyporeninemic hypoaldosteronism
      • Diabetes and renal insufficiency
      • Nonsteroidal anti-inflammatory drugs
      • Calcineurin inhibitors
    • Angiotensin inhibitors
    • Heparin and low-molecular-weight heparin
    • Primary adrenal insufficiency
    • Severe illness
    • Inherited disorders
      • Congenital isolated hypoaldosteronism
      • Pseudohypoaldosteronism type 2 (Gordon's syndrome)
  • Aldosterone resistance
    • Inhibition of the epithelial sodium channel
      • Potassium-sparing diuretics
      • Antibiotics
    • Pseudohypoaldosteronism type 1

Cushing's Syndrome

Adrenal Incidenteloma

Clinical Question
38 yo F with 14 y history of difficult to control HTN is seen in the Clinic. BMP includes the following. 
Work up for secondary HTN shows the following. 

CT Scan to look for adrenal lesion shows 1.3 cm lesion in the right adrenal gland. How should this patient be managed?

1) Right adrenelectomy as it is a functional adrenal gland
2) Adrenal venous sampling as Right Adrenal lesion could be a incidenteloma 

Ans:  2. As incidence of adrenal incidenteloma increases with age, and we need to be as certain as possible prior to resection. However, if this patient was 25 yr and had the lesion, then at that age it is not common to have adneral incidenteloma. Hence, could be resected right away.

Hyperaldosteronism: Please see also under Resistant HTN in Hypertension

Conn's Syndrome
  • Adrenal Escape: After few days of excess Aldosterone, with > 3 Kg weight gain typically, leads to release of other factors that causes natriuresis to restore the volume status towards normal. Hence, edema is typically absent. Of note, the action of aldosterone in Cortical Collecting duct (i.e Prinicpal Cell) remains the same. 
    • Mechanism
      • ANP secretion: Acts of Inner Medullary Collecting Duct
      • Decrease number of thiazide sensitive Na-Cl channels in Cortical DCT
      • Pressure Natriuresis
  • Screening Test: PAC / PRA ratio with high PAC 
    • High PAC with Low PRA: Confirmatory for Primary Hyperaldosteronism
    • High PAC with HIGH PRA: Can be due to effects of medications. May need to stop medications before retest. 
      •  ACEI/ARB decreases aldosterone production, and should  lead to increased Renin. 
  • Confirmatory Test:
    • High dose salt loading for 3 days
    • IV NS infusion 
      • Both should suppress PAC to < 5 g/dL normally.
  • Localization
    • Imaging Study:
      • CT 
    • Bilateral Adrenal Vein Sampling (of Aldosterone and Cortisol; Cortisol to correct for dilution effect) including from the IVC
  • Adrenal Adenoma
    • Usually there is no calcification in adrenal adenoma
    • Adrenal Adenoma are usually are lipid rich (intracytoplasmic), hence likelihood of lesion with <10 HU (with 98% specificity) in NCCT is nearly 100%. But, even if it is 20 HU, the specificity is still around 85%. 
      • There will be around 30% of Adrenal Adenoma will have relatively low lipid in the cytoplasm giving higher than 10 HU in NCCT. 
        • Such adrenal lesions can be accurately diagnosed if the contrast wash out is > 60%. (Indication of Contrast Protocol is if > 10 HU)
        • MRI is better than CT to distinguish such Lipid Poor Adenoma as MRI is sensitive than CT for intracellular Fat. 
    • Adrenal Protocol 
      • Non-contrast CT - 60 sec after giving contrast - 15 min after contrast (look for washout, > 60% washout means Benign Adenoma, Note: Uptodate mentions 10 min for >50% washout)
    • 3 Types
      • Androgen Producing:
        • check DHEAS. DHEAS in adrenal gland is regulated by ACTH. So, undetectable DHEAS points towards chronic suppression of adrenal due to absence of ACTH. This can happen in subclinical Cushings.
      • Aldosterone Producing (Conn's Syndrome)
        • These are probably most active smallest tumor. So, if clinically indicated, i.e patient has HTN, then it is necessary to do PRA even if the lesion is < 1 cm in size
        • In the absence of HTN, no need to do PRA irrespective of size
        • PRA Test
          • Sympathetic Stimulus: Increases Renin and then Aldo production
            • Patient on BB, will have low Renin. So, need to be careful on interpretation.
          • ACEI or ARB
            • Renin will be high, and Aldo will be low. This does not rule out the disease. 
            • But, if Renin is low, and Aldo is high then it is still helpful in diagnosis. 
          • Aldosterone Antagonists i.e. Spironolactone
            • Renin is high due to low volume (feedback). Thus, Aldo is High . 
              • Here, high Aldo is not useful for diagnosis. 
              • However, if patient is still hypokalemic, then Aldosterone effect is not fully blocked. In such case, we can do the test despite being on Aldosterone Antagonist (Ref: Up-to-Date)
      • Cushings (Subclinical Cushings)

      • Usually > 3 cm
      • Highly vascular, cysts could be seen
      • High HU (usually >25 , can be >10)
    • Usually is lipid poor lesions
    • "light bulb bright" like CSF is classic but not common
    • If patient has had previous surgery, and did not have any complications of Pheochromocytoma during surgery, it is likely not Pheo
    • Can have calcification
    • Tests : Values > 4 times normal is highly suggestive ; TCA, ADHD medications highly interfere 
      • Plasma Epi
      • Plasma NEpi
      • Plasma Metaneph : Rarely false positive
      • Plasma Nor-metaneph : Commonly false positive ; Even Tylenol can interfere
      • Urine Meta
      • Urine Nor-Meta

Phaeochromocytoma Lancet 2005

Pheochromocytoma Syndromes
  • Metastasis
    • In the absence of history of cancer, it being a metastatic disease is less likely. In one study Song et al, of 1000 + patients with no history of cancer, none of them had cancer in the adrenal lesion. On the other hand, if they had the history of Cancer, 50 % of those lesions were metastatic lesions
  • Adrenocortical Carcinoma
Case Based Learning
55 yo M is seen for ESRD, Nephrotic Range Protenuria (still making Urine). BP Is 225/130 on presentation. Labs included the following. 

Cathecolamins, Fractionated Plasma is ordered. And results is as below. 

How should one interpret this finding?
  • Typically, plasma catecholamines are 84% sensitive and 81 % specific for Pheochromocytoma 
  • Values > 4 times normal is highly suggestive. Seems to be the case for Nor-epi, but not for Epi. 
Additional Urinary Tests are ordered. 

How to interpret this data?

IN addition, PRA is ordered. Lab is as below. 

  • PAC / PRA ratio is: 16.3 / 0.4 = 40.75 
  • In the screening test, High PAC with Low PRA: Confirmatory for Primary Hyperaldosteronism
What is the next step? 
  • Confirmatory Test:
    • High dose salt loading for 3 days
    • IV NS infusion 
      • Both should suppress PAC to < 5 g/dL normally.
  • Once, confirmatory tests are done, Localization needs to be done by the following tests 
    • Imaging Study:
      • CT 
    • Bilateral Adrenal Vein Sampling (of Aldosterone and Cortisol; Cortisol to correct for dilution effect) including from the IVC

Subpages (1): AACE Adrenal