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==Overview== | ==Overview== | ||
According to the European Society of Endocrinology Clinical Practice Guideline, screening for adrenal incidentaloma includes: family screening for patients with bilateral macronodular [[hyperplasia]], patients with asymptomatic [[vertebral fractures]], patients with possible autonomous [[cortisol]] secretion, patients with a hereditary syndrome leading to [[Adrenal tumor|adrenal tumors]]. Screening test include 24-hour urine [[Metanephrine|fractionated metanephrines]] for [[pheochromocytoma]], 24-hour urinary free [[cortisol]] for patients with symptoms of [[Cushing's syndrome]], and [[Aldosterone|Plasma aldosterone concentration]], [[plasma renin activity]] for patients with [[Primary hyperaldosteronism|Primary aldosteronism]]. | According to the European Society of Endocrinology Clinical Practice Guideline, screening for adrenal incidentaloma includes: family screening for patients with bilateral macronodular [[hyperplasia]], patients with asymptomatic [[vertebral fractures]], patients with possible autonomous [[cortisol]] secretion, and patients with a hereditary syndrome leading to [[Adrenal tumor|adrenal tumors]]. Screening test include 24-hour urine [[Metanephrine|fractionated metanephrines]] for [[pheochromocytoma]], 24-hour urinary free [[cortisol]] for patients with symptoms of [[Cushing's syndrome]], and [[Aldosterone|Plasma aldosterone concentration]], [[plasma renin activity]] for patients with [[Primary hyperaldosteronism|Primary aldosteronism]]. | ||
==Screening== | ==Screening== | ||
According to the European Society of Endocrinology Clinical Practice Guideline, screening for adrenal incidentaloma includes:<ref name="pmid27390021">{{cite journal| author=Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A et al.| title=Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. | journal=Eur J Endocrinol | year= 2016 | volume= 175 | issue= 2 | pages= G1-G34 | pmid=27390021 | doi=10.1530/EJE-16-0467 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27390021 }}</ref> | |||
=== Indications for adrenal incidentaloma screening === | |||
* Patients with possible autonomous [[cortisol]] secretion for [[hypertension]] and [[Diabetes mellitus type 2|type 2 diabetes mellitus.]] | ===Indications for adrenal incidentaloma screening=== | ||
* Patients with asymptomatic [[vertebral fractures]]. | |||
* Screening imaging in patients with a hereditary syndrome leading to [[Adrenal tumor|adrenal tumors]]. | *Patients with possible autonomous [[cortisol]] secretion for [[hypertension]] and [[Diabetes mellitus type 2|type 2 diabetes mellitus.]] | ||
* Family screening with 1 mg [[Dexamethasone suppression test|dexamethasone test]] can be considered in cases of bilateral macronodular [[hyperplasia]], especially in younger patients. | *Patients with asymptomatic [[vertebral fractures]]. | ||
=== Screening measures === | *Screening imaging in patients with a hereditary syndrome leading to [[Adrenal tumor|adrenal tumors]]. | ||
*Family screening with 1 mg [[Dexamethasone suppression test|dexamethasone test]] can be considered in cases of bilateral macronodular [[hyperplasia]], especially in younger patients. | |||
===Screening measures=== | |||
{| class="wikitable" | {| class="wikitable" | ||
!Disease | !Disease | ||
| Line 20: | Line 23: | ||
|[[Pheochromocytoma]]<ref name="pmid12614096">{{cite journal| author=Grumbach MM, Biller BM, Braunstein GD, Campbell KK, Carney JA, Godley PA et al.| title=Management of the clinically inapparent adrenal mass ("incidentaloma"). | journal=Ann Intern Med | year= 2003 | volume= 138 | issue= 5 | pages= 424-9 | pmid=12614096 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12614096 }}</ref> | |[[Pheochromocytoma]]<ref name="pmid12614096">{{cite journal| author=Grumbach MM, Biller BM, Braunstein GD, Campbell KK, Carney JA, Godley PA et al.| title=Management of the clinically inapparent adrenal mass ("incidentaloma"). | journal=Ann Intern Med | year= 2003 | volume= 138 | issue= 5 | pages= 424-9 | pmid=12614096 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12614096 }}</ref> | ||
|'''24-hour urine:''' | |'''24-hour urine:''' | ||
* [[Metanephrine|Fractionated metanephrines]] | *[[Metanephrine|Fractionated metanephrines]] | ||
* [[Catecholamines|Fractionated catecholamines]] | *[[Catecholamines|Fractionated catecholamines]] | ||
'''Blood:''' | '''Blood:''' | ||
* [[Metanephrine|Fractionated metanephrines]] | |||
*[[Metanephrine|Fractionated metanephrines]] | |||
|- | |- | ||
|[[Cushing's syndrome]]<ref name="pmid11275951">{{cite journal| author=Valli N, Catargi B, Ronci N, Vergnot V, Leccia F, Ferriere JM et al.| title=Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas. | journal=Eur J Endocrinol | year= 2001 | volume= 144 | issue= 4 | pages= 401-8 | pmid=11275951 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11275951 }}</ref> | |[[Cushing's syndrome]]<ref name="pmid11275951">{{cite journal| author=Valli N, Catargi B, Ronci N, Vergnot V, Leccia F, Ferriere JM et al.| title=Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas. | journal=Eur J Endocrinol | year= 2001 | volume= 144 | issue= 4 | pages= 401-8 | pmid=11275951 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11275951 }}</ref> | ||
|'''For patients with''' '''symptoms of [[Cushing's syndrome|Cushing's]]''' [[Cushing's syndrome|'''syndrome''']]''':''' | |'''For patients with''' '''symptoms of [[Cushing's syndrome|Cushing's]]''' [[Cushing's syndrome|'''syndrome''']]''':''' | ||
* 24-hour urinary free [[cortisol]] | *24-hour urinary free [[cortisol]] | ||
'''For patients lacking''' '''symptoms of [[Cushing's syndrome|Cushing's]]''' [[Cushing's syndrome|'''syndrome''']]''':''' | '''For patients lacking''' '''symptoms of [[Cushing's syndrome|Cushing's]]''' [[Cushing's syndrome|'''syndrome''']]''':''' | ||
* 1 mg overnight [[dexamethasone suppression test]] | |||
*1 mg overnight [[dexamethasone suppression test]] | |||
|- | |- | ||
|[[Primary hyperaldosteronism|Primary aldosteronism]]<ref name="pmid17287480">{{cite journal| author=Young WF| title=Clinical practice. The incidentally discovered adrenal mass. | journal=N Engl J Med | year= 2007 | volume= 356 | issue= 6 | pages= 601-10 | pmid=17287480 | doi=10.1056/NEJMcp065470 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17287480 }}</ref> | |[[Primary hyperaldosteronism|Primary aldosteronism]]<ref name="pmid17287480">{{cite journal| author=Young WF| title=Clinical practice. The incidentally discovered adrenal mass. | journal=N Engl J Med | year= 2007 | volume= 356 | issue= 6 | pages= 601-10 | pmid=17287480 | doi=10.1056/NEJMcp065470 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17287480 }}</ref> | ||
|[[Aldosterone|Plasma aldosterone concentration]], [[plasma renin activity]] | |[[Aldosterone|Plasma aldosterone concentration]], [[plasma renin activity]] | ||
|} | |} | ||
=== Biochemical Evaluation in Patients with Adrenal Incidentaloma === | |||
==== Mild Autonomous Cortisol Excess ==== | |||
* It refers to an abnormal increase in [[cortisol]] secretion that is independent of normal [[hypothalamic–pituitary]] control without the clinical picture of of [[Cushing's syndrome|Cushing’s syndrome]], also known as [[subclinical]] [[Cushing's syndrome|Cushing’s syndrome]]. | |||
* It is the most common functional disorder in patients with [[adrenal incidentaloma]] with a prevalence of 10%.<ref name="pmid14514341">{{cite journal| author=Barzon L, Sonino N, Fallo F, Palu G, Boscaro M| title=Prevalence and natural history of adrenal incidentalomas. | journal=Eur J Endocrinol | year= 2003 | volume= 149 | issue= 4 | pages= 273-85 | pmid=14514341 | doi=10.1530/eje.0.1490273 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14514341 }}</ref><ref name="pmid10690869">{{cite journal| author=Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Alì A | display-authors=etal| title=A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. | journal=J Clin Endocrinol Metab | year= 2000 | volume= 85 | issue= 2 | pages= 637-44 | pmid=10690869 | doi=10.1210/jcem.85.2.6372 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10690869 }}</ref> | |||
* It is frequently associated with coexisting conditions such as [[obesity]], [[insulin resistance]] or [[Diabetes mellitus type 2|type 2 diabetes mellitus]], [[dyslipidemia]], [[hypertension]], and [[osteoporosis]] than in nonfunctioning [[adrenal]] tumors.<ref name="pmid29510982">{{cite journal| author=Sbardella E, Minnetti M, D'Aluisio D, Rizza L, Di Giorgio MR, Vinci F | display-authors=etal| title=Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas. | journal=Eur J Endocrinol | year= 2018 | volume= 178 | issue= 5 | pages= 501-511 | pmid=29510982 | doi=10.1530/EJE-17-0986 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29510982 }}</ref> | |||
* '''Screening test:''' Overnight [[dexamethasone]] (1 mg) suppression test; an abnormal result is a serum [[cortisol]] level >1.8 μg per deciliter (50 nmol per liter) with confirmation of serum [[dexamethasone]] level (to ensure [[adherence]]); a higher [[serum]] [[cortisol]] cutoff level (e.g., 3–5 μg per deciliter) can be used to reduce the risk of a [[false positive]]. | |||
* '''Confirmatory test:''' Measurement of levels of morning [[serum]] [[corticotropin]] and [[cortisol]] levels, 24-hr urinary [[cortisol]], late-night salivary cortisol, midnight serum cortisol, and [[Dehydroepiandrosterone|DHEAS]]. | |||
* [[False positives]] may occur in patients receiving medications that accelerate [[Liver|hepatic]] [[metabolism]] of [[dexamethasone]] and with nonadherence to dexamethasone. | |||
* Consider a [[Pseudo-Cushing's syndrome|pseudo-Cushing]]’s syndrome state due to [[diabetes]], [[obesity]], [[pregnancy]], [[alcoholism]], [[psychiatric disorders]]. | |||
==== Pheochromocytoma ==== | |||
* Measurement of levels of plasma-free [[metanephrines]] or 24-hr urinary fractionated metanephrines. | |||
* False positives may occur in patients with [[Stress (medicine)|stress]] and illness warranting hospitalization; with medications that increase levels of [[endogenous]] [[Catecholamine|catecholamines]]; with excessive [[caffeine]]; and with recreational drug use (e.g., [[Amphetamine|amphetamines]]). | |||
* Biochemical testing may not be necessary if the [[Adrenal mass causes|adrenal mass]] has CT attenuation of ≤10 Hounsfield units; [[genetic testing]] for inherited syndrome should be performed, regardless of [[family history]], if [[screening test]] is positive. | |||
==== Primary hyperaldosteronism ==== | |||
* '''Screening test:''' Measurement of mid-morning plasma [[aldosterone]] concentration and plasma [[renin]] activity; a ratio of plasma [[aldosterone]] concentration to plasma [[renin]] activity >20 confirms diagnosis. | |||
* '''Confirmatory test:''' If the ratio of plasma [[aldosterone]] concentration to plasma [[renin]] activity <20, confirmatory testing includes 24-hr urinary [[aldosterone]] [[excretion]] test with patient receiving high-[[sodium]] diet, [[aldosterone suppression test]], and testing with [[Saline (medicine)|saline]] infusion while patient is sitting. | |||
* False positives can be caused by [[Beta blockers|beta-blockers]], [[methyldopa]], [[clonidine]], [[nonsteroidal anti-inflammatory drugs]], and [[Oral contraceptive|oral contraceptives]] and [[estrogen]]; false negatives can be caused by [[angiotensin-converting–enzyme inhibitor]]<nowiki/>s, [[angiotensin II receptor blockers]], and [[potassium-sparing diuretics]] (e.g., [[spironolactone]], [[eplerenone]], and [[amiloride]]). | |||
* If patient is a candidate for [[adrenalectomy]] and >35 yr of age, [[adrenal venous sampling]] is recommended to confirm lateralization of [[aldosterone]] to the side of the adrenal mass (some patients have bilateral [[aldosterone]] hypersecretion, or the [[contralateral]] [[adrenal gland]] may be the source of excess [[aldosterone]] and the tumor detected is nonfunctioning) | |||
==References== | ==References== | ||
Latest revision as of 04:38, 9 May 2021
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
Overview
According to the European Society of Endocrinology Clinical Practice Guideline, screening for adrenal incidentaloma includes: family screening for patients with bilateral macronodular hyperplasia, patients with asymptomatic vertebral fractures, patients with possible autonomous cortisol secretion, and patients with a hereditary syndrome leading to adrenal tumors. Screening test include 24-hour urine fractionated metanephrines for pheochromocytoma, 24-hour urinary free cortisol for patients with symptoms of Cushing's syndrome, and Plasma aldosterone concentration, plasma renin activity for patients with Primary aldosteronism.
Screening
According to the European Society of Endocrinology Clinical Practice Guideline, screening for adrenal incidentaloma includes:[1]
Indications for adrenal incidentaloma screening
- Patients with possible autonomous cortisol secretion for hypertension and type 2 diabetes mellitus.
- Patients with asymptomatic vertebral fractures.
- Screening imaging in patients with a hereditary syndrome leading to adrenal tumors.
- Family screening with 1 mg dexamethasone test can be considered in cases of bilateral macronodular hyperplasia, especially in younger patients.
Screening measures
| Disease | Laboratory tests |
|---|---|
| Pheochromocytoma[2] | 24-hour urine:
Blood: |
| Cushing's syndrome[3] | For patients with symptoms of Cushing's syndrome:
For patients lacking symptoms of Cushing's syndrome:
|
| Primary aldosteronism[4] | Plasma aldosterone concentration, plasma renin activity |
Biochemical Evaluation in Patients with Adrenal Incidentaloma
Mild Autonomous Cortisol Excess
- It refers to an abnormal increase in cortisol secretion that is independent of normal hypothalamic–pituitary control without the clinical picture of of Cushing’s syndrome, also known as subclinical Cushing’s syndrome.
- It is the most common functional disorder in patients with adrenal incidentaloma with a prevalence of 10%.[5][6]
- It is frequently associated with coexisting conditions such as obesity, insulin resistance or type 2 diabetes mellitus, dyslipidemia, hypertension, and osteoporosis than in nonfunctioning adrenal tumors.[7]
- Screening test: Overnight dexamethasone (1 mg) suppression test; an abnormal result is a serum cortisol level >1.8 μg per deciliter (50 nmol per liter) with confirmation of serum dexamethasone level (to ensure adherence); a higher serum cortisol cutoff level (e.g., 3–5 μg per deciliter) can be used to reduce the risk of a false positive.
- Confirmatory test: Measurement of levels of morning serum corticotropin and cortisol levels, 24-hr urinary cortisol, late-night salivary cortisol, midnight serum cortisol, and DHEAS.
- False positives may occur in patients receiving medications that accelerate hepatic metabolism of dexamethasone and with nonadherence to dexamethasone.
- Consider a pseudo-Cushing’s syndrome state due to diabetes, obesity, pregnancy, alcoholism, psychiatric disorders.
Pheochromocytoma
- Measurement of levels of plasma-free metanephrines or 24-hr urinary fractionated metanephrines.
- False positives may occur in patients with stress and illness warranting hospitalization; with medications that increase levels of endogenous catecholamines; with excessive caffeine; and with recreational drug use (e.g., amphetamines).
- Biochemical testing may not be necessary if the adrenal mass has CT attenuation of ≤10 Hounsfield units; genetic testing for inherited syndrome should be performed, regardless of family history, if screening test is positive.
Primary hyperaldosteronism
- Screening test: Measurement of mid-morning plasma aldosterone concentration and plasma renin activity; a ratio of plasma aldosterone concentration to plasma renin activity >20 confirms diagnosis.
- Confirmatory test: If the ratio of plasma aldosterone concentration to plasma renin activity <20, confirmatory testing includes 24-hr urinary aldosterone excretion test with patient receiving high-sodium diet, aldosterone suppression test, and testing with saline infusion while patient is sitting.
- False positives can be caused by beta-blockers, methyldopa, clonidine, nonsteroidal anti-inflammatory drugs, and oral contraceptives and estrogen; false negatives can be caused by angiotensin-converting–enzyme inhibitors, angiotensin II receptor blockers, and potassium-sparing diuretics (e.g., spironolactone, eplerenone, and amiloride).
- If patient is a candidate for adrenalectomy and >35 yr of age, adrenal venous sampling is recommended to confirm lateralization of aldosterone to the side of the adrenal mass (some patients have bilateral aldosterone hypersecretion, or the contralateral adrenal gland may be the source of excess aldosterone and the tumor detected is nonfunctioning)
References
- ↑ Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A; et al. (2016). "Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors". Eur J Endocrinol. 175 (2): G1–G34. doi:10.1530/EJE-16-0467. PMID 27390021.
- ↑ Grumbach MM, Biller BM, Braunstein GD, Campbell KK, Carney JA, Godley PA; et al. (2003). "Management of the clinically inapparent adrenal mass ("incidentaloma")". Ann Intern Med. 138 (5): 424–9. PMID 12614096.
- ↑ Valli N, Catargi B, Ronci N, Vergnot V, Leccia F, Ferriere JM; et al. (2001). "Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas". Eur J Endocrinol. 144 (4): 401–8. PMID 11275951.
- ↑ Young WF (2007). "Clinical practice. The incidentally discovered adrenal mass". N Engl J Med. 356 (6): 601–10. doi:10.1056/NEJMcp065470. PMID 17287480.
- ↑ Barzon L, Sonino N, Fallo F, Palu G, Boscaro M (2003). "Prevalence and natural history of adrenal incidentalomas". Eur J Endocrinol. 149 (4): 273–85. doi:10.1530/eje.0.1490273. PMID 14514341.
- ↑ Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Alì A; et al. (2000). "A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology". J Clin Endocrinol Metab. 85 (2): 637–44. doi:10.1210/jcem.85.2.6372. PMID 10690869.
- ↑ Sbardella E, Minnetti M, D'Aluisio D, Rizza L, Di Giorgio MR, Vinci F; et al. (2018). "Cardiovascular features of possible autonomous cortisol secretion in patients with adrenal incidentalomas". Eur J Endocrinol. 178 (5): 501–511. doi:10.1530/EJE-17-0986. PMID 29510982.