Incidentaloma medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
The mainstay of treatment for adrenal incidentaloma is surgery but | The mainstay of treatment for [[Adrenal gland|adrenal]] incidentaloma is surgery but pre-operative medical management is needed for functional masses. Peri-operative medical management of patients with sub-clinical [[Cushing's syndrome]] includes [[glucocorticoid]] therapy during [[surgery]]. Such patients can safely undergo surgical resection of their [[tumor]] and have their [[cortisol]] levels measured post-operatively. Preoperative medical management of patients with [[pheochromocytoma]] includes preoperative treatment to control [[hypertension]] during surgery and [[hypotension]] after it. Three medical regimens for preoperative management of [[pheochromocytoma]]: Combined [[Alpha blocker|alpha]] and [[beta-adrenergic blockers]], [[Calcium channel blocker|calcium channel blockers]], and [[Metyrosine]]. Pre-operative medical management of patients with [[Hyperaldosteronism|aldosteronoma]] include medical therapy with [[mineralocorticoid]] [[Receptor antagonist|receptor antagonists]] should be reserved for those who are unable or unwilling to undergo surgery. | ||
==Medical Therapy== | ==Medical Therapy== | ||
The mainstay of treatment for adrenal incidentaloma is surgery but preoperative medical management is needed for functional [[Mass|masses]]. | The mainstay of treatment for adrenal incidentaloma is surgery but preoperative medical management is needed for functional [[Mass|masses]]. | ||
==== | ==== Peri-operative medical management of patients with subclinical [[Cushing's syndrome]]: ==== | ||
There are two approaches to deal with cases of [[Cushing's syndrome|Cushing's syndrome:]]<ref name="pmid203752102">{{cite journal| author=Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F et al.| title=Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 6 | pages= 2736-45 | pmid=20375210 | doi=10.1210/jc.2009-2387 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20375210 }}</ref><ref name="pmid20823463">{{cite journal| author=Nieman LK| title=Approach to the patient with an adrenal incidentaloma. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4106-13 | pmid=20823463 | doi=10.1210/jc.2010-0457 | pmc=2936073 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823463 }}</ref><ref name="pmid193269852">{{cite journal| author=Marko NF, Gonugunta VA, Hamrahian AH, Usmani A, Mayberg MR, Weil RJ| title=Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation. | journal=J Neurosurg | year= 2009 | volume= 111 | issue= 3 | pages= 540-4 | pmid=19326985 | doi=10.3171/2008.12.JNS081265 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19326985 }}</ref> | *There are two approaches to deal with cases of [[Cushing's syndrome|Cushing's syndrome:]]<ref name="pmid203752102">{{cite journal| author=Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F et al.| title=Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 6 | pages= 2736-45 | pmid=20375210 | doi=10.1210/jc.2009-2387 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20375210 }}</ref><ref name="pmid20823463">{{cite journal| author=Nieman LK| title=Approach to the patient with an adrenal incidentaloma. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 9 | pages= 4106-13 | pmid=20823463 | doi=10.1210/jc.2010-0457 | pmc=2936073 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20823463 }}</ref><ref name="pmid193269852">{{cite journal| author=Marko NF, Gonugunta VA, Hamrahian AH, Usmani A, Mayberg MR, Weil RJ| title=Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation. | journal=J Neurosurg | year= 2009 | volume= 111 | issue= 3 | pages= 540-4 | pmid=19326985 | doi=10.3171/2008.12.JNS081265 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19326985 }}</ref> | ||
* Patients do not require [[glucocorticoid]] therapy during surgery. Such patients can safely undergo surgical resection of their [[tumor]] and have their [[cortisol]] levels measured | ** Patients do not require [[glucocorticoid]] therapy during surgery. Such patients can safely undergo surgical resection of their [[tumor]] and have their [[cortisol]] levels measured post-operatively. | ||
* This would provide an early evaluation of surgical success. [[Hydrocortisone]] may be given to the patient 30 mg in the morning and 10 mg in the afternoon until the result of the [[cortisol]] level becomes available.<ref name="pmid19326985">{{cite journal| author=Marko NF, Gonugunta VA, Hamrahian AH, Usmani A, Mayberg MR, Weil RJ| title=Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation. | journal=J Neurosurg | year= 2009 | volume= 111 | issue= 3 | pages= 540-4 | pmid=19326985 | doi=10.3171/2008.12.JNS081265 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19326985 }}</ref> | ** This would provide an early evaluation of surgical success. [[Hydrocortisone]] may be given to the patient 30 mg in the morning and 10 mg in the afternoon until the result of the [[cortisol]] level becomes available.<ref name="pmid19326985">{{cite journal| author=Marko NF, Gonugunta VA, Hamrahian AH, Usmani A, Mayberg MR, Weil RJ| title=Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation. | journal=J Neurosurg | year= 2009 | volume= 111 | issue= 3 | pages= 540-4 | pmid=19326985 | doi=10.3171/2008.12.JNS081265 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19326985 }}</ref> | ||
* Another approach would be to cover all patients with [[glucocorticoids]] | ** Another approach would be to cover all patients with [[glucocorticoids]] peri-operatively.<ref name="pmid20375210">{{cite journal| author=Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F et al.| title=Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. | journal=J Clin Endocrinol Metab | year= 2010 | volume= 95 | issue= 6 | pages= 2736-45 | pmid=20375210 | doi=10.1210/jc.2009-2387 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20375210 }}</ref> | ||
==== | ==== Pre-operative medical management of patients with pheochromocytoma ==== | ||
* All patients undergoing surgery need preoperative treatment to control [[hypertension]] during surgery and [[hypotension]] after it.<ref name="pmid20823463" /><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> | * All patients undergoing surgery need preoperative treatment to control [[hypertension]] during surgery and [[hypotension]] after it.<ref name="pmid20823463" /><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> | ||
* According to Endocrine Society’s 2014 clinical practice guidelines, there are three medical regimens for preoperative management of [[pheochromocytoma]]:<sup>[[Pheochromocytoma medical therapy#cite note-pmid248931352-1|[1]]][[Pheochromocytoma medical therapy#cite note-pmid14766711-2|[2]]]</sup> | * According to Endocrine Society’s 2014 clinical practice guidelines, there are three medical regimens for preoperative management of [[pheochromocytoma]]:<sup>[[Pheochromocytoma medical therapy#cite note-pmid248931352-1|[1]]][[Pheochromocytoma medical therapy#cite note-pmid14766711-2|[2]]]</sup> | ||
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==== [[Calcium channel blocker]] ==== | ==== [[Calcium channel blocker]] ==== | ||
* It is used to control [[blood pressure]] | * It is used to control [[blood pressure]] pre-operatively and an [[intravenous injection]] is given intra-operatively. | ||
* Its main use is controlling [[blood pressure]] in case of failed [[Alpha blocker|alpha]] and [[beta blockers]] regimen or unaccepted side effects in that regimen.<ref name="pmid10363888">{{cite journal| author=Goldstein RE, O'Neill JA, Holcomb GW, Morgan WM, Neblett WW, Oates JA et al.| title=Clinical experience over 48 years with pheochromocytoma. | journal=Ann Surg | year= 1999 | volume= 229 | issue= 6 | pages= 755-64; discussion 764-6 | pmid=10363888 | doi= | pmc=1420821 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10363888 }}</ref> | * Its main use is controlling [[blood pressure]] in case of failed [[Alpha blocker|alpha]] and [[beta blockers]] regimen or unaccepted side effects in that regimen.<ref name="pmid10363888">{{cite journal| author=Goldstein RE, O'Neill JA, Holcomb GW, Morgan WM, Neblett WW, Oates JA et al.| title=Clinical experience over 48 years with pheochromocytoma. | journal=Ann Surg | year= 1999 | volume= 229 | issue= 6 | pages= 755-64; discussion 764-6 | pmid=10363888 | doi= | pmc=1420821 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10363888 }}</ref> | ||
| Line 34: | Line 34: | ||
* It is the last medical line of treatment. It inhibits [[catecholamine]] synthesis. | * It is the last medical line of treatment. It inhibits [[catecholamine]] synthesis. | ||
* It is used in case of failure of other medical lines of treatment or in patients who cannot tolerate them. | * It is used in case of failure of other medical lines of treatment or in patients who cannot tolerate them. | ||
* Clinicians use combined treatment in difficult cases and if [[radiofrequency ablation]] for [[metastatic]] foci will be used. | * Clinicians use combined treatment in difficult cases and if [[radiofrequency ablation]] for [[metastatic]] foci will be used. | ||
* Side effects of [[Metyrosine]] include:<ref name="pmid15761546">{{cite journal| author=Bravo EL| title=Pheochromocytoma: current perspectives in the pathogenesis, diagnosis, and management. | journal=Arq Bras Endocrinol Metabol | year= 2004 | volume= 48 | issue= 5 | pages= 746-50 | pmid=15761546 | doi=/S0004-27302004000500021 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15761546 }}</ref> | |||
**[[Crystalluria|Crystalluria]] | |||
**[[Extrapyramidal symptom|Extrapyramidal]] manifestations | |||
**High cost. | |||
=====Pre-operative medical management of patients with primary hyperaldosteronism===== | |||
===== | *Medical therapy with [[mineralocorticoid receptor]] [[antagonists]] should be reserved for those who are unable or unwilling to undergo surgery.<ref name="pmid26934393">{{cite journal| author=Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H et al.| title=The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. | journal=J Clin Endocrinol Metab | year= 2016 | volume= 101 | issue= 5 | pages= 1889-916 | pmid=26934393 | doi=10.1210/jc.2015-4061 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26934393 }}</ref><ref name="pmid17492946">{{cite journal| author=Young WF| title=Primary aldosteronism: renaissance of a syndrome. | journal=Clin Endocrinol (Oxf) | year= 2007 | volume= 66 | issue= 5 | pages= 607-18 | pmid=17492946 | doi=10.1111/j.1365-2265.2007.02775.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17492946 }}</ref><ref name="pmid20823463" /> | ||
**[[Adrenalectomy]] in patients with a documented unilateral source of [[Primary hyperaldosteronism|primary aldosteronism]] is more cost effective compared with lifelong medical therapy. | |||
**[[Laparoscopic surgery|Laparoscopic]] [[adrenalectomy]] compared to an open procedure is associated with a shorter hospital stay, fewer complications, and faster recovery. | |||
**Resection of the [[adrenal tumor]] will result in resolution of [[hypokalemia]] and improvement in [[hypertension]] in almost all patients. | |||
====== | ====== Post-operative management of patients with primary hyperaldosteronism====== | ||
* | *Postoperative management in patients with primary [[hyperaldosteronism]] includes:<ref name="pmid16932426">{{cite journal| author=Mattsson C, Young WF| title=Primary aldosteronism: diagnostic and treatment strategies. | journal=Nat Clin Pract Nephrol | year= 2006 | volume= 2 | issue= 4 | pages= 198-208; quiz, 1 p following 230 | pmid=16932426 | doi=10.1038/ncpneph0151 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16932426 }}</ref> | ||
*[[ | **[[Potassium]] supplementation and [[mineralocorticoid]] receptor antagonists should be stopped post-operatively with close monitoring of serum [[potassium]]. | ||
**A temporary state of [[hypoaldosteronism]] may also develop in some patients with [[Primary hyperaldosteronism|primary aldosteronism]] post-operatively and can be managed by increasing salt intake. | |||
* | |||
==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
Latest revision as of 16:09, 9 November 2017
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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
The mainstay of treatment for adrenal incidentaloma is surgery but pre-operative medical management is needed for functional masses. Peri-operative medical management of patients with sub-clinical Cushing's syndrome includes glucocorticoid therapy during surgery. Such patients can safely undergo surgical resection of their tumor and have their cortisol levels measured post-operatively. Preoperative medical management of patients with pheochromocytoma includes preoperative treatment to control hypertension during surgery and hypotension after it. Three medical regimens for preoperative management of pheochromocytoma: Combined alpha and beta-adrenergic blockers, calcium channel blockers, and Metyrosine. Pre-operative medical management of patients with aldosteronoma include medical therapy with mineralocorticoid receptor antagonists should be reserved for those who are unable or unwilling to undergo surgery.
Medical Therapy
The mainstay of treatment for adrenal incidentaloma is surgery but preoperative medical management is needed for functional masses.
Peri-operative medical management of patients with subclinical Cushing's syndrome:
- There are two approaches to deal with cases of Cushing's syndrome:[1][2][3]
- Patients do not require glucocorticoid therapy during surgery. Such patients can safely undergo surgical resection of their tumor and have their cortisol levels measured post-operatively.
- This would provide an early evaluation of surgical success. Hydrocortisone may be given to the patient 30 mg in the morning and 10 mg in the afternoon until the result of the cortisol level becomes available.[4]
- Another approach would be to cover all patients with glucocorticoids peri-operatively.[5]
Pre-operative medical management of patients with pheochromocytoma
- All patients undergoing surgery need preoperative treatment to control hypertension during surgery and hypotension after it.[2][6]
- According to Endocrine Society’s 2014 clinical practice guidelines, there are three medical regimens for preoperative management of pheochromocytoma:[1][2]
- Combined alpha and beta-adrenergic blockers
- Calcium channel blockers
- Metyrosine
Alpha adrenoceptor blocker
- It is used to counteract hypertension and the beta-1 adrenoceptor antagonist atenolol to reduce cardiac output. They can block the sudden release of adrenaline during surgical stress and prevent hypertensive crisis. The patient is ready for surgery after 10 to 14 days of initiation of alpha-adrenergic blockade. Patients should take high sodium diet to prevent orthostatic hypotension due to alpha blockers. After adequate alpha-adrenergic blockade has been achieved, a beta-adrenergic blocker is initiated 3 days before surgery.[7]
- It should never be started first because unopposed alpha-adrenergic receptor stimulation can lead to the brisk increase in blood pressure. It should be used with caution due to the risk of heart failure, pulmonary edema, and asthma.[8]
Calcium channel blocker
- It is used to control blood pressure pre-operatively and an intravenous injection is given intra-operatively.
- Its main use is controlling blood pressure in case of failed alpha and beta blockers regimen or unaccepted side effects in that regimen.[9]
Metyrosine
- It is the last medical line of treatment. It inhibits catecholamine synthesis.
- It is used in case of failure of other medical lines of treatment or in patients who cannot tolerate them.
- Clinicians use combined treatment in difficult cases and if radiofrequency ablation for metastatic foci will be used.
- Side effects of Metyrosine include:[10]
- Crystalluria
- Extrapyramidal manifestations
- High cost.
Pre-operative medical management of patients with primary hyperaldosteronism
- Medical therapy with mineralocorticoid receptor antagonists should be reserved for those who are unable or unwilling to undergo surgery.[11][12][2]
- Adrenalectomy in patients with a documented unilateral source of primary aldosteronism is more cost effective compared with lifelong medical therapy.
- Laparoscopic adrenalectomy compared to an open procedure is associated with a shorter hospital stay, fewer complications, and faster recovery.
- Resection of the adrenal tumor will result in resolution of hypokalemia and improvement in hypertension in almost all patients.
Post-operative management of patients with primary hyperaldosteronism
- Postoperative management in patients with primary hyperaldosteronism includes:[13]
- Potassium supplementation and mineralocorticoid receptor antagonists should be stopped post-operatively with close monitoring of serum potassium.
- A temporary state of hypoaldosteronism may also develop in some patients with primary aldosteronism post-operatively and can be managed by increasing salt intake.
References
- ↑ Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F; et al. (2010). "Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism". J Clin Endocrinol Metab. 95 (6): 2736–45. doi:10.1210/jc.2009-2387. PMID 20375210.
- ↑ 2.0 2.1 2.2 Nieman LK (2010). "Approach to the patient with an adrenal incidentaloma". J Clin Endocrinol Metab. 95 (9): 4106–13. doi:10.1210/jc.2010-0457. PMC 2936073. PMID 20823463.
- ↑ Marko NF, Gonugunta VA, Hamrahian AH, Usmani A, Mayberg MR, Weil RJ (2009). "Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation". J Neurosurg. 111 (3): 540–4. doi:10.3171/2008.12.JNS081265. PMID 19326985.
- ↑ Marko NF, Gonugunta VA, Hamrahian AH, Usmani A, Mayberg MR, Weil RJ (2009). "Use of morning serum cortisol level after transsphenoidal resection of pituitary adenoma to predict the need for long-term glucocorticoid supplementation". J Neurosurg. 111 (3): 540–4. doi:10.3171/2008.12.JNS081265. PMID 19326985.
- ↑ Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F; et al. (2010). "Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism". J Clin Endocrinol Metab. 95 (6): 2736–45. doi:10.1210/jc.2009-2387. PMID 20375210.
- ↑ 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.
- ↑ Adler JT, Meyer-Rochow GY, Chen H, Benn DE, Robinson BG, Sippel RS; et al. (2008). "Pheochromocytoma: current approaches and future directions". Oncologist. 13 (7): 779–93. doi:10.1634/theoncologist.2008-0043. PMID 18617683.
- ↑ Pacak K (2007). "Preoperative management of the pheochromocytoma patient". J Clin Endocrinol Metab. 92 (11): 4069–79. doi:10.1210/jc.2007-1720. PMID 17989126.
- ↑ Goldstein RE, O'Neill JA, Holcomb GW, Morgan WM, Neblett WW, Oates JA; et al. (1999). "Clinical experience over 48 years with pheochromocytoma". Ann Surg. 229 (6): 755–64, discussion 764-6. PMC 1420821. PMID 10363888.
- ↑ Bravo EL (2004). "Pheochromocytoma: current perspectives in the pathogenesis, diagnosis, and management". Arq Bras Endocrinol Metabol. 48 (5): 746–50. doi:/S0004-27302004000500021 Check
|doi=value (help). PMID 15761546. - ↑ Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H; et al. (2016). "The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 101 (5): 1889–916. doi:10.1210/jc.2015-4061. PMID 26934393.
- ↑ Young WF (2007). "Primary aldosteronism: renaissance of a syndrome". Clin Endocrinol (Oxf). 66 (5): 607–18. doi:10.1111/j.1365-2265.2007.02775.x. PMID 17492946.
- ↑ Mattsson C, Young WF (2006). "Primary aldosteronism: diagnostic and treatment strategies". Nat Clin Pract Nephrol. 2 (4): 198–208, quiz, 1 p following 230. doi:10.1038/ncpneph0151. PMID 16932426.