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{{Adrenal metastases}}
{{SI}}
{{CMG}}
{{CMG}} {{AE}} {{Ammu}}


==[[Adrenal metastases overview|Overview]]==
==Overview==
Adrenal metastases are the most common malignant lesions involving the adrenal gland and the second most common tumor of the adrenal gland after benign adenomas. These metastases were primarily found on autopsy. The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of adrenal metastasis. Adrenal metastases  must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include [[dizziness]], [[faintness]], [[fatigue]], [[weakness]], and [[weight loss]]. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.


==[[Adrenal metastases historical perspective|Historical Perspective]]==
==Pathophysiology==
*Adrenal metastases occur secondary to hematogenous seeding of neoplastic cells from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
*On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of an adrenal metastasis.


==[[Adrenal metastases classification|Classification]]==
==Differentiating Adrenal metastases from other Diseases==
Adrenal metastasis must be differentiated from other adrenal tumors such as [[adrenocortical adenoma]], adrenal [[metastasis]], [[Pheochromocytoma|adrenal medullary tumors]], and [[Cushing's syndrome]].
{| style="border: 0px; font-size: 90%; margin: 3px; width: 1000px" align="center"


==[[Adrenal metastases pathophysiology|Pathophysiology]]==
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differential Diagnosis}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Clinical picture}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Imagings}}
! style="background: #4479BA; width: 300px;" | {{fontcolor|#FFF|Laboratory tests}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''Adrenocortica'''l carcinoma
| style="padding: 5px 5px; background: #F5F5F5;" |
* Mass effect symptoms
* Symptoms related to  excess [[glucocorticoid]]
* Symptoms related to  excess [[mineralocorticoid]]
* Symptoms related to  excess [[androgen]] or [[estrogen]] secretion
|
* Irregular shape
* Non-[[homogeneous]] density because of central areas of low attenuation due to [[tumor]] [[necrosis]]
* [[Tumor]] [[calcification]]
* Diameter usually >4 cm
* Unilateral location
* High unenhanced [[Computed tomography|CT]] attenuation values (>20 HU)
* Non-[[homogeneous]] enhancement on [[Computed tomography|CT]] with [[intravenous]] [[Contrast medium|contrast]]
* Delay in [[contrast medium]] washout (10 minutes after administration of [[contrast]], an absolute [[contrast medium]] washout of less than 50 percent)
* Hypointensity compared with [[liver]] on T1 weighted [[Magnetic resonance imaging|MRI]] and high to intermediate signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]]
* High standardized uptake value (SUV) on [[FDG-PET|FDG]]-[[PET scan|PET-CT]] study
* Evidence of local [[invasion]] or [[Metastasis|metastases]]
|
* [[Androgen|Adrenal androgens]] ([[DHEAS|DHEAS)]]
* [[Androstenedione]]
* Bioavailable [[testosterone]] should be measured in every patient.
* [[17-Hydroxyprogesterone|17-hydroxyprogesterone]]
* Serum [[estradiol]] in men and postmenopausal women
* [[Cortisol level]]
* Fasting serum [[cortisol]] at 8 AM following a 1 mg dose of [[dexamethasone]] at bedtime
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Adrenal adenoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Symptoms related to  excess [[glucocorticoid]]
* Symptoms related to  excess [[mineralocorticoid]]
|
* Round, [[homogeneous]] with sharp margination
* Unilateral with diameter less than 4 cm
* Low unenhanced [[Computed tomography|CT]] attenuation values (<10 HU)
* Rapid [[contrast medium]] washout after administration of contrast
* An absolute [[contrast medium]] washout of more than 50 percent
* [[Chemical shift]]: evidence of [[lipid]] on [[Magnetic resonance imaging|MRI]]
* Isointensity with [[liver]] on both T1 and T2 weighted [[Magnetic resonance imaging|MRI]] sequences
|
* [[Cortisol level]]
* Fasting [[serum]] [[cortisol]] at 8 AM following a 1 mg dose of [[dexamethasone]] at bedtime
* [[Renin]] ([[Plasma renin activity|PRA]]) or plasma renin concentration (PRC): very low in patients with [[primary aldosteronism]], usually less than 1 ng/mL per hour for [[Plasma renin activity|PRA]] and usually undetectable for PRC<ref name="pmid26372319">{{cite journal| author=Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R et al.| title=Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays. | journal=J Hypertens | year= 2015 | volume= 33 | issue= 12 | pages= 2500-11 | pmid=26372319 | doi=10.1097/HJH.0000000000000727 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26372319  }}</ref>
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Cushing's syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Rapid [[Obesity|weight gain]], particularly of the [[trunk]] and [[face]] with [[limbs]] sparing ([[central obesity]])
* Proximal [[muscle weakness]]
* A [[round face]] often referred to as a "[[moon face]]"
* Excess [[sweating]]
* [[Headache]]
|
* Imaging may show [[mass]] if presents
|
* 24-hour [[urine]] [[cortisol]]
* Midnight salivary [[cortisol]]
* Low-dose [[dexamethasone]] suppression test; high [[cortisol]] level after the [[dexamethasone]] test is suggestive of [[hypercortisolism]].
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Pheochromocytoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Palpitations]] especially in [[Epinephrine|epinephrine-]]<nowiki/>producing [[Tumor|tumors]].
* [[Anxiety]] often resembling that of a [[panic attack]]
* [[Sweating]]
* [[Headaches]] occur in 90 % of patients.
* Paroxysmal attacks of [[hypertension]] but some patients have normal [[blood pressure]].
* It may be [[asymptomatic]] and discovered incidentally after [[Screening (medicine)|screening]] for [[MEN, type 2|MEN]] patients.
|
* Increased [[attenuation]] on non-enhanced [[Computed tomography|CT]] (>20 HU)
* Increased [[mass]] [[vascularity]]
* Delay in [[contrast medium]] washout (10 minutes after administration of [[contrast]], an absolute [[contrast medium]] washout of less than 50 percent)
* High signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]]
* [[Cystic]] and [[hemorrhagic]] changes
* Variable size and may be [[bilateral]]
|
* [[Plasma]] fractionated [[Metanephrine|metanephrines]] 
* 24-hour [[urinary]] fractionated [[Metanephrine|metanephrines]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Adrenal metastasis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Symptoms]] and [[signs]] of primary [[malignancy]] especially [[lung cancer]]
* General constitutional symptoms:
**[[Fever]]
**[[Fatigue]]
**[[Weight loss]]
|
* Irregular shape and non-[[homogeneous]] nature
* Tendency to be [[bilateral]]
* High un-enhanced [[Computed tomography|CT]] [[attenuation]] values (>20 HU) and enhancement with [[Contrast medium|intravenous contrast]] on [[Computed tomography|CT]]
* Delay in [[contrast medium]] washout (10 minutes after administration of contrast, an absolute [[contrast medium]] washout of less than 50 percent)
* Isointensity or slightly less intense than the [[liver]] on T1 weighted [[Magnetic resonance imaging|MRI]] and high to intermediate signal intensity on T2 weighted [[Magnetic resonance imaging|MRI]] (representing an increased water content)
* Elevated standardized uptake value on [[FDG-PET|FDG]]-[[PET scan]]
|
|}


==[[Adrenal metastases causes|Causes]]==
==Epidemiology and Demographics==
* Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.
== Natural History, Complications and Prognosis==
*If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.<ref name="pmid11849252">{{cite journal| author=Lam KY, Lo CY| title=Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital. | journal=Clin Endocrinol (Oxf) | year= 2002 | volume= 56 | issue= 1 | pages= 95-101 | pmid=11849252 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11849252  }} </ref>
*Complications of adrenal metastases include central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.


==[[Adrenal metastases differential diagnosis|Differentiating Adrenal metastases from Other Diseases]]==
==DIfferentiating Adrenal metastases from other diseases==


==[[Adrenal metastases epidemiology and demographics|Epidemiology and Demographics]]==
<small>
{| style="border: 0px; font-size: 90%; margin: 3px; width: 600px" align="center"


==[[Adrenal metastases risk factors|Risk Factors]]==
|+
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Disease}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Gene}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Chromosome}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differentiating Features}}
! colspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Components of MEN}}
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diagnosis}}
|-
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Parathyroid}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pitutary}}
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pancreas}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[von Hippel-Lindau syndrome]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Von Hippel–Lindau tumor suppressor
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |3p25.3
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Angiomatosis, 
* Hemangioblastomas,
* Pheochromocytoma, 
* Renal cell carcinoma,
* Pancreatic cysts (pancreatic serous cystadenoma)
* Endolymphatic sac tumor,
* Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women)
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | +
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Clinical diagnosis
* In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Carney complex]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"| PRKAR1A
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"| 17q23-q24
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"|
* Myxomas of the heart
* Hyperpigmentation of the skin (lentiginosis)
* Endocrine (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease)
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Clinical diagnosis
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Neurofibromatosis type 1]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"|RAS
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"|17
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold"|
* [[Scoliosis]]
* Learning disabilities
* [[Vision]] disorders
* Cutaneous [[lesion]]s
* [[Epilepsy]].
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |'''<u>Prenatal</u>'''
* Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus.
'''<u>Postnatal</u>'''
Cardinal Clinical Features" are required for positive diagnosis.
* Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals.
* Two or more neurofibromas of any type or 1 plexiform neurofibroma
* Freckling in the axillary (Crowe sign) or inguinal regions
* Optic glioma
* Two or more Lisch nodules (pigmented iris hamartomas)
* A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold"  |[[Li-Fraumeni syndrome]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |TP53
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Early onset of diverse amount of [[cancer]]s such as
* [[Sarcoma]]
* [[Cancer]]s of 
** [[Breast]]
** [[Brain]]
** [[Adrenal gland]]s
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''<u>Criteria</u>'''
* Sarcoma at a young age (below 45)
* A first-degree relative diagnosed with any cancer at a young age (below 45)
* A first or second degree relative with any cancer diagnosed before age 60.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold"  |[[Gardner's syndrome]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | APC
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | 5q21
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Multiple polyps in the colon 
* Osteomas of the skull
* Thyroid cancer,
* Epidermoid cysts,
* Fibromas
* Desmoid tumors
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Clinical diagnosis
* Colonoscopy
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Multiple endocrine neoplasia type 2]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |''RET''
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Medullary thyroid carcinoma]] (MTC)
* [[Pheochromocytoma]]
* Primary [[hyperparathyroidism]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | +
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Hypercalcemia]]
* [[Hypophosphatemia]],
* Elevated [[parathyroid hormone]],
* Elevated [[norepinephrine]]
'''<u>Criteria</u>'''
Two or more specific endocrine tumors
* [[Medullary thyroid carcinoma]]
* [[Pheochromocytoma]]
* [[Parathyroid]] hyperplasia
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Cowden syndrome]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |PTEN
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | Hamartomas
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* ''PTEN'' mutation probability risk calculator
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Acromegaly]]/[[gigantism]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Enlargement of the [[hand]]s, [[feet]], [[nose]], [[lip]]s and [[ear]]s, and a general thickening of the [[skin]]
* [[Hypertrichosis]]
* [[Hyperpigmentation]]
* [[Hyperhidrosis]]
* [[Carpal tunnel syndrome]].
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* An elevated concentration of serum [[Growth hormone|growth hormone (GH)]] and [[Insulin-like growth factor|insulin-like growth factor 1(IGF-1)]] levels is diagnostic of acromegaly.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pituitary adenoma]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | -
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Visual field defect]]s classically [[bitemporal hemianopsia]]
* Increased [[intracranial pressure]]
* [[Migraine]]
* [[Lateral rectus]] palsy
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
:*Elevated serum level of  [[prolactin]]
:*Elevated or decreased serum level of  [[adrenocorticotropic hormone]] (ACTH)
:*Elevated or decreased serum level of  [[growth hormone]] (GH)
:*Elevated or decreased serum level of  [[thyroid-stimulating hormone]] (TSH)
:*Elevated or decreased serum level of  [[follicle-stimulating hormone]] (FSH)
:*Elevated or decreased serum level of  [[luteinizing hormone]] (LH)
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Hyperparathyroidism]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
* [[Kidney stone]]s
* [[Hypercalcemia]],
* [[Constipation]]
* [[Peptic ulcer]]s
* [[Depression]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level is diagnostic of primary hyperparathyroidism.
* Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum [[parathyroid hormone]] level and low to normal serum [[calcium]].
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level in post [[Kidney transplantation|renal transplant]] patients is diagnostic of tertiary hyperparathyoidism.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pheochromocytoma]]/[[paraganglioma]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
''VHL''
''RET''
''NF1''  
''SDHB'' 
''SDHD''
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Characterized by
* Episodic [[hypertension]]
* [[Palpitation]]s
* [[Anxiety]]
* [[Diaphoresis]]
* [[Weight loss]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection.
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Adrenocortical carcinoma]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
*p53
*Retinoblastoma h19
*Insulin-like growth factor II (IGF-II)
*p57<sup>kip2</sup>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17p, 13q 
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* [[Cushing syndrome]] ([[cortisol]] hypersecretion)
* [[Conn syndrome]] ([[aldosterone]] hypersecretion)
* [[virilization]] ([[testosterone]] hypersecretion)
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki>
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
* Increased serum glucose
* Increased urine cortisol
* Serum androstenedione and dehydroepiandrosterone
* Low serum potassium
* Low plasma renin activity
* High serum aldosterone.
* Excess serum estrogen.
|-
| colspan="8" style="padding: 5px 5px; background: #F5F5F5;" |<small>Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013<ref name="pmid23917672">{{cite journal| author=Toledo SP, Lourenço DM, Toledo RA| title=A differential diagnosis of inherited endocrine tumors and their tumor counterparts. | journal=Clinics (Sao Paulo) | year= 2013 | volume= 68 | issue= 7 | pages= 1039-56 | pmid=23917672 | doi=10.6061/clinics/2013(07)24 | pmc=PMC3715026 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23917672  }} </ref> </small>
|}
</small>


==[[Adrenal metastases screening|Screening]]==
== Treatment ==
 
=== Medical Therapy ===
==[[Adrenal metastases natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
*The mainstay of therapy for adrenal metastases is chemotherapy.
 
=== Surgery ===
==Diagnosis==
*Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis is the adrenal gland.
[[Adrenal metastases history and symptoms|History and Symptoms]] | [[Adrenal metastases physical examination|Physical Examination]] | [[Adrenal metastases laboratory findings|Laboratory Findings]] | [[Adrenal metastases chest x ray|Chest X Ray]] | [[Adrenal metastases CT|CT]] | [[Adrenal metastases MRI|MRI]] | [[Adrenal metastases echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Adrenal metastases other imaging findings|Other Imaging Findings]] | [[Adrenal metastases other diagnostic studies|Other Diagnostic Studies]]
=== Prevention ===
 
*There are no primary preventive measures available for adrenal metastases.
==Treatment==
[[Adrenal metastases medical therapy|Medical Therapy]] | [[Adrenal metastases surgery|Surgery]] | [[Adrenal metastases primary prevention|Primary Prevention]]  | [[Adrenal metastases cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Adrenal metastases future or investigational therapies|Future or Investigational Therapies]]
 
==Case studies==
[[Adrenal metastases case study one|Case #1]]


==References==
==References==
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Latest revision as of 07:26, 30 September 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Overview

Adrenal metastases are the most common malignant lesions involving the adrenal gland and the second most common tumor of the adrenal gland after benign adenomas. These metastases were primarily found on autopsy. The pathogenesis of adrenal metastases is characterized by metastases from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma. On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of adrenal metastasis. Adrenal metastases must be differentiated from other diseases that cause tumors in adrenal gland such as nonfunctional adenoma, primary carcinoma in adrenal glands, adrenal cyst, and non-functional pheochromocytoma. Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy. Symptoms of adrenal metastases may include dizziness, faintness, fatigue, weakness, and weight loss. CT is the imaging modality of choice for adrenal metastases. The mainstay of therapy for adrenal metastases is chemotherapy.

Pathophysiology

  • Adrenal metastases occur secondary to hematogenous seeding of neoplastic cells from renal cell carcinoma, melanoma, lung cancer, colorectal cancer, breast cancer and lymphoma.
  • On gross pathology, a unilateral, small asymptomatic lesion is a characteristic finding of an adrenal metastasis.

Differentiating Adrenal metastases from other Diseases

Adrenal metastasis must be differentiated from other adrenal tumors such as adrenocortical adenoma, adrenal metastasis, adrenal medullary tumors, and Cushing's syndrome.

Differential Diagnosis Clinical picture Imagings Laboratory tests
Adrenocortical carcinoma
Adrenal adenoma
Cushing's syndrome
  • Imaging may show mass if presents
Pheochromocytoma
Adrenal metastasis

Epidemiology and Demographics

  • Adrenal metastases are thought to be present in up to 27% of patients with known malignant epithelial tumors at autopsy.

Natural History, Complications and Prognosis

  • If left untreated, 20-35% of patients with cancer may progress to develop adrenal metastases.[2]
  • Complications of adrenal metastases include central necrosis with adrenal hemorrhage and paraneoplastic leukemoid reaction.

DIfferentiating Adrenal metastases from other diseases

Disease Gene Chromosome Differentiating Features Components of MEN Diagnosis
Parathyroid Pitutary Pancreas
von Hippel-Lindau syndrome Von Hippel–Lindau tumor suppressor 3p25.3
  • Angiomatosis, 
  • Hemangioblastomas,
  • Pheochromocytoma, 
  • Renal cell carcinoma,
  • Pancreatic cysts (pancreatic serous cystadenoma)
  • Endolymphatic sac tumor,
  • Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women)
- - +
  • Clinical diagnosis
  • In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations.
Carney complex  PRKAR1A 17q23-q24
  • Myxomas of the heart
  • Hyperpigmentation of the skin (lentiginosis)
  • Endocrine (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease)
- - -
  • Clinical diagnosis
Neurofibromatosis type 1 RAS 17 - - - Prenatal
  • Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus.

Postnatal Cardinal Clinical Features" are required for positive diagnosis.

  • Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals.
  • Two or more neurofibromas of any type or 1 plexiform neurofibroma
  • Freckling in the axillary (Crowe sign) or inguinal regions
  • Optic glioma
  • Two or more Lisch nodules (pigmented iris hamartomas)
  • A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis.
Li-Fraumeni syndrome TP53 17 Early onset of diverse amount of cancers such as - - -

Criteria

  • Sarcoma at a young age (below 45)
  • A first-degree relative diagnosed with any cancer at a young age (below 45)
  • A first or second degree relative with any cancer diagnosed before age 60.
Gardner's syndrome APC  5q21
  • Multiple polyps in the colon 
  • Osteomas of the skull
  • Thyroid cancer,
  • Epidermoid cysts,
  • Fibromas
  • Desmoid tumors
- - -
  • Clinical diagnosis
  • Colonoscopy
Multiple endocrine neoplasia type 2 RET - + - -

Criteria Two or more specific endocrine tumors

Cowden syndrome PTEN -  Hamartomas - - -
  • PTEN mutation probability risk calculator
Acromegaly/gigantism - - - + -
Pituitary adenoma - - - + -
Hyperparathyroidism - - - + - -
  • An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyroidism.
  • Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum parathyroid hormone level and low to normal serum calcium.
  • An elevated concentration of serum calcium with elevated parathyroid hormone level in post renal transplant patients is diagnostic of tertiary hyperparathyoidism.
Pheochromocytoma/paraganglioma

VHL RET NF1   SDHB  SDHD

- Characterized by - - -
  • Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection.
Adrenocortical carcinoma
  • p53
  • Retinoblastoma h19
  • Insulin-like growth factor II (IGF-II)
  • p57kip2
17p, 13q  - - -
  • Increased serum glucose
  • Increased urine cortisol
  • Serum androstenedione and dehydroepiandrosterone
  • Low serum potassium
  • Low plasma renin activity
  • High serum aldosterone.
  • Excess serum estrogen.
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013[3]

Treatment

Medical Therapy

  • The mainstay of therapy for adrenal metastases is chemotherapy.

Surgery

  • Adrenalectomy in conjunction with chemotherapy is the most common approach to the treatment of adrenal metastases if primary disease is well controlled and the only site of metastasis is the adrenal gland.

Prevention

  • There are no primary preventive measures available for adrenal metastases.

References

  1. Manolopoulou J, Fischer E, Dietz A, Diederich S, Holmes D, Junnila R; et al. (2015). "Clinical validation for the aldosterone-to-renin ratio and aldosterone suppression testing using simultaneous fully automated chemiluminescence immunoassays". J Hypertens. 33 (12): 2500–11. doi:10.1097/HJH.0000000000000727. PMID 26372319.
  2. Lam KY, Lo CY (2002). "Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital". Clin Endocrinol (Oxf). 56 (1): 95–101. PMID 11849252.
  3. Toledo SP, Lourenço DM, Toledo RA (2013). "A differential diagnosis of inherited endocrine tumors and their tumor counterparts". Clinics (Sao Paulo). 68 (7): 1039–56. doi:10.6061/clinics/2013(07)24. PMC 3715026. PMID 23917672.