Adrenal metastases

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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

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.

Diagnosis

Symptoms

  • Symptoms of adrenal metastases may include the following:

Physical Examination

  • Patients with adrenal metastases usually appear cachectic.
  • Physical examination may be remarkable for:
  • Abdominal mass

Laboratory Findings

  • There are no specific laboratory findings associated with adrenal metastases.

Imaging Findings

  • CT is the imaging modality of choice for adrenal metastases.
  • On CT, adrenal metastases may demonstrate less than 50% washout.
  • On MRI, adrenal metastases may demonstrate:
  • T1: usually exhibit low signal intensity
  • T2: usually exhibit high signal intensity
  • T1 C+ (Gd): usually has progressive enhancement after administration of contrast material.

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. PMID 26372319. doi:10.1097/HJH.0000000000000727. 
  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. PMC 3715026Freely accessible. PMID 23917672. doi:10.6061/clinics/2013(07)24. 

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