Adrenal cortical adenoma is often hormonally silent and discovered incidentally. In symptomatic patients, the resultant adrenal disease will reflect which hormone(s) is/are produced abundantly. There are specialized biochemical tests and imaging studies to make the diagnosis.
Presentation
Adrenal cortical adenomas are benign tumors that stem from the cortex of the adrenal gland. These adenomas are frequently discovered as adrenal incidentalomas, adrenal tumors confirmed on imaging during a workup for unrelated causes. Nearly 85% of adrenal incidentalomas are benign and nonfunctional [1] [2]. Functioning adrenal cortical adenomas may cause hypertension, orthostatic hypotension, and tachycardia. A physical exam may reveal central obesity, hirsutism, striae, and gynecomastia. An ophthalmologic exam may reveal retinopathy secondary to chronic hypertension. Endocrine diseases resulting from functioning adrenal cortical adenomas reflect the excess production of adrenal gland hormones such as aldosterone (primary aldosteronism), cortisol (Cushing's syndrome), and sex hormones.
Primary aldosteronism is not characterized by a specific clinical presentation. These patients may have unprovoked hypokalemia and hypertension although potassium levels can be normal [3]. As a result of hypernatremia, hypokalemic alkalosis, and other related mechanisms, patients may develop fatigue, weakness, headaches, tetany, and paresthesias. Also, polyuria and polydipsia could result from hypokalemia-induced nephrogenic diabetes insipidus. Complications secondary to chronic hypertension include renal, cardiac, neurologic, and ophthalmologic manifestations.
Cushing's syndrome is characterized by weakness, bruising, weight gain, and depression. Affected individuals may also develop osteoporosis and metabolic syndrome [4].
Finally, androgen or estrogen-secreting tumors may cause virilization in females and feminization in males.
Entire Body System
- Weakness
As a result of hypernatremia, hypokalemic alkalosis, and other related mechanisms, patients may develop fatigue, weakness, headaches, tetany, and paresthesias. [symptoma.com]
Immunohistochemical studies revealed variable immunoreactivity for simple epithelial cell cytokeratins and for synaptophysin (weak staining) in a minority of tumor cells. [ncbi.nlm.nih.gov]
Symptoms caused by aldosterone production The main signs and symptoms caused by aldosterone-producing adrenal tumors are: High blood pressure Weakness Muscle cramps Low blood potassium levels Adrenal adenomas often make aldosterone, but adrenal cancers [cancer.org]
- Virilization
A virilizing, gonadotrophin-responsive adrenal cortical adenoma was removed from a 54-year-old woman. [ncbi.nlm.nih.gov]
Patients with virilization or feminization should be tested for androgens and estrogens respectively. [symptoma.com]
[…] is more commonly associated with ACC, comprises 1-2% of ACC ( J Clin Oncol 2011;29:e127 ) Androgen-secreting adrenal tumors more common in childhood, with ACTs most commonly presenting with virilization with/without Cushing's syndrome Adrenal cortex [pathologyoutlines.com]
- Asymptomatic
Five years after treatment of the Cushing's syndrome by removal of the tumor, asymptomatic mild hypercalcemia was incidentally noticed in both patients, which suggested the occurrence of primary hyperparathyroidism. [ncbi.nlm.nih.gov]
The majority (~95%) of adrenal adenomas are non-functioning, in which case they are asymptomatic. If found incidentally, please refer to the Management of incidental adrenal masses: American College of Radiology white paper. [radiopaedia.org]
However, all abnormalities were asymptomatic. Magnetic resonance imaging (MRI) revealed well-circumscribed masses within the dura mater at the T12-L1 and L3-L4 level. [link.springer.com]
- Fatigue
As a result of hypernatremia, hypokalemic alkalosis, and other related mechanisms, patients may develop fatigue, weakness, headaches, tetany, and paresthesias. [symptoma.com]
Common symptoms of Cushing's syndrome can include upper body obesity; severe fatigue and muscle weakness; high blood pressure ; backache; high blood sugar; easy bruising; and bluish-red stretch marks on the skin. [rarediseases.info.nih.gov]
[…] other types of Cushing syndrome) Periods that become irregular or stop Men may have: Decreased or no desire for sex (low libido) Erection problems Other symptoms that may occur include: Mental changes, such as depression, anxiety, or changes in behavior Fatigue [medlineplus.gov]
She had symptoms of fatigue, palpitations, proximal muscle weakness, abdominal pain, and nausea. Her workup was significant for an AM cortisol level of 9.4 ug/dl (reference range 7.0–25.0 ug/dl). [jomi.com]
In some patients this may result in symptoms of weakness, fatigue, and frequent urination. [sages.org]
- Swelling
The itching, burning and swelling of my labia were simply unbearable. I have purchased several over-the-counter treatments, including Monistat cream to subside the symptoms. [es.slideshare.net]
If your tumour makes too much sex hormone: women might have deepening of the voice, changes in periods, baldness or growth of facial hair men may have loss of sex drive (libido), impotence and sometimes swelling of the breasts Those cancers that don't [cancerresearchuk.org]
There can be a swelling of the cheeks and face, giving your face a rounded appearance. Some people have diabetes, which can make them more thirsty and cause them to pass urine more frequently. [macmillan.org.uk]
Signs of Infection Temperature greater than 100 degrees F for more than 24 hours Swelling, tenderness, redness, unusual drainage from your incisions Nausea, vomiting, or shaking chills When to Call the Surgeon Contact your surgeon for any signs of infection [hopkinsmedicine.org]
[…] other serious complications are uncommon after laparoscopic adrenalectomy When to Call Your Doctor Be sure to call your physician or surgeon if you develop any of the following: Persistent fever over 101 degrees F (39 C) Bleeding Increasing abdominal swelling [sages.org]
Gastrointestinal
- Vomiting
Eleven days later the infant began to have episodes of vomiting with mild diarrhea. [pediatrics.aappublications.org]
This will keep your stomach empty and prevent nausea and vomiting. You will also have one or more intravenous (IV) tubing to give you fluids. [hopkinsmedicine.org]
When to Call Your Doctor Be sure to call your physician or surgeon if you develop any of the following: Persistent fever over 101 degrees F (39 C) Bleeding Increasing abdominal swelling Pain that is not relieved by your medications Persistent nausea or vomiting [sages.org]
Cardiovascular
- Thrombosis
There is evidence of thrombosis and recanalization of vascular channels within the adrenal tumor (IMAGES 04 and 05). [path.upmc.edu]
The procedure can be complicated by venous thrombosis and adrenal hemorrhage. Stephanie L. [healio.com]
[…] neurosecretory granules clinically mimicking a pheochromocytoma ( Arch Pathol Lab Med 2002;126:1530 ) 66 year old woman with laparoscopic adrenalectomy for bilateral metachronous aldosteronomas ( JSLS 2011;15:100 ) 69 year old woman with massive hemorrhage and thrombosis [pathologyoutlines.com]
DVT or deep venous thrombosis). These blood clots can break off and travel to the lungs (i.e. PE or pulmonary embolus). In order to prevent blood clots, sequential compression devices (i.e. [columbiasurgery.org]
Musculoskeletal
- Muscle Cramp
Symptoms caused by aldosterone production The main signs and symptoms caused by aldosterone-producing adrenal tumors are: High blood pressure Weakness Muscle cramps Low blood potassium levels Adrenal adenomas often make aldosterone, but adrenal cancers [cancer.org]
If your tumour makes too much cortisol or aldosterone, you might have: raised blood pressure thirst passing urine frequently muscle cramps weight gain that is more noticeable in the trunk of the body muscle wasting in the legs or arms, making them look [cancerresearchuk.org]
Symptoms of adrenal cancer that produces excess cortisol and aldosterone in adults can include: high blood pressure high blood sugar weight gain irregular periods easy bruising depression frequent urination muscle cramps At this point, scientists don’ [healthline.com]
Mineralocorticoids An increase in mineralocorticoids can lead to a rise in blood pressure, muscle cramps, feeling thirsty, and passing more urine than usual. [macmillan.org.uk]
Other symptoms include weakness, muscle cramps, increased thirst, and increased frequency of urination. Cortisol is a separate steroid hormone produced within the adrenal cortex. [oncolink.org]
- Muscle Spasm
Conventional laparoscopic surgery requires blunt insertion of some ports, resulting in temporary incisional pain or muscle spasms[ 6 ]. [bmcresnotes.biomedcentral.com]
Skin
- Hirsutism
These androgen secreting tumours frequently present in women with increased facial hair growth (hirsutism), irregular periods and infertility sometimes with masculinization. It is a very rare cause of polycytic ovary syndrome. [ensat.org]
A physical exam may reveal central obesity, hirsutism, striae, and gynecomastia. An ophthalmologic exam may reveal retinopathy secondary to chronic hypertension. [symptoma.com]
Physical examination: truncal and centripetal obesity, thin extremities with muscle atrophy, plethoric moon face, echymoses and hirsutism. [endocrine-abstracts.org]
[…] tumors, including cancers, are rare in patients with 21-hydroxylase deficiency but have been reported in patients with large adrenal glands and presumably inadequate cortisol therapy. 2 A 16-year-old girl with 21-hydroxylase deficiency was evaluated for hirsutism [nejm.org]
Postoperatively, her hirsutism regressed, she rapidly went through puberty, and regular monthly menstruation started four months later. Finding the source of testosterone in a virilized patient can be difficult. [jamanetwork.com]
Psychiatrical
- Suggestibility
These findings suggest that Cushing's syndrome resulting from an adrenal cortical adenoma may be another presentation of multiple endocrine neoplasia type I. [ncbi.nlm.nih.gov]
- Fear
[…] slowly Purple-red stretch marks on the belly, thighs or breasts Fatigue Muscle weakness or spasms Weight gain or loss Diabetes Insomnia or other sleep disorders Low potassium levels Headache Rapid or irregular heartbeats Feelings of anxiety, panic, fear [mdanderson.org]
Your feelings Back to top You may have many different emotions including anger, resentment, guilt, anxiety and fear. These are all normal reactions, and are part of the process many people go through in trying to come to terms with their condition. [macmillan.org.uk]
Fear of recurrence, financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by adrenal cancer survivors. [oncolink.org]
Neurologic
- Irritability
She was unable to crawl or stand and was irritable at night. Her appearance was asymmetrical; the right side of her face and her lower right leg were enlarged. [ncbi.nlm.nih.gov]
Symptoms include: sudden attacks of panic and anxiety headaches pallor or flushing sweating palpitations (awareness of a rapid heartbeat) high blood pressure (hypertension) irritability and mood changes weight loss. [macmillan.org.uk]
Patients may also have mental changes, including mood swings, irritability, and in the worst case, psychotic episodes. In children, excessive cortisol can lead to premature sexual development and maturation (also called precocious puberty). [oncolink.org]
- Excitement
Single-port laparoscopy through the umbilicus has been termed E-NOTES, and offers an exciting opportunity for performance of major laparoscopic surgery with no visible scar. [bmcresnotes.biomedcentral.com]
It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. [oncolink.org]
Workup
All individuals suspected to have adrenal cortical adenoma, whether based on symptoms or an incidental finding on imaging, need a detailed assessment. The workup should include a personal and family history, a thorough physical exam, and appropriate studies.
In the evaluation of adrenal incidentalomas, it is very important to consider the possibility of pheochromocytoma [5]. To identify a pheochromocytoma, the first-line test is the measurement of plasma fractionated metanephrines and normetanephrines and/or 24-hour urine collection of metanephrines and catecholamines [6].
Primary aldosteronism is confirmed with the ratio of plasma aldosterone concentration to plasma renin activity [7]. Moreover, the diagnosis is likely when the aldosterone–to–renin ratio is above 30 and the plasma aldosterone level is elevated (>0.5 nmol/L) [8]. Also, an electrolyte panel should be obtained in these patients.
An important test in the diagnosis of Cushing's syndrome is an overnight dexamethasone suppression test [9]. Other considerations in these patients include screening for metabolic syndrome with a lipid panel and glucose tolerance test.
Patients with virilization or feminization should be tested for androgens and estrogens respectively.
On unenhanced computed tomography (CT) scan, adrenal cortical adenoma is characterized by a low attenuation which reflects the presence of an abundant intracytoplasmatic fat [10]. Also, CT and magnetic resonance imaging (MRI) are both effective in discriminating between benign and malignant masses. Additionally, positron-emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) demonstrates excellent sensitivity for confirming adrenal malignancy [11].
Fine-needle aspiration has limited value and is reserved for cases in which all other findings are inconclusive [12].
X-Ray
- Pneumoperitoneum
In LESS, avoiding contact interference between the operative instruments and the laparoscope is essential for maintaining adequate pneumoperitoneum and reducing operative stress. [bmcresnotes.biomedcentral.com]
With the patient in the left lateral decubitus position, the operative technique attained included establishment of the pneumoperitoneum at the umbilicus followed by insertion of two 10 mm trocars at the midclavicular and anterior axillary lines and a [hormones.gr]
Treatment
Literature review revealed the disadvantages of different treatments in this period. [ncbi.nlm.nih.gov]
Treatment of small hepatocellular carcinoma in cirrhotic patients: a cohort study comparing surgical resection and percutaneous ethanol injection. Hepatology 1993 ; 18:1121-1126. [pubs.rsna.org]
Written by experts in the field, each of these sections address level of clinical evidence and provide recommendations and treatment algorithms. Extensive illustrations make this an interactive text. [books.google.it]
Prognosis
The small size and weight of the tumor, the low mitotic rate, and the absence of necrosis and vascular and capsular invasion portend a good prognosis. The patient is currently free of disease 1 year after extirpation of the tumor. [ncbi.nlm.nih.gov]
Prognosis Extremely poor prognosis, with a survival rate at 20% at five years for stage I-II disease.Poor prognostic indicators include: age at diagnosis, tumor size, distant metastases, invasion of vessels, capsule, or adjacent organs, and tumor necrosis [atlasgeneticsoncology.org]
Treatment and prognosis Small adrenal masses with manifestations of hormonal excess require resection, as do large (>3-5 cm) non-functioning adrenal mass lesions, as they are considered potentially malignant (see adrenal carcinoma ). [radiopaedia.org]
[…] other servers: Neurosecretory dense granules Molecular / cytogenetics description Tumorigenesis not well understood Outside of immunohistochemistry for diagnosis, adjunct molecular studies not currently utilized for clinical purposes (i.e. treatment, prognosis [pathologyoutlines.com]
Etiology
We discuss the etiology of myelolipoma and suggest that myelolipoma can develop in the course of endocrine hyperfunction. [ncbi.nlm.nih.gov]
An explanation of the etiology of the tumor is suggested by the unusual clinical course. Past History A. A., a Caucasian infant was born September 8, 1950, to a 31-year-old mother. [pediatrics.aappublications.org]
Other rare etiologies include primary adrenocortical carcinoma, metastasis and various rare benign tumors. Patients with AI should undergo clinical, biochemical and radiological evaluations. [healio.com]
Epidemiology
General Epidemiology: Often an incidental finding. Pathologic/clinical: May be hormonally active. [librepathology.org]
Each entity is extensively discussed with information on clinicopathological, epidemiological, immunophenotypic and genetic aspects of these diseases. The book is an authoritative, concise reference, prepared by 150 authors from 20 countries. [books.google.it]
Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group. Horm Res. 1997;47(4-6):279-83. [PubMed: 9167965] 14. [ncbi.nlm.nih.gov]
Terminology Adrenal cortical adenoma (ACA) Incidentaloma: small adenoma discovered incidentally during workup of other conditions ( Mod Pathol 2011;24:S58 ) Black (pigmented) adenoma: diffusely pigmented, brown-black ACA presumably due to lipofuscin Epidemiology [pathologyoutlines.com]
Pathophysiology
A review of the relevant literature and discussion of the pathophysiology and clinical implications is provided. [ncbi.nlm.nih.gov]
More common in adults, 5th - 7th decade Equal predilection for right and left adrenal glands True incidence unknown because many are not functional, estimates include 8.7% in autopsy series and 4% in radiology series ( Mol Cell Endocrinol 2014;386:67 ) Pathophysiology [pathologyoutlines.com]
Endocrinol Jpn 1986 ; 33 : 57 – 74. 8., : Pheochromocytoma, in, (eds): Hypertension: Pathophysiology, Diagnosis, and Management Raven Press, New York, 1990, pp 1639 – 1659. 9., : Management of pheochromocytoma. [academic.oup.com]
Authors’ Affiliations (1) Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China (2) Institute of Pathology and Pathophysiology, China Medical University, Shenyang [diagnosticpathology.biomedcentral.com]
Pathophysiology The biochemical mechanisms depend on the underlying cell type. The cellular mechanisms for primary adrenocortical tumorigenesis are just beginning to be understood. [emedicine.medscape.com]
Prevention
Evaluation should be performed on this co-occurrence to prevent perioperative complications from resection of an unexpected secretory cortical neoplasm. [mayoclinic.pure.elsevier.com]
Surgical resection of the culprit gland prevents sustained exposure to elevated hormone levels. In subclinical hypercortisolism, the benefit of that resection varies on the level of hypersecretion present. [jomi.com]
[…] staining for MELAN-A, Syn (46 of 50 cases of ACA), NSE (44 of 50 cases of ACA), Vim (42 of 50 cases of ACA) and Ki-67 Conclusion: Prediction of endocrine syndrome in functional ACA was possible based on its structure and morphologic features, which could prevent [dovepress.com]
Benign adrenal tumor care at Mayo Clinic Clinical trials Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease. [mayoclinic.org]
References
- Cawood TJ, Hunt PJ, O'Shea D, Cole D, Soule S. Recommended evaluation of adrenal incidentalomas is costly, has high false-positive rates and confers a risk of fatal cancer that is similar to the risk of the adrenal lesion becoming malignant; time for a rethink? Eur J Endocrinol. 2009;161(4):513-527.
- Nieman LK. Approach to the patient with an adrenal incidentaloma. J Clin Endocrinol Metab. 2010;95(9):4106-4113.
- Cruz DN, Perazella MA. Hypertension and hypokalemia: unusual syndromes. Conn Med. 1997;61(2):67-75.
- Chiodini I, Morelli V, Masserini B, et al. Bone mineral density, prevalence of vertebral fractures, and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian multicenter study. J Clin Endocrinol Metab. 2009;94(9):3207-3214.
- Terzolo M, Bovio S, Pia A, Reimondo G, Angeli A. Management of adrenal incidentaloma. Best Pract Res Clin Endocrinol Metab. 2009;23(2):233-243.
- Zeiger MA, Thompson GB, Duh QY. The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas.Endocr Pract. 2009;15(Suppl1):1-20.
- Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007;356(6):601-610.
- Toniato A, Merante-Boschin I, Opocher G, et al. Surgical versus conservative management for subclinical Cushing syndrome in adrenal incidentalomas: a prospective randomized study. Ann Surg. 2009;249(3):388-391.
- Emral R, Uysal AR, Asik M, et al. Prevalence of subclinical Cushing's syndrome in 70 patients with adrenal incidentaloma: clinical, biochemical and surgical outcomes. Endocr J. 2003;50(4):399-408.
- Szolar DH, Korobkin M, Reittner P, et al. Adrenocortical carcinomas and adrenal pheochromocytomas: mass and enhancement loss evaluation at delayed contrast-enhanced CT. Radiology. 2005;234(2):479-485.
- Yun M, Kim W, Alnafisi N, et al. 18F-FDG PET in characterizing adrenal lesions detected on CT or MRI. J Nucl Med. 2001;42(12):1795-1799.
- Mazzaglia PJ, Monchik JM. Limited value of adrenal biopsy in the evaluation of adrenal neoplasm: a decade of experience. Arch Surg. 2009;144(5):465-470.