Adrenal Adenomas – Causes, Symptoms, Diagnosis, Treatment

Adrenal Adenomas – Causes, Symptoms, Diagnosis, Treatment

Adrenal Adenomas are benign neoplasms of the adrenal cortex. Adrenal adenomas are the most common cause of incidentally found adrenal tumors known as “adrenal incidentalomas.” Adrenal adenomas can be either hormonally active or inactive. These tumors are usually detected incidentally on imaging done for unrelated reasons and only in some cases do patients present with symptoms and/or features of hormonal abnormalities, most commonly overproduction of an adrenal hormone.

There are two main goals in the evaluation of adrenal tumors. The first is to differentiate between benign and malignant masses, and the second goal is to assess if the tumors are producing excessive hormones.

Types of Adrenal Adenomas

The Fourth Edition of the World Health Organization (WHO) classification of endocrine tumors published in 2017 has classified adrenal cancer in two groups. The first includes tumors of the adrenal cortex, and the second group includes tumors of the adrenal medulla and extra-adrenal paraganglia. The key feature of the WHO classification is the role of genetics that may be involved in adrenal cortical carcinoma and pheochromocytoma/ paraganglioma as well as the inclusion of a few rare malignancies of the adrenal cortex and medulla.

The following are tumors of the adrenal cortex:

  • Cortical carcinoma
  • Cortical adenoma
  • Sex cord-stromal tumors

    • Granulosa cell tumor
    • Leydig cell tumor
  • Adenomatoid tumor
  • Mesenchymal and stromal tumors

    • Myelolipoma
    • Schwannoma
  • Hematological tumors
  • Secondary tumors

Adrenocortical adenoma (ACA), Adrenal myelolipoma (mesenchymal and stromal tumors) and adrenal adenomatoid tumor are benign neoplasms of the adrenal cortex. The sex cord-stromal tumor of the adrenal gland is rare, and there are only six reports in the literature. Primary hematological tumors are mostly lymphomas and rarely plasmacytoma. Secondary tumors of the adrenal cortex are usually metastatic lesions due to direct infiltration by adjacent cancer or more commonly via hematogenous spread from a distant site. Adrenal metastases are common in patients with advanced cancer.

Causes of Adrenal Adenomas

There are specific genetic mutations associated with hormonally active and inactive adrenal adenomas. However, the exact pathogenesis is not entirely clear.

  • Mutations of CTNNB1 genes which provide instructions for making beta-catenin (Wnt/beta-catenin pathway) is associated with the larger and non-secreting adrenocortical adenomas.
  • The mutations associated with cortisol-producing adrenal nodules include PRKACA (cortisol producing adenoma) GNAS1 (McCune Albright syndrome), MENIN (multiple endocrine neoplasm type 1) and ARMC5 (hereditary bilateral adrenal adenoma).
  • The mutations associated with aldosterone-producing adrenal adenomas include KCNJ5 , ATP1A1,, ATP2B3,  CACNA1D and CTNNB1.

Symptoms of Adrenal Adenomas

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.

Patients with hyperfunctioning adrenal gland adenomas present with manifestations of excess hormone secretion. The most common disease states caused by functioning adenomas are Cushing syndrome (due to excess cortisol production), Conn syndrome (due to excess aldosterone production), or sex hormone-related symptoms 4.

Some of the common symptoms associated with adrenocortical adenomas include:

Musculoskeletal

  • Osteopenia
  • Muscle weakness/muscle atrophy

Cardiovascular

  • Hypertension

Endocrine and Metabolic

  • Obesity

→More prevalent in males

  • virilization

→More prevalent in females

  • Hyperandrogenism
  • Irregular menstrual cycles

Neuropsychological

  • Sleep disorders
  • Depression

Skin

  • Easy bruising
  • Stretch marks
  • Hirsutism
  • Acne
Others Symptoms
  • Weight gain, usually greatest above the collar bone, in the cheek area (moon face), and around the abdomen
  • Fat deposits behind the neck and shoulders (fatty hump or buffalo hump)
  • Purple stretch marks on the abdomen
  • Excessive hair growth on the face, chest, and back in women
  • Menstrual irregularities
  • Weakness and loss of muscle mass in the legs
  • Easy bruising
  • Depression and/or moodiness
  • Weakened bones (osteoporosis), which can lead to fractures
  • High blood sugar levels, often leading to diabetes
  • High blood pressure

Diagnosis of Adrenal Adenomas

History and Physical
  • Non-secreting adrenal adenomas, or the ones that secrete low levels of hormones, are usually asymptomatic and discovered incidentally on abdominal imaging. The glucocorticoid producing adrenal tumors can present with the symptoms and signs of Cushing syndrome including obesity, hypertension, hyperglycemia, fatigue, depression, menstrual irregularities, proximal muscle weakness, acne, facial plethora, striae, fractures, and osteopenia.
  • Aldosterone-secreting tumors may present with hypertension that is quite frequently resistant hypertension with uncontrolled blood pressure despite the use of three or more antihypertensive medications of different classes. Other symptoms can include muscle weakness, hypokalemia, hypomagnesemia, or hypernatremia.
Clinical Examination
  • One of the first steps in the evaluation of the adrenal mass like any other case begins with a diligent history and physical examination with a focus on symptoms and signs that will be due to hyperfunctioning or malignant nature of the mass. These signs and symptoms are quite well described in the literature [].

Biochemical Evaluation

Cushing’s Syndrome
  • Overnight low-dose dexamethasone suppression test (LDDST) is used as a screening test with a sensitivity of 73–100 and 90 %, respectively []. Values >5 μg/dl (138 nmol/l) are diagnostic. False positives occur with medications that accelerate the hepatic metabolism of dexamethasone like anticonvulsants and with noncompliance to the drug regimen. To decrease this false positivity, a high-dose DST can be used in which a higher dose (2, 3, or 8 mg) is used. The confirmatory test can be done using serum corticotropin, cortisol in blood and 24-h urine specimen, and midnight salivary measurement of cortisol [].
Phaeochromocytoma (PHEO)
  • Fractionated metanephrine and catecholamine in the 24-h urinary specimen are recommended with high sensitivity and specificity (91–96 %). Fractionated plasma-free metanephrine is useful with high sensitivity (96–100 %), albeit with reduced specificity (85–89 %) and in the elderly further reducing to 77 % [–]. This can be used for confirmatory testing. False positives are seen in patients in whom there can be an increased production of endogenous catecholamines like prolonged illness and medications like a tricyclic antidepressants.
Primary Aldosteronism
  • Measurement of serum potassium is not a reasonable screening test for patient with primary aldosteronism in lieu of a normal level. Morning ambulatory plasma aldosterone concentration to plasma renin activity (PRA) is an appropriate investigation. A plasma aldosterone concentration and plasma renin activity ratio of ≥20 and a plasma aldosterone concentration of ≥15 ng/dl are considered positive results. Patients on potassium-sparing diuretics need to discontinue the drug at least 4 weeks prior to testing [, , ].
  • Confirmatory tests include aldosterone suppression testing with either a saline infusion test or 24-h urinary aldosterone excretion test while the patient maintains a high-sodium diet []. Adrenal venous sampling should be considered in patients with bilateral adrenal hyperplasia to confirm that the mass is the cause for hyper-aldosteronism.

Other Biochemical Evaluation

  • Sex hormone evaluation is to be done in patients with clinical manifestations of virilization and hirsutism. Cosyntropin stimulation testing with the measurement of cortisol precursors (e.g., 17-hydroxyprogesterone) is reserved for patients in whom the diagnosis is suspected on the basis of clinical manifestations (e.g., hyperandrogenism) or the presence of bilateral adrenal masses [].

Imaging

  • Various imaging modalities are being used for adrenal pathologies. Of these, CECT of the abdomen and pelvis is the most commonly performed followed by magnetic resonance imaging (MRI), and positron emission tomography CT (PET-CT) is usually reserved for patients with possible extra-adrenal malignancy. Metaiodobenzyl-guanidine (MIBG) and less commonly octreotide scintigraphy may be used to identify pheochromocytomas selectively in patient with a high probability of disease like family history, associated hereditary disorder, and extra-adrenal tumors.
You Might Also Like   Acute Erythroid Leukemia - Causes, Symptoms, Treatment
CECT
  • The adrenal CT imaging protocol consists of a multiphase study including an unenhanced scan followed by a 1-min delayed enhanced scan and a 15-min delayed de enhanced scan. The three phases together are used for calculating absolute percentage washout (APW) and/or relative percentage washout (RPW) in order to differentiate lipid-poor adenomas from primary carcinoma and metastases.

The APW is calculated using the formula:

APW=(enhancedHU)–(15mindelayedHUÞ)×100%(enhancedHU)–(unenhancedHU)

An APW value of greater than 60 % is diagnostic of an adenoma. In the absence of an unenhanced phase, a RPW is calculated as follows:

RPW=(enhancedHU)–(15mindelayedHUÞ)×100%(enhancedHU)
  • A RPW value greater than 40 % is diagnostic of an adenoma []. Adenomas are one of the most common adrenal lesions characterized by intracellular lipid which help in differentiating them from malignant masses. Lipid-rich adenomas usually have a Hounsfield unit (HU) less than 10 with 71 % sensitivity and 98 % specificity [, ]. Washout analyses have been found to be accurate in many studies [–].
  • Pheochromocytomas have a variable appearance on CECT with small lesions being homogenous while the larger ones being heterogeneous with areas of necrosis and hemorrhage [].
  • Adrenocortical carcinomas (ACC) are usually large (>6 cm) heterogeneously enhancing with areas of central necrosis and hemorrhage and calcifications in 30 % []. They may also be invading locally with venous extension being common []. Adrenocortical carcinoma generally has APW and RPW values of less than 60 and 40 %, respectively, compatible with nonadenomas []. Metastases to adrenal are nonspecific with heterogeneous densities, necrosis, and irregular margins in the larger masses, while in smaller masses, they are more homogenous with smooth margin []. Quite often, they are bilateral in location.
MRI
  • An adenoma spears dark on out of phase images while using spleen as reference. They can be differentiated from metastasis with a sensitivity of 81–100 % and specificity of 94–100 % [, ]. Of adrenal adenomas, 20–30 % are lipid-poor; thus, they cannot be diagnosed with CT or MRI.
  • PHEOs on MRI classically appear as markedly hyperintense on T2 weighted (T2W) images, although some of the recent series have found them to be moderately hyperintense or even hypointense [, ]. On MRI, ACC appear heterogeneously iso to slightly hypointense on T1W but hyperintense with hemorrhage. On T2W, they are heterogeneously hyperintense. The advantage of MRI over CT is for patients in whom iodinated contrast cannot be used due to allergy or renal impairment or young/pregnant patients in whom radiation is a concern.
PET-CT
  • Malignant masses have increased metabolic activity and hence being avid to glucose form the basis of PET in radiotracer malignant masses. Comparison with the background liver activity and the qualitative visual assessment of uptake as well as quantitative assessment using standard uptake values (SUV) helps to establish the nature of lesion. Most of the malignant adrenal masses show increased activity while the benign ones do not, with the sensitivity for this being 93–100 % [–].
MIBG
  • This nuclear medicine modality is used to localize pheochromocytoma with a sensitivity of 95–100 % and specificity of 100 % []. It is of particular use in patients with in whom biochemical evaluation is positive but the imaging with CT/MRI is negative []. It is also used in the detection of metastasis in patients with pheochromocytoma. In cases with biochemical evidence of pheochromocytoma but negative MIBG, octreotide scanning can be used as an alternative. Iodine-131 MIBG therapy may be used for the systemic treatment of select patients with metastatic pheochromocytoma [].
Percutaneous Biopsy
  • Biopsy for adrenal lesions is done in an indeterminate adrenal mass with a known primary. An ultrasonography-guided biopsy is feasible but CT guided is more commonly done as it is safe with low complication rate and accurate []. It is done with ipsilateral decubitus position as this compresses the lung and reduces the movements thereby decreasing the chances of pneumothorax. Acaudal to cephalad approach is used and on the right side transhepatic approach may be needed.
CT scan
  • It is the imaging of choice for the evaluation of adrenal tumors.  Adrenal tumor size greater than 4.0 cm has high sensitivity for adrenal cancer. Adrenal lesions that exhibit less than 10 HU (Hounsfield units) on non-contrast CT scan strongly suggest a benign adenoma. Some benign adenomas may have higher than 10 HU. Delayed contrast-enhanced CT scan may help to differentiate them from malignant lesions. MRI is an alternative to the CT scan for the evaluation of adrenal tumors, but it is more expensive than CT scan.
Fine-needle aspiration biopsy
  • Adrenal tumors is rarely necessary for select patients with single adrenal lesion who have a history of non-adrenal malignancy without evidence of other metastasis. In these cases, a pheochromocytoma needs to be ruled out first before any invasive procedure takes place.All patients with adrenal adenoma should be investigated for Cushing syndrome, and pheochromocytoma and patients with hypertension should additionally get investigation for hyperaldosteronism.
Twenty-four-hour urinary
  • It is fractionated metanephrines, or plasma fractionated metanephrines, are measured to assess for pheochromocytoma.
Plasma aldosterone level and plasma renin activity measurements
  • That are indicated in patients with adrenal adenoma who have hypertension. In patients with plasma aldosterone concentration greater than 15ng/dL and aldosterone to plasma renin activity over 20, the diagnosis is confirmed by demonstrating a lack of aldosterone suppressibility with sodium loading. In patients over 40 years of age, a selective adrenal vein sampling is indicated for localization purposes before surgery.
  • Sex-hormone producing adrenal tumors test – are rare and typically present with concomitant clinical symptoms (i.e., feminization or virilization) and therefore systematic screening may not be warranted. However, an incidentaloma suspicious for adrenocortical carcinoma may necessitate screening for sex hormone production (dehydroepiandrosterone [DHEAS], 17-hydroxyprogesterone [17- OHP] and testosterone).
  • Confirmatory hormonal testing – is recommended for all positive screening tests to limit false-positive results and unnecessary surgeries.

Treatment of Adrenal Adenomas

Adrenal tumors that are more than 4 cm in size, hormonally indeterminate, or suspected to be malignant receive treatment with adrenalectomy. Benign appearing on imaging, less than 4 cm in size adrenal adenomas which are hormonally active on biochemical testing (Cushing syndrome, hyperaldosteronism, and pheochromocytoma) are treated with adrenalectomy as well. There is no long-term prospective data available to choose between medical and surgical treatment for patients with subclinical Cushing syndrome.

Patients with hyperaldosteronism who are not good surgical candidates due to advanced age or comorbidities, or the patients who refuse surgery, are treated with aldosterone antagonists such as spironolactone or eplerenone.

Hormonally inactive adenomas are initially managed by reimaging in 3 to 6 months, then annually for 1 to 2 years, and they should also have repeat hormonal assessment once a year for 5 years. If the mass grows more than 1 cm or becomes hormonally active, then adrenalectomy is recommended.

Recruiting clinical trials for PPGL.

Intervention Study design Setting Recruitment target, n patients NCT number
Randomized studies
 Sunitinib Phase II, placebo controlled Palliative 74 Nbib1371201
 Phenoxybenzamine vs doxazosin Phase III Curative and palliative 60 Nbib3176693
 Phenoxybenzamine vs doxazosin Phase IV Curative 134 Nbib1379898
Non-randomized studies
 Cabozantinib Phase II, single arm Palliative 22 Nbib2302833
 SGI-110 (Guadecitabine) Phase II, single arm Palliative 70 Nbib3165721
 Lenvatinib Phase II, single arm Palliative 25 Nbib3008369
 Lu-177-DOTATATE Phase II, single arm Palliative 90 Nbib3206060
Studies investigating multiple disease
 131I-MIBG Phase II, single arm Palliative 80 Nbib107289
 131I-MIBG Phase II, single arm Palliative 100 Nbib1850888
 Nivolumab and ipilimumab Phase II, single arm Palliative 707 Nbib2834013
 ONC-201 Phase II, single arm Palliative 24 Nbib3034200
 Pembrolizumab Phase II, single arm Palliative 250 Nbib2721732
 PEN-221 Phase I/IIa, single arm Palliative 120 Nbib2936323
You Might Also Like   Adrenocortical Carcinoma - Causes, Symptoms, Treatment

NCT, ClinicalTrials.gov registry number; PPGL, pheochromocytoma and paraganglioma.

Recruiting clinical trials for adrenal cortical tumors.

Intervention Design Setting Recruitment target, n patients NCT number
Randomized
 Mitotane Phase III Adjuvant 200 Nbib777244
 ATR-101 Phase II, placebo controlled Palliative (symptom reduction) 16 Nbib3053271
 Surgery + medical therapy vs medical therapy Randomized study Curative 110 Nbib2364089
Non-randomized
 RF-ablation Single-arm study Curative 25 Nbib2756754
 Pembrolizumab Phase II, single arm Palliative 39 Nbib2673333
Studies investigating multiple diseases
 ABBV-176 Phase I, single arm, basket Palliative 100 Nbib3145909
 Cabozantinib-S-malate Phase II, single arm Palliative 110 Nbib2867592
 Nivolumab and ipilimumab Phase II, single arm Palliative 57 Nbib3333616
 Nivolumab and ipilimumab Phase II, single arm Palliative 707 Nbib2834013
 Pembrolizumab Phase II, single arm Palliative 250 Nbib2721732

Radiation Oncology

In localized adrenocortical carcinoma, radiation therapy, in combination with surgery, has been used in only a few patients registered in the National Cancer Data Base. There are no prospective data with which to define the role of adjuvant radiation therapy in ACC since the use of mitotane has become more common. Although postoperative radiation therapy in some studies has been shown to reduce local recurrence rates, this is not a universal observation in other studies. Furthermore, there was no survival benefit has been shown with adjuvant radiation therapy. Based on these data, there is no recommendation for the routine use of adjuvant radiation therapy after initial surgical resection. However, some patients who display a local recurrence pattern without evidence of distant disease may benefit from adjuvant radiation therapy after surgery.

Medical Oncology

HORMONAL MANAGEMENT OF ADRENOCORTICAL CARCINOMA

The combination of cancer burden and hormonal excesses occur in almost 50% of adrenocortical carcinoma patients. Agents to treat Cushing syndrome such as ketoconazole, metyrapone, and mifepristone are often used, with the hope of reducing the morbidity of cortisol excess. Ketoconazole inhibits CYP17A1, CYP11A1, and to a lesser extent, CYP11B1. The starting dose is 200 mg twice daily and can increase to 1200 mg/day. During treatment, liver enzymes require monitoring. Because ketoconazole is an inhibitor of several hepatic metabolizing enzymes, there is a potential for serious drug interactions.

Metyrapone is an inhibitor of steroidogenesis at the level of CYP11B1, and generally is started at 250 mg twice daily and can be elevated to 2 to 3 g/d in 250-mg intervals. Due to the inhibition of CYP11B1, an increase in adrenal androgens may occur, causing or worsening hyperandrogenemia. Mifepristone is a direct glucocorticoid receptor antagonist that is highly effective in controlling clinical comorbidities, mainly glucose intolerance; thus, it is a useful treatment for Cushing syndrome when it is associated with diabetes mellitus. Treatment is initiated at 300 mg daily and titrated up to 1200 mg daily. Adrenal insufficiency is a rare adverse effect of mifepristone.

Spironolactone and eplerenone are mineral corticosteroid receptor antagonists that can be used to counteract edema and hypertension associated with cortisol or aldosterone overproduction. Spironolactone can be used to manage androgen effects in females patients with androgen-secreting tumors as well as mineralocorticoid effects in those patients with mineralocorticoid-secreting tumors. Dosing may need to be as high as 200 to 400 mg/day. In males with gynecomastia, aromatase inhibitors (e.g., anastrozole and letrozole), as well as estrogen receptor antagonists (e.g., tamoxifen and raloxifene), can be used. Because cortisol production is an adverse prognostic factor, every attempt should be made to normalize hormone levels because this not only affects survival parameters but also improve QOL.

The success of hormonal control is contingent on a synchronized approach to reducing hormonal production, counteracting the effects of hormonal overproduction, and reducing disease burden via surgery or systemic chemotherapy.

LOCALIZED DISEASE

Localized ACC encompasses stages I and II disease and most patients with stage III disease. Stage I is relatively uncommon, representing only 3% of all ACC cases, whereas stages II and III make up 37 and 34%, respectively. Surgery is usually the mainstay therapy in these patients, but unfortunately, many experience disease recurrence. The outcomes after surgical resection alone have remained suboptimal. Even with complete resections, rates of local recurrence have typically ranged from at least 19% to 34% in those patients with no residual disease after surgery. The evidence that patients with ACC remain at high risk for tumor recurrence despite complete surgical tumor excision has fueled the search for adjuvant therapies.

Mitotane has been shown to significantly improved recurrence-free survival (RFS) in some studies and not others.  An ongoing international prospective randomized clinical trial (ADIUVO:https://www.epiclin.it/adiuvo) is exploring the efficacy of adjuvant mitotane in ACC patients deemed to have low/intermediate risk of recurrence after radical surgical resection, which is defined by R0 resection, absence of metastases and Ki67 under 10%. This study will compare mitotane treatment with a “watch and see” strategy.

Adjuvant treatment generally starts within three months of post-surgery based on animal studies. Mitotane plasma monitoring is recommended for ACC management as it has a high volume of distribution and low clearance; the drug s lipophilic and tends to accumulate in adipose tissue. Adaptive dosing of the individual based on age, sex, body mass index, lean body mass, and renal function is recommended. Side effects of mitotane include gastrointestinal and neurologic abnormalities. Cortisol supplementation is required to prevent the adverse gastrointestinal effect of mitotane. Contraception, vitamin K antagonist supplementation, and combined antitumor therapies are recommended during mitotane treatment.

ADVANCED DISEASE

More than half of ACC patients present with locally advanced or metastatic disease (Stage III or IV). The advanced stage carries a poor prognosis and only a limited response to any single treatment modality. Thus, the use of a multidisciplinary approach and different treatment methods when feasible, carry the best hope of improving the grim prognosis in these patients.

Systemic therapy for metastatic disease

In metastatic disease, different parameters merit consideration: the tumoral volume, the number of metastatic organs, and the progression rates. Debulking surgery only benefits in ACC patients with a limited number of tumoral organs (less than or equal to 2), resectable tumoral mass, with a light progression and when severe hormone excess that is not manageable medically. However, most patients require medical therapy.

Mitotane remains the only medication approved by the European Medicine Executive Agency (EMEA) and the U.S Food and Drug Administration (FDA) for the treatment of “metastatic ACC.” An overview of collecting different studies showed that the objective response rate is at best, 24%.

Neoadjuvant Approach

The use of neoadjuvant systemic chemotherapy as a bridge to surgery correlated with a favorable outcome in one small study with borderline resectable adrenocortical carcinoma (BRACC), defined as having oligometastases, needing multiorgan or vascular resection, or having a poor performance status preventing surgery. Twelve patients (80%) received combination therapy with mitotane and etoposide/cisplatin-based chemotherapy, two patients (13%) received mitotane alone, and one patient (7%) received chemotherapy alone. Median DFS for resected BRACC patients was 28.0 months [95% confidence interval (CI), 2.9–not attained] vs 13 months (95% CI, 5.8–46.9) (p = 0.40) for initial surgery patients. Five-year OS rates were also similar: 65 % for resected BRACC vs 50 % for initial surgery (p = 0.72).

You Might Also Like   Acute Myelosclerosis - Causes, Symptoms, Treatment

Targeted Therapy Approach

Targeted therapy may also be an option for the management of adrenocortical carcinoma. The first trials targeted epidermal growth factor receptor (EGRF) gefitinib and a combination of erlotinib and gemcitabine. Among vascular endothelial growth factor, sunitinib exhibited a modest anti-tumor effect in the phase 2 trial. VEGF can be administered in patients without mitotane treatment.

Recently, drugs targeting IGF-II seemed to be very promising, as IGF-II is the most-up regulated gene in ACC (80% as described before). Preclinical studies antagonizing this pathway with pharmacological agents resulted in inhibition of growth in vitro and in vivo. This inhibition was more potent than that observed with the use of mitotane alone in decreasing xenograft growth, and the combination of IGF inhibition with mitotane resulted in greater antiproliferative effects than those observed with the use of single-agent treatment. These data establish the role of targeted disruption of IGF-1R signaling to obtain a therapeutic advantage when used with mitotane therapy or possibly other chemotherapeutics in ACC patients. Recently, a phase 2 study used an IMCA12 (cixutumumab), a fully humanized IGF-IR antibody showed a lack of efficacy in a cohort of 19 patients. Also, results of a huge phase 3 trial “GALACTIC” with a highly specific IGF-IR inhibitor linstinib (OSI-906)in a cohort of 138 metastatic ACC have been recently published: the progression-free and overall survival did not differ between the linstinib and placebo groups. However, in another study, 26 heavily pretreated ACC patients received cixutumumab with temsirolimus, an inhibitor of mammalian targets of IGF-1R signaling (mTOR inhibitor)weekly with restaging at eight weeks. Of these 26 patients, 11 (42%) had stable disease for greater than six months. Finally, because of disease heterogeneity, it appears that using one single agent is not sufficient to induce an objective response. Trials with new targeted substances are underway.

Cytotoxic Chemotherapy

Although cisplatin-containing regimens have shown some responses most studies lack power and comparisons between different regimens. The most encouraging results originate from the combinations of etoposide, doxorubicin and cisplatin with mitotane (EDP-M) achieving an overall response of 49% of 18 months duration (FIRMA-CT study). This regimen was equally effective as first-line treatment or after failing of the combination of streptozotocin with mitotane and is currently the preferred scheme. In patients who progress under mitotane monotherapy, EDP treatment is also recommended. The combination of gemcitabine with capecitabine is used for patients failing EDP- and for not responding to patients targeted therapies with tyrosine kinase inhibitors (mainly sunitinib) could be used. Although initially promising treatment with IGF-1R antagonists did not prove to be efficacious suggesting that a combination of therapies may be the way forward.

Staging

The widely adopted staging of adrenocortical carcinoma is by the European Network of Study of Adrenal Tumors (ENSAT) due to its correlation with clinical outcome. This system defines:

  • Stage I with a tumor size of smaller than 5 cm.
  • Stage II is a tumor with a size of over 5 cm; strictly localized both stages.
  • Stage III is characterized by the positive regional lymph nodes, infiltration of the tumor in the surrounding tissue, or a tumor thrombus in the vena cava and/or renal vein.
  • Stage IV is defined by distant metastasis.

Complications

The complications associated with adrenocortical carcinoma are due to excess hormone production. Hormone excess occurs in 40% to 60% of patients with ACC. Hypercortisolism is the most common complication (50% to 80% of hormone-secreting ACCs), causing classic symptoms including diabetes mellitus, fatigue, hypertension, central obesity, muscle weakness/atrophy, and osteoporosis.

Local or regional recurrences:

  • Local or regional recurrences occur in 19% to 34% of patients with no residual (R0) disease after surgery.

Distant metastases:

  • More than half of ACC patients present with locally advanced or metastatic disease.

Postoperative and Rehabilitation Care

The follow-up management is not well-standardized. However, since adrenocortical carcinomas are aggressive tumors, patients should be followed every three months after initial treatment. When the patient has a recurrence free-time of 2 to 3 years, the follow-up may increase to every six months for a total of five years. After five years of disease-free survival, the surveillance can be done every 1 to 2 years, because, although rare, some patients can have a late relapse. Patients should undergo a hormonal investigation, comprehensive imaging work-up, including chest and abdominal CT scan, and complete physical examination. An [18F]FDG-PET can be a consideration, even if it is not regarded as mandatory in the follow-up of ACC patients.

Deterrence and Patient Education

Adrenal cancer happens when healthy cells in the adrenal gland grow out of control. Some people have no symptoms, but in other cases, the lesion gets discovered while undergoing an imaging test for another reason.

When adrenal cancer causes symptoms, it does so via the production of hormones. Depending on the levels of the hormones involved, this can cause symptoms such as:

  • Muscle weakness
  • Weight gain
  • Increased hair growth, usually on the face (in women) and deep voice
  • Fatigue
  • Trouble sleeping
  • The purple coloration on the skin
  • Hypertension

Adrenal tumors can also cause other symptoms that are not related to the level of hormones. These can include:

  • Weight loss or loss of appetite
  • Pain in the abdomen or lower back

All symptoms listed above can result from many other disorders, and hence a thorough workup is required. However, if a patient perceives these symptoms, they need to report it to their doctor or nurse.

Tests for adrenal cancer usually include:

  • Blood analysis and urine tests to determine the levels of different hormones
  • CT or MRI scan

The treatment chosen will depend on the stage of adrenal cancer. Most patients with the adrenal disease are treated with surgery to remove the tumor. After surgery, some patients may require additional treatments that can include:

  • Chemotherapy
  • Radiation therapy

After the initial treatment, the doctor must follow the patient regularly to determine if cancer has been cured or has come back. Follow-up tests include blood and imaging tests. Having symptoms could mean the adrenal tumor has returned. The patient should inform their doctor or nurse if they have any signs or symptoms. Long-term medicinal treatment to correct the hormone levels may be necessary.

References

Loading

If the article is helpful, please Click to Star Icon and Rate This Post!
[Total: 0 Average: 0]

People Also Reading

Default ThumbnailBenign Adrenal Adenomas – Causes, Symptoms, Treatment Default ThumbnailAdrenal Cancer – Causes, Symptoms, Diagnosis, Treatment Default ThumbnailAdrenal Metastases – Causes, Symptoms, Treatment Adrenal Fatigue; Causes, Symptoms, Diagnosis, Treatment Default ThumbnailAdrenal Myelolipoma – Causes, Symptoms, Treatment Default ThumbnailIsolated Adrenal Myelolipoma – Symptoms, Treatment Adrenal crisisAdrenal Crisis / Emergencies; Defination, Types, Causes, Symptoms, Treatment, Complications, Prevention Default ThumbnailAdrenal Insufficiency – Causes, Symptoms, Treatment Default ThumbnailMyelolipomas – Causes, Symptoms, Diagnosis, Treatment Default ThumbnailSpinal Tumor – Causes, Symptoms, Diagnosis, Treatment Default ThumbnailAngiosarcoma – Causes, Symptoms, Diagnosis, Treatment Default ThumbnailPleomorphic Liposarcoma – Causes, Symptoms, Diagnosis, Treatment

About the author

Rx Harun administrator

Translate »