Question 1 of 10

    Adrenocortical Carcinoma (Adrenal Cortical Carcinomas)

    Adrenal cortical carcinoma - low mag[1]

    Adrenocortical carcinoma (ACC) is a rare malignancy that arises from the adrenal cortex. Adrenocortical masses are common, but only approximately 1 per 1500 adrenal tumors are malignant.

    This disorder is associated with the following process: neoplastic.

    Presentation

    The findings during examination are variable and dependent on the endocrine syndromes that occur (if any exist) [6]. The majority of patients with functional tumors shows symptoms of Cushing syndrome including truncal obesity, striae, malar flushing, supraclavicular and dorsocervical fat pads. Hypertension with weakness and ileus resulting from hypokalemia (Conn syndrome), virilization, precocity, feminization and combined hormone excess also may be present. For nonfunctional tumors, signs and symptoms include fever, weight loss, abdominal, flank and back pain.

    Adrenocortical carcinomas may be classified as [7]:

    • Functional
    • Nonfunctional
    • Well differentiated
    • Intermediate
    • Poorly differentiated to anaplastic

    Skin
    Hirsutism
    • Hirsutism, facial acne, oligo/amenorrhea, and increased libido all are possible presenting symptoms.[emedicine.medscape.com]
    • Hirsutism, acne and deepening of the voice may be apparent in both sexes.[orpha.net]
    • , Bishop Auckland General Hospital, Cockton Hill Road, Bishop Auckland, Co Durham DL 14 6AD, UK; s.nag{at}btopenworld.com Statistics from Altmetric.com adrenocortical carcinoma Cushing’s syndrome A 46 year old woman presented with a short history of hirsutism[pmj.bmj.com]
    • One-year later, she was referred to our department with signs of sustained hypertension despite spironolactone treatment, mild hirsutism, irregular vaginal bleeding, increased body weight and central adiposity.[casesjournal.biomedcentral.com]
    • Excessive hair growth (hirsutism)can also be seen.[oncolink.org]
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  • urogenital
    Flank Pain
    • Regarding clinical features, 14 patients presented with flank pain, 8 patients presented generalized edema or general weakness. 3 patients presented with virilizing features.[sages.org]
    • Rarely, pheochromocytoma -like hypersecretion of catecholamines has been reported in adrenocortical cancers. [5] Non-functional tumors (about 40%, authorities vary) usually present with abdominal or flank pain, varicocele and renal vein thrombosis [6][en.wikipedia.org]
    • Case Presentation A 63-year-old female patient presented left flank pain for 1 year associated with a palpated mass in this topography.[karger.com]
    Amenorrhea
    • Hirsutism, facial acne, oligo/amenorrhea, and increased libido all are possible presenting symptoms.[emedicine.medscape.com]
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  • psychiatrical
    Decreased Libido
    • Feminization ( estrogen excess) is most readily noted in men, and includes breast enlargement , decreased libido and impotence . [1] [2] [7] Pathophysiology [ edit ] The main etiologic factor of adrenocortical cancer is unknown.[en.wikipedia.org]
    • Women with virilizing adrenal cancer present with marked body hair growth, male pattern baldness, deepening voice, breast atrophy, clitoral enlargement, decreased libido and irregular periods.[csrf.net]
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  • cardiovascular
    Hypertension
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    • However, cortisol, catecholamines or other hormones were not measured, despite the fact that she was a hypertensive patient.[casesjournal.biomedcentral.com]
    • January 9, 2018 Follow us: Home About Us Acknowledgements Feedback Contact Us Site Map Advertisement Home Genitourinary Adrenal Adrenal Cortical Carcinoma Adrenal Cortical Carcinoma slide 1 of 4 Comments: This patient presented with Cushing’s syndrome and hypertension[webpathology.com]
    • Signs and symptoms of virilisation are present in over 90% of cases, hypertension may also be present.[orpha.net]
    • , Co Durham DL 14 6AD, UK; s.nag{at}btopenworld.com Statistics from Altmetric.com adrenocortical carcinoma Cushing’s syndrome A 46 year old woman presented with a short history of hirsutism, facial plethora, amenorrhoea, progressive weight gain, and hypertension[pmj.bmj.com]
    Palpitations
    • It can cause high blood pressure, headaches, panic attacks, and heart palpitations.[dartmouth-hitchcock.org]
    • Conn syndrome ( mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations ) low plasma renin activity, and high serum[en.wikipedia.org]
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  • musculoskeletal
    Muscle Weakness
    • High levels of cortisol may cause patients to develop Cushing's syndrome, characterized by obesity, high blood pressure, edema, muscle weakness, thin skin, easy bruising and increased blood sugar.[montefiore.org]
    • weakness in the legs bruising in the body excessive weight gain in the chest and abdomen Both functioning and nonfunctioning tumors can cause abdominal pain if they become enlarged.[healthline.com]
    • Conn syndrome ( mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations ) low plasma renin activity, and high serum[en.wikipedia.org]
    Back Pain
    • Although in some cases, they are found incidentally, during either examination or radiologic imaging, nonfunctional ACs typically present with any of the following: Fever Weight loss Abdominal pain and tenderness Back pain Abdominal fullness Symptoms[emedicine.medscape.com]
    • pain caused by mass effect Highly necrotic tumors may cause fever and clinically simulate infectious process Tend to invade adrenal vein, vena cava, adjacent kidney and retroperitoneum; may cause thromboemboli Metastases to liver (60%), regional lymph[pathologyoutlines.com]
    • pain to overt hormonal syndromes when the tumors become biochemically active.[jcancer.org]
    • pain Abdominal fullness Symptoms related to metastases See Clinical Presentation for more detail.[emedicine.medscape.com]
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  • gastrointestinal
    Abdominal Pain
    • Although in some cases, they are found incidentally, during either examination or radiologic imaging, nonfunctional ACs typically present with any of the following: Fever Weight loss Abdominal pain and tenderness Back pain Abdominal fullness Symptoms[emedicine.medscape.com]
    • Symptoms of these tumors include: weight gain fluid retention (leading to bloating) unusual excess hair growth unusual skin changes If the tumor presses against other organs, it may cause symptoms such as abdominal pain, an unusual feeling of fullness[mskcc.org]
    • Adrenocortical carcinoma is discovered as part of a physical examination for abdominal pain.[cancer.uvahealth.com]
    • These symptoms include abdominal pain, a feeling of fullness in the belly, or trouble eating because the stomach feels full quickly.[yalesurgery.org]
    • Hormonally inactive tumours present as palpable masses, abdominal pain or with evidence of metastasis. [radiopaedia.org]
    Abdominal Fullness
    • Although in some cases, they are found incidentally, during either examination or radiologic imaging, nonfunctional ACs typically present with any of the following: Fever Weight loss Abdominal pain and tenderness Back pain Abdominal fullness Symptoms[emedicine.medscape.com]
    • Patients with large adrenal tumors may experience feelings of abdominal fullness or localized pain.[oncolink.org]
    • fullness Symptoms related to metastases See Clinical Presentation for more detail.[emedicine.medscape.com]
    Abdominal Mass
    • INTRODUCTION Adrenocortical carcinomas (ACCs) are rare and frequently aggressive tumors that may be functional (hormone-secreting) and cause Cushing's syndrome and/or virilization, or nonfunctional and present as an abdominal mass or as an incidental[uptodate.com]
    • Most patients (40–60%) present steroid hormone excess (glucocorticoids, mineralocorticoids, androgens) or abdominal mass effects (30%), but 15–20% of patients with ACC are initially diagnosed incidentally ( Else et al., 2014 ).[journal.frontiersin.org]
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  • neurologic
    Confusion
    • Conn syndrome ( mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations ) low plasma renin activity, and high serum[en.wikipedia.org]
    • Renal cell carcinoma and other histologically similar tumors are potentially confused with ACC by conventional light microscopy, and their separation from the latter is often impossible without the aid of additional studies.[dx.doi.org]
    • According to the current World Health Organization (WHO) classification, malignancy is defined by the presence of metastases to a site where pheochromocytoma/paraganglionic tissue is not normally present, e.g. liver or bone, to avoid confusion with multiple[annonc.oxfordjournals.org]
    Headache
    • It can cause high blood pressure, headaches, panic attacks, and heart palpitations.[dartmouth-hitchcock.org]
    • Conn syndrome ( mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations ) low plasma renin activity, and high serum[en.wikipedia.org]
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  • Face, Head & Neck
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  • Entire body system
    Virilization
    • More than 80% present of pediatric patients, however, present with virilization syndromes.[emedicine.medscape.com]
    • , followed by mixed Cushing's and virilization ( glucocorticoid and androgen overproduction).[en.wikipedia.org]
    • INTRODUCTION Adrenocortical carcinomas (ACCs) are rare and frequently aggressive tumors that may be functional (hormone-secreting) and cause Cushing's syndrome and/or virilization, or nonfunctional and present as an abdominal mass or as an incidental[uptodate.com]
    • Some patients have signs of virilization .[adrenaltumors.org]
    • Symptoms of increased cortisol or other adrenal gland hormones may include: Fatty, rounded hump high on the back just below the neck ( buffalo hump ) Flushed, rounded face with pudgy cheeks ( moon face ) Obesity Stunted growth ( short stature ) Virilization[medlineplus.gov]
    Weakness
    • […] bruising Depression or moodiness Weak bones, which can lead to broken bones High blood sugar, often leading to diabetes High blood pressure Symptoms caused by high aldosterone levels Excess aldosterone often causes the following: Weakness High blood[yalesurgery.org]
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    • High levels of cortisol may cause patients to develop Cushing's syndrome, characterized by obesity, high blood pressure, edema, muscle weakness, thin skin, easy bruising and increased blood sugar.[montefiore.org]
    • […] characteristics, including increased body hair (especially on the face), pubic hair, acne , deepening of the voice, and enlarged clitoris (girls) Symptoms of increased aldosterone are the same as symptoms of low potassium, and include: Muscle cramps Weakness[medlineplus.gov]
    Weight Gain
    • Symptoms of these tumors include: weight gain fluid retention (leading to bloating) unusual excess hair growth unusual skin changes If the tumor presses against other organs, it may cause symptoms such as abdominal pain, an unusual feeling of fullness[mskcc.org]
    • […] blood sugar and pressure muscle weakness in the legs bruising in the body excessive weight gain in the chest and abdomen Both functioning and nonfunctioning tumors can cause abdominal pain if they become enlarged.[healthline.com]
    • These tumors may also produce excess hormones that can cause weight gain, excess facial hair or early puberty.[cancercenter.com]
    • You may notice symptoms like sudden weight gain or a flushed face.[webmd.com]
    Buffalo Hump
    • Symptoms of increased cortisol or other adrenal gland hormones may include: Fatty, rounded hump high on the back just below the neck ( buffalo hump ) Flushed, rounded face with pudgy cheeks ( moon face ) Obesity Stunted growth ( short stature ) Virilization[medlineplus.gov]
    • Symptoms Symptoms of increased cortisol or other adrenal gland hormones may include: Fatty, rounded hump high on the back just below the neck ( buffalo hump ) Flushed, rounded face with pudgy cheeks ( moon face ) Obesity Stunted growth ( short stature[mountsinai.org]
    • For Cushing's syndrome ( glucocorticoid excess) these include weight gain , muscle wasting , purple lines on the abdomen, a fatty " buffalo hump " on the neck, a "moonlike" face , and thinning, fragile skin.[en.wikipedia.org]
    • […] an abnormal accumulation of fatty pads in the face (creating the distinctive "moon face" of Cushing's syndrome); in the trunk (termed "truncal obesity"); and over the upper back and the back of the neck (giving the individual what has been called a "buffalo[encyclopedia.com]
    Precocious Puberty
    • Virilization (in girls) or precocious puberty (in boys) is the most common endocrine presentation of a functional AC.[emedicine.medscape.com]
    • […] produced) adrenogenital syndrome (excess sex steroids produced) virilization (acquisition of male traits in a female because of excess testosterone production) feminization (acquisition of female traits in a male because of excess estrogen production) precocious[endocrineweb.com]
    • Most tumors in children are functional, and virilization is by far the most common presenting symptom, followed by Cushing's syndrome and precocious puberty . [1] Among adults presenting with hormonal syndromes, Cushing's syndrome alone is most common[en.wikipedia.org]
    • In children, excessive cortisol can lead to premature sexual development and maturation (also called precocious puberty).[oncolink.org]
    • Pathophysiology Endocrine syndromes associated with AC include the following: Cushing syndrome (30%) Virilization and precocious puberty (22%) Feminization (10%) Combined hormone excess (35%) Non–glucocorticoid-mediated insulin resistance Cachexia (usually[emedicine.medscape.com]
    Fever
    • Although in some cases, they are found incidentally, during either examination or radiologic imaging, nonfunctional ACs typically present with any of the following: Fever Weight loss Abdominal pain and tenderness Back pain Abdominal fullness Symptoms[emedicine.medscape.com]
    • […] function from morphology Lack of function may be due to deletions in enzymes required for cortisol synthesis Hormonally inactive ACCs usually present with gastrointestinal symptoms or back pain caused by mass effect Highly necrotic tumors may cause fever[pathologyoutlines.com]
    • Signs and symptoms Physical examination findings in patients with hormonally active AC include the following: Virilization Cushing syndrome Feminization (rare) Patients with nonfunctional AC typically present with any of the following: Fever Weight loss[emedicine.medscape.com]
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  • Liver, Gall & Pancreas
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  • Workup

    All hormonal syndromes need to be confirmed with laboratory testing. In Cushing syndrome, the laboratory findings include increased urine cortisol and serum glucose. Adrenal virilism is confirmed by the finding of an excess of low serum potassium, low plasma renin activity and also high serum aldosterone. Exces serum estrogen depicts feminization [8]. To identify the site of the tumor, imaging studies of the abdomen, such as CT scans and magnetic resonance imaging are useful. They aid in differentiating ACC from other masses and in determining the extent of invasion of the tumor into surrounding tissues and organs. CT scans of the chest and bone scans are routinely performed to examine for metastases to the bones or lungs.

    Laboratory

    Urine
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  • Serum
    Androgens Increased
    • Testosterone and other androgens: increased facial and body hair, particularly in females deepened voice in females Estrogen: early signs of puberty in children enlarged breast tissue in males Aldosterone: weight gain high blood pressure Cortisol: high[healthline.com]
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  • Imaging

    X-ray
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  • CT
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  • Treatment

    Presently, the major treatment is total surgical excision of the tumor. This can be done even if the tumor has invaded large blood vessels like inferior vena cava or the renal vein. The 5-year survival rate after a successful surgery is around 60% however, majority of the patients are not surgical candidates [9]. For patients who are not surgical candidates, radiation therapy and radiofrequency ablation are used as palliation. For chemotherapy regimens, the drug mitotane and other standard cytotoxic drugs are used. Mitotane is an inhibitor of steroid synthesis and this is toxic to the cells of the adrenal cortex.

    Prognosis

    The efficacy of treatment is largely dependent on the stage of the cancer. Therefore early detection is paramount if the individual is to survive.

    Complications

    Ileus
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    Fever
    • Although in some cases, they are found incidentally, during either examination or radiologic imaging, nonfunctional ACs typically present with any of the following: Fever Weight loss Abdominal pain and tenderness Back pain Abdominal fullness Symptoms[emedicine.medscape.com]
    • […] function from morphology Lack of function may be due to deletions in enzymes required for cortisol synthesis Hormonally inactive ACCs usually present with gastrointestinal symptoms or back pain caused by mass effect Highly necrotic tumors may cause fever[pathologyoutlines.com]
    • Signs and symptoms Physical examination findings in patients with hormonally active AC include the following: Virilization Cushing syndrome Feminization (rare) Patients with nonfunctional AC typically present with any of the following: Fever Weight loss[emedicine.medscape.com]
    Hypertension
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    • However, cortisol, catecholamines or other hormones were not measured, despite the fact that she was a hypertensive patient.[casesjournal.biomedcentral.com]
    • January 9, 2018 Follow us: Home About Us Acknowledgements Feedback Contact Us Site Map Advertisement Home Genitourinary Adrenal Adrenal Cortical Carcinoma Adrenal Cortical Carcinoma slide 1 of 4 Comments: This patient presented with Cushing’s syndrome and hypertension[webpathology.com]
    • Signs and symptoms of virilisation are present in over 90% of cases, hypertension may also be present.[orpha.net]
    • , Co Durham DL 14 6AD, UK; s.nag{at}btopenworld.com Statistics from Altmetric.com adrenocortical carcinoma Cushing’s syndrome A 46 year old woman presented with a short history of hirsutism, facial plethora, amenorrhoea, progressive weight gain, and hypertension[pmj.bmj.com]
    Hypoglycemia
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    • Postoperative care should also focus on glucose levels because hypoglycemia may occur after the reduction of catecholamine levels.[annonc.oxfordjournals.org]
    Hypokalemia
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    • OH-progesterone (serum) androstenedione (serum) testosterone (serum) 17-beta-estradiol (serum, only in men and postmenopausal women) Mineralocorticoid excess potassium (serum) aldosterone/renin ratio (only in patients with arterial hypertension and/or hypokalemia[ensat.org]
    • Six months after surgery, she showed signs of hypertension recurrence accompanied by hypokalemia (serum potassium: 2.9 mEq/l) and hypernatremia (serum sodium: 150 mEq/l).[casesjournal.biomedcentral.com]
    • Conn syndrome ( mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations ) low plasma renin activity, and high serum[en.wikipedia.org]
    • […] serum) Testosterone (serum) 17-beta-estradiol (serum, only in men and postmenopausal women) 24-h urine steroid metabolite examination Mineralocorticoid excess Potassium (serum) Aldosterone/renin ratio (only in patients with arterial hypertension and/or hypokalemia[annonc.oxfordjournals.org]
    Virilization
    • More than 80% present of pediatric patients, however, present with virilization syndromes.[emedicine.medscape.com]
    • , followed by mixed Cushing's and virilization ( glucocorticoid and androgen overproduction).[en.wikipedia.org]
    • INTRODUCTION Adrenocortical carcinomas (ACCs) are rare and frequently aggressive tumors that may be functional (hormone-secreting) and cause Cushing's syndrome and/or virilization, or nonfunctional and present as an abdominal mass or as an incidental[uptodate.com]
    • Some patients have signs of virilization .[adrenaltumors.org]
    • Symptoms of increased cortisol or other adrenal gland hormones may include: Fatty, rounded hump high on the back just below the neck ( buffalo hump ) Flushed, rounded face with pudgy cheeks ( moon face ) Obesity Stunted growth ( short stature ) Virilization[medlineplus.gov]
    Hypernatremia
    • Six months after surgery, she showed signs of hypertension recurrence accompanied by hypokalemia (serum potassium: 2.9 mEq/l) and hypernatremia (serum sodium: 150 mEq/l).[casesjournal.biomedcentral.com]
    Gynecomastia
    • Feminization may occur in men with excess estrogen production, and may cause sexual impotence and/ or breast growth (gynecomastia).[oncolink.org]
    Cushing's Disease
    • This was suggestive of primary adrenal disease as cortisol levels normally suppress to less than 50% of basal levels in pituitary driven Cushing’s disease.[pmj.bmj.com]
    • Mitotane seems to be the drug of choice in Cushing's disease associated with polycystic ovary syndrome because it does not stimulate androgen production as other inhibitors of steroidogenesis do.[scielo.br]
    • Childhood Cushing disease: a challenge in diagnosis and management.[emedicine.medscape.com]
    Renal Vein Thrombosis
    • "Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: a case report" .[en.wikipedia.org]
    Feminization
    • Feminization is confirmed with the finding of excess serum estrogen .[en.wikipedia.org]
    • Feminization as a presentation of AC is quite rare.[emedicine.medscape.com]
    • Some effects of functioning tumors include Cushing's syndrome, hyperaldosteronism, (and less commonly) virilization and feminization.[uclahealth.org]
    • Sex hormone producing cancer leads to virilization in women and feminization in men.[csrf.net]
    Varicocele
    • "Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: a case report" .[en.wikipedia.org]

    Etiology

    Although the mutation-induced inactivation of tumor suppressor genes appears to be a plausible mechanism for ACC development, other potential mechanisms, including activation of various protooncogenes (eg, ras, PKC), inhibition of apoptosis, or changes in various adrenocortical tissue-specific factors (eg, the steroidogenic acute regulatory protein (StaR)) are possible [3]. Potential mechanisms for adrenocortical tumorigenesis are as follows:

    • Activation of various protooncogenes -Ras, PKC, C myc, C fos, G proteins, G protein-coupled receptors (eg, for vasoactive intestinal peptide (VIP), gastric-inhibitory peptide (GIP), luteinizing hormone (LH), and catecholamines)
    • Inactivation of tumor suppressor genes (antioncogenes) -TP53, TP57, TP16, H19, retinoblastoma gene, APC gene, various DNA repair enzyme genes
    • Inhibition of senescence and/or apoptosis - Mutations involving telomerase and/or BCL-2 genes
    • Changes in adrenocortical tissue-specific factors - Mutations involving the genes for StaR, SF-1 (steroidogenic factor), and Dax-1 transcription factor
    • Aberrant expression of receptors to normal adrenocortical trophic agents and ligands - Adrenocorticotropic hormone, angiotensin 2, catecholamines, and endorphins
    • Ectopic expression of receptors on adrenocortical cells to atypical trophic factors and ligands - Cytokines, growth factors, and neurotransmitters

    Causes

    Hypertension
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    • However, cortisol, catecholamines or other hormones were not measured, despite the fact that she was a hypertensive patient.[casesjournal.biomedcentral.com]
    • January 9, 2018 Follow us: Home About Us Acknowledgements Feedback Contact Us Site Map Advertisement Home Genitourinary Adrenal Adrenal Cortical Carcinoma Adrenal Cortical Carcinoma slide 1 of 4 Comments: This patient presented with Cushing’s syndrome and hypertension[webpathology.com]
    • Signs and symptoms of virilisation are present in over 90% of cases, hypertension may also be present.[orpha.net]
    • , Co Durham DL 14 6AD, UK; s.nag{at}btopenworld.com Statistics from Altmetric.com adrenocortical carcinoma Cushing’s syndrome A 46 year old woman presented with a short history of hirsutism, facial plethora, amenorrhoea, progressive weight gain, and hypertension[pmj.bmj.com]
    Hypokalemia
    • Other modes of presentation include profound weakness, hypertension, and/or ileus from hypokalemia related to hyperaldosteronism and hypoglycemia.[emedicine.medscape.com]
    • OH-progesterone (serum) androstenedione (serum) testosterone (serum) 17-beta-estradiol (serum, only in men and postmenopausal women) Mineralocorticoid excess potassium (serum) aldosterone/renin ratio (only in patients with arterial hypertension and/or hypokalemia[ensat.org]
    • Six months after surgery, she showed signs of hypertension recurrence accompanied by hypokalemia (serum potassium: 2.9 mEq/l) and hypernatremia (serum sodium: 150 mEq/l).[casesjournal.biomedcentral.com]
    • Conn syndrome ( mineralcorticoid excess) is marked by high blood pressure which can result in headache and hypokalemia (low serum potassium, which can in turn produce muscle weakness, confusion, and palpitations ) low plasma renin activity, and high serum[en.wikipedia.org]
    • […] serum) Testosterone (serum) 17-beta-estradiol (serum, only in men and postmenopausal women) 24-h urine steroid metabolite examination Mineralocorticoid excess Potassium (serum) Aldosterone/renin ratio (only in patients with arterial hypertension and/or hypokalemia[annonc.oxfordjournals.org]

    Epidemiology

    Internationally, the tumors are uncommon [1] [2]. With approximately 0.6-1.67 cases per 1 million people each year, the incidence is relatively low. Some reports say that incidence is ten times higher in southern Brazilian children for reasons unknown. Overall however, ACC accounts for 0.02-0.2% of all cancer-related deaths so the disease is rightly adjudged as rare.

    ACC does not have any racial predilection and the female to male ration is 2.5-3.1. The male patients tend to be older than the females and the prognosis is better for females. However, the females are more likely than the male counterparts to have an associated endocrine syndrome. Nonfunctional ACCs occur equally between both sexes. ACC has two major periods of occurrence, the first decade of life and the fourth and fifth decade of life. 75% of children who have ACC are younger than 5 years of ages. Nonfunctional tumors are more common in adults but functional tumors are common in children.

    Sex distribution
    Age distribution

    Pathophysiology

    Although some reports point to an increased predilection for the left adrenal, majority of reports show no side preference. The exact etiopathogenesis of sporadic ACC is unclear but analysis of the syndromic variants of the condition provides some insight [4]. The role of tumor suppressor gene mutations is suggested by their association with Li-Fraumeni syndrome, which is characterized by inactivating germline mutations of the TP53 gene (a vital tumor suppressor gene or antioncogene) on chromosome 17. This syndrome also is associated with a predisposition to other malignancies, including breast carcinoma, leukemia, osteosarcoma, and soft-tissue sarcoma.

    A few reports describe an association between AC and familial adenomatous polyposis, which also is due to a germline inactivating mutation of a tumor suppressor gene (in this case, the adenomatous polyposis coli gene, APC) [5]. However, such mutations have not been found in sporadic APC cases.

    Suggestions have been made that adrenal hyperplasia predisposes patients to develop ACC. A few cases of congenital adrenal hyperplasia are associated with functional adrenocortical adenomas but not carcinoma.

    Prevention

    Majority of adrenal gland tumors are not linked to family history but some are linked to genetic defects. This means that there is really no way to prevent the disease. The best bet is to focus on early detection.

    Summary

    Adrenocortical carcinoma (ACC) is a rare malignancy of the adrenal cortex and can be equally referred to as adrenal cortical carcinoma. The adrenal cortex represents the outer layer of the adrenal glands which are located at the upper poles of the kidneys. The adrenal cortex secretes mineralocorticoids, glucocorticoids and adrenal androgen. The presentation varies depending on hormone excess or local tumor growth and adrenal incidentalomas are common [1].

    Patient Information

    Adrenocortical carcinoma is a rare cancerous growth in the adrenal cortex. Patients have to be on the lookout for reoccurrence of growth. This will be dealt with by surgery as well [10]. For healthy individuals or people in a family with history of ACC, family members around the peak years for ACC occurrence should be monitored for symptoms like lump in the abdomen, pain in the abdomen or back, unusual hair growth, irregular menstrual cycles, irregular sexual behavior and in children, early puberty.

    Self-assessment

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    References

    1. Angeli A, Osella G, Terzolo M. Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group. Horm Res. 1997;47(4-6):279-83.
    2. Villelli NW, Jayanti MK, Zynger DL. Use and Usefulness of Adrenal Core Biopsies Without FNA or On-site Evaluation of Adequacy: A Study of 204 Cases for a 12-Year Period. Am J Clin Pathol. Jan 2012;137(1):124-31.
    3. Lau SK, Weiss LM. The Weiss system for evaluating adrenocortical neoplasms: 25 years later. Hum Pathol. Jun 2009;40(6):757-68.
    4. Soon PS, Gill AJ, Benn DE, Clarkson A, Robinson BG, McDonald KL, et al. Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas. Endocr Relat Cancer. Jun 2009;16(2):573-83.
    5. Miller BS, Gauger PG, Hammer GD, et al. Proposal for modification of the ENSAT staging system for adrenocortical carcinoma using tumor grade. Langenbecks Arch Surg 2010; 395:955.
    6. Allolio B, Hahner S, Weismann D, Fassnacht M. Management of adrenocortical carcinoma. Clin Endocrinol (Oxf) 2004; 60:273
    7. Reibetanz J, Jurowich C, Erdogan I, et al. Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma. Ann Surg 2012; 255:363.
    8. Bertagna C, Orth DN. Clinical and laboratory findings and results of therapy in 58 patients with adrenocortical tumors admitted to a single medical center (1951 to 1978). Am J Med 1981; 71:855.
    9. Stojadinovic A, Ghossein RA, Hoos A, et al. Adrenocortical carcinoma: clinical, morphologic, and molecular characterization. J Clin Oncol 2002; 20:941.
    10. Hough AJ, Hollifield JW, Page DL, Hartmann WH. Prognostic factors in adrenal cortical tumors. A mathematical analysis of clinical and morphologic data. Am J Clin Pathol 1979; 72:390.

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