The adrenal glands are hormone producing organs that sit on top of the kidneys.
The outer part is called the cortex – responsible for producing glucocorticoids and mineralocorticoids – (cortisol and aldosterone) as well as small amounts of male and female sex hormones.
The inner part is called the medulla – responsible for producing adrenaline and noradrenaline. These are the fight or flight hormones, which are released when the sympathetic nervous system recognises physical or emotional stress.
Glucocorticoids play a role in converting fats, carbohydrates and proteins into energy, whilst also helping to regulate blood pressure and heart function. They also help regulate the immune system
Mineralocorticoids help control blood pressure by regulating our salt / water balance.
Adrenocorticol Carcinoma is a cancer that starts in the cortex – the outer layer of the adrenal gland.
Causes and potential risk factors for ACC
We do not know exactly what causes ACC – however it is important to follow advice in leading a healthy lifestyle: eat healthily, exercise and avoid smoking and too much alcohol.
Most ACCs do not run in families; however, there may be conditions can increase the risk of it developing. Therefore, if other members of the family have been diagnosed with cancer, (particularly under the age of 50years) or have a known genetic condition, it is important that you tell your specialist team about not only your personal medical history, but also any family medical illnesses or conditions.
Further information about ACC can be found at www.accsupport.org.uk
Symptoms that may or may not include ACC associated syndromes.
In Adrenocortical Carcinoma (ACC) – the tumour may or may not produce too much of a particular hormone – you may hear the terms “Functioning” (meaning “with hormone related symptoms”) or “Non-functioning” (meaning “without hormone related symptoms”).
Non-functioning ACC, is when the tumour does not over produce hormones. Therefore symptoms, if they occur, will be related to the presence /position of the tumour and might include pain or swelling, weight loss or signs that the disease has spread outside of the adrenal gland. Although they may not produce the symptoms of high hormone levels, sometimes these hormones can be found in the blood or urine.
Occasionally, ACC is found by chance, for example, during a scan while investigating something else. These tumours are described as ‘incidental’.
Functioning ACC may make higher than normal amounts of cortisol and aldosterone and may also secrete hormones that a healthy adrenal would not normally produce, such as the male hormone testosterone and the female hormone oestradiol, causing symptoms and maybe even body changes.
Symptoms can include:
• Diabetes – increased thirst, having to pee more often, altered blood sugar levels
• High blood pressure
• Sexual dysfunction,
• Muscle weakness and wasting,
• Weight gain,
• Excess facial or body hair in women
• Baldness in women
• Deepening of the voice in women
• Soreness and increase of the size of the breasts in men
• Easy bruising
• Early puberty in children
• Reduced immunity (impaired response to infections)
• Change in body shape
• Mood changes.
Syndromes that may occur include Cushings and / or Virilising Syndrome – both can produce 2 or more of the symptoms listed above.
Tests that may be used for the diagnosis and / or monitoring of ACC:
Blood / Urine:
Full blood count
Liver and kidney function
Glucocorticoid excess (minimum 3 of 4 tests)
Dexamethasone suppression test (1mg 23:00)
Excretion of free urinary cortisol (24 hr urine)
Basal cortisol (serum) Basal ACTH (plasma)
Sexual steroids and steroid precursors
Serum DHEA-S, 17-OH-progesterone, Androstenedione & Testosterone
17-beta-estradiol (serum, men & postmenopausal women only), 24-h urine steroid metabolite examination
Potassium (serum) Aldosterone/renin ratio (only in those with arterial hypertension +/- hypokalaemia)
Normetanephrine, metanephrine & methoxytyramine (plasma)
Alternatively – fractionated metanephrine excretion (24 hr urine)
In those with a clearly established diagnosis of ACC, catecholamine excess work-up is not required
CT chest & abdomen and / or CT chest &MRI abdomen
Bone scintigraphy/brain imaging – where there is clinical suspicion of metastases
mIBG scintigraphy, DOTA_TATE_PET, Dopa/Dopamine PET or FDG-PET if pheochromocytoma is proven
Differentiation and cellular morphology (Weiss score)
Steroidogenesis Factor-1 (if available)
FNA (Fine Needle Aspiration) should not be performed in suspected cases of ACC since it usually does not obtain enough tissue to distinguish the difference between cancer and non-cancerous growths.
nb. a biopsy is only indicated where surgery is not currently possible and histology is required to plan / access oncological management (treatment).
The key aim of treatment, should be to help you have the best possible care and quality of life – by ensuring access to appropriate treatment, management of symptoms and addressing what’s most important to you.
With ACC cure is not always possible, however, this does not necessarily mean that there are no options for treatment that may extend your life and improve quality of life by controlling the disease and treating symptoms.
Treatment options will depend on the type (functionality & grade, etc), position and size of your ACC – and whether (and to where) it has spread (staging).
It will also depend on whether you have any other health concerns and / or illnesses and your general health and fitness.
One or more of the approaches below may be suggested:
Control of your disease, by slowing or stopping further growth and / or spread
Palliation, or easing, of any symptoms you may be experiencing
Surgery: Removal of the adrenal gland is called an adrenalectomy. Even if the tumour has spread (metastasised) to other organs, it may still be appropriate to remove the initial tumour first and then remove or treat other metastases later.
If you need to have one of your adrenal glands removed, your other gland will carry on making all the hormones you need.
If you have both adrenal glands removed, you will have to take hormone replacement tablets every day for the rest of your life and carry an alert card : https://www.endocrinology.org/media/3563/new-nhs-emergency-steroid-card.pdf
Surveillance and / or Mitotane
If the tumour is judged to have a low risk of returning, then your doctor may discuss giving you the choice between close follow-up (observation only /surveillance) and treatment with mitotane.
If there is a high risk of the tumour returning you may be advised to start a course of two to three years of mitotane treatment, to start within 12 weeks of the surgery.
If the initial surgery is unable to remove all of the tumour or the tumour returns following surgery, Mitotane has been proven to help control the disease. But this is not a ‘cure’ – Mitotane may be continued for life.
For those where the disease is advanced (spread) and surgery is not possible :chemotherapy may be used to try to shrink the tumour(s) and control the disease.
In such a situation your doctors may not only recommend chemotherapy but also Mitotane; however, this depends on individual circumstances.
Mitotane may also help control the symptoms caused by too much hormone being produced.
Radiotherapy is sometimes given to the adrenal area after surgery to kill any cancer cells that might remain there. It may also be used for ACC that has spread beyond the adrenal glands, in particular if disease has spread to the bones – here it is used to help control growth of any spread and alleviate bone pain
Chemotherapy can be given orally (in tablets) or IV (through a vein), to help to slow tumour growth or to try to reduce tumour size. It can be given as a primary therapy on its own – before or instead of surgery, or may be given after surgery. Before surgery the aim may be to try to shrink the tumour so that surgery can take place – after surgery it may be given to reduce the risk of ACC coming back. Instead of surgery – it may be the only treatment available if surgery is not safe or possible.
Clinical Trials – clinical research and safe new treatment development is essential to provide best care for those with Neuroendocrine Cancer – we need to know that treatments not only work but work safely. There are several phases of trial therapy. Each trial will have specific criteria in regards to patient suitability – this can be discussed with your clinical team. You do not have take part in a trial – participation is voluntary.
Symptom Control: Managing symptoms, including pain, is an important part of total care – and therefore occurs throughout care, not just at ‘end-of-life’. Symptom control or ‘palliation’ refers to what is used to alleviate or reduce the impact your cancer, other health issues and /or treatments may be having on you and your physical and mental health. It can include anything from simple medication and / or a combination of some of the treatments mentioned above to counselling and practical support.
There are expert agreed guidelines regarding how and when follow up should occur, however, in practice this varies and often with good reason. Follow up should be expert informed & evidence /research based but also tailored to you and what is appropriate for your best care.
For patients following complete resection:
- CT/MRI* 3 monthly for 2 years, then 3 – 6 monthly for further 3 years
- Ongoing surveillance beyond 5 years is suggested but can be adapted according to clinical indication.
- Regular hormone screen.
Advanced ACC (incomplete resection, metastatic and inoperable disease):
- Imaging and hormone monitoring – follow up as per guidelines – but should be guided by prognosis, expected treatment efficacy and treatment related toxicity. Your health, well-being, physical activity, informed choice and preference for ongoing care as well as aim of treatment should be reviewed and discussed to best plan care.
*Cross sectional imaging: chest, abdomen and pelvis is recommended.