I believe the differential diagnosis is Cushing’s syndrome. Some of its symptoms are ‘truncal obesity, moon face, hypertension, bruising, muscle weakness, mood disorder’ (Wartofsky, 2012), ‘glucose intolerance, moderate weight gain, purple straie and in severe cases diabetes’ (Lavin, 2009). The symptoms I have listed are all symptoms of Cushing syndrome that Richard has and has been diagnosed with, it is also possible to have diabetes if Cushing’s syndrome becomes more severe. Symptoms like moon face and truncal obesity is due to the ‘redistribution of fat to the face, neck and abdominal region’ (Greenstein and wood, 2011). The reason why it is likely diagnosed to be diabetes is due to similar symptoms and due to some of its effects. Cushing syndrome cause is due to ‘excess cortisol circulating in the blood by adrenal adenoma or elevated adrenocorticotropic hormone (ACTH) from pituitary tumors. This in turn leads to excess glucorticoid levels which causes patients to develop severe insulin resistance. Because of this it causes central obesity and can lead to type 2 diabetes’ (Minghan, 2011). ‘Cushing syndrome can also be caused by use of glucorticoid for inflammatory or immunosuppressive treatment’ (Wartofsky, 2012) if the amount given is enough to effect the total levels of glucocorticoid or if the patient is unable to remove it from his circulatory system. ‘A major part of Cushing syndrome is its endogenous family which consist of three types they are:
Pituitary Cushing syndrome – About 68% of all endogenous Cushing syndrome. It is caused by a small pituitary tumour (microadenoma) that produces an excessive amount of ACTH
Adrenal Cushing syndrome’ About 17% of all endogenous Cushing syndrome. It is caused by cortisol production by an adrenal tumour (adenoma or carcinoma)
Ectopic Cushing syndrome ‘ About 15% of all endogenous Cushing syndrome. It is caused by ACTH production due to many malignancies and disorders it is mainly caused by bronchogenic carcinoma.
The reason I came to this conclusion is due to many of Richards symptoms are also part of Cushing’s syndromes symptoms as well as diabetes symptoms and that it can cause diabetes if left untreated.’ (Lavin, 2009)
It is unlikely he has type 1 diabetes as it tends to be inherited (Kenny, et al 2013) genetically by a parent so if you have a family history of type 1 diabetes then you are likely to have it. Some of the symptoms of Cushing’s like purple striae, truncal obesity, bruising, muscle weakness, etc. (Wartofsky, 2012) are symptoms that are not part of diabetes. ‘For both type 1 and 2 diabetes there are some of their most common symptoms like weight loss and tiredness’ (Kenny, et al 2013) are not any of the symptoms that Richard has been diagnosed and he has instead had an increase in weight which is also one of the symptoms for Cushing’s syndrome. They’re only common symptom that has been identified is polydipsia (increased thirst) and polyuria (more urine production), there isn’t another symptom common between Richard and diabetes. It is likely that they came didn’t think about Cushing’s at it isn’t a common disease as it ‘effects about 10-15 people per million’ (Tidy and Bonsall, 2014). Diabetes being a common disease known across the world and advertised to the public and is more well-known and likely the chosen outcome.
Cushing’s syndrome is caused by either taking ‘glucocorticoids for immunosuppressive or anti-inflammatory treatments leading to excess amounts of glucocorticoids’ (Wartofsky, 2012) or the formation of a cancer. These cancer affect endocrine glands and will cause the release of ACTH. They can be ACTH dependant or ACTH independent. ACTH dependant tumours are ‘pituitary tumours which results in bilateral adrenocortical hyperplasia, adrenal cortical tumours such as benign adenomas or malignant carcinomas (Greenstein and wood, 2011) and ‘ectopic corticotropin syndrome which is usually caused by small cell carcinoma of the lungs and bronchial carcinoid tumours but can occur by almost any endocrine tumour’ (Tidy and Bonsall, 2014). There is also ACTH independent tumours which arise most commonly form ‘adrenal adenoma and adrenal carcinoma and rarely by corticotropin- dependent macronodular adrenal hyperplasia, primary pigmented nodular adrenal disease and McCune- Albright syndrome’ (Tidy and Bonsall, 2014). Cushing’s syndrome can be diagnosed by:
‘ ‘A full blood count- white cell count greater than average’ (Tidy and Bonsall, 2014).
‘ Electrolytes and acid- base balance- hypokalemia (low level potassium) which is common in ectopic ACTH secretion due to mineralocorticoid activity and metabolic alkalosis which results in a change in ph.’ (Tidy and Bonsall, 2014).
‘ ’24 hour urinary cortisol- 3 collection also measures creatinine excretion at the same time. Cushing’s syndrome diagnosed if two or more collections measure cortisol excretion to be more than 3 times the laboratory upper limit of normal. Test repeated if creatinine excretion varies more than 10% between collections. False readings may occur with pregnancy, anorexia, exercise, psychoses, alcohol and alcohol withdrawal which can cause an increase in cortisol secretion leading to a positive diagnosis’ (Tidy and Bonsall, 2014).
‘ ‘Low dose dexamethasone suppression test- Used for those who are unreliable for 24 hour collection test. Process requires ingestion of 1mg of dexamethasone at 11pm. Serum cortisol is then measure at 8am the next morning. Mild Cushing’s syndrome is difficult to diagnose from normal cortisol secretion or pseudo Cushing’s syndrome resulting in both a false positive or negative diagnosis’s’ (Tidy and Bonsall, 2014).
‘ ‘Midnight cortisol levels- Taken between 11pm and 1am to demonstrate the loss of normal diurnal variation of reduced cortisol production in the evening compared to the morning. Blood sample taken from an indwelling cannula with the patient being relaxed. Late night salivary cortisol measurement is a simple and reliable screening test’ (Tidy and Bonsall, 2014).
‘ Dexamethasone suppressed corticotropin releasing hormone (CRH) test- Modified version of low dose dexamethasone suppression test. 8 doses of 0.5mg dexamethasone is given in a 48 hour period before an IV of CRH is given 2 hours after. Serum cortisol is then measure 15 minutes after ovine CRH administration.’ (Tidy and Bonsall, 2014).
These are basics test used to determine if you have Cushing’s syndrome in order to find out what is the cause of their Cushing’s syndrome further test are required they are:
‘ ‘Plasma ACTH- Measures the secretion and plasma concentration of ACTH. Both are greater at 8am and lowest at midnight when measured. The rate of secretion increases with stress. If plasma ACTH is undetectable then patient diagnosed with ACTH- independent Cushing’s syndrome which is due to primary cortisol producing adrenal adenoma or carcinoma or exogenous glucocorticoid use. This is then followed by an abdominal CT or MRI scan if exogenous glucocorticoids are not accepted as cause. If ACTH is elevated then patient is predicted to have ACTH dependent Cushing’s syndrome. If plasma ACTH is detectable then the following tests are used: ‘(Tidy and Bonsall, 2014)
‘ ‘High dose dexamethasone suppression test- 8 mg overnight dexamethasone suppression test and 48 hour high dose dexamethasone test may be useful when baseline ACTH is interpreted to have multiple potential diagnosis. They also help determine whether a patient has pituitary or ectopic ACTH production. Greater than 90% reduction in basal urinary free cortisol levels diagnose the patient with pituitary adenoma. Ectopic ACTH causes lesser degrees of suppression’ (Tidy and Bonsall, 2014).
‘ ‘Inferior petrosal sinus sampling (IPS) ‘ This procedure requires a skilled invasive radiologist who can sample blood from IPS veins that drain the pituitary. ACTH and other pituitary hormones reach the bloodstream through these veins. A catheter can be placed in both these veins at the same time and blood sampled for ACTH before and after administration of CRH. CRH stimulates the release of ACTH. It done correctly this will diagnose a patient with great accuracy the presence or absence of an ACTH secreting pituitary tumour.’ (Findling, 2014).
‘ ‘Magnetic resonance imagine (MRI) scan that will help distinguish if there is a tumour growing on the pituitary. Sometimes difficult to distinguish due to their small size so use of a gadolinium enhancement injections used. Once a tumour has been recognized it may require further testing by a skilled pituitary neurosurgeon. In some cases incidental tumours found in pituitary have ectopic ACTH syndrome.’ (Findling, 2014).
‘ ‘Computed Tomography (CT) scan of adrenal glands are for patients who do not have ACTH secreting tumours which means they have low ACTH levels. Normally the problem is normally due to the adrenal glands. CT scans of the adrenal gland will help identify a solitary cortisol- producing tumour from the adrenal gland or large nodules in each adrenal gland resulting in cortisol excess’ (Findling, 2014).
These further test help in diagnosing the cause of the Cushing’s syndrome that they are undergoing so that they can receive the correct treatment to aid in they’re recovery.
‘Based on the type of Cushing’s syndrome you are affected by you will receive the appropriate treatment this mainly being surgery but due to some of the symptoms of Cushing’s like poor healing, weak muscles there is a greater risk when taking surgery. Sometimes the patient or staff are unable to do the surgery straight away so while waiting you will be given drugs like metyrapone, ketoconazole and mitotane which will reduce the release of cortisol by directly inhibiting synthesis and secretion in the adrenal glands. Metyrapone and ketoconazole are enzyme inhibitors that have a fast response but do not last very long due to the over secretion caused by Cushing’s syndrome. This means that they aren’t useful for long term treatments so are instead used on patients who are prepping for surgery or radiotherapy. Mitotane acts as an adrenolytic drug which reacts slow but is long lasting allowing to maintain control of Cushing’s syndrome reducing the effects of over secretion. Drug treatment are also used for patients who are unwilling or unfit to take surgery. This long term treatment is best used for patients with ectopic corticotropin but adrenalectomy which is the removal of the adrenal glands is preferred. Based on the tumour you will receive a different surgery with different conditions.
If you have a pituitary tumour you will receive trans- sphenoidal microsurgery and radiation therapy if the patient was not cured. If you have toxic levels of cortisol levels you will have a bilateral adrenalectomy in order to maintain control.
If you have adrenocortical tumours you will require surgical removal by laparoscopic surgery which is considered the best treatment for unilateral adrenal adenomas.
If you are affected by ectopic ACTH production the neoplastic tissue will be removed. If you have toxic levels of cortisol you will have a bilateral adrenalectomy in order to control cortisol levels.
If you have hypercortiosolaemia after trans- sphenoidal surgery you will have pituitary radiotherapy. Conventional fractioned radiotherapy is very affective but is associated with long term hypopituitarism and can be delayed in effectiveness’ (Tidy and Bonsall, 2014).
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