Explain the causative factors and pathophysiology of Cushing syndrome and how she developed this condition.
Describe the primary signs and symptoms of Cushing syndrome.
What aspects of her clinical history place Sara at increased risk of hypertension and, briefly explain the difference between Graves’ disease and Cushing syndrome.
What treatment and follow up options are there for her condition?
The current paper is a discussion of Cushing’s disease with an aim of understanding the endocrine pathology associated with this disease. the discussion is in response to a case study of a patient, Sara Haines is a 38-year-old female who developed the disorder. The causative factors of this disorder will be outlined and the pathophysiology and clinical manifestations discussed.
Cushing’s Disease Causation and pathophysiology
Cushing syndrome is an inappropriately elevated level of corticosteroids in circulation (Barrett, Barman, Boitano, and Brooks, 2010). Increased circulating glucocorticoids can be either due to endogenous overproduction or iatrogenic exogenous administration (Lacroix, Feelders, Stratakis, & Nieman, 2015). Endogenous Cushing syndrome is characterized as ACTH dependent or non-ACTH dependent. ACTH dependent Cushing syndrome is due to a primary problem with adrenocorticotropic hormone produced by the pituitary gland leading to excess activation of the adrenal cortex to produce cortisol (Barrett, Barman, Boitano, and Brooks, 2010). The possible etiologies of ACTH pathology include:
- A pituitary adenoma secreting excess ACTH also termed Cushing’s disease (Bertagna, Guignat, Raux-Demay, Guilhaume, & Girard, 2011).
- Ectopic production of ACTH by other non-pituitary tumors termed ectopic ACTH syndrome. Such tumors include small cell lung carcinoma and bronchial carcinoids.
Non-ACTH dependent causes include primary adrenal pathologies such as adrenal adenomas, adrenal carcinoma and adrenal macronodular hyperplasia (Lacroix, Feelders, Stratakis, & Nieman, 2015). Iatrogenic exogenous Cushing syndrome is the excess or prolonged administration of synthetic glucocorticoids. This was the cause of Cushing syndrome in Sara’s case. She was on betamethasone, a synthetic steroid, for management of her Asthma.
The clinical manifestations are varied. This is due to the extensive action of cortisol and steroids on all body cells and the effects of cortisol on metabolism (Nieman, Lacroix, & Martin, 2011). Patients will complain of weight gain especially in the trunk, face, and abdomen and associated with increased thirst and appetite. They also have menstrual disturbances, infertility, hirsutism, decreased sexual desire and amenorrhea due to the disruption in the pulsatile production of follicle stimulating hormone and luteinizing hormone. Patients may also notice thinning of their skin causing easy bruising and stria. They also have myopathies leading to proximal muscle weakness (Gupta & Gupta, 2013). This leads to difficulty getting up from sitting positions, climbing stairs or using the toilet. They are prone to fractures and may complain of fracture or loss of height. Psychological symptoms include depression and psychosis (Pivonello et al., 2015).
Common signs on examination include:
The patients have increased fat deposition in the face “moon face”, in the abdomen as centripetal fat, in the back and neck “buffalo hump” and in the supraclavicular area appearing as fat pads in this region (Barrett, Barman, Boitano, and Brooks, 2010).
The skin is thinned leading to wide, extensive stria over the buttocks, abdomen, back, thighs, arms, and breasts. The skin over the face has a visible plethora. Other skin features include ecchymosis, petechia, bruising and purpura. Acne over skin area can also be a feature (Barrett, Barman, Boitano, and Brooks, 2010).
Activation of mineralocorticoid receptors leads to water and sodium retention causing hypertension (Isidori et al., 2015).
- Gastrointestinal features include peptic ulceration leading to peptic ulcer disease (Barrett, Barman, Boitano, and Brooks, 2010).
- Musculoskeletal features include proximal muscle weakness and osteoporosis predisposing the patient to frequent fractures (Gupta & Gupta, 2013).
Sara Haines, the patient has classic symptoms of Cushing syndrome including weight gain, increased thirst and appetite, depression, muscle weakness, facial hair growth, and menstrual abnormalities. She also had the signs of a protuberant abdomen, stria, and hyperpigmentation.
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