Quality-of-life issues COMPLICATIONS OF CUSHINGS What is the damage (complications) of having Cushing’s syndrome? Quality-of-life issues As you have learned, cortisol is a powerful steroid hormone, and excess cortisol has detrimental effects on many cells throughout the body. It can cause numerous symptoms including obesity/weight gain, thin skin, purple striae (stretch marks), hypertension, proximal muscle wasting/weakness, menstrual irregularity in women, decreased libido (sexual drive), hirsutism/virilization (male/female characteristics), precautious puberty in children, glucose intolerance/diabetes, osteoporosis/fractures, delayed bone age and neuropsychiatric symptoms (how we feel and how our brain works). Thus, it is not surprising that both overt and subclinical Cushing’s syndrome may have significant negative effects on the quality-of-life of patients. Two recent studies (November 2019) that patients report fatigue, a variety of mental and physical symptoms, and impairment in quality of life. Mortality (death) and morbidity (disease) are increased even after long-term correction of glucocorticoid (cortisol) excess, including cognitive functioning, indicating irreversible adverse effects of previous hypercortisolism. In addition, structural and functional brain abnormalities were shown to be persistent even after biochemical cure of Cushing syndrome, which was related to both quality of life (mainly disease-specific) and cognitive functioning impairments (mainly memory) in patients with Cushing syndrome. In one study, there was a significant improvement in all measurements of quality of life after treatment (especially after surgery for cortisol producing adrenal tumors). Unfortunately, patients improved, but did not complete get back to normal after successful treatment which brings up 2 major points: 1) The high cortisol (Cushing’s syndrome) in patients is very toxic and cause irreversible damage, 2) The Cushing’s syndrome needs to be identified, diagnosed and treated (ideally with surgery, learn about minimally invasive scope surgery here) as rapidly as possible before irreversible damage occurs. The other study out of Denmark essentially demonstrated the same findings that “… most cognitive domains (meaning how your brain works) were significantly affected by Cushing’s syndrome and responded favorably to surgery. Depressive symptoms and reduced health-related Quality-of-life were present in patients with Cushing’s syndrome and improved after surgery” Dr. Carling, Editorial note: Unfortunately, we see patients every week, where it has taken years to decades to diagnose Cushing’s syndrome, and identify either the adrenal or pituitary tumor. Even though the cortisol levels may not seem alarmingly high, excessive cortisol levels can be very toxic. These patients need to be identified, diagnosed correctly and have curative surgery. Why is there a tremendous need for screening and detection of Cushing’s syndrome? Similar as many other adrenal tumors (Primary hyperaldosteronism; Conn tumor (read here), pheochromocytoma (read here), etc), cortisol-producing adrenocortical tumors are highly underdiagnosed and undertreated. This means, only a fraction of patients with the disease will ever have it diagnosed, and even fewer will have it treated. This is one of the reasons we have developed this website. We want to empower patients with knowledge. We want you to be as informed as possible. This is all we do, but the fact is that many doctors may go through a whole career and not see a single patient with these diseases. It is difficult to be an expert on something you have never seen before. So, if you have any of the above symptoms, you need to be screened to make sure you don’t have a cortisol-producing adrenocortical tumor. Only a fraction of all patients with cortisol-producing adrenocortical tumors are being diagnosed, and an even smaller fraction are being offered surgery. Learn about minimally invasive adrenalectomy here. This toxic (and very silent) disease can often be cured by a 20-30-minute operation. It may save you from developing further obesity, diabetes, hypertension, make you feel better and prevent premature death. Therefore, people with symptoms of Cushing’s syndrome need to be screened for this disease. Overt (meaning the signs and symptoms of the disease are so classic a first-year medical student would be able to figure it out) Cushing’s syndrome is a relatively rare disorder. As you will learn below, subclinical Cushing’s syndrome is much more common, and a very silent but toxic disease. Cushing’s syndrome is 3 times more common in women than in men, approximately 10% of cases occur in children. Unilateral cortisol-producing adrenocortical adenomas account for the majority (∼80 %) of ACTH- independent Cushing’s syndrome cases, while adrenocortical carcinoma is the underlying cause in approximately 15 % of cases. An important feature of adrenocortical carcinoma is its bimodal age distribution, with peaks in childhood and in the fourth to fifth decades of life. Read more about adrenocortical carcinoma here. While the majority of cases of this devastating disease are sporadic, one should bear in mind that this cancer can be part of hereditary syndromes such as the Li–Fraumeni syndrome, Beckwith–Wiedemann syndrome, multiple endocrine neoplasia type 1, congenital adrenal hyperplasia, familial polyposis coli, β-catenin mutations, and germline TP53. mutations without Li–Fraumeni. Learn more about the molecular genetics of Cushing’s syndrome here. Among the less common causes of ACTH-independent Cushing’s syndrome are the familial and sporadic forms of bilateral macronodular (BAIMAH) and micronodular adrenal hyperplasia with its pigmented variant also referred to as primary pigmented nodular adrenocortical disease (PPNAD). Patients with BAIMAH and PPNAD can be excellent candidates for partial (cortex-sparing) adrenalectomy and should have their operations performed at the highest-volume adrenal surgery center, as possible.