Table 1.
Comorbidities in Cushing syndrome
| Comorbidity | Description/pathophysiology in Cushing syndrome | Prevalence in Cushing syndrome (%) (5, 10, 14-17) |
|---|---|---|
| Hypertension | • Mineralocorticoid and glucocorticoid effect of cortisol • Activation of renin-angiotensin system • Impaired balance between vasodilators and vasoconstrictors • Increase in sympathetic nervous system (5, 10) |
70-85 |
| Hyperlipidemia | • Cortisol increases (peripheral) lipolysis and free fatty acid production and very-low-density lipoprotein synthesis • Fatty acid accumulation causes increase in total cholesterol and triglyceride levels • Insulin resistance also plays a role in dyslipidemia (18, 19) |
70 |
| Insulin resistance and impaired glucose tolerance | • Stimulation of gluconeogenesis • Development of insulin resistance • Decrease in insulin secretion from the pancreas (20) |
45-70 |
| Obesity | • Promotion of lipogenesis/adipogenesis resulting in visceral fat accumulation, most commonly abdominal (21) • Adipocyte hypertrophy by increasing synthesis and storage of lipids (22) • Adipose tissue hyperplasia by increasing differentiation of preadipocytes to mature adipocytes (22) • Contribution to weight gain by increasing food intake with a preferential choice of high-caloric, high-fat “comfort foods” (23) |
70-95 |
| Hypercoagulability | • Hypercoagulability from increased clotting factors and impaired fibrinolysis • Prothrombotic state causes venous thromboembolisms (18, 21, 24) |
20 |
| Osteoporosis | • Decrease bone collagenous matrix synthesis • Increase degradation of bone matrix (25) |
50 |
| Cardiovascular disease | • Increased cardiovascular risk factors, cardiac remodeling, dysfunction, and vascular atherosclerosis • Left ventricular hypertrophy and remodeling, reduced systolic function, and impaired relaxation seen • Risk factors for myocardial infarction and stroke include vascular damage and increase in atherosclerotic plaques (10, 25) |
29 |
| Neuropsychiatric | • Emotional lability, depression, irritability • Other symptoms include psychosis, mania, anxiety, paranoia • Associated with decrease in brain volume and impairment of memory, visual and spatial information, verbal learning and language (25, 26) |
70-85 |
| Infectious diseases | • Hypercortisolism causes immunosuppression by impairing both cellular and humoral components of the innate immune system and inhibiting steps in the adaptive immune response • Predisposes patients to opportunistic infections: bacterial, fungal, viral, and parasitic • Susceptibility of infection correlates with degree of hypercortisolism (16, 17, 27) |
21-51 |
| Others (nephrolithiasis, hyperandrogenism gonadal dysfunction) | • High prevalence of nephrolithiasis from synergic effects of several lithogenic factors particularly systemic arterial hypertension and excess urinary of uric acid (28) • Adrenal androgens are the main cause of hirsutism, acne, alopecia (17) • Hypercortisolism can inhibit release of GnRH, LH, and FSH, leading to hypogonadotropic hypogonadism (17) |
21-50 20-75 24-80 |