Cushing's syndrome: aftermath of the cure

Abstract

Cushing's syndrome (CS) is a chronic and systemic disease caused by endogenous or exogenous hypercortisolism, associated with an increase of mortality rate due to the clinical consequences of glucocorticoid excess, especially cardiovascular diseases. After cure, usually obtained by the surgical removal of the tumor responsible for the disease, the normalization of cortisol secretion is not constantly followed by the recovery of the clinical complications developed during the active disease, and it is often followed by the development of novel clinical manifestations induced by the fall of cortisol levels. These evidences were mostly documented in patients with pituitary-dependent CS, after surgical resection of the pituitary tumor. Indeed, despite an improvement of the mortality rate, metabolic syndrome and the consequent cardiovascular risk have been found to partially persist after disease remission, strictly correlated to the insulin resistance. Skeletal diseases, mainly osteoporosis, improve after normalization of cortisol levels but require a long period of time or the use of specific treatment, mainly bisphosphonates, to reach the normalization of bone mass. A relevant improvement or resolution of mental disturbances has been described in patients cured from CS, although in several cases, cognitive decline persisted and psychological or psychiatric improvement was erratic, delayed, or incomplete. On the other hand, development or exacerbation of autoimmune disorders, mainly thyroid autoimmune diseases, was documented in predisposed patients with CS after disease remission. The totality of these complications persisting or occurring after successful treatment contribute to the impairment of quality of life registered in patients with CS after disease cure. A síndrome de Cushing (SC) é uma desordem sistêmica crônica causada por hipercortisolismo endógeno ou exógeno, associada a um aumento da taxa de mortalidade devido às conseqüências clínicas do excesso de glicocorticóides, especialmente a doença cardiovascular. Após a cura, usualmente obtida pela remoção cirúrgica do tumor responsável pela desordem, a normalização da secreção de cortisol não é sistematicamente seguida da recuperação das complicações clínicas desenvolvidas durante a fase ativa da doença, e é freqüentemente seguida pelo surgimento de novas manifestações clínicas induzidas pela queda dos níveis de cortisol. Estas evidências foram, na sua maioria, documentadas em pacientes com SC de origem hipofisária, após a ressecção cirúrgica do tumor na hipófise. Na verdade, a despeito de uma melhoria na taxa de mortalidade, a sín-drome metabólica e seu conseqüente risco cardiovascular têm se mostrado parcialmente persistentes após a remissão da doença, em estrita relação com a resistência à insulina. Anormalidades esqueléticas, especialmente a osteoporose, melhoram após a normalização dos níveis de cortisol, mas requerem um longo tempo ou o uso de tratamento especí-fico, principalmente bisfosfonatos, para se obter a normalização da massa óssea. Um...

Surgical remission of Cushing's syndrome reduces cardiovascular risk

“…After normalization of cortisol excess, all the risk factors returned to a level comparable to control subjects, apart from obesity and triglyceridemia (which may itself relate directly to central obesity), as observed previously (23,24,41). The comparison with a control group including patients who had to seek medical advice is a more appropriate match than normal subjects, to avoid the healthier comparator bias, and strengthens the value of observing a residual cardiovascular risk.…”

“…The number of patients is too small to assess the contribution of replacement therapies to a patient's outcome. It is pertinent to consider that studies showing persistence of metabolic and cardiovascular damage have included only patients with pituitary-dependent CS (13,22,23) and, as Giordano et al (24) clearly pointed out, such patients may be characterized by a less favorable outcome than patients with cortisol-secreting adrenal adenoma for the above-mentioned considerations.…”

“…This is an issue of particular relevance, as mild CS may be more common than previously thought, especially among patients with type 2 diabetes and metabolic syndrome (18,19,20). In addition, recent studies have questioned the reversibility of complications due to hypercortisolism after its surgical treatment (2, 21,22,23,24). These findings suggest that an increased cardiovascular risk may persist despite successful treatment of cortisol excess influencing negative health outcomes in patients who have suffered from CS.…”

THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

“…An increased cardiovascular risk and metabolic syndrome have been associated with Cushing's disease; this increased cardiovascular risk may already manifest in early-stage disease, before clinical symptoms become apparent (8,9,10). In addition, residual increased risk of cardiovascular events has been also reported in patients who have achieved disease control (11). Furthermore, Cushing's disease is associated with excess mortality, reported to be double that of the general population; however, the mortality rate in patients with Cushing's disease who are in remission following treatment tends to be lower than in those who are not in remission (12).…”

DINAMIKA MINERAL'NOY PLOTNOSTI KOSTI, MARKEROV KOSTNOGO OBMENA I KAChESTVA ZhIZNI PATsIENTOV S ENDOGENNYM GIPERKORTITsIZMOM POSLE DOSTIZhENIYa REMISSII ENDOGENNOGO GIPERKORTITsIZMA

“…Ухудшение качества жизни после достижения ремиссии заболевания может быть обусловле-но развитием гипопитуитаризма в исходе трансназальной аденомэктомии и необходимостью пожизненной замести-тельной терапией [13]. Кроме того, развитие необратимых осложнений в активной фазе заболевания или неполная ре-грессия развившихся нарушений может стать причиной не оРИгИнАльныЕ СТАТьИ № 1/2014 остеопороз и остеопатии только ухудшения качества жизни, но и стойкой инвалиди-зации больного [14].…”