Elena Valassi

Potential Cardiac Valve Effects of Dopamine Agonists in Hyperprolactinemia

CONTEXTnAn association has been demonstrated between valvular heart disease and dopamine agonist use in patients treated for Parkinsons disease. Following these reports, concern has been raised among endocrinologists about the safety of long-term treatment with dopamine agonists in hyperprolactinemic patients. The article will summarize all currently published research regarding the possible risk of valvulopathy in hyperprolactinemic patients on dopamine agonists and provide guidance based on current findings.nnnEVIDENCE ACQUISITIONnThe major source of data acquisition included PubMed search strategies. PubMed was searched for publications containing the terms valve, valvular, or valvulopathy, and one of the terms dopamine agonists, cabergoline, bromocriptine, pergolide, prolactin, prolactinoma, or hyperprolactinemia. All publications from 1950 to August, 2008, were screened for use in this review.nnnEVIDENCE SYNTHESISnThe majority of studies showed no risk of valvular regurgitation associated with cabergoline. However, an increased risk of mild to moderate regurgitation, usually at the tricuspid valve, was reported in a few studies. Only one study suggested a relationship with the mean cumulative dose of cabergoline.nnnCONCLUSIONSnAlthough most reports do not show an association between use of dopamine agonists and valvulopathy, caution must be exercised, especially in patients requiring long-term, high-dose medication regimens. Clinicians should recommend the lowest possible doses of dopamine agonists and address the question of echocardiographic monitoring on an individual basis.

Delayed Remission after Transsphenoidal Surgery in Patients with Cushing's Disease

BACKGROUNDnTranssphenoidal surgery (TSS) is the treatment of choice for Cushings disease (CD). Postoperative hypercortisolemia mandates further therapy.nnnOBJECTIVEnThe aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy.nnnDESIGN AND SETTINGnA retrospective case series was conducted at three tertiary care centers.nnnPATIENTS AND INTERVENTIONnWe reviewed the records of 620 patients (512 females, 108 males; mean age, 38 +/- 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007.nnnRESULTSnOutcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 +/- 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02).nnnCONCLUSIONSnHormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.

Gender effects on cardiac valvular function in hyperprolactinaemic patients receiving cabergoline: a retrospective study

Backgroundu2002 Ergot‐derived dopamine agonists are associated with increased risk of valvular dysfunction in Parkinson’s disease. The risk of valvular disease associated with lower doses of cabergoline used to treat prolactinomas remains controversial.

Adipokines and cardiovascular risk in Cushing's syndrome.

Cushing’s syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or ‘cured’ CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS.

Clinical features of nonpituitary sellar lesions in a large surgical series.

Contextu2002 Pituitary adenomas are the most common lesions in the sellar region, but other pathologies need to be considered in the differential diagnosis.

Concomitant medication use can confound interpretation of the combined dexamethasone-corticotropin releasing hormone test in Cushing's syndrome.

CONTEXTnThe ability of combined dexamethasone-corticotropin releasing hormone (Dex-CRH) testing to distinguish pseudo-Cushings syndrome (PCS) from Cushings syndrome is controversial. One factor potentially impairing diagnostic efficacy is the concomitant use of commonly prescribed medications that may alter dexamethasone metabolism.nnnOBJECTIVEnOur objective was to assess the diagnostic accuracy of the Dex-CRH test and evaluate the potential impact of concomitant drugs.nnnDESIGNnThe study was a retrospective one.nnnPARTICIPANTSnParticipants included 101 patients [60 Cushings disease (CD); 41 PCS] who underwent 112 Dex-CRH tests. Patients were divided into two groups, depending on use of medications potentially interfering with dexamethasone metabolism: 58 tests were classified as No Meds (32 CD; 26 PCS) and 54 as Meds (34 CD; 20 PCS). The latter group was further subdivided into patients taking one medication vs. those taking multiple medications.nnnMAIN OUTCOME MEASURESnDiagnostic accuracy of different serum cortisol and ACTH thresholds at baseline and 15 min after CRH injection was assessed.nnnRESULTSnThe specificity of a baseline post-low-dose-dexamethasone-suppressed test cortisol lower than 1.4 microg/dl (38 nmol/liter) was significantly higher in the No Meds vs. the Meds group (P = 0.014). Sensitivity and specificity using a post-CRH cortisol cutoff of 1.4 microg/dl (38 nmol/liter) were 93.1% (95% confidence interval = 88.4-97.8) and 92.3% (95% confidence interval = 87-97.6) in the No Meds group. The specificity of a cortisol lower than 1.4 microg/dl (38 nmol/l) at 15 min after CRH was significantly higher in patients taking only one medication vs. those on multidrug treatment (P < 0.05).nnnCONCLUSIONSnMedications commonly prescribed in hypercortisolemic patients undergoing Dex-CRH testing may contribute to the variable diagnostic accuracy of this test. Prospective studies to address this issue are needed.

Effect of growth hormone replacement therapy on the quality of life in women with growth hormone deficiency who have a history of acromegaly versus other disorders.

OBJECTIVEnTo compare the response in quality of life (QoL) to growth hormone (GH) replacement in women with GH deficiency (GHD) and a history of acromegaly with that in women with GHD of other causes.nnnMETHODSnFifty-five women with GHD were studied: 17 with prior acromegaly and 38 with other causes of GHD. We compared two 6-month, randomized, placebo-controlled studies of GH therapy in women with hypopituitarism conducted with use of the same design-one in women with a history of acromegaly and one in women with no prior acromegaly. QoL was assessed with the following questionnaires: the QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA), the Symptom Questionnaire, and the 36-Item Short-Form Health Survey (SF-36).nnnRESULTSnThe 2 groups had comparable mean pretreatment age, body mass index, and QoL scores and comparable mean GH dose at 6 months (0.61 ± 0.30 versus 0.67 ± 0.27 mg daily). After 6 months of GH replacement therapy, women with GHD and prior acromegaly demonstrated a greater improvement in AGHDA score, four SF-36 sub-scales (Role Limitations due to Physical Health, Energy or Fatigue, Emotional Well-Being, and Social Functioning), and the Somatic Symptoms subscale of the Symptom Questionnaire than did women with GHD of other causes. Poorer pretreatment QoL was associated with a greater improvement in QoL after administration of GH.nnnCONCLUSIONnIn this study, GH replacement therapy improved QoL in women with GHD and a history of acromegaly but not in women with GHD due to other hypothalamic and pituitary disorders. Further studies are needed to determine the long-term risks versus benefits of GH replacement in patients who develop GHD after definitive treatment for acromegaly.

Quality of Life in Cushing's disease: A long term issue?

The purpose of this review is to describe how quality of life (QoL) is impaired in patients with hypercortisolism due to Cushings syndrome of any aetiology, including pituitary-dependent Cushings disease. It is worse in active disease, but improvement after successful therapy is often incomplete, due to persistent physical and psychological co-morbidities, even years after endocrine cure. Physical symptoms like extreme fatigability, central obesity with limb atrophy, hypertension, fractures, and different skin abnormalities severely impair the affected patients everyday life. Psychological and cognitive problems like bad memory, difficulties to concentrate and emotional distress, often associated with anxiety and depression, make it difficult for many patients to overcome the aftermath of treated Cushings syndrome. Recent studies have shown diffuse structural abnormalities in the central nervous system during active hypercortisolism, thought to be related to the wide distribution of glucocorticoid receptors throughout the brain. Even though they improve after treatment, normalization is often not complete. Shortening the exposure to active Cushings syndrome by reducing the often long delay to diagnosis and promptly receiving effective treatment is highly desirable, together with preparing the patient for the difficult periods, especially after surgery. In this way they are prepared for the impairments they perceive in every day life, and live with the hope of later improvement, which can be therapeutic in many instances.