Statin use for nonrheumatic calcific aortic valve stenosis: a review with meta-analysis.

AIMS: To synthesize by meta-analysis the findings of recent experimental studies focusing on possible therapeutic effectiveness of statins for nonrheumatic calcific aortic stenosis. METHODS: Observational studies and randomized controlled trials (RCTs) were selected from the Pubmed database to evaluate the hemodynamic progression of aortic stenosis in statin-treated patients compared with controls (i.e. patients with aortic stenosis taking placebo or no treatment). The endpoints were the annualized changes in one or more of the following ultrasonographic measurements: peak aortic valve jet velocity, peak aortic valve pressure gradient, mean aortic valve pressure gradient aortic valve area (AVA). For estimating the overall effect of statin therapy on each of the above-mentioned continuous variables across the considered studies, we used the weighted mean difference (WMD) as effect size measure. In addition, we calculated the odds of aortic valve replacement surgery and cardiovascular death in both statin-treated patients and controls for subsequently estimating the appropriate odds ratios. RESULTS: Nine studies were selected. A lower annualized increase in peak aortic valve jet velocity was found in statin-treated patients compared with controls (overall WMD: -0.09 m/s per year, 95% CI -0.16, -0.01 P = 0.018). Similarly, a smaller annualized increase in peak aortic valve pressure gradient was found in the statin group (overall WMD: -2.04 mmHg/year 95% CI: -3.56, -0.52, P = 0.0085). However, the overall effects in statin-treated patients on both annualized increases in mean aortic valve pressure gradient and decreases in AVA were not significantly different from those found in controls. Moreover, there was no significant difference in cardiovascular outcomes in the statin groups compared with placebo groups in each of the three analyzed RCTs and overall. CONCLUSION: Significant benefit of statin therapy in retarding hemodynamic deterioration was identified by favorable effects concerning annualized changes in peak aortic valve jet velocity and peak aortic valve pressure gradient; on the contrary, in statin-treated patients with aortic stenosis, no significant improvement was found for annualized changes in mean aortic valve pressure gradient and AVA and clinical outcomes.

Colapsibilidade da Veia Cava Inferior e sinais e sintomas de insuficiência cardíaca: novos insights e possíveis associações / Inferior Vena Cava collapsibility and heart failure signs and symptoms: new insights about possible links

FUNDAMENTO: Nos pacientes com Insuficiência Cardíaca Crônica (ICC) foram propostas medidas ultrassonográficas do Índice de Colapsibilidade da Veia Cava Inferior (ICVCI) para obter uma avaliação e classificação minuciosa da congestão hemodinâmica. OBJETIVO: A finalidade deste estudo era correlacionar os achados no exame físico com o ICVCI em pacientes com ICC. MÉTODOS: De acordo com um projeto de coorte retrospectivo, analisamos 54 pacientes com ICC, direita ou biventricular, classe NYHA III. O plano era determinar se alguma faixa de ICVCI basal poderia predizer uma persistência ou agravamento da congestão clínica achada no final do acompanhamento subsequente (isto é, após 1-2 meses do tratamento oral otimizado). Para essa finalidade, os pacientes foram subdivididos em três grupos de acordo com o valor de ICVCI basal: ≤ 15% (13 pts), 16 - 40% (21 pts) e > 40% (20 pts). Diversos critérios clínicos de congestão foram comparados por meio dos três grupos e incorporados subsequentemente ao modelo multivariado de Cox. RESULTADOS: Preditores multivariados de alto escore de congestão foram distensão da veia jugular (FC: 13,38 95% IC: 2,13 - 84 p = 0,0059) e estertores (FC: 11 95% C.I : 1,45 - 83,8 p = 0,0213). O ICVCI ≤ 15% esteve sempre associado com um alto escore de congestão na segunda visita; todavia, o ICVCI o ≤ 15% não predisse um alto escore de congestão na segunda visita. CONCLUSÃO: No âmbito da ICC, um baixo ICVCI não predisse, em forma confiável, um elevado escore de congestão. Não obstante, o conjunto com ICVCI ≤ 15% sempre se achou associado com sinais e sintomas de uma ICC descompensada, tanto do lado direito como do esquerdo. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

BACKGROUND: In chronic heart failure patients (CHF), ultrasound measurement of inferior vena cava collapsibility index (IVCCI) has been proposed to yield careful assessment and grading of the hemodynamic congestion. OBJECTIVE: The purpose of this study was to correlate the findings of physical examination with IVCCI in CHF patients. METHODS: According to a retrospective cohort design, we analyzed 54 CHF patients with right or biventricular CHF, belonging to III NYHA class. We planned to determine whether any basal IVCCI range would be able to predict persistent or worsening clinical congestion found at the end of subsequent follow up (i.e. after 1-2 months of oral optimized therapy). For this purpose, the patients were subdivided by three groups according to the basal IVCCI value: ≤ 15% (13 pts), 16 - 40% (21 pts) and > 40% (20 pts).Several clinical criteria of congestion were compared across the three groups and subsequently entered in the Cox multivariate model. RESULTS: Multivariate predictors of high congestion score were jugular venous distension (HR: 13,38 95% C.I.: 2,13 - 84 p = 0,0059) and rales (HR: 11 95% C.I : 1,45 - 83,8 p = 0,0213). IVCCI ≤ 15% was always associated with high congestion score at the second visit; but IVCCI ≤ 15% failed to predict high congestion score at the second visit. CONCLUSION: In CHF setting, low IVCCI did not reliably predict high congestion score. Nevertheless, the cluster with IVCCI ≤ 15% was always found associated with signs and symptoms from both right and left-sided decompensated CHF. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

Inferior Vena Cava collapsibility and heart failure signs and symptoms: new insights about possible links.

BACKGROUND: In chronic heart failure patients (CHF), ultrasound measurement of inferior vena cava collapsibility index (IVCCI) has been proposed to yield careful assessment and grading of the hemodynamic congestion. OBJECTIVE: The purpose of this study was to correlate the findings of physical examination with IVCCI in CHF patients. METHODS: According to a retrospective cohort design, we analyzed 54 CHF patients with right or biventricular CHF, belonging to III NYHA class. We planned to determine whether any basal IVCCI range would be able to predict persistent or worsening clinical congestion found at the end of subsequent follow up (i.e. after 1-2 months of oral optimized therapy). For this purpose, the patients were subdivided by three groups according to the basal IVCCI value: ≤ 15% (13 pts), 16 - 40% (21 pts) and > 40% (20 pts).Several clinical criteria of congestion were compared across the three groups and subsequently entered in the Cox multivariate model. RESULTS: Multivariate predictors of high congestion score were jugular venous distension (HR: 13,38 95% C.I.: 2,13 - 84 p = 0,0059) and rales (HR: 11 95% C.I : 1,45 - 83,8 p = 0,0213). IVCCI ≤ 15% was always associated with high congestion score at the second visit; but IVCCI ≤ 15% failed to predict high congestion score at the second visit. CONCLUSION: In CHF setting, low IVCCI did not reliably predict high congestion score. Nevertheless, the cluster with IVCCI ≤ 15% was always found associated with signs and symptoms from both right and left-sided decompensated CHF.

Ultrasound evaluation of the inferior vena cava collapsibility index in congestive heart failure patients treated with intravenous diuretics: new insights about its relationship with renal function: an observational study.

OBJECTIVE: In chronic heart failure (CHF), collapsibility index of the inferior vena cava (IVCCI) is used for noninvasive ultrasonographic appraisal of central venous pressure, but it also may be related both to estimated glomerular filtration rate (eGFR) and renal outcome. METHODS: On the basis of retrospective observational cohort study, we analyzed 49 patients with right or biventricular CHF in III NYHA class, who had undergone intravenous intensive treatment with furosemide. Aggravated renal dysfunction (ARD) was defined by serum creatinine (Cr) increase of ≥0.3 mg/dL from baseline. IVCCI was categorized in three layers (IVCCI ≤15%, IVCCI 16-40% and IVCCI >40%). The predictors of ARD were searched for as well as any relation between basal IVCCI and both eGFR at admission and occurrence of ARD. RESULTS: Overall, 15 cases and 34 controls were compared. Multivariate predictors of ARD were a lower basal eGFR (HR: 0.82 CI: 0.72-0.94 p=0.0045) and intravenous furosemide daily mean dose >80 mg (HR: 48.62 CI: 1.62-3841.5 p=0.0430). A very significant positive correlation was found between IVCCI at admission ≤ 15% and basal eGFR (r=0.96 p<0.0001), while a negative correlation with eGFR was detected in the IVCCI highest (>40%) range (r=-0.696 p=0.0013). Furthermore, the category with basal IVCCI >40% showed a higher rate of ARD compared to that with basal IVCCI 16-40% (p<0.05). CONCLUSION: On the basis of the demonstrated u-shaped relationship between IVCCI and eGFR both the stratum with the highest (>40%) and the one with the lowest (≤15%) basal IVCCI may be associated with increased risk of ARD.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica / ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

The relation between carotid atherosclerotic plaques and ischemic stroke is critically conditioned by the role of arterial hypertension as an effect modifier.

BACKGROUND: Hypertension is a recognized risk factor for ischemic stroke (IS) along with diabetes, smoking, and hypercholesterolemia. Any uncertainty remains about other putative risk factors, ultrasound-derived, such as carotid soft plaques. METHODS: A case-control study was carried out concerning cases of IS or transient ischemic attack (TIA) found in an outpatient population from February 2000 to March 2008. For every patient with documented IS or TIA, 1 to 2 controls without previous cerebrovascular event were recruited. The variables analyzed were: hypertension, defined as mild hypertension (140-160 mm Hg) or moderate-to-severe hypertension (>160 mm Hg); age, divided into 3 classes: 60 to 70, 70 to 80, and 80 to 90 years; diabetes and carotid plaques, categorized as "soft" or "hard" plaques, and as plaques achieving mild (<50%) or moderate (50%-70%) luminal narrowing. RESULTS: Fourty-six cases and 60 controls were analyzed. In univariate analysis, moderate-to-severe hypertension, age between 80 and 90 years, carotid soft plaques and 50% to 70% stenoses predicted ischemic cerebral events. In multivariable analysis, only moderate-to-severe hypertension (odds ratio [OR]: 15.536; 95% confidence interval [CI]: 4.142-58.271; P = 0.0000) and oldest age class (OR: 15.862; 95% CI: 3.836-65.592; P = 0.0001) proved to predict IS or TIA. Soft plaques were found to predict risk of IS (OR: 13.50; 95% CI: 2.9788-61.1821) in hypertensive, but not in patients whose hypertension had been controlled by therapy (OR: 0.2308; 95% CI: 0.0270-1.9720) (qualitative interaction). CONCLUSIONS: Moderate-to-severe hypertension and very old age predicted IS and TIA, whereas carotid soft plaques did not, in the presence of normotensive blood pressure.

Unloading therapy by intravenous diuretic in chronic heart failure: a double-edged weapon?

A well established part of therapeutic approaches applying to cases of chronic heart failure (CHF) with extreme fluid retention is represented by intensive intravenous (i.v.) therapy with loop diuretics. This kind of therapy, if appropriately modulated according to the individual clinical picture and biohumoral pattern, is able to decrease the abnormally high ventricular filling pressures, thereby relieving the breathlessness while being able to retrieve a suitable urine output, so as to propitiate regression or disappearance of edema without unfavorable influences on renal clearance of nitrogenous compounds. Nevertheless, the intensive i.v. diuretic therapy should be tailored on the basis of a close assessment of baseline hemodynamic data and hemodynamic response to the medications, in addition to the careful diuretic dose titration and cautious evaluation of risk/benefit ratio. Actually, by using this kind of therapy, there is a risk that a tubular or glomerular injury can be generated and that a frequently preexisting renal dysfunction can be aggravated, especially when excessive doses of loop diuretics are being erroneously administered, so as to cause hypotension, hypoperfusion and/or relative dehydration in patients with decompensated CHF who could have expressly benefitted from intensive unloading therapy. Recently, the genesis of CHF-related progressive renal deterioration has been highlighted by affirming that a major role may be played rather by neurovegetative disorders, that is, by increase in sympathetic tone and abnormalities in kidney's vasomotility than by cardiac inotropism deficiency. The measures, thought to be able to prevent renal arterial constriction and to impede deterioration of glomerular filtration rate (GFR) due to the ischemic-necrotic tubular injury, as occurring in the set of intensive unloading therapy with i.v. furosemide or other loop diuretic, are represented by application of inotropic and renal vasodilator support by dopamine i.v. infusion at low doses or by other inotropic agents provided with recognized renal vasodilator properties and/or by addition to i.v. furosemide of osmotic agents able to expand the hematic volume, so counteracting or minimizing the reflex renal vasoconstriction induced by furosemide-related reduction in intravascular circulating volume: i.v. infusion of small volumes of hypertonic saline solution, as well as administration of albumin, mannitol and/or plasma expanders. Because renal impairment, as developing in the setting of CHF, has proven to represent a very important indicator of adverse outcome, every effort should be addressed to prevent any significant (>25% of basal value) rise in serum creatinine consequent to diuretic unloading therapy or to other procedures (paracentesis of tense ascites, ultrafiltration) aimed at rapid fluid removal in edematous or ascitic CHF or cardiogenetic anasarca. Ultrafiltration, even though a promising technique highly valued for its acknowledged property to obtain a more rapid fluid and weight loss in CHF patients with marked fluid retention, has been demonstrated so far to produce neurohumoral activation, creatinine abnormalities and symptomatic hypotensions similar to those due to i.v. loop diuretics; thus, the hypothesized advantages of this technique remain to be further clarified and confirmed, with regard to its safety profile and cost-effectiveness.

Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance.

AIM: The aim of the current study was to evaluate the effect of short-term (6 months) and long-term (18 months) treatment with pegvisomant on cardiac structure and performance in patients with acromegaly. PATIENTS: Seventeen patients (nine women, eight men, 27-61 yr) with active acromegaly entered and 12 completed the long-term study. After a baseline evaluation, including measurement of hemodynamic, biochemical, and hormonal parameters, and a standard Doppler echocardiography, treatment with pegvisomant was started at the initial dose of 10 mg/d, increasing by 5 mg/d every 6 wk on the basis of IGF-I levels until normalization or the achievement of a maximal dose of 40 mg/d. RESULTS: After short-term treatment, IGF-I levels were normalized in 10 of the 17 (59%) patients. Left ventricular mass index (LVMi) was significantly decreased without changes in diastolic and systolic performance. After long-term treatment, IGF-I levels were normalized in 10 of the 12 (83%) patients. Blood glucose and serum insulin levels were decreased compared with baseline. LVMi was further decreased compared with short-term treatment, so that the prevalence of left ventricle hypertrophy decreased from 50% at baseline to 17% after 18 months of treatment. Moreover, ejection fraction as well as early to late (atrial) peak velocity ratio (E/A) were significantly increased, whereas isovolumic relaxation time was significantly decreased compared with baseline, demonstrating an improvement of both diastolic and systolic function. A significant correlation was found between the change in IGF-I levels and that of left ventricular ejection fraction. In general, the prevalence of cardiac insufficiency was present in 13 of the 17 (76%) patients at baseline and in one (8%) patient after 18 months of treatment. CONCLUSIONS: Long-term treatment with the GH receptor antagonist improves acromegalic cardiomyopathy by decreasing cardiac hypertrophy and enhancing diastolic and systolic function, and consequently partially or completely reverting the cardiac insufficiency.

The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males.

BACKGROUND: Alterations of sperm number and motility are found in hyperprolactinaemic men. Cabergoline treatment reverses alterations in semen. No information is currently available on the quality of seminal tests in hyperprolactinemia in response to cabergoline treatment. OBJECTIVE: To further investigate the effect of hyperprolactinaemia and its treatment with cabergoline on semen quality. PATIENTS: Forty-three men with hyperprolactinaemia (32 macro- and 11 micro-prolactinomas); 60 healthy men served as control. METHODS: Live spermatozoa count, sperm membrane function, kinetic index, nuclear DNA integrity, sperm curvilinear and linear velocity and amplitude of lateral movement of the sperm head were investigated before and after 6 and 24 months of treatment with cabergoline. STUDY DESIGN: Open prospective. RESULTS: At study entry, semen functional tests were severely and similarly impaired both in patients with macro- and micro-prolactinomas compared to controls. After 6 and 12 months of treatment there was a significant improvement of semen quality in patients achieving normalization of prolactin levels, although most of the parameters remained lower than in controls. After 24 months of treatment, seminal fluid characteristics were similar to the controls except for live spermatozoa count, sperm membrane function, sperm kinetic index and sperm nuclear DNA integrity, which remained abnormal in 9.3-53% of the patients. CONCLUSIONS: Twenty-four months of cabergoline treatment restored gonadal function in 66.7% of men with hyperprolactinaemia.

The epidemiology of prolactinomas.

Prolactin-secreting tumors (prolactinomas), the most frequently occurring pituitary tumor, have a frequency that varies with age and sex. They occur most frequently in females aged 20 to 50 years old, at which time the female-to-male ratio is approximately 10:1. In the pediatric-adolescent age group, prolactinomas have a prevalence of 100/million population, and account for less than 2% of all intracranial tumors. Prolactinomas occur in approximately 30% of patients with multiple endocrine neoplasia type 1 and in this setting, they may be more aggressive than their sporadic counterparts. Patients with Carney complex or McCune-Albright syndrome may exhibit hyperprolactinemia due to a pituitary tumor derived from somatomammotropic cells that secrete both growth hormone and prolactin. Few familial cases of prolactinoma unrelated to MEN-1 are reported in literature.

PRL secreting adenomas in male patients.

Prolactinomas are the most frequent pituitary tumors and their frequency varies with age and sex, occurring most frequently in females between 20-50 yr-old. In men, hyperprolactinaemia is often present for many years without symptoms, as generally the most important symptoms are the decrease in libido and/or sexual potency both underestimated by the majority of the patients. Prolactin (PRL) plays a role in the process of spermatogenesis, and normal serum PRL levels are required for normal testicular function. On the other hand, hyperprolactinaemia has multiple negative effects on the gonadal axis. As a consequences hyperprolactinemic males show alteration of sexual potency and seminal fluid quality. Cabergoline treatments is able to induce normalization of PRL levels and a reduction of tumor mass in the majority of patients and consequently restoring the normal semen quality and ameliorating the quality of life of men with pituitary PRL-secreting adenoma.

Prolactin and prostate hypertrophy: a pilot observational, prospective, case-control study in men with prolactinoma.

In experimental models, prolactin (PRL) displays independent hypertrophic effects on the prostate. To investigate whether hyperprolactinemia is associated with prostate enlargement in humans, we designed this open, prospective, case-control study enrolling 20 men with prolactinoma (aged 34 +/- 10 yr) and 20 age-matched healthy men. The endocrine profile and prostate transrectal ultrasonography were performed before and after 12 and 24 months of cabergoline treatment in the patients and at study entry and after 24 months in the controls. The patients had lower serum testosterone, dihydrotestosterone (DHT), and IGF-I levels and prostate volume (15.4 +/- 3.5 vs. 19.6 +/- 5.1 ml; P < 0.001) and higher PRL levels and prostate-specific antigen density than controls. There was no difference in prostate and transitional zone volumes between patients with normoandrogenemia (n = 8) or hypoandrogenemia (n = 12). After 12 and 24 months of treatment, PRL, testosterone, and DHT levels were normal in all cases, as were IGF-I and IGF-binding protein-3 levels. After 24 months, prostate volume was comparable to that in controls (21.7 +/- 4.5 vs. 22.5 +/- 4.7 ml). There were no changes in prostate structure throughout the study period in either the patients or the controls. In conclusion, in young men with prolactinoma PRL excess is unlikely to have effects on the prostate per se, because it is accompanied by low testosterone and DHT levels that produce the major effects.

Usefulness of pulsed tissue Doppler for the assessment of left ventricular myocardial function in overt hypothyroidism.

BACKGROUND: The aim of this study was to assess the role of tissue Doppler (TD) in the identification of left ventricular (LV) myocardial regionl abnormalities in overt hypothyroidism. METHODS: Fourteen women with newly diagnosed, never treated overt hypothyroidism and 14 healthy women, matched for age, underwent standard echocardiography and pulsed TD, by placing the sample volume at the basal posterior septum and lateral mitral annulus, in the apical 4-chamber view. The myocardial systolic (SM) and diastolic velocities (Em, Am and their ratio) and time intervals (relaxation time [RTm], pre-contraction time [PCTm], contraction time) were measured. RESULTS: The two groups were comparable for body surface area, blood pressure and heart rate. At standard echocardiography, patients with overt hypothyroidism had a significantly greater septal thickness and LV mass index, a longer LV pre-ejection period (PEP), deceleration time and isovolumic relaxation time (IVRT) and a lower E peak velocity and E/A ratio. TD showed a significantly longer PCTm and RTm and a lower Em and Em/Am ratio of both the septum and mitral annulus in overt hypothyroidism. The ratio of the standard Doppler E to Em of the mitral annulus was 5.5 +/- 1.2 in controls and 5.3 +/- 1.7 in overt hypothyroidism (p = NS). In the overall population, PEP, IVRT, PCTm and RTm were correlated negatively with FT3 and FT4, and positively with thyroid-stimulating hormone. After adjusting for age, body surface area and heart rate in separate multivariate analyses, the associations of TD PCTm with the thyroid hormones and thyroid-stimulating hormone were greater than the homologous associations of standard Doppler PEP. CONCLUSIONS: Standard echocardiography confirms itself as a satisfactory diagnostic technique for the identification of LV global dysfunction in overt hypothyroidism. Pulsed TD may be useful to determine the severity of LV myocardial dysfunction in relation to the degree of hormonal impairment.

Thyrotoxic adenoma followed by atypical hyperthyroidism due to struma ovarii: clinical and genetic studies.

OBJECTIVE: Atypical forms of hyperthyroidism represent a diagnostic challenge for clinicians. Struma ovarii is an ovarian teratoma and constitutes a rare cause of ectopic thyroidal hormonal production. We describe a case of struma ovarii that combined two different sources of hyperthyroidism in the same patient and report genetic studies in order to contribute a better understanding of the autonomy and tumorigenesis of the struma ovarii. CASE REPORT: A 73-year-old nulliparous woman presented a thyroid toxic adenoma that was successfully treated with 10 mCi radioiodine. Unexpectedly, a new onset of hyperthyroidism prompted us to look for a second etiology. A whole-body scan with (123)I detected a pelvic hyperfixation suggesting struma ovarii, and a thyroid differentiated left ovarian teratoma 3 cm in size was surgically removed. We screened for mutations of thyroid-stimulating hormone receptor and Gs-alpha protein genes, as these mutations are common in thyroid adenomas. We did not identify any mutations. Androgen receptor study demonstrated a monoclonal status. Comparative genomic hybridization did not reveal any chromosomal abnormality. However, loss of heterozygosity analysis showed several structural abnormalities, compared with the majority of benign ovarian teratomas, which show a normal karyotype. CONCLUSIONS: This is the first well-documented report of thyrotoxic struma ovarii revealed after treatment of a single thyroid toxic adenoma. We have shown in this case that struma ovarii originates from a single germ cell, and, albeit benign, this tumor presents several chromosomal abnormalities. Struma ovarii-induced hyperthyroidism is likely to be mediated by mechanisms different from those of the classical thyroid toxic adenoma.