Cardiac Valve Complications in Prolactinomas Treated With Cabergoline
Condition: Prolactinomas
MeSH terms: Prolactinoma
Study type: Observational

Summary: 
      Dopamine agonists are first-line agents for the treatment of prolactinomas (1) and
      Parkinson's disease (2). There is evidence supporting a causal relationship between the
      occurrence of drug-induced "restrictive" valvular heart disease and treatment with pergolide
      (3): in several cases, the valvulopathy improved when pergolide was discontinued (4).
      Valvular heart damage has also been reported with the ergot-derived dopamine agonists
      bromocriptine and cabergoline (5,6).

      Two recent studies (7,8) have further demonstrated that both pergolide and cabergoline are
      associated with an increased risk of new cardiac valve regurgitation in patients treated for
      Parkinson's disease.

      The valvular abnormalities seen with ergot-derived dopamine agonists are similar to those
      observed in patients receiving ergot alkaloid agents (such as ergotamine and methysergide) in
      the treatment of migraine, or fenfluramine and dexfenfluramine in the treatment of obesity.
      These abnormalities also closely resemble carcinoid-related valvulopathies (9).

      Cardiac valve disease has never been reported in patients with prolactinomas who require
      treatment with dopamine-agonists even life-long (1). At variance with patients with
      Parkinson's disease, patients with prolactinomas are younger and are treated with an average
      dose of dopamine-agonists that is significantly lower (median bromocriptine dose 5 mg/day and
      median cabergoline dose 1 mg/week). Because of the young age of treatment beginning (most
      patients with microprolactinomas start dopamine-agonist treatment in early adulthood),
      treatment might be continued for over 3 decades: the cumulative risk of low doses of dopamine
      agonists for such a long period of treatment is currently unknown.

      To assess the prevalence of cardiac valve disease in patients treated with cabergoline, we
      wish to perform an echocardiography screening in a large representative sample of patients
      with prolactinoma who were treated with cabergoline for at least 12 months and in a group of
      control subjects recruited prospectively. We wish to evaluate the severity of regurgitation
      for the mitral, aortic, and tricuspid valves. Changes in cardiac valve apparatus was compared
      with treatment duration and cumulative cabergoline dose.
    

Detailed description: 
      Within one week from a clinical observation in the outpatient service, all patients will be
      admitted to the hospital for a complete endocrine screening, a cardiological visit that will
      include an electrocardiogram and an echocardiogram.

      The endocrine profile will include measurement of IGF-I, PRL, FSH, LH, 17-β-estradiol,
      testosterone, FT3, FT4, TSH, and cortisol at 8.00 in the morning after an overnight fasting.

      The clinical profile will include blood pressure measurement at the right arm, with the
      subjects in relaxed sitting position. The average of six measurements (three taken by each of
      two examiners, in the same day of echocardiography, between 8.00-9.00 in the morning) with a
      mercury sphygmomanometer will be used in all analysis. According with the seventh report of
      the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High
      Blood Pressure (10), hypertension, if present, is classified as mild (Stage 1) when the SBP
      or DBP were between 140 and 159 mmHg and between 90 and 99 mmHg, respectively; severe (Stage
      2) when the SBP or DBP were >160 and >100 mmHg respectively; pre-hypertension is defined as
      SBP >120¬ and <140 and DBP >80 and <90 mmHg. Heart rate will be also measured.
    

Intervention name(s): Cabergoline
Intervention type(s): Drug
Intervention description(s): According with our previous studies, in the patients with microprolactinoma and in those with non-tumoral hyperprolactinemia, cabergoline treatment was administered orally at a starting dose of 0.25 mg twice weekly for the first two weeks and then 0.5 mg twice weekly. After 2 months of treatment, dose adjustment was carried out every 2 months on the basis of serum PRL suppression.
Other intervention name(s): Dostinex
Intervention MeSH terms: Cabergoline
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Three different study populations will be studied.

          -  Group 1) Patients already receiving treatment with cabergoline for at least 12 months

          -  Group 2) Newly diagnosed patients with hyperprolactinemia who never received treatment
             with dopamine-agonists

          -  Group 3) Non hyperprolactinemic subjects matched with the patients for sex and age to
             be used as controls.
      
Keywords: Prolactin; Prolactinomas; Dopamine-Agonists; Cabergoline; Cardiac valve disease