GENERAL DRUG INFO. for Prolactinomas

NLM CIT. ID: No Cit. ID assigned
TITLE:   Hormone levels and tumour size response to quinagolide and cabergoline
         in patients with prolactin-secreting and clinically non-functioning
         pituitary adenomas: predictive value of pituitary scintigraphy with
         123I-methoxybenzamide.
AUTHORS: Colao A; Ferone D; Lastoria S; Cerbone G; Di Sarno A
      Di Somma C; Lucci R; Lombardi G
AUTHOR AFFILIATION:
      Departments of Molecular & Clinical Endocrinology and Oncology,
      'Federico II' University of Naples; Nuclear Medicine, National Cancer
      Institute, 'Fondazione G. Pascale', Naples, Italy.
PUBLICATION TYPES:
      JOURNAL ARTICLE
LANGUAGES:
      ENG
ABSTRACT:
      BACKGROUND: Dopamine agonists are indicated as primary therapy for
      PRL-secreting pituitary adenomas, while controversial results have
      been reported in nonfunctioning adenomas (NFA). OBJECTIVE: To
      evaluate whether the in vivo visualization of dopamine D2 receptor
      expression detected by pituitary scintigraphy using
      123I-methoxybenzamide (123I-IBZM) was correlated with the response to
      chronic treatment with quinagolide or cabergoline. PATIENTS: 10
      patients affected with NFA (5 men and 5 women, age ranging between 25
      and 50 years), and 10 with PRL-secreting naive macroadenomas (3 men
      and 7 women, age ranging between 22 and 59 years), serving as
      control. STUDY DESIGN: All patients underwent an acute test with
      quinagolide: at 3-day intervals and in random order all patients
      received the drug (0.075 mg at 0800 h), or placebo. Blood samples
      were taken 15 and 5 minutes before and every 30 minutes for 6 h after
      drug or placebo administration. The test was considered positive when
      PRL and/or alpha-subunit levels decreased >/=50% as compared to
      baseline levels. After 6 months of treatment, 10 patients were
      randomised to continue the treatment with quinagolide and the
      remaining 10 received cabergoline for the remaining 6 months. The
      doses of quinagolide and cabergoline ranged from 0.075 to 0.6 mg/day
      and from 0.5 to 3 mg/week, respectively. At study entry, a magnetic
      resonance imaging (MR) study of the pituitary region and 123I-IBZM
      pituitary scintigraphy were performed. MR was repeated after 12
      months of treatment to evaluate tumour shrinkage: reduction of tumour
      volume = 80% in prolactinomas and = 50% in NFA was considered
      significant. Basal PRL levels were 9495.0 +/- 1131.6 mU/l in
      prolactinomas and 602.4 +/- 50.5 mU/l in NFA. RESULTS: The
      scintigraphy was negative in 6 out of 10 patients with NFA. Moderate
      uptake was observed in 3 patients with prolactinoma and 2 patients
      with NFA whereas intense uptake was observed in the remaining 7
      patients with prolactinoma and 2 patients with NFA. Among the 8
      patients with NFA and high circulating alpha-subunit levels, the
      acute test was negative in 5 while it was positive in the remaining 3
      patients. The acute test was positive in all 10 patients with
      prolactinoma. After 12 months of treatment with quinagolide and
      cabergoline, circulating PRL levels were decreased in all 10 patients
      with prolactinoma (571.8 +/- 255.9 mU/l), being normalized in 7
      patients. Suppression of PRL levels was found in all 10 patients with
      NFA (89.5 +/- 2.3 mU/l). A significant reduction of alpha-subunit
      levels was obtained in 9 out of 10 patients with NFA: in 4 out of 8
      patients alpha-subunit levels were normalized. Significant adenoma
      shrinkage was recorded in 4 patients with prolactinoma among the 7
      with intense pituitary uptake of 123I-IBZM. Significant adenoma
      shrinkage was recorded only in the 2 out of 10 patients with NFA with
      intense pituitary uptake of 123I-IBZM. A significant positive
      correlation was found between the degree of uptake (considered as
      score) and the response to quinagolide or cabergoline treatment
      (considered as percent hormone suppression) either in patients
      affected with PRL-secreting adenoma (r = 0.856, P < 0.005) or in
      those affected with NFA (r = 0.787, P < 0.05). CONCLUSIONS: An
      intense 123I-IBZM uptake in patients with non-functioning adenomas
      was predictive of a good response to a chronic treatment with
      quinagolide and cabergoline. This result suggests that a pituitary
      123I-IBZM scintigraphy could be considered in selected patients with
      non-functioning adenomas before starting medical treatment with
      dopamine agonists.
NLM PUBMED CIT. ID:
      10762286
SOURCE:  Clin Endocrinol (Oxf) 2000 Apr;52(4):437-445
         [Record as supplied by publisher]




UI - 99439104
AU - Abe T; Ludecke DK
TI - Mucocele-like formation leading to neurological symptoms in
prolactin-secreting pituitary adenomas under dopamine agonist therapy.
SO - Surg Neurol 1999 Sep;52(3):274-9
AD - Department of Neurosurgery, Showa University School of Medicine,
Tokyo, Japan.
BACKGROUND: Mucocele-like formation associated with pituitary adenomas,
to the best of our knowledge, has been paid little attention. We report
three adult male patients with a mucocele-like formation that developed
behind the tumor and led to neurological symptoms in prolactin-secreting
pituitary adenomas (prolactinomas) under dopamine agonist therapy.
CLINICAL PRESENTATION: Three adult male patients with prolactinomas
developed hyperprolactinemia and new neurological symptoms during
dopamine agonist treatment. In each case, the pathogenesis of these
symptoms was due in part to a mass enlargement with development of a
mucocele-like formation behind a prolactinoma. In our patients, a
prolactinoma with a suprasellar extension originally filled the sphenoid
sinus. When dopamine agonist therapy became ineffective, new symptoms,
such as progressive visual impairment other than typical hemianopsia or
headache, developed and mass enlargement was found on MRI. MRI
demonstrated two different components: an enhancing prolactinoma and a
nonenhancing mucocele-like formation behind the tumor. Two patients had
compression of the optic nerves by a mass. Transnasal removal of
mucoceles and adenomas led to resolution of the neurological symptoms.
CONCLUSION: Early suspicion of a mucocele-like formation under dopamine
agonist therapy for prolactinomas is important in order to avoid a delay
in surgery, because a change in medical treatment will be ineffective. 



UI  - 97035518
AU  - Chanson P
TI  - [Medical treatment of pituitary adenoma]
SO  - Rev Prat 1996;46(12):1509-13
AD  - Service d'endocrinologie Centre hospitalier universitaire de Bicetre.
AB  - Dopamine agonists are able to restore ovulatory cycles in 80-90% of
      hyperprolactinemic patients and to reduce tumoral volume (often
      dramatically) in 80% of macroprolactinomas. Their side-effects will
      be reduced with the use of parenteral forms or new agonists currently
      in preparation. Somatostatin analogues administered either subcutane-
      ously by three daily injections (octreotide) or intramusculary with a
      long-acting formulation every 10-15 days (lanreotide) are able to
      "normalize" GH levels in 70% of acromegalic patients and to shrink
      tumor in half of the patients. Side effects are generally minor but
      an increased incidence of gallstones has been reported. These
      somatostatin analogs are also very effective in the treatment of
      TSH-secreting adenomas. Medical treatment of other pituitary adenomas
      is much more disappointing.





UI  - 96338538
AU  - Ciccarelli E; Camanni F
TI  - Diagnosis and drug therapy of prolactinoma.
SO  - Drugs 1996;51(6):954-65
AD  - Division of Endocrinology, University of Turin, Italy.
AB  - A prolactin-secreting pituitary tumour is the most frequent cause of
      hyperprolactinaemia that commonly occurs in clinical practice.
      Prolactinomas occur more frequently in women than in men and may
      differ in size, invasive growth and secretory activity. At presentat-
      ion, macroadenomas are more frequently diagnosed in men. Specific
      immunohistochemical stains are necessary to prove the presence of
      prolactin in the tumour cells. The main investigations in the
      diagnosis of a prolactin-secreting adenoma are hormonal and
      radiological. As prolactin is a pulsatile hormone, it is a general
      rule to obtain several blood samples by taking a single sample on 3
      separate days or 3 sequential samples (every 30 minutes) in restful
      conditions. Prolactin levels of 100 to 200 micrograms/L are commonly
      considered diagnostic for the presence of a prolactinoma; however,
      prolactinoma cannot be excluded in the presence of lower levels, and
      prolactin levels > 100 micrograms/L are present in some patients with
      idiopathic hyperprolactinaemia. Several dynamic function tests have
      been proposed to differentiate idiopathic from tumorous hyperprolact-
      inaemia. Although they could be used for group discrimination, these
      tests cannot be used for individual patients. To differentiate
      between a prolactinoma and a pseudoprolactinoma, thyrotrophin
      response to a dopamine receptor antagonist may be used, as only
      prolactinomas may have an increased response. A short course of
      dopaminergic drugs may also be of some help, as in macroprolactinomas
      only a shrinkage may be observed. After hyperprolactinaemia is
      confirmed, imaging with computerised tomography (CT) and magnetic
      resonance imaging (MRI) are necessary to define the presence of a
      lesion compatible with a pituitary tumour. There is now a general
      agreement that medical therapy is of first choice in patients with
      prolactinomas. Bromocriptine, the most common drug used in this
      condition, is a semisynthetic ergot alkaloid that directly stimulates
      specific pituitary cell membrane dopamine D2 receptors and inhibits
      prolactin synthesis and secretion. In most patients, a reduction or
      normalisation of prolactin levels is usually observed, together with
      the disappearance or improvement of clinical symptoms. The sensitivi-
      ty to bromocriptine is variable and patients may need different dose
      of the drug. Bromocriptine is also able to shrink the tumour in most
      patients; however, a few reports of disease progression during
      therapy have been described. The need for close follow-up, including
      prolactin levels and CT or MRI studies, is therefore emphasised.
      Bromocriptine is conventionally given in 2 or 3 daily doses; however,
      a single evening dose has been shown to be equally effective.
      Bromocriptine is usually well tolerated by the majority of patients;
      some adverse effects (nausea, vomiting, postural hypotension) may be
      initially present, but they usually wear off in time. To prevent such
      adverse effects it is advisable to start treatment with a low dose
      during the evening meal and gradually increase the dose over days or
      weeks. A few patients are unable to tolerate oral bromocriptine, so
      different formulations of bromocriptine or alternative dopamine
      agonist drugs (lisuride, terguride, metergoline, dihydroergocryptine,
      quinagolide, cabergoline, pergolide) have been proposed. Of
      particular clinical relevance because of their good tolerability and
      sustained activity are cabergoline and quinagolide. Particular
      attention should be paid to pregnancy in prolactinoma patients, as
      tumour enlargement has been reported. As the risk for this occurrence
      is low in patients with microprolactinoma, there is a general
      agreement that the drug can be stopped once pregnancy is diagnosed.
      In patients with macroprolactinoma the risk of tumour enlargement is
      higher. Therefore, primary therapy with bromocriptine until the
      tumour has shrank is suggested before pregnancy is attempted.
      Bromocriptine should be stopped as soon as pregnancy is confirmed,
      but re (63 Refs)


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