SummaryIn June 2005, an ad hoc Expert Committee formed by the Pituitary Society convened during the 9th International Pituitary Congress in San Diego, California. Members of this committee consisted of invited international experts in the field, and included endocrinologists and neurosurgeons with recognized expertise in the management of prolactinomas. Discussions were held that included all interested participants to the Congress and resulted in formulation of these guidelines, which represent the current recommendations on the diagnosis and management of prolactinomas based upon comprehensive analysis and synthesis of all available data.

Cabergoline is more effective and better tolerated than bromocriptine in women with hyperprolactinemic amenorrhea.

Transsphenoidal surgery is a safe and effective treatment for Cushing's disease and our results compare favourably with those from published series, the majority of which comprise relatively small numbers. The presence of an intrasellar lesion and postoperative serum cortisol < 50 nmol/l are good predictors of remission in the long term but historically in our centre this can only be achieved in a significant number of patients at the expense of some degree of hypopituitarism. However, the surgical outcome for Cushing's disease, including a reduced frequency of hypopituitarism, can be improved if patients are operated on by a single pituitary surgeon, using selective adenomectomy as the preferred surgical approach wherever possible.

Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 +/- 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 +/- 6% (mean +/- SD) at baseline to 29 +/- 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 +/- 7 to 129 +/- 10 msec (P = 0.003). Fat mass increased from 20.2 +/- 9.4 to 21.9 +/- 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 +/- 6.8 to 61.5 +/- 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6-49.1) to 15.1 (range, 7.3-83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0-85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 +/- 7% at 3 months to 29 +/- 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.

The primary aim of this review has been to clarify the tumor shrinking effects of dopamine agonists on pituitary macroadenomas of different cell types. Shrinkage is most dramatic for macroprolactinomas and is due to cell size reduction. Seventy-nine percent of 271 definite macroprolactinomas were reduced in size by at least 25%, and 89% shrank to some degree. Most shrinkage occurs during the first 3 months of treatment, although in a minority shrinkage is delayed. Dopamine agonist resistance during long-term therapy is exceptional. Drug withdrawal nearly always leads to a return of hyperprolactinemia, even after several years treatment, although early tumor reexpansion is unusual. About 10% of true macroprolactinomas do not shrink with dopamine agonists; the molecular mechanisms of such resistance have yet to be determined. Alternative formulations of BC and new dopamine agonists (CV 205-502 and cabergoline) are useful for the minority of patients unable to tolerate oral BC, but do not seem to further improve overall shrinkage rates. The risks of pregnancy have probably been overstated, and BC is suitable primary treatment for women with prolactinomas of all sizes; the drug can be used safely during pregnancy in the event of clinically relevant tumor expansion. The interpretation of different degrees of hyperprolactinemia is discussed and management strategies suggested. Most patients with macroprolactinomas now avoid surgery, but drug-induced, time-dependent tumor fibrosis should be remembered if surgery is contemplated. Nonfunctioning pituitary tumors are mostly of gonadotroph cell origin and may be associated with significant disconnection hyperprolactinaemia. Seventy-six of 84 well-characterized tumors showed no tumor shrinkage during dopamine agonist therapy. Possible explanations include abnormalities of dopamine receptor number and function. Preliminary evidence suggests that dopamine agonists may restrain the growth of some functionless tumors; most of these tumors, however, can be satisfactorily debulked using transsphenoidal surgery. In contrast to macroprolactinomas, other functioning pituitary tumors (GH-, TSH-, and ACTH-secreting) rarely shrink during dopamine agonist therapy, although the number of tumors studied is small.