Characterization of resistance to the prolactin-lowering effects of cabergoline in macroprolactinomas: a study in 122 patients.

CONTEXT: Macroprolactinomas poorly responsive to dopamine-agonists are often more aggressive and are usually termed 'resistant' but this clinical concept has always been defined empirically. OBJECTIVE: To define resistance to cabergoline (CAB) on the basis of a dose-response relationship established in a large series of macroprolactinoma patients and to assess the influence of gender and tumor invasiveness on the response to treatment. DESIGN: Retrospective study. METHODS: One hundred and twenty-two patients (72 women and 50 men) primarily treated with CAB for at least 1 year were included. Main outcome measures were serum prolactin (PRL) and tumor size. RESULTS: Normalization of PRL was obtained in 115 out of the 122 patients (94%). The majority of patients (96/115, 83%) were controlled with a CAB dose < or =1.5 mg/week. Most of the other patients (19/26) had only a partial resistance, responding to a further increase of the CAB dose. Beyond the dose of 3.5 mg/week, there was no clear advantage in further increasing the dose instead of continuing the treatment at the same dose. Most tumors (98/119 assessable cases, 82%) showed a significant shrinkage during CAB treatment. It was more likely to occur in cases of PRL normalization. Both cavernous sinus invasion and male gender were significantly and independently associated with partial or complete resistance to treatment. CONCLUSIONS: Most macroprolactinomas primarily treated with CAB are adequately controlled with doses < or =1.5 mg/week. About 20% of patients, mainly men and/or those with invasive tumors will require a higher dose of CAB. We suggest defining such patients as resistant to CAB.

Modification of hormonal secretion in clinically silent pituitary adenomas.

BACKGROUND: Silent pituitary adenomas are a subtype of adenomas characterized by positive immunoreactivity for one or more hormones classically secreted by normal pituitary cells but without clinical expression, although in some occasions enhanced or changed secretory activity can develop over time. Silent corticotroph adenomas are the classical example of this phenomenon. PATIENTS AND METHODS: A series of about 500 pituitary adenomas seen over a period of 20 years were screened for modification in hormonal secretion. Biochemical and immunohistochemical data were reviewed. RESULTS: Two cases were retrieved, one silent somatotroph adenoma and one thyrotroph adenoma, both without specific clinical features or biochemical abnormalities, which presented 20 years after initial surgery with evidence of acromegaly and hyperthyroidism, respectively. While the acromegaly was controlled by a combination of somatostatin analogs and growth hormone (GH) receptor antagonist therapy, neurosurgery was necessary to manage the thyrotroph adenoma. Immunohistochemical examination demonstrated an increase in the number of thyroid stimulating hormone (TSH)-immunoreactive cells compared to the first tissue. Apparently, the mechanisms responsible for the secretory modifications are different, being a change in secretory capacity in the silent somatotroph adenoma and a quantitative change in the silent thyrotroph adenoma. CONCLUSIONS: These two cases, one somatotroph and one thyrotroph adenoma, are an illustration that clinically silent pituitary adenomas may in rare circumstances evolve over time and become active, as previously demonstrated in silent corticotroph adenomas.

The effect of highly active antiretroviral treatment on viral load and antiretroviral drug levels in breast milk.

Viral load and drug levels were measured in the plasma and breast milk of nine mothers treated with highly active antiretroviral therapy (HAART) and one woman treated only with zidovudine during delivery. In all HAART-treated women after delivery the viral load was less than 400 copies/ml in plasma and breast milk. Compared with the plasma concentration, the breast milk concentration was between 68 and 90% for nevirapine, 6 and 24% for nelfinavir and 90 and 540% for indinavir.