Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

Cabergoline (CAB) treatment is an effective, safe and well tolerated approach for hyperprolactinemia. We investigated the efficacy of 24-month treatment with CAB in 37 patients with previously untreated PRL-secreting pituitary adenoma and evaluated the hormonal and neuroradiological changes after the discontinuation of long-term therapy. Eleven patients with macroprolactinoma (1M/10F) and 26 with microprolactinoma (4M/22F) started treatment taking 0.25 mg CAB twice a week for 4 weeks. The dose was increased stepwise in 0.5 mg increments until reaching lowest maximally effective and tolerated dose. CAB was withdrawn before the end of the study in 6 women who became pregnant and in one patient who showed a slight increase of the macroadenoma at MRI. During treatment, PRL levels decreased significantly in macro (11.1+/-1.1 vs 407.8+/-98.3 microg/l, p<0.001) and microprolactinomas (11.1+/-1.6 vs 193.8+/-23.4 microg/l, p<0.05) and normalized in all macro and in 23/26 microprolactinomas. In 3 cases PRL levels decreased but did not normalize because the appearance of side effects, such as nausea or hypotension, prevented the increase of the dose of CAB. The effective dose of drug correlated significantly with basal serum PRL levels (p<0.05) and with the pituitary tumor size (p<0.05). A significant decrease of the mean adenoma size was evident for macro (6.9+/-1.8 vs 16.0+/-1.8 mm, p<0.001) and microprolactinomas (3.0+/-0.5 vs 6.5+/-0.4 mm, p<0.001) at MRI. The tumor disappeared in 4 macroadenomas and in 11 microadenomas after 12 months of treatment. CAB withdrawal was followed by serum PRL increase in 13 cases after 3 months, in 6 after 6 months, in 2 after 9 months, and in one patient at the 12th month. Five patients showed normoprolactinemia with negative MRI after one year. Regular menses were restored in 7/10 macroprolactinomas and in all oligo-amenorrhoic patients with microadenoma; serum testosterone levels normalized in 2/3 hypogonadic men. Five out of 6 women become pregnant and had uneventful pregnancies which resulted in deliveries of normal babies. In conclusion, this study confirms the effectiveness and safety of CAB for patients with PRL-secreting pituitary adenoma and suggests that it can be considered a first choice treatment.

Delay of growth was rarely observed in teenagers with pituitary adenomas. At the onset of the disease, many girls complained of oligoamenorrhoea and galactorrhoea, while headache and delay of pubertal development were the symptoms more frequently referred by boys. Surgery alone was effective in a minority of patients and adjuvant therapies were helpful to obtain the remission of the disease in many cases. In patients with PRL-secreting pituitary adenoma, medical treatment, both as first choice or as adjuvant therapy, normalizes serum PRL levels in 14/27 (52%) cases.

Primary empty sella (PES) is a very frequent neuroradiological finding in the general population, that can induce hypopituitarism. Some studies focused on the association of PES with GH deficiency (GHD) or hypogonadotropic hypogonadism (HH), while data regarding the involvement of hypothalamic-pituitary-thyroid (HPT) axis, despite sporadic reports of central hypothyroidism, or the occurrence of hypoadrenalism (HA) are scanty. In this study, thyroid function and TSH response to exogenous TRH injection (TRH/TSH) were investigated in 43 patients [10 men and 33 women; aged (mean +/- SD), 48+/-12 yr] with PES: 22 patients had total and 21 partial PES. Forty healthy subjects (9 men and 31 women; aged 46+/-12 yr) were enrolled as a control group. Central hypothyroidism was found only in 2/43 cases, whereas one patient showed primary hypothyroidism. In euthyroid patients, mean serum TSH levels were significantly lower than controls (TSH: 1.0+/-0.7 vs 1.4+/-0.6 mU/l, p<0.01) and 79% of them showed abnormal TRH/TSH responses (TRH test was performed in 34 euthyroid patients: 17 cases with total and 17 cases with partial PES), but mean serum free T4 (FT4) and free T3 (FT3) values were not significantly lower than controls (FT4: 15.9+/-0.4 vs 15.0+/-2.1 pmol/l, p=NS; FT3: 5.3+/-1.2 vs 5.8+/-1.5 pmol/l, p=NS). Moreover, no significant differences were evident in mean serum TSH, FT4 and FT3 between patients with total and partial PES (TSH: 1.1+/-0.7 vs 0.9+/-0.8 mU/l, p=NS; FT4: 16.3+/-2.6 vs 15.7+/-2.2 pmol/l, p=NS; FT3: 5.4+/-1.3 vs 5.2+/-0.8 pmol/l, p=NS) and the TRH/TSH peak was impaired or exaggerated/delayed in 9 and 3 patients with total and in 12 and 3 cases with partial PES. No significant differences in the prevalence of abnormal TRH/TSH responsiveness were found between patients with partial or total PES (chi2=1.6, p=NS). Other impairment of pituitary function was detected in 23/43 patients: GHD was present in 15 cases, HH in 11 and central HA in 5 patients. Isolated or combined hypopituitarism was present in 17 and in 6 patients, respectively. In conclusion, pituitary dysfunction is very frequent in patients with PES, but central hypothyroidism occurs rarely. The entity of arachnoid herniation into the sellar fossa does not play a significant role on the degree of HPT axis dysfunction.

Objective: Despite the contribution of national registries and population-based reports, data concerning the epidemiology of acromegaly is scanty. In addition, the role of the environmental context has not been investigated. Design: Epidemiology of acromegaly was studied in the province of Messina (Sicily, Italy), focusing on the influence of environmental factors. Methods: Four zones, characterized by different degrees of exposition to environmental toxins due to industrial pollution, were identified in the province: area A (76 338 inhabitants), area B (287 328 inhabitants), area C (243 381 inhabitants), and area D (47 554 inhabitants) at low, middle-low, middle, and high industrial density respectively. We identified all acromegalics who were born and resided in the province of Messina, among patients either referred to our endocrine unit or referred elsewhere but recorded in the archives of the provincial healthcare agency.