We report four female patients with nodular goiter (in two of the four due to Hashimoto's thyroiditis) and one male patient with frank hypothyroidism due to Hashimoto's thyroiditis in whom TSH-suppressive or replacement L-T4 therapy failed to suppress or, respectively, normalize serum TSH. As is typical in our country, our patients took L-T4 15-20 min before a light breakfast. Gastrointestinal or other diseases and drugs known to interfere with the intestinal absorption of L-T4 were not the cause of this failure. The gastrointestinal absorption test of L-T4 (1000 micrograms) was performed in four patients; in three patients it revealed peculiar abnormalities in that (i) the absorption peak was > 70% but occurred at 4 hr vs an average of 2 hr in 12 euthyroid controls (EC) and 3 hr in the 10 primary hypothyroid controls (HC); (ii) 50% of the maximal absorption occurred at 110 min vs 45 min in EC and 50 min in HC; (iii) the maximal increment in T4 absorption was between 90 and 120 min (+111%) vs between 30 and 60 min in EC (+312%) and HC (+354%). In sum, only the first part of the absorption curve of T4 was shifted to the right (in three of the four women) and this shift was more pronounced and extended to the second part of the curve in the fourth patient; in this last patient absorption peak was 44% at 180 min. Based on these results, we obtained full suppression or normalization of TSH by postponing breakfast for at least 60 min after T4 ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

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 CAB was withdrawn before the end of the study in 6 women who became pregnant and in one patient who showed a slight increase of the macroadenoma at MRI.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.

In our study, the integrated evaluation of FS and AS showed that 41% of acromegalics are at risk for coronary atherosclerosis and that coronary calcifications were evident in about half of them despite the fact that myocardial infarction was not more frequent in acromegalic patients than the general population. Moreover, the control of acromegaly did not influence significantly the extent of coronary atherosclerosis.

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.

Coexistence of pituitary adenoma, intracranial meningioma and cerebral aneurysm has never been described. We report on a patient with GH-secreting pituitary macroadenoma associated with a right frontal meningioma and with two intracavernous asymptomatic aneurisms. A 61-year-old woman was referred to our Endocrine Unit 13 years after a right frontal craniotomy for a pituitary tumour. Endocrine investigation showed high levels of IGF-1 (560 ng/ml) and increased basal serum GH (56 ng/ml) levels, not suppressed after OGTT. MRI showed persistence of a homogeneously enhancing intra- and suprasellar lesion, compressing the visual pathways, with bilateral intracavernous invasion and simultaneous coexistence of a right intracavernous internal carotid artery (ICA) aneurysm in direct contact with the pituitary tumour. Somatostatin analog treatment normalized GH and IGF-1 levels. Eight months later, the patient underwent a balloon ICA occlusion with disappearance of the right ICA aneurysm. One year later, a new MRI confirmed the presence of the pituitary mass showing also a right intracranial frontal meningioma and a new ICA aneurysm on the left side. Previous studies have suggested that prolonged GH hypersecretion could play a role in the genesis of intracranial aneurysms, inducing atherosclerotic and/or degenerative modification of the arterial walls. Other aetiological factors include a mechanical effect due to a direct contact between adenoma and aneurysm. Coexistence of pituitary adenoma and intracranial meningioma is a rare event, but also for this association it has been suggested that GH or other growth factors could play a role in appearance or in growth of meningioma. In our case, meningioma appeared and grew, despite the effective treatment of acromegaly.