Carlo Antonio Rota

Giant prolactinomas in men: efficacy of cabergoline treatment

objective The term ‘giant prolactinoma’ can be used for tumours larger than 4 cm in diameter and/or with massive extrasellar extension. Cabergoline (CAB), a long‐lasting dopamine agonist (DA), safe and well tolerated, is effective in normalizing PRL levels and inducing tumour shrinkage in micro‐ and macroprolactinomas. The purpose of this prospective study was to evaluate the efficacy and safety of CAB also for giant prolactinomas.

Quantification of cancer risk of each clinical and ultrasonographic suspicious feature of thyroid nodules: a systematic review and meta-analysis

OBJECTIVE In order to quantify the risk of malignancy of clinical and ultrasonographic features of thyroid nodules (TNs), we did a systematic review and meta-analysis of published studies. METHODS We did a literature search in MEDLINE for studies published from 1st January 1989 until 31st December 2012. Studies were considered eligible if they investigated the association between at least one clinical/ultrasonographic feature and the risk of malignancy, did not have exclusion criteria for the detected nodules, had histologically confirmed the diagnoses of malignancy, and had a univariable analysis available. Two reviewers independently extracted data on study characteristics and outcomes. RESULTS The meta-analysis included 41 studies, for a total of 29678 TN. A higher risk of malignancy expressed in odds ratio (OR) was found for the following: nodule height greater than width (OR: 10.15), absent halo sign (OR: 7.14), microcalcifications (OR: 6.76), irregular margins (OR: 6.12), hypoechogenicity (OR: 5.07), solid nodule structure (OR: 4.69), intranodular vascularization (OR: 3.76), family history of thyroid carcinoma (OR: 2.29), nodule size ≥4 cm (OR: 1.63), single nodule (OR: 1.43), history of head/neck irradiation (OR: 1.29), and male gender (OR: 1.22). Interestingly, meta-regression analysis showed a higher risk of malignancy for hypoechoic nodules in iodine-sufficient than in iodine-deficient geographical areas. CONCLUSIONS The current meta-analysis verified and weighed out each suspicious clinical and ultrasonographic TN feature. The highest risk was found for nodule height greater than width, absent halo sign, and microcalcifications for ultrasonographic features and family history of thyroid carcinoma for clinical features. A meta-analysis-derived grading system of TN malignancy risk, validated on a large prospective cohort, could be a useful tool in TN diagnostic work-up.

The treatment of neuroendocrine tumors with long-acting somatostatin analogs: A single center experience with lanreotide autogel

The aim of this retrospective study was to evaluate the efficacy, safety, and tolerability of lanreotide autogel given to metastatic well-differentiated (WD) neuroendocrine tumors (NET) patients observed in our Institute between 2005 and 2008. Patients with metastatic NET referred to our tertiary referral center were given lanreotide autogel 120 mg/month by deep sc injection for a period of at least 24 months. The efficacy was evaluated by the relief of disease symptoms, behavior of tumor markers and response rate in terms of time to tumor progression. Safety and tolerability were evaluated by assessing the onset of adverse events and treatment feasibility. Twenty-three patients (13 males), median age 62 yr (range 32–87) were considered for the study. All patients were affected by WD metastatic NET and had tumor progression in the last 6 months before the enrolment in the study. Median duration of response was 28 months (range 6–50 months). Fourteen patients (60.9%) showed flushing and diarrhea which improved by 85.7% and 55.6%, respectively, bronchoconstrinction and abdominal pain also ameliorated. A complete, partial or no-changed response in the tumor markers behavior was observed, respectively, in 42.9%, 22.9%, and 17.1% of cases. According to RECIST (Response Evaluation Criteria In Solid Tumors) criteria (version 1.1), there were 2 partial regression (8.7%) and 15 stable disease (65.3%); 6 patients (26.0%) progressed. No patient complained from any severe adverse reaction. The results of our study suggest that lanreotide autogel is effective in the symptoms, biochemical markers, and tumor progression control of WD metastatic NET and confirm that the treatment is well tolerated.

Paroxystic hypertension in a long-term hemodialyzed patient. Successful adrenalectomy for a dopamine-producing pheochromocytoma

Pheochromocytoma (Pheo) is an uncommon neoplasm producing blood pressure troubles and it may be undiagnosed in chronic dialyzed patients in whom hypertension is a common finding. The symptoms in Pheo syndrome depends on the prevalent catecholamine released, the most common being epinephrine (E) and norepinephrine (NE). Recently, a particular clinical picture has been described for dopamine (DA)-producing Pheos, in whom a normo-hypotensive status is more often observed. The authors report a case of mainly dopamine-producing Pheo in a long-term dialyzed patient, successfully treated with adrenalectomy. The main steps in diagnosis and preoperative management are described and debated also in view of the particular background produced by the end-stage renal failure. The common imaging techniques adopted for adrenal medullary neoplasms (US, CT, MIBG scintiscan) confirmed to be decisive for diagnosis; HPLC assay of plasma catecholamines is the only biochemical test available in these patients although its significance is questionable due to the poor knowledge of catecholamine metabolism in chronic renal failure. The clinical findings observed in this case seem in disagreement with those already reported in DA producing Pheos. Pheo in hemodialyzed patients is a rare event and it may be hidden by other more common causes of hypertension. However, more awareness from the medical staff allows to diagnose the neoplasm correctly by the currently available methods and to plan a safe surgical therapy also in high-risk patients.

Levothyroxine therapy in preventing nodular recurrence after hemithyroidectomy: a retrospective study

Aim: To determine the effect of levothyroxine (L-T4) therapy on the recurrence rate of nodular disease in patients previously treated with lobectomy for benign nodular goiter. Methods: Two hundred and thirty-tree patients (38 males, 195 females; age 49.9±13.1 yr) with no post-surgical evidence of nodular disease in the remnant, were followed-up yearly with serum TSH and ultrasound (US). Nodular recurrence was defined as a lesion of at least 5 mm at US. Patients were divided in 2 groups based on whether or not they had been treated with L-T4 after surgery: Group 1 (45 patients) who did not receive any L-T4, and Group 2 (188 patients) treated with L-T4. Group 2 was further subdivided in Group 2a (123 patients) receiving L-T4 substitutive therapy (TSH≥0.5 and ≤3 mUI/l) and Group 2b (65 patients) receiving L-T4 at TSH-suppressive dose (TSH<0.5 mUI/l). Results: Mean observation period was 5.8±4.7 yr. Overall, 71 out of 233 (30.5%) patients experienced recurrence of thyroid nodular disease: 29 patients (64.4%) in Group 1, 24 (19.5%) patients in Group 2a, and 18 (27.7%) patients in Group 2b. The recurrence rate was significantly lower (p<0.001) in Group 2 compared with Group 1, but no significant difference was observed between Groups 2a and 2b. Conclusion: In patients who have undergone hemithyroidectomy for benign monolobar nodular disease, L-T4 therapy may prevent recurrence of nodular disease. TSH suppression may not be required for prevention of recurrence in the remnant thyroid tissue.

Effects of Sex and Age on Pyridostigmine Potentiation of Growth Hormone-Releasing Hormone-Induced Growth Hormone Release

Previous studies have shown that pyridostigmine (PD) is capable of increasing the growth hormone (GH) response to GH-releasing hormone (GHRH) in young healthy subjects. In order to investigate the influence of age and sex on the PD potentiation of GHRH-induced GH release, we have studied the GH response to GHRH (50 micrograms i.v.) 1 h after oral administration of placebo or PD (60 mg) in 8 young healthy men (aged 19-28 years) and 8 age-matched young women (aged 18-25 years) during the follicular phase of the menstrual cycle, as well as in 8 postmenopausal women (aged 57-62 years) and 8 age-matched elderly men (aged 56-64 years). In the same subjects the effect of PD alone (60 mg p.o.) was also studied. Furthermore, in 6 postmenopausal women and 6 elderly men, the effect of a 30-mg PD oral dose on GH secretion and GH response to GHRH was evaluated with a similar protocol. The GH responses (mean +/- SE) to GHRH + placebo were similar in young men (peak 20.1 +/- 2 ng/ml, AUC 1,250 +/- 113 ng/ml/min) and women (peak 29.3 +/- 2.3 ng/ml, AUC 1,769 +/- 305 ng/ml/min). PD 60 mg was capable of significantly increasing the GH response to GHRH in young men (peak 43.5 +/- 5.1 ng/ml, AUC 3,734 +/- 472 ng/ml/min, p less than 0.005) but not in women (peak 39 +/- 2.3 ng/ml, AUC 2,479 +/- 205 ng/ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Corticotropin-releasing hormone inhibition of paradoxical growth hormone response to thyrotropin-releasing hormone in insulin-dependent diabetics

A paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) has been observed in type 1 diabetic patients and was hypothetically attributed to a reduced hypothalamic somatostatin tone. We have previously reported that corticotropin-releasing hormone (CRH) inhibits GH response to growth hormone-releasing hormone (GHRH) in normal subjects, possibly by an increased release of somatostatin. To study the effect of CRH on anomalous GH response to TRH, we tested with TRH (200 micrograms intravenously [IV]) and CRH (100 micrograms IV) + TRH (200 micrograms IV) 13 patients (six males and seven women) affected by insulin-dependent diabetes mellitus. A paradoxical GH response to TRH was observed in seven of 13 patients, one man and six women. In these subjects, the simultaneous administration of CRH and TRH significantly reduced the GH response to TRH, as assessed by both the maximal GH mean peak +/- SE (2.18 +/- 0.67 v 9.2 +/- 1.26 micrograms/L, P less than 0.005) and the area under the curve (AUC) +/- SE (187 +/- 32 v 567 +/- 35 micrograms.min/L, P less than .001). CRH had no effect on TRH-induced thyroid-stimulating hormone (TSH) release. Our data demonstrate that the paradoxical GH response to TRH in patients with type 1 diabetes mellitus is blocked by CRH administration. This CRH action may be due to an enhanced somatostatin release. Our data also show that exogenous CRH has no effect on TSH response to TRH, thus suggesting the existence of separate pathways in the neuroregulation of GH and TSH secretion.