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>or=0.5 and

Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas.

OBJECTIVE: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. DESIGN: We studied 26 patients (nine male, 17 female; 42.5+/-12.7 years, mean+/-s.e.) with ACTH-secreting pituitary macroadenoma (tumor diameter: 11-40 mm). METHODS: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78+/-10 months. RESULTS: Before surgery, dexa decreased ACTH (>50% of baseline) in only 14/22 patients. The CRH-stimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P<0.05) and cured (P<0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P<0.02) and in normalized patients (P<0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. CONCLUSIONS: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.

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. PATIENTS AND METHODS: Ten men with giant prolactinomas with a median age of 44.8 years were treated with CAB. Before CAB, four patients had previously undergone transsphenoidal surgery without modifying the parasellar extension of the tumour or their visual defects. Pretreatment serum prolactin (PRL) levels ranged between 1230 and 22 916 micro g/l (mean +/- SEM: 5794 +/- 1996) and tumour volume was between 21.8 and 105.5 cm3 (mean +/- SEM: 50.7 +/- 8.8). CAB was administered at an initial low dose of 0.5 mg three times a week and, in five patients who did not achieve serum PRL normalization, the dose was progressively increased up to 10.5 mg/week. The duration of treatment was 13-68 months (mean 38.9). PRL levels and pituitary target organ hormones were assayed before, after 30 days and then every 3 months after the beginning of CAB treatment. Magnetic resonance imaging (MRI) was carried out before, after 1-3 months, after 6 months and then every 10-12 months to evaluate tumour shrinkage. RESULTS: In every patient, a significant PRL decrease (P = 0.0086) of at least 96% of the pretreatment values occurred (from 5794 +/- 1996 to 77 +/- 38, mean +/- SEM); a persistent normalization of PRL levels was achieved in five out of 10 patients (50%) beginning from the first 3-6 months of CAB treatment (only one patient needed 12 months of therapy). A significant tumour shrinkage (P = 0.0003) was achieved after 12 months of therapy in nine out of 10 patients (90%), with a volume reduction greater than 95% in three, of 50% in four and 25% in two patients. Tumour volume decreased from 50.7 +/- 8.8 to 28.6 +/- 9.4 and then to 22.3 +/- 8.8 cm3 (mean +/- SEM) after 6 and 12 months of CAB treatment, respectively. An improvement of visual field defects (VFD) was obtained in six of the seven patients presenting visual impairment before CAB treatment. Among the eight patients presenting libido and potency (L-P) failure, five normalized their PRL levels. In two of these a complete restoration of libido and potency was observed. Three patients with secondary hypoadrenalism and a patient with secondary hypothyroidism were treated with substitutive therapy during all the study time. The drug was well tolerated by all patients and no one discontinued the therapy. CONCLUSIONS: These data suggest that, in giant, aggressive prolactinomas, CAB represents a first-line therapy effective in reducing PRL levels and determining tumour shrinkage.

Diagnostic approach, genetic screening and prognostic factors of medullary thyroid carcinoma.

Medullary thyroid carcinoma is the least frequent thyroid neoplasm; it originates in thyroid parafollicular cells (calcitonin secreting C cells). In 80% of cases it is sporadic, in the remaining 20% it is familial, associated or not to other endocrinopathies as pheochromocytoma and hyperparathyroidism (MEN 2A, MEN 2B, and isolated familial medullary thyroid carcinoma). Preclinical diagnosis in relatives of affected subjects (preferably at pediatric age) is essential for successful therapy and is performed with genetic and biochemical screening tests. The genetic screening is based on DNA analysis (RET proto-oncogene mutations) of the patient, and if positive of all first degree relatives, to separate sporadic (somatic mutations) from familial (germline mutations) forms. The biochemical screening is based on calcitonin determination and its increase after pentagastrin stimulation, (a peculiar characteristic of medullary thyroid carcinoma, the first biochemical disorder in a subject at risk) and is mainly used in genetically silent familial medullary thyroid carcinoma. The principal negative prognostic factors of medullar thyroid carcinoma and the debate concerning the use of calcitonin determination in the diagnosis of the "cold" thyroid nodule have been analyzed.

Medical therapy of benign thyroid diseases.

Main guide-lines of medical therapy of benign thyroid diseases are reviewed. The most common drug therapy of the various forms of hyperthyroidism is represented by thionamide drugs (methimazole and propylthiouracil). Therapeutic protocols are diversified according to the disease. In Graves'disease medical therapy may present the definitive treatment, leading to remission in little less than 50% of cases while in hyperfunctioning nodular thyroid diseases, medical therapy is merely in preparation for ablation therapy. Other drugs used in hyperthyroidism are also mentioned (inorganic iodine, potassium perchlorate, beta-blockers). Thyroxine replacement therapy in the various forms of hypothyroidism is then analyzed, discussing in particular the therapeutic protocols and follow-up of the various forms of hypothyroidism. Finally, the controversy about the indications and efficacy of TSH-suppressive thyroxine therapy is considered.