Gaetana Cerbone

Increased arterial intima‐media thickness by B‐M mode echodoppler ultrasonography in acromegaly

BACKGROUND Patients with acromegaly have an increased morbidity and mortality for cardiovascular diseases. Despite the increasing evidence for the existence of a specific cardiomyopathy in acromegaly, the presence of vascular abnormalities has been never investigated.

Revised Guidelines for Neonatal Screening Programmes for Primary Congenital Hypothyroidism

Since the first guidelines for neonatal screening for congenital hypothyroidism (CH) were issued by ESPE in 1993 [1], there have been considerable advances in our understanding of CH and our appreciation of the various geographical and logistic difficulties involved. Therefore, an updating of the guidelines is overdue. Experience from countries where screening began in the late 1970s and early 1980s has indicated that treatment should be started no later than the first 2 weeks of life using a ‘high’ dosage regime of L-thyroxine (10–15 Ìg/kg/day). It has also been shown that the quality of long-term outcome is closely related to the quality of follow-up. In Eastern Europe, screening programmes for CH have either been started or will start soon in almost all countries, and although many programmes are operating satisfactorily, it is important to standardise screening procedures and management of suspected cases as much as possible in order to optimise outcome. A degree of uniformity throughout Europe would not only facilitate early detection and treatment of individual patients but give insight into the economic and epidemiological aspects of the screening programmes as well as the epidemiological aspect of CH.

The effect of quinagolide and cabergoline, two selective dopamine receptor type 2 agonists, in the treatment of prolactinomas

To compare effectiveness and tolerability of quinagolide (CV 205–502) and cabergoline (CAB) treatments in 39 patients with prolactinoma.

Effect of surgery and radiotherapy on visual and endocrine function in nonfunctioning pituitary adenomas

The effect of surgery alone or followed by radiotherapy in recovering visual abnormalities, debulking tumor mass and restoring hormone impairments was evaluated in 84 patients with clinically nonfunctioning pituitary adenomas (NFPA) subjected to 1–10 yr follow-up. All patients underwent surgery via transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy was performed after surgery in 59 of 72 patients with incomplete tumor removal. The assessment of pituitary function was performed in all patients before and every 1–2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic assessment was performed before and 3, 6 and 12 months after surgery, then yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58 patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was documented in 55, 7, 19, 47 and 6 patients, respectively. After surgery, gonadal function recovered in 12 women, visual disturbances improved in 43 patients (15 regained normal vision), pituitary function improved in 8 of 62 patients, worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of 84 patients. After surgery alone, tumor regrowth was observed in 7 patients between 3–7 yr. After radiotherapy, vision improved in 9, remained unchanged in 49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was documented in 9 patients between 2–12 yr and the prevalence of hypopituitarism raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is effective only in a minority of patients (14.3%) and radiotherapy causes hypopituitarism in rather the totality of patients after 10 yr. The prevalence of tumor regrowth was similar in irradiated ones (15%) and non irradiated patients (28%; χ2, p=0.4). Therefore, a careful radiological follow-up is suggested after surgery so that radiotherapy can be performed promptly on the basis of clinical data, tumor regrowth and/or invasiveness documented at histology.

New Medical Approaches in Pituitary Adenomas

Recently, the medical approach to patients with secreting and clinically non-functioning pituitary adenomas has received great impulse thanks to the availability of new, selective and long-lasting compounds with dopaminergic activity, such as cabergoline, and of somatostatin analogues provided in slow-release formulations, such as lanreotide and octreotide long acting release (LAR). In particular, the use of cabergoline has induced control of hyperprolactinaemia and tumour shrinkage in the great majority of patients with micro- and macroprolactinomas. Cabergoline treatment restores fertility both in women and men, and partially improves osteoporosis, one of the major complications of hyperprolactinaemia. In acromegaly, disease control (growth hormone [GH] <2.5–1.0 μg/l as a fasting or glucose-suppressed value, respectively, together with age-normalised insulin-like growth factor [IGF]-I) is achievable in more than half of patients receiving treatment with lanreotide or octreotide-LAR. Improvement in cardiomyopathy, sleep apnoea and arthropathy has been reported during GH/IGF-I suppression after pharmacotherapy. A synthetic GH analogue, B2036-PEG, that antagonises endogenous GH binding to its receptor-binding sites and a GH-releasing hormone antagonist that blocks the effect of this releasing factor on the hypothalamus and pituitary are presently under investigation in acromegaly. Preliminary studies have clearly demonstrated the effectiveness of the GH receptor antagonist in suppressing IGF-I levels in acromegalic patients previously unresponsive to somatostatin analogues. Beneficial effects of subcutaneous octreotide and lanreotide have also been reported in adenomas secreting thyroid-stimulating hormone, while the results of treatment with dopamine agonists or somatostatin analogues remain disappointing in patients with clinically non-functioning adenomas. In these patients the possibility of visualising in vivo the expression of D2 receptors using specific radiotracers such as 123I-methoxybenzamide has allowed selection of patients likely to respond to cabergoline. Scant effects of pharmacotherapy have also been reported in patients with adenomas secreting adrenocorticotropic hormone. However, some preliminary data suggest a potential use of cabergoline in combination with ketoconazole, or alone, in selected cases of Cushing’s disease or Nelson’s syndrome.

Power Doppler Improves the Diagnostic Accuracy of Color Doppler Ultrasonography in Cold Thyroid Nodules: Follow-Up Results

The usefulness of a recent color Doppler (CD) ultrasonography technique, named power Doppler (PD), was evaluated in the diagnosis of thyroid nodules showing low or absent uptake of 99mTc-pertechnetate, in order to investigate the possibility to improve the diagnostic accuracy of ultrasonography. The rationale was the evidence that at PD the color map displays the total integrated Doppler power in color, while CD generally displays an estimate of the mean Doppler shift. The vascular patterns recorded at PD and CD evaluation of 322 thyroid nodules were compared to the results of cytology and/or histology, when surgery was performed. In respect to the results of cytology, PD has a higher sensitivity (100 vs. 91%) and specificity (95.1 vs. 86.2%) than CD. A similar result was found when PD and CD were compared to the results of histology, sensitivity being 100 vs. 89% and specificity 98.1 vs. 93.7%, respectively. During the follow-up the 2 nodules considered false positive at PD resulted to be tumoral lesions. On this basis, the final specificity of PD in our series was 100%. In conclusion, in the current series including 322 thyroid nodules characterized by a low or absent uptake of 99mTc-pertechnetate, PD seems to provide a better characterization of thyroid nodules, possibly allowing a more accurate selection of the patients to subject to fine-needle biopsy.

Hormone levels and tumour size response to quinagolide and cabergoline in patients with prolactin‐secreting and clinically non‐functioning pituitary adenomas: predictive value of pituitary scintigraphy with 123I‐methoxybenzamide

BACKGROUND Dopamine agonists are indicated as primary therapy for PRL‐secreting pituitary adenomas, while controversial results have been reported in nonfunctioning adenomas (NFA).

Does the age of onset of growth hormone deficiency affect cardiac performance? A radionuclide angiography study

BACKGROUND GH and IGF‐I seem to play a relevant role in cardiac development and performance. Longstanding GH deficiency (GHD) causes several abnormalities in cardiac structure and performance which ultimately determine an increased cardiovascular morbidity and mortality.

Analysis of color Doppler signal intensity variation after levovist injection: a new approach to the diagnosis of thyroid nodules.

The objective of this study was to evaluate the usefulness of a galactose‐based ultrasonographic contrast agent, Levovist (Schering AG, Berlin, Germany), in differentiating benign from malignant thyroid nodules by analysis of the time‐intensity curves correlating the variation of the intensity signal value during the contrast transit time. Fifty‐four patients scheduled for surgical removal of a nodule or the thyroid gland or both after cytologic examination were enrolled in this study; all of the nodules underwent a baseline color and power Doppler evaluation and then to a color Doppler examination after an intravenous bolus injection of Levovist. The time‐intensity curves were analyzed with respect to the histologic results. Carcinomas showed a significantly earlier arrival time of Levovist than nodular hyperplastic benign nodules and adenomas (8.1 +/‐ 1.41 versus 19.6 +/‐ 2.2 and 16.1 +/‐ 2.8 seconds; P < .0001), although no significant difference occurred between hyperplastic benign nodules and adenomas; carcinomas and adenomas showed an earlier time to peak than hyperplastic benign nodules (14.6 +/‐ 1.2 and 23.1 +/‐ 3.8 versus 33.0 +/‐ 3.0 seconds; P < .0001). No significant difference was found in baseline, peak, final intensity signal, and percent variation of intensity signal among hyperplastic benign nodules, adenomas, and carcinomas. Although cytologic examination still remains the standard of reference for the presurgical diagnosis of thyroid nodules, the preliminary data of this pilot study demonstrate that the analysis of time‐intensity curves after Levovist injection might provide useful, complementary, and quantitative information to differentiate benign from malignant thyroid nodules.

Failure of long-term therapy with sodium valproate in Cushing’s disease

The aim of the current study was to evaluate the effectiveness of a long-term treatment with sodium valproate in 19 patients with Cushing’s disease. Before therapy beginning, the patients were subjected to acute test with 600 mg sodium valproate. Then, they were subjected to a 3-month therapy with sodium valproate at the dose of 600 mg/day before surgery (presurgical study). The 7 patients not surgically cured were subjected again to a 3-month therapy with sodium valproate at the dose of 600 mg/day after surgery (postsurgical study). Circulating ACTH and cortisol and urinary free cortisol levels were evaluated before and monthly after the beginning of the therapy. A decrease of plasma ACTH and serum cortisol levels greater than 50% of baseline was considered as positive response to acute test whereas the normalization of plasma ACTH, serum cortisol and urinary free cortisol levels and the clinical remission were considered as positive response to the long-term treatment. At acute test, 8 patients were considered responders and 11 patients non-responders. In no patient plasma ACTH, serum cortisol and urinary free cortisol were normalized during the long-term treatment. Urinary free cortisol levels significantly decreased (483.2±33.8 vs 699.4±67.0 ug/24 h), whereas plasma ACTH (302.8±17.7 vs 183.3±25.0 ng/l) and serum cortisol (466.5±23.2 vs 356.7±19.6 µg/l) significantly increased during sodium valproate administration in the 19 patients enrolled in the presurgical study. Plasma ACTH (247.7±22.3 vs 168.6±15.0 ng/l), serum cortisol (387.4±35.8 vs 282.0±16.0 µg/l) and urinary free cortisol (370.9±70.6 vs 261.3±37.8 µg/24 h) levels significantly increased in the 7 patients enrolled in the postsurgical study. No patient had clinical remission of Cushing’s disease. In conclusion, the current study showed that long-term therapy with sodium valproate is not useful in the therapeutic management of Cushing’s disease neither as alternative nor as adjunctive therapy to surgery.