A new radioguided procedure for localization and surgical treatment of neck node metastasis of papillary thyroid cancer.

AIM OF THE STUDY: We intended to use a radioguided technique for pre-operative localization of neck node recurrences in patients with papillary thyroid cancer (PTC) already submitted to thyroidectomy and radioiodine treatment. PATIENTS AND METHODS: We selected 20 patients affected by PTC with evidence of neck nodes recurrences at ultrasound examination. Our method has been derived from the Radioguided Occult Lesion Localization technique used for pre-operative localization of occult breast lesions. The technique involves the inoculation of human albumin macroaggregates labeled with radioactive technetium (0.4 mCi in a volume of 0.05 ml) directly in the suspicious lesion, under ultrasound guidance. The persistence of the radioactive tracer in the nodes is confirmed by a scintigraphy performed 2 h after injection. During surgery, a gamma detecting probe is used to locate the suspicious lesions as "hot spots". RESULTS: Fifty lymph-nodes were injected with the tracer. All radiolabeled lymph-nodes were located and removed during surgery. At histology, metastasis of PTC was confirmed in 38/50 (76%) lymph-nodes. At least one metastatic lymph-node per patient was removed. In 8/20 (40%) patients, reactive lymphoid hyperplasia was found in 12/50 (24%) lymph-nodes. CONCLUSIONS: This radioguided technique has been highly effective for localization and surgical treatment of suspicious lymph-node detected at neck ultrasound and may play a valuable role in case of node metastases of thyroid cancer that show no radioiodine uptake.

Long-term follow-up of achalasia patients treated with botulinum toxin.

AIMS: To evaluate long-term efficacy of intrasphincteric injection of botulinum toxin in untreated achalasia patients; to analyse whether age can be a predictor of response; and to verify whether any objective measurements correlate with symptom relief MATERIALS AND METHODS: A total of 37 patients (mean age 61.4+/-17.5 years) were enrolled, all of whom injected endoscopically with 100 U of botulinum toxin. Symptom score, oesophageal manometry and oesophageal radionuclide emptying were assessed prior to treatment and 4 weeks, 3 months and 1 year after botulinum toxin. In the case of failure or relapse (symptom score >2), treatment was repeated. RESULTS: All but 6 patients (83.7%) were in clinical remission one month after botulinum toxin. At 12 months, mean symptom score was 0.9+/-0.5 (p<0.05 vs basal); mean lower oesophageal sphincter pressure was 22.0+/-6.3 (p<0.05 vs basal), and 10-min radionuclide retention was 14.0%+/-7.2 (p<0.05 vs basal). Of the 35 patients followed, 12 (34.3%) had a relapse and were re-treated; 4 out of 12 did not respond after re-treatment. Efficacy of first injection of botulinum toxin lasted for a mean period of 15.6 months (range 2-30). Up to day 31 (83.7%) patients were still in remission. We observed a trend towards a better response to botulinum toxin treatment in patients over 50 years (p=0.053). Moreover no correlation was found between any objective achalasia measurements and symptom relief (r coefficient between 0.1 and 0.5) CONCLUSIONS: Results show that: 1) one or two intrasphincteric injections of botulinum toxin result in clinical and objective improvement in about 84% of achalasia patients and are not associated with serious side-effects; 2) patients over 50 years showed better benefit than younger patients; 3) no correlation was found between any objective measurements and symptom relief.

Effect of trimetazidine on 99Tcm-tetrofosmin uptake in patients with coronary artery disease.

Myocardial uptake of 99Tcm-tetrofosmin in vivo is determined by a combination of flow and metabolic status of myocytes. The accumulation of tetrofosmin in the mitochondria is related to their ability to transduce metabolic energy into electronegative membrane potential. Trimetazidine (TMZ), an anti-ischaemic drug, appears to have a metabolic cytoprotective effect related to mitochondrial function, since it does not induce systemic or coronary haemodynamic changes. In this study, we evaluated the effects of TMZ on tetrofosmin uptake in hypoperfused myocardial regions in patients with coronary artery disease (CAD). Twenty-two patients, 14 with previous myocardial infarction (group A) and eight with a history of angina (group B), with angiographically documented CAD were studied. All patients underwent two tetrofosmin SPET studies at rest, before (baseline) and 1 week after TMZ administration (post-TMZ). On quantitative analysis, 131 segments showed less tetrofosmin uptake at baseline. In these segments, tetrofosmin uptake was 51 +/- 13% at baseline and 55 +/- 15% post-TMZ (P < 0.001 vs control). In the 86 hypoperfused segments of group A, tetrofosmin uptake was 48 +/- 14% at baseline and 52 +/- 17% post-TMZ (P < 0.001 vs control). In the 45 hypoperfused segments of group B, tetrofosmin uptake was 56 +/- 9% at baseline and 60 +/- 10% post-TMZ (P < 0.001 vs control). In the remaining 309 segments, no significant difference in tetrofosmin uptake before and after TMZ was observed. In conclusion, our results suggest that TMZ administration may increase myocardial uptake of tetrofosmin in hypoperfused regions at rest in patients with CAD, based on its metabolic effect.

Long-term follow-up of achalasic patients treated with botulinum toxin.

Botulinum toxin A (BoTx), a potent inhibitor of acetylcholine release from nerve endings both within the myenteric plexus and at the nerve-muscle junction, has been shown to decrease the lower esophageal sphincter (LES) pressure in patients with achalasia. Because of this property, the esophageal injection of BoTx has been suggested as an alternative treatment in achalasia. The objective of this study was to determine the long-term efficacy and safety of intrasphincteric injection of BoTx in a group of achalasic patients. Nineteen patients (mean age 56.1 +/- 19.2 years) were enrolled in the study. All of them were injected endoscopically with 100 U of BoTx by sclerotherapy needle at different sites of the LES. Symptom score (dysphagia, regurgitation and chest pain, each on a 0-3 scale), esophageal manometer and esophageal radionuclide emptying were assessed before the treatment and at 4 weeks, 3 months and 1 year after BoTx injection. In case of failure or relapse (symptom score > 2), the treatment was repeated. All but five patients (74%) were in clinical remission at 1 month. Mean symptom score after 1 month of BoTx decreased from 7.1 +/- 0.9 to 2.2 +/- 2.5 (p < 0.05). LES pressure decreased from 38.4 +/- 13.7 to 27.4 +/- 13.5 mmHg (p < 0.05) and 10-min radionuclide retention decreased from 70.9 +/- 20.7% to 33.8 +/- 27.0% (p < 0.05). Side-effects (transient chest pain) were mild and infrequent. At 12 months, the clinical score was 0.9 +/- 0.5 (p < 0.05 vs. basal); mean LES pressure was 22.0 +/- 7.1 (p < 0.05 vs. basal) and 10-min radionuclide retention was 15.8 +/- 6.0% (p < 0.05 vs. basal). The efficacy of the first injection of BoTx lasted for a mean period of 9 months (range 2-14 months). At the time of writing (follow-up period mean 17.6 months, range 2-31), 14 patients (10 with one injection) were still in remission (74%). Our results showed that one or two intrasphincteric injections of BoTx resulted in clinical and objective improvement in about 74% of achalasic patients and are not associated with serious adverse effects; the efficacy of BoTx treatment was long lasting; this procedure could be considered an attractive treatment, especially in elderly patients who are poor candidates for more invasive procedures.

Comparison of anterior pituitary hormone levels in the inferior petrosal sinuses and peripheral blood in various pituitary disorders during perihypophysial phlebography.

The present study aimed at evaluating the anterior pituitary hormone levels in the inferior petrosal sinuses and in the peripheral blood of 55 patients affected by various pituitary disorders and undergoing perihypophysial phlebography on neurosurgical indication or for diagnostic purposes. The results indicated that in 6 patients with Cushing's disease and in 4 with hyperprolactinemia the secreting adenoma could be localized by inferior petrosal sinus sampling. Furthermore, the concentrations of all the pituitary hormones were found to be higher in the right and/or in the left inferior petrosal sinus than in peripheral blood, showing a clear gradient between central and peripheral samples. Moreover, the evaluation of hormone central/peripheral concentration ratios revealed noteworthy differences, namely, that central/peripheral concentration ratios of GH, ACTH, and PRL were significantly higher than those of TSH, FSH, and LH (p less than 0.01). On the contrary, no significant differences were found when the concentration ratios of GH, ACTH and PRL or TSH, FSH and LH were compared among themselves. This finding may be attributed to at least two factors: the increased pulsatility and the relatively short biological halftime of polypeptic hormones (GH, ACTH, and PRL) compared with glycoprotein hormones (TSH, FSH, and LH).

Rapid and long-lasting suppression of prolactin secretion and shrinkage of prolactinomas after injection of long-acting repeatable form of bromocriptine (Parlodel LAR).

Five patients with PRL-secreting macroadenoma and nine patients with PRL-secreting microadenoma or idiopathic hyperprolactinaemia were treated with monthly administrations of long-acting bromocriptine suitable for repeatable injections (Parlodel LAR) for 1-12 cycles of treatment. A significant shrinkage of tumour mass and the recovery of visual field defects were observed in patients with macroprolactinoma. Plasma PRL levels decreased to 16.8 and 18.1% of pretreatment values, in macroprolactinoma and idiopathic or microadenomatous hyperprolactinaemic subjects, respectively, during the first cycle of treatment, reaching the normal range in three patients of each group. During the following cycles of treatment, two patients with macroprolactinoma and one patient with idiopathic or microadenomatous hyperprolactinaemia became normoprolactinaemic. Adverse reactions generally did not last beyond the first days of administration and decreased with the progression of the treatment. In conclusion, its effectiveness and the fact that it is well tolerated, may suggest that this form of bromocriptine may be used as a first therapeutic approach for patients with PRL-secreting adenomas, particularly when shrinkage of a macroadenoma is urgently required.

Effectiveness of a single injectable dose of bromocriptine long acting in the treatment of macroprolactinomas.

The aim of the present study was to investigate the effect of a new galenic injectable form of bromocriptine (Parlodel LA), characterized by sustained release of bromocriptine for 4-6 weeks, in 3 patients with prolactin-secreting macroadenomas through a 42-day follow-up. The following parameters were considered: decrease of plasma prolactin levels, reduction of tumor size studied by seriate CT scan controls and recovery of eventual visual fields impairments. Parlodel LA induced a sharp decrease of plasma prolactin levels for at least 42 days, without reaching normal values. This treatment also caused a rapid and marked shrinkage of tumors in all patients. Moreover, in two patients with constriction of visual fields a clear and progressive improvement in one and only a slight amelioration in the other were observed. There were almost no side effects except for mild nausea in one patient and transient orthostatic in another. These results demonstrate that Parlodel LA produces a long-lasting reduction of plasma prolactin levels and a rapid shrinkage of the tumor with almost no side effects.

Hyperthyroidism due to a thyroid-stimulating hormone (TSH)-secreting pituitary adenoma associated with functional hyperprolactinaemia. A case report.

This paper reports the case of a 31-year-old woman with hyperthyroidism, increased TSH and thyroid hormone levels, evidence of a pituitary adenoma, hyperprolactinaemia, amenorrhoea, and galactorrhoea. Following trans-sphenoidal pituitary adenomectomy, mild hyperthyroidism and increased TSH and alpha subunit levels persisted, whereas hyperprolactinaemia, amenorrhoea, and galactorrhoea disappeared. Serum TSH levels were not affected by administration of TRH, metochlopramide, domperidone, l-dopa or somatostatin. Serum TSH chromatography showed a normal pattern. Following a second trans-sphenoidal pituitary adenomectomy and radiotherapy, hyperthyroidism disappeared, and the TSH and alpha subunit levels returned to normal. Light microscopy showed no specific TSH immunostaining although electron microscopy revealed numerous secretory granules alined along the plasma membrane. The post-operative follow-up confirmed the presence of a TSH-secreting pituitary adenoma associated to functional hyperprolactinaemia.

Plasma prolactin levels in the inferior petrosal sinuses in various pituitary disorders during perihypophyseal phlebography.

The use of intercavernous sinus phlebography for the diagnosis and neurosurgical treatment of pituitary adenomas has enabled the collection of selective venous samplings of the inferior petrosal sinuses (IPSs), where prolactin (PRL) levels can be measured before the hormone becomes excessively diluted in the systemic circulation. In the present study, plasma PRL levels were studied in the right and/or left IPS and, simultaneously, in the peripheral circulation of: (1) normoprolactinemic patients affected with various pituitary disorders which required phlebographic procedures; (2) hyperprolactinemic patients with negative radiological and computed tomographic (CT) signs of pituitary adenomas and (3) adenomatous hyperprolactinemic patients. In the 17 normoprolactinemic patients, the plasma PRL concentration in the IPSs was significantly higher (3.5 times; p less than 0.01) than in the peripheral circulation. In the 11 hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas, the central gradient for PRL was significantly higher (2.8 times; p less than 0.05) than in the peripheral circulation. No significant difference was detected between PRL concentrations in the left and right IPSs. In the 11 adenomatous hyperprolactinemic patients, there was a significant (p less than 0.01) central gradient for PRL 3.8 times higher than in the peripheral circulation on the ipsilateral side of the tumor. Furthermore, the plasma PRL concentration in the ipsilateral IPS was significantly higher (3.4 times; p less than 0.05) than that in the contralateral sinus. In conclusion, the present study shows that a clear-cut concentration gradient exists between plasma PRL levels in the IPSs and in the peripheral circulation of normoprolactinemic and hyperprolactinemic patients with negative radiological and CT signs of pituitary adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin and TSH response to TRH and metoclopramide before and after l-thyroxine therapy in subclinical hypothyroidism.

The effects of the dopamine (DA) receptor antagonist metoclopramide on the plasma thyroid stimulating hormone (TSH) and prolactin (PRL) levels were studied in 8 patients with subclinical hypothyroidism (defined as absence of clinical signs of hypothyroidism with normal thyroid hormone levels, normal or slightly increased basal plasma TSH levels and increased and long-lasting TSH response to TRH) before and after l-thyroxine replacement therapy. Metoclopramide induced a significant (p less than 0.01) TSH release in the subclinical hypothyroid patients. Two weeks after l-thyroxine replacement therapy (50 micrograms/day), the TSH response to metoclopramide was completely blunted in subclinical hypothyroidism. In these patients a significant (p less than 0.01) inhibition of TSH response to intravenous thyrotropin-releasing hormone (TRH) was also observed after treatment with thyroid hormone. In analogy to the TSH behavior, plasma PRL secretion in response to metoclopramide and TRH administration was significantly (p less than 0.05) inhibited in the subclinical hypothyroid patients after l-thyroxine replacement therapy.