Functional assessment of patients with systemic sclerosis by the use of 'Six-minutes-walking-test'.

AIMS: Systemic Sclerosis (SS) is a chronic inflammatory disease of the connective tissues, characterised by alterations in the functions and structures of the small blood vessels (capillaries and arterioles) and by modifications associated with the disposition of collagen in the tissues. One of the most frequent complication of the SS is the pulmonary arterial hypertension (PAH). Aim of this study was to assess the various pathophysiological relationships betweens SS and PAH in order to establish whether the presence of this systemic disease can represent a risk factor. MATERIALS AND METHODS: Ten patients affected by SS (9 women and 1 man, with a mean age of 55.7 +/- 11.4 years) were enrolled in our study, as inpatients at Dept. of Internal Medicine and Rheumatology Unit of Perugia University School of Medicine in the "Santa Maria" General Hospital in Terni, Italy. A control group of 10 clinically healthy subjects (CHS, 9 women and 1 man, ranging in age from 35 to 55 years) was also recruited in order to obtain normal clinical data of reference In subjects recruited, we have conducted a functional evaluation, based on physical tests (6-minute-walking-test, 6MWT), equipment and laboratory, on subjects suffering from SS with suspected PAH, in order to calculate the degree of cardio-pulmonary compromission brought on by this disease, taking into consideration important variables such as age and gender. RESULTS: The 6 MWT showed that the mean value at rest of the O2 saturation (%) was 97.1 +/- 1.20, heart rate (hr/min) 76 +/- 8.8, and respiratory rate (rr/min) 20.4 +/- 2.8. HS had 98.6 +/- 0.52, 75.7 +/- 6.86, and 16.8 +/- 1.61, respectively. After the the test, the results showed that the patients had O2 saturation 93.8 +/- 3.42, hr 113 +/- 20.27, and rr 31 +/- 2.86. HS had 97.6 +/- 0.69, 90.7 +/- 5.67, and 20.1 +/- 1.59, respectively. CONCLUSIONS: Our study has confirmed the high involvement of PAH and other cardio-respiratory disturbances in patients with SS. In fact, we have verified PAP to be above the normal range in 3 out of 10 patients, while the other 3 patients presented borderline values. Because it is a simple method to conduct at low cost, in addition to being non-invasive, reproducible and well accepted, we must affirm that the 6MWT should be more utilized and exploited, especially during the fi rst phases of diagnosis. This in turn can help us to assess the patients and to determine a course of treatment which is more complex and onerous, as in therapeutic monitoring for verifying efficacy.

Surgical treatment of sporadic medullary thyroid carcinoma: strategy and outcome.

BACKGROUND: Medullary Thyroid Carcinoma (MTC) originates from the thyroid C cells and accounts for approximately 5-9% of all thyroid cancers. Aim of this study was to retrospectively evaluate the outcomes of 41 patients with MTC who underwent treatment at our institution. PATIENTS AND METHODS. We reviewed the records of 41 patients who underwent surgery between 1995 and 2004. The patients were divided into two groups: A) patients (n 30) without any previous surgery. B) patients (n 11) previously thyroidectomized and high calcitonin levels with or without radiological evidence of local regional or distant metastases. We performed total thyroidectomy with central compartment lymphadenectomy and ipsilateral modified radical neck dissection in group A patients. Group B patients underwent re-excision of the central neck compartment and bilateral modified radical neck dissection if it had not been previously performed. RESULTS: Most patients had major reduction in postoperative calcitonin levels. Compartmental dissection of the cervical node significantly improved the results of primary surgery and calcitonin returned to normal levels in approximately 60% of the patients in group A, but only the 30% of the patients in group B. CONCLUSIONS: The extent of the primary surgical resection and the evidence of local or distant metastases significantly influence the outcome of MTC patients. An extensive lymphadenectomy performed early in the treatment and re-operative cervical lymphadenectomy in patients with persistently high calcitonin levels after thyroidectomy significantly improved the outcome, although re-operation rarely results in normalized calcitonin levels and is associated with a higher incidence of complications.

Recurrences of thyroid well differentiated cancer: ultrasonography-guided surgical treatment.

AIM: Differentiated thyroid carcinomas (DTC) have a favourable outlook overall. Cornerstone of treatment is total thyroidectomy (TT), followed, if needed, by radiometabolic therapy. Such lesions however show a definite tendency to recur (about 35% of cases), generally in the first decade of follow-up: in 70% of patients such recurrence is local. Surgical resection is the only curative treatment option for local recurrence of well-differentiated thyroid cancer. Intraoperative ultrasonography (US) can be of significant help in facilitating localization and complete resection of lesions. The aim of the study was to review the authors' own experience with the use of such diagnostic method in the clinical setting of thyroid neoplasm recurrence. METHODS: Between January 2005 and March 2008 31 patients with DTC recurrences underwent intraoperative US exploration. Recurrences were easily identified and resected in all patients. Postoperative tireoglobuline (TG) was undetectable. RESULTS: In all 31 patients preoperative US confirmed the presence of the lesion. In 26 patients digital exploration of the surgical field did not yield a definitively positive finding, whereas in 5 the lesion was easily palpable. Intraoperative US revealed the presence of pathologic tissue in all cases, with examination time ranging from 4 to 14 minutes (median 8 minutes). In all cases surgical resection was complete, with pathologic confirmation of the sample, and no necessity to extend ablation. CONCLUSION: Intraoperative US can be of significant help in the identification of DTC recurrences, in particular when lesion dimensions are smaller than 10 mm in diameter and can facilitate a more radical excision of the tumor in a surgical field were anatomical landmarks can be altered by previous surgery and/or radiometabolic therapy.

Thyroid function tests in acute viral hepatitis: relative reduction in serum thyroxine levels due to T4-TBG binding inhibitors in patients with severe liver cell necrosis.

Thyroid function tests were evaluated in 34 patients with acute viral hepatitis (AVH) and in 38 healthy controls (C). As expected, AVH patients displayed a significant increase in T4, rT3 and TBG serum levels with respect to C, while FT4 and TSH concentrations were similar. A positive correlation between TBG and T4 was evident in C, but not in AVH. In this group there was, instead, an inverse correlation between the sum of serum levels of GOT + GPT and T4 concentrations. When AVH patients were divided in "high necrosis" (HN, serum GOT + GPT greater than 2000 UI/l) and "low necrosis" (LN, serum GOT + GPT less than 2000 UI/ml) groups, we found a significant reduction in both T4 and T3 serum concentrations in HN with respect to LN, despite similar levels of TBG, albumin, FT4 and TSH. The hypothesis that thyroid-hormone binding inhibitors (THBI), released during severe liver cell injury, accounted for an impaired serum binding capacity in HN-AVH, was confirmed by the significant increase in FT4/T4 ratio and by the demonstration of THBI activity in pooled sera of these patients, with respect to LN subgroup. Our present finding may clarify the unexplained observation of reduced T4 levels in patients with fulminant hepatitis and the ominous prognostic significance of a "low T4 syndrome" in subjects with severe liver disease and/or other systemic illnesses.

Catecholamines and pituitary function. VII: Effects of acute and chronic dopamine-receptor blockade on pituitary response to TRH-GNRH in normal women and in patients with hyperprolactinemic amenorrhea.

To investigate whether an enhanced dopamine (DA) inhibition on pituitary thyrotrophs and gonadotrophs may account for the abnormal TSH and LH dynamics in pathological hyperprolactinemia, we examined the effect of an acute lysis of the putative DA overinhibition, as obtained with continuous domperidone (DOM) infusion, on both basal and TRH-GnRH stimulated PRL, TSH and LH release in both normal cycling women and patients with pathological hyperprolactinemia. The effect of TRH-GnRH administration was also examined in women with DA-antagonist induced hyperprolactinemia, in order to evaluate the effect of a chronic lack of the physiological DA inhibition on pituitary hormone dynamics. Patients with both pathological and DA-antagonist induced hyperprolactinemia displayed an evident TSH and LH hyper-responsiveness to TRH-GnRH. The PRL response was reduced in the former but enhanced in the latter group. Domperidone infusion resulted in a marked increase in serum PRL levels in normal cycling women, but not in patients with pathological hyperprolactinemia. The abolition of the putative DA-overinhibition at the pituitary level with DOM infusion in patients with pathological hyperprolactinemia was followed by a slight increase in basal TSH output but did not modify the TSH and LH hyperresponsiveness to TRH-GnRH. The similarities in TSH and LH dynamics between patients with pathological and DA-antagonist induced hyperprolactinemia and the ineffectiveness of DOM infusion in modifying the TSH and LH hyper-responses to TRH-GnRH in the former group, seem to exclude the widely accepted idea that endogenous DA overactivity is responsible for the abnormal thyrotroph and lactotroph dynamics in women with hyperprolactinemic amenorrhea.

Catecholamines and pituitary function. VI. Effect of different dopamine doses on TRH-induced prolactin release in women with pathological hyperprolactinemia.

The present study was designed to examine the effect of low-dose dopamine (DA) infusion rates (0.02 and 0.1 microgram/kg X min) on both basal and TRH-stimulated prolactin release in normal and hyperprolactinemic individuals. Sixteen normally menstruating women in the early follicular phase of a cycle and 23 hyperprolactinemic patients were studied. 0.1 microgram/kg X min DA was infused in 8 normal women and 15 patients with pathological hyperprolactinemia, while 8 normal controls and 8 patients received 0.02 microgram/kg X min DA TRH (200 micrograms, i.v.) was administered alone and at the 180th min of the 5-hour DA infusion in all controls and patients. A significant reduction in serum PRL levels, which was similar in normal women (-59.5 +/- 4.0%, mean +/- SE) and hyperprolactinemic patients (-48.2 +/- 5.5) was observed in response to 0.1 microgram/kg X min DA. In normal cycling women DA infusion significantly (P less than 0.02) reduced the PRL response to TRH with respect to the basal TRH test (delta PRL 45.0 +/- 7.0 vs. 77.9 +/- 15.4 ng/ml). On the contrary, the PRL response to TRH was significantly higher during 0.1 microgram/kg X min DA than in basal conditions in hyperprolactinemic patients, both in absolute (delta PRL 91.8 +/- 17.6 vs. 38.4 +/- 6.8, P less than 0.03) and per cent (198.5 +/- 67.6 vs. 32.1 +/- 7.5, P less than 0.02) values. A normal PRL response to TRH, arbitrarily defined as an increase greater than 100% of baseline, was restored in 11 out of 15 previously unresponsive hyperprolactinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid function tests in patients undergoing maintenance dialysis: characterization of the 'low-T4 syndrome' in subjects on regular hemodialysis and continuous ambulatory peritoneal dialysis.

Thyroid function tests were evaluated in 38 patients on regular hemodialysis (HD), in 36 on continuous ambulatory peritoneal dialysis (CAPD) and in 39 healthy controls. A significant reduction in total thyroxine (TT4), total triiodothyronine (TT3), reverse (rT3), and free T4 (fT4) mean levels and normal TSH, free T3, TBG and albumin concentrations was found in both HD and CAPD patients. A 'low-T4 syndrome' (serum T4 less than 5 micrograms/dl) was found in 9 CAPD (25%) and 20 HD (53%) patients, but none of them had fT4 levels below the normal laboratory range. The only striking difference between low-T4 HD and low-T4 CAPD patients was the significantly lower TBG and albumin serum levels in CAPD group. Low-T4 HD displayed normal TBG levels but enhanced fT4/TT4 and fT4/TT4 X TBG ratios. We concluded that: the abnormalities in thyroid function tests in patients on long-term dialysis (HD and CAPD) do not express the existence of a true hypothyroidism; a different pathogenesis of the low-T4 syndrome in the CAPD and HD groups may be hypothesized: in the former it could be attributed to a reduction in serum-binding capacity for thyroid hormones, in the latter the relative increase in fT4 percentage despite normal TBG levels suggests either the presence of T4-TBG-binding inhibitor(s), or structural abnormalities of thyroid-hormone-binding proteins.

Catecholamines and pituitary-function. V. Effect of low-dose dopamine infusion on basal and gonadotropin-releasing hormone stimulated gonadotropin release in normal cycling women and patients with hyperprolactinemic amenorrhea.

To verify the role of dopaminergic mechanisms in the control of gonadotropin secretion in normal and hyperprolactinemic women, we examined the gonadotropin response to GnRH (100 micrograms i.v.) administration in both basal conditions and during low-dose dopamine (DA, 0.1 microgram/kg/min) infusion. Hyperprolactinemic women, either with microadenoma or without radiological signs of pituitary tumor, showed significantly enhanced LH and FSH responses to GnRH in comparison with normal cycling women. 0.1 microgram/kg/min DA infusion did not result in any appreciable suppression of serum gonadotropin levels but significantly reduced the LH and FSH responses to GnRH in both normal and amenorrheic hyperprolactinemic women. Although both LH and FSH levels remained higher in hyperprolactinemic patients than in normal women after GnRH, the gonadotroph's sensitivity to DA inhibition was normal in the hyperprolactinemic group, as both control subjects and patients with hyperprolactinemic showed similar per cent suppression of GnRH-stimulated gonadotropin release during DA. These data confirm that hypothalamic DA modulates the gonadotroph's responsiveness to GnRH. The increased LH and FSH responses to GnRH in hyperprolactinemic patients and their reduction during low-dose DA infusion seem to indicate that endogenous DA inhibition of pituitary gonadotropin release is reduced rather than enhanced in women with pathological hyperprolactinemia.

Catecholamines and pituitary function. IV. Effects of low-dose dopamine infusion and long-term bromocriptine treatment on the abnormal thyrotroph (TSH) dynamics in patients with pathological hyperprolactinaemia.

In order to gain further insight into the role of dopamine (DA) in the control of TSH release and to investigate whether an increased or defective DA inhibition on pituitary thyrotrophs may be considered responsible for the abnormal TSH dynamics in pathological hyperprolactinaemia, we examined the effect of low-dose DA infusion on TRH stimulated TSH secretion in normally cycling women and in patients with pathological hyperprolactinaemia. The effect of long-term bromocriptine therapy on TSH dynamics was also evaluated in a selected group of hyperprolactinaemic women. Fifty-two hyperprolactinaemic patients with no other signs of pituitary or thyroid dysfunction had significantly higher mean TSH serum concentrations and mean TSH peak values after TRH administration than 75 healthy controls. Furthermore, the TSH rises induced by the DA-synthesis inhibitor alpha-methyl-p-tyrosine (AMPT, 500 mg orally) were enhanced in both prolactinoma and 'idiopathic hyperprolactinaemia' patients as compared with controls. There was a positive correlation between the TRH- and AMPT-induced TSH rises in the hyperprolactinaemic group. Low-dose DA infusion (0.1 microgram/kg X min) reduced TSH response to TRH in both regularly cycling women and patients with hyperprolactinaemic amenorrhoea. Longterm bromocriptine therapy (2.5 mg tid over 60-150 days) not only normalized serum Prl levels, but also reduced the TSH response to TRH in 7 hyperprolactinaemic women who had presented exaggerated TSH responses to the basal TRH test.(ABSTRACT TRUNCATED AT 250 WORDS)