Low free thyroxine concentrations and deficient nocturnal surge of thyroid-stimulating hormone in haemodialysed patients compared with undialysed patients.

BACKGROUND: There is little information on the differences in pituitary-thyroid function between undialysed and haemodialysed patients. METHODS: Serum concentrations of free thyroxine (T(4)) and free triiodothyronine (T(3)), measured by enhanced chemiluminescence immunoassay, and thyroid-stimulating hormone (TSH) were compared in undialysed (n=22) and haemodialysed patients (n=85). The response of the serum TSH concentration to exogenously administered thyrotropin-releasing hormone (TRH) and circadian variation in serum TSH were also studied in the two groups. RESULTS: Serum free T(4) concentration was significantly lower in haemodialysed than in undialysed patients (1.02+/-0.02 vs 1.33+/-0.06 ng/dl, P<0.0001). Serum concentrations of free T(3) and TSH were essentially the same for the two groups. The response of serum TSH concentration to TRH was basically the same. Serum TSH concentration in undialysed patients during the night and in the morning were 142.4+/-15.4% and 121.7+/-4.1% of that during the day, the differences being significantly different. A nocturnal surge of TSH was not observed in haemodialysed patients. CONCLUSIONS: Low serum free T(4) concentration and a deficient nocturnal surge of TSH were found in haemodialysed patients compared with undialysed patients. The deficient nocturnal surge of TSH may contribute to the lower serum free T(4) concentration in haemodialysed patients.     

Improvement of thyroid hormone profile and thyrotrophin (TSH) surge alterations in hemodialysis patients on erythropoietin treatment.

BACKGROUND, MATERIAL AND METHODS: This study was performed in 20 patients with end-stage chronic renal failure (CRF) and 10 healthy volunteers. All of the patients were on regular hemodialysis treatment (RHD), 10 of whom were on recombinant human erythropoietin (rHuEPO) therapy. Hematocrit levels of the patients with CRF on rHuEPO were between 0.30 to 0.33 and not on rHuEPO were below 0.24. Baseline serum T3, T4, fT3, fT4 and TSH levels were measured and TRH stimulation test was performed in patients and control subjects. Serum TSH levels were measured hourly during the afternoon (2 to 5 p.m.) and at night (10 p.m. to 2 a.m.) to determine the nocturnal rhythm of TSH. RESULTS: The mean T3 in rHuEPO, not rHuEPO and control groups were 98.01 +/- 5.54, 70.55 +/- 7.09, 98.29 +/- 4.2 ng/dl; T4 6.47 +/- 0.68, 6.39 +/- 0.59, 8.35 +/- 0.46 ng/dl; fT3 2.24 +/- 0.19, 1.52 +/- 0.24, 2.29 +/- 0.17 pg/ml and fT4 0.88 +/- 0. 14, 0.75 +/- 0.14, 0.97 +/- 0.10 ng/dl, respectively. These values were significantly lower in patients not on rHuEPO compared to controls (p < 0.05). In patients on rHuEPO only T4 values were lower than in the controls (p < 0.05). In patients not on rHuEPO the T3, and fT3 were significantly lower than the values of patients on rHuEPO treatment (p < 0.05). Normal in 8 (80%), blunted in 1 (10%), no TSH response in 1 (10%) to TRH stimulation were obtained in rHuEPO group. TSH response was normal in 1 (10%), and delayed in 9 (90%) patients not on rHuEPO. The circadian nocturnal rhythm of TSH was abnormal in 8 (80%) patients not on rHuEPO, in 2 (20%) patients on rHuEPO. As a result, CRF and RHD distorts the circadian TSH rhythm and substantially change the thyroid hormone profile probably by affecting hypothalamic-pituitary-thyroid axis. Distortion of the circadian rhythm of TSH and TSH response to TRH points to a defect at the level of hypothalamus and pituitary gland. CONCLUSION: rHuEPO treatment has some beneficial effects on hypothalamo-pituitary-thyroid axis in the patients on RHD.     

Comparison of pituitary-thyroid function in patients with endstage renal disease and in age- and sex-matched controls

The response to i.v. bolus thyrotropin-releasing hormone (TRH) of 14 dialysis patients with end-stage renal disease (ESRD) was compared to the response of 14 age- and sex-matched renal clinic patients (controls) with normal renal function (serum creatinine concentrations less than 1.2 mg/dl). The mean basal serum levels of thyrotropin (TSH) were similar in the two groups. There was no difference between the two groups in the mean maximal increase in TSH after TRH (6.3 microU/ml and 7.2 microU/ml in ESRD and control groups, respectively); The rate of fall in TSH from 60 to 90 min after TRH was slower in the ESRD group than in the controls. The mean increase in serum triiodothyronine (T3) concentration after TRH was similar in both groups (25.4 ng/dl, ESRD; 18.4 ng/dl, controls). As previously reported, basal serum T3 content was subnormal in the ESRD patients. Serum thyroxine (T4) concentrations were comparable in control and ESRD groups and did not change significantly during the 90-min TRH test in either group. We conclude that ESRD patients, clinically stable on dialysis, have normal pituitary TRH responsiveness and normal thyroidal response to endogenous TSH secretion, as compared with an age- and sex-matched group of patients with normal renal function. The results of this study support the contention that ESRD patients are eumetabolic.     

Thyrotropin-releasing hormone: pharmacokinetic and pharmacodynamic properties in chronic renal failure.

The pharmacokinetics of thyrotropin-releasing hormone (TRH) were determined following a single i.v. administration in ten patients with chronic renal failure (CRF) maintained on chronic hemodialysis and in six normal subjects. A TRH-test (200 micrograms) was performed in all subjects on nondialysis days and was followed by sequential venous blood sampling at 0, 2, 5, 10, 20, 30 and 60 min. Plasma TRH and serum concentrations of TSH, T4, FT4 and T3 were measured by specific and sensitive RIA's. Serum thyroid hormone concentrations were lower in the hemodialysis patients than in the normals (p < 0.001). Basal TRH and TSH levels were similar in patients and in controls, however, a blunted response of TSH to TRH in CRF (3.8 +/- 2.4 vs. 11.2 +/- 2.6 mU/l, p < 0.001) was observed. Mean peak TRH concentrations (Cmax) were 34.445 (11.085, SD) fmoles/ml in CRF and only (13,400 (1.020) in the normals 2 min after TRH administration (tmax). The mean elimination half-life (t1/2) of TRH was 16 min in CRF and 6.5 min in normals (p < 0.001). The metabolic clearance rate (MCR) was markedly lowered in CRF, 58.3 (19.1) compared to normals (82.2 [15.3] l/m2/day, p < 0.001). The area under the plasma concentration-time curve (AUC) was 57.529 (28.562) fmoles.ml-1.min in CRF and 37.339 (5.026) (p < 0.005) in normals. These findings indicate that the pharmacokinetic properties of TRH are impaired in CRF. The kidney might be an important catabolic organ for exogenous TRH. Dosing schedules of TRH require possible adaptation to renal function.     

Short-term recombinant human growth hormone therapy does not modify growth hormone, thyrotropin and prolactin responses to thyrotropin-releasing hormone in adult dialysis patients.

BACKGROUND: We recently have reported the first randomized, controlled study on the effects of short-term recombinant human growth hormone (rhGH|| therapy on the nutritional status of a group of malnourished adult dialysis patients. In order to evaluate whether rhGH administration exerts any influence on GH, thyrotropin (TSH|| and prolactin (PRL|| responses to TSH-releasing hormone (TRH||, we assessed these responses before and after rhGH therapy. METHODS: GH, PRL and TSH responses to TRH before and 1 month after rhGH therapy in a group of adult dialysis patients were evaluated. Seventeen dialysis patients (11 on continuous ambulatory peritoneal dialysis/six on haemodialysis|| were studied (rhGH group, n=8; control group, n=9||. In the rhGH group, 0.2 IU/kg/day rhGH was administered subcutaneously. Each patient was tested with TRH (400 microg bolus i.v.|| on two separate occasions, just before and immediately after the treatment period. RESULTS: rhGH treatment did not modify baseline serum GH concentrations (6.6+/-2.7 vs 4.1+/-1.1 microg/l||, paradoxical GH responses to TRH (six out of eight patients||, GH peak (11.9+/-4.6 vs 11.2+/-5.3 microg/l, NS|| or area under the secretory curve of GH (GH AUC; 19.1+/-4.5 vs 12.1+/-3.1 microg/h/l||. Both basal PRL (35.5+/-7.1 vs 36.7+/-8.6 microg/l|| and TSH (2.3+/-1.1 vs 2.8+/-1.7 mU/l|| concentrations, as well as their responses to TRH stimulation (PRL peak, 59.9+/-16.6 vs 59. 5+/-11.8 microg/l; TSH peak, 6.2+/-2.6 vs 7.1+/-3.9 mU/l||, were also unaffected by rhGH therapy. CONCLUSION: These results suggest that short-term rhGH therapy does not significantly influence the magnitude of the somatotropic, lactotropic or thyrotropic response to TRH in adult dialysis patients. However, this finding has to be interpreted with caution due to the two different patient groups included in this study.     

Primary hypothyroidism in chronic renal failure

Serum thyroid hormone concentrations have been measured in 8 patients with chronic renal failure (CRF) who are currently enrolled on a chronic hemodialysis program. Three of these patients were diagnosed to be suffering from coexistent primary hypothyroidism whereas the other 5 were considered euthyroid. There was a variable decline in serum thyroid hormone levels in both groups. However, the serum TSH response to TRH was normal or blunted in the euthyroid group but was characteristically brisk in subjects with CRF and coexistent primary hypothyroidism. The TRH test may be useful in the diagnosis of primary hypothyroidism coexistent with CRF.     

Hypothalamic-pituitary thyroid abnormalities in children after renal transplantation

Patients with a successful renal transplant may have abnormalities in thyroid function. We evaluated serum thyroid hormone levels, serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH), and the circadian pattern of serum TSH in 18 children aged 6.6 – 19.4 years (median 12.6 years), 4.0 ± 2.9 years after renal transplantation. In 14 children, immunosuppressive therapy included methylprednisone [mean (± SD) 0.17 ± 0.05 mg/kg per day], while in 11 it included deflazacort (0.32 ± 0.1 mg/kg per day). Seven children were studied twice, under methylprednisone and again while on deflazacort therapy. Mean total and free thyroxine (T₄) values were significantly below the mean control levels (total T₄ 108.5 ± 21.5 vs. 118.7 ± 22.1 nmol/l, P <0.05 and free T₄ 14.4 ± 4.0 vs. 18 ± 4.9 pmol/l, P <0.001). Morning basal TSH levels were within the normal range. The mean TSH increment after TRH was 4.4 ± 3.5 mU/l, significantly lower than that of controls (10.8 ± 4.26, P <0.001). Of 7 patients on methylprednisone, 4 had nocturnal TSH surges below the normal range (95% confidence limits 47% – 300%); this occurred in 3 of 8 patients on deflazacort therapy. The TSH response to TRH was correlated with deflazacort dose. Patients on methylprednisone and deflazacort therapy had similar thyroid alterations. Our findings support the hypothesis that after renal transplantation some children have hypothalamic-pituitary thyroid abnormalities in which glucocorticoids may play a significant role. Received August 11, 1995; received in revised form and accepted December 6, 1995     

Cervical sympathectomy affects adrenocorticotropic hormone and thyroid-stimulating hormone in rats

To examine the effects of bilateral cervical sympathectomy on the secretion of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin (PRL), 18 male rats were divided into three groups: control (Cont), sham operation (Sham), and bilateral cervical sympathectomy (Symp). All rats were kept under a normal circadian rhythm for 2 weeks. Subsequently, blood was collected and plasma ACTH as well as serum TSH, GH, and PRL levels were measured. The difference in ACTH levels between the Cont and Sham groups was not significant, but ACTH levels in the Symp group were significantly higher than those in the other groups. The difference in TSH levels between the Cont and Sham groups was also not significant, but TSH levels in the Symp group were significantly lower than those in the Cont group. There were no statistically significant differences in GH and PRL levels among these groups. The present results suggest that cervical sympathectomy in the rat increases ACTH secretion and decreases TSH secretion in the pituitary. These effects seem to be due to a mildly increased secretion of melatonin in the pineal body that probably in turn increases corticotropin-releasing factor (CRF) secretion and decreases thyrotropin-releasing hormone (TRH) secretion in the hypothalamus. Extrapolation of these findings to humans suggests that longterm and repeated stellate ganglion block would affect the pituitary secretions of ACTH and TSH.     

Influence of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid axis in patients undergoing capd

OBJECTIVE: Treatment of anemia with recombinant human erythropoietin (rHuEpo) in hemodialysis patients has been associated with improvement of several abnormalities in hypothalamic-pituitary function. The aim of the present study is to investigate the effects of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid hormone axis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Single center, prospective study. PATIENTS AND METHODS: Ten patients who were clinically stable and had been on CAPD were evaluated. Eleven age and sex matched healthy volunteers were chosen as controls. All of the patients were clinically euthyroid. All patients were on CAPD therapy and none of them had received rHuEpo treatment previously. In all patients after basal estimations of free T3, free T4, TSH, GH and prolactin levels, a bolus of 400 microg TRH was administered intravenously. Levels of TSH, GH and prolactin were measured in blood samples collected every 30 min of the 3 h test period. After the treatment with rHuEpo, TRH test with the same protocol was repeated. RESULTS: Before the improvement in serum hemoglobin levels with rHuEpo treatment, the patients on CAPD showed abnormal hypothalamic-pituitary-thyroidal functions, including delayed and prolonged TSH (NS), paradoxically elevated GH (p < 0.001) and increased and prolonged prolactin (p = 0.001) responses to TRH. After improvement of anemia with rHuEpo no significant difference was found between the patients and control groups for baseline TSH levels. In the patients peak TSH level and AUC of TSH secretion were significantly reduced after the treatment (p < 0.05 for both). Furthermore the improvement in anemia did not eliminate the paradoxic GH and prolonged prolactin responses to TRH administration. CONCLUSION: Some hypothalamic-pituitary-thyroid function abnormalities including delayed and blunted TSH, increased and prolonged prolactin and paradoxical GH responses to TRH administration were observed in uremic patients treated with CAPD and the improvement in anemia with rHuEpo seems to cause slight changes on the hypothalamic-pituitary-thyroid axis and peripheral thyroid hormones.     

A longitudinal evaluation of thyroid function in critically ill surgical patients.

Thyroid hormone alterations (known as the "sick-euthyroid syndrome") are common following major surgery, but the time course for appearance and recovery from these alterations has not previously been longitudinally studied in a large group of surgical patients. The authors prospectively studied 59 patients undergoing major surgery (coronary artery bypass grafting, pneumonectomy, or subtotal colectomy). Compared with preoperative values, the mean serum T4, T3, free T3, and TSH concentrations decreased significantly (p less than 0.05) following surgery. Serum reverse T3 and T3 resin uptake index increased, while free T4 levels remained unchanged. These changes were seen within 6 hours of surgery and normalized by 1 week after surgery. Although the serum TSH response to TRH was normal before and after surgery in 56 of the 59 patients, the maximal TRH-induced increase in serum TSH and the integrated serum TSH response to TRH were suppressed in the early perioperative period. This postoperative TSH suppression correlated with elevated postoperative plasma dopamine concentrations (r = 0.57, p less than 0.05). Three patients with compensated primary hypothyroidism were detected in the study and represent the first documentation of serial thyroid hormone and TSH levels in hypothyroid patients undergoing major surgery. These patients had similar changes in thyroid hormone values compared with euthyroid patients. The serum TSH response to TRH was suppressed into the normal range in two of these patients on the day following surgery. The authors conclude that the sick-euthyroid syndrome occurs within a few hours of major surgery and remits with convalescence. Postoperative decreases in serum TSH may mask the diagnosis of hypothyroidism. Surgical consultants should be aware of these rapid postoperative changes so that thyroid function tests are properly interpreted in patients who have undergone major surgery.     

Spontaneous pituitary-thyroid function after surgical treatment of nontoxic goitre. A controlled long-term study

The free thyroxine index (FT4I), triiodothyronine (T3) and thyroid stimulating hormone (TSH) in serum and the peak serum TSH (TRH test) were measured in 18 patients with nontoxic uninodular goitre and 32 patients with nontoxic multinodular goitre before and 3, 6, 12, 24 and 36 months after goitre resection. Thyroid hormone therapy was not given postoperatively. Resection of non-toxic goitre provoked a transient rise in TSH baseline level, with peak about one year after surgery. Three years after the resection the TSH baseline had returned to the preoperative level. The TSH changes were significantly more pronounced in the multinodular goitrous group, in which resection was bilateral, than in the uninodular goitrous group. The changes in serum FT4I and serum T3 were of moderate degree and most pronounced in the multinodular group. During long-term observation, serum FT4I increased slightly but significantly in both groups, but serum T3 showed significant reduction, albeit within reference range. The results of the study suggest that thyroid hormone therapy as a routine procedure after simple goitre resection lacks a tenable rational basis.     

Function of the thyroid gland after subtotal resection for hyperthyroidism in relation to remnant size.

The size of the remnant gland after subtotal thyroidectomy varied between 5 and 12 g in 85 hyperthyroid patients. The patients were then examined 6 weeks and 6 months after surgery with estimation of TSH and TRH stimulation test as well as thyroxine and triiodothyronine. A significant correlation between TSH response to TRH and remnant weight was found ( r= 0.94, p less than 0.01). The frequency of raised S-TSH was higher in the group with small remnants compared with those with larger ones. There was only minor correlation between raised S-TSH or high TSH response to TRH and remnant size expressed in per cent of the total thyroid weight (relative remnant size). No significant difference in thyroxine and triiodothyronine was found between the weight groups. Hypothyroidism developed in two patients with small remnants (6 g) and in one patient with a remnant weight of 8 g. Recurrent hyperthyroidism occurred in one patient in the 8-gram weight group. These results indicate that the remnant size may be one factor influencing the outcome of thyroid function after surgery.     

Long term effects of non-invasive mechanical ventilation on pulmonary haemodynamics in patients with chronic respiratory failure

BACKGROUND: It is not known whether long term nocturnal mechanical ventilation (NMV) reduces pulmonary hypertension in patients with chronic respiratory failure (CRF). METHODS: Pulmonary haemodynamics, spirometric values, and gas exchange were studied in 33 patients requiring NMV due to CRF (20 with thoracic restriction, 13 with chronic obstructive pulmonary disease (COPD)) at baseline and after 1 year of NMV given in the volume cycled mode. Patients with COPD also received supplemental oxygen. RESULTS: Long term NMV improved gas exchange while lung function remained unchanged. Mean pulmonary artery pressure at rest before NMV was higher in patients with thoracic restriction than in those with COPD (33 (10) mm Hg v 25 (6) mm Hg). After 1 year of NMV mean pulmonary artery pressure decreased in patients with thoracic restriction to 25 (6) mm Hg (mean change -8.5 mm Hg (95% CI -12.6 to -4.3), p<0.01) but did not change significantly in patients with COPD (mean change 2.2 mm Hg (95% CI -0.3 to 4.8)). CONCLUSIONS: Long term NMV in CRF improves pulmonary haemodynamics in patients with thoracic restriction but not in patients with COPD.     

Thyroid hormone changes after cardiovascular surgery and clinical implications

Alterations in serum concentrations of total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) frequently occur in patients with nonthyroidal illnesses. These changes correlate with the severity of the illness and the prognosis. In this study, 44 patients undergoing a cardiovascular operation had significant declines in serum TT3 and TT4 levels during cardiopulmonary bypass and thereafter. Serum TT3 and TT4 concentrations reached their nadir at 30 minutes after the start of cardiopulmonary bypass with values (mean +/- standard error of the mean) of 0.77 +/- 0.12 nmol/L (50.4 +/- 7.6 ng/dL) and 68.2 +/- 10.2 nmol/L (5.30 +/- 0.79 micrograms/dL), respectively. The mean serum concentrations of TSH and TT4 returned to preoperative levels by the sixth day after operation, whereas TT3 levels remained low throughout the study period. The patients whose recovery was uneventful had higher serum TT3, TT4, and TSH levels than those who had complications or died. The trend toward recovery was initiated by a sharp increase in the serum TSH level and increases in serum TT3 and TT4 concentrations on the fourth day after operation. Patients with complications either did not show these changes or had only a transient increase in TT3 and TT4 levels. All of the patients had a normal serum free T4 level before anesthesia. Those with an uneventful recovery had a higher serum free T4 level on the sixth day after operation than those with complications. Two patients in the latter group had serum free T4 levels less than normal at that time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recombinant human TSH modulates in vivo C-telopeptides of type-1 collagen and bone alkaline phosphatase, but not osteoprotegerin production in postmenopausal women monitored for differentiated thyroid carcinoma.

In women monitored for thyroid carcinoma, short-term stimulation with rhTSH induced an acute decrease in serum C-telopeptides of type-1 collagen and an increase in serum BALP levels without any effect on OPG production. The inhibitory effect of TSH on bone resorption occurred only in postmenopausal women who showed low BMD and a high bone turnover rate as an effect of L-thyroxine suppressive therapy. INTRODUCTION: It has been recently shown that thyrotropin (TSH) has an inhibitory activity on skeletal remodeling in in vitro conditions. Here, we have aimed at evaluating whether TSH has similar effects in vivo. For this purpose, we have evaluated the sequential profile of serum bone metabolism markers during acute stimulation with recombinant human TSH (rhTSH) in thyroidectomized women monitored for thyroid carcinoma. MATERIALS AND METHODS: The study group included 66 thyroidectomized patients, of whom 38 were premenopausal and 28 postmenopausal, who underwent routine rhTSH-assisted whole body radioactive iodine scanning for differentiated thyroid carcinoma. The patients were sequentially evaluated for TSH, free triiodothyronine (FT3), free thyroxine (FT4), bone alkaline phosphatase (BALP), C-telopeptides of type-1 collagen (CrossLaps), and osteoprotegerin (OPG) levels during rhTSH stimulation. The samples were drawn just before and 2 and 7 days after the first administration of rhTSH. BMD was evaluated by ultrasonography at baseline. Seventy-one healthy women (41 premenopausal and 30 postmenopausal) acted as a control group. RESULTS AND CONCLUSIONS: At study entry, all patients had subclinical thyrotoxicosis as effect of L-thyroxine (L-T4) treatment. The patients had higher serum CrossLaps and OPG levels and lower BMD than healthy subjects. Postmenopausal patients showed comparable serum FT4 and FT3 concentrations with those found in premenopausal patients. However, postmenopausal patients showed higher serum CrossLaps (p < 0.001), OPG (p = 0.03), and BALP (p < 0.001) levels and lower BMD (p < 0.001) than those measured in premenopausal patients. Two days after the first administration of rhTSH, all patients had serum TSH values >100 mUI/liter. At this time, serum CrossLaps levels decreased significantly (p < 0.001) and BALP values increased (p = 0.001) with respect to the baseline values in postmenopausal but not in premenopausal patients. rhTSH did not induce any significant change in serum OPG values either in premenopausal or in postmenopausal patients. One week after the first rhTSH administration, serum CrossLaps values decreased again to values comparable with those measured at baseline, whereas serum BALP values remained high. This study shows that subclinical thyrotoxicosis is accompanied by high bone turnover rate with an increase in serum OPG levels compared with euthyroid healthy subjects. Acute increase in serum TSH levels is accompanied by a reversible inhibition of bone resorption. This effect is characterized by a decrease in serum CrossLaps and an increase in BALP levels without any evident effect on OPG production. The activity of TSH occurs specifically in postmenopausal women in whom the negative effects of L-T4 suppressive therapy on bone mass and metabolism are more marked compared with premenopausal women.     

Elevated Basal Levels and Exaggerated Responses to Thyrotrophin-Releasing Hormone of Prolactin and Thyrotrophin in Turner-Noonan-Syndrome

Basal levels of prolactin (Prl), FSH, LH, testosterone, estradiol, total thyroxine (T4), total triiodothyronine (T3) and thyrotrophin (TSH) were determined in four males with Turner-Noonan-Syndrome. The responsiveness of gonadotrophins to LH-RH (100 micrograms i.v.) and of Prl and TSH (200 micrograms i.v.) was studied. High basal levels and exaggerated responses to TRH of Prl were found in all patients. However no evidence of any of the well known causes of hyperprolactinaemia could be detected in them. The four men were with normal levels of T4 and T3 and showed exaggerated TSH responses to TRH. It is suggested that the alterations in Prl and TSH release are reflections of a congenital disorder in Turner-Noonan-Syndrome not yet well studied.     

Melatonin in chronic renal failure.

The melatonin status of patients in end-stage chronic renal failure (CRF) was evaluated by the determination of daytime plasma melatonin levels and by the investigation of the circadian rhythmicity of melatonin secretion. A significant increase in plasma melatonin concentration was found in all CRF patient groups investigated, i.e. CRF patients on conservative treatment (CT; n = 48), CRF patients on maintenance haemodialysis treatment (HD; n = 39) and CRF patients on peritoneal dialysis (PD; n = 32). Successful transplantation led to a marked reduction in plasma melatonin levels. The circadian rhythm of melatonin secretion would appear to be suppressed in CRF as the nocturnal secretory surge was absent in all HD patients and in 80% of the posttransplantation patients studied.     

Prevalence of Subclinical Hypothyroidism in a Morbidly Obese Population and Improvement after Weight Loss Induced by Roux-en-Y Gastric Bypass

Background:There are many studies concerning thyroid function in obesity, and some of them describe higher TSH levels in obese subjects. Few studies evaluated long-term changes in thyroid function caused by weight loss after bariatric surgery. Our aims were to evaluate the prevalence of subclinical hypothyroidism (SH) in a morbidly obese population and to analyze the effect of weight loss induced by Roux-en-Y gastric bypass (RYGBP) on TSH and thyroid hormone (TH) levels. Methods: TSH, free thyroxine (fT4) and total triiodothyronine (T3) levels were analyzed before and 12 months after RYGBP in patients with grade III or grade II obesity with co-morbidities. Subjects taking TH and/or with positive antithyroid antibodies and/or with overt hypothyroidism were excluded. Results: 72 subjects (62F/10M), with mean age 39.6±9.8 years and mean BMI 53.0±10.4 kg/m² were studied. The prevalence of SH before RYGBP was 25% (n=18). There was a significant post-surgical decrease in BMI in the whole population, as well as in SH patients. In the SH group and normal TSH group, there was a decrease in TSH and T3, but not in fT4. TSH was not correlated with initial BMI or percent change in BMI. TSH concentrations reached normal values in all SH patients after RYGBP. Conclusion: Our data confirm that severe obesity is associated with increased TSH. The decrease in TSH was independent of BMI, but occurred in all SH patients. A putative effect of weight reduction on the improvement of SH in all patients may be an additional benefit of bariatric surgery.     

A new approach to the evaluation of hyperphosphatemia in chronic kidney disease

AIMS: Hyperphosphoremia, main contributor to cardiovascular calcifications, has a major impact on the morbidity and mortality of chronic renal failure (CRF) patients. Phosphate binders and dietary phosphate limitation are not effective enough to abolish hyperphosphoremia-induced cardiovascular abnormalities, therefore, the identification of other and more timely approaches for serum phosphorous reduction is necessary. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000 - 1,800 ml), deserves attention as a marker for an earlier start of pharmacologic treatment for phosphorous removal. In ESRD patients under dialysis we have shown increased salivary phosphate closely to be related with serum phosphorous and interpreted as compensatory. This study evaluates salivary phosphate secretion in 77 nondialyzed CRF compared with healthy subjects and its relationship with renal function. METHODS: Saxon's test confirmed normal salivary function in patients and controls. Serum phosphorous, creatinine and GFR were also measured. RESULTS: Salivary phosphorous was significantly higher in CRF patients compared with controls: 38.60 mg/dl (range 12.20 - 95.60) vs 16.30 (10.30 - 27.10), p < 0.0001; serum phosphate was also significantly higher: 3.70 (2.10 - 6.80) vs 3.50 (2.3 4.6), p = 0.013. In CRF patients, salivary phosphorous positively correlated with serum phosphorous (r - 0.45, p < 0.0001) and with serum creatinine (r = 0.72, p < 0.0001), while negatively correlated with GFR (r = -0.72, p < 0.0001). CONCLUSIONS: The results of our study show also in CRF patients increased salivary phosphate secretion, which is related with renal function. On this basis the use of salivary phosphate secretion as a marker for an earlier start of the abnormal phosphate, metabolism pharmacologic treatment could be proposed.     

A clinical investigation of nocturnal polyuria in patients with nocturia: a diurnal variation in arginine vasopressin secretion and its relevance to mean blood pressure

PURPOSE: Nocturia is a common lower urinary condition in the elderly population and nocturnal polyuria is recognized as a major factor responsible for nocturia. A functional change in osmotic or nonosmotic control regarding the water-salt balance with aging may contribute to nocturnal polyuria. This study evaluated plasma arginine vasopressin secretion function in symptomatic patients with nocturnal polyuria and the impact of mean blood pressure on nocturnal polyuria. MATERIALS AND METHODS: A total of 29 patients who had nocturnal polyuria with 3 or more voids nightly and were screened with a 24-hour voiding diary were evaluated for their diurnal rhythm of arginine vasopressin secretion and osmotic response during a 5% hypertonic saline infusion test. Moreover, the relationships between the severity of nocturnal polyuria, ie the nocturnal polyuria index, or mean voided volume and mean blood pressure were assessed. RESULTS: Decreased nocturnal baseline arginine vasopressin according to plasma osmolality was found in 11 patients (38%) and the lack of a diurnal rhythm for arginine vasopressin secretion was observed in high proportion. A positive correlation between plasma arginine vasopressin and plasma osmolality was described with a linear regression line, expressed as arginine vasopressin = 0.27 (plasma osmolality - 285), resulting in a 2 to 3 mmol/l upward shift in the threshold of overall plasma arginine vasopressin secretion, although various osmotic sensitivities in arginine vasopressin secretion were observed in individuals. Mean voided volume increased during the night more than during the day (p <0.0001). A significant positive correlation of mean blood pressure with the mean daytime-to-nighttime single voided volume ratio and the nocturnal polyuria index was found (p = 0.0343 and 0.0109, respectively). CONCLUSIONS: An abnormal diurnal variation in arginine vasopressin secretion is highly prevalent in nocturnal polyuria. Moreover, it is relevant to mean blood pressure or sympathetic tone, such that the effects of nonosmotic control seem clinically implicated. Particular emphasis has been applied to the importance of considering comprehensive assessments not only of arginine vasopressin secretion function, but also of the possible underlying cardiovascular condition or hypertension in the treatment modality of nocturnal polyuria.