"Low T3 Syndrome" in Cirrhosis: Effect of β-Blockade

The so-called "low T3 syndrome" has frequently been reported in patients with cirrhosis. In this study, we aimed to determine whether administration of propranolol to such patients leads to further changes in plasma thyroid hormones, since it can affect their peripheral metabolism. Twenty cirrhotics (11 with ascites) whom we investigated showed no clinical evidence of thyroid dysfunction. The free fractions of plasma T3 and T4 (FT3, FT4) were determined by radioimmunoassay before and after the achievement of an effective beta-blockade by propranolol. The activity of the sympathetic nervous system also was evaluated by measuring plasma norepinephrine concentration. Under basal conditions, cirrhotics showed a reduced FT3 (2.45 +/- 0.11 SEM vs 3.55 +/- 0.16 pg/ml; p less than 0.001) and comparable FT4 (7.62 +/- 0.79 vs 9.2 +/- 0.42 pg/ml) and FT3/FT4 ratio (0.38 +/- 0.04 vs 0.42 +/- 0.013) with respect to healthy controls. When patients with ascites were considered apart, a reduction of FT4 was also found (6.78 +/- 0.74 pg/ml; p less than 0.01). In these patients, many of whom showed an increased plasma norepinephrine concentration, an inverse correlation between log FT3/FT4 and log plasma norepinephrine concentration was found (r = -0.79; p less than 0.01). The effective beta-blockade did not lead to significant changes in either FT3 or FT4 or FT3/FT4, whether the patients were considered as a whole (2.52 +/- 0.19 pg/ml, 9.3 +/- 1.41 pg/ml, and 0.36 +/- 0.04, respectively), or were split into groups according to the presence of ascites. When administered to cirrhotics, propranolol did not worsen thyroid hormone abnormalities, thus appearing to be safe in this respect. This may result from an impaired influence of the sympathoadrenergic system on thyroid hormone metabolism.     

Thyroid status in fifty patients with alcoholic cirrhosis.

Because the liver is of considerable importance in metabolism of thyroid hormones, plasma levels of thyroxine (T4), triiodotyronine (T3) with their unbound fractions (FT4 and FT3), reverse T3 (rT3)--an inactive isomer of T3-tyrotropin (TSH) and TSH response to thyrotropin releasing hormone (TRH; 250 micrograms i.V.) were determined by radioimmunoassays in 50 clinically euthyroid patients with alcoholic cirrhosis. T4 mean concentration (7.3 micrograms/dl) did not differ from normal values but T3 was decreased (101 vs 154 ng/dl; p less than 0.001) and was correlated with the degree of liver damage appreciated by a clinico-biological index. FT4 was elevated in patients (17.1 vs 13.1 pg/ml; p less than 0.02) although FT3 was slightly decreased (3.4 vs 4.5 pg/ml; p less than 0.10) with an increased FT4: FT3 ratio (7.0 vs 3.0; p less than 0.02). rT3 was elevated (592 vs 206 ng/100 ml; p less than 0.001) and correlated with FT4/FT3: rT3/T3 ratio (p less than 0.01) and with the severity of the cirrhosis. Basal TSH levels (3.3 microU/ml) and TSH responsiveness to TRH was normal though very scattered, and independant from T3 and T4 values. It may be concluded that: 1. euthyroidy in cirrhosis assessed by a normal responsiveness to TRH, results from a compensatory increase in FT4. 2. The low T3 and FT3 levels may proceed from an impairment of peripheral T4 in to T3 conversion with a deviation pathway towards rT3. 3. T3 and rT3 levels provide valuable index of the severity of the cirrhosis.     

Plasma thyrotropin, thyroxine, triiodothyronine, free thyroxine, free triiodothyronine, and cortisol levels in blind prepubertal boys

Findings on thyroid function in blind subjects are lacking. The aim of this study was to investigate the thyroid hormonal pattern in prepubertal blind subjects. Six healthy and 8 blind males, aged 7-10 yr, in Tanner stage one puberty, living at Institute "Martuscelli" for blind young subjects, Napoli, Italy, were studied. Each had a TRH (200 micrograms) test at 08:00 h after nocturnal rest. Plasma TSH, T4, T3, free T4(FT4), free T3(FT3) and cortisol (F) were measured by RIA. Our blind subjects show levels of TSH (basal values and absolute peak after TRH), T4, T3 and F normal but FT4 levels significantly higher than controls (39 pg/ml +/- 4.7 vs 12 +/- 0.6, p less than 0.001; 14 pg/ml +/- 1.3 vs 4.7 +/- 0.2, p less than 0.001, respectively). Our results, similar to those found in some patients with euthyroid hyperthyroxinemia, suggest that the prolonged inability to receive light signal could influence the metabolism of thyroid hormones and/or cause a tissue resistance to their action, even if this hypothesis must be verified by future more extensive investigations.     

Sex hormone-binding globulin in the diagnosis of peripheral tissue resistance to thyroid hormone: the value of changes after short term triiodothyronine administration

Thyroid hormone is one of several factors that modulate the level of sex hormone-binding globulin (SHBG) in serum. SHBG levels are usually elevated in thyrotoxicosis and have been reported to be normal in a few patients with generalized resistance to thyroid hormone (GRTH). This study was designed to determine whether basal serum SHBG levels or the SHBG response to short term T3 administration could be used as an index of thyroid hormone action and thus serve as a test for the evaluation of patients suspected of having peripheral tissue resistance to thyroid hormone. Serum SHBG, total T4, free T4 index (FT4I), total T3, and TSH levels were measured in 21 normal subjects, 28 hypothyroid patients, 20 thyrotoxic patients, and 10 patients with GRTH. Excluding patients with GRTH, serum basal SHBG values were correlated with FT4I values (r = 0.66; P less than 0.0001). Mean SHBG levels in the patients with GRTH [37.6 +/- 16.2 (+/- SD) nmol/L] were not significantly different from those in the normal subjects (35.1 +/- 19.3 nmol/L) or hypothyroid patients (26.3 +/- 17.1 nmol/L), but were significantly lower than those in the thyrotoxic group (64.7 +/- 19.2 nmol/L; P less than 0.001). All 10 patients with GRTH had basal SHBG values in the normal range, but 7 of 20 (35%) thyrotoxic patients also had normal basal SHBG values. T3 was given orally for three sequential 3-day periods at doses of 50, 100, and 200 micrograms daily to 7 normal subjects, 11 hypothyroid and 3 thyrotoxic patients, and all 10 patients with GRTH. The serum SHBG concentration was measured on the last day at each dosage level. During T3 administration, SHBG levels increased in all individuals with normal tissue responsiveness. The increase above the basal value (delta SHBG) at each T3 dose was similar in normal, hypothyroid, and thyrotoxic individuals (non-resistant subjects). After administration of 50 micrograms T3 daily, the mean delta SHBG level was decreased [-2.9 +/- 5.3 (+/- SD) nmol/L] in the resistant patients and increased (4.0 +/- 4.9 nmol/L; P less than 0.005) in the nonresistant subjects. After administration of 100 micrograms T3 daily, the mean delta SHBG was -4.5 +/- 6.8 nmol/L in the resistant patients and 8.6 +/- 5.1 nmol/L (P less than 0.0001) in the nonresistant subjects. Serum SHBG decreased by more than 2 nmol/L in 6 of 10 (60%) resistant patients, but in no nonresistant subject.(ABSTRACT TRUNCATED AT 400 WORDS)     

Concentrations of somatomedin-C and triiodothyronine in patients with thyroid dysfunction and nonthyroidal illnesses

We studied the possibility of an association between serum somatomedin-C (Sm-C) and thyroid hormone concentrations. For this purpose 34 hyperthyroid patients, 39 patients with primary hypothyroidism, 36 patients with severe nonthyroidal illnesses (NTI), and 63 euthyroid healthy control subjects were examined. The mean concentration of serum dialyzable free triiodothyronine (FT3) was 26.6 +/- 15.4 pmol/l (+/- SD) in hyperthyroidism, 2.8 +/- 1.2 in hypothyroidism, 4.2 +/- 1.1 in NTI, and 5.3 +/- 0.7 in controls. The lowest mean concentration of serum Sm-C (10.1 +/- 3.0 nmol/l) was found in the NTI group and the highest in the hyperthyroid group (16.8 +/- 3.2): these concentrations differed significantly from the mean control level (12.2 +/- 2.2). In NTI patients the serum FT3 and T3 levels correlated significantly with the serum Sm-C levels (r = 0.63; p less than 0.001, r = 0.65; p less than 0.001, respectively). In hypothyroid patients there was a weak correlation between the serum FT3 and Sm-C levels (r = 0.36; p less than 0.05), but no correlations were found in hyperthyroid and healthy subjects. We conclude that the lowered Sm-C levels in NTI do not reflect a hypothyroid state, as normal Sm-C levels were found in hypothyroidism, and that impaired nutritional state of the patients is the most likely explanation for the association between Sm-C and FT3 (and T3) in NTI.     

Decreased thyroid gland volume in alcoholic cirrhosis of the liver

Thyroid function and thyroid gland volume were studied in 40 consecutive alcoholic patients with histologically proven cirrhosis of the liver, and compared with data obtained from 40 sex-, age-, and weight-matched normal subjects. Thyroid volume, measured ultrasonically, was significantly decreased in the patients with cirrhosis: median, 11 ml (range, 6-16 ml); compared to normal subjects: median, 20 ml (range, 10-31 ml) (P less than 0.001). Serum T3 concentrations were significantly reduced: median, 1.5 nmol/liter (range, 0.1-2.5 nmol/liter); compared to normal subjects: median, 2.2 nmol/liter (range, 1.5-2.8 nmol/liter) (P less than 0.001). The free T3 index was reduced accordingly. Serum TSH levels were significantly increased in cirrhosis: median, 2.1 microU/ml (range, 0.4-5.3 microU/ml); compared to normal subjects: median, 1.1 microU/ml (range, 0.3-3.8 microU/ml) (P less than 0.05). No significant differences were found in T3 resin uptake, free T4 index, or serum T4 levels between the two groups. No significant correlations could be demonstrated between thyroid gland volume and biochemical indices of liver function or thyroid function tests. It is suggested that alcohol might have a direct effect on the thyroid gland.     

Serum concentrations of adiponectin and resistin in hyperthyroid Graves' disease patients

This study was undertaken to determine whether serum adiponectin and resistin levels are influenced by hyperthyroidism and autoimmune factors and to find out whether their levels are dependent on the presence of ophthalmopathy. We measured serum concentrations of adiponectin and resistin in 76 patients (63 women, 13 men) with Graves' disease (GD) and compared them with levels of the control group which consisted of 30 healthy subjects. Patients were separated into two groups according to the presence or the absence of thyroid-associated ophthalmopathy (TAO). TAO (-) group consisted of 26 subjects without eye signs of GD and TAO (+) group included 50 subjects with ophthalmopathy. The latter group was further divided into 2 subgroups: with active TAO [26 patients, clinical activity score (CAS)> or =4] and with inactive TAO (24 patients, CAS<4). Groups did not differ in age, sex, body mass index (kg/m2) and smoking habits. Compared with euthyroid subjects, hyperthyroid GD patients had elevated mean serum adiponectin concentrations (19.96+/-4.97 microg/ml vs 15.01+/-3.99 microg/ml, p<0.001). However we did not observe any disparity between the TAO (-) and TAO (+) groups (20.60+/-5.06 microg/ml vs 19.63+/-4.94 microg/ml, p=ns). Comparing patients with a CAS> or =4 and patients with a CAS<4, we found similar mean serum concentrations of adiponectin (20.04+/-5.01 microg/ml vs 18.74+/-4.83 microg/ml, p=ns). Serum levels of resistin did not differ between the hyperthyroid patients and control subjects (13.11+/-4.26 ng/ml vs 12.82+/-4.75 ng/ml, p=ns). Serum resistin levels did not differ between TAO (+) and TAO (-) groups nor in patients with active and inactive TAO. Serum adiponectin correlated significantly with free T4 (FT4), free T3 (FT3), and TSH-R antibodies (TRAb) in GD patients (r=0.40, 0.41, and 0.37, respectively; p<0.001 for each). Serum resistin levels were not correlated with thyroid hormones and thyroid antibodies. The variables that in simple linear regression analyses were found to be correlated with serum adiponectin were then used in multiple regression analysis. In a model including adiponectin as dependent variable and FT4, FT3 and TRAb levels as independent variables, FT3 and TRAb remained as parameters independently related to adiponectin level (R2=0.35, p<0.001). CONCLUSIONS: Elevated serum adiponectin levels in GD patients are related to the degree of hyperthyroidism and autoimmune process. The presence and activity of ophthalmopathy is not a modifier of serum adiponectin and resistin.     

Fractional hepatic extraction of insulin in man: is it constant?

The present study was designed to compare insulin extraction by the liver following oral glucose administrations of different size, in order to evaluate insulin removal by the liver in relation to the insulin exposure, and to the amount of ingested glucose. Insulin secretion by the pancreas was estimated by the measurement of peripheral C-peptide levels, and insulin extraction by the liver by the analysis of peripheral C-peptide to insulin ratios and relations. Ten healthy subjects (5 males and 5 females), aged 16 to 66 yr, with normal bw, and without family history of diabetes mellitus were investigated by means of the administration, on alternate days, of 50 and 150 g oral glucose loads. After the 150 g oral glucose load plasma glucose levels were significantly higher than after the 50 g oral glucose administration: glucose incremental areas of 1.45 +/- 0.12 vs. 0.55 +/- 0.04 mmol/l X min, respectively (p less than 0.001). Similarly, insulin concentrations were significantly higher following 150 g than after 50 g glucose ingestion: insulin incremental areas of 0.52 +/- 0.09 vs. 0.20 +/- 0.04 nmol/l X min (p less than 0.001). Also C-peptide levels were higher after 150 vs. 50 g oral glucose load: C-peptide incremental areas of 1.85 +/- 0.41 vs. 0.64 +/- 0.13 nmol/l X min (p less than 0.01). C-peptide to insulin molar ratios were similar during the two glucose challenge, and averaged 5.25 +/- 0.42 vs. 5.08 +/- 0.50 after 50 and 150 g oral glucose loads, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum triiodothyronine sulfate in man measured by radioimmunoassay

In humans deiodination and perhaps glucuronidation are important pathways of thyroid hormone metabolism. In animals, sulfation plays an important role in T4 and especially in T3 metabolism, but little is known about sulfate conjugation of thyroid hormone in humans. In this study we used a specific T3 sulfate (T3S) RIA to address this question. Eight normal subjects were given oral T3 (1 microgram/day.kg BW) for 7 weeks. During the fifth week they also received propylthiouracil (PTU; four doses of 250 mg/day) for 2 days and during the seventh week iopanoic acid (IOP; 1 g/day) for 3 days. The mean pre-T3 serum iodothyronine values were: T4, 92 +/- 6 (+/- SE) nmol/L; rT3, 0.24 +/- 0.02 nmol/L; T3, 2.30 +/- 0.10 nmol/L; and T3S, less than 0.1 nmol/L (at or below the detection limit of the RIA). After 4 weeks of T3 administration the mean serum values were: T4, 39 +/- 6; rT3, 0.11 +/- 0.01; T3, 5.31 +/- 0.39; and T3S, 0.10 +/- 0.01 nmol/L. After 2 days of PTU administration, mean serum T4 increased to 48 +/- 7 (P less than 0.005), rT3 to 0.20 +/- 0.03 (P less than 0.025), and T3S to 0.13 +/- 0.01 nmol/L (P = NS), but serum T3 did not change (4.91 +/- 0.35 nmol/L). The effect of IOP was more pronounced; after its administration for 3 days the mean serum T4 was 49 +/- 8 (P less than 0.001), rT3 was 0.48 +/- 0.09 (P less than 0.005), and T3S was 0.29 +/- 0.04 nmol/L (P less than 0.005), and serum T3 decreased to 3.95 +/- 0.25 nmol/L (P less than 0.005). The T3S/T3 ratio was increased by PTU from 0.018 +/- 0.003 to 0.024 +/- 0.004 (P less than = NS) and by IOP to 0.055 +/- 0.007 (P less than 0.005). In conclusion, 1) serum T3S is virtually undetectable (less than 0.1 nmol/L) in normal subjects; 2) low serum T3S concentrations are detected in humans given T3; 3) serum T3S in T3-treated subjects is increased by inhibition of type I deiodinase activity with PTU and especially IOP; and 4) in comparison with previous estimates of the serum T3S/T3 ratio in rats, the low ratio in humans may indicate that sulfation is not an important mechanism of T3 metabolism in humans and/or the kinetics of plasma T3 and T3S differ in humans and rats.     

Serum free thyroid hormones in subclinical hypothyroidism

Serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations were measured in a group of 52 patients with subclinical hypothyroidism (SH) and in an equal group of age and sex-matched normal controls. SH was defined by normal total T4 (TT4) and total T3 (TT3) concentrations, normal FT4 and FT3 indices, raised TSH levels, in the absence of signs and symptoms of hypothyroidism. Serum FT4 levels averaged 6.1 +/- 1.6 pg/ml (mean +/- SD, p less than 0.001 vs controls), with values below lower normal limits in 33/52 patients; mean FT3 concentrations averaged 3.1 +/- 0.7 pg/ml (p less than 0.001 vs controls), with values below lower normal limits in 8/52 patients. The analysis of results by the Galen and Gambino predictive value model demonstrated a higher sensitivity, but a lower specificity of FT4 as compared to FT3 in the diagnosis of SH. These results indicate that FT4 should be measured in addition to TSH for the diagnosis of impending thyroid failure, thus showing that in many cases patients with so-called subclinical hypothyroidism are actually already mild hypothyroid.     

Autoimmune thyroid disease in the puerperium. Predictive value of thyroid enlargement and related hormonal changes occurring during pregnancy

The incidence of goiter detected during pregnancy and its significance as an indicator of autoimmune thyroid disease after delivery was investigated in a sample of 707 pregnant women (81% in their 2nd trimester of gestation). Goiter was detected in 106 subjects (15%). Blood T4, T3, TSH, free T4 index (FT4I), antimicrosomal antibodies (AMA) and urinary iodine excretion were measured in these women and in a control group of gravidas without goiter. These measurements were repeated at 1 and 3 months after delivery. Compared with controls during pregnancy, subjects with goiter had lower FT4I values (11.0 +/- 2.8 vs 9.0 +/- 1.8; p less than 0.01) and higher TSH values (2.9 +/- 0.6 microU/ml vs 4.2 +/- 2.1 microU/ml; p less than 0.01). In contrast, T4, T3, AMA and urinary iodine excretion values were similar in both groups. In subjects with goiter FT4I values increased over pregnancy levels at 1 month (11.2 +/- 2.0; p less than 0.05) and 3 months (14.0 +/- 3.0; p less than 0.05) after delivery; in 29% a biochemical hyperthyroidism (FT4I greater than 13.5) was detected. During the same period TSH values decreased significantly (1 month: 1.9 +/- 0.7 microU/ml; p less than 0.05; 3 months: 2.7 +/- 3.0 microU/ml; p less than 0.05). Frequency of positive AMA increased from 8.6% during pregnancy up to 32.1% in the post-delivery period (p less than 0.01). In the control group no variation in the FT4I, TSH or AMA were observed after delivery. These results indicate that goiter during pregnancy is common in Chilean gravidas and that it has predictive value for the appearance of autoimmune thyroid disease after delivery.     

Chronic administration of amiodarone and thyroid function: a follow-up study

In order to evaluate the effects of amiodarone on thyroid function in chronically treated patients, 43 consecutive patients, who had been taking a mean weekly dose of 1420 +/- 488 mg for more than 9 months (mean 16.5 months), were studied. In a first evaluation, three patients with hypothyroidism and two with hyperthyroidism were discovered. In the remaining 38 patients, mean T4 (131 +/- 38 nmol/L) and rT3 (0.85 +/- 0.3 nmol/L) levels were significantly higher than reference values (p less than 0.05 and p less than 0.001, respectively), and mean T3 levels (1.89 +/- 0.73 nmol/L) were significantly lower (p less than 0.001). Thirteen patients showed hyperresponsiveness to thyrotropin-releasing hormone (TRH) stimulation testing. In a second evaluation, performed 12 to 18 months later, two new cases of hypothyroidism were discovered. T3 levels showed significantly lower values (p less than 0.02) than in the first evaluation, whereas basal thyroid-stimulating hormone levels and levels 30 and 60 minutes after TRH stimulation were significantly higher than those in the first evaluation (p less than 0.001). Five new hyperresponders to TRH were found. In the present series, the progressive appearance of clinical thyroid dysfunction with an elevated total incidence (16%) is demonstrated. Moreover, a progressively high prevalence of hyperresponsiveness to TRH stimulation is shown. These findings indicate that chronic amiodarone administration may carry a high risk of thyroid dysfunction.     

Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children

OBJECTIVE: The effects of GH therapy on thyroid function among previous reports have shown remarkable discrepancies, probably due to differences in hormone assay methods, degree of purification of former pituitary-derived GH preparations, dosage schedules, diagnostic criteria, patient selection, duration of treatment and study design. These considerations motivated us to investigate whether and how GH replacement therapy changes serum thyroid hormone levels, including the much less studied rT3 levels, in a group of unequivocally GH-deficient children receiving long-term recombinant human GH therapy. PATIENTS AND DESIGN: Twenty clinically and biochemically euthyroid children were studied in two therapeutic conditions: on GH replacement therapy for at least 6 months and without GH replacement, either before GH was started or after GH was withdrawn for 30-60 days. Eight patients were on thyroxine replacement treatment and thyroxine doses were kept constant during the study. Blood was collected before and after 15, 20 and 60 minutes of TRH administration in both therapeutic conditions (with GH and without GH). MEASUREMENTS: Concentrations of thyroid hormone levels were determined only in sera obtained before TRH administration. FT4, T3 and TSH were measured by immunoflourimetric assays and rT2 was measured by immunoradioassay. RESULTS: Patients were classified into two groups, according to basal TSH levels: group I (TSH > 0.4 mU/l, n = 12) and group II (on thyroxine and TSH < 0.05 mU/l, n = 8). In both groups, serum FT4 levels decreased (17. 0 +/- 1.1 vs. 14.3 +/- 0.9 mU/l, P < 0.001, and 18.0 +/- 1.7 vs. 14. 2 +/- 1.7 mU/l, P < 0.01, respectively), serum T3 levels increased (1.8 +/- 0.1 vs. 2.4 +/- 0.2 nmol/l, P < 0.001, and 1.9 +/- 0.3 vs. 2.4 +/- 0.2 nmol/l, P < 0.05, respectively), and serum rT3 levels decreased (0.35 +/- 0.03 vs. 0.25 +/- 0.03 nmol/l, P < 0.01, and 0. 48 +/- 0.06 vs. 0.34 +/- 0.06 nmol/l, P < 0.01, respectively). Basal (3.2 +/- 0.50 vs. 2.6 +/- 0.72 mU/l, P = 0.28, paired t-test), TRH-stimulated peak TSH levels (13.9 +/- 5.3 vs. 15.9 +/- 8.0 mU/l, P = 0.35, paired t-test) and TRH-stimulated TSH secretion, expressed as area under the curve (609 +/- 97 vs. 499 +/- 53 mU/l.minutes-1, P = 0.15, paired t-test), remained unchanged during GH replacement in group I patients. Low serum FT4 and high serum T3 levels were observed in only one patient each, but low serum rT3 levels were found in six patients (four in group I and two in group II) during GH replacement. CONCLUSIONS: These results show that long-term GH replacement therapy in children with unequivocal GHD significantly decreases serum FT4 and rT3 levels and increases serum T3 levels; that these changes are independent of TSH and result from increased peripheral conversion of T4 to T3 and that GH replacement therapy in GH deficient children does not induce hypothyroidism, but simply reveals previously unrecognized cases whose serum FT4 values fall in the low range during GH replacement.     

THYROID FUNCTION IN PATIENTS WITH MYOTONIC DYSTROPHY

In order to investigate endocrine disturbances in patients with myotonic dystrophy (MD), 12 patients and 20 normal controls were studied. All patients were clinically euthyroid and there were no significant differences between circulating levels (mean +/- SD) of T4 (114.7 +/- 26.8 vs 129.9 +/- 28.3 nmol/l), FT4 (16.6 +/- 4.5 vs 18.4 +/- 3.8 pmol/l), T3 (1.61 +/- 0.29 vs 1.86 +/- 0.33 pmol/l), TSH (2.7 +/- 1.3 vs 2.4 +/- 1.4 mU/l), TBG (26.7 +/- 5.5 vs 27.6 +/- 4.9 mg/l), T4/T3 (84.3 +/- 18.4 vs 82.1 +/- 15.3), and FT4/FT3 (0.28 +/- 0.05 vs 0.33 +/- 0.08). Serum FT3 (4.3 +/- 1.4 pmol/l) in patients were significantly lower than those (5.3 +/- 0.9 pmol/l) in normal controls (P less than 0.02). Thyroidal 131I-uptakes (8.7 +/- 4.3%) in patients were significantly lower than those (25.8 +/- 7.4%) in controls (P less than 0.01). The mean maximal TSH responses following TRH stimulation were significantly less in patients with MD (11.4 +/- 4.5 vs 17.0 +/- 6.2 mU/l; P less than 0.02). Neither circulating thyroid microsomal nor thyroglobulin antibodies were detectable in the 11 patients tested. Serum thyroglobulin concentrations were within the normal range in all patients but one. In conclusion, it is suggested that normal levels of serum T4, T3, FT4, TSH, TBG, T4/T3 and FT4/FT3, slight but significant decrease of serum FT3, reduced TSH response to TRH and a decrease of thyroidal radioiodine uptake might be due to a slight functional failure of TSH secretion in patients with myotonic dystrophy.     

3,5-DIIODOTYROSINE AND THYRONINE IN THE URINE OF PATIENTS WITH CHRONIC RENAL DISEASE

Urinary 3,5-diiodotyrosine (DIT) and thyronine (T0) excretion was investigated in 18 patients with chronic renal disease. In accord with previous findings serum T4 and thyroid hormone binding proteins measured in 17 patients were in the low or normal range. Urinary albumin excretion was elevated in all 18 and T4 binding prealbumin (TBPA) in 15 of the 18. Urinary T0 excretion measured in 12 patients was also significantly lower than normal (mean +/- SD 4.4 +/- 2.6 vs 15.8 +/- 5.8 nmol/24 h renal vs normal 2 P less than 0.001). In contrast urinary DIT excretion was significantly elevated in renal patients compared with normal subjects (2.0 +/- 1.5 vs 0.75 +/- 0.41 nmol/24 h, respectively). Possible sources of the increased DIT are discussed.     

Thyroid function tests in ageing and their relation to associated nonthyroidal disease

Thyroid function tests of 179 euthyroid geriatric inpatients (83 +/- 6 yr) unaffected by acute diseases or malnutrition were investigated and compared with those of 76 ambulatory healthy younger subjects (42 +/- 13 yr). Elderly population was divided in three groups, respectively: group G I (n = 37, 65-78 yr), group G II (n = 64, 79-85 yr) and group G III (n = 78, over 85 yr). Severity-of-illness index of the patients was evaluated at entry in the study protocol. While total thyroxine (TT4), free triiodothyronine (FT3) and TSH levels remained unchanged, circulating total triiodothyronine (TT3) was significantly lower (113 +/- 32 vs 150 +/- 31 ng/dl, p less than 0.05) and free thyroxine (FT4) was significantly higher (12.4 +/- 2.7 vs 10.3 +/- 2.3 pg/ml, p less than 0.05) in aged people. Furthermore, TT3 decreased significantly from 130 +/- 36 in G I to 110 +/- 33 in G II and to 108 +/- 25 in G III (p less than 0.01), and FT4 increased progressively although not significantly in the same groups. A close correlation was found between TT3 and severity index in male observations only (r = -0.43, p less than 0.01), as well as between FT4 and severity index in both sexes (r = 0.51, p less than 0.001 for men, r = 0.21, p less than 0.01 for women). These data suggest that thyroid function tests have to be cautiously interpreted in a geriatric population, particularly in relation to the severity of the clinical state, and reference values should be determined for TT3 and FT4 in the ageing process.     

Thyroid function in patients with proteinuria and normal or increased serum creatinine concentration

The thyroid function of 13 patients with proteinuria and normal serum creatinine level (Group 1) and 15 patients with proteinuria and increased creatinine level (Group 2) was investigated. The daily urinary T41- and T3 excretion was much higher in Group 1 patients than in Group 2 patients (37.1 +/- 25.9 nmol T4 vs 17.5 +/- 8.7 nmol T4, 3.3 +/- 1.6 nmol T3 vs 1.1 +/- 0.8 nmol T3, respectively) and correlated in both groups with the protein loss. None of the patients suffered from hypothyroidism as a consequence of this hormone loss. Although the mean serum T4-, T3-, FT4-, FT3-, TBG- and TBPA concentrations in both groups of patients were within the normal range, the urinary hormone loss appeared to influence these values considerably. It was striking that the rT3 concentration in the patients with the highest hormone loss was frequently less than 0.08 nmol/l, the lower limit of detectability. The basal TSH levels in serum of the nephrotic patients were similar to those of normal individuals. The thyroid function of patients with proteinuria accompanied by retention of creatinine due to renal failure was more difficult to assess because different pathological mechanisms may exert their influence on the thyroidal hormone secretion as well as on the peripheral hormone metabolism.     

Early adaptation of thyrotropin and thyroglobulin secretion to experimentally decreased iodine supply in man.

Five healthy male volunteers (aged 25 to 28 years) were studied both after 4 weeks of treatment with 200 micrograms iodine/d orally (PO) and following experimental iodine depletion by treatment with 3 x 300 mg perchlorate/d PO over a 4-week period, in an attempt to better define the early adaptive responses to an alteration in iodine supply in thyroid function. Intrathyroidal iodine, serum triiodothyronine (T3), free T3 (FT3), thyroxine (T4), free T4 (FT4), reverse T3 (rT3), thyroxine-binding globulin (TBG), thyroglobulin (Tg), and thyrotropin (TSH) levels (10-minute sampling over 24 hours) were measured at the end of iodine administration and at the end of perchlorate treatment. Thyroid volume was determined by sonography, and iodine content was determined by fluorescence scintigraphy. TSH pulses were analyzed by computer-assisted programs. Comparing both experimental situations, perchlorate treatment significantly reduced intrathyroidal iodine concentration (4.0 +/- 1.3 to 3.0 +/- 1.2 nmol/mL, P less than .05), but thyroid volume and total serum T4, T3, FT3, and TBG levels were not altered. Mean 24-hour serum TSH levels (1.8 +/- 0.3 to 1.0 +/- 0.3 mU/L, P less than .001), amount of TSH secreted/pulse (0.5 +/- 0.1 to 0.3 +/- 0.1 mU/L, P less than .001), and FT4 levels (15.7 +/- 1.7 to 14.3 +/- 1.4 pmol/L, P less than .005) were significantly diminished, whereas Tg levels (18.6 +/- 10.0 to 35.1 +/- 14.0 ng/mL, P less than .01) were significantly increased. Thyroid-specific antibodies were normal and were not altered by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating soluble interleukin 2 receptor concentration is increased in both immunogenic and nonimmunogenic hyperthyroidism.

High serum concentration of soluble interleukin-2 receptor (sIL-2R) is considered a reliable marker of T lymphocyte activation. It has been recently reported that sIL-2R levels are increased in untreated Graves' disease. This finding has been interpreted as the consequence of an active autoimmune state, but the relevance of the thyroid function per se was not investigated. In the present study we assayed sIL-2R by ELISA in 20 normal subjects and in a series of patients with immunogenic (Graves' disease, GD) or nonimmunogenic (toxic adenoma, TA) hyperthyroidism. Significant increased concentrations of sIL-2R were found in 46 patients with untreated hyperthyroid GD (mean +/- SD: 1,683 +/- 1016 U/ml, vs 461 +/- 186 U/ml in normal controls, p less than 0.0001) and in 21 with untreated TA (1,111 +/- 617 U/ml, p less than 0.0001 vs normals). Restoration of the euthyroid state by antithyroid drugs or 131I administration was associated with a normalization of sIL-2R (516 +/- 174 U/ml in 38 patients with GD and 365 +/- 90 U/ml in 12 with TA; p = NS vs normals and p less than 0.001 vs the untreated state for both groups). A highly significant positive correlation between serum sIL-2R and free triiodothyronine (FT3) (r = 0.724, p less than 0.0001) or free thyroxine (FT4) (r = 0.698, p less than 0.0001) concentrations was found in combined sera obtained from all untreated and treated patients, irrespectively of the autoimmune or nonautoimmune nature of the underlying hyperthyroid disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glucagon-induced changes in plasma thyroid hormone concentrations in healthy dogs resemble "euthyroid sick syndrome"

We recently demonstrated that glucagon infusion induced a decline in T3 and a rise in rT3 in anesthetized dogs. These changes in T3 and rT3 may be attributed, at least in part, to anesthesia itself, since general anesthesia is known to cause lowering of T3 and an elevation in rT3 during the perioperative period. Therefore, to eliminate the contribution, if any, of anesthesia to these changes in T3 and rT3, we assessed plasma glucose, T3 resin uptake (T3RU), T4, free T4, T3 and rT3 concentrations following intravenous glucagon (0.5 mg) or normal saline (0.5 ml) administration at frequent intervals for 3 h in 6 conscious dogs fasted for 16 h. No significant alterations were noted in T4, free T4, and T3RU levels during either study. However, glucagon infusion alone induced a significant fall in T3 (0.33 +/- 0.06 in nmol/l vs -0.03 +/- 0.03 nmol/l with normal saline; p less than 0.01) and marked elevations in glucose (3.66 +/- 0.22 mmol/l vs 0.61 +/- 0.11 nmol/l with normal saline, p less than 0.001) and rT3 concentrations (0.11 +/- 0.02 nmol/l vs 0.005 nmol/l; p less than 0.001). Furthermore, the integrated responses of T3 and rT3 as assessed by cumulative changes and areas under the curves were markedly greater during glucagon infusion when compared with saline administration (p less than 0.01 for all comparisons). Since the elevations in levels of stress hormones known to ensue during anesthesia do not occur during a conscious resting state, we believe that hyperglucagonemia may be a major contributor of thyroid hormone alterations observed in several euthyroid sick states, not associated with stress, and may enhance these changes during euthyroid sick syndrome associated with stressful crises. Finally, these changes may be attributed to altered metabolism of iodothyronines in peripheral tissues as reflected by lowered T3/T4 and increased rT3/T4 ratios.