Defective thyroidal iodine concentration in protein-calorie malnutrition

Although protein-calorie malnutrition (PCM) is known to result in various abnormalities of thyroid function, the exact relationship between the two is not clearly understood. Therefore, the thyroid function of 10 men, 13-55 yr of age, with severe PCM was studied in a clinical research ward before and 3-4 months after protein-calorie repletion. Before repletion, all subjects had low serum T4 (mean +/- SEM, 5.1 +/- 0.5 micrograms/dl) and T3 (74 +/- 6 ng/dl) concentrations. Eight subjects were chemically euthyroid, and their free T4 (1.5 +/- 0.1 ng/dl) and serum TSH (2.9 +/- 1.4 microU/ml) values were normal. Two subjects were chemically hypothyroid, with low free T4 values and high serum TSH values. After repletion, the 8 euthyroid subjects had significant increases in serum T4 (P less than 0.01) and T3 (P less than 0.005), but TSH did not change. Serum T4 and T3 were still lower (P less than 0.05-0.001) and TSH higher (P less than 0.01) than in 28 normal men of comparable age coming from the same area. After repletion, values remained unchanged in the 2 hypothyroid subjects, except for moderate increases in serum T3 and slight decreases in TSH. In all PCM subjects, values of thyroidal exchangeable iodine (23.1 +/- 7 vs. 42.9 +/- 8 mg; P less than 0.02), estimated thyroidal I per g wet wt (1.05 +/- 0.3 vs. 1.99 +/- 0.36 mg; P less than 0.02), and thyroidal iodide clearance (13.8 +/- 1.6 vs. 19.4 +/- 1.3 ml/min; P less than 0.002) were lower before repletion than after; the protein-bound 131I level (72 h; 0.27% vs. 0.08 dose/liter; P less than 0.05) was higher, but thyroid hormone secretion rates (200 +/- 49 vs. 153 +/- 25 micrograms/day) were not significantly different. Thyroid iodide clearance was lower even though plasma inorganic iodine (6.3 +/- vs. 12.5 +/- 3 micrograms/liter; P less than 0.05) and daily urinary iodine excretion (158 +/- 43 vs. 395 +/- 62 micrograms; P less than 0.01) were lower before than after repletion. In 2 PCM euthyroid subjects, baseline thyroid 131I uptake was lower before than after repletion, and the magnitude of the increase after TSH (10 U, im) stimulation was greater when the malnourished state improved. TSH increased concentrations of serum T4 and T3 both before and after protein repletion. After repletion, one hypothyroid patient failed to respond to TSH; the other had a small increase in 131I uptake but not in serum T4 or T3. The results indicate defective thyroid iodine concentration in human PCM, but adequate hormone secretion. This situation leads to depletion of thyroid iodine stores. This alteration, if extreme, might result in hypothyroidism. Adequate protein-calorie intake tends to reverse these abnormalities.     

Decreased nocturnal surge of thyrotropin in nonthyroidal illness

To evaluate the regulation of TSH secretion in nonthyroidal illness (NTI) we studied the nocturnal TSH surge in 11 healthy controls and 26 NTI patients; none of the patients was on medication known to interfere with TSH secretion. The presence of a nocturnal TSH surge was defined as a mean nighttime TSH (the mean of 5 samples taken hourly from 0000-0400 h) significantly greater than the mean daytime TSH (the mean of 5 samples taken from 1500-1900 h). A nocturnal TSH surge was present in 11 of 26 NTI patients and in 11 of 11 controls (P less than 0.01). Both the absolute (0.3 +/- 0.1 vs. 1.0 +/- 0.2 mU/L; P less than 0.01) and relative (11 +/- 6% vs. 71 +/- 12%; P less than 0.001) nocturnal TSH surges were lower in NTI patients than in controls. NTI patients had lower plasma T3 (1.11 +/- 0.08 vs. 1.84 +/- 0.11 nmol/L; P less than 0.001) and higher plasma rT3 (0.81 +/- 0.24 vs. 0.23 +/- 0.01 nmol/L; P less than 0.001) concentrations than controls, but T4, FT4, and TSH values were similar in both groups. No differences were found between the 15 NTI patients without nocturnal TSH surge and the 11 patients with a nocturnal TSH surge in sex distribution, age, caloric intake, or plasma T4 and T3, but hospital mortality was slightly, although not significantly, higher in those with an absent nocturnal TSH surge. An absent nocturnal TSH surge occurred in 2 of 2 patients with a low TSH (less than 0.4 mU/L), in 11 of 20 patients with a normal TSH (0.4-4.0 mU/L), and in 2 of 4 patients with a high TSH (greater than 4.0 mU/L). Pituitary TSH responsiveness to TRH was similar in patients with or without a nocturnal TSH surge. We conclude that NTI is frequently associated with a decreased nocturnal TSH surge. This phenomenon is not related to ambient plasma T4, T3, or TSH concentrations or pituitary TSH responsiveness to TRH. A decreased nocturnal TSH surge appears to be one of the features of the sick euthyroid syndrome and is probably related to hypothalamic dysregulation.     

The effect of fasting on thyroidal T4-5' monodeiodinating activity in mice

Complete fasting induces a significant decrease of serum T3 and a fall in TSH in rodents and man. To evaluate the effect of starvation on thyroidal T4 5'monodeiodinating activity, in vitro conversion of T4 to T3 by thyroid and liver homogenate from one to three days fasted mice was compared with homogenates from control mice on animal chow. 5'monodeiodinating activity was significantly lower in thyroid homogenates of fasted mice than in those of chow-fed control [100 +/- 5.0 and 92 +/- 5.0 pmol T3.(mg protein)-1.h-1 at 48 and 72 h fasting, respectively, vs 132 +/- 5.0 pmol T3.(mg protein)-1.h-1 of fed control, p less than 0.01]. A similar decrease in thyroidal 5'monodeiodinating activity was seen in the liver. The decrease in thyroidal 5'monodeiodinating activity induced by fasting was not reversed by the supplementation of homogenates with the thiol-protecting agent, dithiothreitol (0.2-4.0 mmol/l). Physiological replacement of T4, 0.58 nmol.(100 g)-1.day-1, did not alter the effect of starvation in either the thyroid or liver. TSH (0.02 IU/day) injection, on the other hand, stimulated 5'monodeiodinating activity in homogenates of thyroids from 3-days fasted mice which was no different from TSH-treated fed control. It is postulated that starvation-induced decrease in thyroidal T4 to T3 converting activity may play a role, together with decreased hepatic 5'monodeiodinating activity, in fasting-induced low serum T3 in mice.     

Disturbance of the fetal thyroid hormone state has long-term consequences for treatment of thyroidal and central congenital hypothyroidism

BACKGROUND: During T(4) supplementation of patients with thyroidal (primary) congenital hypothyroidism (CH) TSH concentrations are frequently elevated despite free T(4) (FT(4)) concentrations being well within the reference range. To examine the thyroid's regulatory system, we analyzed thyroid function determinants in children with congenital and acquired thyroid disorders and in controls. METHODS: Retrospectively, plasma FT(4), TSH, and T(3) concentrations were analyzed in T(4)-supplemented children aged 0.5-20.0 yr with thyroidal CH, central (secondary or tertiary) CH, or autoimmune thyroid disease and in control children with type 1 diabetes mellitus. RESULTS: When TSH was within the reference range (0.4-4.0 mU/liter), mean FT(4) in thyroidal CH [1.65 ng/dl; 95% confidence interval (CI), 1.62-1.67] was significantly higher than in autoimmune thyroid disease (1.15 ng/dl; 95% CI, 1.11-1.19) and diabetes (1.08 ng/dl; 95% CI, 1.06-1.10). In central CH, when TSH was less than or equal to 0.02 mU/liter, mean FT(4) was 1.27 ng/dl (95% CI, 1.24-1.29). When FT(4) was within the reference range (0.78-1.79 ng/dl), 43% of the TSH measurements in thyroidal CH were more than 4.0 mU/liter, compared with 18% in autoimmune thyroid disease and 0% in type 1 diabetes mellitus; in central CH, 95% of TSH measurements were less than 0.4 mU/liter. CONCLUSIONS: In T(4)-supplemented patients with thyroidal CH, when TSH concentrations are established within the reference range, FT(4) concentrations tend to be elevated, and vice versa. Because this phenomenon could not be observed in acquired thyroidal hypothyroidism, we hypothesize that a pre- and/or perinatal hypothyroid state shifts the setpoint of the thyroid's regulatory system. In central CH, when FT(4) concentrations are established within the reference range, the pituitary secretes only minute amounts of TSH. For monitoring T(4) supplementation, reference ranges for FT(4) and TSH should be adapted to the etiology of hypothyroidism.     

Plasma norepinephrine kinetics, dopamine-beta-hydroxylase, and chromogranin-A, in hypothyroid patients before and following replacement therapy

Whether the increased plasma norepinephrine level reported in hypothyroidism is the result of impaired norepinephrine (NE) clearance or increased NE release by nerve terminals is unknown. We, therefore, measured plasma NE levels and clearance in 11 hypothyroid patients before [T4 index, 41.2 +/- 7.7 nmol/L (mean +/- SEM); TSH, 71.4 +/- 23.0 mU/L] and 4 +/- 0.5 months after thyroid replacement (T4 index, 136.4 +/- 24.4 nmol/L; TSH, 3.2 +/- 1.2 mU/L) and in 8 healthy volunteers. Plasma dopamine-beta-hydroxylase and chromogranin-A, which are coreleased with NE by sympathetic nerve endings, were also measured. Plasma NE was higher in the hypothyroid (2.37 +/- 0.24 nmol/L) than in the euthyroid state (1.86 +/- 0.24 nmol/L; P less than 0.02) or in the controls (1.87 +/- 0.27 nmol/L). Plasma clearance of NE, however, was not affected after thyroid replacement (hypothyroid, 2.08 +/- 0.31 L/min; euthyroid, 1.94 +/- 0.21 L/min; controls, 1.86 +/- 0.15 L/min). There was no significant change in plasma dopamine-beta-hydroxylase (hypothyroid, 720 +/- 139 nmol/mL.h; euthyroid, 553 +/- 97 nmol/mL.h) or plasma chromogranin-A (hypothyroid, 48.9 +/- 7.1 ng/mL; euthyroid, 42.9 +/- 5.3 ng/mL) after thyroid replacement. We conclude that the increased plasma NE in hypothyroid patients is not due to a change in plasma clearance, but is more likely secondary to increased NE release.     

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.     

Alterations of serum concentrations of thyroid hormones and sex hormone-binding globulin, nuclear binding of tri-iodothyronine and thyroid hormone-stimulated cellular uptake of oxygen and glucose in mononuclear blood cells from patients with non-thyroidal illness

Nuclear tri-iodothyronine (T3) binding and thyroid hormone-stimulated oxygen consumption and glucose uptake were examined in mononuclear blood cells from patients with non-thyroidal illness (NTI) in which serum T3 was significantly (P less than 0.05) depressed (0.62 +/- 0.12 (S.D.) nmol/l) compared with healthy control subjects (1.45 +/- 0.30 nmol/l). Neither serum TSH nor sex hormone-binding globulin differed from that of the control group. Nuclear T3 binding capacity was increased (P less than 0.05) in patients with NTI (10.1 +/- 3.0 fmol/100 micrograms DNA) compared with controls (2.5 +/- 0.9 fmol/100 micrograms DNA). Unstimulated glucose uptake was increased in cells from patients with NTI (2.03 +/- 0.49 mmol/l per mg DNA per h, P less than 0.01) compared with controls (1.13 +/- 0.20 mmol/l per mg DNA per h). Thyroxine-stimulated glucose uptake (stimulated glucose uptake--unstimulated glucose uptake) was increased in cells from patients with NTI (2.06 +/- 1.67 mmol/l per mg DNA per h, P less than 0.01) compared with controls (0.26 +/- 0.12 mmol/l per mg DNA per h), and T3-stimulated glucose uptake was also increased in cells from patients with NTI (1.34 +/- 0.81 mmol/l per mg DNA per h, P less than 0.05) compared with controls (0.24 +/- 0.10 mmol/l per mg DNA per h). In contrast, neither unstimulated nor thyroid hormone-stimulated oxygen consumption differed. We conclude that both increased nuclear T3 binding and increased thyroid hormone-induced glucose uptake may represent counter-regulatory mechanisms which tend to maintain intracellular homeostasis.     

Pulsatile secretion of thyrotropin during fasting: a decrease of thyrotropin pulse amplitude

The effect of fasting on circadian and pulsatile TSH secretion was investigated in eight healthy subjects (four men and four women in the follicular phase). Each subject was studied twice, once during 24 h with normal food intake and once during the last 24 h of a 60-h fast. Blood was sampled every 10 min during 24 h for measurement of TSH by a sensitive immunoradiometric assay. Fasting induced a decrease in plasma T3 [1.73 +/- 0.06 vs. 1.36 +/- 0.04 nmol/L; P less than 0.01 (mean +/- SE), control period vs. fasting] and thyroglobulin (52 +/- 8 vs. 35 +/- 7 pmol/L; P less than 0.001) and an increase in plasma rT3 (0.30 +/- 0.06 vs. 0.44 +/- 0.09 nmol/L; P less than 0.02). Plasma T4, thyroid hormone binding index, and free T4 were not statistically different in both periods. The mean plasma 24-h TSH concentration was lower during fasting than in the control period (2.0 +/- 0.3 vs. 1.0 +/- 0.2 mU/L; P less than 0.005). This was associated with a decrease in mean TSH pulse amplitude during fasting (Desade program: 0.6 +/- 0.1 vs. 0.3 +/- 0.1 mU/L; P less than 0.01; Cluster program: 0.5 +/- 0.1 vs. 0.2 +/- 0.1 mU/L; P less than 0.05), whereas TSH pulse frequency during fasting was unchanged (Desade program: 8.4 +/- 0.9 vs. 9.8 +/- 0.8 pulses/24 h; Cluster program: 9.5 +/- 0.5 vs. 7.9 +/- 0.9 pulses/24 h). There was a highly significant correlation between the mean 24-h TSH concentration and the mean TSH pulse amplitude during both the control period and fasting. Although the decrease in TSH concentration during fasting was evident over 24 h, fasting especially decreased the absolute (1.3 +/- 0.3 vs. 0.4 +/- 0.1 mU/L, P less than 0.02) and the relative (101 +/- 18% vs. 40 +/- 14%; P less than 0.02) nocturnal TSH surge (mean TSH 0000-0400 h vs. mean TSH 1500-1900 h). The decreased nocturnal TSH surge during fasting was associated with a significantly decreased TSH pulse amplitude, but with an unaltered number of TSH pulses between 2000-0400 h. In conclusion, fasting decreases 24-h TSH secretion and the nocturnal TSH surge in the absence of a change in plasma T4 concentration. This is associated with a decreased TSH pulse amplitude, whereas TSH pulse frequency remains unchanged.     

Secretion of thyrotropin with reduced concanavalin-A-binding activity in patients with severe nonthyroid illness

Patients with nonthyroid illness (NTI) often have reduced serum T3, free T3, T4, and free T4 concentrations. Paradoxically, serum TSH is usually in the normal range. The data suggest a diagnosis of hypothalamic hypothyroidism, in which TSH may have reduced biological activity because TRH, which is necessary for key steps in the glycosylation of TSH, is deficient. To study the glycosylation of TSH in patients with NTI, we measured the serum TSH concentration in 36 such patients hospitalized on our intensive care units and compared the results with those from a group of 18 normal subjects. Serum TSH was measured in 2 assays: 1) a sensitive TSH RIA of unextracted serum (TSH-RIA) and 2) a RIA of serum TSH after its extraction with Concanavalin-A (Con-A), a lectin which binds glycoproteins containing mannose residues in their oligosaccharide side-chains (TSH-Con-A). The ratio of TSH-Con-A to TSH-RIA was significantly reduced in the NTI patients [0.61 +/- 0.03 (+/- SE) vs. 0.89 +/- 0.05 in the normal subjects] due to reduced binding of the TSH to the Con-A. This change was not dependent on the extent of the abnormalities of thyroid hormone levels. The data suggest that the TSH secreted in NTI has altered glycosylation which is associated with reduced biological activity. This finding may explain in part the low serum T4 level in NTI patients in the face of an apparently normal immunoreactive TSH level.     

Thyrotropin action is impaired in the thyroid gland of old rats.

Aging in rats is characterized by low plasma concentrations of thyroid hormones with unchanged levels of TSH, suggesting an altered TSH action in addition to the impaired regulation of TSH secretion. To evaluate TSH action we determined TSH binding to thyroid membranes of young and old male rats (3-4 and 24-26 months of age), as well as the activity of adenylate cyclase in basal and stimulated conditions. Saturation analyses of [125I]-bTSH to thyroid membranes in the presence of increasing quantities of unlabelled bTSH (0.03-100 mU) show two types of binding sites, one of high affinity (Ka 1.5 10(9) mol l-1) the other of lower affinity (Ka 1.2 10(8) mol l-1), which are similar in both age groups. The number of TSH binding sites of high affinity is less in old rats than in young rats (7.6 +/- 0.9 vs 14.8 +/- 1.1 TSH mU/mg protein, N = 11 and 10 respectively, p less than 0.001), whereas the number of binding sites of low affinity is not significantly different (76.0 +/- 8.2 vs 99.1 +/- 9.0 TSH mU/mg protein). The activity of adenylate cyclase determined in basal conditions is similar in both old and young rats (1.11 +/- 0.12 vs 1.04 +/- 0.9 nmol cAMP/2 h x mg/protein). TSH (10 mU) induced a significant increase in cAMP formation with the thyroid membranes from young rats but not with those from old rats. In contrast, the stimulation of cAMP formation by GTP (2 mmol/l) or forskolin (10 mmol/l), two direct stimulators of adenylate cyclase, is similar in both groups of rats (200% and 250%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of thyroid status and paraventricular area lesions on the release of thyrotropin-releasing hormone and catecholamines into hypophysial portal blood

TRH is a potent stimulator of pituitary TSH release, but its function in the physiological regulation of thyroid activity is still controversial. The purpose of the present study was to investigate TRH and catecholamine secretion into hypophysial portal blood of hypothyroid and hyperthyroid rats, and in rats bearing paraventricular area lesions. Male rats were made hypothyroid with methimazole (0.05% in drinking water) or hyperthyroid by daily injections with T4 (10 micrograms/100 g BW). Untreated male rats served as euthyroid controls. On day 8 of treatment they were anesthetized to collect peripheral and hypophysial stalk blood. In euthyroid, hypothyroid and hyperthyroid rats plasma T3 was 1.21 +/- 0.04, 0.60 +/- 0.04, and 7.54 +/- 0.33 nmol/liter, plasma T4 50 +/- 3, 16 +/- 2, and 609 +/- 74 nmol/liter, and plasma TSH 1.58 +/- 0.29, 8.79 +/- 1.30, and 0.44 +/- 0.03 ng RP-2/ml, respectively. Compared with controls, hyperthyroidism reduced hypothalamic TRH release (0.8 +/- 0.1 vs. 1.5 +/- 0.2 ng/h) but was without effect on catecholamine release. Hypothyroidism did not alter TRH release, but the release of dopamine increased 2-fold and that of noradrenaline decreased by 20%. Hypothalamic TRH content was not affected by the thyroid status, but dopamine content in the hypothalamus decreased by 25% in hypothyroid rats. Twelve days after placement of bilateral electrolytic lesions in the paraventricular area plasma thyroid hormones and TSH levels were lower than in control rats (T3: 0.82 +/- 0.05 vs. 1.49 +/- 0.07 nmol/liter; T4: 32 +/- 4 vs. 66 +/- 3 nmol/liter; TSH: 1.08 +/- 0.17 vs. 3.31 +/- 0.82 ng/ml). TRH release in stalk blood in rats with lesions was 15% of that of controls, whereas dopamine and adrenaline release had increased by 50% and 40%, respectively. These results suggest that part of the feedback action of thyroid hormones is exerted at the level of the hypothalamus. Furthermore, TRH seems an important drive for normal TSH secretion by the anterior pituitary gland, and thyroid hormones seem to affect the hypothalamic release of catecholamines.     

Aging alters the activity of 5'-deiodinase in the adenohypophysis, thyroid gland, and liver of the male rat

Aging is characterized by a decreased secretion of thyroid hormones in rats associated with unchanged plasma TSH suggestive of impairments in the hypothalamo-pituitary-thyroid axis. Since it is known that pituitary T3 is more determinant on TSH secretion than plasma T3, we measured in young (4 months) and old (26 months) male rats the concentration of T3 in the anterior pituitary gland and found that it was similar in young and old animals despite the low circulating levels of thyroid hormones. This was suggestive of age-related differences in the intrapituitary T4 to T3 conversion. We therefore determined the activity of 5'-deiodinase (5'-D, type I and type II) in the adenohypophysis and investigated possible age-related changes in this enzyme activity in peripheral tissues by its determination in the thyroid gland and liver (type I) of young and old rats. Intrapituitary 5'-D activity was increased in old compared to young rats (type I 5'-D: 4.59 +/- 0.13 vs. 2.92 +/- 0.33 pmol rT3/h x mg protein; type II: 0.54 +/- 0.5 vs. 0.21 +/- 0.03 pmol rT3/h x mg protein; P less than 0.001). In contrast, in the thyroid gland and in the liver, type I 5'-D was reduced with age (4.7 +/- 0.6 vs. 7.4 +/- 0.8 and 3.1 +/- 0.4 vs. 5.6 +/- 0.5 nmol rT3/h x mg protein, respectively; P less than 0.01). These data are illustrative of age-related changes in the activity of 5'-D, different according to the tissues in agreement with the known tissue-specific regulation of the 5'-Ds. The reduced activity of 5'-D in the thyroid and liver of old rats is indicative of an impaired thyroid hormones disposal in peripheral tissues with age. In contrast, in the adenohypophysis of old rats, the increase in the activity of 5'-D is similar to that reported in hypothyroid animals and suggests the development with age of an adaptative mechanism in the presence of low circulating thyroid hormones; this mechanism leads to unchanged intrapituitary concentration of T3 and consequently to unaltered plasma levels of TSH in old rats.     

Fatty acid induced changes in circulating total and free thyroid hormones: in vivo effects and methodological artefacts

Elevated levels of nonesterified fatty acids (NEFA) are frequently found in acute illnesses, and they may contribute to changes in serum thyroid hormone concentrations in nonthyroidal illnesses (NTI) by displacing protein bound hormones. We therefore examined the effects of low and raised plasma NEFA levels on circulating total and free thyroxine (TT4 and FT4) and triiodothyronine (TT3 and FT3) concentrations, the Free T4 Index (FT4I) and TSH, in a randomized crossover study in 10 normal subjects. Subjects ate either a high carbohydrate breakfast (low NEFA protocol) or a high fat breakfast followed by an iv injection of 1000 u heparin (high NEFA protocol). Possible biological effects of changes in FT4 and FT3 were evaluated by a 200 micrograms iv TRH test. Free T4 and T3 were measured by a direct analogue method (AFT4 and AFT3). In a similar high NEFA study, but without TRH, FT4 was also measured by equilibrium dialysis (DFT4) and a 2-step RIA method (2-step FT4). Acute elevations of plasma NEFA from 0.67 +/- 0.08 mmol/L to a peak of 2.6 +/- 0.54 mmol/L resulted in a prompt reciprocal fall of mean TT4 (-8.7%, p less than 0.01), AFT4 (-30%, p less than 0.005) and TT3 (-11.5%, p less than 0.01) and AFT3 (-16%, p less than 0.005); DFT4 rose significantly from 23.7 +/- 1.9 pmol/L to 33.0 +/- 3.7 pmol/L (+39%, p less than 0.025) and 2-step FT4 rose by 16% (p less than 0.05). TSH levels declined consistently from 3.3 +/- 0.5 mIU/L to 2.6 +/- 0.4 mIU/L (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Plasma leptin concentrations in relation to sick euthyroid syndrome in elderly patients with nonthyroidal illnesses

BACKGROUND: Leptin, the ob gene product, seems to be involved in regulating energy expenditure in humans, but its role in the pathophysiology of the energy imbalance in chronically ill patients is largely unknown. OBJECTIVE: To evaluate plasma leptin concentrations and thyroid function in elderly patients with nonthyroidal illnesses (NTI). METHODS: Sixty-four NTI elderly patients (75.0 +/- 6.3 years, 27 males and 37 females) and 21 age- and sex-matched healthy controls (73.0 +/- 5.5 years, 9 males and 12 females) were enrolled in the study. In all subjects tri-iodothyronine (T(3)), thyroxine (T(4)), reverse T(3) (rT(3)), free T(3) (fT(3)), free T(4) (fT(4)), TSH, and plasma leptin concentrations were measured. Nutritional status was also evaluated in all subjects studied by the measurement of body mass index (BMI), lymphocytes, serum iron, hemoglobin, plasma albumin, transferrin and total cholesterol. RESULTS: The data on thyroid hormones enabled us to identify three groups: group A, subjects (15 patients) with T(3) and fT(3) levels comparable to those of controls; group B, subjects (25 patients) with T(3) and fT(3) levels lower than controls and rT(3) levels comparable to those of controls; group C, subjects (24 patients) with T(3) and fT(3) levels lower than those of controls and high rT(3) levels. The patients of group C showed lower plasma leptin levels than the controls, 6.6 (5.5-14.2) and 16.3 (7.2-23.7) ng/ml (median with interquartile range in parentheses, p < 0.05), respectively. Females also showed higher plasma leptin levels than males in the controls, group A and group B, but not in group C. Moreover, plasma leptin concentrations were directly correlated to BMI in all the groups studied, while a negative correlation between leptin and rT(3) was detectable in group C (r = -0.44, p < 0.05), also after adjusting for BMI and sex. CONCLUSIONS: The concurrence of modifications in plasma leptin and thyroid hormones concentrations found in elderly NTI patients with a sick euthyroid syndrome could reflect a particular neuroendocrine status, leading to a reduction in the catabolic processes in the course of chronic diseases.     

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.     

Decreased sensitivity to alpha-adrenergic stimulation in hypothyroid patients

Nine hypothyroid patients had blood pressure and pulse rate responses to the alpha-adrenergic agonist phenylephrine measured before [T4 index, 45.045 +/- 9.009 nmol/L (mean +/- SEM); TSH, 57.1 +/- 23.6 mU/L] and after 4 +/- 0.5 months of thyroid replacement therapy (T4 index, 141.570 +/- 29.601 nmol/L; TSH, 2.6 +/- 1.0 mU/L). Hypothyroid patients had a smaller blood pressure increment and heart rate decrement at both 66.7 and 100 micrograms/min infusion rates of phenylephrine. Furthermore, the slope of the dose-response curves for systolic (2.06 +/- 0.22 vs. 1.32 +/- 0.19; P less than 0.01) and diastolic (1.04 +/- 0.18 vs. 0.62 +/- 0.08; P less than 0.01) blood pressures were significantly greater after thyroid replacement therapy. Pulse rate changes remained proportional to blood pressure changes in hypothyroid patients, so there was no change in baroreflex sensitivity. Plasma norepinephrine levels were higher before than after thyroid replacement (2.41 +/- 0.28 vs. 1.82 +/- 0.29 nmol/L, respectively; P less than 0.01). Thus, hypothyroid patients have diminished pressor sensitivity to an alpha-adrenergic agonist and increased plasma levels of the alpha-adrenergic neutrotransmitter norepinephrine.     

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.     

Effects of phenobarbital on hypothalamic-pituitary-thyroid axis in the rat

It has been reported that phenobarbital (PB) increases the peripheral clearance of T4 and T3 and decreases serum T4 and T3 concentrations in the rat, but serum TSH remains unchanged. To explore a possible direct effect of PB on TSH secretion at the hypothalamic-pituitary level, adult male rats were given PB 100 mg/kg or vehicle IP for 10 days. No difference in their thyroid weights was observed. In the PB-treated group serum T4 was decreased (PB, 3 +/- 0.2 micrograms/dl vs. control, 3.8 +/- 0.1 micrograms/dl, mean +/- SE, p less than .002), as was serum T3 (PB, 51 +/- 6 ng/dl vs. control, 70 +/- 5 ng/dl, p less than .05), but serum TSH remained unchanged. Pituitary TSH and hypothalamic TRH contents also were unchanged. Further studies were carried out similarly in the thyroidectomized hypothyroid rat to eliminate the effect of PB on serum T4 and T3 levels. PB or vehicle were started two days after thyroidectomy. By postoperative day 12, TSH levels in the PB-treated rats were lower than in the controls (PB, 697 +/- 62 microU/ml vs. control, 891 +/- 53 microU/ml, p less than .05). Pituitary TSH and hypothalamic TRH contents again were similar in both groups. When TRH (500 ng/kg body weight, IV) was given, the increment in serum TSH at 10 minutes was significantly lower in the PB group (PB, 53 +/- 26 microU/ml vs. control, 131 +/- 18 microU/ml, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)