Nineteen patients with essential hypertension (EH) were studied as outpatients. After administration of chlorthalidone, 50 mg/day for 4 weeks, prazosin 1-4 mg/day (1.82 +/- 0.33 mg/day) was added for a period of 12 weeks. Prazosin lowered supine blood pressure from 149.7 +/- 2.85/102.0 +/- 2.75 mm Hg to 128.2 +/- 3.0/86.1 +/- 1.04 mm Hg (p less than 0.001). Prazosin did not alter heart rate significantly. Prazosin increased the thyroid stimulating hormone (TSH) from 3.63 +/- 0.33 microunits/ml to 4.83 +/- 0.45 microunits/ml (p less than 0.025), thyroxine (T4) from 10.03 +/- 0.29 micrograms/ml to 10.85 +/- 0.42 micrograms/ml (p less than 0.005), and decreased triiodothyronine (T3) from 36.65 +/- 0.62% to 35.42 +/- 0.56%, which was not significant. The free thyroxine index (FTI) increased slightly from 3.67 +/- 0.12 to 3.83 +/- 0.14 (p less than 0.025). However, all values remained within the normal range for the laboratory. Serum cholesterol increased insignificantly. Triglycerides decreased significantly from 223.4 +/- 50.6 mg/dl to 161.7 +/- 29.0 mg/dl (p less than 0.05). High density lipoproteins (HDL) increased significantly from 30.1 +/- 2.1% to 36.0 +/- 3.06 (p less than 0.025). Low density lipoproteins (LDL) decreased insignificantly and very low density lipoproteins (VLDL) decreased from 20.9 +/- 3.44 to 16.3 +/- 2.85 (p less than 0.005). The cholesterol ratio increased from 45.51 +/- 4.3 to 64.71 +/- 10.7 (+42.1%). These results indicate that, in patients with essential hypertension, prazosin is an effective antihypertensive agent and that it significantly increases HDL, decreases VLDL, and improves the cholesterol ratio.

Growth hormone replacement in adult growth hormone deficient patients improves psychological well-being and the quality of life. The aim of this study was to investigate relationship between changes in mood, cognitive functioning, quality of life, changes in body composition and hormone concentration at baseline and six months after treatment with human recombinant growth hormone. Eighteen adult patients with growth hormone deficiency syndrome were recruited to the study. Growth hormone was administered in doses of 12 IU per week in an open design. After 6 months of growth hormone replacement therapy the psychological functioning improved significantly on mood scales (Profile of Mood State) and on a cognitive performance tests. Changes in quality of life scale were trivial. After growth hormone treatment serum concentration of Insulin like growth factor -1 (IGF-1) and triiodothyronine increased and concentration of serum free thyroxine decreased significantly in comparison to basal concentration. There were no significant differences in changes of plasma cortisol, thyrotropin and growth hormone concentrations. Improvement on Profile of Mood State global score as well as on Vigor-Activity subscale correlated significantly with increase in IGF-1 concentration. Improvement on Profile of Mood State Vigor-Activity subscale correlated with increase in water body mass and improvement on Hospital Anxiety and Depression scale depression subscale correlated with decrease in cortisol concentration. The study shows that growth hormone replacement improves mood and cognition in adult growth hormone deficient patients. This improvement is related to changes in water body mass as well as to endocrine changes.

Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects (7 days) of ILP on thyroid hormone metabolism with respect to induction and recovery of the euthyroid sick syndrome in six cancer patients. After ILP, when the limb is reconnected to the systemic circulation, leakage of residual rTNF resulted in systemic peak levels at 10 minutes postperfusion followed by a parallel increase in plasma interleukin-6 (IL-6) and cortisol, with maximum levels at 4 hours (P < .05). A rapid decrease was observed at 5 minutes for plasma triiodothyronine (T3), reverse T3 (rT3), thyroxine (T4), and thyroxine-binding globulin (TBG) (P < .05), whereas free T4 (FT4) and T3-uptake showed a sharp increase, with peak levels at 5 minutes (P < .05). T3, T4, and TBG levels remained low until 24 hours after ILP In contrast, rT3 increased above pretreatment values to maximum levels at 24 hours (P < .05). Plasma thyrotropin (TSH) showed an initial decrease at 4 hours postperfusion (P < .05) but exceeded pretreatment values from day 1 to day 7 (by +94%+/-43% to +155%+/-66%, P < .05), preceding the recovery of T4 and T3 levels. T3 and rT3 returned to initial values at day 4. T4 and TBG levels recovered at day 2. T4 exceeded basal values at days 5 to 7 (P < .05). It is concluded that ILP with rTNF induces a euthyroid sick syndrome either directly or indirectly through other mediators such as IL-6 or cortisol. The recovery from this euthyroid sick syndrome is, at least in part, TSH-dependent, since the prolonged elevation of TSH values preceded and persisted during the normalization of T3 and the elevation of T4 levels. This biphasic pattern of induction of and recovery from the euthyroid sick syndrome may be a general feature of nonthyroidal disease. The euthyroid sick syndrome should be interpreted not only in relation to the presence of nonthyroidal diseases but also in relation to the recovery from these diseases.

To explore the hypothesis that alteration of T3 receptor expression may be an important mechanism controlling the tissue effects of thyroid hormones in the "sick euthyroid" syndrome, specific triiodothyronine (T3) receptor mRNAs were measured in tissues from normal subjects and from patients with liver disease, chronic renal failure, or with multiple organ failure on an intensive care unit (ICU). In all patient groups circulating free thyroxine and free T3 were reduced, while thyroid stimulating hormone remained normal. In patients with liver or renal disease, there were significant increases in levels of both alpha and beta T3 receptor mRNAs in peripheral mononuclear cells (PMNCs); in ICU patients there was a significant increase in beta mRNA. In patients with liver disease increases in T3 receptor mRNAs were not confined to PMNCs but were also found in liver biopsy specimens when levels were compared with those in normal donor liver. After liver transplantation, receptor mRNAs in PMNCs were similar to those in controls; likewise beta mRNA was similar in liver tissue to normal liver. There was, however, persistent elevation in alpha receptor mRNA. Increases in T3 receptor expression in non-thyroidal illness may be responsible for the maintenance of euthyroidism in the face of reduced levels of circulating thyroid hormones.

OBJECTIVE

To determine if maternal thyroid function in the first trimester is altered in pregnancies that subsequently develop preeclampsia (PE).

METHODS

Mean arterial pressure (MAP), uterine artery pulsatility index (PI) maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) at 11 to 13 weeks of gestation were measured in 102 singleton pregnancies that subsequently developed PE, and the values were compared to the results of 4318 normal pregnancies.

RESULTS

In both the PE groups that required delivery before 34 weeks (early-PE) and the late-PE group, compared with the unaffected group, the median MAP multiple of the normal median (MoM) and uterine artery PI MoM were significantly increased. In late-PE but not in early-PE, compared with the unaffected group, the median TSH MoM was significantly increased and the median FT4 MoM was decreased. Logistic regression analysis demonstrated that TSH MoM provided a significant contribution in the prediction of late-PE.

CONCLUSIONS

Impaired thyroid function may predispose to the development of late-PE, and measurement of maternal serum TSH can improve the prediction of late-PE provided by a combination of factors in the maternal history and the measurements of MAP and uterine artery PI.

After entering cells from plasma, molecules must permeate through the cytoplasm before they can be metabolized or excreted. If sufficiently slow, cytoplasmic transport may determine the overall rate of cellular elimination at steady state. Cytoplasmic transport of amphipathic molecules should be particularly slow because of extensive binding to intracellular membranes and proteins. Traditional transport models assume that molecules become instantly available for metabolism and canalicular excretion after entering the cell and thus cannot be used to assess cytoplasmic transport. We therefore extended the traditional multiple-indicator dilution (MID) method of Goresky to explicitly incorporate cytoplasmic transport and used the resulting model to estimate the rate constant for cytoplasmic transport of the amphipathic thyroid hormone 3,5,3'-triiodothyronine (T3). We chose T3 because control studies indicated that it is neither metabolized nor excreted during the brief period of an MID experiment (40-90 s). The traditional MID model was unable to account for the data unless we postulated rapid metabolism or excretion of T3. In contrast, the new diffusion MID model fit the data closely without this false assumption and gave values for the influx and efflux rate constants that agreed with previously published data. The half-time for equilibration of T3 across the cytoplasm of the hepatocyte averaged 50 s. This corresponds to an effective cytoplasmic diffusion constant of 3.1 x 10(-8) cm2/s, which is>> 100 times slower than expected for free T3 in water. Our results indicate that cytoplasmic transport of this model amphipathic compound is much slower than membrane transport.(ABSTRACT TRUNCATED AT 250 WORDS)

To examine whether catecholamines have a direct effect on myosin heavy chain expression of heart myocytes or whether they act via an altered work load, myocytes from neonatal rat hearts were cultured in thyroid hormone-free media containing various positive inotropic and chronotropic agents. The velocity and frequency of contraction of the myocytes were monitored using an optoelectronic system. After 3-5 days of culture, myosin isozyme populations, cellular cAMP content, and 2-deoxy-D-glucose uptake of the myocytes were determined. Compared with myocytes cultured in the absence of inotropic agents (32.6 +/- 3.5% V1), the proportion of myosin V1 was significantly (p less than 0.05) increased in the case of 1 microM isoproterenol (48.2 +/- 5.9% V1), 1 microM forskolin (57.1 +/- 11.7% V1), and 1 mM dibutyryl cAMP (79.1 +/- 2.0% V1). Dibutyryl cAMP increased V1 to a similar level as 30 nM triiodothyronine did (70.2 +/- 13.0% V1). Only a small increase was observed in myocytes cultured in the presence of 10 microM phenylephrine (40.4 +/- 8.4% V1), 10 microM ouabain (40.6 +/- 11.9% V1), or 10 microM Bay K 8644 (40.7 +/- 11.7% V1). The agents with a marked effect on myosin heavy chain expression resulted in a higher cAMP content; isoproterenol and forskolin also stimulated 2-deoxy-D-glucose uptake. All agents resulted in a higher velocity of contraction; with the exception of ouabain, frequency of contraction was also increased. A change in Ca2+ concentration in the medium from 1.3 to 2.4 mM resulted in a small increase in V1 (40.7 +/- 5.2% V1) but had the same effect on contraction velocity as dibutyryl cAMP did. Furthermore, 10 nM isoproterenol also increased V1 in myocytes that were arrested with 10 microM verapamil. The increase in V1 in the case of dibutyryl cAMP, isoproterenol, and forskolin is thus most probably not a correlate of the increased mechanical activity but of the high cellular cAMP content.

The effects of human growth hormone (hGH) on proliferation and differentiation of primary adipocyte precursor cells isolated from rat epididymal fat pads were studied under serum-free culture conditions. hGH markedly reduced the formation of new fat cells and the expression of glycerophosphate dehydrogenase activity, a marker enzyme of adipose differentiation, in a dose-dependent manner. To find an explanation for this inhibitory effect, we investigated the action of GH on (1) cell proliferation and on (2) lipid accumulation, the latter in the absence and presence of corticosterone. In undifferentiated cells, 5 nmol/L hGH increased both cell number and [3H]-thymidine incorporation (1.3- and 2.6-fold over basal, respectively). This effect was mediated by insulin-like growth factor-I (IGF-I), since hGH stimulated IGF-I production in undifferentiated cells by 12-fold and addition of an anti-IGF-I monoclonal antibody (IGF-I MAb) abolished the mitogenic effect of hGH but did not prevent hGH-induced suppression of adipose differentiation. In developing fat cells, hGH significantly reduced cellular 2-deoxyglucose uptake and glucose incorporation into lipids. In addition, hGH exhibited a lipolytic action in the presence of insulin and triiodothyronine. These effects were not prevented by IGF-I MAb. Specific binding of [125I]-hGH to precursor cells increased significantly during adipose conversion. In differentiated cells Scatchard analysis yielded linear plots with an apparent Kd of 0.16 nmol/L and 8,400 sites per cell. Taken together, these data show that hGH reduces adipose conversion in primary cultures of rat adipocyte precursor cells while promoting cell proliferation through an increase in IGF-I production.

Carbamazepine (CBZ) decreases the serum concentration of thyroid hormones. It is proposed that CBZ increases the extra-thyroidal metabolism of thyroid hormones. In order to test this hypothesis CBZ was given to nine hypothyroid patients substituted with thyroxine (T4). A significant decrease in serum concentrations of T4, calculated free T4 (FT4), triiodothyronine (T3), and calculated free T3(FT3) was found after 3 weeks of CBZ medication. The serum concentrations of TSH and the T4:T3 ratios were unaltered, while the serum concentrations of T4-binding globulin (TBG) increased markedly in eight of the nine patients. These findings support the hypothesis of a CBZ induced increase in the extra-thyroidal metabolism of thyroid hormones.

OBJECTIVE

In a whole-body (18)F-FDG PET/CT, non-specific (18)F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial (18)F-FDG uptake.

METHODS

F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before (18)F-FDG injection from all subjects. Myocardial (18)F-FDG uptake was measured as the mean (SUVmean) and maximal (SUVmax) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI). We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI).

RESULTS

Overall, 92 subjects (mean age 50.28 ± 8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUVmax was 4.57, respectively and there was a strong linear correlation between SUVmean and SUVmax (r = 0.98). FFA and fasting duration showed significant negative correlation with myocardial (18)F-FDG uptake, respectively (r = -0.40 in FFA; r = -0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI.

CONCLUSIONS

Myocardial (18)F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve (18)F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

The objective of this study was to investigate the relationship between growth hormone (GH) dynamic tests (thyrotropin-releasing hormone [TRH] test and oral glucose tolerance test [OGTT]), insulin-like growth factor-I (IGF-I) plasma values, tumor size, and clinical outcome in patients with GH-secreting pituitary adenomas. Furthermore, we investigated the potential prognostic utility of the above biochemical parameters in the follow-up of patients with acromegaly. We studied 50 acromegalic patients (18 males and 32 females; mean age, 40 years; range, 16 to 69) who underwent trans-sphenoidal removal of a GH-secreting pituitary adenoma from 1990 to 1994. Preoperatively, we evaluated (1) GH plasmatic levels after an oral glucose load (OGTT) (blood samples were drawn at -15, 0, 30, 60, 90, 120, 150, and 180 minutes after oral administration of 0.75 g/kg body weight [BW] of glucose), (2) GH plasma levels after a TRH test (200 microg as an intravenous [IV] bolus), and (3) basal IGF-I plasma levels after an overnight fast. From 3 to 12 months after surgery we evaluated (1) GH plasma values after an OGTT, and (2) basal plasma IGF-I, free triiodothyronine (FT(3)), free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and urinary free cortisol. The same tests were performed every year for 5 years. All of the patients were classified into 4 subgroups according to the system of Hardy and Vezina. Preoperatively, "controlled" patients (n = 29) had a GH paradoxical response to TRH (n = 28) and an unresponsiveness to OGTT (n = 29); 23 of them belonged to the I and II classes. Only 5 poorly controlled patients (n = 21) showed a preoperative paradoxical response to TRH and 9 had a preoperative GH partial inhibition after OGTT; 19 of them belonged to the III and IV classes. Our data suggest that in the preoperative period in acromegalic patients the simultaneous presence of a GH paradoxical response to TRH and lack of GH inhibition after OGTT is inversely related to the tumor size and therefore more likely to be restored to normal by surgical treatment.

Graves' disease (GD) is a common autoimmune disease mainly caused by thyroid-stimulating antibodies (TSAbs). Interleukin 21 (IL-21) has recently been reported to play a vital role in the production of pathogenic autoantibodies in several autoimmune diseases, but less is known about GD. This study aimed to investigate the serum levels of IL-21 in GD patients and to explore their association with disease activity. We performed a case-control association study of 152 patients with GD and 32 healthy controls. All patients were further classified into three subgroups: the GD-untreated group (n = 70), the GD-recurrence group (n = 41), and the GD-remission group (n = 41). Serum IL-21 levels were assayed with ELISA. TSAb activity was measured by an in vitro bioassay. Changes in serum IL-21 were also observed in 12 GD patients before and after treatment. Additionally, correlations among the serum IL-21 and free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), thyrotropin receptor antibody (TRAb), and TSAb were also analyzed. The serum IL-21 levels in all GD patients were significantly higher than those in the control group (P < 0.001), and specifically, both the GD-untreated and GD-recurrence groups had elevated serum IL-21 compared to the control group (P < 0.001). Moreover, serum IL-21 in newly diagnosed patients markedly decreased after treatment (P < 0.001). Additionally, the serum IL-21 levels in GD-goiter patients were higher than those of the GD-non-goiter patients (P < 0.001). However, no significant differences were found in the serum IL-21 levels in patients with or without Graves' ophthalmopathy. Importantly, serum IL-21 positively correlated with FT3, FT4, TPOAb, TGAb, and TRAb (r = 0.5053, r = 0.3266, r = 0.1792, r = 0.2445, and r = 0.4096, respectively; all P < 0.0001), and particularly with TSAb activity (r = 0.8171, P < 0.0001), negatively correlated with TSH (r = -0.2713, P < 0.0001). Serum IL-21 levels were significantly elevated in patients with GD and decreased after treatment; moreover, IL-21 may be associated with the clinical disease activity. These observations suggest that IL-21 may play an important role in the pathogenesis of GD.

To investigate the mechanism of thyroid hormone action on pulmonary surfactant synthesis, we characterized the effect of triiodothyronine on phosphatidylcholine synthesis in cultured fetal rabbit lung. Since glucocorticoids stimulate surfactant synthesis and reduce the incidence of Respiratory Distress Syndrome in premature infants, we also examined the interaction of triiodothyronine and dexamethasone. The rate of choline incorporation into phosphatidylcholine was determined in organ cultures of rabbit lung maintained in serum-free Waymouth's medium. In 23-d lung cultured for 72 h, the increase in choline incorporation with triiodothyronine alone, dexamethasone alone, and triiodothyronine plus dexamethasone was 50, 62, and 161%, respectively. Both triiodothyronine and dexamethasone also increased incorporation rates with glucose, glycerol, and acetate as precursors, and stimulation with triiodothyronine plus dexamethasone was at least additive. Dexamethasone, but not triiodothyronine, affected distribution of radioactivity from [3H] acetate among phospholipids. Stimulation was first detected 8-12 h after addition of triiodothyronine, and then increased in a linear fashion. With triiodothyronine plus dexamethasone, stimulation was maximal at 48-72 h, and was supra-additive at all times. Exposure of cultured lung to dexamethasone enhanced the subsequent response to triiodothyronine, but not vice versa. When triiodothyronine was removed from cultures, there was no further stimulation and the triiodothyronine effect was partially reversed within 24 h. Half-maximal stimulation of choline incorporation occurred at a triiodothyronine concentration (0.10 nM) very similar to the dissociation constant for triiodothyronine binding to nuclear receptor (0.11 nM). The relative potencies of thyroid hormone analogs for nuclear binding and stimulation of phosphatidylcholine synthesis were also similar: triiodothyroacetic acid greater than triiodothyronine-proprionic acid greater than L-triiodothyronine approximately D-triiodothyronine much greater than thyroxine much greater than 3,5-diethyl-3'-isopropyl-DL-thyronine approximately 3,5-dimethyl-3'-isopropyl-L-thyronine approximately reverse triiodothyronine. The effect of triiodothyronine was blocked by the presence of either actinomycin D or cycloheximide, inhibitors of ribonucleic acid and protein synthesis, respectively. We conclude that triiodothyronine stimulates phosphatidylcholine synthesis by a process involving nuclear receptors and de novo ribonucleic acid and protein synthesis. These findings support the concept that endogenous triiodothyronine has a physiologic role in lung maturation and suggest that a combined antenatal therapy with thyroid hormone and glucocorticoid may be useful for prevention of Respiratory Distress Syndrome in the premature infant.

Madin Darby canine kidney cells can grow in synthetic medium supplemented with 5 factors--insulin, transferrin, prostaglandin E1, hydrocortisone and triiodothyronine--as a serum substitute. These 5 factors permit growth for one month in the absence of serum, and a growth rate equivalent to that observed in serum-supplemented medium. Dibutyryl cAMP substitutes for prostaglandin E1 in the medium, suggesting that increased growth of Maden Darby canine kidney cells results from increased intracellular cAMP. Potential applications of the serum-free medium are discussed. The medium permits the selective growth of primary epithelial cell cultures in teh absence of fibroblast overgrowth, and a defined analysis of the mechanisms by which hormones regulate hemicyst formation.

OBJECTIVE

The purpose of this study was to assess the long-term efficacy of percutaneous ethanol injection (PEI) for the treatment of hyperfunctioning thyroid nodules.

METHODS

One hundred twenty-five patients (88 women, 37 men; age range, 17-76 years; mean age, 53 years) with 127 hyperfunctioning thyroid nodules (volume, 1.2-90 mL; mean, 10.3 mL) were treated with PEI. There were 1-11 PEI sessions per patient (average, 3.9) performed, with injection of 1-14 mL of ethanol per session (total injected ethanol per patient, 3-108 mL; mean, 14.0 mL). Efficacy of the treatment was assessed with color Doppler sonography; scintigraphy; and free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) assays. Follow-up (9-144 months; median, 60 months) was performed with TSH and color Doppler sonography every 2 months for 6 months and every 6 months thereafter.

RESULTS

Three (2.4%) of 125 patients refused completion of PEI therapy because of pain. Results are reported in 122 patients with 124 nodules. All 122 patients showed posttreatment normal levels of FT3, FT4, and TSH. A complete cure (absent uptake in the nodule and recovery of normal uptake in the thyroid parenchyma) was obtained in 113 (93%) of 122 patients-115 (92.7%) of 124 treated nodules. Residual hyperfunctioning nodular tissue along with decreased thyroid parenchyma uptake (partial cure) was present in nine patients accounting for nine (7.3%) of 124 nodules. Rates of complete cure after PEI were: overall nodules, 115 (92.7%) of 124; nodules < or = 10 mL, 63 (94.0%) of 67; nodules>> 10 to < or = 30 mL, 32 (91.4%) of 35; nodules>> 30 to < or = 60 mL, 17 (89.5%) of 19; nodules>> 60 mL, three (100%) of three. The overall rate of major complications (transient laryngeal nerve damage, two patients; abscess and hematoma, one patient each) was four (3.2%) of 125 patients. Follow-up examinations showed marked shrinkage of 112 treated nodules ranging from 50% to 90% of the pretreatment volume (mean, 66%) and new growth of hyperfunctioning tissue in four patients at color Doppler sonography and scintigraphy at 12, 18, 18, and 48 months' follow-up, respectively. However, all patients remained euthyroid (low or normal TSH and normal FT3 and FT4) during follow-up.

CONCLUSIONS

PEI of hyperfunctioning thyroid nodules seems to be an effective and safe alternative to traditional treatment. It also appears to be effective in patients with hyperfunctioning thyroid nodules larger than 30 mL.

Anorexia Nervosa (AN) is a psychiatric disorder characterized by the classic triad: amenorrhea, weight loss, and behavioral changes. It is generally seen in young, white women under 25 and is particularly common in adolescence. The mortality of the disease varies between 5.1% and 13%. The endocrine changes associated with AN have been studied in depth and provide strong evidence for hypothalamic dysfunction. All are secondary and reverse with weight gain. In general, gonadotropin (FSH, LH) levels are decreased in patients with AN, as well as the response to Gonadotropin releasing hormone (GnRH). Fasting growth hormone levels are elevated, but the stimulated response of Growth hormone (GH) to Growth hormone releasing hormone (GHRH) is normal and inversely correlated to body weight. Serum Growth hormone binding protein (GHBP), insulin growth factor I (IGF-I) and IGF binding protein (IGFBP) - 3 levels are all significantly decreased in patients with AN and return to normal with refeeding. IGFBP-1 and 2 are increased and return also to normal with weight gain. Serum IGF-II is decreased but not significantly. The IGFBP-3 proteolytic activity is normal. Thyroxine (T4) and Triiodothyronine (T3) while reverse T3 (rT3) is elevated. Thyrotropin stimulating hormone (TSH). TSH levels are normal with a delayed response to thyrotropin releasing hormone (TRH). Cortisol levels are normal or elevated as well as urinary free cortisol. Corticotropin (ACTH) levels are normal with decreased response to Corticotropin releasing hormone (CRH). Dexamethasone suppression test is abnormal. Sex steroids are decreased. Finally leptin levels are decreased in patients with AN while ghrelin levels are elevated. Both leptin and ghrelin levels return to control values after renutrition.

A unique 16-year old female patient presented after acute Epstein-Barr virus (EBV) infection with severe primary hypothyroidism. Her thyroid test results were thyrotropin level (TSH) of 198 mU/L (normal, 0.4-4 mU/L), free thyroxine [FT(4)], 2.5 pmol/L (normal, 10-25 pmol/L), total triiodothyronine (TT(3))>> 19.5 nmol/L (normal, 1.3-2.7 nmol/L), and free triiodothyronine (FT(3)), 0.77 pmol/L (normal, 3.3-6.3 pmol/L). She had high titers of thyroglobulin and thyroid peroxidase autoantibodies. In vitro triiodothyronine (T(3))-binding measured by radioimmunoprecipitation was 86% (normal, up to 8.5%) and thyroxine (T(4))-binding 8.2% (normal, 6.4%). Serum immunoglobulin G (IgG) absorption, achieved by protein-G Sepharose beads, decreased TT(3) toward normal. Levothyroxine treatment normalized the low baseline FT(4) and FT(3) values, and suppressed TSH to normal. However, TT(3) remained highly elevated and returned to normal after 20 months, while T(3 )binding gradually decreased. Thus, her severe hypothyroidism was masked by this unusual phenomenon. Thirty-four patients with EBV infection (15 with acute disease and 19 with previous infection) were tested for thyroid hormone levels. EBV antibodies (early antigen immunoglobulin M [IgM] and IgG and anti-Epstein-Barr virus nuclear antigen [EBNA] IgG) were measured by enzyme-linked immunosorbent assay (ELISA). In 15 patients with acute EBV the mean TT(3) level was 2.47 +/- 0.39 nmol/L (5 had TT(3) values above normal) compared to a mean TT(3) of 1.70 +/- 0.53 nmol/L in 19 subjects with previous infection (p < 0.0005; only 1 had a TT(3) result above normal), with no differences in FT(4) and TSH concentrations between the two groups. Acute EBV infection may be associated with transient mild to severe TT(3) elevation as a result of assay interference by anti-T(3) autoantibodies.

OBJECTIVE

An important side effect of lithium therapy is an influence on thyroid function. It is unclear whether there is a significant association between thyroid function and duration of lithium administration. The aim of the present cross-sectional study was to measure levels of thyroid hormones and antibodies in patients with bipolar disorder receiving lithium for more than ten years.

METHODS

The study was performed in 66 patients (21 males, 45 females) with bipolar mood disorder, receiving lithium for 10-44 (21 ± 9; mean ± standard deviation) years. Thyroid-stimulating hormone (TSH), free thyroxine (fT3), and free triiodothyronine (fT4) were measured by the microparticle enzyme immunoassay. Thyroid peroxidase (TPO) antibodies, thyroglobulin (TG) antibodies, and TSH receptor (TSH-R) antibodies were measured by the radioimmunoassay.

RESULTS

Some features of hypothyroidism were found in ten (22%) female patients (seven received levothyroxine and three had increased TSH). No abnormality in thyroid hormones was found in male patients. A significant percentage of patients had abnormally high levels of anti-TPO, and anti-TG antibodies, which correlated with TSH and fT3 concentrations. There were no differences in thyroid function between patients receiving lithium for 10-20 years and those taking the drug for more than 20 years.

CONCLUSIONS

These results confirm the greater susceptibility of female subjects for disturbances of thyroid hormones during lithium therapy, with one-fifth of them showing some features of hypothyroidism. Abnormally high levels of anti-TPO and anti-TG antibodies were shown in a significant proportion of patients. However, in contrast to the effect of lithium on kidney function, our results do not show an association between the duration of lithium therapy and thyroid dysfunction.

The rdw rat is a new strain of dwarf mutant that has decreased blood thyroxine (T4) and growth hormone (GH) concentrations and testicular enlargement during development and aging. To confirm whether this strain can be used as a new hypothyroid model, the experiments reported here were carried out, using adult rdw rats, rdw rats treated with thyroxine, and clinically normal (N) Wistar-Imamichi rats. Clinical parameters of deficient thyroid function in rdw rats were chosen for evaluation and characterization. Body weight, hemoglobin (Hb) concentration, hematocrit (Hct), glucose (GLU), and systolic blood pressure were significantly lower, and serum values for aspartate transaminase (AST), total cholesterol (TC), total protein (TP), and blood urea nitrogen (BUN) were higher in rdw than in N rats. Serum concentrations of total T4 and free triiodothyronine (FT3) were significantly lower, and serum thyroid-stimulation hormone (TSH) concentration was markedly higher in rdw than in N rats. Serum GH concentration was significantly lower in rdw than in N rats. Results of histologic examination indicated that the thyroid gland of rdw rats was markedly atrophied, compared with that of N rats. Results of clinical examination of organs and hematologic and biochemical values in rdw rats corresponded to those of the hypothyroid state in humans. Most organ weights (heart, kidney, spleen, and adrenal gland), hematologic and biochemical values (Hb, Hct TC, TP, BUN), blood pressure, and serum hormone (TSH and GH) values underwent substantial restoration (partial or complete) toward normal in response to replacement therapy. In conclusion, the rdw rat is a useful model of congenital hypothyroidism.

Mouse embryo cells derived in a serum-free medium formulation (SFME cells) do not exhibit growth crisis or chromosomal abnormalities and are nontumorigenic in vivo; these cells are also reversibly growth inhibited by serum or platelet-free plasma (Loo et al.; Science, 236:200-202, 1987). A portion of the inhibitory activity of serum could be extracted by charcoal, a procedure that removes steroid and thyroid hormones. Both L-3,5,3'-triiodothyronine (T3) and hydrocortisone inhibited growth of SFME cells in a reversible manner. The inhibitory activity of serum also was partially removed by treatment with anion exchange resin in a procedure designed to deplete serum of thyroid hormone. However, the effect of serum on untransformed SFME cells could not be prevented by addition of the antiglucocorticoid RU38486, and ras-transformed clones of SFME cells, which are capable of growing in serum-containing medium, retained inhibitory responses to glucocorticoid and, with some clonal variability, to T3. These results suggest that glucocorticoid or thyroid hormones may contribute to the inhibitory activity of serum on SFME cells, but additional factors are also involved.

BACKGROUND

Infantile hepatic hemangioma with consumptive hypothyroidism is a rare condition.

METHODS

A 4-month-old girl presented with diffuse hepatic hemangiomas during treatment of congenital hypothyroidism. Serum reverse triiodothyronine was elevated, and her hypothyroidism improved concomitant with involution of the hemangioma following prednisolone and interferon-alpha administration. At 20 months of age, 7 months after discontinuing prednisolone and interferon-alpha, a focal hemangioma regrew from one of the previous lesions and was surgically resected. The expression and activity of type 3 iodothyronine deiodinase (D3) were elevated in the resected tumor tissue compared with placenta.

CONCLUSIONS

Here, we describe a patient with consumptive hypothyroidism and diffuse infantile hepatic hemangiomas, one of which regrew after involution following pharmacotherapy. The etiology of elevated D3 activity is also discussed.

CONCLUSIONS

It is important to identify infantile hepatic hemangioma in patients with hypothyroidism refractory to hormone replacement therapy, who have low free triiodothyronine despite high thyrotropin and normal free thyroxine levels, and long-term follow-up will be needed for these patients.

Biosynthesis of thyroxine in the thyroid gland involves a reaction between two diiodotyrosyl residues within the same molecule of thyroglobulin, a large, thyroid-specific glycoprotein. This reaction, generally referred to as the coupling reaction, is catalyzed in the thyroid by the heme-containing glycoprotein enzyme, thyroid peroxidase, also a thyroid-specific protein. The coupling reaction is, however, not specific for thyroid peroxidase; it is also efficiently catalyzed by other heme-containing peroxidases. Peroxidase-catalyzed coupling may also occur between a monoiodotyrosyl and a diiodotyrosyl residue in thyroglobulin to form the more potent thyroid hormone, 3',3,5-triiodothyronine. Under most conditions, thyroxine formation in the thyroid is greatly favored over that of 3',3,5-triiodothyronine. Two mechanisms have been proposed for the coupling reaction, a radical mechanism and an ionic mechanism. In this, and in the following paper, we present evidence favoring a radical mechanism. This view is bsed primarily on the observation that peroxidase-catalyzed coupling is markedly stimulated by substoichiometric concentrations of free diiodotyrosine (DIT). Evidence obtained in this and in the following paper leads us to conclude that the stimulatory effect of DIT on coupling involves peroxidase-catalyzed oxidation of the added DIT to a radical form. We propose that this stimulation involves a radical chain propagation mechanism. This implies that peroxidase-catalyzed coupling in the absence of DIT must also be a radical-mediated reaction.

The acute effects of long-distance swimming in cold water on selected hormonal and metabolic variables were evaluated on 22 long-distance swimmers (16 males and 6 females) during a 32-km swimming competition (La Traversée Internationale du Lac St-Jean). The water temperature was 18.5 degrees C and the mean performance times were 8 h and 32 min for men (M) and 9 h and 1 min for women (F). The blood samples were withdrawn in the fasting state during the week preceding the event and within 30 min after completion of the race. A positive correlation was obtained, for both groups, between percent body fat and rectal temperature measured at the end of the competition. After the competition, an increase in plasma epinephrine, norepinephrine, cortisol, thyroxine, free fatty acids, lactate, a decrease in glucose and insulin and no change in growth hormone, triiodothyronine, triglycerides, and cholesterol concentrations were observed in both groups. The increase in plasma thyroxine was more pronounced in the slower swimmers while the change in blood cortisol concentrations was higher in the subjects having the most acute decrease in body temperature. Male and female swimmers have a similar metabolic and hormonal response to a long-distance swimming competition in cold water.

The effects of exogenous L-thyroxine therapy (0.2-0.3 mg/day) on spontaneously occurring thyroid hormone autoantibodies (THAA) and on serum levels of thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) are described in a boy with lymphocytic thyroiditis. Prior to T4 medication, THAA bound virtually all thyroid hormones as noted by serum gamma globulin binding of tracer hormones. During T4 therapy, however, gamma globulin binding of tracer thyroid hormones decreased markedly. T4 and T3 levels as determined by radioimmunoassay (RIA) were grossly distorted prior to thyroxine therapy and bore no relation to clinical status, the single antibody technics yielding falsely low values whereas the double antibody procedures spuriously exaggerating serum hormone concentration. That spontaneously occurring THAA interfered in RIA hormone measurements was clearly shown by the lack of inconsistencies in laboratory and clinical evaluation when hormone determinations were performed in protein free serum extracts (to remove circulating THAA), or when RIAs were carried out in sera during thyroxine therapy when THAA were saturated by exogenous hormones. The thyroid stimulating hormone (TSH) level prior to therapy was 300 microunits/ml which decreases to less than 3 microunits/ml during T4 medication (0.3 mg/day). There was a gross inverse correlation between TSH secretion and T4 antibody saturation. The marked inhibition of antibody binding of tracer thyroid hormones observed during therapy suggested possible masking of thyroid hormone antibody activity during T4 treatment; experiments involving addition of tracer thyroid hormones to hormone stripped serums from thyroxine treated patients confirmed the hypothesis in two cases of hypothyroidism--one of which was diagnosed in the boy with chronic thyroiditis and the other a woman with postradioactive iodine-induced hypothyroidism. The pathophysiologic significance of thyroid hormone autoantibodies in the transport of thyroid hormones is briefly discussed.