Impairment in cognitive and exercise performance during prolonged antarctic residence: effect of thyroxine supplementation in the polar triiodothyronine syndrome.

Humans who work in Antarctica display deficits in cognition, disturbances in mood, increased energy requirements, a decline of thyroid hormone products, and an increase of serum TSH. We compared measurements in 12 subjects, before deployment (baseline), with 11 monthly studies during Antarctic residence (AR). After 4 months of AR (period 1), half of the subjects (T(4) group) received L-thyroxine [64 nmol.day(-)(1) (0.05 mg.day(-)(1))]; and the other half, a placebo (placebo group) for the next 7 months of AR (period 2). During period 1, there was a 12.3 +/- 5.1% (P < 0.03) decline on the matching-to-sample (M-t-S) cognitive task and an increase in depressive symptoms, compared with baseline. During the intervention in period 2, M-t-S scores for the T(4)-treated group returned to baseline values; whereas the placebo group, in contrast, showed a reduced M-t-S score (11.2 +/- 1.3%; P < 0.0003) and serum free T(4) (5.9 +/- 2.4%; P < 0.02), compared with baseline. The change in M-t-S score was correlated with the change in free T(4) (P < 0.0003) during both periods, and increases in serum TSH preceded worsening scores in depression, tension, anger, lack of vigor, and total mood disturbance (P < 0.001) during period 2. Additionally, the submaximal work rate for a fixed O(2) use decreased 22.5 +/- 4.9% in period 1 and remained below baseline in period 2 (25.2 +/- 2.3%; P < 0.005) for both groups. After 4 months of AR, the L-thyroxine supplement was associated with improved cognition, which seems related to circulating T(4). Submaximal exercise performance decrements, observed during AR, were not changed with this L-thyroxine dose.

Circannual pattern of hypothalamic-pituitary-thyroid (HPT) function and mood during extended antarctic residence.

The seasonal variation in thyroid function and mood was examined in 10 men and two women who spent the 1997 or 1998 austral winter at McMurdo Station, Antarctica. Serum samples of TSH, free T3 and free T4 were collected each month over a 10-month period (October-August), along with responses to the Profile of Mood States (POMS) and the Center for Epidemiologic Studies - Depression (CES-D) Scale. Both TSH and mood (a summary score created from the POMS depression, anger, fatigue and confusion subscales) exhibited a circannual pattern with peaks during the months of November and July and a trough during the months of March and April. High levels of tension-anxiety and confusion were preceded by declines in free T3 and T4. However, increases in tension-anxiety and total mood disturbance also preceded a decline in free T3 levels, suggesting a feedback of mood on T3 levels. Levels of free T4 were independently associated with preceding increases in anger scores. These results support the hypothesis that the symptoms characteristic of the winter-over syndrome is a state of relative CNS hypothyroidism. This model of seasonal variation in thyroid function and mood also has implications for an understanding of potential mechanisms underlying the association between latitude and SAD or S-SAD.

Thyroid hormones: positive relationships with cognition in healthy, euthyroid older men.

BACKGROUND: Although the association of clinical hypothyroidism with cognitive deficits is well known, the cognitive effects of thyroid hormones in euthyroid subjects are less studied and understood. The purpose of this study was to examine thyroid-cognition relationships in healthy, euthyroid older men. METHODS: We examined healthy men (N = 44, mean age = 72), excluding clinically hypothyroid/hyperthyroid or diabetic/hyperglycemic subjects and those with dementia, depression, CNS medications, or recent illness. Plasma samples obtained across a 24-hour period were pooled, then assayed for total thyroxine (TT4), total triiodothyronine (TT3), and T3 resin uptake. Free thyroxine index (FT4I) was calculated. A broad cognitive battery (including the Wechsler Adult Intelligence Scale-Revised [WAIS-R], the Dementia Rating Scale [DRS], and the Rivermead Behavioral Profile [PROFILE]) was administered to all subjects. RESULTS: Regression analyses controlling age and education showed TT4 and FT4I to have significant positive relationships with measures of overall cognition; TT4 accounted for 8% to 12% of the variance in omnibus cognitive measures such as WAIS Performance, WAIS Verbal score, and GLOBAL cognitive scores. CONCLUSIONS: Our findings suggest that within "normal" range of variation in plasma thyroid hormones, TT4 but not T3 positively associates with general cognition in healthy elderly men.

Fine needle aspiration of thyroid nodules. Determinants of insufficiency rate and malignancy yield at thyroidectomy.

OBJECTIVE: To evaluate patient- and practice-specific determinants of the thyroid nodule fine needle aspiration (FNA) insufficiency rate and malignancy yield at a tertiary-care teaching hospital. STUDY DESIGN: All FNAs of thyroid nodules performed from August 1990 to October 1993 at the Walter Reed Army Medical Center Endocrinology Clinic were reviewed and the results analyzed for correlation with surgical outcome, scintiscanning result and operator experience. Provider-specific factors influencing the FNA insufficiency rate, surgical referral pattern and malignancy yield were evaluated. RESULTS: A total of 504 aspirations in 422 patients with thyroid nodules were included in the analysis. The sensitivity of FNA for detecting malignancy was 80%, specificity was 73.2%, and accuracy was 75.2%. A significant negative correlation was found between recent aspirator experience and the insufficiency rate. Repeat aspiration of nodules previously yielding benign cytology increased the malignancy yield. Surgical excision of nodules with insufficient aspirations gave a low malignancy yield, and aspiration of nodules that were "hot" on scintiscanning rarely yielded false positive FNA results. CONCLUSION: Specific limitations of thyroid nodule FNA include a large number of aspirates containing insufficient cytologic material and a variable malignancy yield. Specific recommendations based on the findings in this report are: the establishment of uniform criteria for judging specimen adequacy, the performance of repeat aspiration on thyroid nodules with previously benign aspirates, the abandonment of scintiscanning in the routine management of thyroid nodules and a conservative approach to clinically indolent nodules repeatedly found to have scant cellularity on FNA. Based on these findings, an algorithm for the diagnostic evaluation of a solid thyroid nodule can be constructed.

Increase in rT3 serum levels observed during extended Alaskan field operations of Naval personnel.

Members of a US Navy Special Warfare platoon had blood samples drawn by venipuncture and other baseline measurements carried out prior to departure for a three-month period of field operations in Alaska. Assays of serum reverse triiodothyronine (rT3), free thyroxine (fT3), free T4 (fT4), and thyroid stimulating hormone (TSH) were subsequently done at the Naval Medical Research Institute (NMRI), Bethesda, Maryland. In the field and at baseline, hematocrits and urine specific gravities were also measured to track hydration status, and body weights and fat were recorded to track nutritional status. After plasma volume change and weight change corrections, an approximate 30% increase in serum rT3 level and 20% decrease in free T3 level over 76 days of cold exposure were recorded. The necessity for an rT3 kinetic study is indicated. The mean residence time for rT3 in the circulation is about 8 hours with respect to about 36 hours for free T3, so rT3 kinetic studies would be advantageous with respect to long term cold exposure of military personnel.

Pituitary and peripheral thyroid hormone responses to thyrotropin-releasing hormone during sustained sleep deprivation in freely moving rats.

Sleep deprivation is associated with poor cognitive ability and impaired physical health, but the ways in which the brain and body become compromised are not understood. In sleep-deprived rats, plasma total T4 and T3 concentrations decline progressively to 78% and 47% below baseline values, respectively, brown adipose tissue 5'-deiodinase type II activity increases 100-fold, and serum TSH values are unknown. The progressive decline in plasma thyroid hormones is associated with a deep negative energy balance despite normal or increased food intake and malnutrition-like symptoms that eventuate in hypothermia and lethal systemic infections. The purpose of the present experiment was to evaluate the probable causes of the low plasma total T4 during sleep deprivation by measuring the free hormone concentration to minimize binding irregularities and by challenging the pituitary-thyroid axis with iv TRH to determine both 1) the pituitary release of TSH and 2) the thyroidal response of free T4 (FT4) and free T3 (FT3) release to the TSH increment. Sleep-deprived rats were awake 91% of the total time compared with 63% of the total time in yoked control rats and 50% of the total time during the baseline period. Cage control comparison rats were permitted to sleep normally. Sustained sleep deprivation resulted in a decline from baseline in plasma FT4 of 73 +/- 6% and FT3 of 45 +/- 12%, which were similar to the declines in total hormone concentrations observed previously; nonstimulated TSH was unchanged. In the yoked and cage control groups, FT4 also declined, but much less than that of the sleep-deprived group. The relative changes in free compared with total hormone concentrations over the study were also less parallel than those in the sleep-deprived group. The plasma TSH response to TRH was similar in all groups across experimental days. The plasma FT4 and FT3 concentrations in sleep-deprived rats increased after TRH-stimulated TSH release to an extent comparable to control values. Taken together, low basal FT4 and FT3 hormone concentrations and unchanged TSH and thyroidal responses to TRH suggest a pituitary or hypothalamic contribution to the hypothyroxinemia during sleep deprivation.

Circannual changes in thyroid hormone physiology: the role of cold environmental temperatures.

Hypothyroid subjects given a constant dose of thyroxine (T4) show both an increase in serum thyrotrophin (TSH) of approximately 50% and a decline of serum T4 by approximately 15% during the winter months. Euthyroid subjects who are older than 41 years of age show an increase of approximately 30% in serum TSH during the winter months without a change in T4. Young euthyroid subjects, between the ages of 19 and 41 years, show neither a circannual pattern of TSH nor T4 but have an increase in triiodothyronine (T3) plasma clearance rate and production rate of approximately 30% during the winter seasons. Additionally, young subjects living for greater than 5 months in Antarctica show a doubling in T3 plasma clearance rate and production rate, as well as elevations of approximately 30-50% in TSH and small declines in T4. Repeated exposure to cold air has recently been reported to induce declines in serum T3, and T4 and increases in T3 clearance and production rate, thus linking a possible physiological stimulus to these seasonal observations. This collection of studies from several laboratories supports the concept that T3 kinetic changes have a seasonal dependence and that cold exposure provides one possible mechanism. As the subjects age, have a fixed thyroid hormone dosage for hypothyroxinemia, or spend an extended number of months in polar conditions, a reflex TSH rise occurs. This rise in TSH signals a hypothalamic-pituitary hypothyroxinemia whose clinical significance is unknown.

Changes in serum triiodothyronine kinetics and hepatic type I 5'-deiodinase activity of cold-exposed swine.

Swine exposed to cold air have elevated serum values of total triiodothyronine (TT3) and free T3 (FT3). To characterize the mechanism of these increases, we measured in vivo kinetic parameters after a bolus intravenous injection of 125I-labeled T3 by use of both multicompartmental (MC) and noncompartmental (NC) methods and in vitro hepatic type I iodothyronine 5'-deiodinase (5'D-I) activity. Ten ad libitum-fed 5-mo-old boars were divided into two groups, living for 25 days in either control (22 degrees C) or cold (4 degrees C) conditions. Cold-exposed animals consumed 50% more calories than control animals but showed no difference in total body weight, percent body fat, or plasma volume. Thyroid gland weight was increased 86% (P < 0.004), as was serum total thyroxine (TT4) (48%), free T4 (FT4) (61%), TT3 (103%), and FT3 (107%), whereas serum thyrotropin (TSH) was not different in cold-exposed compared with control animals. The T3 plasma clearance rate was similar between groups when both MC and NC techniques were used. However, T3 plasma appearance rate (PAR) was elevated in cold-treated animals 110% over controls by MC (P < 0.001) and 83% by NC methods (P < 0.001). The animal total hormone pool of T3 was increased 76% (MC) and 53% (NC) compared with control (P < 0.01). The Michaelis constant of hepatic 5'D-I was not different between groups, but the maximum enzyme velocity increased (106%; P < 0.02). Therefore cold exposure for 25 days is associated with increased energy intake, thyroid size, T3 PAR, and hepatic 5'D-I activity with little change in serum TSH.

Changes in triiodothyronine (T3) mononuclear leukocyte receptor kinetics after T3 administration and multiple cold-air exposures.

Repeated cold-air exposures increase human triiodothyronine (T3) plasma clearance rates. To study the response of the nuclear T3 receptor (NT3R) in this condition, binding characteristics were analyzed in human mononuclear leukocytes (MNL). In addition, we supplemented one group of individuals with a daily oral replacement dose of T3 to isolate the influence of serum thyroxine (T4) and thyrotropin (TSH) levels on receptor kinetics. The subjects were exposed to cold air (4 degrees C) twice/d, 30 min/exposure, for a total of 80 exposures. The T3-subjects received placebo [n = 8] and the T3 + subjects received T3 (30 micrograms/d) [n = 8] in a double-blind fashion. Mononuclear leukocytes were isolated from peripheral blood before the cold exposure and drug regimen began, and then after every 20 exposures. The dissociation constant (Kd) and maximum binding capacity (MBC) of the NT3R values were log transformed to minimize between-subject variability. In the T3+ group, serum total thyroxine (TT4), free T4 (FT4), and TSH were approx 50% lower than both basal and T3-values. The log10Kd increased 0.304 +/- 0.139 (p < 0.04) and the log10MBC increased 0.49 +/- 0.10 (p < 0.001) in the T3+ subjects compared to baseline. This change in MBC represents a 311% increase in the MBC over baseline and a fivefold increase over placebo-treated subjects. The T3- group showed no change in MBC over the study. These results describe for the first time the rapid modulation of the NT3R in response to the combined influence of cold exposure and reduced circulating T4 and TSH.

Relationship between changes in serum thyrotropin and total and lipoprotein cholesterol with prolonged Antarctic residence.

Antarctic residence (AR) is associated with a 50% increase in the thyrotropin (TSH) response to TSH-releasing hormone (TRH) and an expanded triiodothyronine (T3) distribution volume and extravascular hormone pool, collectively called the polar T3 syndrome. To investigate the possible biologic significance of this syndrome, we studied the relationship between nonstimulated TSH and serum lipid profiles in nine subjects, once while in California and monthly during 9 months of AR. We measured serum levels of TSH, total thyroxine (TT4), free T4 (FT4), total T3 (TT3), free T3 (FT3), thyroid-binding globulin (TBG), total cholesterol (T-CHOL), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), dietary cholesterol (D-CHOL), dietary fat (D-FAT), and dietary kilocalories at each month. The paired mean monthly change from baseline was used to determine significance. The group's mean levels of TSH (approximately 30%), TBG (approximately 16%), T-CHOL (approximately 4%), HDL-C (approximately 10%), and D-CHOL (approximately 19%) increased with AR (P < .05). Small but significant decreases (P < .05) were observed in the mean changes of TT4 (approximately 8%), FT4 (approximately 6%), and TT3 (approximately 6%). FT3, D-FAT, dietary kilocalories, body weight, TG, and the calculated low-density lipoprotein (LDL-C) were unchanged with AR. A significant rate of change (P < .05) during AR was also calculated from the slope of a fitted logarithmic function for TSH (0.96 +/- 0.31 mU.L-1 x mo-1), TBG (61.19 +/- 12.29 nmol.L-1 x mo-1), TT3 (0.09 +/- 0.04 nmol.L-1 x mo-1), TT4/TBG (-0.06 +/- 0.01/mo), TT3/TBG (-8.49 +/- 1.98 x 10(-4)/mo), and TG (-0.33 +/- 0.15 mmol.L-1 x mo-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the Iditarod Sled Dog Race on serum thyroid hormones and body composition.

Cold exposure, activity and energy deficit have been associated with changes in body composition and/or changes in serum thyroid hormones. Because these conditions are present during the Iditarod Sled Dog Race, 10 volunteer participants were studied before and after the race. Body composition, total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and free triiodothyronine (FT) levels were determined. There was a significant decrease in body weight (p < 0.05) and a decrease in body fat (p < 0.01). There were no significant changes in TT4, FT4, TT3 or FT3. On the basis of this study, it can be concluded that the strenuous activity of the Iditarod mitigates against the classic perturbation in thyroid axis brought on by the hypocaloric state.

The effect of endurance training on serum triiodothyronine kinetics in man: physical conditioning marked by enhanced thyroid hormone metabolism.

OBJECTIVE: We studied the relationship between endurance training, aerobic capacity, and T3 metabolism in healthy euthyroid men. DESIGN: T3 kinetic studies performed on two groups of subjects differentiated on the basis of physical activity status and aerobic capacity. SUBJECTS: Five endurance-trained athletes and five sedentary controls (mean +/- SD VO2 max = 48.2 +/- 7.1 vs 23.2 +/- 4.5 ml/kg/min, respectively) matched for age, body surface area, lean body mass, and baseline thyroid function. MEASUREMENTS: Kinetic analysis performed using serial serum T3 levels measured following oral T3 administration. Metabolic clearance rate, total volume of distribution, disposal rate, and total body pool calculated using non-compartmental analysis. RESULTS: When normalized for lean body mass, all kinetic parameters were 25-38% greater in the athletic group compared to controls (P < 0.05). Total volume of distribution, disposal rate, and total body pool were positively correlated with aerobic capacity (r = +0.69 to +0.79; P < 0.05). Metabolic clearance rate was positively correlated to a non-significant degree. CONCLUSIONS: These results confirm the findings of prior studies that thyroid hormone metabolism is altered by physical conditioning. In addition, we demonstrated a positive correlation between aerobic capacity and several parameters of T3 kinetics. Differences in absolute lean body mass cannot explain these findings; rather it appears that there is something qualitatively different in the way endurance-trained tissue processes thyroid hormone, compared to untrained tissue. The study was not designed to elucidate these differences at the cellular level; however, it does support a link between muscle physiology and T3 activity and may suggest a physiological role for thyroid hormone in physical conditioning.

Multiple cold air exposures change oral triiodothyronine kinetics in normal men.

The influence of cold exposure on triiodothyronine (T3) kinetics was studied in 16 men before, during (biweekly), and after 80 (10/wk) cold (4 degrees C) air exposures. We used serum values before and up to 24 h after a pharmacological oral (o) dose of T3 [76.8 nmol (50 micrograms)] to calculate noncompartmental kinetic parameters. To assess the role of thyroxine (T4) and thyrotropin (TSH), we administered a replacement dose of T3 [46.0 nmol/day (30 micrograms)] to eight men (+T3 group) and placebo to eight others (-T3 group) for the 2-mo study. There was no group effect of T3 treatment (+T3) on oral total volume of distribution (TVdo), metabolic clearance rate (MCRo), or disposal rate (DRo). TVdo was not changed over the study. Cold increased MCRo by 5.4 +/- 2.0 l.day-1.m-2. DRo increased with cold by 10.2 +/- 4.4 nmol.day-1.m-2. Although serum TSH, total T4, and free T4 decreased by approximately 50% in the +T3 group, the changes in MCRo and DRo with cold were not different from those in -T3. We describe that human T3 kinetics are changed with brief repeated exposures to cold air and that these increases in MCRo and DRo do not appear to be dependent on TSH or T4.

Human cold air habituation is independent of thyroxine and thyrotropin.

Thyroxine (T4) is required in species possessing brown adipose tissue (BAT) for the maintenance of cold tolerance and adaptation. In humans, who possess negligible quantities of BAT, the importance of T4 has not been demonstrated. We studied the effects of decreased serum T4 and thyrotropin (TSH) on human cold habituation after repeated cold air exposures. Eight men (T3+) received a single daily dose of triiodothyronine (T3; 30 micrograms/day), and another eight men (T3-) received a placebo. All 16 normal thyroid men underwent a standardized cold air test (SCAT) under basal conditions in January and again in March after eighty 30-min 4.4 degrees C air exposures (10/wk). Measurements of basal metabolic rate (BMR), O2 consumption (VO2), mean arterial pressure (MAP), plasma norepinephrine (NE), serum TSH, free and total T4, and free and total T3 were repeated before and after 8 wk of exposure. TSH, free T4, and total T4 were 50% lower for T3+ than for T3- subjects. Total and free T3 were not different between groups. BMR was unchanged after habituation, whereas the cold-stimulated VO2, MAP, and NE were significantly reduced for all subjects in March. The relationship between VO2 and NE (r2 = 0.44, P less than 0.001) during the initial SCAT was unchanged with habituation. We suggest that human cold habituation is independent of major changes in circulating T4 and TSH.

Hematological parameters are altered during cold air exposure.

Whole blood hematocrit (HCT) decreases during multiple exposures to cold air. To better understand this finding, we have analyzed hematological profiles in 27 normal adult men exposed repeatedly to cold air in one of two experimental protocols. Experiment I was a cold air acclimatization study (CAA) conducted with two groups of 8 men in each group before, during, and after 80 separate 30-minute cold (4 degrees C) air exposures. As part of a metabolic study, half of the men received placebo daily (n = 8), and the other half received an oral daily maintenance dose of the thyroid hormone triiodothyronine (T3) (30 micrograms/day). Blood was analyzed prior to and after every 20 cold exposures. Both groups reacted similarly. When compared with basal conditions, hematocrit (HCT) and erythrocyte counts (RBC) were decreased (p less than 0.05); mean corpuscular hemoglobin concentration (MCHC) and plasma volume (PV) were increased with cold exposure (p less than 0.05). Hemoglobin (Hb), leukocyte counts (WBC), and mean corpuscular volume (MCV) were unchanged. Experiment II was carried out with 9 military volunteers during extended arctic winter field operations (EAO) in Utah and Alaska. Blood was analyzed prior to and after completion of EAO. A changing hematological profile similar to that in the CAA protocol was found. Hematocrit and RBC were decreased (p less than 0.02); MCHC and PV were increased (p less than 0.02). Hemoglobin, WBC, and MCV were unchanged. In addition, there was a negative correlation between HCT and the absolute reticulocyte count in this second experiment. It would appear that in instances of cold stress, whether induced or naturally occurring, certain blood cellular elements respond in a similar adaptive manner.

Effect of animal sex and size on effort when pelting lambs.

Pelting load data were collected and analysed for 304 lambs (comprising 46% ewes, 26% cryptorchids and 28% rams), all of which came from one farm. Although typically about 24% more impulse (Ns) had to be applied for pelting ram lambs than for ewe or cryptorchid lambs, only one-third of this increase was attributable to the distinct sexual category of rams; the rest was due to rams being heavier. Carcass size had a much greater effect on pelting load than animal sex: a change in dressed carcass weight of slightly less than 1 kg has the same effect on impulse requirement as the net sex effect. These findings suggest that the differences in pelting effort associated with animal sex are of relatively minor significance compared with the large differences occurring over the range of lamb size normally processed.

Propranolol fails to lower the increased blood pressure caused by cold air exposure.

Cold air exposure stimulates a rise in mean arterial blood pressure (MAP) and plasma norepinephrine (NE). The specific contribution of the beta-adrenergic receptor to this pressor response is unknown. Therefore, we pretreated 12 normal men with placebo or a bradycardia-inducing amount of propranolol prior to exposing them to either 25 degrees C or 4 degrees C air. At 25 degrees C, propranolol pretreatment lowered heart rate (HR) and MAP. When we compared changes in MAP after their respective 30-min exposure at 25 degrees C and 4 degrees C, the cold elevated MAP by 18.4 +/- 1.5 mm Hg in subjects pretreated with propranolol compared with 13.0 +/- 2.5 mm Hg in subjects pretreated with placebo. Fingertip skin temperature (Tfing) measured at 4 degrees C, 9.5 +/- 0.8 degrees C in propranolol-pretreated subjects was lower than the 11.1 +/- 0.7 degrees C with that of placebo. Plasma NE increased equally during cold exposure with both placebo and propranolol pretreatment. We conclude that the beta receptor plays a minor role in generating the pressor response to cold air. Therefore, the effectiveness of acute administrations of propranolol for maintaining normotension in subjects exposed to cold environments may be attenuated.

Decreased free fraction of thyroid hormones after prolonged Antarctic residence.

We investigated the effects of Antarctic residence (AR) on serum thyroid hormone and cardiovascular responses to a 60-min standard cold air (0 degree C) test (SCAT). Serum total thyroxine (TT4) and serum total triiodothyronine (TT3), free T4 (FT4) and T3 (FT3), thyrotropin (TSH), and percent free fraction of T4 (%FT4) and T3 (%FT3) were measured in normal men (n = 15) before and after each of three SCATs. The SCAT was first carried out in California and then repeated after 24 and 44 wk AR. Mean arterial pressure (MAP) and sublingual oral temperature (Tor) were measured before and during each SCAT. The SCAT did not alter thyroid hormones before or after AR. The %FT4 decreased from 0.0334 +/- 0.0017 to 0.0295 +/- 0.0007% (P less than 0.002) with 44 wk AR but without a significant change in TT4 or FT4 for the same period. The %FT3 also decreased from 0.2812 +/- 0.0128 to 0.2458 +/- 0.0067% (P less than 0.005) after 44 wk AR. FT3 decreased (P less than 0.003) but TT3 and TSH were unchanged with 44 wk AR. The decrease in %FT4 and %FT3 may be theoretically accounted for by a 10% increase in either the capacity or the affinity of the serum binding proteins. The SCAT in California increased MAP and did not change Tor. After 44 wk AR, the SCAT no longer increased MAP but did lower Tor. The shift in the Tor and MAP response to the SCAT is consistent with the associated occurrence of cold adaptation during AR. We describe for the first time a decrease in the free fraction of both serum T3 and T4 present with extended polar residence and independent of a SCAT, further characterizing the recently reported "polar T3 syndrome."

Changes in serum triiodothyronine (T3) kinetics after prolonged Antarctic residence: the polar T3 syndrome.

Humans who live in Antarctica for greater than 5 continuous months demonstrate alterations in the hypothalamic-pituitary-thyroid axis. These changes are characterized by 1) increased pituitary release of TSH in response to iv TRH, 2) increased serum clearance of orally administered T3, and 3) normal serum total, free T4, and unstimulated TSH levels. To clarify the mechanism responsible for these findings, serum kinetic studies of 125I-labeled T4 and T3 were carried out in a group of normal men, first in California, then after 20 and 42 weeks of continuous Antarctic residence. The kinetic parameters were calculated by noncompartmental analysis. The mean T4 residence time (MRT) was not different before and after 42 weeks (5.54 +/- 0.50 and 5.08 +/- 0.43 days). The total T4 volume of distribution (TVd) tended to fall over the same period (4.30 +/- 0.12, 3.56 +/- 0.27 L/m2), but was not significantly different (P = 0.075). In contrast to T4, there was an increase from control values for the T3 MRT from 0.83 +/- 0.03 to 1.10 +/- 0.03 days (P less than 0.002) and a more than doubling of the T3 TVd from 15.55 +/- 0.52 to 47.24 +/- 5.09 L/m2 (P less than 0.002) after 42 wk of Antarctic residence. Energy intake increased approximately 40% throughout the study without a change in body weight. The changes in T3 kinetic parameters may be accounted for by increased extravascular tissue binding. The marked increase in T3 TVd and the small increase in MRT are associated with increased T3 production and clearance and only minor changes in T4 kinetics. This is the first description of a mechanism for the change in thyroid hormone economy occurring with extended residence in Antarctica.

Effects of collection methods and storage on the in vitro stability of canine plasma catecholamines.

Norepinephrine (NE) and epinephrine (EPI) collected from dogs were sequentially and temporally measured in blood and plasma at 24 C. Heparin and EDTA anticoagulants, in combination with reduced glutathione and EDTA as a preservative, were also compared. Norepinephrine and EPI concentrations were measured by high-pressure liquid chromatography with electrochemical detection. In heparinized plasma, NE and EPI concentrations were relatively stable in the absence or presence of preservative after 24 hours at 24 C. In EDTA plasma, NE and EPI values were less stable when compared with those in heparinized samples. Norepinephrine concentrations in EDTA plasma without preservative decreased by 163.2 +/- 8.88 pg over 24 hours, compared with an 86.6 +/- 7.92 pg loss of NE in heparinized plasma. The degradation of EPI in EDTA plasma without preservative was also twofold greater, compared with that in heparinized plasma. Addition of preservative had no stabilizing effect on NE or EPI in heparinized or EDTA plasma. During long-term storage at -70 C, plasma NE and EPI values decreased less than 0.6 and less than 0.1 pg/d, respectively. Norepinephrine and EPI values were stable in heparinized blood for 6 hours but decreased to less than 25% and less than 6% of initial base line values, respectively, when plasma separation was delayed 24 hours.