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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 11 3700-3704
Copyright © 1997 by The Endocrine Society

From the Clinical Research Centers

Thyrotropin Levels during Hydrocortisone Infusions That Mimic Fasting-Induced Cortisol Elevations: A Clinical Research Center Study1

M. H. Samuels and P. A. McDaniel

Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health Sciences University, Portland, Oregon 97201

Address all correspondence and requests for reprints to: Dr. M. H. Samuels, Division of Endocrinology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Both short term fasting and administration of high doses of glucocorticoids lead to marked suppression of serum TSH levels in healthy subjects. However, it is not known whether the more mild serum cortisol elevations seen during fasting can account for fasting-induced TSH suppression. To study this question, eight healthy subjects each underwent three 2-day studies: 1) baseline (ad libitum diet), 2) fasting (56 h of total caloric deprivation), 3) hydrocortisone (HC) infusions at a dose and pulsatile pattern that reproduced cortisol levels measured during each subject’s fasting study. Subjects required 34–46 mg HC/24 h to achieve these cortisol levels. During each study, blood samples were drawn every 15 min during the final 24 h for serum cortisol and TSH levels. A TRH stimulation test was performed at the end of each study. By design, fasting and HC infusions induced similar mild increases in 24-h serum cortisol levels (32% over baseline), with the most significant increases seen between 1400–0200 h. Fasting decreased 24-h mean and pulsatile TSH levels 65% from baseline, whereas HC infusions decreased mean and pulsatile TSH levels 51% from baseline. Daytime (0800–0200 h) TSH levels were identical in the two studies, whereas nocturnal (0200–0800 h) TSH levels during HC infusions fell midway between baseline and fasting studies. Serum total T3 and TSH responses to TRH were decreased to a similar degree by fasting or HC infusions. These results suggest that mild elevations in endogenous cortisol levels may mediate at least in part fasting-induced changes in TSH secretion and thyroid hormone levels. In addition, these data show that near-physiological doses of HC and resulting changes in serum cortisol levels within the normal range can cause significant decreases in serum TSH levels.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
IN HEALTHY subjects, short term caloric deprivation leads to marked decreases in serum TSH levels and abolition of the normal nocturnal TSH surge (1, 2). The cause of this suppression in TSH secretion is unknown, but one possible mediator may be elevated serum cortisol levels. Exogenous glucocorticoid administration or endogenous hypercortisolemia due to Cushing’s syndrome are associated with TSH suppression (3, 4, 5, 6), similar to that seen during fasting. However, serum cortisol levels only increase 50–100% over baseline during fasting (1, 7), which is not as marked as cortisol elevations in Cushing’s syndrome. Therefore, it is unclear whether the mild elevations in cortisol levels seen during fasting are sufficient to cause TSH suppression.

To answer this question, we designed a hydrocortisone (HC) infusion protocol that reproduced serum cortisol levels measured during fasting in healthy subjects. In each subject, TSH levels were measured in the fed state, during fasting, and during the HC infusions. This allowed us to isolate one variable, serum cortisol levels, from the many variables that change during fasting and investigate whether this variable was sufficient to account for the observed TSH suppression. We measured serum TSH levels over 24 h during these studies and analyzed dynamic TSH secretion, because single or random TSH measurements may underestimate the severity of TSH suppression during fasting or glucocorticoid administration.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Eight healthy nonobese subjects (four men and four women, aged 20–43 yr) were recruited for the study. Each subject underwent a history, physical examination, and laboratory testing (complete blood count, SMA-20, free T4, and TSH) to exclude chronic illness, medication use, or thyroid or adrenal disease. Each subject signed a consent form approved by the Oregon Health Sciences University institutional review board before starting the study.

Studies

Each subject underwent three in-patient studies conducted at the Oregon Health Sciences University General Clinical Research Center, performed at least 1 month apart and in random order.

Baseline. The subject was admitted at 0800 h on day 1, and iv saline was administered at 75 cc/h for the next 48 h. The subject was allowed ad libitum access to food and beverages. Blood samples (3 cc) were withdrawn every 15 min over 24 h from an iv catheter starting at 0800 h on day 2. At 0800 h on day 3, 250 µg TRH were administered iv, and blood samples were withdrawn 20, 30, and 60 min later.

Fasting. The subject was instructed not to consume any food or beverages starting at midnight the night before admission. He or she was admitted at 0800 h on day 1, and saline was administered as described above. The subject was allowed unlimited access to water, but was not allowed to consume any calorie-containing food or beverages for the next 48 h, for a total fasting time of 56 h. Blood samples were withdrawn as described above starting at 0800 h on day 2 (i.e. during the final 24 h of the 56-h fasting period), and a TRH test was performed at 0800 h on day 3. This protocol is identical to previous protocols used by the investigators to study TSH suppression during fasting (1).

HC. The subject was admitted at 0800 h on day 1, and an iv infusion of HC in saline was administered for the next 48 h in a dose designed to mimic the subject’s fasting-induced cortisol elevations (see below). The subject was allowed unlimited access to food and beverages. Blood samples were withdrawn as in the other studies starting at 0800 h on day 2, and a TRH test was performed at 0800 h on day 3.

HC doses

In a previous study, investigators at the NIH developed an iv HC infusion that reproduces normal serum cortisol levels in subjects with Addison’s disease (8). This protocol includes a variable basal HC infusion rate with superimposed HC pulses to mimic the normal circadian and pulsatile patterns of cortisol secretion. The total amount of HC infused over 24 h is 19 mg. The protocol was obtained from the investigators (J. Zawadzki, personal communication) and was verified to reproduce normal 24-h serum cortisol levels in seven subjects with Addison’s disease (data not shown).

For the current study, this HC infusion protocol was initially increased by 40% (24-h dose = 27 mg) based on our previous study in fasted subjects that found that mean serum cortisol levels increased 40% over those in fed studies (1). The resulting serum cortisol levels in the first two subjects were compared in fasting and HC studies by visual inspection. In both cases, the HC infusion rate was too low to mimic fasting-induced cortisol elevations. Further modifications in the HC infusion rates were made until each subject’s 24-h cortisol profiles during fasting and HC studies were comparable. The 24-h HC infusion protocol was given from 0800 h on day 1 until 0800 h on day 2 and was then repeated until 0800 h on day 3. Blood samples were withdrawn during the second 24-h infusion. Subjects required a mean HC dose of 47 mg/24 h (24 mg/m2·24 h) to achieve adequate cortisol levels (dose range, 32–93 mg/24 h or 19–41 mg/m2·24 h). Five subjects required a single HC study, one subject required two HC studies, and two subjects required three HC studies to optimize doses. In each case, the optimal infusion profile was chosen without knowledge of serum TSH levels to avoid potential bias in determining HC doses. Figure 1Go illustrates a typical 24-h HC infusion protocol for a subject.



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  		Figure 1. HC infusion rate (cubic centimeters per h; concentration of HC, 25 mg/liter) that reproduced fasting-induced serum cortisol levels in a representative subject. The total HC dose per 24 h in this study was 46 mg; the range of doses in the eight subjects was 32–93 mg/24 h. This infusion protocol was repeated during the second 24-h period of the HC study.

 
Hormone assays

Serum samples were assayed for cortisol and TSH by chemiluminescent assays (Nichols Institute, San Juan Capistrano, CA). All samples from a single study were run in the same assay. Assay sensitivity levels were 0.8 µg/dL for cortisol and 0.01 mU/L for TSH. Mean intraassay coefficients of variation were 4% for cortisol at serum levels measured in the current study, 5% for serum TSH levels above 0.5 mU/L, and 13% for serum TSH levels below 0.5 mU/L. The mean interassay coefficients of variation were 11% for cortisol, 7% for TSH levels above 0.5 mU/L, and 20% for TSH levels below 0.5 mU/L. Serum total T3 levels were measured by RIA, and serum free T4 levels were measured by equilibrium dialysis (Nichols Institute) at 0800 h on day 3 of each study.

Data analysis

TSH pulses were located by cluster analysis, using dose-dependent coefficients of variation calculated from sample replicates in each subject’s hormone series. Cluster parameters were two points for test nadirs and one point for test peaks. The t statistics were 2.0 for both up- and down-strokes. These parameters yield false positive and negative peak detection rates less than 5%, as determined by analysis of pooled serum samples and simulated hormone series (1).

To compare serum cortisol levels at different times, 24-h cortisol profiles for each study were divided into four 6-h frames (0800–1345, 1400–1945, 2000–0145, and 0200–0745 h). To compare daytime and nocturnal TSH levels, 24-h TSH levels were divided into two 12-h frames (daytime, 0800–1945 h; nocturnal, 2000–0745 h). All 24, 12, and 6 h hormone levels, TSH pulse parameters, TSH responses to TRH (peak minus baseline), and serum T3 and free T4 levels were compared among the studies by repeated measures ANOVA with Bonferroni t tests. Daytime and nocturnal TSH levels were compared within a study by paired t tests. Results are presented as the mean ± SEM.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Serum cortisol levels (Table 1Go and Fig. 2Go)

Twenty-four-hour mean serum cortisol levels increased 32% over baseline during fasting (from 6.84 ± 0.66 to 9.04 ± 0.54 µg/dL; P < 0.03) and 37% during HC infusions (to 9.39 ± 0.79 µg/dL; P < 0.03). Six-hour mean cortisol levels did not differ among the studies from 0800–1345 h or from 0200–0745 h. Between 1400–1945 h, serum cortisol levels increased 42% during fasting (from 5.98 ± 0.58 to 8.52 ± 0.82 µg/dL; P < 0.01) and 58% during HC infusions (to 9.43 ± 0.84 µg/dL; P < 0.01). Between 2000–0145 h, serum cortisol levels increased 128% during fasting (from 2.50 ± 0.44 to 5.70 ± 1.06 µg/dL; P < 0.003) and 170% during HC infusions (to 6.74 ± 0.72 µg/dL; P < 0.003). Cortisol levels in fasting and HC studies were not statistically different during any time period.


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  		Table 1. Mean serum cortisol levels during each of the three studies over 24 h and in 6-h increments

 


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  		Figure 2. Mean serum cortisol levels measured every 15 min over 24 h in the eight subjects at baseline (solid line), during the final 24 h of a 56-h fasting period (dashed line), and during the final 24 h of a HC infusion designed to reproduce the cortisol levels measured during fasting (dotted line).

 
Serum TSH levels (Table 2Go and Fig. 3Go)

Twenty-four-hour mean serum TSH levels decreased 65% from baseline during fasting (from 2.33 ± 0.32 to 0.82 ± 0.07 mU/L; P < 0.001) and 51% during HC infusions (to 1.14 ± 0.19 mU/L; P < 0.001). Daytime (0800–1945 h) TSH levels decreased 55% during fasting (from 1.80 ± 0.25 to 0.81 ± 0.06 mU/L; P < 0.001) and 53% during HC infusions (to 0.84 ± 0.12 mU/L; P < 0.001). Nocturnal (2000–0745 h) TSH levels decreased 71% during fasting (from 2.85 ± 0.44 to 0.83 ± 0.11 mU/L; P < 0.001) and 49% during HC infusions (to 1.45 ± 0.27 mU/L; P < 0.001). Twenty-four-hour TSH pulse frequency did not change, whereas TSH pulse amplitude was suppressed to a similar degree as mean TSH levels by fasting or HC infusions.


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  		Table 2. Mean serum TSH levels, TSH pulse parameters, and TSH responses to TRH during each of the three studies

 


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  		Figure 3. Mean serum TSH levels measured every 15 min over 24 h in the eight subjects at baseline (solid line), during the final 24 h of a 56-h fasting period (dashed line), and during the final 24 h of a HC infusion designed to reproduce the cortisol levels measured during fasting (dotted line).

 
During the daytime, mean serum TSH levels and TSH pulse amplitude were not different during HC vs. fasting studies. At night, mean serum TSH levels and TSH pulse amplitude during HC studies were significantly different from those during fasting studies, falling midway between fasting and baseline levels.

The normal nocturnal surges in TSH levels and TSH pulse amplitude were evident at baseline, with a 58% increase in mean TSH levels at night (2000–0800 h, 2.85 ± 0.44; 0800–1945 h, 1.80 ± 0.25 mU/L; P < 0.001). The nocturnal TSH surge was abolished by fasting (0.83 ± 0.11 vs. 0.81 ± 0.06 mU/L), but not by HC infusions (1.45 ± 0.27 vs. 0.84 ± 0.12 mU/L; a 73% increase; P < 0.01).

Mean TSH responses to TRH were decreased 45% by fasting (from 14.03 ± 1.67 to 7.74 ± 0.75 mU/L; P < 0.01) and 32% by HC infusions (to 9.56 ± 1.53 mU/L; P < 0.01).

Thyroid hormone levels (Table 3Go)

Serum total T3 levels were decreased 21% at the end of the fasting studies compared to those at the end of the baseline studies (66.8 ± 7.8 vs. 84.3 ± 5.2 ng/dL; P < 0.05) and were decreased 19% at the end of the HC studies (68.0 ± 8.9 ng/dL; P < 0.05). There were no significant changes in serum free T4 levels at the end of any of the studies.


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  		Table 3. Mean total T3 and free T3 levels at 0800 h at the end of each study

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In the current study, short term fasting led to a 40% increase in mean serum cortisol levels between 1400–2000 h and a 148% increase between 2000–0200 h. In contrast, there were no significant changes in mean serum cortisol levels between 0800–1400 h or between 0200–0800 h in fed vs. fasted studies. We were able to closely approximate these mild fasting-induced elevations in cortisol levels by administering a variable infusion of HC to subjects in the fed state. To our knowledge, this is the first study to reproduce serum cortisol levels in the near-physiological range with a protocol that combines basal and pulsed HC infusions to mimic the normal pattern of cortisol secretion. In addition, we tailored each subject’s HC infusion to best match his or her fasting cortisol levels. In this fashion, we were able to isolate serum cortisol levels from other variables that change during fasting.

Using this protocol, we found a 51% decrease in 24-h mean serum TSH levels, which is close to the 65% decrease observed in the same subjects during fasting. Decreases in daytime mean TSH levels and TSH pulse amplitude were identical between the fasting and HC studies (55% vs. 53%), suggesting that cortisol can completely account for fasting-induced TSH suppression during the day. This finding is especially interesting because serum cortisol levels did not increase between 0800–1400 h and only increased 2–4 µg/dL over baseline between 1400–2000 h during either study. As evident in Fig. 3Go, TSH suppression was already apparent before these changes in serum cortisol levels became significant. There are two possible explanations for this. 1) Figure 2Go suggests that there were slight increases in cortisol levels between 0800–1400 h during fasting or HC infusions that were not significant due to small sample size. Such minor cortisol elevations may be sufficient to suppress TSH secretion. 2) As Fig. 2Go shows cortisol elevations were more pronounced at night during either fasting or HC infusions. Similar nocturnal cortisol elevations probably occurred during the night before blood drawing started (i.e. at the end of the first 24 h of HC infusions or fasting) and could have caused TSH suppression that lasted into the next day (when blood drawing began).

In contrast to daytime TSH levels, nocturnal TSH levels during HC infusions fell between levels in baseline (fed) and fasting studies. These data suggest that cortisol can account for over 50% of fasting-induced TSH suppression at night, but that other factors must also contribute to TSH suppression during this time. Possible other mediators of TSH suppression include the inflammatory cytokines, dopamine, or somatostatin (9, 10, 11, 12). In the case of dopamine, studies using the dopamine antagonist metoclopramide suggest that dopaminergic tone is not increased during fasting (13). In the case of the cytokines, it appears that these compounds stimulate the hypothalamic-pituitary-adrenal axis (14, 15). Therefore, the changes in thyroid hormone levels observed during increased levels of cytokines may still occur via increased cortisol levels.

In addition to fasting-induced TSH suppression, our study has broader implications for glucocorticoid-induced changes in serum TSH levels. Previous studies reported decreased TSH levels with acute glucocorticoid administration, but at much higher glucocorticoid doses than in the current study (5, 6). Studies in patients with Addison’s disease or in healthy subjects given metyrapone suggest that more physiological doses of glucocorticoids decrease TSH levels within the normal range, but these data may be confounded by coexisting thyroid disease in patients with Addison’s disease (16, 17, 18, 19, 20, 21, 22, 23). Hangaard et al. performed the most detailed study to date of serum TSH levels during variable infusions of HC in patients with Addison’s disease (24). They measured serum TSH levels in subjects given no HC, an infusion of HC that led to normal serum cortisol levels, and an infusion of HC that led to high serum cortisol levels. Serum TSH levels showed a progressive decline with increasing doses of HC in the same range as the results in our study. Together with Hangaard’s study, our results suggest that low doses of glucocorticoids, which cause either no or mild elevations in serum cortisol levels, are sufficient to suppress TSH secretion. These findings have implications for the interpretation of TSH levels in patients who receive near-physiological doses of glucocorticoids as antiinflammatory treatment or for Addison’s disease.

In our study, both fasting and HC infusions blunted TSH responses to exogenous TRH, suggesting that the observed TSH suppression occurs directly at the pituitary level. Previous studies in humans support these findings (1, 5, 6, 25, 26, 27), although other studies suggest that fasting- or glucocorticoid-induced TSH suppression may occur via hypothalamic TRH suppression in animals (28, 29, 30).

The changes in serum T3 levels we measured during fasting or HC infusions are also consistent with published reports, although the current doses of HC are much lower than glucocorticoid doses previously shown to decrease serum T3 levels (1, 2, 5, 31, 32, 33, 34). This suggests that the mild cortisol elevations induced by fasting may mediate the observed decreases in T3 levels. However, it should be noted that alterations in peripheral T4 metabolism induced by fasting may differ from those induced by glucocorticoids. For example, fasting causes decreased rT3 clearance without changes in rT3 production (35), whereas dexamethasone administration causes increased rT3 production without changes in rT3 clearance (36). Thus, the same changes in peripheral thyroid hormone levels may be mediated via different mechanisms in states of fasting or hypercortisolemia.

A potential limitation of our study was that subjects received the same HC dose on both days of the infusion, whereas their cortisol levels were only documented to be in the same range on the second day of the fasting period. Therefore, subjects may have had slightly higher cortisol levels during the first day of HC infusion compared to those on the first day of fasting. Practical difficulties in measuring cortisol levels over 48 h and matching each subject’s cortisol levels precluded us from changing the HC dose between the first and second days. However, the overall changes in serum cortisol levels were so mild and the resulting changes in serum TSH levels so marked that we expect this limitation did not markedly affect our results.

In conclusion, by employing a variable infusion of HC tailored to each individual, we were able to mimic the mild increases in serum cortisol levels seen during short term fasting in healthy subjects. These HC infusions led to decreases in 24-h serum TSH levels, TSH responses to TRH, and serum T3 levels similar to those seen during fasting. These results suggest that cortisol may at least in part mediate fasting-induced changes in thyroid hormone levels. In addition, these results prove that marked decreases in serum TSH levels can be induced by near-physiological doses of HC, with resulting changes in serum cortisol levels within the normal range.


   Acknowledgments
 
The authors thank the Oregon Health Sciences University General Clinical Research Center staff for excellent patient care, sample collection, and assay performance.


   Footnotes
 
1 This work was supported by NIH Grant R29-DK-48366 (to M.H.S.) and the Oregon Health Science University Clinical Research Center (NIH GCRC Grant M01-RR-00334) Back

Received April 3, 1997.

Revised June 26, 1997.

Accepted July 9, 1997.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Samuels MH, Kramer PK. 1996 Differential effects of short-term fasting on pulsatile thyrotropin, gonadotropin, and alpha-subunit secretion in healthy men. J Clin Endocrinol Metab. 81:32–36.[Abstract]
  2. Romijn JA, Adriaanse R, Brabant G, Prank K, Endert E, Wiersinga WM. 1990 Pulsatile secretion of thyrotropin during fasting: a decrease of thyrotropin pulse amplitude. J Clin Endocrinol Metab. 70:1631–1636.[Abstract]
  3. Bartalena L, Martino E, Petrini L, et al. 1991 The nocturnal serum thyrotropin surge is abolished in patients with adrenocorticotropin (ACTH)-dependent or ACTH-independent Cushing’s syndrome. J Clin Endocrinol Metab. 72:1195–1199.[Abstract]
  4. Adriaanse R, Brabant G, Endert E, Wiersinga WM. 1994 Pulsatile thyrotropin secretion in patients with Cushings’ syndrome. Metabolism. 43:782–786.[CrossRef][Medline]
  5. Samuels MH, Luther M, Henry P, Ridgway EC. 1994 Effects of hydrocortisone on pulsatile pituitary glycoprotein secretion. J Clin Endocrinol Metab. 78:211–215.[Abstract]
  6. Brabant A, Brabant G, Schuermeyer T, et al. 1989 The role of glucocorticoids in the regulation of thyrotropin. Acta Endocrinol (Copenh). 121:95–100.[Medline]
  7. Bergendahl M, Vance ML, Iranmanesh A, Thorner MO, Veldhuis JD. 1996 Fasting as a metabolic stress paradigm selectively amplifies cortisol secretory burst mass and delays the time of maximal nyctohemeral cortisol concentrations in healthy men. J Clin Endocrinol Metab. 81:692–699.[Abstract]
  8. Esteban NV, Loughlin T, Yergey AL, et al. 1991 Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab. 71:39–45.
  9. Van der Poll T, Romijn JA, Wiersinga WM, Sauerwein HP. 1990 Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. J Clin Endocrinol Metab. 71:1567–1572.[Abstract]
  10. Boelen A, Platvoet-ter Schiphorst MC, Wiersinga WM. 1993 Association between serum interleukin-6 and serum 3,5,3'-triiodothyronine in nonthyroidal illness. J Clin Endocrinol Metab. 77:1695–1699.[Abstract]
  11. Stouthard JML, Van der Poll T, Endert E, et al. 1994 Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans. J Clin Endocrinol Metab. 79:1342–1346.[Abstract]
  12. Samuels MH, Henry P, Ridgway EC. 1992 Effects of dopamine and somatostatin on pulsatile pituitary glycoprotein secretion. J Clin Endocrinol Metab. 74:217.[Abstract]
  13. Samuels MH, Kramer P. 1996 Effects of metoclopramide on fasting-induced TSH suppression. Thyroid6 :85–89.
  14. Mastorakos G, Chrousos GP, Weber JS. 1993 Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab. 77:1690–1694.[Abstract]
  15. Denicoff KD, Durkin TM, Lotze MT, et al. 1989 The neuroendocrine effects of interleukin-2 treatment. J Clin Endocrinol Metab. 69:402–410.[Abstract]
  16. McHardy-Young S, Lessof MH, Maisey MN. 1972 Serum TSH and thyroid antibody studies in Addison’s disease. Clin Endocrinol (Oxf). 1:45–56.[Medline]
  17. Topliss DJ, White EL, Stockigt JR. 1980 Significance of thyrotropin excess in untreated primary adrenal insufficiency. J Clin Endocrinol Metab. 50:52–56.[Medline]
  18. Barnett AH, Donald RA, Espiner EA. 1982 High concentrations of thyroid-stimulating hormone in untreated glucocorticoid deficiency: indication of primary hypothyroidism? Br Med J. 285:172–173.
  19. Grubeck-Loebenstein B, Vierhapper H, Waldhausl W, Nowotny P. 1983 Thyroid function in adrenocortical insufficiency during withdrawal and re-administration of glucocorticoid substitution. Acta Endocrinol (Copenh). 103:254–258.[Medline]
  20. Ismail AAA, Burr WA, Walker PL. 1989 Acute changes in serum thyrotrophin in treated Addison’s disease. Clin Endocrinol (Oxf). 30:225–230.[Medline]
  21. Shigemasa C, Kouchi T, Ueta Y, Mitani Y, Yoshida A, Mashiba H. 1992 Evaluation of thyroid function in patients with isolated adrenocorticotropin deficiency. Am J Med Sci. 304:279–284.[Medline]
  22. Stryker TD, Molitch ME. 1985 Reversible hyperthyrotropinemia, hyperthyroxinemia, and hyperprolactinemia due to adrenal insufficiency. Am J Med. 79:271–276.[Medline]
  23. Re RN, Kourides IA, Ridgway EC, Weintraub BD, Maloof F. 1976 The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin. J Clin Endocrinol Metab. 43:338–346.[Abstract]
  24. Hangaard J, Andersen M, Grodum E, Koldkjaer O, Hagen C. 1996 Pulsatile thyrotropin secretion in patients with Addison’s Disease during variable glucocorticoid therapy. J Clin Endocrinol Metab. 81:2502–2507.[Abstract]
  25. Borst GC, Osburne RC, O’Brian JT, Georges LP, Burman KD. 1983 Fasting decreases thyrotropin responsiveness to thyrotropin-releasing hormone: a potential cause of misinterpretation of thyroid function tests in the critically ill. J Clin Endocrinol Metab. 57:380–383.[Abstract]
  26. Sowers JR, Carlson HE, Brautbar N, Hershman JM. 1977 Effect of dexamethasone on prolactin and TSH responses to TRH and metoclopramide in man. J Clin Endocrinol Metab. 44:237–241.[Abstract]
  27. Spencer CA, Lum SMC, Wilber JF, Kaptein EM, Nicoloff JT. 1983 Dynamics of serum thyrotropin and thyroid hormone changes in fasting. J Clin Endocrinol Metab. 56:883–888.[Abstract]
  28. Blake NG, Eckland DJA, Foster OJF, Lightman SL. 1991 Inhibition of hypothalamic thyrotropin-releasing hormone messenger ribonucleic acid during food deprivation. Endocrinology. 129:2714–2718.[Abstract]
  29. Rondeel JMM, Heide R, de Greef WJ, et al. 1992 Effect of starvation and subsequent refeeding on thyroid function and release of hypothalamic thyrotropin-releasing hormone. Neuroendocrinology. 56:348–353.[Medline]
  30. Van Haasteren GA, Linkels E, Klootwijk W, et al. 1995 Starvation-induced changes in the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA and the hypothalamic release of proTRH-derived peptides: role of the adrenal gland. J Endocrinol. 145:143–53.[Abstract]
  31. Gamstedt A, Jarnerot G, Kagedal B. 1981 Dose related effect of betamethasone on iodothyronines and thyroid hormone-binding proteins in serum. Acta Endocrinol (Copenh). 96:482–490.
  32. Chopra IJ, Williams DE, Orgiazzi J, Solomon DH. 1975 Opposite effects of dexamethasone on serum concentraions of 3,3'5'-triiodothyronine (reverse T3) and 3,3'5'-triiodothyronine (T3). J Clin Endocrinol Metab. 41:911–920.[Abstract]
  33. DeGroot LJ, Hoye K. 1976 Dexamethasone suppression of serum T3 and T4. J Clin Endocrinol Metab. 42:976–978.[Abstract]
  34. Burr WA, Griffiths RS, Ramsden DB, et al. 1976 Effect of a single dose of dexamethasone on serum concentraions of thyroid hormones. Lancet. 2:58–61.[Medline]
  35. LoPresti JS, Gray D, Nicoloff JT. 1991 Influence of fasting and refeeding on 3,3',5'-triiodothyronine metabolism in man. J Clin Endocrinol Metab. 72:130–136.[Abstract]
  36. LoPresti JS, Elgen A, Kaptein E, Anderson KP, Spencer CA, Nicoloff JT. 1989 Alterations in 3,3',5'-triiodothyronine metabolism in response to propythiouracil, dexamethasone, and thyroxine administration in man. J Clin Invest. 84:1650–1656.



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K. M Oltmanns, B. Dodt, B. Schultes, H. H Raspe, U. Schweiger, J. Born, H. L Fehm, and A. Peters
Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients
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 EndocrinologyHome page
C. Fekete, D. L. Marks, S. Sarkar, C. H. Emerson, W. M. Rand, R. D. Cone, and R. M. Lechan
Effect of Agouti-Related Protein in Regulation of the Hypothalamic-Pituitary-Thyroid Axis in the Melanocortin 4 Receptor Knockout Mouse
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 J Intensive Care MedHome page
E. S. Nylen and B. Muller
Endocrine Changes in Critical Illness
J Intensive Care Med, March 1, 2004; 19(2): 67 - 82.
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 Am. J. Physiol. Endocrinol. Metab.Home page
R. M. Ortiz, D. P. Noren, B. Litz, and C. L. Ortiz
A new perspective on adiposity in a naturally obese mammal
Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1347 - E1351.
[Abstract] [Full Text] [PDF]

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R. M. Ortiz, C. E. Wade, and C. L. Ortiz
Effects of prolonged fasting on plasma cortisol and TH in postweaned northern elephant seal pups
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2001; 280(3): R790 - R795.
[Abstract] [Full Text] [PDF]

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 J. Neurosci.Home page
C. Fekete, E. Mihaly, L.-G. Luo, J. Kelly, J. T. Clausen, Q. Mao, W. M. Rand, L. G. Moss, M. Kuhar, C. H. Emerson, et al.
Association of Cocaine- and Amphetamine-Regulated Transcript-Immunoreactive Elements with Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Hypothalamic Paraventricular Nucleus and Its Role in the Regulation of the Hypothalamic-Pituitary-Thyroid Axis during Fasting
J. Neurosci., December 15, 2000; 20(24): 9224 - 9234.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
M. H. Samuels
Effects of Metyrapone Administration on Thyrotropin Secretion in Healthy Subjects-A Clinical Research Center Study
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3049 - 3052.
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 J. Clin. Endocrinol. Metab.Home page
M. H. Samuels
Effects of Variations in Physiological Cortisol Levels on Thyrotropin Secretion in Subjects with Adrenal Insufficiency: A Clinical Research Center Study
J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1388 - 1393.
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 J. Clin. Endocrinol. Metab.Home page
L. Plat, R. Leproult, M. L’Hermite-Baleriaux, F. Fery, J. Mockel, K. S. Polonsky, and E. Van Cauter
Metabolic Effects of Short-Term Elevations of Plasma Cortisol Are More Pronounced in the Evening Than in the Morning
J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3082 - 3092.
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