help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mersebach, H.
Right arrow Articles by Feldt-Rasmussen, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mersebach, H.
Right arrow Articles by Feldt-Rasmussen, U.
The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 12 5689-5695
Copyright © 2003 by The Endocrine Society

Abnormal Sympathoadrenal Activity, but Normal Energy Expenditure in Hypopituitarism

Henriette Mersebach, Ole Lander Svendsen, Arne Astrup and Ulla Feldt-Rasmussen

Department of Endocrinology (H.M., O.L.S., U.F.-R.), Copenhagen University Hospital, DK-2100 Copenhagen, Denmark; and The Research Department of Human Nutrition (A.A.), The Royal Veterinary and Agricultural University, DK-1958 Frederiksberg, Denmark

Address all correspondence and requests for reprints to: Henriette Mersebach, M.D., Department of Endocrinology, PE 2131, Copenhagen University Hospital, 9 Blegdamsvej, DK-2100 Copenhagen Ø, Denmark. E-mail: mersebach{at}rh.dk.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
In this study of 23 hypopituitary patients and 26 healthy controls, we have addressed whether the obese state of substituted hypopituitary patients is facilitated by abnormal sympathoadrenal activity or energy expenditure (EE). All patients received adequate substitution therapy including GH therapy. The investigation program included assessment of sympathoadrenal activity (urinary catecholamines), body composition (dual-energy x-ray absorptiometry), appetite sensations (visual analog scale), and EE (indirect calorimetry in respiration chamber). Twenty-four-hour urinary epinephrine adjusted for lean body mass and fat mass was significantly lower in patients compared with controls. GH and hydrocortisone were single negative predictors of urinary epinephrine. The major determinants of EE in patients were lean body mass and fat mass, explaining 96, 95, and 80% of the variance in 24-h EE, sleeping EE, and basal metabolic rate, respectively. Addition of urinary catecholamines explained another 1–4% of the variance in 24-h EE and basal metabolic rate, respectively. Lean patients exhibited significantly more hunger than obese patients and lean controls. In conclusion, hypopituitary patients have lower sympathoadrenal activity but normal EE, compared with healthy controls. This may reflect a central defect in hypopituitarism, however the possible impact of long-term GH and hydrocortisone treatment requires further attention.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
IT IS WELL recognized that hypothalamic-pituitary injury often produces severe obesity related to hyperphagia. Hypopituitarism and in particular GH deficiency (GHD) are significant contributory factors to increased body fat and central obesity (1), linked partly to an altered cortisol metabolism. We have previously reported that 44% of GHD patients were obese, with a body mass index (BMI) above 30 kg/m2, despite adequate hormonal substitution (2).

Because of, or besides, direct hypothalamic damage, abnormalities in sympathoadrenal activity, appetite regulation, energy expenditure (EE), and substrate oxidations might have an impact on the pathogenesis of obesity in hypopituitarism.

The sympathetic nervous system (SNS) and the adrenal medulla, overall referred to as the sympathoadrenal system, play an important role in the regulation of both energy intake and EE, and several experimental studies have appointed low sympathoadrenal activity as a risk factor for weight gain (3, 4).

Obese, hypopituitary patients have been shown to metabolize and oxidize fat less efficiently than their lean counterparts (5). Short-term GH treatment stimulated basal metabolic rate (BMR) (6), resting EE, total EE, and lipid oxidation in both GHD adults (7, 8) and healthy individuals (9, 10, 11). It has been suggested that the calorigenic actions of GH are secondary to increments in lean body mass (LBM). On the contrary, other studies confirm that GH may acutely stimulate EE independent of body composition (9, 10, 12).

The aim of the present study was to assess whether the obese state of substituted hypopituitary patients is facilitated by an abnormal sympathoadrenal activity, EE, or appetite.


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

A total of 23 hypopituitary patients (15 obese, 8 lean) with a mean age of 42 (range, 25–56) yr were examined. Twenty-six healthy individuals (16 obese, 10 lean) with a mean age of 39 (range, 25–57) yr served as controls. Patients and controls were matched for age, gender, and BMI. All hypopituitary patients had multiple pituitary hormone deficiencies, due mainly to pituitary adenoma or craniopharyngioma. Fifteen patients had undergone surgical hypophysectomy, and two patients had received radiotherapy. Mean duration of pituitary disease was 15 (range, 2–34) yr. All patients had severe GHD verified by insulin tolerance test with maximal stimulated GH less than 3.0 µg/liter during hypoglycemia (blood glucose, <2.2 mmol/liter). Replacement therapies were stable at all deficient hormones including GH before entry. All patients, including females of postmenopausal age, received sex steroid replacement therapy. Females were measured in the ovulatory phase (or d 1–10, if substituted). One lean hypopituitary patient had had previously treated Cushing’s disease with a stable substituted adrenal axis before entry. Exclusion criteria were active metabolic disease (including Cushing or diabetes mellitus), cardiovascular disease, unstable hypertension, pregnancy, breast-feeding, abuse of alcohol or narcotics, and treatment with anorectics 3 months before entry. Data on body weight, body composition, leptin, incretins, thyroid hormones, and IGF-I were previously reported (13). Data on original pituitary diagnoses, treatment, and additional pituitary deficiencies are presented in Table 1Go.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Characteristics of 23 hypopituitary patients

 
GH, hydrocortisone, and thyroxine replacement therapy

GH was administered by a daily sc injection at bedtime. GH doses were 1.8 ± 0.9 IU/d and 1.9 ± 0.7 IU/d in obese and lean hypopituitary patients, respectively. A total of 73% of obese patients and 88% of lean hypopituitary patients received steroid replacement therapy with a mean hydrocortisone dose of 20 and 22 mg in the two patient groups, respectively. Sixty percent and 88% of the obese and lean hypopituitary patients, respectively, were substituted with thyroxine. The mean thyroxine dose was 111 and 104 µg in the two groups, respectively.

Study design

The present study was undertaken to examine the influence of pituitary disease on EE, appetite sensations, and sympathetic activity. The study was designed as an observational, cross-sectional case-control study of hypopituitary patients and healthy controls. The study was approved by the regional ethical committee (registration no. KF 01-127/00), and written informed consent was obtained from all patients and controls.

EE

The 24-h EE and substrate oxidation rates were measured by indirect whole-body calorimetry during a 32-h stay in an independently working open-circuit 15-m3 respiration chamber as previously reported (14, 15). The gas exchange of the subjects was calculated from measurements of oxygen and carbon dioxide concentrations (Hartmann and Braun analysers, Frankfurt, Germany) at the outlet of the chamber and from measured outflow through the chambers. Protein oxidation was calculated from urinary nitrogen content in the 24-h collection. Oxidation of lipid and carbohydrate was calculated from oxygen uptake and carbon dioxide production after subtraction of estimated gas exchange arising from protein combustion. The room temperature was maintained constant at 24 C in the daytime and 18 C during the night. Heart rate (HR) was continuously monitored by a telemetry system (Dialogue 2000; Danica Electronics, Copenhagen, Denmark) and stored in a computer for subsequent analysis. Spontaneous physical activity (SPA) in the respiration chambers was assessed by two microwave radars (Sisor MiniRadar; Static Input System SA, Lausanne, Switzerland). The SPA measurements indicate the percentage of time the subjects are active to a detectable degree.

A standard protocol with fixed sessions of physical activity, including two walking sessions and two bouts of bicycling of 15 min each (75 W), was followed during the stay. Sleeping EE (SEE) was measured from 0100–0600 h, and BMR was measured from 0800–0900 h on the second morning after 13 h of fasting, with the subjects awake but still lying relaxed in bed. Physical activity is expressed by the physical activity level (PAL) = 24-h EE/(BMR, extrapolated to 24 h).

To ensure optimal compliance, the study subjects were kept under 24-h surveillance by a laboratory technician during the day and by trained medical students at night. To accustom the subjects to the environment, they spent the night (8 h) preceding the experiment in the chamber.

Energy intake

The energy intake during the chamber stay was based on a weight-maintenance diet determined according to an equation including fat-free mass (FFM), fat mass (FM), SPA (0.056 in females and 0.058 in males), duration of exercise (DE; 30 min), and age (16): EE (kJ/24 h)females = 818 + 119.7 FFM + 25.2 FM + 4009 SPA + 30.5 DE - 6.37 age; and EE (kJ/24 h)males = -1034 + 122.2 FFM + 29.1 FM + 5783 SPA + 64.0 DE + 2.78 age. The diet provided 50% of energy from carbohydrate, 35% from fat, and 15% from protein. The dietary energy content and composition were calculated by DANKOST dietary assessment software (National Food Agency, Søborg, Denmark). Water and decaffeinated coffee and tea were allowed ad libitum.

Appetite ratings

Visual analog scale (VAS) for assessment of appetite sensations was completed in relation to meals for recording of hunger, satiety, fullness, prospective food consumption, and desire to eat meat/fish or something fatty, salty, or sweet. The VAS lines were 100 mm in length with words anchored at each end, expressing the most negative (=0) and positive (=100) ratings, respectively. The reliability of VAS concerning reproducibility and validity was previously reported by Flint et al. (17).

Urinary analysis

Sympathoadrenal function was estimated by assessment of 24-h urinary catecholamine excretion. Samples were collected in acid holding polyethylene containers during the chamber stay and stored at -20 C until they were thawed for further analyses. Catecholamines were isolated by solid phase extraction, separated by chromatography, and detected by amperometric assessment as described by Odink et al. (18).

Anthropometrics and body composition

Body weight was measured after voiding on a decimal scale (model Lindeltronic 8000S, Samhall Griben, Malmø, Sweden). Height was measured barefoot to the nearest 0.5 cm (Seca stadiometer, Kirudan, Broendby, Denmark), and waist and hip circumference was ascertained by tape measure. BMI was calculated as body weight in kilograms divided by height in meters squared. Dual-energy x-ray absorptiometry (DEXA) (Norland XP-26, Norland Medical Systems, Fort Atkinson, WI) measurements were performed as whole body scans with separate assessment of the three compartments: total FM, total LBM, and total bone mineral content (BMC). The sum of these compartments provided the total body weight. During the study period, the scanner was equilibrated daily against a phantom provided from the manufacturer. The software was unchanged, and all DEXA scans were performed by the same skilled laboratory technician. The intraoperator variation was previously assessed to 5% (19).

Statistical analysis

Power calculations were made according to the method of Altman (20) using a nomogram. These data are presented as means and SD values. Group differences were evaluated by t test (for independent samples) or multivariate ANOVA followed by post hoc testing using Bonferroni. Simple and multiple regression analyses were performed by forward stepwise regression and presented with R2 values, P values for the last determinant added, and relative SE values (%). Adjustments of the EE, respiratory quotient (RQ), and catecholamines data for comparison between different groups were made according to Ravussin and Bogardus (21) by using the following equation: Adjusted value = Valuemeasured + slope * (determinantmean - determinantmeasured). Slope is the parameter that derives from the multiple regression equations. All statistical analyses were performed by Statistica version 6.0 (StatSoft Inc., Tulsa, OK).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Metabolic rate and substrate oxidation

The 24-h EE adjusted for LBM and FM showed no difference between hypopituitary patients and healthy controls (Table 2Go). Neither presence of pituitary disease nor obesity could predict EE. The major determinants of all measurements of EE in hypopituitary patients were LBM and FM, explaining 96% of the variance in 24-h EE and 95 and 80% of the variance in SEE and BMR, respectively (Table 3Go). Addition of urinary catecholamines explained another 1–4% of the variance in 24-h EE and BMR, respectively. Waist circumference, age, sex, total T3, or thyroxine dose did not explain further variance in EE when body composition was taken into account.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Metabolic rate and substrate oxidation in 23 hypopituitary patients and 26 healthy controls

 

View this table:
[in this window]
[in a new window]
  		TABLE 3. Determinants of metabolic rates by single and multiple regression analyses in 23 hypopituitary patients

 
The 24-h RQ adjusted for differences in energy balance and relative fat amount (RQadj) was comparable between groups (Table 2Go). RQ increased significantly during exercise compared with 24-h RQ. Macronutrient oxidations were similar between obese and lean hypopituitary patients and controls (Table 2Go).

Urinary catecholamines

The 24-h urinary excretion of epinephrine adjusted for LBM and FM was significantly lower in obese and lean hypopituitary patients compared with their healthy counterparts (P < 0.02 and P < 0.01) (Table 4Go). There were no significant differences between obese and lean hypopituitary patients as well as between obese and lean controls in urinary epinephrine. Urinary epinephrine was significantly lower in hypopituitary patients (all) than healthy controls (all) (Fig. 1Go; P < 0.001). The 24-h urinary excretion of norepinephrine and dopamine adjusted for LBM and FM did not differ between hypopituitary patients and controls.


View this table:
[in this window]
[in a new window]
  		TABLE 4. 24-h urinary excretion of catecholamines in 23 hypopituitary patients and 26 healthy controls

 


View larger version (11K):
[in this window]
[in a new window]
  		FIG. 1. The 24-h urinary excretion of epinephrine adjusted for LBM and total FM in 23 hypopituitary patients and 26 healthy controls. Data are presented in means ± SD. P < 0.001, hypopituitary patients vs. healthy controls.

 
Pituitary disease was a significant negative determinant of urinary epinephrine (R2 = 27%; P < 0.001). GH dose and hydrocortisone dose were single negative predictors of urinary epinephrine (R = 19 and 17%; both P < 0.01), but neither GH nor hydrocortisone could explain additional variance in epinephrine when pituitary disease was taken into account. IGF-I SD score did not correlate with urinary epinephrine.

The 24-h urinary excretion of catecholamines was negatively correlated to hunger and prospective food consumption and positively correlated to satiety and fullness in hypopituitary patients but not in controls. No correlations were observed between urinary excretion of catecholamines and the PAL, 24-h SPA, RQadj, or 24-h HR in hypopituitary patients.

Physical activity

The PAL assessed by the ratio of total 24-h EE divided by BMR extrapolated to 24-h was similar in all groups (Table 2Go). The SPA% was significantly higher in all groups compared with the normal reference level of males and females (5.8 and 5.6%, respectively), but no between-group differences were found (Table 2Go).

HR

Mean 24-h HR (beats per minute) was 74.4 ± 12.2 in hypopituitary patients vs. 73.5 ± 8.0 in controls (not significant). The increment in HR in response to exercise did not differ between groups.

Appetite ratings

Lean hypopituitary patients reported significantly more hunger (at all times), less satiety (at all times), less fullness (at 1230, 1400, and 2000 h) and higher prospective food consumption (at 1230, 2000, and 0900 h) than obese hypopituitary patients. Lean hypopituitary patients also felt significantly more hunger (at 2000 h), less fullness (at 1400 and 2000 h), and higher prospective food consumption than lean controls (at 2000 h). Appetite sensations were comparable between obese hypopituitary patients and obese controls as well as in obese and lean controls.

Body composition and waist circumference

Central obesity (given by the truncal-to-total FM) and body composition were comparable in obese and lean hypopituitary patients and controls (Table 5Go). Body weight was the main predictor of waist circumference in hypopituitary patients, explaining 90% of the variance.


View this table:
[in this window]
[in a new window]
  		TABLE 5. Body composition, BMC, and bone mineral density measured by DEXA of 23 hypopituitary patients and 26 healthy controls

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The results presented here demonstrate a significantly lower urinary excretion of epinephrine in well-substituted hypopituitary patients than in healthy controls. Furthermore, we observed that differences in body composition explained most of the variation in 24-h EE, BMR, and SEE in hypopituitary patients (and controls). Addition of urinary catecholamines explained another 1–4% of the variance in 24-h EE and BMR, respectively. This is in accordance with the finding in normal subjects of Toubro et al. (22). Buemann et al. (23) also reported a contribution of 2–3% from the sympathoadrenal system in the difference in 24-h EE in healthy individuals.

The SNS is recognized to play a role in obesity through its impact on energy intake and/or EE. The reverse relation between SNS activity and energy intake is well described in several experimental studies (24). Besides, sympathomimetic compounds are known to reduce energy intake and increase EE. A mixture of ephedrine and caffeine (20 mg/200 mg) exerted an antiobesity effect due to 80% suppression of energy intake and 20% thermogenic stimulation (25).

It was shown previously that the calorigenic effect of GH caused reduced plasma epinephrine but unchanged plasma norepinephrine after 4 d of GH administration in healthy subjects (10). In the same experiment, it was suggested that the GH-induced increase in resting HR was not mediated by sympathetic pathways, because they did not find evidence of increased sympathetic activity after GH administration (10). We now show that hypopituitary patients after long-term GH treatment have lower urinary epinephrine, but normal norepinephrine, compared with healthy controls. Furthermore, that GH dose is a significant negative predictor of urinary epinephrine. To what extent GH treatment may influence the sympathoadrenal system needs to be established.

It is noteworthy that the hydrocortisone dose explained 17% of the variation in urinary epinephrine. On the other hand, hydrocortisone dose did not explain further variance in epinephrine when pituitary disease was taken into account. The impact of steroid replacement therapy on the chromaffin cells is, however, not fully comprehended. Intraadrenal glucocorticoids are required for the maintenance of chromaffin cells and their production of epinephrine (26). Reduced epinephrine levels, but normal norepinephrine have been reported in children with ACTH deficiency (27), and recently, patients with isolated glucocorticoid deficiency were characterized by minimal resting epinephrine, minimal epinephrine response to stress, but a slight compensatory increase of norepinephrine (28). Thus, the sympathoadrenal activity may somewhat be influenced by the impaired adrenal function in some hypopituitary patients.

Several techniques for assessment of sympathetic or sympathoadrenal activity are available, but none was established as "the gold standard". Quantification of RR intervals reflects both parasympathetic and sympathetic function (29), and the use of microneurography may not reflect whole body sympathetic activity. If plasma norepinephrine is applied to assess whole body SNS activity, arterial sampling is preferred (30), whereas the use of plasma epinephrine concentrations as an indicator of adrenal medullary activity is more straightforward. Nevertheless, the timing of sampling should be taken into consideration. By contrast, urinary excretion of catecholamines provides information of the whole sympathoadrenal system, integrated over the period of the urine collection; however, fluctuations in release and metabolism of catecholamines could invalidate the index of SNS activity (31).

Destruction of the ventromedial hypothalamus produces hyperphagia accompanied by hyperinsulinemia and hypertriglyceridemia, due to vagus dominance and reduced sympathetic activity (32). Appetite sensations may, however, be influenced by different physiological and psychological parameters as well as external factors, such as prior meals, physical activity, temperature, and weather.

Recent data hypothesize that abnormal metabolism of exogenously delivered glucocorticoid might be involved in the development of hypothalamic obesity due to up-regulated 11ß-hydroxysteroid dehydrogenase activity (33). Deficiency of hypothalamic mediators (after injury) induced an intracrine effect of enhanced cortisol activity. Presently, it is unknown whether the sympathoadrenal system, CRH and ACTH, or cytokines may regulate 11ß-hydroxysteroid dehydrogenase activity.

Impaired sympathoadrenal activity (and obesity) can to some degree be associated with reduced physical activity in hypopituitarism. Hypopituitary patients often complain about fatigue, lethargy, and lack of energy (34) that may cause a sedentary lifestyle in these patients. Chong et al. (7) showed a significant proportion of energy expended in physical activity and thermogenesis in GHD adults, similar to that observed in healthy volunteers, despite reports of lethargy and weakness. The physical activity within a respiratory chamber has previously been shown to correlate to habitual, free-living activity (35). Snitker et al. (35) recommended the use of SPA in the chamber as an index of an individual’s propensity to locomotion under standardized conditions. Our study protocol included fixed sessions of physical activity (both walking and bicycling) to imitate free-living activity. The results on PAL imply a sedentary activity level within the chamber. However, both PAL and SPA imply an equal activity level in hypopituitary patients and healthy controls.

GHD has been associated with a subnormal metabolism (6), and discontinuation of daily GH injection is known to reduce overall EE and lipid oxidation in GHD patients (36). It is firmly established that short-term GH exposure stimulates overall EE (7, 8, 9, 10), but the exact mechanisms are not fully known. Previous studies have shown that the acute calorigenic effect of GH is not mediated by changes in leptin secretion or sympathetic activity but is probably related to enhanced cardiac workload (10) and to some degree to increased levels of insulin (12) or iodothyronines (11, 37). The findings in hypopituitary patients of EE and substrate oxidations equal to that observed in healthy controls propose that long-term GH replacement therapy tends to normalize fuel metabolism in hypopituitary patients. The specific mechanisms by which GH exerts this effect may differ in the acute and chronic state. Our data suggest that the GH-induced changes in body composition (and mainly LBM) play a key role in EE during long-term GH replacement therapy; however other pathways certainly exist.

The present study showed a lower sympathoadrenal activity in well-substituted hypopituitary patients than in healthy controls, but normal metabolic rates and substrate oxidations. This may reflect a central defect in hypopituitarism, however the possible impact of long-term GH and hydrocortisone treatment on the SNS requires further attention. Healthy individuals with low SNS activity are susceptible to weight gain, and low urinary excretion of catecholamines could be involved in the development of obesity in hypopituitarism. Whether hypopituitary patients with lower sympathoadrenal activity will achieve an inferior weight loss to intervention than patients with higher levels needs to be confirmed.


   Acknowledgments
 
We thank John Lind for excellent management of the respiratory unit; Betty Fischer for performance of DEXA scans; Lisbeth Kirkegaard, Birthe Nielsen, Margit Grome, and Inge Timmermann for analyzing the blood and urine samples; Charlotte Kostecki for preparation of experimental meals; Victoria Wadsworth for linguistic support; and Benjamin Buemann for statistical support.


   Footnotes
 
This study was supported by Pharmacia, Denmark. H.M. was supported by Copenhagen University Hospital.

Abbreviations: BMC, Bone mineral content; BMI, body mass index; BMR, basal metabolic rate; DE, duration of exercise; DEXA, dual-energy x-ray absorptiometry; EE, energy expenditure; FFM, fat-free mass; FM, fat mass; GHD, GH deficiency; HR, heart rate; LBM, lean body mass; PAL, physical activity level; RQ, respiratory quotient; SEE, sleeping EE; SNS, sympathetic nervous system; SPA, spontaneous physical activity; VAS, visual analog scale.

Received May 19, 2003.

Accepted September 10, 2003.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Rosen T, Bosaeus I, Tolli J, Lindstedt G, Bengtsson BA 1993 Increased body fat mass and decreased extracellular fluid volume in adults with growth hormone deficiency. Clin Endocrinol (Oxf) 38:63–71[Medline]
  2. Mersebach H, Sneppen SB, Feldt-Rasmussen U Long-term growth hormone treatment improves body composition despite increased BMI. Program of the 7th International Pituitary Congress, Phoenix, AZ, 2001, p 107
  3. Bray GA, York DA, Fisler JS 1989 Experimental obesity: a homeostatic failure due to defective nutrient stimulation of the sympathetic nervous system. Vitam Horm 45:1–125[Medline]
  4. Tataranni PA, Young JB, Bogardus C, Ravussin E 1997 A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men. Obes Res 5:341–347[Medline]
  5. Sonksen PH, Salomon F, Cuneo R 1991 Metabolic effects of hypopituitarism and acromegaly. Horm Res 36:27–31
  6. Salomon F, Cuneo RC, Hesp R, Sonksen PH 1989 The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 321:1797–1803[Abstract]
  7. Chong PK, Jung RT, Scrimgeour CM, Rennie MJ, Paterson CR 1994 Energy expenditure and body composition in growth hormone deficient adults on exogenous growth hormone. Clin Endocrinol (Oxf) 40:103–110[Medline]
  8. Stenlof K, Johansson JO, Lonn L, Sjostrom L, Bengtsson BA 1997 Diurnal variations in twenty-four-hour energy expenditure during growth hormone treatment of adults with pituitary deficiency. J Clin Endocrinol Metab 82:1255–1260[Abstract/Free Full Text]
  9. Jorgensen JO, Pedersen SB, Borglum J, Moller N, Schmitz O, Christiansen JS, Richelsen B 1994 Fuel metabolism, energy expenditure, and thyroid function in growth hormone-treated obese women: a double-blind placebo-controlled study. Metabolism 43:872–877[CrossRef][Medline]
  10. Wolthers T, Grofte T, Norrelund H, Poulsen PL, Andreasen F, Christiansen JS, Jorgensen JO 1998 Differential effects of growth hormone and prednisolone on energy metabolism and leptin levels in humans. Metabolism 47:83–88[CrossRef][Medline]
  11. Moller J, Jorgensen JO, Moller N, Christiansen JS, Weeke J 1992 Effects of growth hormone administration on fuel oxidation and thyroid function in normal man. Metabolism 41:728–731[CrossRef][Medline]
  12. Bak JF, Moller N, Schmitz O 1991 Effects of growth hormone on fuel utilization and muscle glycogen synthase activity in normal humans. Am J Physiol 260:E736–E742
  13. Mersebach H, Svendsen OL, Holst JJ, Astrup A, Feldt-Rasmussen U 2003 Comparisons of leptin, incretins and body composition in obese and lean patients with hypopituitarism and healthy individuals. Clin Endocrinol (Oxf) 58:65–71[CrossRef][Medline]
  14. Astrup A, Thorbek G, Lind J, Isaksson B 1990 Prediction of 24-h energy expenditure and its components from physical characteristics and body composition in normal-weight humans. Am J Clin Nutr 52:777–783[Abstract/Free Full Text]
  15. Astrup A, Buemann B, Christensen NJ, Madsen J, Gluud C, Bennett P, Svenstrup B 1992 The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women. J Clin Endocrinol Metab 74:279–286[Abstract]
  16. Klausen B, Toubro S, Astrup A 1997 Age and sex effects on energy expenditure. Am J Clin Nutr 65:895–907[Abstract/Free Full Text]
  17. Flint A, Raben A, Blundell JE, Astrup A 2000 Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord 24:38–48[CrossRef][Medline]
  18. Odink J, Sandman H, Schreurs WH 1986 Determination of free and total catecholamines and salsolinol in urine by ion-pair reversed-phase liquid chromatography with electrochemical detection after a one-step sample clean-up. J Chromatogr 377:145–154[Medline]
  19. Zimmermann-Belsing T, Dreyer M, Holst JJ, Feldt-Rasmussen U 1998 The relationship between the serum leptin concentrations of thyrotoxic patients during treatment and their total fat mass is different from that of normal subjects. Clin Endocrinol (Oxf) 49:589–595[CrossRef][Medline]
  20. Altman DG 1999 Practical statistics for medical research. 1st (reprint) ed. London/Florida: Chapmann, Hall/CRC; 456–460
  21. Ravussin E, Bogardus C 1989 Relationship of genetics, age, and physical fitness to daily energy expenditure and fuel utilization. Am J Clin Nutr 49:968–975
  22. Toubro S, Sorensen TI, Ronn B, Christensen NJ, Astrup A 1996 Twenty-four-hour energy expenditure: the role of body composition, thyroid status, sympathetic activity, and family membership. J Clin Endocrinol Metab 81:2670–2674[Abstract]
  23. Buemann B, Astrup A, Madsen J, Christensen NJ 1992 A 24-h energy expenditure study on reduced-obese and nonobese women: effect of ß-blockade. Am J Clin Nutr 56:662–670[Abstract/Free Full Text]
  24. Bray GA 1991 Reciprocal relation between the sympathetic nervous system and food intake. Brain Res Bull 27:517–520[CrossRef][Medline]
  25. Astrup A, Toubro S, Cannon S, Hein P, Madsen J 1991 Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study. Metabolism 40:323–329[CrossRef][Medline]
  26. Doupe AJ, Landis SC, Patterson PH 1985 Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity. J Neurosci 5:2119–2142[Abstract]
  27. Rudman D, Moffitt SD, Fernhoff PM, Blackston RD, Faraj BA 1981 Epinephrine deficiency in hypocorticotropic hypopituitary children. J Clin Endocrinol Metab 53:722–729[Abstract]
  28. Zuckerman-Levin N, Tiosano D, Eisenhofer G, Bornstein S, Hochberg Z 2001 The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: a study in isolated glucocorticoid deficiency. J Clin Endocrinol Metab 86:5920–5924[Abstract/Free Full Text]
  29. Pomeranz B, Macaulay RJ, Caudill MA, Kutz I, Adam D, Gordon D, Kilborn KM, Barger AC, Shannon DC, Cohen RJ 1985 Assessment of autonomic function in humans by heart rate spectral analysis. Am J Physiol 248:H151–H153
  30. Hjemdahl P 1993 Plasma catecholamines–analytical challenges and physiological limitations. Baillieres Clin Endocrinol Metab 7:307–353[CrossRef][Medline]
  31. Snitker S, Macdonald I, Ravussin E, Astrup A 2000 The sympathetic nervous system and obesity: role in aetiology and treatment. Obes Rev 1:5–15[CrossRef][Medline]
  32. Bray GA 1985 Autonomic and endocrine factors in the regulation of food intake. Brain Res Bull 14:505–510[CrossRef][Medline]
  33. Tiosano D, Eisentein I, Militianu D, Chrousos GP, Hochberg Z 2003 11 ß-Hydroxysteroid dehydrogenase activity in hypothalamic obesity. J Clin Endocrinol Metab 88:379–384[Abstract/Free Full Text]
  34. Rosen T, Wiren L, Wilhelmsen L, Wiklund I, Bengtsson BA 1994 Decreased psychological well-being in adult patients with growth hormone deficiency. Clin Endocrinol (Oxf) 40:111–116[Medline]
  35. Snitker S, Tataranni PA, Ravussin E 2001 Spontaneous physical activity in a respiratory chamber is correlated to habitual physical activity. Int J Obes Relat Metab Disord 25:1481–1486[CrossRef][Medline]
  36. Jorgensen JO, Moller J, Alberti KG, Schmitz O, Christiansen JS, Orskov H, Moller N 1993 Marked effects of sustained low growth hormone (GH) levels on day-to-day fuel metabolism: studies in GH-deficient patients and healthy untreated subjects. J Clin Endocrinol Metab 77:1589–1596[Abstract]
  37. Wolthers T, Groftne T, Moller N, Christiansen JS, Orskov H, Weeke J, Jorgensen JO 1996 Calorigenic effects of growth hormone: the role of thyroid hormones. J Clin Endocrinol Metab 81:1416–1419[Abstract]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mersebach, H.
Right arrow Articles by Feldt-Rasmussen, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mersebach, H.
Right arrow Articles by Feldt-Rasmussen, U.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals