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*LEVOTHYROXINE
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 10 3493-3497
Copyright © 1998 by The Endocrine Society

Original Studies

Changes in Thyroid Hormone Levels during Growth Hormone Therapy in Initially Euthyroid Patients: Lack of Need for Thyroxine Supplementation1

David T. Wyatt, Neil Gesundheit and Barry Sherman

Department of Pediatrics, Medical College of Wisconsin (D.T.W.), Milwaukee, Wisconsin 53226; and the Department of Medical Affairs, Genentech, Inc. (N.G., B.S.), South San Francisco, California 94080

Address all correspondence and requests for reprints to: David T. Wyatt, M.D., Medical College of Wisconsin, Department of Pediatrics, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226. E-mail: dtwyatt{at}mcw.edu


   Abstract
Top
 Abstract
Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 
The occurrence of central hypothyroidism in previously euthyroid children during GH therapy has been reported with widely varying incidence. We monitored the acute effects on the hypothalamic-pituitary-thyroid axis in 15 euthyroid children with classic GH deficiency during the first year of GH therapy. All were initially euthyroid, as assessed by normal baseline TSH, T4, free T4, and T3 levels and negative antithyroid antibodies. A thyroid profile (T4, free T4 index, T3, rT3, and TSH) was performed at baseline and 1, 3, 6, 9, and 12–15 months after GH therapy began; a TRH stimulation test was performed at baseline and after 1, 3, and 9 months of therapy. By 1 month, there were significant decreases in T4, free T4 index, and rT3, and significant increases in T3 and the T3/T4 ratio. The changes from baseline values were greatest at 1 month, were almost universal for all thyroid values, and showed a gradual return to baseline from 3–12 months. There were no clinical signs of hypothyroidism and no change in baseline or TRH-stimulated TSH levels or in cholesterol levels, and all patients grew at velocities expected for the treatment schedule. There is little evidence for the development of clinically significant hypothyroidism in the great majority of initially euthyroid patients after GH therapy is begun. T4 supplementation is seldom needed in such patients.


   Introduction
Top
 Abstract
 Introduction
Experimental Subjects
 Materials and Methods
 Results
 Discussion
 References
 
THE DEVELOPMENT of central hypothyroidism has been reported during GH therapy in children initially thought to have normal thyroid function. The actual incidence is controversial, however, with some studies showing a rare (1, 2, 3, 4, 5, 6) and others a high (7, 8, 9, 10, 11) occurrence. The reasons for this wide discrepancy are unclear, but may be related to the complex interaction between GH and the hypothalamic-pituitary-thyroid axis. The issue has important clinical implications. A recent analysis of endocrine therapy in over 2300 patients showed that 29% of children with idiopathic GH deficiency and 61% of children with organic GH deficiency were also receiving thyroid hormone therapy (12). To clarify this issue, we monitored the acute effects of GH on the hypothalamic-pituitary-thyroid axis in euthyroid children with previously untreated GH deficiency during the first year of therapy.


   Experimental Subjects
Top
 Abstract
 Introduction
 Experimental Subjects
Materials and Methods
 Results
 Discussion
 References
 
Fifteen naive GH-deficient patients were sequentially recruited. GH deficiency was defined as a peak GH level of 10 ng/dL or less (Kallestad Quantitope, Austin, TX) in response to two standard stimulation tests (iv arginine followed by oral clonidine) in a patient with a growth velocity of 6 cm/yr or less if younger than 5 yr or of 5 cm/yr or less if older than 5 yr. All patients were prepubertal (bone age, <=10 yr for females and <=11 yr for males), were taking no thyroid supplementation, and had normal baseline endogenous thyroid function, as assessed by normal TSH, T4, free T4, and T3 levels and negative thyroid antibodies (antimicrosomal and antithyroglobulin). No patient was taking any medication known to interfere with thyroid metabolism (13). Eleven patients had idiopathic GH deficiency. Four patients had organic GH deficiency, three had received central nervous system radiation, and two had central diabetes insipidus treated with desmopressin acetate (Rorer Pharmaceuticals, Fort Washington, PA). Patients were randomized for 1 yr to either daily (n = 8) or three times weekly (n = 7) recombinant human GH therapy (Protropin, Genentech, Inc., South San Francisco, CA) at a standard sc dose of 0.30 mg/kg·week as part of a multicenter treatment study. No other endocrine therapy was given during the year of the study. This study was approved by the human research review committee of the Medical College of Wisconsin and the human rights review board of Childrens Hospital of Wisconsin. Written informed consent was obtained from all families.


   Materials and Methods
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
Results
 Discussion
 References
 
A thyroid profile [T4, free T4 index (FT4I), T3, rT3, and TSH] was performed before and 1, 3, 6, 9, and 12–15 months after GH therapy began. Serum T4 and T3 were determined by RIA (Diagnostic Products, Los Angeles, CA), with a normal adult range of 64–154 nmol/L for T4 and 1.38–2.84 nmol/L for T3 (14). The FT4I was calculated as the product of T4 and the normalized T4 resin uptake, with a normal range of 80–135 (15). Serum rT3 was measured by RIA (Serono Laboratories, Norwell, MA), with a normal adult range of 0.22–0.46 nmol/L (14). Standard TSH stimulation (Protirelin, Abbot Labs, North Chicago, IL, 7 µg/kg iv; TSH drawn at 0, 10, 20, 30, 60, and 120 min) was performed before and 1, 3, and 9 months after GH therapy. TSH was measured by an immunoradiometric assay (Serono Laboratories), with a normal range of 0.5–4.0 mU/L (14). The TSH area under the curve was calculated by the trapezoidal rule. The large number of samples required four assay runs for T4, T3, and TSH, and two assay runs for rT3. Each run had its own standard curve, internal control, and duplication. The interassay coefficient of variation for T4 was 3.8% for 50–180 nmol/L; those for T3 were 5.6%, 2.6%, and 3.2% for mean values of 0.08, 1.95, and 2.95 nmol/L, respectively; those for TSH were 22%, 3.4%, and 2.5% for mean values of 0.5, 7.3, and 27.2 mU/L, respectively (14). Insulin-like growth factor I (IGF-I) was measured at baseline and 12 months (16). Fasting cholesterol was obtained at baseline and after 6 and 12 months of therapy. At each clinic visit, attention was given to signs or symptoms of hypothyroidism, such as constipation, fatigue, cold intolerance, skin or hair changes, delayed Achilles reflex relaxation phase, or poor response to GH therapy.

Statistical analysis was performed with SigmaStat for Windows (version 2.0, 1995, Jandel Scientific, San Rafael, CA). Data were analyzed for normality (Kolmogorov-Smirnov test) and equal variance (Levine Median); nonparametric testing was performed whenever data did not meet both these criteria. Data from thrice weekly patients (n = 7) were compared to those from daily patients (n = 8) by either Student’s t test or the Mann-Whitney rank sum test. Baseline auxological and laboratory data were compared within each group, between groups, and as a combined group (n = 15) with end of year data by either paired t test or Wilcoxon signed rank test. As there were no significant differences in thyroid data between the daily and the thrice weekly groups, all reported analyses were for the combined group. Comparisons between the sampling points for thyroid values were made with Friedman repeated measures ANOVA on ranks and the Student-Newman-Keuls method for pairwise multiple comparisons (P < 0.05 was considered significant). Exploratory analyses with Pearson product-moment correlations were performed between clinical variables (age; baseline and year-end height or height age; baseline and year-end weight, ponderal index; baseline and year-end growth velocity; and baseline and year-end height and velocity SD score), between lab variables (all thyroid values; baseline and year-end IGF-I), and between both clinical and lab variables to detect possible predictive variables for the first year growth velocity response (Vel-1 or Vel-1 SD score). To allow for the large number of comparisons, we used a significance level of P <= 0.01 for correlations. Both best subsets (for optimum Cp and adjusted r2) and forward stepwise regression analyses were then used to confirm significant predictive variables with minimal multicollinearity for final models of prediction of first year velocity (17). SD scores (z-scores) were calculated from the National Center for Health Statistics data (18).


   Results
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
Discussion
 References
 
The daily group weighed less at baseline (18.3 vs. 25.4 kg; P = 0.04) and had a lower baseline (14.4 vs. 17.1; P = 0.007) and end of year ponderal index (14.9 vs. 17.2; P = 0.04). For all other auxological or biochemical parameters, there were no significant differences between the daily and thrice weekly groups. These included age; baseline or end of year height, height age, or height SD score; baseline or end of year growth velocity (Vel-1) or velocity SD score (Vel-1 z); baseline or end of year IGF-I, or cholesterol; or any thyroid value at any time point.

All patients in both subgroups (daily and thrice weekly) and as a combined group showed the expected increases in growth parameters and IGF-I (Table 1Go). These growth rates are slightly better than those reported in the first year of therapy for naive patients with GH deficiency by the National Cooperative Growth Study (9.8 cm/yr for daily; 8.9 cm/yr for thrice weekly) (1, 19). There was a significant negative correlation between the first year growth velocity (Vel-1) and age, baseline height, baseline and year-end height age, and baseline and year-end bone age. Thus, better treatment velocity tended to occur in younger, shorter children who had lower bone ages. However, there was no correlation between Vel-1 and baseline or year-end height SD score; baseline velocity; baseline or year-end predicted adult height or height SD score; or baseline or year-end IGF-I values. The Vel-1 z-score did not correlate with any auxological value or with any IGF-I level.


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  		Table 1. Changes in height z, velocity, velocity z, IGF-I, and cholesterol during 1 yr of GH therapy

 
Individual changes in T4 are shown in Fig. 1Go. No patient had any clinical indication of hypothyroidism, and all remained without T4 supplementation for the year of the study. One T4 value was below the normal range: 57 nmol/L after 3 months of GH therapy (normal adult range, 64–154 nmol/L). The T3 and TSH levels for the same sample were 2.0 nmol/L (normal, 1.38–2.84 nmol/L) and 2.3 mIU/mL; baseline T4 was 69 nmol/L, the lowest of the group; growth velocity increased from 3.6 to 7.4 cm/yr. Although about half of the patients showed a substantial return to baseline values by 3 months, one half remained well below baseline until later in the treatment year.



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  		Figure 1. Changes in T4 during the first year of GH therapy. n = 15 for all months (some symbols overlap) except month 12, where n = 13.

 
Changes in mean T4, FT4I, rT3, T3, and T3/T4 ratio are shown in Figs. 2Go and 3Go. The greatest change from baseline always occurred by month 1, with a gradual recovery during months 3–12. The declines in T4, FT4I, and rT3 were mirrored by increases in T3 and the T3/T4 ratio. The changes were seen by month 1 in nearly all patients, occurring in the same direction in 11 of 15 patients for T4 (mean decline, -15.5%; baseline mean, 106.4 nmol/L; month 1 mean, 88.6 nmol/L), in 14 of 15 patients for FT4I (mean decline, -17.3%), in 14 of 15 patients for rT3 (mean decline, -21.3%; baseline mean, 0.30 nmol/L; month 1 mean, 0.23 nmol/L), in 13 of 15 patients for T3 (mean rise, 14.0%; baseline mean, 2.37 nmol/L; month 1 mean, 2.66 nmol/L), and in all 15 patients for T3/T4 ratio (mean rise, 35.9%). There were no significant changes in either baseline TSH values or TRH-stimulated peak TSH or area under the curve values during the year (Table 2Go).



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  		Figure 2. Changes in T4, FT4I, rT3, T3, and T3/T4 ratio during the first year of GH therapy. The mean ± [scap]sd are shown for each sampling point. n = 15 for all months except where noted. Significant (P <= 0.05, by repeated measures ANOVA) changes from baseline (marked by downward arrow) are shown by asterisks above the error bar. Significant changes from month 1 (marked by upward arrow) are shown by asterisks below the error bar. Thus, when the series of top asterisks ends, the value is no longer significantly different from and has essentially returned to baseline. The series of bottom asterisks marks recovery from the point of maximal change, which was always the month 1 point.

 


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  		Figure 3. See Fig. 2Go for details.

 

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  		Table 2. Basal and TRH-stimulated peak TSH values with associated area under the curve TSH sums (AUC)

 
The rT3 month 1 level correlated with Vel-1 (r = 0.659; P = 0.008); the T4 baseline level correlated with Vel-1 SD score (r = 0.641; P = 0.010). There were no correlations (at P <= 0.01) between Vel-1 or Vel-1 SD score and any other thyroid value or with the change from month 0 to month 1 for any thyroid value. There were no significant changes in cholesterol levels (Table 1Go), nor were there any correlations between any cholesterol level at any time point and any thyroid hormone level at any time point, including peak TSH levels or the change in thyroid levels between baseline and month 1.

Baseline T4, FT4I, and T3 correlated with all subsequent values, respectively (except month 1 for FT4I and T3). Thus, patients remained for the most part in the same respective positions for all thyroid hormone levels; each showed approximately the same percent changes. Both T4 and FT4I correlated positively with T3 at all time points (except month 9). Thus, patients with higher T4 values also had higher T3 values throughout the study. T4 and FT4I also correlated positively with rT3 at all but baseline values. However, T3 did not correlate (even negatively) with rT3 at any time point.

All clinical and laboratory variables selected with best subsets regression analysis for a predictive model of Vel-1 showed high multicollinearity; no sets could be produced with forward stepwise regression. All models reduced to simple correlations between at most one single independent variable and Vel-1; thus, it was not possible to develop a multiple linear regression model to account for the variance in Vel-1. As only the baseline T4 value correlated with the Vel-1 SD score, no multiple regression analysis was attempted for that dependent variable.


   Discussion
Top
 Abstract
 Introduction
 Experimental Subjects
 Materials and Methods
 Results
 Discussion
References
 
This study shows that shifts in thyroid hormone levels are very common during the first year of GH therapy in children who are initially euthyroid. Clinical hypothyroidism, however, is very uncommon. Although almost all children showed a decline in T4 values, only one T4 value was below the normal range, and all T3 levels were within or slightly above the normal adult range (14). There were no clinical signs of hypothyroidism, no change in baseline or TRH-stimulated TSH levels, and no changes in cholesterol levels as might be seen with hypothyroidism (20), and all patients grew at the velocities expected for the treatment schedule.

The mechanism of these shifts remains unclear. They are of rapid onset (16, 21, 22) and gradual resolution; they occur in children (21, 23, 24, 25) and adults with GH deficiency, even during T4 therapy (23, 26), and in normal adults (16, 22, 27). Some of these changes may be due to a GH-induced increase in peripheral conversion of T4 to T3 and a decrease in conversion of T4 to rT3 (16, 23, 24, 26, 27, 28, 29). GH produces increases in extracellular water, which could have indirect effects on thyroid hormone kinetics. However, this study was not designed to evaluate such kinetics. Whatever the mechanism, the increase in T3 levels and the decreases in T4 and rT3 levels can be seen as temporary perturbations, with the patient remaining euthyroid as evidenced by a normal growth response to GH and a lack of change in TSH levels.

Some have suggested that GH inhibits TSH release (16, 23, 28, 29), perhaps via increased somatostatinergic tone or by the negative feedback of an increased T3 level. Jorgensen found decreased nocturnal TSH surge in GH-deficient adults treated with GH (30), but Rose could not find such a change in children with idiopathic short stature (6). Sato reported increased TSH release in GH-deficient children treated with GH (24), whereas Demura reported a mixed population, with some children showing no change in TSH and some developing a delayed and sustained response to TRH during GH therapy (31). Conners (32) and Porter (33) found a reversible suppression of TRH-stimulated TSH in GH-deficient children, which returned to pretherapy responses after several months of continuing GH therapy. Others, like us, have found no change in either baseline or TRH-stimulated TSH levels in GH-deficient children (3, 21, 34), in normal adults (35), or in GH-deficient adults (26) during GH therapy. All of these studies differ somewhat in subjects, GH dose, sample timing, and TSH assays. None, including ours, determined whether there were changes in relative distribution volumes, relative clearance rates, or production rates of thyroid hormones.

In a recent survey of pediatric endocrinologists (36), we found that 86% of respondents routinely recheck thyroid hormone status during the first year of GH therapy, with 28% retesting at 3 months, 29% at 6 months, and 22% at 12 months. Total and free T4 and TSH are usually measured (79%, 49%, and 82%, respectively), whereas total and free T3 are rarely determined (14% and 4%, respectively). As we have shown, about one half of patients will have T4 levels below baseline with unchanged TSH levels after 3–6 months of GH therapy, a bichemical combination that could lead to the frequent impression that a dysfunctional hypothalamic-pituitary-thyroidal axis had been uncovered. Supplemental thyroid hormone might then be prescribed as a prophylactic measure regardless of the clinical status or growth response, because the balanced rise in T3 levels would not have been recognized. Indeed, such a policy of rechecking T4 levels 3 months after GH therapy had begun and supplementing those with declining levels resulted in T4 treatment of almost 50% of previously euthyroid, GH-deficient patients at our institution. At best, such inappropriate supplementation would be an unnecessary expense and inconvenience, but it may add some risk of excess bone age advancement with reduction of final height (37), decreased bone mineral density (38, 39), or cardiac conduction abnormalities (40).

In summary, a transient decrease in T4, rT3, and FT4I and a transient increase in T3 occur almost universally in previously euthyroid children during the first year of GH therapy. These children remain clinically euthyroid and do not require T4 supplementation. All thyroid values return to pretreatment levels by 3–6 months of continued GH therapy. T4 supplementation should be considered only if there is a persistent decline in both T3 and T4 levels.


   Acknowledgments
 
We thank Sam Refetoff, M.D., for performing the thyroid assays, and Joyce Kuntze, R.N., for help in obtaining the data.


   Footnotes
 
1 This work was supported in part by a grant from Genentech, Inc. Back

Received April 15, 1998.

Revised August 9, 1998.

Revised May 28, 1998.

Accepted July 8, 1998.


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

  1. Tanner JM, Whitehouse RH, Hughes PCR, Vince FP. 1971 Effect of human growth hormone treatment for 1 to 7 years on growth of 100 children, with growth hormone deficiency, low birthweight, inherited smallness, Turner’s syndrome, and other complaints. Arch Dis Child. 46:745–782.
  2. Aceto T, Frasier SD, Hayles AB, et. al. 1972 Collaborative study of the effects of human growth hormone in growth hormone deficiency. I. First year of therapy. J Clin Endocrinol Metab. 35:483–496.[Medline]
  3. Cacciari E, Cicognani A, Pirazzoli P, et. al. 1979 Effect of long-term growth hormone administration on pituitary-thyroid function in idiopathic hypopituitarism. Acta Pediatr Scand. 68:405–409.[Medline]
  4. Winter RJ, Thompson RG, Green OC. 1979 Serum cholesterol and triglycerides in children with growth hormone deficiency. Metabolism. 28:1244–1249.[CrossRef][Medline]
  5. Municchi G, Malozowski S, Nisula BC, Cristiano A, Rose SR. 1992 Nocturnal thyrotropin surge in growth hormone deficient children. J Pediatr. 121:214–220.[CrossRef][Medline]
  6. Rose SR, Leong GM, Yanovski JA, et. al. 1995 Thyroid function in non-growth hormone deficient short children during a placebo-controlled double blind trial of recombinant growth hormone therapy. J Clin Endocrinol Metab. 80:320–324.[Abstract]
  7. Goodman HG, Grumbach MM, Kaplan SL. 1968 Growth and growth hormone. II. A comparison of isolated growth hormone deficiency and multiple pituitary hormone deficiencies in 35 patients with idioipathic hypopituitary dwarfism. N Engl J Med. 278:57–68.
  8. Lippe BM, Van Herle AJ, LaFranchi SH, Uller RP, Lavin N, Kaplan SA. 1975 Reversible hypothyroidism in growth hormone-deficient children treated with human growth hormone. J Clin Endocrinol Metab. 40:612–618.[Abstract]
  9. Ranke M, Weber B, Bierich JR. 1979 Long-term response to human growth hormone in 36 childern with idiopathic growth hormone deficiency. Eur J Pediatr. 132:221–238.[CrossRef][Medline]
  10. Rosenbloom AL, Riley WJ, Silverstein JH, Garnica AD, Netzloff ML, Weber FT. 1980 Low dose single weekly injections of growth hormone: response during first year of therapy of hypopituitarism. Pediatrics. 66:272–276.[Abstract/Free Full Text]
  11. Stahnke N, Koehn H. 1990 Replacement therapy in hypothalamus-pituitary insufficiency: management in the adolescent. Horm Res. 33(Suppl 4):38–44.
  12. August GP, Lippe BM, Blethen SL, et. al. 1990 Growth hormone treatment in the United States: demographic and diagnostic features of 2331 children. J Pediatr. 116:899–903.[CrossRef][Medline]
  13. Wenzel KW. 1981 Pharmacological interference with in vitro tests of thyroid function. Metabolism. 30:717–732.[CrossRef][Medline]
  14. Lewis GF, Alessi CA, Imperial JG, Refetoff S. 1991 Low serum free thyroxine index in ambulating elderly is due to a resetting of the threshold of thyrotropin feedback suppression. J Clin Endocrinol Metab. 73:843–849.[Abstract]
  15. Robin NI, Hagfen SR, Collaco F, Refetoff S, Selenkow HA. 1971 Serum tests for measurement of thyroid function. Hormones. 2:266–279.[Medline]
  16. Grunfeld C, Sherman BM, Cavalieri RR. 1988 The acute effects of human growth hormone administration on thyroid function in normal men. J Clin Endocrinol Metab. 67:1111–4.[Abstract]
  17. Glantz SA, Slinker BK. 1990 Primer of applied regression and analysis of variance. New York: McGraw-Hill.
  18. Hamill PVV, Drizd TA, Johnson CL, Reed RB, Roche AF, Moore WM. 1979 Physical growth: National Center for Health Statitsics percentiles. Am J Clin Nutr. 32:607–629.[Abstract/Free Full Text]
  19. Genentech National Cooperative Growth Study. 1994 Summary report. South San Francisco: Genentech.
  20. Heimberg M, Olubadewo JO, Wilcox HG. 1985 Plasma lipoproteins and regulation of hepatic metabolism of fatty acids in altered thyroid states. Endocr Rev. 6:590–607.[CrossRef][Medline]
  21. Rezvani I, DiGeorge AM, Dowshen SA, Bourdony CJ. 1981 Action of human growth hormone (hGH) on extrathyroidal conversion of thyroxine (T4) to triiodothyronine (T3) in children with hypopituitarism. Pediatr Res. 15:6–9.[Medline]
  22. Brixen K, Neilsen HK, Bouillon R, Flyvbjerg A, Mosekilde L. 1992 Effects of short-term growth hormone treatment on PTH, calcitriol, thyroid hormones, insulin and glucagon. Acta Endocrinol (Copenh). 127:331–336.[Medline]
  23. Root AW, Snyder PJ, Rezvani I, DiGeorge AM, Utiger RD. 1973 Inhibition of thyrotropin-releasing hormone-mediated secretion of thyrotropin by human growth hormone. J Clin Endocrinol Metab. 36:103–107.[Medline]
  24. Sato T, Suzuki Y, Taketani T, et al. 1977 Enhanced peripheral conversion of thyroxine to triiodothyronine during hGH therapy in GH deficient children. J Clin Endocrinol Metab. 45:324–329.[Medline]
  25. Pirazzoli P, Cacciari E, Mandini M, et al. 1992 Growth and thyroid function in children treated with growth hormone. J Pediatr. 121:210–213.[CrossRef][Medline]
  26. Jorgensen JOL, Pedersen SA, Laurberg P, Weeke J, Skakkebaek NE, Christiansen JS. 1989 Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism. J Clin Endocrinol Metab. 69:1127–1132.[Abstract]
  27. Ho KY, Weissberger AJ, Stuart MC, Day RO, Lazarus L. 1989 The pharmacokinetics, safety and endocrine effects of authentic biosynthetic human growth hormone in normal subjects. Clin Endocrinol (Oxf). 30:335–345.[Medline]
  28. Root AW, Bongiovanni AM, Eberlein WR. 1970 Inhibition of thyroidal radioiodine uptake by human growth hormone. J Pediatr. 76:422–429.[CrossRef][Medline]
  29. Cobb WE, Reichlin S, Jackson IMD. 1981 Growth hormone secretory status is a determinant of the thyrotropin response to thyrotropin-releasing hormone in euthyroid patients with hypothalamic-pituitary disease. J Clin Endocrinol Metab. 52:324–329.[Abstract]
  30. Jorgensen JOL, Moller J, Laursen T, Orskov H, Christiansen JS, Weeke J. 1994 Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotrophin levels: studies in GH-deficient adults. Clin Endocrinol (Oxf). 41:609–614.[Medline]
  31. Demura R, Yamaguchi H, Wakabayashi I, Demura H, Shizume K. 1980 The effect of hGH on hypothalamic-pituitary-thyroid function in patients with pituitary dwarfism. Acta Endocrinol (Oxf). 93:13–19.
  32. Conners MH. 1977 Alteration of stimulated TSH and prolactin response in children treated with growth hormone. Life Sci. 21:1505–1510.[CrossRef][Medline]
  33. Porter BA, Refetoff S, Rosenfield RL, DeGroot LJ, Fang VS, Stark V. 1973 Abnormal thyroxine metabolism in hyposomatotrophic dwarfism and inhibition of responsiveness to TRH during growth hormone therapy. Pediatrics. 51:668–674.[Abstract/Free Full Text]
  34. Rubio GR, Mellinger RC, Zafar S, Wolf CB. 1976 Evaluation of thyroid function during growth hormone therapy. Metabolism. 25:15–21.[CrossRef][Medline]
  35. Moller J, Jorgensen J, 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]
  36. Wyatt DT, Mark D, Slyper A. 1995 Survey of growth hormone treatment practices by 251 pediatric endocrinologists. J Clin Endocrinol Metab. 80:3292–3297.[Abstract]
  37. Brande JLVd, Van Wyk JJ, French FS, Strickland AL, Radcliffe WB. 1973 Advancement of skeletal age of hypopituitary children treated wtih thyroid hormone plus cortisone. J Pediatr. 82:22–27.[CrossRef][Medline]
  38. Radetti G, Castellan C, Tato L, Platter K, Gentili L, Adami S. 1993 Bone mineral density in children and adolescent females treated with high doses of L-thyroxine. Horm Res. 39:127–131.[Medline]
  39. Franklyn JA, Sheppard MC. 1992 The thyroid and osteoporosis. Trends Endocrinol Metab. 3:113–116.
  40. Fazio S, Biondi B, Carella C, et al. 1995 Diastolic dysfunction in patients on thyroid-stimulating homrone suppressive therapy with levothyroxine: beneficial effect of ß-blockade. J Clin Endocrinol Metab. 80:2222–2226.[Abstract]



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Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals