Action of Human Growth Hormone (hGH) on Extrathyroidal Conversion of Thyroxine (T4) to Triiodothyronine (T3) in Children with Hypopituitarism

Rezvani, Iraj; DiGeorge, Angelo M.; Dowshen, Steven A.; Bourdony, Carlos J.

doi:10.1203/00006450-198101000-00002

Cited by 64 publications

(49 citation statements)

References 2 publications

(3 reference statements)

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“…i.e. a GH-induced en hanced peripheral conversion of T4 to T3 [ 12,13,19], and similar findings were later reported following short-term administration in healthy adults [ 11], At first glace, these different findings may seem diffi cult to reconcile. There arc.…”

Section: Gh Therapy In Normal Subjectsmentioning

confidence: 66%

Thyroid Function during Growth Hormone Therapy

et al. 1992

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Administration of growth hormone (GH) in GH-deficient patients has been reported to cause a variety of perturbations in thyroid function. Reports range from decreased sensitivity of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation and induction of hypothyroidism to increased energy expenditure and enhanced peripheral thyroxine (T₄) to triiodothyronine (T₃) conversion. Some of the diversities may relate to the fact that earlier studies were uncontrolled case reports, which furthermore employed pituitary GH preparations, which may have been contaminated with TSH. A confounding variable in terms of incipient TSH insufficiency in some patients may also have been present. Data from a placebo-controlled crossover study of 4-months GH therapy in GH-deficient adults, some of whom were on ongoing T₄ substitution, revealed that the most prominent effect on thyroid function was increased peripheral T₄ to T₃ conversion without significantly affecting TSH levels or secretion from the thyroid gland. It was furthermore observed that T3 levels during placebo were significantly decreased compared to an untreated healthy control group. Comparable findings have been made in a controlled study of 6-months GH therapy in adult-onset GH-deficient patients. More recent data suggest that these effects prevail after long-term (16 months) therapy. Similar findings have also been reported in healthy subjects receiving pharmacological GH doses. It is likely that this effect is not caused by GH per se inasmuch as reduced T₄ to T₃ conversion is a common observation in catabolic states with concomitant GH hypersecretion. It remains to be shown whether insulin-like growth factor I (IGF-I) stimulates peripheral deiodination.

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Section: Gh Therapy In Normal Subjectsmentioning

confidence: 66%

Thyroid Function during Growth Hormone Therapy

et al. 1992

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“…The latter findings led the authors to conclude that observations made in previous studies could represent an unmasking by GH of incipient central hypothyroidism or, alternatively, relate to the fact that T 4 levels normally decline during childhood. Finally, five studies in hypopituitary patients revealed a decline in T 4 concomitant with an increase in triiodothyronine (T 3 ) during GH therapy for between 2 weeks and 18 months [6, 7, 8, 9, 10]. Rezvani et al [9]also reported a decline in reverse T 3 (rT 3 ) levels, which, put together, suggested a GH-induced enhancement of extrathyroidal T 4 to T 3 conversion.…”

Section: Thyroid Hormonesmentioning

confidence: 94%

Impact of Growth Hormone Administration on Other Hormonal Axes

et al. 1999

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Growth hormone regulates several other hormonal systems and vice versa. The present review focusses on the effect of GH administration in adults on selected hormonal systems. Growth hormone treatment has been linked to development of central hypothyroidism in hypopituitary children. We now know that GH enhances the extra-thyroidal conversion of T₄ to T₃. Lowering of T₄ during GH treatment therefore reflects biochemical unmasking of subclinical central hypothyroidism. In normal adults GH administration does not affect the pituitary-gonadal axis. There is, however, evidence to suggest that GH substitution in hypopituitary adults enhances peripheral actions of sex steroids (males) and stimulates gonadal function (females). Both increased, unchanged and reduced basal and ACTH stimulated glucocorticoid levels have been reported during GH treatment. Several groups have recorded reduced levels of cortisol binding globulin with unchanged free cortisol concentrations. Regular assessment of thyroid and glucocorticoid status during GH substitution in GH-deficient patients is recommended.

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“…A few years ago, Jorgensen et al [9] showed that GH administration stimulated peripheral T 4 to T 3 conversion in a dose-dependent manner in GHD adults, and Rezvani et al [21] observed the same data in GHD children. These findings are partially concordant with our study.…”

Section: Discussionmentioning

confidence: 62%

“…Following GH administration, some studies have demonstrated different degrees of thyroid hormone level changes, such as a reduction in serum fT 4 [8,29] or an increase in fT 3 [10,11,16,30], while other studies have not confirmed these observations [18,20,21,30,31,32]. It has been suggested that the incidence of both central and peripheral hypothyroidism should be taken into account during recombinant human GH administration, as hypothyroidism may worsen the response to therapy.…”

Section: Discussionmentioning

confidence: 70%

“…In addition, the hypothesis that GH alters the peripheral deiodination of thyroxine (T 4 ) to triiodothyronine (T 3 ) is supported by the findings from most studies, but with controversial data [10,11,12,13,14,15,16,17]. Previous studies have been unable to demonstrate overt changes in the HPT [18,19] or the clinical relevance of these changes during GH therapy [20,21]. Conversely, a number of studies have shown changes in HPT in children to be transient [13,16] or persistent up to 12 months [15].…”

Section: Introductionmentioning

confidence: 73%

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Correlation between Severity of Growth Hormone Deficiency and Thyroid Metabolism and Effects of Long-Term Growth Hormone Treatment on Thyroid Function in Children with Idiopathic Growth Hormone Deficiency

Ciresi

Guarnotta²,

Amato³

et al. 2014

Horm Res Paediatr

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Background/Aim: The significance of changes in thyroid function in children during growth hormone (GH) treatment remains uncertain. We aimed to evaluate the impact of GH replacement on thyroid status in children with idiopathic GH deficiency (GHD). Methods: Data of 105 GHD children (82 M, 23 F; aged 11.13 years) during a 36-month follow-up were analyzed. At diagnosis the areas under the curve of GH (AUC_GH) were calculated during a GH-releasing hormone + arginine (GHRH-Arg) and insulin tolerance test. Results: A significant ΔfT₃ (p < 0.001) was documented at 12 months, without any further change at 24 and 36 months and without fT₄ and TSH modifications. Grouping patients according to ΔfT₃ at 12 months into those with lower (n = 80, 76%) or greater values than the 75th percentile (n = 25, 24%), the latter showed lower AUC_GH and GH peak during a GHRH-Arg (p = 0.018 and 0.014, respectively) and insulin tolerance test (p = 0.023 and 0.020, respectively) at diagnosis. In addition, children with lower GH at diagnosis showed a greater ΔfT₃ at 12 months (p = 0.030). Conclusions: In GHD children, GH treatment is associated with a significant increase in fT₃ in the first 12 months, more pronounced in patients with more severe GHD, highlighting the strong correlation between severity of GHD and thyroid metabolism.

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Action of Human Growth Hormone (hGH) on Extrathyroidal Conversion of Thyroxine (T4) to Triiodothyronine (T3) in Children with Hypopituitarism

Abstract: h u m a n growth hormone thyroxine hypopituitarism triiodothyronine metabolism

Cited by 64 publications

References 2 publications

Thyroid Function during Growth Hormone Therapy

Thyroid Function during Growth Hormone Therapy

Impact of Growth Hormone Administration on Other Hormonal Axes

Correlation between Severity of Growth Hormone Deficiency and Thyroid Metabolism and Effects of Long-Term Growth Hormone Treatment on Thyroid Function in Children with Idiopathic Growth Hormone Deficiency

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