Effects of Growth Hormone Therapy on Thyroid Function of Growth Hormone-Deficient Adults with and without Concomitant Thyroxine-Substituted Central Hypothyroidism*

Jørgensen, Jens Otto Lunde; Pedersen, Susanne Juhl; Laurberg, Peter; Weeke, Jørgen; Ne, Skakkebæk; Js, Christiansen

doi:10.1210/jcem-69-6-1127

Cited by 194 publications

(131 citation statements)

References 35 publications

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“…Since monitoring of CH is based on serum fT 4 levels, the decline of its levels during GH treatment will usually lead to an increase in the L-T 4 dose (29,31). This was indeed observed in the present retrospective study, but mainly in male patients.…”

Section: Discussionsupporting

confidence: 75%

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Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

et al. 2004

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Objective: We studied the clinical and hormonal profiles of patients with central hypothyroidism (CH), the adequacy of levothyroxine (L-T4) treatment and the influence of other pituitary hormone replacement therapies. Methods: We reviewed medical records of 108 adult patients with child-onset (CO; n ¼ 26) or adultonset (AO; n ¼ 82) CH. Results: At diagnosis, the most frequently reported symptoms were fatigue and headaches in AO patients, and growth retardation in CO patients. Serum TSH was normal in a majority of CH patients, low in 8% and elevated in 8%. Serum free thyroxine (fT 4 ) was usually reduced, but remained within the low normal range in 28% of the study population (mostly CO patients). Similarly, serum total T 4 (tT 4 ), total triiodothyronine (tT 3 ) and free T 3 (fT 3 ) were found to be within the normal range in significant subsets of patients. Interestingly, the clinical and biochemical characteristics of CH patients with normal f/t T 4 levels were not different from those of the patients with low fT 4 values. The thyroid hormonal profile was not influenced by gender, etiology or by the number of hormone deficiencies. At last evaluation, the mean dose of L-T 4 was 1.6^0.5 mg/kg/day and was negatively correlated to current age (P , 0.001) but positively correlated to the number of hormone deficiencies (P , 0.05). Treatment suppressed TSH in 75% of the patients, induced normal fT 4 in 94%, but normal fT 3 in only 49% of them. Male GH-treated patients and estrogen-treated females needed a higher L-T 4 dose compared with non-treated patients. Conclusions: fT 4 is clearly the best indicator of CH, but remains in the low normal range in a significant subset of patients, especially in those with CO disease. Adequacy of therapy is mostly reflected by the combination of upper normal fT 4 and low normal fT 3 levels. Pituitary hormone replacement therapy may require an adjustment of T 4 treatment, as female patients under estrogen treatment and male patients under GH treatment will need a higher T 4 dose in order to remain in the euthyroid range.European Journal of Endocrinology 150 1-8

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Section: Discussionsupporting

confidence: 75%

“…It has been well documented that exogenous GH administration enhances peripheral deiodination of T 4 to T 3 (27)(28)(29)(30). Since monitoring of CH is based on serum fT 4 levels, the decline of its levels during GH treatment will usually lead to an increase in the L-T 4 dose (29,31).…”

Section: Discussionmentioning

confidence: 99%

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

et al. 2004

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“…Baseline and TRH-stimulated TSH levels were signi®cantly lower in acromegalics than in controls, as reported in other studies (46). Suppression of TSH levels in euthyroid acromegalics has been accounted for by a chronic suppression of TRH neurons by a compensatory hypersecretion of somatostatin (47), and by a GHstimulated increase in the conversion of T4 into T3 (48). TSH responses to its physiological releasing hormone are not in¯uenced by acute infusion of rhEPO in acromegalic patients or in normal subjects.…”

Section: Discussionsupporting

confidence: 78%

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

Iglesias²,

Sastre³

et al. 2000

European Journal of Endocrinology

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Objective: Our aim has been to evaluate the effects of i.v. infusion of recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH), prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) stimulation in acromegalic patients. Methods: We studied 16 patients (8 females, aged 29±68 years) with active acromegaly and 12 control subjects (7 females, 24±65 years). All participants were tested with TRH (400 mg i.v. as bolus) and with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15 min before TRH injection) on different days. Blood samples were obtained between À30 and 120 min for GH and PRL determinations, and between À30 and 90 min for TSH determinations. Hormone responses were studied by a time-averaged (area under the secretory curve (AUC)) and time-independent (peak values) analysis. Results: Twelve patients exhibited a paradoxical GH reaction after TRH administration with great interindividual variability in GH levels. When patients were stimulated with rhEPO plus TRH there were no changes in the variability of GH responses or in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any signi®cant change in GH secretion in normal subjects. Baseline and TRH-stimulated PRL concentrations in patients did not differ from those values found in controls. When TRH was injected during the rhEPO infusion, a signi®cant (P < 0.05) increase in PRL concentrations at 15±120 min was found in acromegalic patients. Accordingly, the PRL peak and the AUC for PRL secretion were signi®cantly increased in patients. Infusion with rhEPO had no effect on TRH-induced PRL release in control subjects. Baseline TSH concentrations, as well as the TSH peak and the AUC after TRH, were signi®cantly lower in patients than in controls. Infusion with rhEPO modi®ed neither the peak TSH reached nor the AUC for TSH secretion after TRH injection in acromegalic patients and in healthy volunteers. Conclusion: Results in patients with acromegaly suggest that (i) the paradoxical GH response to TRH is not modi®ed by rhEPO infusion, (ii) rhEPO has no effect on TRH-induced TSH release, and (iii) acute rhEPO administration increases the TRH-induced PRL release in acromegalic patients.

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“…It is well documented that GHD can mask central hypothyroidism or central hypoadrenalism in a significant proportion of hypopituitary patients, and that this is exposed upon commencement of GH treatment. The mechanisms seem to be GH-induced enhancement of the peripheral deiodination of T 4 to T 3 , and reduction of cortisone to cortisol conversion (36,37). However, precipitation by initiation of GH therapy does not entirely explain the observed evolution in pituitary function in either IGHD or MPHD patients since half of the patients developed new deficiencies 3-6 years after commencement of GH therapy.…”

Section: Discussionmentioning

confidence: 93%

From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum – a KIMS analysis

Klose

Jonsson²,

Abs³

et al. 2009

European Journal of Endocrinology

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Objective: To describe baseline clinical presentation, treatment effects and evolution of isolated GH deficiency (IGHD) to multiple pituitary hormone deficiency (MPHD) in adult-onset (AO) GHD. Design: Observational prospective study. Methods: Baseline characteristics were recorded in 4110 patients with organic AO-GHD, who were GH naïve prior to entry into the Pfizer International Metabolic Database (KIMS; 283 (7%) IGHD, 3827 MPHD). The effect of GH replacement after 2 years was assessed in those with available follow-up data (133 IGHD, 2207 MPHD), and development of new deficiencies in those with available data on concomitant medication (165 IGHD, 3006 MPHD). Results: IGHD and MPHD patients had similar baseline clinical presentation, and both groups responded similarly to 2 years of GH therapy, with favourable changes in lipid profile and improved quality of life. New deficiencies were observed in 35% of IGHD patients, which was similar to MPHD patients with one additional deficit other than GH. New deficiencies most often presented within the first year but were observed up to 6 years after GH commencement. Conversion of IGHD into MPHD was not predicted by aetiology, baseline characteristics, surgery or radiotherapy, whereas in MPHD additional deficits were predicted by age (P!0.001) and pituitary disease duration (P!0.01). Conclusion: Both AO-IGHD and -MPHD patients have similar baseline clinical presentation and respond equally well to 2 years of GH replacement. Hypopituitarism in adults seems to be a dynamic condition where new deficiencies can appear years after the initial diagnosis, and careful endocrine follow-up of all hypopituitary patients, including those with IGHD, is warranted. European Journal of Endocrinology 161 S75-S83

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Effects of Growth Hormone Therapy on Thyroid Function of Growth Hormone-Deficient Adults with and without Concomitant Thyroxine-Substituted Central Hypothyroidism*

Cited by 194 publications

References 35 publications

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

Effects of acute infusion of erythropoietin on paradoxical responses of growth hormone to thyrotropin-releasing hormone in acromegalic patients

From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum – a KIMS analysis

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