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Cited by 81Growth Hormone and Insulin-like Growth FactorsThyroid Disorders and TreatmentsPituitary Gland Disorders and Treatments

Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children

Portes, Evandro S., Oliveira, Juliana H. A., Maccagnan, Paulo, Abucham, Julio·2000·Clinical Endocrinology
DOI 10.1046/j.1365-2265.2000.01071.x
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Abstract

OBJECTIVE: The effects of GH therapy on thyroid function among previous reports have shown remarkable discrepancies, probably due to differences in hormone assay methods, degree of purification of former pituitary-derived GH preparations, dosage schedules, diagnostic criteria, patient selection, duration of treatment and study design. These considerations motivated us to investigate whether and how GH replacement therapy changes serum thyroid hormone levels, including the much less studied rT3 levels, in a group of unequivocally GH-deficient children receiving long-term recombinant human GH therapy. PATIENTS AND DESIGN: Twenty clinically and biochemically euthyroid children were studied in two therapeutic conditions: on GH replacement therapy for at least 6 months and without GH replacement, either before GH was started or after GH was withdrawn for 30-60 days. Eight patients were on thyroxine replacement treatment and thyroxine doses were kept constant during the study. Blood was collected before and after 15, 20 and 60 minutes of TRH administration in both therapeutic conditions (with GH and without GH). MEASUREMENTS: Concentrations of thyroid hormone levels were determined only in sera obtained before TRH administration. FT4, T3 and TSH were measured by immunoflourimetric assays and rT2 was measured by immunoradioassay. RESULTS: Patients were classified into two groups, according to basal TSH levels: group I (TSH > 0.4 mU/l, n = 12) and group II (on thyroxine and TSH < 0.05 mU/l, n = 8). In both groups, serum FT4 levels decreased (17. 0 +/- 1.1 vs. 14.3 +/- 0.9 mU/l, P < 0.001, and 18.0 +/- 1.7 vs. 14. 2 +/- 1.7 mU/l, P < 0.01, respectively), serum T3 levels increased (1.8 +/- 0.1 vs. 2.4 +/- 0.2 nmol/l, P < 0.001, and 1.9 +/- 0.3 vs. 2.4 +/- 0.2 nmol/l, P < 0.05, respectively), and serum rT3 levels decreased (0.35 +/- 0.03 vs. 0.25 +/- 0.03 nmol/l, P < 0.01, and 0. 48 +/- 0.06 vs. 0.34 +/- 0.06 nmol/l, P < 0.01, respectively). Basal (3.2 +/- 0.50 vs. 2.6 +/- 0.72 mU/l, P = 0.28, paired t-test), TRH-stimulated peak TSH levels (13.9 +/- 5.3 vs. 15.9 +/- 8.0 mU/l, P = 0.35, paired t-test) and TRH-stimulated TSH secretion, expressed as area under the curve (609 +/- 97 vs. 499 +/- 53 mU/l.minutes-1, P = 0.15, paired t-test), remained unchanged during GH replacement in group I patients. Low serum FT4 and high serum T3 levels were observed in only one patient each, but low serum rT3 levels were found in six patients (four in group I and two in group II) during GH replacement. CONCLUSIONS: These results show that long-term GH replacement therapy in children with unequivocal GHD significantly decreases serum FT4 and rT3 levels and increases serum T3 levels; that these changes are independent of TSH and result from increased peripheral conversion of T4 to T3 and that GH replacement therapy in GH deficient children does not induce hypothyroidism, but simply reveals previously unrecognized cases whose serum FT4 values fall in the low range during GH replacement.

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  • Hypopituitary patients without defined TSH deficiency and not on levothyroxine replacement demonstrate a reduction in serum T4 after initiation of GH replacement and decompensate the axis into a hypothyroid state, although serum T3 remained constant or increased.

    “Hypopituitary patients without defined TSH deficiency and not on levothyroxine replacement were shown to demonstrate a reduction in the serum T4 concentration after initiation of GH replacement and decompensate the axis into a hypothyroid state, although serum T3 remained constant (Agha et al., 2006;Jørgensen et al., 1992Jørgensen et al., , 1994) ) or increased (Portes et al., 2000).”

    From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Portes et al., 2000

  • Estrogens and GH influence thyroid hormone transport and/or metabolism and consequently interfere with central hypothyroidism management.

    “Both estrogens and GH influence thyroid hormone transport and/or metabolism and consequently interfere CeH management (33, 60).”

    From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [60]

  • Sex steroid and GH deficiencies can mask an underlying central hypothyroidism.

    “Sex steroid and GH deficiencies can mask an underlying CeH”

    From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [60]

  • Introduction of sex steroid or GH replacement therapies often requires uptitration of L-T4.

    “the introduction of these replacement therapies often requires an uptitration of L-T4”

    From The diagnosis and management of central hypothyroidism in 2018 (2019) · cites this paper as [60]

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Authors
Portes, E. S., Oliveira, J. H. A., Maccagnan, P., & Abucham, J.
Affiliations
Universidade Federal de São Paulo (BR)
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2000-08
Volume
53
Issue
2
Pages
183-189
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1046/j.1365-2265.2000.01071.x
OpenAlex
W2055156709
Cited by
81
References
25
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 2 · 2021: 8 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 3
FWCI
1.70
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 510 d)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
Funders
Bijzonder Onderzoeksfonds UGent
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
growth hormone deficiency, growth hormone replacement therapy, recombinant human growth hormone, thyroid function, free thyroxine, triiodothyronine, reverse T3, thyroid-stimulating hormone, thyroxine replacement, TRH stimulation test, children, long-term treatment, thyroid hormone metabolism, pituitary hormone secretion, hypothalamic-pituitary-thyroid axis
MeSH terms
Adolescent, Adult, Child, Female, Follow-Up Studies, Growth Disorders, Humans, Hypothyroidism, Male, Growth Hormone, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine, Triiodothyronine, Reverse, Hormone Replacement Therapy

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