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Cited by 60Thyroid Disorders and TreatmentsPituitary Gland Disorders and TreatmentsGrowth Hormone and Insulin-like Growth Factors

Circadian and Stimulated Thyrotropin Secretion in Cranially Irradiated Adult Cancer Survivors

Darzy, Ken H., Shalet, Stephen M.·2005·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2005-1593
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Abstract

CONTEXT: It has been claimed that with the use of the TRH test and knowledge of the nocturnal TSH surge, the diagnosis of so-called hidden central hypothyroidism might be uncovered in a substantial proportion of euthyroid cranially irradiated children. STUDY SUBJECTS: We conducted 24-h TSH profiles and TRH tests in 37 euthyroid adult cancer survivors 2-29 yr (median, 11.5) after irradiation (18-64 Gy) and in 33 matched normal controls. RESULTS: Basal and stimulated TSH levels (during the TRH test) were significantly (P < 0.05) higher in the patients who had received craniospinal irradiation, more so in those with severe GH deficiency. Six patients (16%) had a hypothalamic TSH response to TRH. The maximum TSH surge calculated from the highest peak (average of the highest three sequential samples) and the smallest nadir (average of the smallest three sequential samples) in the whole 24-h profile period was above the cutoff value of 50% in all except one control subject and two patients. However, the nocturnal TSH surge was greatly reduced or absent in eight normal subjects (24%) and six patients (16%), not due to a genuine loss of diurnal rhythm, but simply to a shift in the timing of the peak TSH and/or the nadir TSH to outside the recommended sampling times (for the nocturnal surge) of 2200-0400 and 1400-1800 h, respectively; thereby potentially leading to an erroneous diagnosis of hidden central hypothyroidism. Overall, the maximum TSH surge was significantly (P = 0.01) reduced only in the GH-deficient patients (100.7 +/- 11%) compared with normal subjects (154.9 +/- 18.2%). Free T4 levels did not correlate with TSH surge results. CONCLUSIONS: The normality of free T4 levels and the wide discrepancy between the high rate of these TSH abnormalities and the very low rate of overt secondary hypothyroidism (3-6%) after prolonged periods of postirradiation follow-up strongly suggest that in the vast majority of patients, these abnormalities in TSH dynamics represent subtle functional disturbances in the hypothalamic-pituitary axis rather than genuine pathology that may progress with time. We suggest that in this context, use of the term hidden central hypothyroidism is inappropriate, because these subtle changes may not have any clinical significance.

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Authors
Darzy, K. H., & Shalet, S. M.
Affiliations
The Christie Hospital (GB)
Corresponding author
Shalet, Stephen M.
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2005-12
Volume
90
Issue
12
Pages
6490-6497
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2005-1593
OpenAlex
W2145583541
Cited by
60
References
58
Citations by year
2026: 2 · 2024: 1 · 2023: 1 · 2021: 1 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 4
FWCI
2.07
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
cranial irradiation, thyrotropin secretion, hypothalamic-pituitary axis, growth hormone deficiency, TRH stimulation test, cancer survivors, free thyroxine, radiation-induced thyroid dysfunction, central hypothyroidism, pituitary irradiation
MeSH terms
Adolescent, Adult, Brain Neoplasms, Circadian Rhythm, Female, Humans, Hypothyroidism, Male, Middle Aged, Spinal Cord, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Case-Control Studies, Cranial Irradiation, Survivors, Human Growth Hormone

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