Isolated central hypothyroidism in short stature
Abstract
Mild hypothyroidism can be difficult to diagnose, particularly when it is caused by deficiency of TSH or TSH-releasing hormone (TRH). Such central hypothyroidism occurs most often in association with growth hormone deficiency (GHD). Isolated central hypothyroidism has been considered rare. The TSH surge test is the most sensitive test currently available for confirming the diagnosis. Results are abnormal in many cases where response to TRH is normal. Short children referred between 1986 and 1994 for evaluation (n = 235, 74 girls; height 2 or more SD below mean for age; no history of radiation therapy) were selected for study. TSH samples were obtained hourly for study of TSH surge (1400-1800 h and 2200-0400 h). Growth hormone (GH) samples were obtained every 20 min (2000-0800 h). GH stimulation tests included arginine, insulin, and L-dopa. Thirty-nine children were found to have GHD (peak GH < or = 7 micrograms/L) and 15 had mild primary hypothyroidism (TSH 5-15 mU/L). Of the remaining 181 children with apparent idiopathic short stature (ISS), 30 had a blunted TSH surge. All 30 had free thyroxine (FT4) in the lowest third of the normal range, consistent with values seen in documented central hypothyroidism. They were 13% of the total group, 16% of the ISS children, and 32% of the ISS children with FT4 in the lowest third of normal. (In comparison, diagnosis of GHD was made in 16% of the total group.) In conclusion, use of a direct FT4 assay to screen short children for possible subtle hypothyroidism (along with other appropriate testing) identifies a subgroup with a one in three possibility of an easily treated cause--isolated central hypothyroidism.
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These children showed a significant increase in growth velocity during levothyroxine therapy compared to short children with FT4 in the lowest third of normal who had a normal TSH surge.
“These children showed a significant increase in growth velocity during levothyroxine therapy compared to the growth response of short children with FT4 in the lowest third of normal who had a normal TSH surge [70].”
From Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury (2015) · cites this paper as [70]
In a prior report of children with short stature, approximately 13 per 100 short children had a blunted TSH surge associated with low or low-normal Free T4 in the absence of other pituitary hormone disturbance; incidence was 33% in those with height shorter than -2 SD and Free T4 in the lowest third of normal.
“In a prior report of children with short stature, an incidence of approximately 13 per 100 short children had a blunted TSH surge associated with low or low–normal Free T4 in the absence of any other pituitary hormone disturbance. The incidence was 33% of those with both with height shorter than –2 SD and a Free T4 in the lowest third of the normal range.”
From Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury (2015) · cites this paper as [70]
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Diagnosis of Hidden Central Hypothyroidism in Survivors of Childhood Cancer<sup>1</sup>
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Self-citationUpdate of Endocrine Dysfunction following Pediatric Traumatic Brain Injury
Reifschneider, K., Auble, B., & Rose, S. (2015) · Journal of Clinical Medicine · doi:10.3390/jcm4081536 · Cited by 66 · see citing works
“These children showed a significant increase in growth velocity during levothyroxine therapy compared to the growth response of short children with FT4 in the lowest third of normal who had a normal TSH surge [70].”
ResultSelf-citationCircadian and Stimulated Thyrotropin Secretion in Cranially Irradiated Adult Cancer Survivors
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Cranial irradiation and central hypothyroidism
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Self-citationFilipsson, H., & Johannsson, G. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0319 · Cited by 50 · see citing works
Hypopituitarism in pediatric survivors of inflicted traumatic brain injury
Auble, B. A., Bollepalli, S., Makoroff, K., Weis, T., Khoury, J., Colliers, T., & Rose, S. R. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.2916 · Cited by 38 · see citing works
Self-citationLevothyroxine Replacement Therapy in Central Hypothyroidism: A Practice Report
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Improved diagnosis of mild hypothyroidism using time-of-day normal ranges for thyrotropin
Rose, S. R. (2010) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2010.04.047 · Cited by 27 · see citing works
Self-citationThe metabolic consequences of thyroxine replacement in adult hypopituitary patients
Filipsson Nyström, H., Feldt-Rasmussen, U., Kourides, I., Popovic, V., Koltowska-Häggström, M., Jonsson, B., & Johannsson, G. (2012) · Pituitary · doi:10.1007/s11102-011-0356-6 · Cited by 18 · see citing works
- Authors
- Rose, S. R.
- Affiliations
- University of Tennessee Health Science Center (US)
- Corresponding author
- Rose, Susan R
- ORCID
- Rose, Susan R
- Venue
- Pediatric Research
- Published
- 1995-12
- Volume
- 38
- Issue
- 6
- Pages
- 967-973
- ISSN
- 0031-3998 (ISSN-L)
- 1530-0447
- OpenAlex
- W2036986466
- Cited by
- 61
- References
- 7
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 3 · 2012: 1
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- National Institutes of Health (5M01-RR00997)
- National Institute of Child Health and Human Development
- National Center for Research Resources (5M01-RR00997, M01RR-00211, M01RR000211, M01RR000997)
- 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 › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- short stature, growth hormone deficiency, free thyroxine, primary hypothyroidism, growth hormone stimulation test, idiopathic short stature
- MeSH terms
- Analysis of Variance, Child, Circadian Rhythm, Female, Growth Disorders, Humans, Hypothyroidism, Male, Pilot Projects, Secretory Rate, Thyrotropin, Thyroxine
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