Elevated Plasma TSH and Hypothyroidism in Children with Hypothalamic Hypopituitarism

Illig, R; Krawczyńska, H; Torresani, Toni; Prader, A.

doi:10.1210/jcem-41-4-722

Cited by 85 publications

(24 citation statements)

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“…Although unexpected, blood TSH levels were elevated in the TRH Ϫ͞Ϫ mice. There have been no patients with isolated TRH deficiency defined, but similar elevation has also been reported in some patients with central hypothyroidism (21). These patient's TSH activities were observed to be significantly reduced (22,23).…”

Section: Discussionsupporting

confidence: 55%

Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene

Yamada

Saga

Shibusawa

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

200

105

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Thyrotropin-releasing hormone (TRH) is a brain hypothalamic hormone that regulates thyrotropin (TSH) secretion from the anterior pituitary and is ubiquitously distributed throughout the brain and other tissues including pancreas. To facilitate studies into the role of endogenous TRH, we have used homologous recombination to generate mice that lack TRH. These TRH ؊͞؊ mice are viable, fertile, and exhibit normal development. However, they showed obvious hypothyroidism with characteristic elevation of serum TSH level and diminished TSH biological activity. Their anterior pituitaries exhibited an apparent decrease in TSH immunopositive cells that was not due to hypothyroidism. Furthermore, this decrease could be reversed by TRH, but not thyroid hormone replacement, suggesting a direct involvement of TRH in the regulation of thyrotrophs. The TRH ؊͞؊ mice also exhibited hyperglycemia, which was accompanied by impaired insulin secretion in response to glucose. These findings indicate that TRH ؊͞؊ mice provide a model of exploiting tertiary hypothyroidism, and that TRH gene abnormalities cause disturbance of insulin secretion resulting in marked hyperglycemia.Thyrotropin-releasing hormone (TRH) was originally isolated as the first hypothalamic hormone (1, 2) and has been shown to be present in many organs, including the central nervous system, reproductive system, and gastrointestinal tract (3, 4). Administration of exogenous TRH to animals and humans has been observed to cause a variety of endocrine and nonendocrine biological activities (3-5). The results of these studies have led to the suggestion that TRH may act as a neurotransmitter or neuromodulator in many organs.Because of the ubiquitous distribution of TRH in many organs and the lack of a suitable method to produce selective changes in in vivo TRH level, it has been difficult to examine the mechanism by which TRH regulates different biological activities. For example, TRH is the major regulator of synthesis and secretion of thyrotropin (TSH) in the anterior pituitary and, thus, it plays a pivotal role in the regulation of the hypothalamic-pituitary-thyroid axis. However, the contribution of TRH in the functional maturation of pituitary thyrotrophs during development remains obscure. Second, although isolated deficiency of TRH has been suggested to be the cause of tertiary (hypothalamic) hypothyroidism, there is neither direct clinical evidence nor an animal model to support this hypothesis. In the pancreas, TRH exists in the islets of Langerhans and more specifically within the ␤ cells producing insulin (6-9). However, due to technical difficulties associated with selective depletion of TRH in the ␤ cells, it has been difficult to discern its role in insulin physiology.In view of the aforementioned observations, it is clear that the availability of a TRH-deficient animal model will greatly enhance our ability to clarify the precise role of the peptide in many organ functions.We recently cloned and characterized a mouse hypothalamic cDNA and genomic DNA...

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Section: Discussionsupporting

confidence: 55%

Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene

Yamada

Saga

Shibusawa

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

200

105

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“…It is reported that patients with hypothalamic lesions and IGHD often, but not invariably (Snyder et al 1974;Roitman et al 1980), show delayed and prolonged TSH responses to TRH (Hall et al 1972; Kaplan et al 1972;Faglia et al 1973;Illig et al 1975;Burger and Patel 1977;Okada et al 1978 ;Gamier et al 1983). In this study, all IGHD patients were of euthyroid state, but they showed delayed TSH responses to TRH as was seen also in 2ry GHD patients.…”

Section: Discussionsupporting

confidence: 60%

“…trartration (Hall et al 1972 ; Kaplan et al 1972 ;Faglia et al 1973 ; Illig et al 1975 ; Burger and Patel 1977 ;Okada et al 1978 ; Gamier et al 1983). Generally, there are two hormone pools, one is a readily releasable pool and the other is a newly synthesized pool, in endocrine cells (Hall et al 1972; Orci et al 1972;Bremner and Paulsen 1974).…”

mentioning

confidence: 99%

GHRH and TRH tests in patients with idiopathic and secondary GH deficiency. With special reference to GH response patterns to GHRH.

Hanew

Sugawara

Utsumi

et al. 1990

Tohoku J. Exp. Med.

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Tests in Patients with Idiopathic and Secondary GH Deficiency -With Special Reference to OH Response Patterns to GHRH . Tohoku J. Exp. Med., 1990, 160 (3), [189][190][191][192][193][194][195][196][197][198][199][200][201][202] To study whether patients with idiopathic GH deficiency (IGHD) show a delayed GH response pattern to GHRH, 42 patients with IGHD, 14 patients with hypothalamic tumor (try GHD), and 23 normal short children (NSC) were examined as to their GH response patterns to GHRH together with their TSH and PRL response patterns to TRH. After TRH injection, the mean time of the TSH peak in IGHD (67.5 + 6.5 min, n = 36) and try GHD patients (81.7± 14.8 min, n = 9) was clearly delayed comparing to that of NSC (29.1 + 2.9 min, n =16 ; both p <0.01). Similarly, the mean time of the PRL peak in IGHD (38.3 + 3.6 min, n = 36) and try GHD patients (39.5 + 5.8, n =11) was significantly delayed comparing to NSC (22.0+3.5 min, both p <0.01). In IGHD patients, the delayed response pattern of TSH and PRL was more remarkable in patients who had breech delivery than in those with normal delivery. In contrast, the mean time of the GH peak was similar in I GHD (62.1±4.0 min, n =41), try GHD (64.1± 8.1 min, n =11) and NSC (58.0± 6.1 min, n =23). However, the decline from peak GH (120 min GH/peak GH) was significantly smaller in IGHD (54.3+ 4.2%) and try GHD (60.7+7.3%) than in NSC (39.0+8.1%) (both p<0.05). Further, in IGHD patients plasma GH response was greater in patients with normal delivery than in those with breech and asphyxia delivery. These results seem to indicate : 1) the stimulus-secretion mechanism is different between somatotrophs and thyrotrophs or lactotrophs in man, 2) IGHD patients have hypothalamic lesions as well as pituitary lesions, 3) such hypothalamo-pituitary lesions in IGHD patients are greater in patients with abnormal delivery than in those with normal delivery, idiopathic GH deficiency ; GHRH ; TRH ; GII ; TSH It is known that patients with hypothalamic lesions and idiopathic growth hormone deficiency (IGHD) often show delayed TSH responses to TRH adminis-

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“…TSH deficiency was confirmed by a TRH test at the age of 1 yr after temporary discontinuation of T (22,23,30). Clinicians are accustomed to interpreting TRH tests by plotting the results at several time points after the administration of TRH, looking at the height of the peak TSH elevation and the shape of the curve.…”

Section: Trh Testsmentioning

confidence: 99%

Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants

Tijn

Vijlder

Vulsma

2008

The Journal of Clinical Endocrinology &Amp; Metabolism

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lp;&-8qContext:A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency. In the case of congenital hypothyroidism of central origin (CH-C), the majority of patients have multiple pituitary hormone deficiencies (MPHD). This condition poses an additional threat to postnatal central nervous system development, primarily on account of neuroglycopenia due to ACTH/cortisol deficiency with or without additional GH deficiency. Therefore, in CH-C, rapid diagnosis is even more urgent than in congenital hypothyroidism of thyroidal origin. Objective:In the assessment of hypothalamic-pituitary-thyroid function, we considered the pituitary response to iv administration of TRH (TRH test) pivotal. We evaluated the usefulness of the TRH test in a cohort of infants with neonatal congenital hypothyroidism screening results indicative of CH-C by analyzing the results within the framework of investigations of the anatomical and functional integrity of the hypothalamo-hypophyseal system. Design and Setting:The study was a Dutch nationwide prospective study (1994 -1996). Patients were included if neonatal congenital hypothyroidism screening results were indicative of CH-C and patients could be tested within 3 months of birth. Patients:Ten male and five female infants with CH-C, detected by neonatal screening, and six infants with false-positive screening results, nonthyroidal illness, or transient hypothyroidism, were included in the study. Main Outcome Measures:Results of TRH tests, within the framework of extensive endocrinological examinations and cerebral magnetic resonance imaging, were measured.Results: All patients with type 3 TSH responses to TRH had MPHD, and the majority (67%) of patients with type 2 responses had isolated TSH deficiency. Conclusions:The TRH test has a pivotal role in the diagnosis of TSH deficiency in young infants. Abnormal TRH test results, especially a type 3 response, urge immediate assessment of integral hypothalamic-pituitary function because the majority of patients have MPHD. T hyroid hormone is extremely important for normal brain development. A shortage of thyroid hormone during prenatal life and the first years after birth results in a spectrum of neuropsychological disorders, depending on the duration and severity of the deficiency (1, 2). In the case of congenital hypothyroidism (CH), the damage appears to be especially related to postnatal T 4 deficiency (3). Apparently, central nervous system development can at least be partly preserved by

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Elevated Plasma TSH and Hypothyroidism in Children with Hypothalamic Hypopituitarism

Cited by 85 publications

References 0 publications

Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene

Tertiary hypothyroidism and hyperglycemia in mice with targeted disruption of the thyrotropin-releasing hormone gene

GHRH and TRH tests in patients with idiopathic and secondary GH deficiency. With special reference to GH response patterns to GHRH.

Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants

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