Effect of Endogenous Thyroid Stimulating Hormone Levels on the Secretion of Thyroid Hormones in Man

Carpi, Angelo; Bianchi, R.; Zucchelli, G.C.; Corso, L Del; Levanti, C; Cocci, Franca; Giannessi, Daniela; Mariani, Giuliano

doi:10.1530/acta.0.0920073

Cited by 8 publications

(4 citation statements)

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“…The T3 to T4 molar ratio values in Patient 1 correlated well with serum TSH levels (R 2 =0.48, p=0.0028) and high T3 to T4 molar ratio was observed when serum TSH levels were also high. This TSH-dependent elevation of T3 to T4 molar ratio indicates that increased T3 is derived from the thyroid (but not converted from T4 in peripheral tissues), because secretion of T3 from the thyroid varies depending on serum TSH levels [13]. Similar high T3 to T4 molar ratio phenotype has also been described in patients with adult-onset Tg deficiency [14][15][16].…”

Section: Discussionsupporting

confidence: 54%

Mild thyroid peroxidase deficiency caused by <i>TPO</i> mutations with residual activity: Correlation between clinical phenotypes and enzymatic activity

et al. 2017

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Thyroid peroxidase (TPO) deficiency, caused by biallelic TPO mutations, is a well-established genetic form of congenital hypothyroidism (CH). More than 100 patients have been published, and the patients have been diagnosed mostly in the frame of newborn screening (NBS) programs. Correlation between clinical phenotypes and TPO activity remains unclear. Here, we report clinical and molecular findings of two unrelated TPO mutation-carrying mildly hypothyroid patients. The two patients were born at term after an uneventful pregnancy and delivery, and were NBS negative. They sought medical attention due to goiter at age 8 years. Evaluation of the thyroid showed mild elevation of serum TSH levels, normal or slightly low serum T levels, high serum T to T molar ratio, high serum thyroglobulin levels, and high thyroidal I uptake. We performed next-generation sequencing-based genetic screening, and found that one patient was compound heterozygous for two novel TPO mutations (p.Asp224del; c.820-2A>G), and the other was homozygous for a previously known mutation (p.Trp527Cys). In vitro functional analyses using HEK293 cells showed that the two amino acid-altering mutations (p.Asp224del and p.Trp527Cys) caused partial loss of the enzymatic activity. In conclusion, we report that TPO mutations with residual activity are associated with mild TPO deficiency, which is clinically characterized by marked goiter, mild TSH elevation, high serum T to T molar ratio, and high serum thyroglobulin levels. Our findings illuminate the hitherto under-recognized correlation between clinical phenotypes and residual enzymatic activity among patients with TPO deficiency.

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Section: Discussionsupporting

confidence: 54%

Mild thyroid peroxidase deficiency caused by <i>TPO</i> mutations with residual activity: Correlation between clinical phenotypes and enzymatic activity

et al. 2017

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“…TSH has been shown to trigger preferential release of T3 from the thyroid gland in man. 34 Although TSH was not significantly different between the diet treatment conditions, preferential T3 secretion represents a possible mechanism by which isoflavones increase plasma T3 concentration.…”

Section: Discussionmentioning

confidence: 84%

Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis)

Silverstein

Kaplan

Appt³

et al. 2014

Menopause

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Objectives Soy isoflavones are commonly used to alleviate menopause-related symptoms. Menopausal women are at an increased risk for hypothyroidism and there are concerns that isoflavones may be detrimental to thyroid health. The aim of this study was to examine the effects of soy protein and isoflavones on thyroid function and the relationship between thyroid and ovarian function. Methods Adult female cynomolgus monkeys (Macaca fascicularis) were randomized to consume two diets differing only in protein source: casein-lactalbumin (n = 44) or soy protein with isoflavones (n = 41). After 34 months all animals were ovariectomized via laparotomy. Half of the monkeys from each diet treatment group continued to consume their Pre-Ovariectomy treatment phase diet (either SOY [n = 19] or CL [n = 21]) for an additional 34 months. The remaining animals did not continue their diets, and thus were not considered further. Circulating progesterone, triiodothyronine, thyroxine, and thyroid stimulating hormone were measured at baseline. Thyroid hormones were remeasured during each treatment phase. Results Dietary soy increased triiodothyronine in pre-ovariectomized monkeys and prevented a decline in thyroxine following surgical menopause (both p’s < 0.05). Mean progesterone concentrations were positively correlated with triiodothyronine at baseline in pre-ovariectomized monkeys (p < 0.01). Conclusions Progesterone levels and triiodothyronine are positively correlated in macaques. Dietary soy increases triiodothyronine in pre-ovariectomized monkeys and prevents a decline in thyroxine following surgical menopause. The outcomes observed in this study suggest soy protein and isoflavone consumption does not adversely affect and may even preserve thyroid function in postmenopausal women.

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“…Injec¬ tion of TSH in man preferentially increases plasma concentrations of T3 (Carpi, Bianchi, Zuchelli et al 1979). Fourthly, numerous reports indicate that, in several mammalian species, TSH stimulates the intrathyroid conversion of T4 to T3 (see Introduction).…”

Section: Basal Levels Of Hormonesmentioning

confidence: 99%

Preferential release of tri-iodothyronine following stimulation by thyrotrophin or thyrotrophin-releasing hormone in sheep of different ages

Peeters

Buys²,

Vanmontfort³

et al. 1992

Journal of Endocrinology

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The influence of TRH and TSH injections on plasma concentrations of tri-iodothyronine (T3) and thyroxine (T4) was investigated in neonatal (injection within 0.5 h after delivery) and growing lambs and in normal, pregnant and lactating adult ewes (all 2 years old and originating from Suffolk, Milksheep and Texal crossbreeds). Neonatal lambs had higher levels of T3, T4 and GH compared with all other groups, whereas prolactin and TSH were higher in lactating ewes. In all animals, injections of TRH increased plasma concentrations of prolactin and TSH after 15 min but not of GH at any time. Small increases in T3 and T4 were observed in neonatal lambs, without any effect on the T3 and T4 ratio, after prolactin administration, whereas prolactin did not influence plasma concentrations of T3 or T4 in all other experimental groups. Similar results for thyroid hormones were obtained after TRH or TSH injections. It was therefore concluded that the effects observed after TRH challenge were mediated by the release of TSH. With the possible exception of neonatal lambs, plasma concentrations of T3 after administration of TRH or TSH were always increased before those of T4; the increase in T3 occurred within 0.5-1 h compared with 2-4 h for T4 in all experimental groups. This resulted in an increased ratio of plasma T3 to T4 up to 4 h after injection. It is concluded that, in sheep, TRH and TSH preferentially release T3 from the thyroid gland probably by a stimulatory effect of TSH on the intrathyroidal conversion of T3 to T4.

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Effect of Endogenous Thyroid Stimulating Hormone Levels on the Secretion of Thyroid Hormones in Man

Cited by 8 publications

References 8 publications

Mild thyroid peroxidase deficiency caused by <i>TPO</i> mutations with residual activity: Correlation between clinical phenotypes and enzymatic activity

Mild thyroid peroxidase deficiency caused by <i>TPO</i> mutations with residual activity: Correlation between clinical phenotypes and enzymatic activity

Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis)

Preferential release of tri-iodothyronine following stimulation by thyrotrophin or thyrotrophin-releasing hormone in sheep of different ages

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