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Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis.

ABSTRACT: Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin (TSH). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine (L-T4). In this paper, we extend a mathematical model of the pituitary-thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a TSH-T3-shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine (FT3). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of TSH and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g., in the differential diagnosis of subclinical hypothyroidism.

SUBMITTER: Berberich J

PROVIDER: S-EPMC5871688 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis.

Berberich Julian J Dietrich Johannes W JW Hoermann Rudolf R Müller Matthias A MA

Frontiers in endocrinology 20180321

Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin (TSH). Diagnostical problems also apply to subjects affected by syndrome T, i.e., those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine (L-T4). In th ...[more]

PMID: 29619006

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Project description:BackgroundThyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) with coexisting thyroid cancer is extremely rare, and proper treatment of both diseases may pose a unique clinical challenge. When TSHoma has plurihormonality, particularly involving the co-secretion of growth hormone (GH), management can be more complicated. Herein, we present a difficult-to-manage case of papillary thyroid cancer with an incurable TSH/GH-secreting pituitary adenoma.Case presentationA 59-year-old man was referred to our hospital due to memory impairment and inappropriate TSH level. Sella magnetic resonance imaging revealed a huge pituitary mass extending to the suprasellar area. Clinical diagnosis of TSH/GH co-secreting pituitary adenoma was made based on elevated free T4, total T3, serum α-subunit, insulin-like growth factor-1 levels and non-suppressible GH levels after oral glucose loading. Rectal cancer and multifocal papillary thyroid microcarcinoma (PTMC) were diagnosed during initial screening for internal malignancy; lower anterior resection was performed and close observation was planned for PTMC. Long-acting octreotide therapy was commenced, which resulted in a dramatic reduction in TSHoma size and facilitated control of hormonal excess. Total thyroidectomy and radioactive iodine (RAI) therapy were needed during follow up due to the growth of PTMC. After the surgery, the pituitary adenoma represented resistance to somatostatin analogue therapy and the tumor size gradually increased despite the addition of dopamine agonist therapy. Furthermore, TSH suppressive therapy with levothyroxine was impossible and an adequate TSH level for RAI therapy was unmountable. Late debulking pituitary surgery was ineffective, and the patient gradually deteriorated and lost to follow up.ConclusionWe report the first aggravated case of TSH/GH co-secreting pituitary tumor after total thyroidectomy for concomitant multifocal PTMC. Deferring of thyroid surgery until the TSHoma is well controlled may be the optimal therapeutic strategy in patients with TSHoma and coexistent thyroid cancer; ablative thyroid surgery may result in catastrophic pituitary tumor growth.

Dataset Information

Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T3-Shunt and Sensitivity Analysis.

Publications

Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T<sub>3</sub>-Shunt and Sensitivity Analysis.

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