Bernard Corvilain

Duox expression and related H2O2 measurement in mouse thyroid: onset in embryonic development and regulation by TSH in adult

In the thyroid, H(2)O(2) is produced at the apical pole of thyrocytes by one or two NADPH oxidases (NOX), Duox1/2 proteins. The onset of Duox expression was analysed by immunohistochemistry in the developing mouse thyroid in parallel with thyroglobulin (Tg) iodination and the expression of other thyroid differentiation markers. Duox proteins were found at embryonic day (E) 15.5 and were mainly localised at the apical pole of thyrocytes. Tg was detected 1 day before (E14.5) and Tg iodination was concomitant with the expression of both Duox and Na(+)/I(-) symporter (NIS; E15.5). The role of TSH in regulating Duox expression and H(2)O(2) accumulation was evaluated in thyroids of adult mice with reduced (Tshr(hyt/hyt) or mice treated with thyroxine) or increased (methimazole or perchlorate treatment) TSH/Tshr activity. In mice with suppressed TSH/Tshr activity, Duox expression was only partially decreased when compared with wild-type, as observed by western blot. In Tshr(hyt/hyt) strain, Duox was still expressed at the apical pole and H(2)O(2) measurements were normal. On the other hand, chronic TSH stimulation of the gland led to a decrease of H(2)O(2) measurements without affecting Duox expression. The onset of Duox protein expression is compatible with their proposed function in thyroid hormone synthesis and it can be considered as a functional marker of the developing thyroid. However, Duox expression in adult is much less regulated by TSH than NIS and thyroperoxidase. It is not always correlated with the overall thyroid H(2)O(2) accumulation, highlighting the importance of additional regulatory mechanisms which control either the production or H(2)O(2) degradation.

Transducing Systems in the Control of Human Thyroid Cell Function, Proliferation and Differentiation

Our laboratory has been involved in the study of thyroid regulation at the cellular level for many years. The complex picture emerging from these studies leads to conclusions of general relevance. The regulation of the thyroid cell was once a classical example of the concept one hormone — one cell type — one intracellular secondary messenger with its pleiotypic effects. It should now rather be considered as a network of crosslinked regulatory steps where the extracellular and intracellular signal-molecules act on their receptors as bits of information in an electronic circuit, i.e., express on/off regulations with no definite general physiological meaning per se. Such networks differ from one cell type to another and for a given cell type from one species to another. In the case of the thyroid many apparent discrepancies in the literature are explained if this is taken into account. In this presentation, we wish to draw mainly on the results of our group to illustrate this point with regard to the regulation of function, proliferation and differentiation of the thyroid cell.

The Control of Human Thyroid Cell Function, Proliferation and Differentiation

The study of thyroid regulation at the cellular level is the main interest of our laboratory since many years. The complex picture emerging from these studies leads to conclusions of general relevance. The regulation of the thyroid cell was once a classical example of the concept one hormone — one cell type — one intracellular secondary messenger with its pleiotypic effects. It should now rather be considered as a network of crosslinked regulatory steps where the extracellular and intracellular signal-molecules act on their receptors as bits of information in an electronic circuit, i.e., express on/off regulations with no definite general physiological meaning per se. Such networks differ from one cell type to another and for a given cell type from one species to another. In the case of the thyroid, many apparent discrepancies in the literature are explained if this is taken into account. In this presentation, we wish to draw mainly on the results of our group to illustrate this point with regard to the regulation of function, proliferation and differentiation of the thyroid cell.

Unilateral adrenalectomy could be a valid option for Primary Nodular Adrenal Disease. Evidence via twins

Primary pigmented nodular adrenal disease (PPNAD) accounts for <1% of ACTH-independent Cushing syndrome. We describe the case of twin female patients with PPNAD who both had sustainable disease control after unilateral adrenalectomy, which corroborates current evidence in favor of unilateral adrenalectomy for a subset of patients with PPNAD. Patient A presented with a 10-kg weight gain over the past year and facial plethora. Diagnostic evaluation revealed abolition of normal cortisol rhythm with suppressed ACTH levels, normal adrenal CT and MRI imaging and a slightly left-predominant adrenal uptake on 131I iodomethyl norcholesterol scintigraphy coupled with single-photon emission CT/CT. PPNAD was confirmed after genetic testing revealed a known pathogenic PRKA1A mutation (c.709 (-7-2) del6). At that time, her twin sister (patient B) was asymptomatic. Patient A underwent successful unilateral adrenalectomy and histology confirmed PPNAD. Two years after initial onset of symptoms in patient A, patient B was seen for the same subtle symptoms of progressive weight gain. Diagnostic test results were identical, revealing the same clinical features and mutational status as patient A. Patient B also underwent unilateral adrenalectomy with a favorable outcome. Follow-up 3 years after surgery for patient A and 18 months for patient B showed sustained disease control without recurrence and uncompromised quality of life, with no adrenal insufficiency having occurred. Unilateral adrenalectomy can be a successful therapeutic approach for patients with PPNAD with a mild phenotype without the risk and the inconvenience of subsequent adrenal insufficiency, which alters quality of life.