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Cellular thyroid hormone homeostasis requires adequate function of: (1) thyroid hormone transporter proteins at the plasma membrane, (2) deiodinating enzymes and (3) nuclear thyroid hormone receptors (TRs). Defects in any of these processes give rise to distinct disease entities, collectively called thyroid hormone signaling disorders. Thyroid hormone analogues hold therapeutic potential in thyroid hormone signaling disorders by bypassing defective transporters or binding to mutant TRs. This review will focus on the application of analogues in thyroid hormone signaling disorders, particularly monocarboxylate transporter (MCT)8 deficiency, and resistance to thyroid hormone due to mutations in TRβ (RTHβ)., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objectives: Multinodular goiter is a common disorder, found in 5% of the general population. If only one thyroid lobe is affected, hemithyroidectomy may be preferred to total thyroidectomy, to limit the risk of complications and avoid hormone replacement therapy, but incurs a risk of subsequent completion thyroidectomy. The aim of the present study is to determine whether the arguments in favor of hemithyroidectomy are justified and whether it still provides real benefit., Methods: A retrospective observational study based on prospective data included all patients who underwent surgery for goiter or nodule in our center between September 2010 and September 2014. Rates of hormone replacement 6 months after hemithyroidectomy, postoperative complications and completion thyroidectomy during the postoperative year due to the discovery of carcinoma were analyzed., Results: Four hundred and ninety-three patients were studied: 335 with total thyroidectomy and158 with hemithyroidey. The rate of hormone replacement 6 months after hemithyroidectomy was 84.4%. The rate of definitive hypocalcemia was 6.3% in total thyroidectomy and zero in hemithyroidectomy (P<0.05). There was no significant difference between groups in terms of recurrent laryngeal nerve palsy (1.8% versus 1.9%; P=1) or hematoma (1.2% versus 3.5%; P=0.15). A total of 11.3% of hemithyroidectomies required completion due to discovery of carcinoma (mean interval between surgeries 3.58±2.5 months)., Conclusions: This study suggests that hemithyroidectomy does not in fact avoid the risk of hormone replacement and places the patient at risk of completion thyroidectomy. However, it does avoid a 6% rate of hypocalcemia. We would recommend hemithyroidectomy only in case of single toxic or euthyroid nodule with healthy contralateral lobe and/or refusal of hormone replacement by the patient., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Thyroid hormones [predominantly 3, 5, 3 -I- iodothyronine (T3)] regulate cholesterol and lipoprotein metabolism but cardiac effects restrict their use as hypolipidemic drugs. New molecules have been developped which target specifically the thyroid hormone receptor ss, predominant isoform in liver. The first thyroid hormone agonist, called GC1, has selective actions compared to T3. In animals, GC1 reduced serum cholesterol and serum triglycerides, probably by stimulation important steps in reverse cholesterol transport. Other selective thyromimetic, KB- 2115 and KB - 141 have similar effects. Another class of thyroid hormone analogs, the thyronamines have emerged recently but the basic biology of this new class of endogenous thyroid hormone remains to better understood. Therefore, these molecules may be a potentially treatment for obesity and reduction cholesterol, triglycerides and lipoprotein (a). To date the studies in human are preliminary. Tolerance and efficacy of these drugs are still under investigation.

In critically ill patients, pronounced alterations in the hypothalamic-pituitary-thyroid axis occur without any evidence for thyroid disease. T3 decreases and rT3 increases within a few hours of the onset of disease. Severity and duration of disease are related to the magnitude of these changes. This manuscript discusses whether these changes in thyroid hormone levels during critical illness should be treated, and was in part published elsewhere.

Infraclinical hypothyroidism is a recognized entity defined in terms of laboratory results which occurs more readily in women. The appropriateness of thyroid hormone multicentric prospective study initiated in 1997 has established that infraclinical hypothyroidism occurred in about 3% of women over 45 years of age undergoing routine check-ups at eleven health screening centers. Associated clinical signs and laboratory findings were reported. The purpose of the present study was to describe findings in a 3-year follow-up of these women with infraclinical hypothyroidism in order to assess natural history and appropriate care. Ninety-seven women of the 151 women with a TSH level between 4 and 12 mU/l in the 1997 survey were reviewed during the last three months of 2000. Forty-three of them had taken thyroid hormone replacement drugs since 1997. About 44% of the women examined still had infraclinical hypothyroidism or developing hypothyroidism. There was not significant difference between treated (33%) and non-treated (55%) patients. Clinical and biological signs associated with infraclinical hypothyroidism at the initial examination (elevated serum cholesterol, abnormal ECG, eyelid edema, recent weight gain) were unchanged at the second examination, both in treated and not treated women. A logistic model including all these factors demonstrated that the probability of prescription of thyroid hormone replacement therapy increased 5.4-fold when the starting TSH level was above 6 mU/l and 3.2-fold if ECG abnormalities were present. Using a statistical model with anti TPO antibodies, a level above 64 U/l increased the probability of treatment 7-fold, with ECG findings being related to probability of treatment. Age, cholesterol level, use to lipid lowering drugs, presence of eyelid edema or weight gain were not associated with replacement therapy in this model. No consistent conclusion concerning the appropriateness of screening for infraclinical hypothyroidism can be drawn from these three-year follow-up findings. Another examination scheduled for 2003 should provide further precision concerning the natural history of infraclinical hypothyroidism as well as long-term medical practices and therapeutic impact.

Most thyroid nodules discovered during pregnancy are benign. In this article, we propose a pragmatic attitude for the diagnosis and treatment of such nodules, insisting particularly on the importance of thyroid echography and fine needle aspiration. For women who have successfully been treated for thyroid cancer before pregnancy, we discuss the adaptation of thyroxine substitution when they become pregnant, the obstetrical and fetal risks (spontaneous miscarriage, fetal abnormalities of the thyroid gland and others), and also potential later risks for the child, in relation with previous radioactive iodine administration to the mother. Finally, we evoke more difficult questions, such as the rare instances in which thyroid cancer is discovered during pregnancy, pregnancy occurring during the months immediately following radioiodine treatment, and exceptional cases where therapeutic radioiodine was inadvertently given during pregnancy.

Papillary and follicular carcinomas are the most frequent thyroid cancers. The choice of the treatment is dependent on the prognostic scoring systems. A good prognosis is linked to the small size of the nodule (especially) microcarcinoma) the age of the patient (less than 40), the lack of extra-thyroid (for papillary cancer) or extra capsular (for follicular carcinoma) extension. Total thyroidectomy decreases the number of recurrences but does not modify the mortality. The risk of laryngeal nerve palsy and hypoparathyroidism is not negligible. Lobo-isthmectomy thus can be used in the low risk tumors. Radioactive iodine administration is rational after total thyroidectomy but its efficacy is questioned. Thyroxine treatment is always prescribed. Taking into account the risk of osteopenia and cardiovascular disturbances induced by iatrogenic thyrotoxicosis, the desirable serum TSH level is debated.

Since TSH favors thyroid cells growth and proliferation, thyroid hormone administration is widely used to reduce TSH secretion in patients treated for thyroid cancers. But what degree of TSH suppression is required to inhibit tumorgenesis and prevent recurrences remains unknown. High doses of thyroid hormone can determine undesirable effects on quality of life, bone mass, or cardiac function. These effects have to be evaluated and eventually prevented by specific therapies. Probably the degree of TSH suppression has to be adjusted to the prognosis of the thyroid cancer and the specific risks for every patient.

The usual clinical presentation of Hashimoto's chronic lymphocytic thyroiditis is a firm and painless goiter. We report two atypical observations with painful symptoms. Case 1: a 33 year old woman with a two months history of L-thyroxine treated primary hypothyroidism associated with elevated antithyroglobulin and antithyroperoxydase antibodies (respectively 36.000 and 7.000 U/l, normal values < 100 U/l) presents with anterior cervical pain. She is euthyroid, but displays biological inflammatory syndrome. Neck ultrasonography reveals low amplitude echoes of the thyroid gland. Antithyroid antibodies remain at high titers. After failure of NSAI drugs, prednisolone (oral 30 mg/day for 10 days, followed by degression) allows rapid disappearance of both pain inflammatory syndrome. When treatment was stopped pain recurred and required steroids for 3 months. After one year, the patient is painless and only receives L-thyroxine. Case 2: a 36 year old woman is referred for anterior neck pain, fever and hypothyroidism. Biological inflammation is also noted. High levels of antithyroglobulin and antithyroperoxydase antibodies are found. Thyroid uptake was maintained. L-thyroxine and prednisolone (oral 20 mg/day) therapies are associated with rapid pain relief. After two months, steroids are stopped. The patient remains normothyroid under L-thyroxine. Antithyroid antibodies persist at high levels. Other aetiological diagnosis of painful thyroid include acute infectious thyroiditis, cancers, intracystic hemorrhages and mainly subacute De Quervain's thyroiditis. Beyond clinical symptoms (revelation with hypothyroidism), persistent scintiscan uptake and prolonged elevated levels of antithyroglobulin and antithyroperoxydase antibodies remain the strongest arguments in favor of the 33 reported cases of painful Hashimoto's chronic lymphocytic thyroiditis. Eventually, among various therapies used, steroids in conjunction with thyroid hormones, seem the most efficient.

Hemithyroidectomy is the basic operation for isolate thyroid nodules or unilateral multinodular goiters. However, surgeons must check the absence of contralateral nodules by palpation, in order to avoid residual nodules that are not readily amenable to hormone therapy. In a review of 1456 goiters operated between 1968 and 1983, the authors identify only the multinodular nature as a significant risk factor of recurrence. In view of the prevention of residual nodules, they note only 2.5% recurrence. Although some studies demonstrate an increase in the TSH level after hemithyroidectomy, these results do not allow recommending systematic postoperative hormone therapy. This seems to be justified only in a population at risks, namely patients with multinodular goiter, increased postoperative TSH levels, thyroiditis or a family history.

It is debatable whether treatment of thyroid nodules with thyroid hormones is effective, results of clinical trials, even randomized, being inconclusive, none of them showing significant efficacy of this therapy. Two questions remain unanswered: what is the natural history of these nodules and is it possible to identify patients with these heterogeneous lesions who will respond to treatment? Currently available study data show a marked level of spontaneous regression or even total disappearance of the nodules. Further long-term clinical trials appear indicated, including a sufficient number of patients and a large cohort of untreated patients.

The frequency of recurrence of thyroid nodule following hemithyroidectomy is variably assessed according to the individual authors. Few studies put a figure to ultrasonographic recurrence, clinical recurrence only being taken into account: its percentage ranges from 10 to 20%, increasing with the time lapse after thyroidectomy. Attempts to prevent recurrence are based on an approach of the physiopathology of thyroid nodules. Clinical and epidemiological studies of patients with goiters suggest that TSH may play a role in the generation of goiters, as has been confirmed by experimental work. However, several other local autocrine or paracrine growth factors may also be involved in the generation of goiters, including IGF I and IGF II (Insulin Growth Factors), FGF (Fibroblast Growth Factor), EGF (Epidermal Growth Factor), TGFB (Transforming Growth Factor beta). On the basis of the possible role of TSH in goiter generation, some teams have advocated a postoperative course of thyroid hormones aimed at limiting thyreostimulin production. These studies, most of them retrospective studies, do not allow drawing a meaningful conclusion because their methods are open to criticism and the results observed are disparate. On a whole, although thyroid hormone therapy is often used after hemithyroidectomy, the physiopathological bases of its prescription are disputable, and the results obtained in terms of recurrence of nodules are not conclusive enough. It is therefore desirable to set up randomized studies.

The appropriateness of treating thyroid nodules with thyroid hormone is being debated: in fact, the development of nodules is not caused by an iodothyronine deficiency or a desuppression of TSH, and T4 seems to be able to regain control on cell proliferation. A very great number of authors have reported their experience with suppression of thyroid nodules with thyroid hormone, but treatment efficacy has been variably appreciated (9 to 69% regression). On the other hand, the four randomized prospective studies available at present, which analyze the evolution of nodules, especially on ultrasonography, have not demonstrated that hormone therapy is more effective than a placebo. The methodology of these studies is not free from criticism, and other prospective surveys are required, especially to establish whether this treatment is innocuous and whether some varieties of nodules may be more amenable to hormone therapy than others.

A decreased bone mineral density is a well known complication of thyrotoxicosis. If bone is also adversely affected by a subclinical hyperthyroidism is still debated. Such a situation is deliberately induced for treatment of thyroid differentiated carcinoma. We compared bone mineral measurements in case of thyroid carcinoma exposed to prolonged suppressive hormonal treatment (288 patient year, LT3 in 87%) and in age and weight matched controls. We did not find any difference in both sexes between the two populations in term of fracture rate and vertebral mineral density measured by dual photon absorptiometry, nor any influence of gonadal status in women.

Early continuous hormonal treatment, inhibiting TSH secretion, reduces the volume of recent homogeneous goiters. This treatment is usually well tolerated, but can induce thyrotoxicosis in subjects with blunted response of TSH to TRH stimulation before treatment. Surgery is used for large goiters, compressive goiters or suspicion of cancer and after failure of the hormonal treatment. In all cases, hormonal treatment must be associated to surgery. Radio-iodine can be used for large or compressive goiters, when surgery is inadvisable. Despite the risk of thyrotoxicosis, iodine addition in food intake is useful to prevent goiters. The frequency of thyrotoxicosis can be decreased by ruling out subjects over 50 years old, with nodular goiters or with blunted response of TSH to TRH stimulation.

Serum TSH (Thyroid Stimulating Hormone) was measured before and 30 minutes after a 200 microgram intravenous TRH (Protiréline*) injection in 270 patients. These patients have been treated for one year at least, by a suppressive thyroid therapy after thyroidectomy for a differentiated thyroid carcinoma. 314 tests were performed. We used an ultrasensitive TSH method (Ciba-Corning-Diagnostics). The normal range (mean :1.68 mUI/l; range: 0.45 to 3.80 mUI/l) was determined in 116 euthyroid patients. Minimal response to TRH was studied in 35 untreated patients with hyperthyroidism (TSH TO: less than 0.30 mUI/l and delta TSH: less than 0.09 mUI/l). There was a relationship (r = 0.916) between TSH response 30 minutes after TRH stimulation (T30) and basal TSH value: in a logarithmic scale (fitting of the data by a bi-gaussian model). TRH tests were classified too, by basal TSH values (TO) and delta TSH (TSH at T30-TSH at TO). In 201 tests in which TO TSH was less than 0.30 mUI/l (maximal value in hyperthyroidism), 50 showed a delta TSH higher than 0.15 mUI/l (25% of the cases) and in 6 cases (3%), delta TSH was even higher than 2.0 mul/l; in 67 of the 75 tests (89.3%) where TSH TO is less than 0.15 mUI/l, delta TSH is no (less than 0.15 mUI/l). In 93 tests where TO TSH was upper than 0.45 mUI/l (minimal value in euthyroidism), delta TSH was higher than 2.0 mUI/l in 87 cases (93.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty five patients with hypopituitarism have been studied. Nine had a mild hyponatremia (126-137 mEq/l) and five a profound hyponatremia (105-124 mEq/l). None of them had hemodilution (plasma protein, potassium were normal). Hyponatremia was present even in the absence of deficit in GH and/or TSH, and/or FSH-LH. All the pateints had a complete ACTH deficiency. There was a negative correlation between age and natremia (r = -0,39; p0.02). 2/5 patients with severe hyponatremia had mental confusion. These two patients had a complete TSH deficiency. Natremia increased with cortisone therapy in all cases but reached the normal range only in one case. Mental confusion disappeared and natremia became normal in all patients with therapy with cortisone and thyroid hormones.