Postpartum mood disorders and thyroid autoimmunity

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Refractory Hypothyroidism Due to Improper Storage of Levothyroxine Tablets

ContextA not negligible part of hypothyroid patients on levothyroxine therapy do not normalize serum thyrotropin (TSH) concentrations. “Refractory hypothyroidism,” i.e., a condition characterized by persistently abnormal serum TSH levels despite adequate titration of l-T4 substitution therapy, requires biochemical and instrumental investigation, but no definite etiology is found in up to 15% of cases.ObjectiveTo report patients presenting with refractory hypothyroidism with proven improper storage of levothyroxine tablets.DesignPatients on l-T4 substitution therapy referred to three Italian outpatient Clinics of Endocrinology between January 2013 and December 2015 for refractory hypothyroidism were investigated for levothyroxine tablet exposure to humidity, light, and high temperature.ResultsWe report eight patients, accounting for approximately 1% of all hypothyroid patients and 5% of those with refractory hypothyroidism in our series. Careful anamnesis disclosed that these patients stored levothyroxine tablets inappropriately. Normalization of serum TSH concentrations was obtained in all cases by simply recommending to store the new levothyroxine tablets away from heat, light, and humidity.ConclusionRefractory hypothyroidism linked to improper storage of l-T4 tablets does exist and might be an underrecognized entity. In addition to proper modalities of ingestion of l-T4 tablets, patients need to be instructed on proper modalities of storage, as well

Psoriasis, Psoriatic Arthritis, and Thyroid Autoimmunity

Psoriasis (PsO) is a chronic relapsing/remitting autoimmune skin disease, associated with an increased risk of other autoimmune disorders. Psoriatic arthritis (PsA) is a chronic inflammatory arthritis occurring approximately in 30% of PsO patients. Sporadic cases of association between PsO and autoimmune thyroid disorders (AITDs) have been reported. However, two different recent studies did not find any association between them. In patients with PsO and PsA, an association with AITD has been shown by most of the studies in adults, but not in the juvenile form. In PsA women and men, thyroid autoimmunity [positive antithyroid peroxidase (AbTPO) antibodies, hypoechoic thyroid pattern] and subclinical hypothyroidism were more prevalent than in the general population. An association has been shown also in patients with PsO, arthritis, and inflammatory bowel disease, who have more frequently AITD. A Th1 immune predominance has been shown in early PsO, and PsA, with high serum CXCL10 (Th1 prototype chemokine), overall in the presence of autoimmune thyroiditis. This Th1 immune predominance might be the immunopathogenetic base of the association of these disorders. A raised incidence of new cases of hypothyroidism, thyroid dysfunction, positive AbTPO, and appearance of a hypoechoic thyroid pattern in PsA patients, especially in women, has been shown recently, suggesting to evaluate AbTPO levels, thyroid function, and thyroid ultrasound, especially in PsA women. Thyroid function follow-up and suitable treatments should be performed regularly in PsA female patients at high risk (thyroid-stimulating hormone within the normal range but at the higher limit, positive AbTPO, hypoechoic, and small thyroid)

Homology between TSH-R/Tg/TPO and Hashimoto's encephalopathy autoantigens.

Hashimoto's encephalopathy (HE) is a syndrome occurring in some patients with Hashimoto's thyroiditis or, less frequently, Graves' disease. Three known autoantigens are involved in HE: alpha-enolase, dimethylargininase-I (DDAHI) and aldehyde reductase-I (AKRIAI). We searched for amino acid sequence homologies between these proteins and the three classical thyroid autoantigens (thyroperoxidase (TPO), thyroglobulin (Tg), TSH-receptor (TSH-R)), which are also expressed in the central nervous system (CNS). TSH-R shows homologies with alpha-enolase (n=4), DDAHI (n=2) and AKRIAI (n=5); of these segments, two, two and four, respectively, overlap totally or partially with epitope-containing TSH-R segments. Tg has 10 homologies with alpha-enolase, five with DDAHI, and eight with AKRIAI; epitope-containing segments of Tg overlap four, three and four segments, respectively. TPO has six segments homologous to alpha-enolase, three to DDAHI and seven to AKRIAI; of these segments, five, one and four, respectively, are located in epitope-containing parts. These data suggest that cross-reactivity between CNS autoantigens and thyroid autoantigens might contribute to the HE pathogenesis, together with other proposed mechanisms, including autoimmunity involving autoantigens common to CNS and thyroid

Thyroid Autoimmunity and Lichen

Lichen planus (LP) and lichen sclerosus (LS) are cutaneous-mucous diseases with uncertain epidemiology. Current data, which are likely to be underestimated, suggest a prevalence in the general population of 0.1–4% for cutaneous LP, 1.27–2.0% for oral LP, and 0.1–3.3% for LS. While etiology of lichen is still unknown, clinical and histological evidence show an (auto)immune pathogenesis. Association of lichen with autoimmune thyroid disease (AITD) has been investigated in few studies. This association appears better defined in the case of LS, while is more controversial for LP. In both situations, the frequency of the association is higher in females. We review the available literature on the correlation between the different types of lichen and AITD, and the literature on the genetic risk factors which are shared by both conditions. Such data suggest that a common pathogenic mechanism could be the cause for co-occurrence of lichen and AITD, at least in some patients. Additionally, analyzing literature data and in continuity with our previous work on other autoimmune diseases, we suggest that molecular mimicry could trigger both diseases, and thus explain their co-occurrence

Refractory hypothyroidism due to improper storage of levothyroxine tablets

Context: A not negligible part of hypothyroid patients on levothyroxine therapy do not normalize serum thyrotropin (TSH) concentrations. "Refractory hypothyroidism," i.e., a condition characterized by persistently abnormal serum TSH levels despite adequate titration of l-T4 substitution therapy, requires biochemical and instrumental investigation, but no definite etiology is found in up to 15% of cases. Objective: To report patients presenting with refractory hypothyroidism with proven improper storage of levothyroxine tablets. Design: Patients on l-T4 substitution therapy referred to three Italian outpatient Clinics of Endocrinology between January 2013 and December 2015 for refractory hypothyroidism were investigated for levothyroxine tablet exposure to humidity, light, and high temperature. Results: We report eight patients, accounting for approximately 1% of all hypothyroid patients and 5% of those with refractory hypothyroidism in our series. Careful anamnesis disclosed that these patients stored levothyroxine tablets inappropriately. Normalization of serum TSH concentrations was obtained in all cases by simply recommending to store the new levothyroxine tablets away from heat, light, and humidity. Conclusion: Refractory hypothyroidism linked to improper storage of l-T4 tablets does exist and might be an underrecognized entity. In addition to proper modalities of ingestion of l-T4 tablets, patients need to be instructed on proper modalities of storage, as well

A Patient-Specific Treatment Model for Graves’ Hyperthyroidism

Background: Graves’ is disease an autoimmune disorder of the thyroid gland caused by circulating anti-thyroid receptor antibodies (TRAb) in the serum. TRAb mimics the action of thyroid stimulating hormone (TSH) and stimulates the thyroid hormone receptor (TSHR), which results in hyperthyroidism (overactive thyroid gland) and goiter. Methimazole (MMI) is used for hyperthyroidism treatment for patients with Graves’ disease. Methods: We have developed a model using a system of ordinary differential equations for hyperthyroidism treatment with MMI. The model has four state variables, namely concentration of MMI (in mg/L), concentration of free thyroxine - FT4 (in pg/mL), and concentration of TRAb (in U/mL) and the functional size of the thyroid gland (in mL) with thirteen parameters. With a treatment parameter, we simulate the time-course of patients’ progression from hyperthyroidism to euthyroidism (normal condition). We validated the model predictions with data from four patients. Results: When there is no MMI treatment, there is a unique asymptotically stable hyperthyroid state. After the initiation of MMI treatment, the hyperthyroid state moves towards subclinical hyperthyroidism and then euthyroidism. Conclusion: We can use the model to describe or test and predict patient treatment schedules. More specifically, we can fit the model to individual patients’ data including loading and maintenance doses and describe the mechanism, hyperthyroidism → euthyroidism. The model can be used to predict when to discontinue the treatment based on FT4 levels within the physiological range, which in turn help maintain the remittance of euthyroidism and avoid relapses of hyperthyroidism. Basically, the model can guide with decision-making on oral intake of MMI based on FT4 levels

A case of amiodarone-induced hypothyroidism in a mild to moderate iodine deficiency area

Thyroid dysfunction associated to amiodarone treatment depends on iodine intake, as thyrotoxicosis occurs more frequently in iodine deficiency areas, whereas hypothyroidism in iodine sufficient areas. We present here a case of severe overt hypothyroidism induced by prolonged treatment with amiodarone for atrial fibrillation in a man living in a low iodine intake area. The case was managed with levothyroxine (LT4) replacement and amiodarone withdrawal. Euthyroidism was restored after two months, and atrial fibrillation has not relapsed to date

Support for the upregulation of serum thyrotropin by estrogens coming from the increased requirement of levothyroxine in one gynecomastic patient with excess of thyroxine-binding globulin secondary to exposure to exogenous estrogens

Thyroxine-binding globulin (TBG) is the liver-synthesized and estrogen-upregulated major plasma carrier of thyroid hormones with an affinity binding greater for T4 than T3. It is known that pregnancy, a physiologic state of estrogen-driven elevation of serum TBG, raises the requirement of L-T4 dose in hypothyroid women, especially those with no residual thyroid function. Similar increased requirement was reported for postmenopausal women during estrogen therapy. One known cause of relative hyperestrogenemia, gynecomastia and acquired TBG excess is liver disease, but very rarely chronic liver disease is mentioned as a cause of increased L-T4 requirement. One hypothyroid man with cirrhosis-associated gynecomastia and increased serum levels of both estradiol and TBG was reported recently. His requirement of L-T4 was no longer increased after liver transplantation. We now report the case of a man with primary hypothyroidism under stable replacement therapy with L-T4 until exposure to an exogenous cause of hyperestrogenemia caused increased L-T4 requirement associated to TBG excess. In addition to increased TBG, the high levels of estrogens had caused the appearance of gynecomastia. We fully corrected primary hypothyroidism upon eliminating his exposure to the source of estrogens. Hyperestrogenism can be a cause of increased L-T4 requirement through the rise of circulating levels of TBG also in man with no residual thyroid function. Keywords: Thyroxine-binding globulin, Estrogens, Thyrotropin, Levothyroxine therapy, Refractory hypothyroidis