Doses Of Thyroid Hormone Research Articles

Physician-reported barriers and facilitators to thyroid hormone deprescribing in older adults.

Thyroid hormone is one of the most commonly prescribed medications in the United States. Misuse of and overtreatment with thyroid hormone is common in older adults and can lead to cardiovascular and skeletal adverse events. Even though deprescribing can reduce inappropriate care, no studies have yet explored specific barriers and facilitators to guide thyroid hormone deprescribing in older adults (defined as discontinuation of thyroid hormone when initiated without an appropriate indication or dose reduction in those overtreated). We conducted semi-structured interviews with 19 endocrinologists, geriatricians, and primary care physicians who prescribe thyroid hormone. Interviews were completed between July 2020 and December 2021 via two-way video conferencing. We used both an inductive and deductive content analysis guided by the Theoretical Domains Framework to evaluate transcribed and coded participant responses. Thematic analysis characterized themes related to barriers and facilitators to thyroid hormone deprescribing practices in older adults. The most commonly reported barriers to thyroid hormone deprescribing were related to patient-level factors, followed by physician- and system-level factors. Patient factors included patients' perceived need for thyroid hormone use and patient anxiety/concerns about potential side effects related to thyroid hormone dose reduction, patient lack of knowledge, and misinformation regarding deprescribing. Physician- and system-level barriers included clinic visit time constraints, physician inertia, physician lack of knowledge about deprescribing, perceived lack of sufficient patient follow-up, and electronic health record limitations. The most prominent physician-reported facilitators to thyroid hormone deprescribing were effective physician-to-patient communication, and positive physician-patient relationship, including patients' trust in their treating physician. Barriers and facilitators to thyroid hormone deprescribing in older adults were reported at multiple levels including patient-, physician-, and system-level factors. Interventions to improve thyroid hormone deprescribing in older adults should aim to improve patient education and expectations, increase multidisciplinary physician awareness, and overcome physician inertia.

Regulation of Thyroid Hormone: An Important Aspect During Pregnancy

Abstract: This paper provides a synopsis of maternal and fetal thyroid hormone stimulation during pregnancy. Treatment of thyroid illness during pregnancy is critical for avoiding negative maternal and fetal outcomes. Thyroid disorders are frequently asymptomatic and difficult to detect without specialized monitoring programs. Even mild maternal thyroid hormone insufficiency can result in fetal neurodevelopment difficulties. The thyroid is over-stimulated during pregnancy, resulting in alterations in thyroid hormone concentrations. Accurate thyroid function testing during pregnancy is crucial for both initiating thyroid hormone therapy and adjusting thyroid hormone dose in people who are already on thyroid hormone. Trimester-specific intervals are particularly critical during pregnancy, when thyroid insufficiency has been linked to poor obstetric outcomes and neuro-developmental impairments in the fetus. Knowing the natural changes in hormone concentrations that occur throughout pregnancy allows for customized supplementation of iodine when needed.

Graves' orbitopathy development in thyroid cancer patients: a 16-year nationwide cohort study in South Korea.

We aimed to investigate the prevalence, risk factors, and prognosis of Graves' orbitopathy (GO) in patients with thyroid cancer without a history of hyperthyroidism. This retrospective cohort study analysed a sample from the Korean National Health Insurance Service database, which included 1,137,861 subjects from 2002 through 2019. Patients diagnosed with thyroid cancer, without a history of hyperthyroidism, were identified according to the Korean Standard Classification of Disease codes. The study compared the type of surgery, dose of radioactive iodine (RAI), and daily average thyroid hormone dose between patients who developed GO after being diagnosed with thyroid cancer and those who did not develop GO. We analysed the course of GO and the type of treatment. A total of 8499 cancer patients without a history of hyperthyroidism were identified, among whom 7836 underwent thyroidectomy. Of those who underwent thyroidectomy, 12 developed GO postoperatively. Among the 663 patients who did not undergo thyroidectomy, none developed GO. The prevalence of GO among thyroid cancer patients was 0.14%. The GO group received a significantly higher total RAI dose than the non-GO group (p = 0.036). There were no significant differences in sex, age, type of surgery, rate of RAI treatment, or average thyroid hormone dose between the two groups. One of the 12 patients who developed GO required intravenous steroids. Although GO rarely develops in thyroid cancer patients without coexisting hyperthyroidism, the total RAI dose may increase its risk. Further research would help clarify GO's association with thyroid cancer.

Dynamic Observation in Children and Adolescents Following Management of Differentiated Thyroid Cancer

Differentiated thyroid cancer (DTC) is one of the most common malignancies within the endocrine system, with a progressively increasing incidence over recent decades. In the structure of DTC, occurrence in the pediatric age group is relatively rare and is associated with excellent prognoses in terms of disease-specific survival. However, the prevalence of advanced disease in children and the frequency of recurrences present interdisciplinary teams with questions regarding the optimal management approach for such patients, focusing not on achieving disease eradication but preserving and maintaining quality of life. Notably, the presence of oncological pathology, coupled with fluctuations in thyroid hormone levels due to therapeutic interventions, underscores the importance of maintaining psychological and physiological well-being that are affected by the increased frequency of anxiety and depressive symptoms in children and their parents, as well as cognitive and physical functioning. These symptoms may exacerbate against the backdrop of hypothyroidism and directly correlate with TSH levels. To maintain quality of life during the period of dynamic observation and risk group re-stratification, we proposed a method of reduced thyroid hormone doses as an alternative to discontinuing thyroid hormones to assess stimulated thyroglobulin when reaching a threshold TSH level >30 mIU/L. The method was implemented in 2 pediatric patients, showing positive outcomes in terms of absence of hypothyroidism-related complaints, preservation of free thyroid hormone fractions, achievement of adequate target TSH levels, and informative tumor marker indicators. The results of our study underscore the importance of an individualized approach to the management of children with DTC and demonstrate the potential effectiveness of the reduced dose method in maintaining the quality of life of these patients. Further research and clinical observations are necessary for a deeper understanding of the applicability of this method and its impact on longterm outcomes.

SAT553 A Case of Metastatic Functional Papillary Thyroid Cancer in the Setting of Graves’ Disease

Abstract Disclosure: N. Manuel: None. S.J. Sternlieb: None. J. Dendy: None. Q.Z. Iqbal: None. A Case of Metastatic Functional Papillary Thyroid Cancer In the Setting of Graves’ DiseaseManuel, N., Sternlieb, S., Grissett, B., Iqbal, Q., Dendy, J. Background: Grave’s disease (GD) and papillary thyroid cancer (PTC) can be concomitant diseases. We report a rare case of metastatic PTC with concomitant GD leading to symptomatic hyperthyroidism despite total thyroidectomy. Clinical Case: A 58-year-old woman with longstanding history of thyroid nodules and left dominant nodule with benign biopsy on multiple occasions presented to her PCP with dyspnea, weight loss and globus sensation. CT of the chest was obtained revealing tracheal deviation from neck mass, mediastinal lymphadenopathy and multiple pulmonary nodules. Biopsy of lung nodule showed follicular features consistent with tumor cells of thyroid origin. She had a total thyroidectomy with central neck dissection with a final diagnosis of left sided 5 cm infiltrative follicular variant papillary thyroid carcinoma. Thyroid hormone replacement was initiated and on follow up 4 weeks later she was noted to be tachycardic at weight-based dose. At that time TSH was <0.010 uIU/mL (0.400 - 4.00), free T4 was 1.96 ng/dL (0.71 – 1.51) and Thyroglobulin was found to be 31516 ng/dL (Athyrotic <0.1). Prior to planned RAI she developed symptoms of dyspnea on exertion and edema and was sent to the ER for abnormal D. Dimer. Workup for PE was negative including CTA of the chest. A follow up visit showed further symptoms of hyperthyroidism with worsening fatigue, dyspnea, palpitations and new onset tremor. Levothyroxine dose was decreased further but 2 weeks later she returned to the ER with worsened thyroid function tests, and she was admitted for symptomatic hyperthyroidism. Levothyroxine was held and she was placed on PTU and propranolol. Given the overt symptomatic hyperthyroidism there were concerns for either Jod-Basedow phenomenon from iodine load with recent imaging or for hyperfunctioning PTC metastasis as the cause. Thyrotropin receptor antibody level was checked to further clarify and was elevated at 22 IU/L (0.00 – 1.75) consistent with GD. An I-131 diagnostic whole-body scan demonstrated small foci of right thyroid bed remnant and iodine-avid metastases involving mediastinal nodal disease as well as pulmonary and osseous metastases. She then underwent RAI therapy with 104.5 mCi I-131 without Thyrogen stimulation. Follow up whole body scan showed persistence of iodine-avid metastasis without any new foci of uptake compared to pretreatment scans. Conclusion: Although the coexistence of them is rare, GD should be put into the differential of rapidly progressive metastatic PTC especially if patient markedly hyperthyroid on lower doses of thyroid hormone. While functional thyroid carcinoma is rare, with less than 100 cases in literature, thorough investigation should be completed in order to not miss this concomitant disease process. Presentation Date: Saturday, June 17, 2023

FRI511 Bexarotene: A Deceptive Cause Of Iatrogenic Hypothyroidism

Abstract Disclosure: S. Ghaith: None. A. Ramachandran: None. C. Alcorn: None. F. Amer: None. A. Thompson: None. A. Ramachandran: None. Background: Bexarotene, an antineoplastic agent used for the treatment of cutaneous T cell lymphoma, is associated with a rapid and profound suppression of thyrotropin, which may lead to central hypothyroidism. Case: A Seventy-four-year-old female with a recent diagnosis of Cutaneous T cell lymphoma presented with a 1-week history of progressive fatigue, lightheadedness, and night sweats. She was found to have hypotension and hypothermia. She was started on oral Bexarotene chemotherapy 225 mg daily five days prior to admission. The physical exam was unremarkable except for sinus bradycardia and hypothermia. Labs were significant for TSH 0.48 [0.4-4.2 uIU/mL] dropped from 3.3 uIU/mL one week prior, FT4 0.5 [0.8-1.7 ng/dL] and Total T3 111 ng/dL [87- 187 ng/dL] consistent with central hypothyroidism. Bexarotene was held during her hospitalization per hematology recommendations. The patient was started on Levothyroxine 50 mcg, which was later advanced to 75 mcg daily based on free T4 levels. At one month follow up, free T4 level normalized while on Levothyroxine and Bexarotene was restarted again by her hematologist. Discussion: Bexarotene, an antineoplastic agent approved for treating cutaneous T cell lymphoma, can rapidly suppress TSH levels by directly inhibiting its secretion and affect thyroid hormone metabolism, leading to central hypothyroidism. The degree of suppression of TSH increases with higher doses of Bexarotene while reduction in free T4 and TSH are reversible. Patients already receiving thyroid hormone therapy may require increased thyroid hormone doses to achieve therapeutic levels. If bexarotene is permanently discontinued, levothyroxine can either be stopped or can be resumed to doses used prior to bexarotene therapy. Recovery of thyroid function usually occurs within weeks of Bexarotene discontinuation. Conclusion: Oral Bexarotene can cause central hypothyroidism therefore, thyroid function tests should be measured at baseline and treatment. Thyroid hormone replacement should be considered if central hypothyroidism is suspected. Presentation: Friday, June 16, 2023

Impact of thyroid hormone replacement on the risk of second cancer after thyroidectomy: a Korean National Cohort Study

We aimed to investigate the effect of thyroid hormone administration on the risk of second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer. Data were extracted from the medical billing data of the Health Insurance Review and Assessment Service in South Korea. Patients between 19 and 80 years old who underwent thyroid surgery at least once between January 2009 and June 2020 were included. Data of patients with second primary cancer and control patients with matched age, sex, operation date, and follow-up duration were extracted at a ratio of 1:4. A nested case–control analysis was performed to exclude length bias to confirm the correlation between the duration of thyroid hormone administration, dose, and incidence of second primary cancer. Of the 261,598 patients who underwent surgery for thyroid cancer included in the study, 11,790 with second primary cancer and 47,160 without second primary cancer were matched. The average dose of thyroid hormone increased the adjusted odds ratio (OR) for both low (≤ 50 μg, OR 1.29, confidence interval (CI) 1.12–1.48) and high (< 100 μg, OR 1.24, CI 1.12–1.37) doses. Analyzing over time, the adjusted OR of second primary cancer increased, especially in short (≤ 1 year) (OR 1.19; CI 1.06–1.34) and long (> 5 years) duration (OR 1.25; CI 1.10–1.41). In conclusion, insufficient and excessive thyroid hormone replacement might be linked to increased second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer.

Effect of Dietary Thyroxine Supplementation to Brood Nsh on Early Larval Development of Climbing Perch, &lt;i&gt;Anabas testiidineus&lt;/i&gt;

Effect of dietary thjroxine (T4) supplementation to Anabas testudineus brood fish on growth of their larvae were evaluated. The brood fish were divided into four groups - one group was fed with control diet and rest three groups were fed with 2 mg T4/kg diet, 5 mg T^/kg diet and 10 mg T^/kg diet, respectively for a period of 4 weeks. After 4 weeks, the fish were induced to breed using Ovaprim and the larvae were reared separately for a period of two weeks. The results indicated that larvae of T4 treated spawners exhibited significant increase in growth and also tended to show better survival compared to larvae of control group spawners. When larvae of control and T4 treated spawners were reared in thyroid hormone containing rearing medium (0.05 ppm), it was indicated that T4 at 0.05 ppm accelerated growth in larvae of control spawners and consistently, the same did not induce growth increment in the case of T4 treated spawners larvae. Hence, it was considered that in the case of T4 treated spawners, there might be transfer of thyroid hormone from mother to the oocytes and subsequently to the larvae and further treatment through immersion might have resulted in over dose of thyroid hormone leading to thyrotoxicosis and thereby growth retardation.

Drugs for hypothyroidism.

Primary hypothyroidism is usually the result of Hashimoto's (autoimmune) thyroiditis, thyroidectomy, or radioactive iodine therapy. Treatment of hypothyroidism with replacement doses of thyroid hormone is usually lifelong. Levothyroxine (LT4; synthetic thyroxine; Synthroid, and others) is the drug of choice.

PSAT307 Patient with Myxedema Coma and Subsequent Iatrogenic Thyrotoxicosis - Role of COVID-19 Pandemic

Abstract Introduction Myxedema coma is a rare presentation of severe hypothyroidism. The low incidence of this life-threatening disease may be attributed to easy availability of TSH testing and thyroid hormone replacement therapy. Well documented cases of thyroiditis and thyrotoxicosis due to SARS-CoV-2 are now available in medical literature. Additionally, COVID-19 pandemic has also caused higher rates of non-compliance with medications and appointments. This has resulted in higher rates of exacerbations of most chronic illnesses, including thyroid diseases. We present a case of myxedema coma and subsequent iatrogenic hyperthyroidism during the COVID-19 pandemic. Clinical Case 57-year-old male with paroxysmal atrial fibrillation, CHF, CKD stage IV, type 2 diabetes mellitus, hypertension, and post ablative hypothyroidism was found unresponsive at home. Initial vitals were temperature 95.1F, HR 52 beats per minute, RR 14 breaths per min, BP 90/62 mmHg, and glucose 68 mg/dL. There was no evidence of goiter, and he had generalized edema. Initial labs showed hyponatremia, elevated CPK, TSH 111uIU/mL (0.27-4.2 uIU/mL) and free T4 was &amp;lt;0.1 ng/dL (0.93-1.7 ng/dL). He was intubated, needed vasopressor support, and was treated with empiric antibiotics. He was diagnosed with myxedema coma which was treated with 200 mcg IV levothyroxine, and stress dose hydrocortisone. He was extubated on day 4 of hospital admission after which oral levothyroxine 275 mcg daily was initiated, and steroids were tapered off. Patient's pharmacy confirmed that Levothyroxine was not last filled more than eight months ago. Patient was hospitalized 3 weeks later for pneumonia and Levothyroxine dose was further increased to 300 mcg due to persistently elevated TSH levels. Three months later, patient was admitted for Atrial fibrillation in rapid ventricular response with difficult to control tachycardia. His TSH was 0.01 uIU/mL and thyroxine of 1.93 ng/dL despite not taking any medication for 2 weeks. He admitted to not following up with endocrinologist due to the surge in COVID-19 cases. Dose of levothyroxine was decreased to weight-based dose of 225 mcg, and patient discharged with instructions to repeat labs in 6 weeks and follow up with a clinical provider. Conclusion This case highlights the consequences of under and over replacement of thyroid hormone. Viral illnesses including SARS-CoV-2 can precipitate myxedema coma in patients with severe hypothyroidism. A high index of suspicion is needed to treat this disease in a timely manner. Providers must make allowances for the limitations in our system to function in a pandemic. Prescribing extra medication refills and offering virtual medicine appointments may help lower hospitalizations. Also, understanding the effect of non-thyroidal illness on thyroid function tests and knowing that TSH takes six weeks to normalize after starting/ adjusting thyroid hormone dose will avoid premature adjustment in hormone doses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Evaluating health outcomes in the treatment of hypothyroidism.

Clinical hypothyroidism is defined by the inadequate production of thyroid hormone from the thyroid gland to maintain normal organ system functions. For nearly all patients with clinical hypothyroidism, lifelong treatment with thyroid hormone replacement is required. The primary goal of treatment is to provide the appropriate daily dose of thyroid hormone to restore normal thyroid function for each individual patient. In current clinical practice, normalization of thyrotropin (TSH) level is the primary measure of effectiveness of treatment, however the use of a single biomarker to define adequate thyroid hormone replacement is being reevaluated. The assessment of clinical health outcomes and patient-reported outcomes (PROs), often within the context of intensity of treatment as defined by thyroid function tests (i.e., undertreatment, appropriate treatment, or overtreatment), may play a role in evaluating the effectiveness of treatment. The purpose of this narrative review is to summarize the prominent health outcomes literature in patients with treated hypothyroidism. To date, overall mortality, cardiovascular morbidity and mortality, bone health and cognitive function have been evaluated as endpoints in clinical outcomes studies in patients with treated hypothyroidism. More recent investigations have sought to establish the relationships between these end results and thyroid function during the treatment course. In addition to clinical event outcomes, patient-reported quality of life (QoL) has also been considered in the assessment of adequacy of hypothyroidism treatment. From a health care quality perspective, treatment of hypothyroidism should be evaluated not just on its effectiveness for the individual patients but also to the extent to which patients of different sociodemographic groups are treated equally. Ultimately, more research is needed to explore differences in health outcomes between different sociodemographic groups with hypothyroidism. Future prospective studies of treated hypothyroidism that integrate biochemical testing, PROs, and end result clinical outcomes could provide a more complete picture into the effectiveness of treatment of hypothyroidism.

On the Fundamental Efficacy of Thyroid-Hormone Therapy in Eating Disorders: Review of Mechanisms and Case Study

Context: Calorie restriction reduces circulating triiodothyronine (T3) – the most active thyroid hormone – inducing hypothyroidism, constipation, and reduced appetite that inhibit eating, acting to sustain and sometimes precipitate eating disorders. Thyroid-hormone treatment can be effective but is rarely employed. Case description: A 12-year-old girl experienced chronic nausea and constipation after antibiotics for strep throat, resulting in restricted eating. Energy decreased for 2 months as anxiety and depression increased, culminating in withdrawal and school refusal. Blood tests were normal except for below-range free T3. She began a trial of incremental, 1-μg dose increases of T3 every 3 days using sustained-release capsules added to her established triiodothyronine–levothyroxine (T3–T4) protocol for hypothyroidism. Her energy and mood began improving after 10 days and depression resolved after 7 weeks. An 18-day stay in a hospital eating-disorders unit helped her regain some weight and strength. To address nausea and anxiety, the extended medical team then tried two antidepressants and cyproheptadine – each caused increased nausea and reduced eating – and a 5-day prednisone burst for possible neuroinflammation; all were ineffective and discontinued. After 14 weeks without improvement, we resumed adjusting thyroid-hormone dose. Anxiety, energy, food intake, and weight improved for 5 months. She began attending a new school, developed new friendships, and started menses. The major illness lasted 21 months. T3 intake increased from 5 to 27 μg, T4 from 50 to 110 μg, weight from 36.4 to 52.7 kg, and height from 1.63 to 1.71 m. Conclusions: Thyroid hormones should be studied further as fundamentally effective treatment for eating disorders. Keywords: Eating disorder; Low-triiodothyronine syndrome; Hypothyroidism

Derivation of thyroid progenitors from human induced pluripotent stem cells

Abstract Objective Despite the availability of synthetic thyroid hormone for therapeutic use, a significant number of patients with hypothyroidism do not feel well on replacement doses of thyroid hormones suggesting that better-individualized therapy is needed. For this reason, hypothyroidism resulting from congenital lack of functional thyrocytes, surgical tissue removal, or gland ablation, represents a particularly attractive endocrine disease target that may be conceivably cured by transplantation of long-lived functional thyroid progenitors or mature follicular epithelial cells. Methods To generate thyroid follicular progenitors from human induced pluripotent stem cells (hiPSCs), we sought to develop a directed differentiation approach by activating or inhibiting endogenous developmental signaling pathways previously identified in the mouse. To facilitate tracking and purification of candidate human thyroid progenitors, we engineered a hiPSC-line carrying a tdTomato reporter targeted to the PAX8 locus and a GFP reporter targeted to the NKX2-1 locus. Results We adapted our published in vitro differentiation protocol previously used to differentiate mouse PSCs into thyroid progenitors and observed tdTomato/GFP co-expressing cells first emerging from our hiPSC line by day 12 of culture and persisting for at least 2 months of further culture in thyroid maturation media, supplemented with TSH. Thus, we profiled all cells deriving from hiPSCs by single-cell RNA sequencing &amp;gt;6,000 cells captured on days 12 and 29 of in vitro differentiation. At day 12, tdTomato/GFP co-expression was observed in 12% of all cells and these cells appeared to be early thyroid follicular progenitors as they uniquely co-expressed the tetrad of thyroid lineage selective transcription factors, NKX2-1, PAX8, FOXE1, and HHEX. By day 29 tdTomato+/GFP+ cells represented 69% of all cells and had upregulated TG, TSHR, NIS and TPO expression in addition to the previously described four thyroid lineage markers, suggesting time-dependent differentiation and maturation of thyroid follicular epithelial cells. Conclusion Thus, we have employed a novel hiPSC line to optimize a protocol able to generate human thyroid progenitors and mature follicular epithelial cells, representing a purifiable source of human thyroid lineage cells whose functional and thyroid reconstituting potential can be tested in vivo in animal models of hypothyroidism.

Initial treatment of myxedema coma using oral levothyroxine: a case report from Tanzania.

SummaryMyxedema coma is a severe complication of hypothyroidism, commonly affecting women over 60 years of age, causing slow, progressive multi-organ dysfunction, and mental deterioration. Due to improved diagnostics and treatment of hypothyroidism, myxedema coma has become uncommon. However, it is hardly reported in resource-limited settings. We present an elderly female with a history of total thyroidectomy due to multi-nodular goiter. She presented with features of heart failure, excessive weight gain, and cold sensation. Although the patient was on levothyroxine replacement therapy, her laboratory tests were suggestive of overt primary hypothyroidism. During the course of her hospitalization, she developed subcutaneous bleeding with frank hematuria. This led to an altered mental state and hypotension that were suggestive of myxedema coma. Stroke and pulmonary embolism were ruled out as potential differential diagnoses of her current state. She was treated with a high dose of oral levothyroxine followed by 150 μg of oral levothyroxine daily, which resulted in a favorable outcome despite being a fatal emergency. She was also treated with intravenous hydrocortisone and furosemide. Oral thyroid hormone replacement may be an effective option in those resource-limited settings where intravenous thyroid hormone replacement is not available. However, early diagnosis and treatment with an adequate dose of thyroid hormones are crucial to achieve a favorable outcome.Learning pointsMyxedema coma is an uncommon complication of hypothyroidism with a fatal outcome.The diagnosis of myxedema coma is based on clinical suspicion, especially in patients with hypothyroidism and in the presence of precipitating factors. Although diagnostic and scoring criteria based on clinical, laboratory, and imaging features have been proposed, no consensus has been reached.This article shows an alternative treatment option for myxedema coma using oral levothyroxine, which led to a favorable outcome.

Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease.

Thyroid hormones (TH) have a cardinal role in the development of the central nervous system during embryogenesis and early infancy. However, the TH-responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems. Cognitive decline, dysphoria, and depression are common manifestations of overt hypothyroidism while hyperthyroidism can cause agitation, acute psychosis, and apathy, especially in older people. Whereas levothyroxine treatment can reverse dementia in the setting of hypothyroidism, the effect of levothyroxine on depressive symptoms in subjects with subclinical hypothyroidism is controversial. The use of supraphysiologic doses of TH to treat depression refractory to antidepressant remains a viable therapeutic tool with the caveat that excessive doses of thyroid hormone to treat depression may have potentially damaging effects on other organ systems. The present communication describes the pathophysiology of neuropsychiatric manifestations of thyroid disease, including changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier dysfunction, increased risk of cerebrovascular disease, and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease. Elucidating the molecular mechanisms of TH effect on cerebral tissue will help identify novel therapeutic targets for managing people with neuropsychiatric disorders.

Клініко-лабораторні особливості застосування замісної тиреоїдної терапії в пацієнтів похилого віку

Клінічний і субклінічний гіпотиреоз — один з найпоширеніших станів у практиці лікаря-ендокринолога після цукрового діабету 2-го типу. Частка пацієнтів, у яких латентний (субклінічний) гіпотиреоз переходить у клінічний, щороку становить до 5 %. Попри відносно виражену симптоматику діагностика гіпотиреозу, особливо в людей похилого віку, становить певні труднощі. Це обумовлено переважанням у цій категорії хворих симптомів із боку певної системи. Розпочинати терапію в таких людей слід із мінімальних доз препаратів тиреоїдних гормонів, а титрування дози необхідно проводити поступово й повільно, з постійним контролем як тиреоїдного гормонального статусу, так і кардіальних показників.

Patterns of clinical management of hypothyroidism in adults: An electronic survey of physicians from the Middle East and Africa

Background: Hypothyroidism is a common endocrine disorder that is managed by a wide range of physicians. There are no data on the pattern of clinical management of hypothyroidism in the Middle East and Africa (MEA) region. Objectives: We sought to document current practices in the management of primary hypothyroidism in the MEA region and compare these with international recommendations and practices elsewhere. Materials and Methods: A convenience sample of physicians practicing in the MEA in relevant disciplines were invited to take a web-based survey consisting of previously validated multiple-choice questions dealing with investigation and treatment of an index case of overt primary hypothyroidism in general and in three special situations. Results: Out of complete 397 responses, 368 were eligible for inclusion in the analysis. The majority were endocrinologists and internal medicine specialists; 82.2% of them have been in clinical practice for 10 years or more. Overt hypothyroidism would be treated using L-T4 alone by 97.2% of respondents; 1.7% would use a combination of L-T4 and liothyronine (L-T3) therapy. The rate of replacement would be gradual (66.5%), an empiric dose, adjusted to achieve target levels (14.7%); or a calculated full replacement dose (18.5%). A target thyroid-stimulating hormone (TSH) of 2.0–2.9 mU/L was favored in the index case of overt hypothyroidism (by 34.4%) followed by a target of 3.0–3.9 mU/L (by 26.0%) of respondents. However, a target of 4.0–4.9 mU/L was the most commonly selected TSH target for an octogenarian (by 33.5% of respondents). Persistent hypothyroid symptoms despite achieving a target TSH would prompt testing for other causes by 86.9% of respondents, a change to L-T4 plus L-T3 therapy by 5.8%, and an increase in the thyroid hormone dose by 4.6%. Evaluation of persistent symptoms would include measurements of complete blood count (82.4%), complete metabolic panel (68.7%), morning cortisol (65.3%), Vitamin B12 levels (54.5%), and serum T3 levels (27.9%). Subclinical disease with a TSH 7.8 mU/L would be treated without further justification by 9.0% of respondents, or in the presence of positive thyroid peroxidase antibodies (65.3%), hypothyroid symptoms (65.0%), high low-density lipoprotein (51.7%), or a goiter (36.7%). The TSH target for a newly pregnant patient was 2.0–2.4 mU/L for 28.5% of respondents, with 15.8% preferring a TSH target of 1.5–1.9 mU/L. Thyroid hormone levels would be checked every 4 weeks during pregnancy by 62.9% and every 8 weeks by an additional 17.6%. A hypothyroid patient with a TSH of 0.5 mU/L who becomes pregnant would receive an immediate L-T4 dose increase by only 28.5% of respondents. Conclusions: The survey revealed that (1) nearly exclusive preference for L-T4 alone for therapy, (2) use of age-specific TSH targets for replacement therapy, (3) a low threshold for treating mild thyroid failure, (4) complacent and variable attention to TSH targets in the pregnant and prepregnant woman, and (5) a highly variable approach to both the rate and means of restoring euthyroid status for overt disease. Both alignments with and divergence from guidelines were detected. The results should help in directing focused educational activities in the region, providing a baseline for future monitoring of practices.

Thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones in conscious dogs

This study was conducted to clarify the relationship between thyroid function and gastrointestinal motility. We established an experimental configuration in which the feedback of thyroid function was completely removed using conscious dogs. With hypothyroidism, time of phase I of interdigestive migrating contractions (IMC) was longer, time of phase II and phase III was significantly shortened, and both the continuous time of strong tetanic contraction at antrum and 10-h frequency of phase III counted from the first IMC after meal significantly decreased. Whereas, hyperthyroidism caused the opposite events to those with hypothyroidism. Furthermore, We found giant migrating contractions (GMC) occurred from the upper gastrointestinal tract when we administrated high dose of thyroid hormone. One GMC occurred from anal sides propagated to cardiac, and this propagation was similar to the emesis-like interdigestive motor activity, the other GMC occurred from oral sides propagated to anal sides and this was similar to the diarrhea-like interdigestive motor activity. We examined the relationship between thyroid function and gastrointestinal hormones including of ghrelin, GLP-1, and cholecystokinin (CCK). However, we could not find significant differences under different thyroid hormone status. This is the first report that thyroid hormone activated upper gastrointestinal motility without mediating gastrointestinal hormones.

The Growth Stimulatory Effects of Thyrotropin and Thyroid Hormones on Thyroid Cancer Depend on Expression of Thyrotropin Receptor and Integrins

Abstract Background: The long-term management of metastatic thyroid cancer (TC) consists of thyrotropin (TSH) suppression with supraphysiologic doses of thyroid hormones (TH) via a negative feedback loop. The goal of TSH suppression is to prevent TSH stimulation of the TSH receptor (TSHR), as it has been shown to promote proliferation of cancer cells. However, TH (T3 and T4) have also been shown to stimulate cancer cell proliferation via αvβ3 integrin signaling. Since both TSH and TH have mitogenic potential, we aimed to investigate which one is a more potent growth stimulus-TSH or TH by analyzing its growth stimulatory effects in TC models. Methods: We analyzed the mRNA expression of TSHR and ITGAV (αv), ITGB3 (β3) integrins in 496 human TC tissue samples, including 65 paired samples of normal tissue (NT) and the corresponding tumor included in The Cancer Genome Atlas (TCGA). We used 13 TC cell lines and analyzed the mRNA expression of 24 genes (4 thyroid-specific genes, 2 TH receptor genes, and 18 integrin genes) with an emphasis on the expression of cell surface receptors αv, β3 integrins, and TSHR. The protein expression of αv, β3, and TSHR was analyzed by immunoblotting. To test the effects of TH and TSH on cell proliferation and expression of αv, β3, and TSHR, cells were treated with varying concentrations of TSH (0.01, 0.1, 1, 10 mIU/mL), T3 (0.1, 1, 10 100 nM) and T4 (1, 10, 100, 1000 nM) for 72 h. Results: Analysis of the RNA seq data from TCGA revealed a significantly higher expression of TSHR in NT compared with TC (log fold change 0.59, p&amp;lt;0.001), lower expression of αv integrin in NT compared with TC (log fold change -0.3, p=0.001), and comparable expression of β3 integrin (log fold change 0.20, p=0.3). Based on the mRNA expression data of 13 TC cell lines, we selected 6 cell lines (FTC133, TPC1, XTC1, OCUT2, C643, THJ16T) characterized by variable αv, β3, and TSHR expression. The TPC1 and OCUT2 cells with high to moderate αVβ3 expression responded to T4 (1000nM; p&amp;lt;0.001) and T3 treatment (100nM; p&amp;lt;0.001) respectively, with increased proliferation, while the cell lines characterized by low to no β3 and/or low αV expression (FTC133, XTC1, C643, and THJ16T) did not change their growth rate in response to TH. The C643 and XTC1 cells characterized by a preserved low-to-moderate TSHR expression responded to TSH treatment (10mIU/mL) with increased proliferation (p&amp;lt;0.05), while the growth curve of cell lines with very low to no TSHR expression (FTC133, TPC1, OCUT1, THJ16T) was not affected. Analysis of the effects of TH and TSH on the mRNA expression of αV, β3, and TSHR was observed to be cell-line specific. Conclusion: The growth stimulatory effects of TSH and TH on TC cells depend on its concentration and expression of TSHR and αVβ3, respectively. Since TC is characterized by relatively lower TSHR and higher αV integrin expression than NT, treatment with supraphysiologic doses of TH in patients with metastatic TC needs to be individualized.

Understanding Osteoporosis Screening Practices in Men: A Nationwide Physician Survey

To understand osteoporosis screening practices, particularly in men, by a diverse cohort of physicians, including primary care physicians, endocrinologists, and geriatricians. We surveyed randomly selected members of the American Academy of Family Practice, Endocrine Society, and American Geriatrics Society. Respondents were asked to rate how often they would screen for osteoporosis in four different clinical scenarios by ordering a bone density scan. Multivariable logistic regression analyses were conducted to determine factors associated with offering osteoporosis screening in men in each clinical scenario. Physicians were also asked to note factors that would lead to osteoporosis screening in men. Response rate was 63% (359/566). While 90% respondents reported that they would always or frequently screen for osteoporosis in a 65-year-old post-menopausal woman, only 22% reported they would screen a 74-year-old man with no significant past medical history. Endocrinologists were more likely to screen a 74-year-old man compared to primary care physicians (odds ratio, 2.32; 95% confidence interval, 1.10 to 4.88). In addition to chronic steroid use (94%), history of nontraumatic fractures (88%), and androgen-deprivation therapy for prostate cancer (82%), more than half the physicians reported suppressive doses of thyroid hormone (64%) and history of falls (52%) as factors leading to screening for osteoporosis in men. Our survey results highlight heterogeneity in osteoporosis screening in men, with underscreening in some scenarios compared to women, and identify factors that lead to screening in men. These findings can help design interventions to improve osteoporosis screening in men.