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Thyroid Gene Mutations in Pregnant and Breastfeeding Women Diagnosed With Transient Congenital Hypothyroidism: Implications for the Offspring's Health.
Opazo, MC, Rivera, JC, Gonzalez, PA, Bueno, SM, Kalergis, AM, Riedel, CA
Frontiers in endocrinology. 2021;:679002
Abstract
Fetus and infants require appropriate thyroid hormone levels and iodine during pregnancy and lactation. Nature endorses the mother to supply thyroid hormones to the fetus and iodine to the lactating infant. Genetic variations on thyroid proteins that cause dyshormonogenic congenital hypothyroidism could in pregnant and breastfeeding women impair the delivery of thyroid hormones and iodine to the offspring. The review discusses maternal genetic variations in thyroid proteins that, in the context of pregnancy and/or breastfeeding, could trigger thyroid hormone deficiency or iodide transport defect that will affect the proper development of the offspring.
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Slipped capital femoral epiphysis with hypopituitarism in adults: A case report and literature review.
Niu, Z, Tang, J, Shen, X, Xu, S, Zhou, Z, Liu, T, Zuo, J
Medicine. 2021;(51):e28256
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RATIONALE Slipped capital femoral epiphysis (SCFE) is a common disease in pediatric orthopedics. Most research on SCFE has focused on high-risk groups or the whole population, and studies focusing on adult SCFE patients are rare. In the present study, we report the case of an adult patient with SCFE. PATIENT CONCERN A 37-year-old man presented to our clinic with persistent pain that was poorly localized to both hips, groin regions, and thighs for more than 1 year. DIAGNOSES A bilateral hip X-ray examination was performed, and the femoral epiphyses were found to be unfused on both sides. Low levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), triiodothyronine (T3), thyroxine (T4), follicle-stimulating hormone, luteinizing hormone, estradiol, and testosterone, and high levels of thyroid-stimulating hormone, prolactin, and cortisol. INTERVENTIONS Hormone-substitution therapies (levothyroxine sodium to treat hypothyroidism and testosterone enanthate to treat hypogonadism) were prescribed. Total hip arthroplasty was performed to treat femoral epiphysis slippage. OUTCOMES After 6 months of postoperative follow-up, the patient's gait improved significantly, and bilateral hip pain was relieved. LESSONS When treating adults with SCFE, clinicians must be alert to endocrine disorders. Comprehensive imaging evaluation is crucial for the accurate diagnosis and selection of an appropriate treatment.
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The Clinical Spectrum of Resistance to Thyroid Hormone Alpha in Children and Adults.
Erbaş, İM, Demir, K
Journal of clinical research in pediatric endocrinology. 2021;(1):1-14
Abstract
Resistance to thyroid hormone alpha occurs due to pathogenic, heterozygous variants in THRA. The entity was first described in 2012 and to date only a small number of patients with varying severity have been reported. In this review, we summarize and interpret the heterogeneous clinical and laboratory features of all published cases, including ours. Many symptoms and findings are similar to those seen in primary hypothyroidism. However, thyroid-stimulating hormone levels are normal. Free triiodothyronine (T3) levels are in the upper half of normal range or frankly high and free thyroxine (T4) levels are low or in the lower half of normal range. Alterations in free T3 and free T4 may not be remarkable, particularly in adults, possibly contributing to underdiagnosis. In such patients, low reverse T3 levels, normo- or macrocytic anemia or, particularly in children, mildly elevated creatine kinase levels would warrant THRA sequencing. Treatment with L-thyroxine results in improvement of some clinical findings.
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The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine.
Antonelli, A, Elia, G, Ragusa, F, Paparo, SR, Cavallini, G, Benvenga, S, Ferrari, SM, Fallahi, P
Frontiers in endocrinology. 2021;:633587
Abstract
Approximately, 5% of the population is affected by hypothyroidism, mainly women and persons aged more than 60 years. After the diagnosis of hypothyroidism the usual therapy is tablet levothyroxine (L-T4), with a monitoring of the thyroid-stimulating hormone (TSH) level in primary hypothyroidism every 6-8 weeks and L-T4 is adjusted as necessary to reach an euthyroid state. Once TSH is stabilized in the normal range, it is recommended to conduct annual testing in the treated subjects to warrant suitable replacement. More recently advances regarding L-T4 treatment are the introduction of new oral formulations: the liquid solution, and soft gel capsule. The soft gel capsule permits a quick dissolution in the acid gastric pH. The liquid preparation does not require an acid gastric environment. Many pharmacokinetic studies demonstrated a more rapid absorption for the liquid L-T4, or capsule, than with tablet. Many studies have shown that the liquid, or capsule, formulations can overcome the interaction with foods, drugs or malabsorptive conditions, that are able to impair the tablet L-T4 absorption. Lately studies have suggested that liquid L-T4 can permit to maintain more efficiently normal TSH levels in hypothyroid patients in the long-term follow-up, than tablet L-T4, both in patients with malabsorptive states, and in those without malabsorption. Further large, prospective, longitudinal studies are needed to evaluate the stability of TSH, in hypothyroid patients treated with different L-T4 formulations.
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Individualized Therapy for Hypothyroidism: Is T4 Enough for Everyone?
Ettleson, MD, Bianco, AC
The Journal of clinical endocrinology and metabolism. 2020;(9):e3090-104
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CONTEXT It is well recognized that some hypothyroid patients on levothyroxine (LT4) remain symptomatic, but why patients are susceptible to this condition, why symptoms persist, and what is the role of combination therapy with LT4 and liothyronine (LT3), are questions that remain unclear. Here we explore evidence of abnormal thyroid hormone (TH) metabolism in LT4-treated patients, and offer a rationale for why some patients perceive LT4 therapy as a failure. EVIDENCE ACQUISITION This review is based on a collection of primary and review literature gathered from a PubMed search of "hypothyroidism," "levothyroxine," "liothyronine," and "desiccated thyroid extract," among other keywords. PubMed searches were supplemented by Google Scholar and the authors' prior knowledge of the subject. EVIDENCE SYNTHESIS In most LT4-treated patients, normalization of serum thyrotropin levels results in decreased serum T3/T4 ratio, with relatively lower serum T3 levels; in at least 15% of the cases, serum T3 levels are below normal. These changes can lead to a reduction in TH action, which would explain the slower rate of metabolism and elevated serum cholesterol levels. A small percentage of patients might also experience persistent symptoms of hypothyroidism, with impaired cognition and tiredness. We propose that such patients carry a key clinical factor, for example, specific genetic and/or immunologic makeup, that is well compensated while the thyroid function is normal but might become apparent when compounded with relatively lower serum T3 levels. CONCLUSIONS After excluding other explanations, physicians should openly discuss and consider therapy with LT4 and LT3 with those hypothyroid patients who have persistent symptoms or metabolic abnormalities despite normalization of serum thyrotropin level. New clinical trials focused on symptomatic patients, genetic makeup, and comorbidities, with the statistical power to identify differences between monotherapy and combination therapy, are needed.
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Effect of levothyroxine on the progression of carotid intima-media thickness in subclinical hypothyroidism patients: a meta-analysis.
Zhao, T, Chen, B, Zhou, Y, Wang, X, Zhang, Y, Wang, H, Shan, Z
BMJ open. 2017;(10):e016053
Abstract
BACKGROUND Subclinical hypothyroidism (SCH) has been associated with increased carotid intima-media thickness (C-IMT) in recent studies, but the effects of levothyroxine (L-T4) therapy on C-IMT in SCH patients are still controversial. AIM: To evaluate the effect of L-T4 therapy on endothelial function as determined by C-IMT in patients with SCH. METHODS BeforeJuly 2016, we searched the PubMed, Embase, Cochrane Library and Google Scholar databases, selecting published randomised controlled trials (RCTs) and self-controlled trials for the meta-analysis. RESULTS Three RCTs with 117 patients were considered appropriate for the meta-analysis. The results of the meta-analysis indicated that L-T4 significantly decreased the development of C-IMT (weighted mean difference (WMD) -0.05 mm, 95% CI -0.08 to -0.01 mm; p=0.025). We also analysed nine studies (self-controlled trials) with 247 patients and extracted the IMT of SCH patients before and after L-T4 treatment. After L-T4 therapy, the pooled estimate of the WMD of decreased C-IMT was -0.04 mm (95% CI -0.07 to -0.02 mm; p=0.05). Subgroup analysis showed that L-T4 therapy was associated with a decrease in C-IMT among patients of mixed genders (WMD -0.03 mm, 95% CI -0.06 to -0.01 mm; p=0.145). L-T4 therapy was associated with a decrease in C-IMT among female patients (WMD -0.07 mm, 95% CI -0.14 to -0.01; p=0.186). Longer treatment (>6 months) also resulted in a significant decrease in C-IMT (WMD -0.05 mm, 95% CI -0.08 to -0.02; p=0.335). CONCLUSION This meta-analysis indicates that L-T4 treatment of SCH patients can reduce C-IMT, possibly as a result of the reduction of total cholesterol, triglyceride, low density lipoprotein, systolic blood pressure, diastolic blood pressure, lipoprotein(a), and flow-mediated dilatation. Decreased C-IMT was observed in SCH patients after long-term (>6 months) L-T4 treatment. RCTs with larger samples are needed to verify these observations.
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Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis.
Winther, KH, Wichman, JE, Bonnema, SJ, Hegedüs, L
Endocrine. 2017;(2):376-385
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By a systematic review and meta-analysis to investigate clinically relevant effects of selenium supplementation in patients with chronic autoimmune thyroiditis. Controlled trials in adults (≥18 years) with autoimmune thyroiditis, comparing selenium with or without levothyroxine substitution, versus placebo and/or levothyroxine substitution, were eligible for inclusion. Identified outcomes were serum thyrotropin (thyroid stimulating hormone) levels in LT4-untreated patients, thyroid ultrasound and health-related quality of life. Eleven publications, covering nine controlled trials, were included in the systematic review. Random effects model meta-analyses were performed in weighted mean difference for thyroid stimulating hormone, ultrasound and health-related quality of life. Quality of evidence was assessed per outcome, using GRADE. Meta-analyses showed no change in thyroid stimulating hormone, or improvements in health-related quality of life or thyroid echogenicity (ultrasound), between levothyroxine substitution-untreated patients assigned to selenium supplementation or placebo. Three trials found some improvement in wellbeing in patients receiving levothyroxine substitution, but could not be synthesized in a meta-analysis. The quality of evidence ranged from very low to low for thyroid stimulating hormone as well as ultrasound outcomes, and low to moderate for health-related quality of life, and was generally downgraded due to small sample sizes. We found no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound, in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients. Future well-powered RCTs, evaluating e.g. disease progression or health-related quality of life, are warranted before determining the relevance of selenium supplementation in autoimmune thyroiditis.
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Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis.
Maraka, S, Ospina, NM, O'Keeffe, DT, Espinosa De Ycaza, AE, Gionfriddo, MR, Erwin, PJ, Coddington, CC, Stan, MN, Murad, MH, Montori, VM
Thyroid : official journal of the American Thyroid Association. 2016;(4):580-90
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BACKGROUND The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the impact of SCH during pregnancy on maternal and neonatal outcomes, and (ii) the effect of levothyroxine replacement therapy in these patients. METHODS Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015. Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included. Reviewers extracted data and assessed methodological quality in duplicate. Eighteen cohort studies at low-to-moderate risk of bias were included. Compared with euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (relative risk [RR] 2.01 [confidence interval (CI) 1.66-2.44]), placental abruption (RR 2.14 [CI 1.23-3.70]), premature rupture of membranes (RR 1.43 [CI 1.04-1.95]), and neonatal death (RR 2.58 [CI 1.41-4.73]). One study at high risk of bias compared pregnant women with SCH who received levothyroxine to those who did not and found no significant decrease in the rate of pregnancy loss, preterm delivery, gestational hypertension, low birth weight, or low Apgar score. CONCLUSIONS SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes. The value of levothyroxine therapy in preventing these adverse outcomes remains uncertain.
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Psychiatric and cognitive manifestations of hypothyroidism.
Samuels, MH
Current opinion in endocrinology, diabetes, and obesity. 2014;(5):377-83
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PURPOSE OF REVIEW Overt hypothyroidism has major effects on neuropsychiatric function, but patients with mild hypothyroidism may attribute unrelated neuropsychiatric symptoms to their thyroid condition. This review will summarize data on neuropsychiatric effects of hypothyroidism, and provide guidelines regarding the relationship between hypothyroidism and neuropsychiatric issues, and treatment indications. RECENT FINDINGS Clinical investigations and functional imaging studies confirm that overt hypothyroidism is associated with affective and cognitive decrements, largely reversible with treatment. In contrast, subclinical hypothyroidism is not associated with major neuropsychiatric deficits, although studies utilizing sensitive measures show small deficits in memory and executive function. Neuropsychiatric complaints are more common when patients are aware of their thyroid disease, regardless of their thyroid function at the time of testing. SUMMARY Neuropsychiatric dysfunction is common in overt hypothyroidism and will improve (perhaps not completely resolve) with therapy. Deficits related to thyroid dysfunction are usually mild in subclinical hypothyroidism, and realistic expectations need to be set regarding symptom reversibility with treatment. Patients with mild hypothyroidism and significant distress related to neuropsychiatric symptoms, most likely, have independent diagnoses that should be evaluated separately.
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Therapeutic approach of fetal thyroid disorders.
Polak, M, Van Vliet, G
Hormone research in paediatrics. 2010;(1):1-5
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Recent advances in fetal imaging techniques and fetal hormonology allow the identification in the fetus of thyroid function disorders that can potentially be treated in utero by giving drugs to the mother. In women with Graves' disease (when fetal hyperthyroidism is present), it can generally be treated in a noninvasive way by optimizing treatment of the mother. For goitrous nonimmune fetal hypothyroidism leading to hydramnios, intra-amniotic injections of thyroxine have been reported to decrease the size of the fetal thyroid. Experience with such a procedure is limited and the risk of provoking premature labor or infections should be carefully evaluated. Thus, follow-up of the efficacy and the possible long-term undesired consequences of medical interventions administered to the fetus are of great importance. Such interventions should only be performed by specialized teams with extensive experience in perinatal care.