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Nature Reviews. Endocrinology Oct 2017Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to... (Review)
Review
Central hypothyroidism is a rare and heterogeneous disorder that is characterized by a defect in thyroid hormone secretion in an otherwise normal thyroid gland due to insufficient stimulation by TSH. The disease results from the abnormal function of the pituitary gland, the hypothalamus, or both. Moreover, central hypothyroidism can be isolated or combined with other pituitary hormone deficiencies, which are mostly acquired and are rarely congenital. The clinical manifestations of central hypothyroidism are usually milder than those observed in primary hypothyroidism. Obtaining a positive diagnosis for central hypothyroidism can be difficult from both a clinical and a biochemical perspective. The diagnosis of central hypothyroidism is based on low circulating levels of free T in the presence of low to normal TSH concentrations. The correct diagnosis of both acquired (also termed sporadic) and congenital (also termed genetic) central hypothyroidism can be hindered by methodological interference in free T or TSH measurements; routine utilization of total T or T measurements; concurrent systemic illness that is characterized by low levels of free T and normal TSH concentrations; the use of the sole TSH-reflex strategy, which is the measurement of the sole level of TSH, without free T, if levels of TSH are in the normal range; and the diagnosis of congenital hypothyroidism based on TSH analysis without the concomitant measurement of serum levels of T. In this Review, we discuss current knowledge of the causes of central hypothyroidism, emphasizing possible pitfalls in the diagnosis and treatment of this disorder.
Topics: Female; Humans; Hypothalamus; Hypothyroidism; Male; Neglected Diseases; Pituitary Gland; Rare Diseases; Risk Assessment; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Thyroxine; Treatment Outcome
PubMed: 28549061
DOI: 10.1038/nrendo.2017.47 -
Journal of the American Academy of... May 2020Hypothyroidism has been associated with quetiapine, but the underlying mechanism is not well understood and has been presumed to result from thyroid gland dysfunction...
Hypothyroidism has been associated with quetiapine, but the underlying mechanism is not well understood and has been presumed to result from thyroid gland dysfunction (primary hypothyroidism). We present a case of symptomatic quetiapine-induced hypothyroidism due to hypothalamic/pituitary gland dysfunction (central [secondary] hypothyroidism).
Topics: Humans; Hypothyroidism; Quetiapine Fumarate
PubMed: 32036034
DOI: 10.1016/j.jaac.2020.01.018 -
The Journal of Clinical Endocrinology... Nov 2015The association between subclinical hypothyroidism (sHT) and cognitive impairment or risk of dementia is not well-defined, especially in the elderly, where the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between subclinical hypothyroidism (sHT) and cognitive impairment or risk of dementia is not well-defined, especially in the elderly, where the assessment of central nervous system function is challenging. The aim of this systematic review and meta-analysis was to evaluate the possible effect of sHT on cognitive decline and the risk of dementia.
METHODS
Cognitive function was the primary outcome, evaluated as composite endpoint of incidence or prevalence of dementia or difference of Mini Mental State Examination, Wechsler Adult Intelligence Scale, and Wechsler Memory Scale-Revised scores.
RESULTS
Thirteen studies were included in the meta-analysis. A significant risk of cognitive alteration was observed only in sHT individuals younger than age 75 years: composite endpoint odds ratio (OR) 1.56 (95% confidence interval [CI] 1.07-2.27, P = .02, I(2) = 82.5%), risk of dementia OR 1.81 (95% CI 1.43-2.28, P < .01, I(2) = 35%). Mean serum thyroid-stimulating hormone (TSH) levels and the OR of composite endpoint were positively correlated. No significant effect of sHT was found when considering all the studies as a whole: composite endpoint OR 1.26 (95% CI 0.96-1.66, P = .09, I(2) = 87.2%), risk of dementia OR 1.42 (95% CI, 0.97-2.07, P = .07, I(2) = 66.8%), Mini Mental State Examination mean difference -0.059 (95% CI -0.464 to 0.346 P = .78, I(2) = 51.8%).
CONCLUSIONS
This meta-analysis demonstrates a relationship between sHT and cognitive impairment only in individuals younger than 75 years of age and those with higher TSH concentrations. No correlation was found while considering all the studies as a whole. The lack of utilization of age-related serum TSH reference ranges and consequent potential misdiagnosis of sHT in older people may account for this.
Topics: Adult; Aged; Aged, 80 and over; Cognition Disorders; Female; Humans; Hypothyroidism; Male; Middle Aged; Neuropsychological Tests; Thyroid Function Tests; Treatment Outcome
PubMed: 26305618
DOI: 10.1210/jc.2015-2046 -
Frontiers in Endocrinology 2023Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.
BACKGROUND
Although observational studies have found an association between hypothyroidism and alopecia areata, the causality of this relationship remains unclear.
OBJECTIVES
This study aimed to investigate the genetic variants associated with hypothyroidism and their potential impact on the risk of developing alopecia areata.
METHODS
genome-wide association study summary statistics for hypothyroidism (30,155 cases and 379,986 controls) and alopecia areata (289 cases and 211,139 controls) were obtained from the IEU OpenGwas project. The inverse variance-weighted method was used as the primary analysis method to evaluate the causality between hypothyroidism and alopecia areata, supplemented by the weighted median, MR-Egger, simple mode and weighted mode. Furthermore, the function of causal SNPs was evaluated by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction networks.
RESULT
Utilizing two-sample Mendelian randomization analysis, we found that the single-nucleotide polymorphisms (SNPs) of hypothyroidism (OR = 1.40, 95% CI: 1.12-1.75, = 3.03×10) significantly increased the risk of alopecia areata ( 289 cases and 211,139 controls ). KEGG pathway analysis showed that the candidate genes were mainly enriched in virion-herpesvirus, Th1 and Th2 cell differentiation, Th17 cell differentiation, T-cell receptor signaling pathway, PD-L1/PD-1 checkpoint pathway in cancer and Toll-like receptor signaling pathway. Protein-protein interaction networks results showed that CTLA4, STAT4, IL2RA, TYK2, IRF7, SH2B3, BACH2, TLR3, NOD2, and FLT3.
CONCLUSION
This study provided compelling genetic evidence supporting a causative association between hypothyroidism and alopecia areata, which could potentially inform the development of more efficacious treatment strategies for patients afflicted by alopecia areata.
Topics: Humans; Alopecia Areata; Genome-Wide Association Study; Mendelian Randomization Analysis; Hypothyroidism
PubMed: 38292771
DOI: 10.3389/fendo.2023.1309620 -
Auris, Nasus, Larynx Feb 2022Hypothyroidism is a common endocrine disorder affecting various systems of the body. Only a few studies have focused on the effect of primary hypothyroidism on voice... (Observational Study)
Observational Study
OBJECTIVE
Hypothyroidism is a common endocrine disorder affecting various systems of the body. Only a few studies have focused on the effect of primary hypothyroidism on voice with objective parameters, and none of them compared the effect of subclinical and overt hypothyroidism on voice. The aim of the present study is to evaluate and compare the acoustic and perceptual parameters of voice in patients newly diagnosed with subclinical and overt hypothyroidism.
METHODS
The study included 26 subclinical hypothyroidism, 26 overt hypothyroidism patients and 30 euthyroid control participants. Perceptual evaluation of voice with GRBAS (grade, roughness, breathiness, asthenia, strain) scale, voice handicap index (VHI)-10, and acoustic voice analysis by using Multi-Dimensional Voice Program were performed for all the participants.
RESULTS
The voice parameters which showed a statistically significant difference between the groups were frequency parameters (Fo; p= 0.003, Fhi; p=0.010, Flo; p= 0.002) and VHI-10 (p= 0.047). A statistically significant decrease in frequency parameters and a statistically significant increase in VHI-10 were found in overt hypothyroidism group comparing with control group (Fo; p= 0.002, Fhi; p=0.009, Flo; p= 0.001 and VHI-10; p= 0.046). Voice parameters in subclinical hypothyroidism group did not show a statistically significant difference comparing with both control and overt hypothyroidism groups.
CONCLUSION
In the present study, overt hypothyroidism is found to affect frequency parameters and patients' own subjective assessment of voice. Primary hypothyroidism does not seem to have significant effect on voice parameters until thyroxine levels are affected.
Topics: Adult; Female; Humans; Hypothyroidism; Middle Aged; Prospective Studies; Speech Acoustics; Statistics, Nonparametric; Voice Disorders; Voice Quality
PubMed: 34615613
DOI: 10.1016/j.anl.2021.09.003 -
Deutsches Arzteblatt International Apr 2022Neonatal screening in Germany currently comprises 19 congenital diseases, 13 of which are metabolic diseases. Approximately one in 1300 newborns suffers from one of... (Review)
Review
BACKGROUND
Neonatal screening in Germany currently comprises 19 congenital diseases, 13 of which are metabolic diseases. Approximately one in 1300 newborns suffers from one of these target diseases. Early diagnosis and treatment enable the affected children to undergo better development and even, in many cases, to have a normal life.
METHODS
This review is based on pertinent publications retrieved by a selective search in the PubMed and Embase databases.
RESULTS
Positive screening findings are confirmed in approximately one out of five newborns. The prompt evaluation of suspected diagnoses is essential, as treatment for some of these diseases must be initiated immediately after birth to prevent longterm sequelae. The most commonly identified diseases are primary hypothyroidism (1:3338), phenylketonuria/hyperphenylalaninemia (1 : 5262), cystic fibrosis (1 : 5400), and medium-chain acyl-CoA dehydrogenase deficiency (1 : 10 086). Patient numbers are rising as new variants of the target diseases are being identified, and treatments must be adapted to their heterogeneous manifestations. Precise diagnosis and the planning of treatment, which is generally lifelong, are best carried out in a specialized center.
CONCLUSION
Improved diagnosis and treatment now prolong the lives of many patients with congenital diseases. The provision of appropriate long-term treatment extending into adulthood will be a central structural task for screening medicine in the future.
Topics: Acyl-CoA Dehydrogenase; Cystic Fibrosis; Early Diagnosis; Germany; Humans; Hypothyroidism; Infant, Newborn; Lipid Metabolism, Inborn Errors; Neonatal Screening; Phenylketonurias
PubMed: 35140012
DOI: 10.3238/arztebl.m2022.0075 -
The Science of the Total Environment Apr 2023While fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy...
BACKGROUND
While fluoride can have thyroid-disrupting effects, associations between low-level fluoride exposure and thyroid conditions remain unclear, especially during pregnancy when insufficient thyroid hormones can adversely impact offspring development.
OBJECTIVES
We evaluated associations between fluoride exposure and hypothyroidism in a Canadian pregnancy cohort.
METHODS
We measured fluoride concentrations in drinking water and three dilution-corrected urine samples and estimated fluoride intake based on self-reported beverage consumption. We classified women enrolled in the Maternal-Infant Research on Environmental Chemicals Study as euthyroid (n = 1301), subclinical hypothyroid (n = 100) or primary hypothyroid (n = 107) based on their thyroid hormone levels in trimester one. We used multinomial logistic regression to estimate the association between fluoride exposure and classification of either subclinical or primary hypothyroidism and considered maternal thyroid peroxidase antibody (TPOAb) status, a marker of autoimmune hypothyroidism, as an effect modifier. In a subsample of 466 mother-child pairs, we used linear regression to explore the association between maternal hypothyroidism and child Full-Scale IQ (FSIQ) at ages 3-to-4 years and tested for effect modification by child sex.
RESULTS
A 0.5 mg/L increase in drinking water fluoride concentration was associated with a 1.65 (95 % confidence interval [CI]: 1.04, 2.60) increased odds of primary hypothyroidism. In contrast, we did not find a significant association between urinary fluoride (adjusted odds ratio [aOR]: 1.00; 95%CI: 0.73, 1.39) or fluoride intake (aOR: 1.25; 95%CI: 0.99, 1.57) and hypothyroidism. Among women with normal TPOAb levels, the risk of primary hypothyroidism increased with both increasing water fluoride and fluoride intake (aOR water fluoride concentration: 2.85; 95%CI: 1.25, 6.50; aOR fluoride intake: 1.75; 95%CI: 1.27, 2.41). Children born to women with primary hypothyroidism had lower FSIQ scores compared to children of euthyroid women, especially among boys (B coefficient: -8.42; 95 % CI: -15.33, -1.50).
DISCUSSION
Fluoride in drinking water was associated with increased risk of hypothyroidism in pregnant women. Thyroid disruption may contribute to developmental neurotoxicity of fluoride.
Topics: Male; Female; Humans; Pregnancy; Child, Preschool; Fluorides; Drinking Water; Canada; Hypothyroidism; Thyroid Hormones; Pregnancy Complications; Thyrotropin
PubMed: 36764861
DOI: 10.1016/j.scitotenv.2022.161149 -
Frontiers in Endocrinology 2023Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from...
INTRODUCTION
Previous observational studies have reported a positive correlation between obesity and susceptibility to hypothyroidism; however, there is limited evidence from alternative methodologies to establish a causal link.
METHODS
We investigated the causal relationship between obesity and hypothyroidism using a two-sample bidirectional Mendelian randomization (MR) analysis. Single-nucleotide polymorphisms (SNPs) associated with obesity-related traits were extracted from a published genome-wide association study (GWAS) of European individuals. Summarized diagnostic data of hypothyroidism were obtained from the UK Biobank. Primary analyses were conducted using the inverse variance-weighted (IVW) method with a random-effects model as well as three complementary approaches. Sensitivity analyses were performed to ascertain the correlation between obesity and hypothyroidism.
RESULTS
MR analyses of the IVW method and the analyses of hypothyroidism/myxedema indicated that body mass index (BMI) and waist circumference (WC) were significantly associated with higher odds and risk of hypothyroidism. Reverse MR analysis demonstrated that a genetic predisposition to hypothyroidism was associated with an increased risk of elevated BMI and WC, which was not observed between WC adjusted for BMI (WCadjBMI) and hypothyroidism.
DISCUSSION
Our current study indicates that obesity is a risk factor for hypothyroidism, suggesting that individuals with higher BMI/WC have an increased risk of developing hypothyroidism and indicating the importance of weight loss in reducing the risk of hypothyroidism.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Hypothyroidism; Causality; Obesity
PubMed: 38260160
DOI: 10.3389/fendo.2023.1287463 -
Child's Nervous System : ChNS :... Mar 2021Pituitary hyperplasia following primary hypothyroidism in pediatric age group population is considered rare with reports of unnecessary neurosurgical intervention for... (Review)
Review
INTRODUCTION
Pituitary hyperplasia following primary hypothyroidism in pediatric age group population is considered rare with reports of unnecessary neurosurgical intervention for this medically treatable condition. Given the paucity of information on this topic, it is timely to provide clinicians with a comprehensive summary of available research.
METHODS
A search of published studies in Pubmed, PsychInfo and Cochrane Database with the terms "pituitary hyperplasia" or "pituitary hypertrophy" and "hypothyroidism" was performed and the results filtered for English language, pediatric (0-18 years) population and CT or MRI confirmed findings. 55 studies met the inclusion criteria. Data for a total of 110 patients with pituitary hyperplasia following primary hypothyroidism were extracted. The study population included 29 males and 81 females (M: F= 0.35:1). Patient age varied from 3 weeks to 18 years with a mean age of 10.22 years.
RESULTS
The most common clinical presentations included growth retardation, constipation and features of myxedema which were present in 78, 36 and 18 percent of children included in our review. Neuroimaging showed the mean (SD) pituitary height being 13.48 mm (4.72 mm). All of the patients achieved resolution of their pituitary mass and clinical as well as biochemical abnormalities 1 to 26 months after initiation of thyroid hormone replacement therapy, with an average time interval of 7.22 months. Our review has tried to delve in the pathophysiology as well as clinical, biochemical and radiological aspects of pediatric pituitary hyperplasia secondary to primary hypothyroidism and provide recommendations for treatment and follow-up. This may help anyone concerned gain a substantial knowledge on this topic.
Topics: Child; Female; Hormone Replacement Therapy; Humans; Hyperplasia; Hypothyroidism; Male; Pituitary Diseases; Pituitary Gland
PubMed: 33404718
DOI: 10.1007/s00381-020-05014-6 -
Current Opinion in Endocrinology,... Oct 2020The aim of the article is to present the basics of oral levothyroxine (LT4) absorption, reasons why patients may have persistently elevated serum thyroid stimulation... (Review)
Review
PURPOSE OF REVIEW
The aim of the article is to present the basics of oral levothyroxine (LT4) absorption, reasons why patients may have persistently elevated serum thyroid stimulation hormone (TSH) levels, and alternative strategies for LT4 dosing.
RECENT FINDINGS
Although oral LT4 tablets are most commonly used for thyroid hormone replacement in patients with hypothyroidism, case studies report that liquid oral LT4, intravenous, intramuscular, and rectal administration of LT4 can successfully treat refractory hypothyroidism.
SUMMARY
Hypothyroidism is one of the most common endocrine disorders encountered by primary care physicians and endocrinologists. LT4 is one of the most widely prescribed medications in the world and it is the standard of care treatment for hypothyroidism. Generally, hypothyroid patients will be treated with LT4 tablets to be taken orally, and monitoring will occur with routine serum thyroid tests, including TSH concentrations. However, many patients fail to maintain serum TSH levels in the target range while managed on oral LT4 tablets. A subset of these patients would be considered to have poorly controlled hypothyroidism, sometimes termed refractory hypothyroidism. For these patients, optimization of ingestion routines and alternative formulations and routes of administration of LT4 can be considered, including oral liquid, intravenous, intramuscular, and even rectal formulations.
Topics: Administration, Oral; Dosage Forms; Drug Administration Routes; Drug Compounding; Gels; Humans; Hypothyroidism; Tablets; Thyrotropin; Thyroxine
PubMed: 32740045
DOI: 10.1097/MED.0000000000000558