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Endocrine May 2024To provide an overview of consequences of undertreatment with levothyroxine (LT4) in the common non-communicable disease, hypothyroidism. (Review)
Review
PURPOSE
To provide an overview of consequences of undertreatment with levothyroxine (LT4) in the common non-communicable disease, hypothyroidism.
METHODS
Narrative review of the literature.
RESULTS
Hypothyroidism is globally very prevalent at all age groups and represents a non-communicable disease in which the risks and consequences are preventable. In children and adolescents, the most devastating consequences of undertreatment are poor growth and development. Lack of early treatment in congenital hypothyroidism can lead to permanent damage of brain function. In young to middle-aged adults, consequences are often overlooked, and treatment delayed by many years. The resulting consequences are also at this age group compromised brain and physical functioning but less severe and partly reversible with treatment. The undertreated condition often results in a higher risk of several secondary devastating diseases such as increased cardiovascular disease burden, obesity, hypertension, poor physical capacity, poor quality of life. In young women of fertile age the consequences of undertreatment with LT4 are subnormal fertility, recurrent pregnancy loss, preeclampsia, compromised fetal growth and neurocognitive development. There is a further risk of 30-50% of developing postpartum thyroiditis. In the elderly population care must be given to avoid confusing a slightly high serum TSH as result of physiological age adaptation with a requirement for LT4 treatment in a truly hypothyroid patient.
CONCLUSION
Undertreatment of the preventable non-communicable disease hypothyroidism requires more focus both from caretakers in the healthcare system, but also from the global political systems in order to prevent the personally devastating and socioeconomically challenging consequences.
Topics: Humans; Hypothyroidism; Thyroxine; Female; Pregnancy; Undertreatment
PubMed: 37556077
DOI: 10.1007/s12020-023-03460-1 -
Diagnostics (Basel, Switzerland) May 2023Early diagnosis of pregnancy- and lactation-associated osteoporosis (PLO) is mandatory for a good outcome. Standard care is not a matter of conventional guidelines,... (Review)
Review
Early diagnosis of pregnancy- and lactation-associated osteoporosis (PLO) is mandatory for a good outcome. Standard care is not a matter of conventional guidelines, rather it requires an individualized strategy while true overall incidence and pathogeny remain open issues. This is a narrative review based on full-length English articles, published between January 2021 and March 2023 and accessed via PubMed (no traumatic fractures or secondary osteoporosis are included). Our case-sample-based analysis included 836 females with PLO (the largest cohort based on published cases so far) through 12 studies and 24 single case reports. Except for one survey, these involved retrospective cohorts of small size (6-10 females/study) to medium size (23-47 women/study), and large cohorts with >50 subjects per study (a maximum of 379). Age of diagnosis: from 24 to 40 years for case reports (most subjects being over 30 and primigravida), while original studies indicated an average age between 31 and 34.18 years. Type of fractures underlined a most frequent vertebral phenotype (a mean of 2 to 5.8 vertebral fractures per patient) versus a most severe non-vertebral phenotype (hip and femoral neck fractures mostly requiring surgery). Potential contributors varied: smoking (1/3-1/2 of subjects), family history of osteoporosis (1/3), heparin and glucocorticoid use in pregnancy, low body mass index (majority of cases), hypovitaminosis D; and (with a low level of statistical significance) anti-psychotic medication, gestational diabetes, lupus, thrombophilia, anemia, in vitro fertilization (1/3 in one study), twin pregnancy, tocolysis with MgSO4, and postpartum thyroiditis. Most remarkably, up to 50% of PLO patients harbor mutations of , and (more damaged form with potential benefits from osteoanabolic drugs); gene testing might become the new norm in PLO. The low index of clinical suspicion should be supported by performing magnetic resonance imaging (gold standard in pregnancy) with DXA (in lactation). Low bone mineral density is expected (Z-score varying from -2.2 SD to -4 SD, unless normal which does not exclude PLO). Bone turnover markers might be useful in individuals with normal DXA, in pregnancy when DXA cannot be performed, and in following the response to anti-osteoporosis drugs. Alternatively, microarchitecture damage might be reflected by DXA-trabecular bone score and high-resolution peripheral quantitative computed tomography. Specific medical interventions are currently focused on teriparatide (TPT) use (3 studies; = 99 females treated with TPT and an additional subgroup of 18 patients from the gene-analysis-based study, thus a total of 117 females) which seems to be the therapy of choice as reflected by these new data: 6-24 months, 20 µg/day, no sequential therapy needed; case selection based on high fracture risk is necessary). The first case using romosozumab was reported in 2022. PAO/LAO remains a challenging condition which is a battle for the wellbeing of two individuals, on one hand, considering maternal-fetal outcomes and taking care of the offspring, but it is a battle for a multidisciplinary team, on the other hand, since a standardized approach is lacking.
PubMed: 37175006
DOI: 10.3390/diagnostics13091615 -
Journal of Clinical Medicine Feb 2023Vitamin D (VitD) deficiency has garnered significant attention in contemporary medical research. Although the canonical biological activity of VitD manifests itself... (Review)
Review
Vitamin D (VitD) deficiency has garnered significant attention in contemporary medical research. Although the canonical biological activity of VitD manifests itself mainly in the regulation of calcium-phosphorus metabolism, recent studies show that, thanks to the presence of numerous receptors, VitD may also play an important role in regulating the immune system. VitD deficiency has been demonstrated to impact autoimmune disease, coeliac disease, infections (including respiratory/COVID-19), and patients with cancer. Recent studies also show that VitD plays a significant role in autoimmune thyroid diseases (AITDs). Many studies have shown a correlation between low VitD levels and chronic autoimmune thyroiditis - Hashimoto thyroiditis (HT), Graves' disease (GD), and postpartum thyroiditis (PPT). This review article, therefore, describes the current state of knowledge on the role of VitD in AITDs, including HT, GD, and PTT.
PubMed: 36835987
DOI: 10.3390/jcm12041452 -
Frontiers in Endocrinology 2021SARS-CoV-2 infection (COVID-19) is currently a tremendous global health problem. COVID-19 causes considerable damage to a wide range of vital organs most prominently the... (Review)
Review
SARS-CoV-2 infection (COVID-19) is currently a tremendous global health problem. COVID-19 causes considerable damage to a wide range of vital organs most prominently the respiratory system. Recently, clinical evidence for thyroidal insults during and after COVID-19 has been accumulated. As of today, almost all non-neoplastic thyroid diseases, i.e., Graves' disease, Hashimoto's thyroiditis, subacute, painless and postpartum thyroiditis, have been reported as a complication of COVID-19, and causality by the virus has been strongly implicated in all of them. Similar thyroid problems have been reported in the past with the SARS-CoV outbreak in 2002. In this review, we briefly look back at the reported evidence of alteration in thyroid functionality and thyroid diseases associated with SARS-CoV and then proceed to examine the issue with COVID-19 in detail, which is then followed by an in-depth discussion regarding a pathogenetic link between Coronavirus infection and thyroid disease.
Topics: COVID-19; Humans; Thyroid Diseases; Thyroid Gland
PubMed: 34276567
DOI: 10.3389/fendo.2021.708333 -
The Quarterly Journal of Nuclear... Jun 2021Hyperthyroidism is a clinical condition characterized by inappropriately high synthesis and secretion of thyroid hormones by the thyroid gland. It has multiple... (Review)
Review
Hyperthyroidism is a clinical condition characterized by inappropriately high synthesis and secretion of thyroid hormones by the thyroid gland. It has multiple aetiologies, manifestations and potential therapies. Graves' disease is the most common form of hyperthyroidism, due to the production of autoantibodies against thyrotropin receptor, capable of over-stimulating thyroid function. A reliable diagnosis of hyperthyroidism can be established on clinical grounds, followed by the evaluation of serum thyroid function tests (thyrotropin first and then free thyroxine, adding the measurement of free triiodothyronine in selected specific situations). The recent guidelines of both the American and European Thyroid Associations have strongly recommended the measurement of thyrotropin receptor autoantibodies for the accurate diagnosis and management of Graves' disease. If autoantibody test is negative, a radioiodine uptake should be performed. Considering the most recent laboratory improvements, binding assays can be considered the best first solution for the measurement of thyrotropin receptor autoantibodies in diagnosis and management of overt cases of Graves' disease. In fact, they have a satisfactory clinical sensitivity and specificity (97.4% and 99.2%, respectively) being performed in clinical laboratories on automated platforms together with the other thyroid function tests. In this setting, the bioassays should be reserved for fine and complex diagnoses and for particular clinical conditions where it is essential to document the transition from stimulating to blocking activity or vice versa (e.g. pregnancy and post-partum, related thyroid eye disease, Hashimoto's thyroiditis with extrathyroidal manifestations, unusual cases after LT4 therapy for hypothyroidism or after antithyroid drug treatment for Graves' disease). Undoubtedly, technological advances will help improve laboratory diagnostics of hyperthyroidism. Nevertheless, despite future progress, the dialogue between clinicians and laboratory will continue to be crucial for an adequate knowledge and interpretation of the laboratory tests and, therefore, for an accurate diagnosis and correct management of the patient.
Topics: Animals; Antithyroid Agents; Autoantibodies; Biosensing Techniques; Cell Line; Humans; Hyperthyroidism; Iodine Radioisotopes; Protein Binding; Receptors, Thyrotropin; Sensitivity and Specificity; Thyroid Gland
PubMed: 33565846
DOI: 10.23736/S1824-4785.21.03344-6 -
Nutrients May 2022Selenium (Se) is an essential trace element with antioxidant and anti-inflammatory properties and a pivotal role in thyroid metabolism. Ensuring a sufficient Se supply... (Review)
Review
Selenium (Se) is an essential trace element with antioxidant and anti-inflammatory properties and a pivotal role in thyroid metabolism. Ensuring a sufficient Se supply is possible via a balanced, wholesome diet; however, Se content in foods may be different throughout geographical areas. Se supplementation is expected to improve inflammatory status in patients with autoimmune thyroiditis, especially in those with high activity, and has been demonstrated as effective in reducing the thyroid peroxidase antibodies titer. Se status seems to affect thyroid function in pregnancy, which prompts the potential role of Se supplementation in such patients. Few clinical trials have investigated the effectiveness of Se supplementation in pregnant women with thyroiditis, and their results suggest the safety and effectiveness of this element in reducing autoantibody levels and preventing postpartum thyroiditis development, although limited. Hence, more robust evidence is needed to confirm these data. The current study aims to summarize published data on the relationship between Se and thyroid status in pregnant women with thyroiditis and the potential use of Se. Moreover, an algorithm for Se supplementation is proposed for pregnant women with thyroiditis to help endocrinologists in daily clinical practice to consider Se status.
Topics: Dietary Supplements; Female; Hashimoto Disease; Humans; Pregnancy; Pregnant Women; Selenium; Thyroiditis, Autoimmune
PubMed: 35684035
DOI: 10.3390/nu14112234 -
European Journal of Endocrinology Aug 2023Postpartum depression (PPD) has a major impact on maternal and offspring well-being, with multiple possible risk factors: Studies on the association of thyroid... (Meta-Analysis)
Meta-Analysis
Association of gestational thyroid function and thyroid peroxidase antibody positivity with postpartum depression: a prospective cohort study and systematic literature review with meta-analysis.
IMPORTANCE
Postpartum depression (PPD) has a major impact on maternal and offspring well-being, with multiple possible risk factors: Studies on the association of thyroid peroxidase antibody (TPOAb) positivity and thyroid function with PPD provide heterogeneous results.
OBJECTIVE
To study the association of thyroid function and TPOAb positivity with PPD.
DESIGN
We assessed the association of TPOAb and thyroid function with PPD in a population-based prospective cohort study and performed a systematic literature review and meta-analysis.
METHODS
We measured thyroid stimulating hormone (TSH), free thyroxine (FT4), and TPOAb between 9- and 17-week gestation. Postpartum depression was assessed with Edinburgh Postpartum Depression Scale at 2-month postpartum and Brief Symptom Inventory at 2-, 6-, and 36-month postpartum. Additionally, we performed a systematic literature review and meta-analysis assessing this association.
RESULTS
In the present study, there was no association of thyroid function with PPD (TSH: odds ratio [OR] 0.83, 95% CI 0.58-1.19, P = .32; FT4: OR 0.99, 95% CI 0.95-1.05, P = .86) or TPOAb positivity with PPD (OR 0.79, 95% CI 0.47-1.33, P = .37). An impaired thyroidal response to human chorionic gonadotropin (hCG), a surrogate marker for TPOAb positivity, was associated with a lower risk of PPD (P for interaction TSH = 0.04; FT4 = 0.06). Our systematic review and meta-analysis included 3 articles that were combined with the present study. There was no statistically significant association of TPOAb positivity with PPD (OR 1.93, 95% CI 0.91-4.10, P = .08), but the results were heterogeneous (I2 = 79%).
CONCLUSIONS AND RELEVANCE
There was no significant association of TPOAb positivity, TSH, or FT4 with PPD. Our systematic review and meta-analysis revealed high heterogeneity of the current literature. Although TPOAb-positive women should be monitored for postpartum thyroiditis, our findings do not support routinely screening for PPD.
Topics: Female; Humans; Thyroid Gland; Iodide Peroxidase; Prospective Studies; Depression, Postpartum; Autoantibodies; Thyrotropin; Thyroxine
PubMed: 37486224
DOI: 10.1093/ejendo/lvad092 -
Frontiers in Endocrinology 2020Postpartum thyroiditis (PPT) has a prevalence of 1-22%, with an ~50% rate of evolution into permanent hypothyroidism (PH). PPT risk is assessed by measuring serum...
Postpartum thyroiditis (PPT) has a prevalence of 1-22%, with an ~50% rate of evolution into permanent hypothyroidism (PH). PPT risk is assessed by measuring serum thyroid antibodies during gestation, as 1/3-1/2 of Ab+ve pregnant women will develop PPT. Family and personal history positive for autoimmune non-thyroid diseases (AINTDT), and consumption of swordfish increases while consumption of small oily fish decreases the risk of PPT. Monitoring thyroid function in a very high-risk subgroup avoids the costs of the Ab-based universal screening. We aimed at identifying such subgroup in 412 women followed from week 7-11 of gestation to month 12 postpartum. At study entry, we measured serum TPOAb, TgAb, TSH, FT4, FT3, and evaluated seafood consumption, familial history for thyroid diseases and AINTD, and personal history for AINTD. We measured TSH, FT4, FT3 at 1.5, 3, 6, and 12 months postpartum. PPT occurred in 63 women (15.3%), and PH in 34/63 (54%). Based on positivity/negativity for the three histories, women were classified into 8 categories, with PPT rates of 3.8-100%. Seafood consumption allowed further separation of subgroups having different PPT risks. We considered 11 possible strategies, termed [a] through [k]. Strategy [a] consisted in omitting gestational screening, while performing universal postpartum monitoring with TSH and one thyroid hormone; strategy [k] consisted in selective gestational screening with TPOAb and TgAb, based on history and fish consumption, and selective postpartum monitoring in TPOAb and/or TgAb+ve women. The 100% sensitivity, specificity and diagnostic accuracy of strategy [a] were counterbalanced by the highest costs (Euro 32,960 or 523 per each PPT caught). The corresponding numbers for strategy [k] were 78, 95, 93%, and Euro 8,920 or 182/PPT caught. These savings stem from gestational screening being done in 186 women, and postpartum monitoring done in 65/186 women. One gestational screning-free strategy was the cheapest (Euro 2,080 or 83/PPT caught), because based on postpartum monitoring of only 26 women, but had the lowest sensitivity (40%). Identification of pregnant women having different risks for PPT is feasible, with the costless evaluation of history and seafood consumption driving gestational screening of thyroid antibody status and postpartum monitoring of thyroid function.
Topics: Adolescent; Adult; Autoantibodies; Biomarkers; Cohort Studies; Female; Follow-Up Studies; Humans; Hypothyroidism; Postpartum Thyroiditis; Pregnancy; Prenatal Diagnosis; Prognosis; Thyroiditis, Autoimmune; Young Adult
PubMed: 32362873
DOI: 10.3389/fendo.2020.00220 -
Endocrinology, Diabetes & Metabolism... Jul 2021Hypothyroidism occurring in the postpartum period can be due to pituitary or hypothalamic disease as in Sheehan's syndrome and postpartum autoimmune hypophysitis or due...
SUMMARY
Hypothyroidism occurring in the postpartum period can be due to pituitary or hypothalamic disease as in Sheehan's syndrome and postpartum autoimmune hypophysitis or due to a primary thyroid disease as in postpartum thyroiditis. It is important that the correct diagnosis is ascertained because hypothalamic or pituitary disorders are often associated with other pituitary hormone deficiencies, especially life-threatening adrenal insufficiency or adrenal crisis. A combination of various symptoms and biochemical markers, especially serum thyroid-stimulating hormone levels dictate the initial diagnostic pathway. We present a case of a woman who presented with a 2-month history of tiredness and neck discomfort following delivery. A thyroid function test demonstrated results, which we initially interpreted as central hypothyroidism. Follow-up results indicated that this was in fact the transition period between the thyrotoxic phase and hypothyroid phases of postpartum thyroiditis. This case highlights the potential for diagnostic confusion between central hypothyroidism and postpartum thyroiditis.
LEARNING POINTS
Postpartum thyroiditis affects one in twenty mothers within 12 months of delivery. The majority of patients have transient thyrotoxicosis only, some have transient hypothyroidism only, and the rest has a triphasic pattern (thyrotoxic, hypothyroid then a euthyroid phase). During the transition from the thyrotoxic phase to hypothyroid phase, when serum TSH is still suppressed, the biochemical results can resemble that of central hypothyroidism. If central hypothyroidism is suspected, then urgent diagnostic investigations should be carried out along with the assessment of adrenal function. There is a potential for diagnostic confusion between postpartum central hypothyroidism and postpartum thyroiditis; however, the obstetric history, clinical symptoms, and signs (headaches, breastfeeding, goitre, etc.) and serum adrenocorticotropic levels should help with the differential diagnosis.
PubMed: 34280894
DOI: 10.1530/EDM-21-0069 -
Endocrine Practice : Official Journal... Jun 2022Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of...
OBJECTIVE
Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment.
METHODS
Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly.
RESULTS
After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery.
CONCLUSION
For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.
Topics: Female; Humans; Hypothyroidism; Postpartum Period; Pregnancy; Pregnancy Complications; Thyroid Neoplasms; Thyrotropin; Thyroxine
PubMed: 35278704
DOI: 10.1016/j.eprac.2022.03.002