Isolated maternal hypothyroxinemia (IMH) during pregnancy is defined as a low maternal T
in the absence of TSH elevation. As IMH is common, with a prevalence of 1-2% in iodine-sufficient populations, ...and early research has suggested adverse effects on fetal neurodevelopment, it has been the focus of many studies in the last decade. In the current review, we first discuss the significance of IMH based on data from animal models and recent discoveries regarding the role of thyroid hormone on neurodevelopment. We address issues surrounding the definition and prevalence of this entity and discuss new insights into the etiologies, clinical consequences and management of IMH. A number of large cohort studies have investigated the effects of IMH on the risk of various pregnancy complications and child neurodevelopment. We review these studies in detail and describe their limitations. We discuss the available research on management of IMH, including two recent randomized controlled trials (RCTs). Finally, we delineate the remaining uncertainties in this field and emphasize the need for a sufficiently powered, placebo-controlled RCT on the treatment of IMH early in the first trimester of pregnancy.
Thyroid eye disease (TED) is a sight-threatening and debilitating autoimmune condition, with limited therapies available, that often poses diagnostic and therapeutic challenges. In recent years, the ...treatment landscape has shifted to early intervention with targeted therapy.
A PubMed review of the literature was conducted for the period between 1979 and 2021. Search terms included thyroid eye disease, teprotumumab, targeted therapy, Graves disease, Graves ophthalmopathy, dysthyroid optic neuropathy, and related terms in different combinations. Novel biologic therapies for TED have emerged as alternatives to traditional steroid regimens in recent years. New insights into TED pathophysiology have uncovered the role of the insulin-like growth factor 1 receptor (IGF-1R) and led to the development of teprotumumab, an IGF-1R-inhibiting monoclonal antibody.
Randomized clinical trials demonstrating the efficacy of teprotumumab for TED led to Food and Drug Administration approval. Teprotumumab is gradually replacing immunosuppressive agents as first-line therapy in the United States for active moderate-to-severe TED, while emerging reports also show its use in other stages of the disease. Recent data highlight risk factors for adverse events and screening protocols to maximize patient safety. Personalized therapeutic plans developed through effective partnership between endocrinologists and ophthalmologists aim to enhance the safety and outcomes of TED treatments and improve care for this complex disease.
TED management is shifting to an era of targeted therapy with multidisciplinary care. Teprotumumab has demonstrated superior efficacy to conventional treatments and has transformed our therapeutic and surgical algorithms. Clinical guidelines and additional studies are needed to further guide and refine therapy.
Thyroid disease in pregnancy is a common clinical problem. Since the guidelines for the management of these disorders by the American Thyroid Association (ATA) were first published in 2011, ...significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid disease in women during pregnancy, preconception, and the postpartum period.
The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. The guideline task force had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members.
The revised guidelines for the management of thyroid disease in pregnancy include recommendations regarding the interpretation of thyroid function tests in pregnancy, iodine nutrition, thyroid autoantibodies and pregnancy complications, thyroid considerations in infertile women, hypothyroidism in pregnancy, thyrotoxicosis in pregnancy, thyroid nodules and cancer in pregnant women, fetal and neonatal considerations, thyroid disease and lactation, screening for thyroid dysfunction in pregnancy, and directions for future research.
We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid disease in pregnant and postpartum women. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with these disorders.
The endocrine system and the immune system interact closely during implantation and maintenance of pregnancy. One of the most striking examples of this communication is at the level of the decidua ...(endometrium of pregnancy). Here, under the influence of sex steroids, there is a dramatic increase of a unique population of lymphocytes, the uterine natural killer (uNK) cells, in early pregnancy. These cells derive predominantly from a subset of peripheral blood NK cells, which under hormonal influence gets recruited to the uterus. In mice, uNK cells play an important role in the development of placental vasculature. The role of these cells in human pregnancy is still not definitively established; however, they are believed to promote placental and trophoblast growth and provide immunomodulation at the maternal-fetal interface. In contrast to their presumptive role in the maintenance of a healthy pregnancy, uNK cells and peripheral NK cells are dysregulated in unexplained recurrent pregnancy loss. Herein, we review NK cell populations, their changes in number and function in altered endocrine environments during the menstrual cycle and pregnancy, the current data on their potential role in unexplained recurrent pregnancy loss, and mechanisms for potential therapies targeted to NK cell function for this enigmatic disorder.
Context:
Hypothyroidism in pregnancy can lead to adverse maternal and fetal outcomes. Although screening of high-risk women is advocated, universal screening remains controversial.
Objective:
The ...objective of the study was to compare the cost-effectiveness of universal screening of pregnant women for autoimmune thyroid disease (AITD) with screening only high-risk women and with no screening.
Design, Setting, and Participants:
A decision-analytic model compared the incremental cost per quality-adjusted life-year (QALY) gained among the following: 1) universal screening, 2) high-risk screening, and 3) no screening. Screening consisted of a first-trimester thyroid-stimulating hormone level and antithyroid peroxidase antibodies. Women with abnormal results underwent further testing and, when indicated, levothyroxine therapy. Randomized controlled trials provided probabilities for adverse obstetrical outcomes. The model accounted for the development of postpartum thyroiditis and overt hypothyroidism. Additional scenarios in which therapy prevented cases of decreased child intelligence quotient were explored.
Main Outcome Measures:
Medical consequences of AITD in pregnancy, QALY, and costs were measured.
Results:
Risk-based screening and universal screening were both cost-effective relative to no screening, with incremental cost-effectiveness ratios (ICERs) of $6,753/QALY and $7,138/QALY, respectively. Universal screening was cost-effective compared with risk-based screening, with an ICER of $7,258/QALY. Screening remained cost-effective in various clinical scenarios, including when only overt hypothyroidism was assumed to have adverse obstetrical outcomes. Universal screening was cost-saving in the scenario of untreated maternal hypothyroidism resulting in decreased child intelligence, with levothyroxine therapy being preventive.
Conclusions:
Universal screening of pregnant women in the first trimester for AITD is cost-effective, not only compared with no screening but also compared with screening of high-risk women.
The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown.
We conducted a cross-sectional electronic survey of American and ...European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions.
Two hundred fifty-two eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%, 114/227), white (79.7%, 181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%, 106/227), caring for 10 or more TED patients over the last 12 months (40.5%, 92/227), and reported not having a multidisciplinary TED clinic in their institution (52.8%, 120/227). The majority reported that new TED cases per annum have not changed in the past 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported a higher use of selenium (73%96/132 vs. 32%20/62 of respondents from North America and 24%8/33 of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous (IV) steroids (73%96/132, and 42%14/33) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important" concerns about TED management according to participants were: the cost of TED treatment (31.3%, 71/227), lack of effective TED treatments (19.8%, 45/227), and difficulty in predicting whether TED will develop (18.9%, 43/227).
There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies.
Teprotumumab is a novel insulin-like growth factor-1 receptor inhibitor approved for the treatment of thyroid eye disease, but growing reports of hearing loss require further investigation. To date, ...an effective protocol for managing hearing loss in this setting has not been determined. Here, we present the first report of the resolution of teprotumumab-related hearing loss with prompt oral prednisone. A 70-year-old woman on teprotumumab experienced sudden hearing loss and tinnitus after her first infusion. An audiogram demonstrated a mild down-sloping to moderately severe mixed conductive and sensorineural hearing loss that was promptly treated with prednisone 60 mg for 6 days with a 1-week gradual taper. An audiogram 3 weeks later demonstrated return of hearing to normal thresholds, and the whole teprotumumab treatment course was completed without further issue. This case highlights the importance of audiometric monitoring, prompt identification of hearing symptoms, and the potential for oral steroids to reverse teprotumumab-related hearing loss.
Abstract
Background: Plant extracts from species of Lycopus (bugleweed) and Melissa officinalis (lemon balm) have long been used as folk remedies in the treatment of hyperthyroidism1. In vitro ...studies have shown that extracts from bugleweed and lemon balm inhibit stimulation of thyroid hormone production by both TSH and Graves’ antibodies1. An in vivo study in rats showed that oral bugleweed extract alters extra-thyroidal T4 conversion2.
Case 1: A 64 year-old woman presented for routine examination and was found to have a TSH of 0.01 mIU/L on 6/6/2016. Labs the next month showed FT4 1.4ng/dL (0.8-1.8) and FT3 4.7pg/mL (2.3-4.2). TSI was elevated to 275% (Normal<140%), consistent with Graves’. She did not have symptoms of hyperthyroidism. The patient’s cat had been treated for hyperthyroidism with Thyrosoothe (TS), a formulation containing extracts from bugleweed and lemon balm. After being diagnosed with hyperthyroidism, the patient began taking TS. On 9/12/16 the patient’s labs were improved with TSH 0.02mIU/L, FT4 0.88 ng/dL (0.8-1.8) and Total T3 86 (76-181). Three months later, the patient’s TSH was 1.89 with normal FT4, Total T3 and TSI. She took TS for 9 months. Her thyroid function tests have remained normal since starting TS, without the need for any other anti-thyroid medications.
Case 2: A 46 year-old female presented with periorbital edema in July 2018 and was referred to an ophthalmologist, who diagnosed her with thyroid eye disease. She was also complaining of palpitations and “jitteriness”. She was found to be hyperthyroid on labs and was treated with methimazole (MMI) between August 2018 and February 2019, requiring doses of up to 10mg BID. In March 2019 she stopped MMI due to transaminitis and began taking a thyroid tincture containing bugleweed and lemon balm extract. She has remained euthyroid on the herbal tincture, her transaminitis has resolved, and she has not required any further anti-thyroid medication. Her TSI, which was 0.84 IU/L (Normal<0.55) in May 2019, normalized to 0.36 IU/L in June 2020, after 15 months on this tincture, which she is still taking.
Conclusion: In vitro and rat studies of bugleweed and lemon balm extract have demonstrated anti-thyroidal effects. This is the first report of the use of these plant extracts in the treatment of two patients with Graves’ disease, in whom it led to restoration of euthyroidism and normalization of TSI titers. Further study of the anti-thyroidal effects of bugleweed and lemon balm in humans is warranted to evaluate its potential role as an adjunctive therapy in Graves’ disease.References: 1. Auf’Mkolk, M., et al. “Extracts and Auto-Oxidized Constituents of Certain Plants Inhibit the Receptor-Binding and the Biological Activity of Graves’ Igs*.” Endocrinology, vol. 116, no. 5, May 1985, pp. 1687–93. 2. Winterhoff, H., et al. “Endocrine Effects of Lycopus Europaeus L. Following Oral Application.” Arzneim. Forsch., vol. I, no. 44, 1944.
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