Graves’ disease and recurrence in ectopic thyroid tissue after total thyroidectomy

We report a case of a 46-year-old woman who presented with a midline neck mass 2 years after total thyroidectomy for Graves’ disease. Despite levothyroxine treatment withdrawal, she remained biochemically with subclinical hyperthyroidism. Her thyroid stimulating hormone receptor antibodies were consistently elevated. Neck ultrasonography revealed an infrahyoid solid nodule and pertechnetate scintigraphy confirmed an increased uptake at the same level, without any uptake in the thyroid bed. Treatment with methimazole 5 mg/day was initiated with clinical improvement and achievement of euthyroidism. After that, she received 10 mCi of radioactive iodine. Since then, she experienced regression of the neck mass and is doing well on a replacement dose of levothyroxine. Recurrence of Graves’ disease in ectopic thyroid following total thyroidectomy is extremely rare. This diagnose should be considered in patients who underwent total thyroidectomy and remained with thyrotoxicosis despite decreasing the levothyroxine dose.

Subclinical Hypothyroidism in Children: A Review

Subclinical hypothyroidism is defined as serum levels of TSH above the upper limit of the reference range in the presence of normal concentrations of total T4 or free T4. This biochemical profile might be an indication of mild hypothyroidism, with a potential increased risk of metabolic abnormalities and cardiovascular disease among adults. Whether subclinical hypothyroidism results in adverse health outcomes among children is a matter of debate and so management of this condition remains challenging. Mild forms of untreated subclinical hypothyroidism do not seem to be associated with impairments in growth, bone health or neurocognitive outcome. However, ongoing scientific investigations have highlighted the presence of subtle proatherogenic abnormalities among children with modest elevations in their TSH levels. Although current findings are insufficient to recommend levothyroxine treatment for all children with mild asymptomatic forms of subclinical hypothyroidism, they highlight the potential need for assessment of cardiovascular risk among children with this condition. Increased understanding of the early metabolic risk factors associated with subclinical hypothyroidism in childhood will help to improve the management of affected individuals. DS (Child) H J 2020; 36(2): 146-151

Subclinical hypothyroidism or isolated high TSH in hospitalized patients with chronic heart-failure and chronic renal-failure

Sub-clinical hypothyroidism (SCH) is common in heart failure (HF) and advanced renal failure (RF), but it is unclear whether there is a thyroid disease or a transient increase in TSH level. This is a retrospective study of hospitalized patients in medical departments. All patients with SCH and a TSH level up to less than 12 mIU/L were identified. Those who had at least one recurring admission within at least 6 months were included. A change in thyroid function during the last re-admission was determined and classified as an improvement, no change, or worsening of thyroid function. Overall, 126 cases of SCH met the inclusion criteria for re-admission. Analysis of the most recent hospitalization showed that in 100 (79.4%) patients thyroid function improved, in 15 (11.9%) patients thyroid function remained unchanged and only in 11 (8.7%) patients did thyroid function worsen. In most cases, worsening of hypothyroidism was determined by initiation of a low dose levothyroxine treatment. Of the 126 participants, 43 (34.1%) and 22 (17.5%) had a diagnosis of HF and RF (CKD stages 4 and 5), respectively. There was no association between HF or advanced RF and worsening of SCH. No association was found between worsening of hypothyroidism and gender, age, TSH, or creatinine levels in the first hospitalization. A borderline association between elevated CRP levels at first hospitalization and hypothyroidism worsening was found (p = 0.066). Mildly elevated TSH in hospitalized patients with HF and advanced RF is transient and most probably not related to thyroid disease and not associated with age or gender.

Understanding the Pathogenesis of Gestational Hypothyroidism

Pregnancy is a complex state with many endocrinological challenges to a woman’s physiology. Gestational Hypothyroidism (GHT) is an emerging condition where insufficiency of the thyroid gland has developed during pregnancy in a previously euthyroid woman. It is different to overt hypothyroidism, where marked elevation of thyroid-stimulating hormone with corresponding reduction in free thyroxine levels, is well known to cause detrimental effects to both the mother and the baby. During the past couple of decades, it has been shown that GHT is associated with multiple adverse maternal and fetal outcomes such as miscarriage, pre-eclampsia, placental abruption, fetal loss, premature delivery, neurocognitive and neurobehavioral development. However, three randomized controlled trials and a prospective cohort study performed within the last decade, show that there is no neurodevelopmental improvement in the offspring of mothers who received levothyroxine treatment for GHT. Thus, the benefit of initiating treatment for GHT is highly debated within the clinical community as there may also be risks associated with over-treatment. In addition, regulatory mechanisms that could possibly lead to GHT during pregnancy are not well elucidated. This review aims to unravel pregnancy induced physiological challenges that could provide basis for the development of GHT. During pregnancy, there is increased renal clearance of iodine leading to low iodine state. Also, an elevated estrogen level leading to an increase in circulating thyroglobulin level and a decrease in free thyroxine level. Moreover, placenta secretes compounds such as human chorionic gonadotropin (hCG), placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (s-Flt1) that could affect the thyroid function. In turn, the passage of thyroid hormones and iodine to the fetus is highly regulated within the placental barrier. Together, these mechanisms are hypothesized to contribute to the development of intolerance of thyroid function leading to GHT in a vulnerable individual.

Levothyroxine Treatment and Cardiovascular Outcomes in Older People With Subclinical Hypothyroidism: Pooled Individual Results of Two Randomised Controlled Trials

BackgroundThe cardiovascular effects of treating older adults with subclinical hypothyroidism (SCH) are uncertain. Although concerns have been raised regarding a potential increase in cardiovascular side effects from thyroid hormone replacement, undertreatment may also increase the risk of cardiovascular events, especially for patients with cardiovascular disease (CVD).ObjectiveTo determine the effects of levothyroxine treatment on cardiovascular outcomes in older adults with SCH.MethodsCombined data of two parallel randomised double-blind placebo-controlled trials TRUST (Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism – a randomised placebo controlled Trial) and IEMO80+ (the Institute for Evidence-Based Medicine in Old Age 80-plus thyroid trial) were analysed as one-stage individual participant data. Participants aged ≥65 years for TRUST (n=737) and ≥80 years for IEMO80+ (n=105) with SCH, defined by elevated TSH with fT4 within the reference range, were included. Participants were randomly assigned to receive placebo or levothyroxine, with titration of the dose until TSH level was within the reference range. Cardiovascular events and cardiovascular side effects of overtreatment (new-onset atrial fibrillation and heart failure) were investigated, including stratified analyses according to CVD history and age.ResultsThe median [IQR] age was 75.0 [69.7–81.1] years, and 448 participants (53.2%) were women. The mean TSH was 6.38± SD 5.7 mIU/L at baseline and decreased at 1 year to 5.66 ± 3.3 mIU/L in the placebo group, compared with 3.66 ± 2.1 mIU/L in the levothyroxine group (p<0.001), at a median dose of 50 μg. Levothyroxine did not significantly change the risk of any of the prespecified cardiovascular outcomes, including cardiovascular events (HR 0.74 [0.41–1.25]), atrial fibrillation (HR 0.69 [0.32–1.52]), or heart failure (0.41 [0.13–1.35]), or all-cause mortality (HR 1.28 [0.54–3.03]), irrespective of history of CVD and age.ConclusionTreatment with levothyroxine did not significantly change the risk of cardiovascular outcomes in older adults with subclinical hypothyroidism, irrespective of a history of cardiovascular disease and age.Clinical Trial Registration [ClinicalTrials.gov], identifier [NCT01660126] (TRUST); Netherlands Trial Register: NTR3851 (IEMO80+).

A Unique Presentation of Metastatic Follicular Thyroid Cancer Associated with Hyperthyroidism and an Active Graves’ Orbitopathy

Background: Graves orbitopathy (GO) developing in a thyroidectomized patient with hormonally active metastatic follicular thyroid cancer (FTC) is an extremely rare event. We report a unique patient with GO and hyperthyroidism developing 13 years after FTC diagnosis. Case: A 79-year-old Caucasian female diagnosed with FTC T3N0M1 with lung metastases in 2005, was treated with total thyroidectomy and cumulative radioiodine (RAI) activity of 700 mCi between 2005 and 2010, with post-treatment scans revealing RAI-avid disease. Despite RAI treatment-associated stable disease in the lungs, the patient developed bone metastases and required external beam radiation (EBRT; 30 Gy in 10 fractions) to the left acetabular lesion in 2011. In 2015, she presented with clinically symptomatic tumor growth in the lungs and bones and biochemical disease progression with thyroglobulin levels rising from 255 ng/ml in 2014 to 273141 ng/mL in 2019. The patient completed repeat EBRT to the left iliac bone in December 2019 (30 Gy in 10 fractions). She was on weight-based suppressive levothyroxine treatment between 2005 and 2019 until she developed atrial fibrillation with a rapid ventricular response and was diagnosed with thyrotoxicosis with TSH < 0.01 mIU/mL (normal0.36 - 5.60) and free T4 5.93 ng/dL (normal 0.9 - 1.7). An iatrogenic cause of thyrotoxicosis was ruled out on the basis of persistent clinical and biochemical hyperthyroidism after reduction, and subsequently, cessation of levothyroxine treatment. Further workup was significant for elevated thyroid stimulated immunoglobulin (TSI) of 23.9 IU/l (normal: < 1.3) and thyrotropin receptor antibodies (TRAb) of 10.39 IU/L (< or =1.75), consistent with Graves’ disease. The patient achieved and maintained euthyroidism on methimazole treatment. In April 2019, she was diagnosed with active GO and was treated with intravenous methylprednisolone, which was discontinued four weeks later due to steroids-induced severe myopathy. Given a high clinical activity score of 6 and magnetic resonance imaging of the orbits revealing a significant bilateral symmetric extraocular muscle enlargement and increased retro-orbital fat with no evidence of optic nerve compromise, she underwent radiation therapy to the orbits (20 Gy in 10 fractions), which was completed in December 2019. Subsequently, in 2020, the patient underwent 8 cycles of treatment with a monoclonal antibody against insulin-like growth factor I receptor - teprotumumab. Subjectively, she reported improved eye swelling and no vision changes, but developed drug-induced partial hearing loss, which is thought to be reversible. Conclusion: Metastatic, progressive FTC can be associated with an autoimmune response, leading to stimulation of well-differentiated cancer tissue to overproduce thyroid hormones resulting in overt hyperthyroidism, as well as retroorbital fibroblasts activation leading to GO.