Maraka, Spyridoula

Abstract Evidence regarding the effects of subclinical hypothyroidism (SCH) on adverse pregnancy outcomes and the ability of levothyroxine (LT4) treatment to prevent them is unclear. Available recommendations for the management of SCH during pregnancy are inconsistent. We conducted a nationwide survey among physicians assessing their knowledge of and current practices in the care of SCH in pregnancy and compared these with the most recent American Thyroid Association (ATA) recommendations. In this cross-sectional study, an online survey was sent to active US members of the Endocrine Society. This survey included questions about current practices and clinical scenarios aimed at assessing diagnostic evaluation, initiation of therapy, and follow-up in pregnant women with SCH. In total, 162 physicians completed the survey. ATA guidelines were reviewed by 76%, of whom 53% indicated that these guidelines actually changed their practice. Universal screening was the preferred screening approach (54%), followed by targeted screening (30%). For SCH diagnosis, most respondents (52%) endorsed a TSH level >2.5 mIU/L as a cutoff, whereas 5% endorsed a population-based cutoff as recommended by the ATA. The decision to initiate treatment varied depending on the specific clinical scenario; however, when LT4 was initiated, respondents expected a small/very small reduction in maternofetal complications. In conclusion, despite recently updated guidelines, there is still wide variation in clinical practices regarding the care of women with SCH in pregnancy. Highly reliable randomized trials are required to evaluate the effectiveness of the most uncertain treatment practices on the care of pregnant women with SCH.

Purpose of review Subclinical hypothyroidism (SCH) is a common diagnosis among women of reproductive age. The importance of sufficient maternal thyroid supply during pregnancy is well known. Nevertheless, the effects of SCH during pregnancy and the efficacy of its treatment on maternofetal outcomes are not well established. This review discusses the recent evidence on SCH in pregnancy and how this evidence is reflected in current clinical care. Recent findings Recent observational studies have found a positive association between SCH during pregnancy and adverse maternal, neonatal and offspring outcomes, mainly in thyroid peroxidase autoantibody positive women. Although interventional studies have shown a benefit of levothyroxine (LT4) treatment on selected pregnancy outcomes, there was no effect on offspring neurodevelopment. Summary Current evidence strengthens the association between SCH with both maternofetal and offspring adverse outcomes. An earlier and more individualized diagnostic assessment taking into consideration predictors of thyroid dysfunction and major risk factors for complications could result in better management of SCH during pregnancy. The effectiveness of LT4 on improving maternofetal and long-term offspring outcomes is still not fully elucidated.

Thyroid cancer recurrence can occur decades after initial diagnosis despite excellent response to therapy. Thyroid cancer recurrence is evaluated using serum thyroglobulin (Tg) and imaging studies including I-131 WBS and neck ultrasound. Limitations in Tg measurement and WBS may result in failure to detect recurrence. We report the case of a 63-year-old man who was noted to have rhonchi during a routine visit. He had a past history of follicular thyroid cancer that was diagnosed 40 years ago and treated with total thyroidectomy and radioactive iodine. He had excellent response to therapy with undetectable Tg levels, normal neck ultrasounds, and multiple negative whole body scans (WBS) due to which he was discharged from endocrinology clinic after 37 years of follow-up. Chest X-ray revealed a left lung mass with biopsy positive for thyroid cancer. Tg remained undetectable with negative anti-Tg antibody. Left pneumonectomy was done which revealed a mix of 70% differentiated thyroid cancer and 30% poorly differentiated/anaplastic thyroid cancer. He received two cycles of Doxorubicin and Paclitaxel. At 4 months follow-up after surgery, he had 3 subcentimeter nodules in his right lung. This case highlights that physical exam remains an essential tool to evaluate for recurrence. Since the lungs are the most common site of metastasis in follicular thyroid cancer, a chest X-ray may help detect metastasis that is missed on other modalities.

AbstractSubclinical hypothyroidism (SCH), a mild form of hypothyroidism defined as elevated TSH with normal free thyroxine levels, is a common diagnosis among women of reproductive age. In some, but not all, studies, it has been associated with infertility, an increased risk of adverse pregnancy and neonatal outcomes, and possibly with an increased risk of neurocognitive deficits in offspring. Despite well-established recommendations on treatment of overt hypothyroid pregnant women, a consensus has not yet been reached on whether to treat women with SCH. This review focuses on examining the evidence informing the clinical strategy for using levothyroxine (LT4) in women with SCH during pregnancy and those who are planning conception. A crucial first step is to accurately diagnose SCH using the appropriate population-based reference range. For pregnant women, if this is unavailable, the recommended TSH upper normal limit cutoff is 4.0 mIU/L. There is evidence supporting a decreased risk for pregnancy loss and preterm delivery for pregnant women with TSH > 4.0 mIU/L receiving LT4 therapy. LT4 treatment has been associated with better reproductive outcomes in women with SCH undergoing artificial reproductive techniques, but not in those who are attempting natural conception. Thyroid function tests need to be repeated throughout pregnancy to monitor LT4 therapy. In addition to potential harms, LT4 contributes to treatment burden. During a consultation, clinicians and patients should engage in a careful consideration of the current evidence in the context of the patients’ values and preferences to determine whether LT4 therapy initiation is the best next step.

SummaryObjectiveEvidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18F‐fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT imaging in a high‐risk population for adrenal malignancy using an optimal reference standard.DesignRetrospective cohort study.MethodsImaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra‐adrenal malignancy.ResultsUnenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7‐15) cm and median radiodensity was 33 (−21‐78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18FDG‐PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7‐9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3‐29.4] vs 3.7 [1.4‐24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74‐13.4] vs 1.2 [0.5‐6.6], respectively, P<.0001). 18FDG‐PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%.ConclusionNoncontract CT radiodensity of ≤10 HU excludes malignancy even in a high‐risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG‐PET/CT could be considered as a second stage imaging study.

We describe a family with multiple endocrine neoplasia type 2A (MEN2A) caused by the D631Y RET mutation resulting in an atypical phenotype. The index case was a 24-year-old man with history of recurrent anaplastic ependymoma incidentally found to have the D631Y RET mutation. At first assessment, four family members had evidence of large pheochromocytomas. One patient was found to have micromedullary thyroid cancer at 79 years of age. None of the patients had primary hyperparathyroidism. Patients with MEN2A caused by a D631Y RET mutation most commonly present with pheochromocytomas. Medullary thyroid cancer is a less common part of the syndrome when compared with other RET mutations.