Israel Medical Association Journal

Background: Previous surveys demonstrated variations in the clinical practices relating to the treatment and screening of maternal thyroid dysfunction.

Objectives: To study the current practices in the management of subclinical hypothyroidism (SCH) and thyroid nodules during pregnancy of obstetricians/gynecologists (OB/GYNs) and endocrinologists in Israel.

Methods: An electronic questionnaire was sent by email to all members of the Israeli Endocrine Society and the Israel Society of Obstetrics and Gynecology. Questionnaires included demographic data and clinical scenarios with questions regarding the screening and management of pregnant women with SCH, hypothyroxinemia, and a palpable thyroid nodule. The questionnaire for OB/GYNs was slightly modified.

Results: We received 90 responses from endocrinologists and 42 responses from OB/GYNs. Among endocrinologists, 39% would repeat a thyroid-stimulating hormone (TSH) test of 2.9 mU/L with normal free thyroxine and treat with thyroxine if the second result was above 2.5 mU/L. Among OB/GYNs, 73% would manage a woman with SCH at the beginning of her pregnancy by themselves and only 22% would start thyroxine after a first TSH result above 2.5 mU/L. Concerning screening, 57% endocrinologists and 71% OB/GYNs recommended screening for thyroid dysfunction in every woman at the beginning of her pregnancy. Among endocrinologists, 54% would order an ultrasound for a palpable thyroid nodule and perform a fine needle aspiration only for suspicious lesions.

Conclusions: The medical approach to thyroid disease in pregnant women remains a matter of controversy. Our results support the need for larger and prospective clinical studies.

Background: Direct aspiration from suspected pathological tissue and rapid parathyroid hormone analysis may offer a reliable, cost effective alternative to currently used “gold standard” tests.

Objectives: To validate the accuracy of intraoperative measurements of parathyroid hormone levels in parathyroid adenomas.

Methods: A prospective study included 22 patients diagnosed with primary hyperparathyroidism who underwent parathyroidectomy due to an adenoma or hyperplasia. Aspirations of tissues extracted from three adjacent areas (the pathological parathyroid, thyroid, and muscle tissues) were sent for rapid parathyroid hormone analysis. The assay values of these tissue aspirates were compared to the results of the pathology report based on frozen section analysis and the final pathology report.

Results: All assay results were significantly higher for parathyroid tissue 16,800 to 1,097,986 pmol/L (median 26,600), than for either thyroid 1.7 to 415 pmol/L (median 6.5), P < 0.001, or muscle tissue 1.1 to 1230 pmol/L, (median 11.3), P < 0.001. All tissues showing high parathyroid assay values were also verified by pathology examinations: 7 had adenomas and 15 had a differential diagnosis of adenoma or hyperplasia. The frozen section identified all but one (false negative). Rapid intraoperative parathyroid levels > 1500 predicted parathyroid tissue with a 99% level of confidence, while levels between 1000 and 1500 predicted it with 95% confidence. The intraoperative parathyroid hormone assay showed > 70% decrease in 15/21 cases.

Conclusions: Rapid intraoperative parathyroid hormone analysis is a reliable and precise technique, equally accurate for frozen section analysis in predicting with high certainty intraoperative parathyroid tissue.

Background: Evidence has shown that pregnancy failure (PF) in women with systemic sclerosis (SSc) consists mainly of preterm delivery (PD) and intrauterine growth restriction (IUGR). Thyroid dysfunction (TD) and Hashimoto's thyroiditis (HT) represent a common feature of SSc. Since TD has been associated with PF, its presence in SSc women may potentially affect pregnancy outcome. 

Objectives: To analyze the interplay between TD and PF in a cohort of SSc women. 

Methods: SSc women (n=77) and age-matched controls from the general obstetric population (n=50) were included. Clinical/biochemical/instrumental data exploring TD and the visceral involvement were collected in the context of a clinical practice setting. Pregnancy outcome was assessed by registering the history of primary infertility, recurrent spontaneous abortion, PD (≤ 37 gestational week), IUGR, and intrauterine fetal death. 

Results: A higher prevalence of PD/IUGR was recorded in the SSc cohort than the controls (P = 0.04). SSc women with PF showed a higher prevalence of diffuse SSc than women without PF (P = 0.03). Scl-70 positive SSc women had a higher prevalence of PF than women with anti-centromere positivity (P = 0.01). A higher prevalence of HT was recorded in SSc women with PF than in patients without (P = 0.04). 

Conclusions: Our findings support the evidence that women with SSc can have successful pregnancies despite a higher prevalence of PD/IUGR. Diffuse SSc and Scl-70 positivity may predispose SSc women to PF. Routine thyroid workup may be included in the multi-specialist monitoring of SSc women for the early detection of thyroid dysfunctions.

 

Background: Thyroid-associated ophthalmopathy (TAO) is an inflammatory disease that affects the thyroid gland and the eye orbit. Of patients with TAO, 3%–5% have severe sight-threatening disease due to optic neuropathy Optical coherence tomography (OCT), the non-invasive imaging technology that yields high-resolution cross-sectional images of the retina, provides qualitative and quantitative data on the retina.

Objectives: To apply this technique to quantitatively assess retinal nerve fiber layer (RNFL) and macular ring thicknesses in healthy subjects and in patients with TAO to determine their relationship to the severity of the orbital disease.

Methods: All patients in the ophthalmology clinic who were diagnosed with TAO and underwent OCT imaging as part of their ocular examination comprised the study group, and healthy patients who volunteered to undergo OCT examination served as controls. Results of the complete ophthalmologic examination and OCT findings were collected from medical files, including the thickness of the RNFL and the macula.

Results: The study comprised 21 patients and 41 healthy controls. TAO patients exhibited RNFL thickening and inner macula thinning compared to healthy subjects. Mean RNFL thickness was correlated with the severity of the orbital disease.

Conclusion: The OCT findings suggest that the retina is involved in TAO, probably as early as the subclinical stage. This highlights the ability of OCT to identify retinal changes earlier and far more accurately than is detected today, enabling earlier diagnosis and more timely treatment to prevent severe visual sequelae.

Background: Four-dimensional parathyroid computed tomography (4DCT) is a relatively new parathyroid imaging technique that provides functional and highly detailed anatomic information about parathyroid tumors.

Objective: To assess the accuracy of 4DCT for the preoperative localization of parathyroid adenomas (PTAs) in patients with biochemically confirmed primary hyperparathyroidism (PHPT) and a history of failed surgery or unsuccessful localization using ^99mTc-sestamibi scanning and ultrasonography.

Methods: Between January 2013 and January 2015, 55 patients with PHPT underwent 4DCT at Hillel Yaffe Medical Center, Hadera, Israel. An initial unenhanced scan was followed by an IV contrast injection of nonionic contrast material (120 ml of at 4 ml/s). Scanning was repeated 25, 60, and 90 seconds after the initiation of IV contrast administration. An experienced radiologist blinded to the earlier imaging results reviewed the 4DCT for the presence and location (quadrant) of the suspected PTAs. At the time of the study, 28 patients had undergone surgical exploration following 4DCT and we compared their scans with the surgical findings.

Results: 4DCT accurately localized 96% (27/28) of abnormal glands, all of which were hypervascular and showed characteristic rapid enhancement on 4DCT that could be distinguished from Level II lymph nodes. Surgery found hypovascular cystic PTA in one patient who produced a negative 4DCT scan. All patients had solitary PTAs. The scan at 90 seconds provided no additional information and was abandoned during the study.

Conclusions: 4DCT accurately localized hypervascular parathyroid lesions and distinguished them from other tissues. A three-phase scanning protocol may suffice.

Background: More than 90% of all thyroid cancers are differentiated thyroid carcinomas (DTC) with a 10 year survival rate greater than 90%. The commonly used risk stratification systems for DTC include: European Organization for Research and Treatment of Cancer (EORTC), AGES (Age, histologic Grade, Extent of tumor, Size), AMES (Metastasis) and MACIS (Completeness of resection, local Invasion). Other systems are also utilized. Several new factors that may be involved in DTC risk stratification have emerged in recent studies, with other "traditional" factors being challenged. 

Objectives: To present recent updates in the literature on new potential prognostic factors for DTC.

Methods: We conducted a literature review and analysis of publications regarding DTC prognostic factors or risk stratification published in the last 10 years. 

Results: Several new factors with potential prognostic implications for DTC were noted, including family history, lymph node involvement parameters, positive PET-CT findings, multifocal disease, thyroglobulin level and several molecular markers including BRAF. Increasing age is associated with poorer outcome in DTC; however, recent studies suggest that the cutoff point of 45 years may be contested. Furthermore, several studies have shown contradictory results regarding male gender as a negative prognostic factor, thus questioning its prognostic significance. 

Conclusions: A number of new factors with potential prognostic implications for DTC have emerged and should be addressed. However, their role and possible inclusion in new staging systems has yet to be determined.

 

Background: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect on outcome of age at initial exposure have yet to be determined. 

Objectives: To identify the characteristics of radiation-induced thyroid carcinoma.

Methods: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. 

Results: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS).

Conclusions: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

 

Background: Treatment guidelines for well-differentiated papillary thyroid carcinoma (PTC) are based on retrospective studies and vary among different professional thyroid associations.

Objectives: To evaluate physician adherence to guidelines, overall and by specialty.

Methods: Questionnaires on the approach to low risk PTC were distributed among 51 surgeons and endocrinologists treating patients with PTC in tertiary medical centers.

Results: A wide range of answers was recorded among physicians regarding the danger posed by low risk PTC to the patient’s life, urgency with which treatment should be administered, type of treatment, and risks associated with this treatment. There was a significant between-group difference in treatment preference: endocrinologists chose total thyroidectomy with radioactive iodine, while surgeons favored hemithyroidectomy alone.

Conclusions: There is a wide difference in treatment recommendations between treating physicians and different specialties with regard to low risk PTC. The wide variation within and between specialties may be explained by biases. 

Background: The prevalence of thyroid dysfunction in early pregnancy in Israel is not known.

Objectives: To assess the rate of abnormal thyroid-stimulating hormone (TSH) tests in low risk pregnant women attending a community clinic in Israel.

Methods: We conducted a retrospective analysis of the charts of low risk pregnant women (n=303) who had undergone a TSH screening during the first trimester of pregnancy at Clalit Health Services Women's Health Centers in Ashkelon and Tel Aviv. The TSH normal range during first trimester was considered to be 0.1–2.5 mIU/L.

Results: The TSH levels ranged from 0.04 to 13.3 mIU/L (median 1.73 mIU/L, mean 1.88 mIU/L). The rate of abnormal TSH was 25.6%, with low TSH 2.3% and high TSH 23.4%. The prevalence of abnormal TSH was not influenced by gravidity (primigravidas versus multigravidas) or place of residence (Ashkelon or Tel Aviv).

Conclusions: In view of the high prevalence of abnormal TSH (25.6%) in pregnant women in Israel during the first trimester, a universal country-wide screening should be considered.