APPROACH TO THE PATIENT Fetal and neonatal thyroid dysfunction

Fetal and neonatal dysfunctions include rare serious disorders involving abnormal thyroid function during the second half of gestation, which may persist throughout life, as for most congenital thyroid disorders, or be transient, resolving in the first few weeks of life, as in autoimmune hyperthyroidism or hypothyroidism and some cases of congenital hypothyroidism (CH) with the thyroid gland in situ. Primary CH is diagnosed by neonatal screening, which has been implemented for 40 years in developed countries and should be introduced worldwide, as early treatment prevents irreversible neurodevelopmental delay.Central CH is a rarer entity occurring mostly in association with multiple pituitary hormone deficiencies. Other rare disorders impair the action of thyroid hormones. Neonatal Grave’s disease (GD) results from the passage of thyrotropin receptor antibodies (TRAb) across the placenta, from mother to fetus. It may affect the fetuses and neonates of mothers with a history of current or past GD, but hyperthyroidism develops only in those with high levels of stimulatory TRAb activity. The presence of antibodies predominantly blocking TSH receptors may result in transient hypothyroidism, possibly followed by neonatal hyperthyroidism, depending on the balance between the antibodies present. Antithyroid drugs taken by the mother cross the placenta, treating potential fetal hyperthyroidism,but they may also cause transient fetal and neonatal hypothyroidism. Early diagnosis and treatment are key to optimizing the child’s prognosis. This review focuses on the diagnosis and management of these patients during the fetal and neonatal periods. It includes the description of a case of fetal and neonatal autoimmune hyperthyroidism.

Thyroid Storm: A Diagnostic Conundrum

Thyroid storm is a life threatening complication of hyperthyroidism which comes with multi-system involvement and is associated with a mortality of 8-25% despite modern advancements in treatment and supportive measures. A 47 year old woman with past medical history of hypertension and morbid obesity presented to the emergency room with 3 week history of shortness of breath and chest pain associated with productive cough, bilateral leg swelling, orthopnea and palpitations. Upon evaluation, she was in moderate respiratory distress, restless, tachypneic and tachycardic. She had bilateral proptosis and visible jugular venous pulsation along-with bibasilar crackles and pitting edema bilaterally. Lab tests revealed BNP 539 pg/ml and D-Dimer 6401 ng/ml. ECG showed atrial flutter, Chest X-Ray showed bilateral pleural effusions, and CT Chest was negative for pulmonary embolism but revealed anterior mediastinal mass, differential of which included thymoma or teratoma. She was admitted to CCU for aggressive diuresis, control of heart rate and was started on anticoagulation. A review of medical records from outside hospital revealed patient was hyperthyroid 8 months ago, however, was not on any medications. Given a Burch-Wartofsky score >70, she was started on IV hydrocortisone and cholestyramine for severe thyrotoxicosis. Endocrinology was consulted and added PTU to management. TFTs revealed a TSH 0.006 IU/ml, FT4 4 ng/dL and T3 2.5 ng/ml. Bedside ECHO showed LVEF of 14% with global hypokinesis and thyroid ultrasound revealed an enlarged, heterogenous thyroid with a solid, isoechoic, calcified left lobe nodule measuring 0.8 x 0.4 x 0.5 cm. Her serum TSI and thyrotropin receptor antibodies were elevated at 17.20 IU/L and 20.20 IU/L, respectively. She responded to treatment and was discharged on metoprolol, losartan, spironolactone, and furosemide for new-onset heart failure, apixaban for atrial flutter, and PTU and cholestyramine for hyperthyroidism, with Cardiology and Endocrinology follow-ups. Thyroid disease is a common illness affecting 9 to 15 percent of the adults. Thyrotoxicosis refers to the clinical syndrome of hyper-metabolism due to excessive amount of circulating thyroid hormones. The incidence of thyroid storm is 0.57 to 0.76 per 100,000 people per year in the US. It most commonly occurs in women and is more common in patients with underlying Grave’s Disease. The exact underlying mechanism that leads to thyroid storm is not well understood but adrenergic activation seems to have a major role. Our patient had long standing untreated hyperthyroidism with a solid nodule which led to the crisis. The most common cause of death is cardiopulmonary failure and hence treatment should be initiated as soon as diagnosis is suspected owing to high mortality. Awareness of thyroid pathology affecting the heart is important to remember in evaluating the etiology of heart failure in patients.

Comparison of three methods for determining anti-thyrotropin receptor antibodies (TRAb) for diagnosis of Graves’ disease: a clinical validation

Objectives Graves’ disease is secondary to the presence of anti-thyrotropin receptor antibodies (TRAb), which stimulate thyroid hormones. TRab determination is crucial for etiological diagnosis. The objectives of this study were (i) to compare two methods for determining TRab by chemoluminiscence vs. standard TRACE-immunofluorescence; (ii) to determine the diagnostic validity of the three methods. Methods A retrospective study in 194 patients with a TRAb determination request. TRAb were determined by immunofluorescence (Kryptor, ThermoFisher) and chemiluminescence (Immulite, Siemens and Maglumi, Snibe). Clinical validation: medical records were reviewed and categorized according to thyroid function. Statistical analysis: Differences in quantitative variables were assessed by intraclass correlation coefficient, Bland–Altman plot, and mean differences (mD). Qualitative variables were dichotomized by cut-off points; Kappa coefficient was calculated. Correlations were evaluated by Pearson’s coefficient and Passing-Bablok regression analysis. The diagnostic validity of the three methods was investigated. Results Kryptor-Immulite: mD: 1.2 (95%CI: −16 to >18). Passing-Bablok: Constant error (95%CI: −0.8349 to −0.5987). Proportional error (95%CI: 0.7862–1.0387). ICC: 0.86 (95%CI: 0.82–0.89). Kappa coefficient: 0.68 (95%CI 0.59–0.78). Kryptor-Maglumi: mD: −0.3 (95%CI: −12 to >12). Passing-Bablok: Constant error (95%CI: −0.7701 to >0.1621. Proportional error (95%CI: 0.8571 to 1.3179. ICC: 0.93 (95%CI: 0.89–0.97). Kappa coefficient: 0.53 (95%CI: 0.32–0.74). Diagnosis of Graves’ disease was confirmed in 113 patients (Kryptorf showed better specificity and positive predictive value, whereas Immulite demonstrated better sensitivity and negative predictive value). Conclusions The three methods have a good diagnostic performance for Graves’ disease, with superimposable results on Bland–Altman plot. Interchangeability was not confirmed on the regression and agreement analysis, with the presence of biases.