Serena Ippolito

Endothelial-mediated coronary flow reserve in patients with mild thyroid hormone deficiency

CONTEXT Although coronary flow reserve (CFR) is reduced in patients with subclinical hypothyroidism (SHypo), the endothelial response of coronary vasomotion has never been explored in this clinical setting. OBJECTIVE To investigate the endothelial response of coronary flow in young and middle-aged patients with SHypo, without associated cardiovascular risk factors compared with healthy control subjects. PATIENTS AND METHODS The study population consisted of 20 women (mean age 38.4+12.1 years) with newly diagnosed, untreated and persistent SHypo due to Hashimotos thyroiditis. A total of 15 volunteers served as controls. Age, gender, body surface area, glucose, insulin levels, heart rate, systolic, diastolic, and mean blood pressure were similar in patients and controls. Body mass index was significantly higher in SHypo patients. Total cholesterol and low-density lipoprotein cholesterol, despite not significant, tended to be higher, and high-density lipoprotein cholesterol to be lower in SHypo. Coronary blood flow velocities were recorded in patients at rest and after the cold pressor test (CPT), a stimulus that can be considered totally endothelium-dependent. CFR was calculated as the ratio of hyperemic-to-resting diastolic peak velocities. RESULTS Coronary diastolic peak velocities at rest did not differ between the two groups but were significantly lower after CPT in patients with SHypo, thereby resulting in a lower CFR. The difference remained significant after adjusting resting and CPT velocities for the respective mean blood pressures. TSH was inversely correlated with CFR in the pooled population. CONCLUSION Patients with SHypo without associated cardiovascular risk factors have a coronary endothelial dysfunction that appears in response to a physiological stimulus (the CPT).

Ultimobranchial Body Remnants (Solid Cell Nests) as a Pitfall in Thyroid Pathology

We report the history of a pitfall in thyroid histopathology of a 47-yr-old man with a euthyroid nodular goiter involving the right lobe. The ultrasound-guided fineneedle aspiration of the dominant (3 cm) nodule, showing benign-appearing follicular cells, colloid, and scattered Hurthle cells, was consistent with a benign hyperplastic nodule (1). Because the left lobe had not shown evidence of nodular disease, the patient was submitted to a right lobectomy. The pathologist described a heavy lymphoplasmacyticbackgroundwithoccasionalgerminalcenter formation, as observed in Hashimoto thyroiditis, and a microscopic ( 1cm) follicularproliferationofepithelial thyroidcellswhose nucleidisplayedmembrane irregularityandchromatinclearing with occasional grooves. Thus, a histological report of a follicular variant of papillary microcarcinoma was issued. The patient underwent a completion thyroidectomy at the Federico II UniversityofNaples.At thatoccasion, thecompletesetofslides from both surgeries was reviewed by expert pathologists in the field of thyroid disease.

Spindle epithelial tumor with thymus-like differentiation (SETTLE): clinical-pathological features, differential pathological diagnosis and therapy

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid gland. An algorithm for the diagnosis and treatment of SETTLE has yet to be established. The aim of this study was to identify all case reports of SETTLE and to compare the clinical-pathological features and therapy of the cases identified. We performed a PubMed search for case reports of SETTLE in English published up to November 2014 in which “SETTLE” and “Spindle epithelial tumor with thymus-like differentiation” were keywords. We identified 35 articles for a total of 42 cases. We found that SETTLE usually occurs in children and adolescents as an asymptomatic neck mass. Thyroid function tests and tumor markers are invariably within normal range in all patients, and fine needle aspiration biopsy is rarely diagnostic for SETTLE. All 42 patients had undergone thyroidectomy. After surgical resection, chemotherapy (adjuvant or first/second-line treatment) and/or radiotherapy were administered to control tumor growth in cases with metastatic involvement. Although SETTLE presents a low-grade malignancy, it can metastasize to lymph nodes, the mediastinum, lung, vertebrae, and kidney even many years after the initial diagnosis. SETTLE may have a good prognosis if appropriately treated at initial presentation and if patients undergo long-term monitoring with regular clinical and morphological evaluations.

Treatment of refractory and severe hypothyroidism with sublingual levothyroxine in liquid formulation

The aim of replacement therapy in hypothyroid patients is to restore clinical and biochemical euthyroidism [1, 2]. Current guidelines recommend oral L-thyroxine (L-T4) in tablets as treatment of choice in patients with hypothyroidism [2]. The cause and severity of thyroid hormone deficiency, age, sex, and lean body mass may affect the L-T4 replacement dosage [1]. The starting optimal replacement dose of L-T4 related to body weight (BW) is about 1.6–1.8 μg/kg/d in hypothyroid adults [1]. Serum thyrotropin (TSH) levels represent the best marker to assess the adequacy of L-T4 dosage during replacement therapy [1, 2]. Reaching the target TSH can be problematic in some patients with poor adherence to therapy, malabsorption, or drug interferences [1]. Higher L-T4 doses are required in these conditions, and increased TSH with frequent serum fluctuations may be observed [1]. An efficient absorption of oral L-T4 is necessary to obtain euthyroidism with stable serum TSH levels [3–5]. L-T4 must be taken regularly while fasting because food ingestion delays and reduces the absorption of oral L-T4 in the intestinal mucosa [2]. Only 70–80% of the L-T4 administered dose is absorbed [3–5] and a normal gastric acid secretion environment is needed to allow an adequate L-T4 assimilation [1–5], which occurs within the first 90min after tablet ingestion [3, 5] and is influenced by food and drinks, soy protein, and supplements [1]. The contemporary ingestion of drugs (iron, sucralfate, calcium carbonate, antiacids, and prompton pump inhibitors) may reduce L-T4 absorption [1, 4, 5]. Moreover, malabsorption of L-T4 may occur in patients with gastrointestinal disorders such as coeliac disease [1], Helicobacter pylori infection [5], congestive gastropathy, autoimmune gastritis [6], short bowel syndrome [1], lactose intolerance [7], and chronic giardiasis [1]. Novel oral formulations of L-T4 have been developed to improve this problematic issue. Oral liquid L-T4 formulations and soft gel capsules are useful in patients with contemporary assumption of L-T4 with food or beverages during breakfast, pharmacological interferences, and gastrointestinal disorders [8–13]. They can improve the L-T4 assimilation in patients with and without malabsorption [12]. In fact, soft gel capsules contain L-T4 dissolved in glycerin, while L-T4 is dissolved in glycerol and ethanol in liquid solutions. These characteristics allow a faster absorption of novel formulations because they do not need a gastric dissolution and can enter directly into the small bowel where L-T4 is absorbed [8–11]. Here we report three cases of patients with severe hypothyroidism and persistent TSH increase despite the administration of high doses of tablet L-T4. Hypothyroidism suddenly improved and euthyroidism was progressively restored in these patients after sublingual administration of L-T4 in liquid formulation.

Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis

Background Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto’s thyroiditis (HT) and SSc. Case report Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. Conclusion A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

Importance of recombinant human thyrotropin as an adjuvant in the radioiodine treatment of thyroid cancer

ABSTRACT Introduction: Radioiodine (RAI) therapy for treatment of differentiated thyroid cancer (DTC) requires high serum thyroid-stimulating hormone (TSH) levels to induce a sufficient iodine uptake within thyroid cells. Recombinant Human TSH (rhTSH) induces an exogenous TSH level increase without LT4 withdrawal. It is a valid alternative to LT4-withdrawal (LT4-W) to achieve the TSH levels required for RAI therapy. According to the recent American Thyroid Association (ATA) guidelines, candidates for RAI therapy should be selected based on their DTC risk of recurrence. Areas covered: In this review, we report the studies assessing the effects of rhTSH on RAI ablation compared to thyroid hormone withdrawal in patients with thyroid cancer at different ATA risk of recurrence. We focus our attention on high risk patients and metastatic disease in which RAI treatment is routinely recommended although there are few controversial data about the best possible way of preparing for it. Expert commentary: rhTSH-aided therapy is associated to a better quality of life and to a lower body radiation exposure. Several studies have reported an equivalent efficacy of RAI ablation after TSH stimulation with rhTSH or LT4-W in patients with DTC at low and intermediate risk of recurrence. Although more studies are required, the results are promising even in patients with high risk DTC and metastatic disease.