Loredana Pagano

Thyroid incidentaloma identified by 18F-fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT): clinical and pathological relevance

Objective  The percentage of patients with thyroid cancer incidentally diagnosed during a 18F‐fluorodeoxyglucose Positron Emission Tomography with computed tomography (CT) (FDG‐PET/CT) for nonthyroid diseases ranges between 26% and 50%.

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).

Hypopituitarism following brain injury: when does it occur and how best to test?

Aim of this review is to highlight how and when Traumatic Brain Injury (TBI) as well as Subarachnoid Haemorrhage (SAH) and primary Brain Tumours (pBT) of the Central Nervous System (CNS) can induce hypopituitarism, an under-diagnosed clinical problem. Moreover, this review aims to clarify, on the basis of the recent evidences, how these patients have to be tested for pituitary-function. Both retrospective and prospective studies recommended that patients with more severe form of Brain Injuries (BI) and in particular, those with fractures of the base of the skull or early diabetes insipidus, have to be closely monitored for signs and symptoms of endocrine dysfunction. Further studies will be crucial to raise awareness and remind physicians on the prevalence of hypopituitarism in patients with BI and to elucidate any incremental benefits these patients may receive from hormone replacement.

Autophagy and thyroid carcinogenesis: genetic and epigenetic links

Thyroid cancer is the most common cancer of the endocrine system and is responsible for the majority of deaths from endocrine malignancies. Although a large proportion of thyroid cancers belong to well differentiated histologic subtypes, which in general show a good prognosis after surgery and radioiodine ablation, the treatment of radio-resistant papillary-type, of undifferentiated anaplastic, and of medullary-type thyroid cancers remains unsatisfactory. Autophagy is a vesicular process for the lysosomal degradation of protein aggregates and of damaged or redundant organelles. Autophagy plays an important role in cell homeostasis, and there is evidence that this process is dysregulated in cancer cells. Recent in vitro preclinical studies have indicated that autophagy is involved in the cytotoxic response to chemotherapeutics in thyroid cancer cells. Indeed, several oncogenes and oncosuppressor genes implicated in thyroid carcinogenesis also play a role in the regulation of autophagy. In addition, some epigenetic modulators involved in thyroid carcinogenesis also influence autophagy. In this review, we highlight the genetic and epigenetic factors that mechanistically link thyroid carcinogenesis and autophagy, thus substantiating the rationale for an autophagy-targeted therapy of aggressive and radio-chemo-resistant thyroid cancers.

Pituitary Metastases from Follicular Thyroid Carcinoma

BACKGROUND Metastatic carcinomas to the pituitary gland are uncommon, occurring in only 1% of the pituitary masses. They often originate from breast or lung carcinomas and may resemble a nonfunctioning pituitary adenoma both clinically and radiologically. Here we describe a patient with pituitary metastasis from follicular thyroid carcinoma and discuss the unique features of these lesions. SUMMARY A 45-year-old woman was admitted to the emergency rescue room of our hospital with a 2-month history of progressive headache and blurred vision. Evaluation revealed right eye amaurosis, with a mild abducens and oculomotor palsy. Pituitary magnetic resonance imaging showed a mass that was hypo-intense in T1-weighted and hyper-intense in T2-weighted-images, located from the sphenoid sinus up to chiasmatic cisterns, raising and deflecting the optic chiasm, down to hypopharynx region, and distorting the cavernous sinuses. No evidence of anterior or posterior hypopituitarism was recorded. The immediate trans-sphenoidal surgery was uncomplicated with partial improvement of the visual fields and headache. Histopathology revealed a metastasis with well-differentiated follicular thyroid architecture. Total thyroidectomy and lymph node dissection was performed with a final histopathological diagnosis of follicular thyroid carcinoma. Subsequently, her headache became more severe. 131-I ablation treatments were performed 15 days and 12 months after thyroidectomy with decrease in headache and a decline in serum thyroglobulin levels. CONCLUSIONS Pituitary metastases from thyroid carcinoma are very uncommon. As this patient illustrates, they tend to produce symptoms relating to space-occupying expansion in the parasellar region rather than to those due to destruction of the pituitary gland. Although rare, pituitary metastases caused by thyroid malignancy should be considered in patients with expanding parasellar lesions if they have thyroid cancer or uncharacterized thyroid diseases. They are unlikely to be amenable to complete resection and should be considered for 131-I treatment, perhaps avoiding the need for extensive neurological surgery.

8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2)

Differentiated thyroid cancer (DTC) has become one of the most frequently diagnosed malignancies, especially among women and young adults (Davies & Welch 2014). The outcomes are generally very good: disease recurrence rates are low (Durante et al. 2013), and survival rates are excellent (Tuttle et al. 2017a). Evidence-based management is crucial to avoid overtreatment of these low-risk tumors, which can reduce quality of life and yet identify accurately those requiring more aggressive therapy. Several staging systems have been generated to inform DTC management. One of the most widely used is the tumor-node-metastasis (TNM) classification elaborated by the American Joint Committee on Cancer (AJCC), which allows to predict the risk of cancer-related death. The 8th edition of the AJCC staging system for thyroid cancer (AJCC-8) was recently published (Tuttle et al. 2017b) and is scheduled to be implemented on 1 January 2018. Revision of the system was undertaken to address several specific limitations identified in the 7th edition (AJCC-7), which has been in use since 2009 (Tuttle et al. 2017a,b). The main changes (described in detail below and summarized in Table 1) are as follows: (1) an increase in the age threshold for defining high risk of thyroid cancer-related death and (2) a decrease in the unfavorable prognostic significance attributed to certain findings (i.e., cervical lymph node metastases and microscopic extrathyroidal extension (ETE), which has been re-defined to include only invasion of the perithyroidal muscle). To assess the impact of transitioning to the new AJCC-8 in terms of stage distribution and prevalence of each stage class, we analyzed data extracted from the web-based database of the Italian Thyroid Cancer Observatory (ITCO) (www.itcofoundation.org), a network of thyroid cancer centers (including primary and tertiary centers) located throughout Italy. The database includes prospectively updated, observational data provided by ITCO member centers on patients consecutively diagnosed with thyroid cancer since 2013 (Lamartina et al. 2017). Cases included in our study met all the following criteria: (1) histological diagnosis of thyroid cancer of follicular origin; (2) date of diagnosis between 1 January 2013 and 1 March 2017; (3) complete data on primary tumor pathology, including minimal ETE, and initial treatment. The selected cohort analyzed included 1765 patients, 76% of whom were females. The median age at diagnosis was 48 years (range: 10–87). Total thyroidectomy (or lobectomy + completion thyroidectomy) was performed in 1727 (98%) cases and followed by radioiodine remnant ablation in 954 (55%). Neck dissection was performed in 711 (40%) of the 1765 patients. Most of the tumors (n = 1657, 94%) were papillary thyroid cancers; the remaining 108 (6%) were follicular or Hürthle cell carcinomas. Estimated risks of recurrence calculated according to the criteria recommended in 2015 by the American Thyroid Association were low in 1046 (59%), intermediate in 612 (35%) and high in 107 (6%) of the cases. Microscopic ETE was found in 410 (23%), but only 40 (2%) of these patients had gross invasion of the strap muscles (sternohyoid, sternothyroid, thyroidhyoid and/or omohyoid muscles). Lymph node status for the 711 patients who underwent lymph node dissection was as follows: pN0 (no metastasis) in 338 (19%); pN1a (central compartment metastases) in 221 (12%) and pN1b (lateral compartment metastases) 152 (9%). Distant metastases were found in 32 (1.8%) patients. As noted above, in the AJCC-8, the age threshold for high risk of disease-specific mortality was raised from 45 years – the median age at diagnosis in several published series – to 55 years (Nixon et al. 2016). This change increases the proportion of relatively young patients whose mortality risk can be defined solely on the basis of the absence or presence of distant metastases (stages I and II, respectively) (Table 1). As shown in Fig. 1A, the percentage of patients classified as ‘younger’ in our 3 25

Screening in von Hippel-Lindau disease: concurrent pheochromocytomas, paragangliomas and spinal hemangioblastomas revealed by helical-CT, MIBG scintigraphy and MRI in an asymptomatic patient

Abstract Early detection of visceral as well as neurological abnormalities in von Hippel-Lindau (VHL) disease is highly recommended and usually accomplished by a combination of radiological and nuclear medicine techniques. We report a case of an asymptomatic 30-year-old male with VHL disease who was found to have concurrent bilateral pheochromocytomas, a carotid body tumor, sacral para-gangliomas and spinal hemangioblastomas during a screening performed by contrast-enhanced helical computed tomography, 131I-metaiodobenzylguanidine scintigraphy and magnetic resonance imaging. Despite their common embriogenetic origin from the neural crest, the concurrence of pheochromocytomas and para-gangliomas in VHL disease is rare. Although frequently asymptomatic, the occurrence of spinal hemangioblastomas in the clinical context of the screening has not been previously reported.

Baseline glucose homeostasis predicts the new onset of diabetes during statin therapy: A retrospective study in real life

OBJECTIVEWe evaluated the risk of altered glucose levels and new-onset diabetes (NOD) associated with statins according to glucose levels at baseline in a population treated for dyslipidemia on primary prevention for >5 years. DESIGN. The retrospective study included 308 subjects (265 on statins and 43 controls on diet) with a follow-up of 5–15 years. The cohort was classified according to glucose tolerance at both baseline and follow-up.RESULTSThe cumulative incidence of NOD was 13.6% (9.3% in controls and 13.5% in treated patients). NOD was diagnosed after 3.4±1.8 years. In the group with normal glucose levels at baseline, a family history of diabetes (OR: 3.4, 95% CI 1.3–8.9), BMI >30 kg/m2 (OR: 8.5, 95% CI 2.0–35.8), treatment with thiazide (OR: 21.9, 95% CI 1.2–384.2) and no alcohol consumption (OR: 0.3, 95% CI 0.1–0.8) reduced the risk of developing altered glucose levels or NOD. No effects of statins were seen. In the group with altered glucose levels at baseline, hypertension (OR: 5.0, 95% CI 1.0–25.3) and hypertriglyceridemia (OR: 3.5, 95% CI 1.0–11.8) increased the risk of remaining with altered glucose levels or developing NOD. Treatment with statins (OR: 7.5, 95% CI 1.5–37.4), in particular atorvastatin, was associated with an increased risk. In the whole population, statin therapy (OR: 4.0, 95% CI 1.1–14.1, p<0.020), and in particular simvastatin and atorvastatin, was associated with increased risk of altered glucose levels or NOD. Patients who developed or maintained altered glucose levels or NOD had a poor metabolic phenotype at baseline.CONCLUSIONSStatins were associated with an increased risk of NOD or altered glucose levels, mainly in subjects with altered glucose levels before the beginning of therapy. Poor metabolic phenotype and unhealthy behaviors or family history of diabetes contributed to that risk.

Unusual metastases from tall cell variant of papillary thyroid cancer

Tall cell variant (TCV) cancer is considered more aggressive than the classic variant of papillary thyroid cancer (PTC). Distant metastases are more common among this variant and affect survival. Little is known about the molecular pattern of this histotype.

Adjuvant treatment with thyrotropin alpha for remnant ablation in thyroid cancer

Various studies have demonstrated the safety and efficacy of recombinant human thyroid-stimulating hormone (rhTSH) for radioiodine remnant ablation. On this basis, rhTSH was approved in Europe for the radioiodine ablation of low-risk differentiated thyroid cancer (DTC) during thyroid hormone therapy with L-thyroxine (L-T4). Moreover, in December 2007, the US Federal Drug Administration approved the use of rhTSH for adjuvant treatment with radioiodine in patients with DTC without evidence of metastatic thyroid cancer. Quality of life was found to be better with rhTSH preparation than with L-thyroxine withdrawal, thereby resulting in benefits for society as a whole. Furthermore, rhTSH for radioiodine remnant ablation results in a longer effective radioiodine half-life within remnant thyroid tissue and a lower specific absorbed dose in the blood and exposure of bone marrow to X-rays. More studies are required to establish the amount of radioiodine to be administered especially in high-risk patients.