Michele Zini

Italian consensus for the classification and reporting of thyroid cytology

Thyroid nodules are diagnosed with increasing frequency in clinical practice. The first step in the management of patients presenting with thyroid nodules is an accurate triage of those who should be referred to surgery [1–5]. In spite of the advances in ultrasound (US) imaging [6–8] and the promising results of molecular analysis [9–16], this basic step still strongly relies on cytology [3]. Among the acronyms used to indicate the sampling technique for thyroid cytology (FNA, FNAB, FNAC, FNC), fine-needle aspiration (FNA) is the most frequently adopted and it will be employed in this document. When the cytologic specimen is obtained without aspiration the term FNC (fine-needle cytology) may be used [2]. In the recent years, a variety of fourto six-tiered reporting schemes for thyroid cytology have been proposed by different societies and institutions, with the aim of improving the communication between cytopathologists and clinicians [17]. With the aim to standardize the diagnostic terminology in thyroid FNA, in 2007 the United States National Cancer Institute (NCI) has proposed a reporting system for thyroid cytology based on the NCI Thyroid FNA State-Of-Science Consensus Conference [18]. This system has gained wide diffusion and the atlas ‘‘The Bethesda System for Reporting Thyroid Cytology’’ (BSRTC) provided well-defined criteria with exhaustive explanatory notes [19]. Following the recommendations of the 2009 European Federation of Cytology Societies (EFCS) symposium aiming at the worldwide unification of the reporting systems for thyroid cytology [20], a working group of the Royal College of Pathologists (RCPath) updated the reporting system already in use in UK since 2007 [21] using criteria that are similar to those used in BSRTC [22]. In Italy, a 5-tiered classification, proposed in 2007 by the Italian Society for Anatomic Pathology and Cytology joint with the Italian Division of the International Academy of Pathology (SIAPEC-IAP) [2], is currently used by most institutions. In 2012 the Italian Societies of Endocrinology, i.e., the Italian Thyroid Association (AIT), the Italian Association of Clinical Endocrinologists (AME), the Italian Society of Endocrinology (SIE) and the SIAPEC-IAP appointed a working panel of experts to update the former consensus in line with the indications of the EFCS. The present document provides a reporting scheme for thyroid cytology and the suggested clinical actions. This Consensus is not meant to address in detail all the morphological All authors contributed equally to this work.

Melatonin stimulates growth hormone secretion through pathways other than the growth hormone‐releasing hormone

OBJECTIVE There is evidence that melatonin plays a role in the regulation of GH secretion. The aim of this study was to investigate the neuroendocrine mechanisms by which melatonin modulates GH secretion. Thus we assessed the effect of oral melatonin on the GH responses to GHRH administration and compared the effects of melatonin with those of pyridostigmine, a cholinergic agonist drug which is likely to suppress hypothalamic somatostatin release.

ALPHA‐2‐ADRENERGIC PATHWAYS RELEASE GROWTH HORMONE VIA A NON‐GRF‐DEPENDENT MECHANISM IN NORMAL HUMAN SUBJECTS

Administration of a supramaximal dose of GRF 1‐44 (200 μg, i.v.) to normal human volunteers increased GH levels while a further bolus of GRF (200 μg i.v.) given 2 hours later failed to increase plasma GH levels. In contrast, alphaadrenergic receptor agonism with either propranolol‐adrenaline infusion or clonidine increased plasma GH levels at a time when GH responses to this supramaximal dose of GRF were absent. This indicates that alpha‐adrenergic pathways stimulate GH secretion through a non‐GRF‐dependent mechanism in normal human subjects.

Detection and diagnosis of parathyroid incidentalomas during thyroid sonography.

The aim of our study was to evaluate the incidence of incidentally found parathyroid adenomas (incidentalomas) in patients undergoing sonography of the neck for thyroid disease.

Influence of hyperthyroidism on growth hormone secretion

OBJECTIVE Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue.

Association of elevated insulin-like growth factor binding protein-1 with insulin resistance in hyperthyroidism

Insulin‐like growth factor binding‐protein‐1 (IGFBP‐1) has a role in glucose homeostasis and is present at high concentrations in hyperthyroidism. We have investigated the relationship between IGFBP‐1 concentration and glucose homeostasis in hyperthyroidism.

Effect of pyridostigmine and pirenzepine on GH responses to GHRH in hyperthyroid patients

Summary. objective We wished to investigate whether thyrotoxicosis can influence the cholinergic modulation of GH secretion.

Triiodothyronine administration reduces serum growth hormone levels and growth hormone responses to thyrotropin-releasing hormone in patients with anorexia nervosa

The aim of this study was to test the hypothesis that low serum T3 concentrations may promote an abnormal growth hormone (GH) response to thyrotropin-releasing hormone (TRH) in patients with anorexia nervosa. Eight anorexic women and two anorexic men, ages 15-25 years, with low free T3 circulating levels (mean +/- SEM = 2.8 +/- 0.3 pmol/l) were studied. A TRH test (200 micrograms IV) was carried out under basal conditions and repeated following treatment with oral T3 (1.5 micrograms/kg BW/day) for eight days. Following T3 administration, GH levels dropped significantly from a baseline of 7.1 +/- 1.3 micrograms/l to 3.1 +/- 0.7 micrograms/l (p less than 0.02), as did GH peak responses to TRH (9.0 +/- 1.0 micrograms/l vs 4.4 +/- 0.8 micrograms/l, p less than 0.01). ANOVA and analysis of area under the curve (AUC) confirmed that after T3 treatment there was a significant reduction in TRH-induced GH release in these patients (GH AUC: 902 +/- 132 micrograms/l vs. 456 +/- 91 micrograms/l, p less than 0.02). TSH responses to TRH, which were normal prior to T3 treatment, completely disappeared following it, and PRL responses to TRH also were diminished. Although our experimental approach does not permit a conclusion that low T3 levels were the primary reason for these changes, the data support the theory that low T3 circulating levels may facilitate abnormal GH secretion and the GH-releasing activity of intravenous TRH.

Lateral neck recurrence from papillary thyroid carcinoma: Predictive factors and prognostic significance.

The aim of this study was to identify any possible predictive factors of lateral neck recurrence in patients with papillary thyroid carcinoma with no ultrasonographic and/or cytological evidence of lymph node metastasis at time of diagnosis. The influence of lateral neck recurrence on survival was also investigated.

The late growth hormone rise induced by oral glucose is enhanced by cholinergic stimulation with pyridostigmine in normal subjects.

OBJECTIVE We have investigated the late GH rise occurring 3–5 hours after oral glucose administration. We have assessed the effect of endogenous cholinergic enhancement with pyridostigmine on the delayed GH rise following oral glucose loading in normal subjects.