Chiara Carzaniga

Elastosonographic evaluation of thyroid nodules in acromegaly

OBJECTIVE Ultrasound-elastography (US-E) appears to be a helpful tool for the diagnosis of thyroid cancer. In acromegaly, the prevalence of thyroid cancer is still debated. The aims of this study were to evaluate thyroid nodules in acromegaly and to establish the accuracy of US-E in providing information on their nature, using cytological analysis as a reference. SUBJECTS AND METHODS US-E was applied to 90 nodules detected in 25 acromegalic patients and to 94 nodules found in 31 non-acromegalic goitrous subjects. The lesions were classified according to the elasticity scores (ES) as soft (ES 1-2) or hard (ES 3-4). Fine needle aspiration cytology could be performed in 60.8% of hard nodules in acromegalics and in 86.7% of hard nodules in controls. RESULTS The prevalence of hard nodules was significantly higher in the whole group of acromegalic patients than in controls (56.8 vs 16.0%, P<0.0001). The prevalence of hard nodules in patients with active acromegaly (68.9%) was greater, though not to a statistically significant extent, than that observed in cured (44.4%) and controlled (52.5%) patients. Cytology revealed malignancy or suspect malignancy in four of the nodules of non-acromegalic subjects and in none of the nodules of acromegalic patients. CONCLUSIONS This study has demonstrated a high prevalence of stiff thyroid nodules in acromegaly, greater than that found in non-acromegalic goitrous subjects. In acromegalics, hard nodules appeared not to be malignant on cytopathological examination and are probably of fibrous nature. Thus, US-E appears to be of limited value for the diagnosis of thyroid cancer in acromegaly.

Standardized Ultrasound Report for Thyroid Nodules: The Endocrinologist's Viewpoint

Background: Ultrasonography (US) plays a crucial role in the diagnostic management of thyroid nodules, but its widespread use in clinical practice might generate heterogeneity in ultrasound reports. Objectives: The aims of the study were to propose (a) a standardized lexicon for description of thyroid nodules in order to reduce US reports of interobserver variability and (b) a US classification system of suspicion for thyroid nodules in order to promote a uniform management of thyroid nodules. Methods: Relevant published articles were identified by searching MEDLINE at PubMed combining the following search terms: ultrasonography, thyroid, nodule, malignancy, carcinoma, and classification system. Results were supplemented with our data and experience. Results: A standardized US report should always document position, extracapsular relationships, number, and the following characteristics of each thyroid lesion: shape, internal content, echogenicity, echotexture, presence of calcifications, margins, vascularity, and size. Combining the previous US features, each thyroid nodule can be tentatively classified as: malignant, suspicious for malignancy, borderline, probably benign, and benign. Conclusions: We propose a standardized US report and a tentative US classification system that may become helpful for endocrinologists dealing with thyroid nodules in their clinical practice. The proposed classification does not allow to bypass the required cytological confirmation, but may become useful in identifying the lesions with a lower risk of neoplasm.

Thyroid nodules in acromegaly: The role of elastography

INTRODUCTION Ultrasound elastography (US-E) is a helpful tool for the diagnosis of thyroid cancer. In acromegaly, multinodular goiter is a common occurrence while the prevalence of thyroid cancer is still matter of debate. Our aims were to evaluate thyroid nodules in acromegaly and to assess the accuracy of US-E in providing information on their nature (benign vs. malignant) using cytological analysis as a reference. MATERIALS AND METHODS US-E was performed in 25 patients with acromegaly (active in 10 cases, medically controlled in 8, and cured by pituitary surgery in 7), each of whom had at least one solid thyroid nodule. A total of 90 nodules were classified according to the elastography scores (ES): ES1 and ES2 for soft nodules, ES3 and ES4 for an elastic lesions. FNAC was performed in 78.6% of the ES 4 lesions and 54.1% of the ES 3 nodules. RESULTS Fourteen of the 90 nodules (15.5%) displayed an ES of 1, 25 (27.7%) an ES of 2, 37 (41.3%) an ES of 3, and 14 (15.5%) an ES of 4. The prevalence of hard nodules in patients with active acromegaly (68.9%) was greater than that observed in patients with cured (44.4%) or controlled (52.5%) acromegaly. The prevalence of hard nodules in the total series (56.7%) was higher than that reported in nonacromegalic goitrous subjects. All thyroid nodules subjected to FNAC were negative for malignant cells and follicular lesions. DISCUSSION Acromegaly (particularly active forms) is associated with a high prevalence of stiff thyroid nodules that exceeds that observed in nonacromegalic patients with goiters (33.7%). However, these nodules were never malignant at cytology, and their firmness is probably due to fibrosis. US-E therefore appears to be of limited value for the diagnosis of thyroid cancer in patients with acromegaly.

Decreased adrenergic tone in acromegaly: evidence from direct recording of muscle sympathetic nerve activity

Sympathovagal imbalance has been shown in acromegaly by indirect measurements of adrenergic tone. Data regarding direct measurement of sympathetic activity are lacking as yet. Aim of this study was to assess the adrenergic tone through direct recording of muscle sympathetic nerve activity (MSNA) in acromegalic patients.

Differential patterns of regional neuroadrenergic cardiovascular drive in acromegalic disease.

It has been shown that acromegaly is characterized by an autonomic imbalance and by marked sympathoinhibition. However, there is no information available as to whether adrenergic inhibition is confined to selected vascular districts or, rather, is generalized. We examined 17 newly diagnosed active acromegalic patients without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy and 14 healthy subjects matched for age, sex and body mass index. For each subject, we collected information regarding anthropometric parameters and echocardiography, and collected plasma samples to investigate anterior pituitary function, glucose and lipid metabolism and plasma leptin levels. Beat‐to‐beat mean arterial pressure, heart rate and efferent post‐ganglionic muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively; determined by microneurography) were measured. Both MSNA and SSNA were recorded in a randomized sequence over two 30 min periods. Measurements also included evaluation of SSNA responses to emotional stimulus. In addition to significant reductions in plasma leptin levels, acromegalic patients had markedly decreased MSNA compared with the healthy controls. There were no significant differences in SSNA between the two groups, either under basal conditions or in responses to arousal stimuli. There was a significant and direct correlation between MSNA and plasma leptin levels, but not between plasma leptin and SSNA. These data provide the first evidence that the sympathetic inhibition characterizing the early phase of acromegaly is not generalized to the entire cardiovascular system.

Assessment of biochemical control of acromegaly during treatment with somatostatin analogues by oral glucose load and insulin-like growth factor I

Background: The use of oral glucose tolerance test (OGTT) in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) has recently been questioned. Aim: To gain further insights into this topic, we analyzed basal and nadir GH levels during OGTT in acromegalic patients on SSA. Subjects and methods: Basal IGF-I and GH values, as well as GH levels along the test, were analyzed in 115 standard OGTT performed in 33 acromegalic patients followed up between 1993 and 2009. All patients were on SSA at the time of the study; 22 of them had previously undergone unsuccessful surgery. No patient had undergone radiotherapy. GH suppression was considered normal when the hormonal value fell to <1 µg/l during OGTT. Diagnostic accuracy was analyzed by receiver operating characteristic (ROC) curves. Results: ROC analysis showed that the GH basal value yielding the best specificity (100%) was 3.9 µg/l. All patients with basal GH>3.9 µg/l displayed lack of GH suppression after OGTT and 80% also displayed high IGF-I. Conversely, patients with basal GH<3.9 µg/l presented a variable biochemical pattern with half of them failing to suppress GH after OGTT and 36.6% displaying high IGF-I levels. Conclusions: Our results show that baseline GH levels >3.9 µg/l are predictive of absent OGTT-dependent GH suppression; however, 20% of these patients display partial biochemical control (normal IGF-I levels). On the other hand, basal GH values <3.9 µg/l are not predictive of GH suppressibility by glucose and are often discordant with IGF-I levels.

Effects of somatostatin analogues on muscle sympathetic nerve activity in acromegaly

muscle sympathetic nerve activity (MSNA), in spite of insulin resistance (Seravalle et al., Clin Endocrinol 77:262, 2012). Our data pointed to a phenomenon mediated by hypoleptinaemia rather than a direct action of the GH-IGF-I system. Aim: It has been shown that centrally administered somatostatin (SS) inhibits peripheral sympathetic outflow in rodents (Rettig et al., Am J Physiol 257:R588, 1989). Based on the above, we elected to study MSNA in acromegalic patients before and during treatment with SS analogues (SSA)

La gestione clinica del paziente con ipoparatiroidismo post-chirurgico

RiassuntoIdati epidemiologici indicano che l’ipoparatiroidismo post-chirurgico è la più frequente tra le complicanze della chirurgia tiroidea. Si manifesta in percentuale variabile a seconda della casistiche, e può essere transitorio o permanente. Il rischio di sviluppare ipocalcemia post-operatoria dipende principalmente dalla indicazione chirurgica (rischio superiore per malattia di Graves, inferiore in caso di carcinoma e di gozzo nodulare) e dalla estensione chirurgica (inferiore per tiroidectomia totale, superiore per svuotamento linfatico del compartimento centrale e del compartimento laterale). Non sono disponibili indicatori affidabili in grado di prevedere quali pazienti ipoparatiroidei lo rimarranno in modo stabile e quali invece recupereranno una normale funzione paratiroidea. Il trattamento si basa essenzialmente sulla somministrazione in dosi adeguate di calcitriolo e di calcio per via orale. La somministrazione endovenosa di calcio è riservata ai casi di ipocalcemia severa sintomatica. Normalmente si inizia il trattamento se la calcemia scende sotto i 7,8-8 mg/dl. I valori di calcemia vengono monitorati ogni 3–7 giorni, modificando la posologia dei farmaci in accordo con l’andamento della calcemia. Nella maggior parte dei casi l’ipoparatiroidismo è transitorio, ed è possibile ridurre progressivamente l’apporto esogeno di calcio e vitamina D fino a sospensione completa (strategia “reattiva”). Questo è l’atteggiamento più diffuso, e comporta un certo numero di ipocalcemie sintomatiche. è stato riportato che un dosaggio di PTH eseguito 6 ore dopo la tiroidectomia è un indicatore affidabile dello sviluppo di successiva ipocalcemia. Qualora l’organizzazione locale consenta di disporre di questo dato, pertanto, è possibile iniziare trattamento precoce con calcitriolo/calcio in caso di riduzione del PTH di più del 90% rispetto al valore basale (strategia “predittiva”). In alcuni Centri si procede a iniziare la somministrazione di calcitriolo/calcio a tutti i pazienti operati, a prescindere dai valori e dall’andamento della calcemia (strategia “preventiva”), evitando così l’insorgenza di ipocalcemia ma trattando anche pazienti che non ne avrebbero avuto necessità. Una scelta operativa pratica può essere di adottare la strategia reattiva, riservando la strategia preventiva ai casi ad alto rischio di sviluppo di successiva ipocalcemia.