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L’amiodarone è un antiaritmico che esercita importanti effetti sulla fisiologia tiroidea e nel 20% dei casi determina lo sviluppo di ipotiroidismo o di tireotossicosi. La tireotossicosi indotta da amiodarone (AIT) è gravata da alti tassi di morbidità e mortalità, dovuti alla lunga esposizione di un cuore “malato” a un importante eccesso di ormoni tiroidei spesso poco responsivo alla terapia medica. Negli ultimi anni recenti acquisizioni in tema di diagnosi e terapia hanno permesso un approccio più moderno all’AIT.

Fewer than 100 cases of amiodarone-induced thyrotoxicosis (AIT) managed surgically have been reported worldwide. This study aims to assess the outcome of thyroidectomy under general anesthesia in a relatively large case series. A retrospective analysis of the clinical records of 53 patients who underwent thyroidectomy for AIT between 1995 and 2019 was conducted. There were 48 (90%) males and 5 females with an average age of 63.7 years. Type 1 and 2 AIT were present in 35 (66%) and 18 (34%) of patients, respectively. The mean preoperative ejection fraction (EF) was 45 ± 13%. Salvage surgery was performed in 6 (11%) patients due to decompensating heart failure and/or malignant arrhythmias. 35 (66%) patients underwent urgent surgery due to a predicted late response to medical therapy and/or the need to discontinue it. Elective surgery was performed in the remainder. A considerable improvement in mean EF occurred 12 months post-surgery (44% vs. 49%; p< 0.001). The overall survival rate following thyroidectomy was 96% at 12 months, and 83% at 5 years. No survival differences were observed based on systolic function. Cardiac-specific mortality was 11%, and these patients demonstrated a considerably shorter survival post-surgery compared to those who died of a non-cardiac cause (27 ± 18 vs. 77.5 ± 54 months; p< 0.05). Total thyroidectomy can be safely performed under general anesthesia despite severe cardiac disease. It considerably improves cardiac function and confers a survival advantage. Therefore, it should be considered early in the treatment plan of select cases.

PEIR is a rare, possibly dysembriogenetic, anomaly of the pituitary stalk. Awareness of this clinical entity is of paramount importance to correctly diagnose cystic lesions of the sellar region.

Treatment with amiodarone is associated with changes in thyroid function tests, but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in apparently normal thyroid glands or in the presence of underlying thyroid abnormalities. AIH does not require amiodarone withdrawal, and is treated with levothyroxine replacement if overt, whereas subclinical forms may be followed without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a form of iodine-induced hyperthyroidism occurring in nodular goitres or latent Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic mechanisms. AIT 1 is best treated with thionamides that may be combined for a few weeks with sodium perchlorate to make the thyroid gland more sensitive to thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has been restored, AIT 2 patients are followed up without treatment, whereas AIT 1 patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite forms of AIT are treated with thionamides. Oral glucocorticoids can be added from the beginning if a precise diagnosis is uncertain, or after a few weeks if response to thionamides alone is poor. The decision to continue or to stop amiodarone in AIT should be individualized in relation to cardiovascular risk stratification and taken jointly by specialist cardiologists and endocrinologists. In the presence of rapidly deteriorating cardiac conditions, emergency thyroidectomy may be required for all forms of AIT.

Treatment with amiodarone is associated with changes in thyroid function tests, but also with thyroid dysfunction (amiodarone-induced hypothyroidism, AIH, and amiodarone-induced thyrotoxicosis, AIT). Both AIH and AIT may develop in apparently normal thyroid glands or in the presence of underlying thyroid abnormalities. AIH does not require amiodarone withdrawal, and is treated with levothyroxine replacement if overt, whereas subclinical forms may be followed without treatment. Two main types of AIT are recognized: type 1 AIT (AIT 1), a form of iodine-induced hyperthyroidism occurring in nodular goitres or latent Graves disease, and type 2 AIT (AIT 2), resulting from destructive thyroiditis in a normal thyroid gland. Mixed/indefinite forms exist due to both pathogenic mechanisms. AIT 1 is best treated with thionamides that may be combined for a few weeks with sodium perchlorate to make the thyroid gland more sensitive to thionamides. AIT 2 is treated with oral glucocorticoids. Once euthyroidism has been restored, AIT 2 patients are followed up without treatment, whereas AIT 1 patients should be treated with thyroidectomy or radioiodine. Mixed/indefinite forms of AIT are treated with thionamides. Oral glucocorticoids can be added from the beginning if a precise diagnosis is uncertain, or after a few weeks if response to thionamides alone is poor. The decision to continue or to stop amiodarone in AIT should be individualized in relation to cardiovascular risk stratification and taken jointly by specialist cardiologists and endocrinologists. In the presence of rapidly deteriorating cardiac conditions, emergency thyroidectomy may be required for all forms of AIT.

L’ipofisite autoimmune deve essere presa in considerazione nella diagnosi differenziale delle masse ipofisarie, in particolare l’adenoma, da cui si distingue per alcune caratteristiche epidemiologiche, cliniche e neuroradiologiche. È l’unica lesione ipofisaria che può beneficiare della terapia con farmaci immunosoppressivi, pertanto una corretta diagnosi clinica potrebbe evitare un intervento chirurgico non necessario. Negli ultimi anni, con l’avvento di terapie oncologiche atte a potenziare la risposta immunitaria, l’incidenza dell’ipofisite autoimmune è aumentata.

Background: Thyrotropin (TSH)–secreting pituitary adenoma (TSHoma) and resistance to thyroid hormone (RTH) are two forms of inappropriate TSH secretion. Thyroid blood flow is largely TSH dependent. Objective: To assess whether thyroid blood flow may help to differentiate TSHoma and RTH. Design: Intrathyroidal color flow Doppler sonography (CFDS) pattern and peak systolic velocity (PSV) were assessed at baseline and during T3suppression test on eight consecutive patients with TSHoma and 10 with RTH. Main outcome: All controls had CFDS pattern 0. Three RTH patients had pattern I and seven had pattern II. Two TSHoma patients had pattern I, five had pattern II, and one had pattern III. PSV at baseline was 3.8 ± 1.3 cm/s in controls, 8.8 ± 2.5 cm/s in RTH, 11.1 ± 2.7 cm/s in TSHoma (p< 0.0003 vs. controls, p= 0.087 RTH vs. TSHoma). After T3 suppression test, PSV values were lower in RTH than in TSHoma (4.6 ± 1.8 vs. 7.7 ± 2.6 cm/s, p= 0.008). PSV values and CFDS pattern normalized in nine and eight RTH patients, respectively, after T3suppression test; conversely, only one TSHoma patient had a normalization of PSV values, and none had a normalization of CFDS pattern (p< 0.003 vs. RTH). Conclusions: Both RTH and TSHoma have increased CFDS pattern and PSV values; however, after T3both parameters normalized in most patients with RTH but not in those with TSHoma. Accordingly, CFDS pattern and PSV are adjunctive tools to differentiate these two forms of inappropriate TSH secretion.

Objective: To investigate, in a large group of postmenopausal primary hyperparathyroidism (PHP) women, whether the concomitance of GH deficiency (GHD) may contribute to the development of changes in bone mineral density (BMD).Design: GH secretion, bone status and metabolism were investigated in 50 postmenopausal women with PHP and in a control group of 60 women with no evidence of PHP, matched for age, age at menopause and body mass index (BMI).Methods: GH response to growth hormone-releasing hormone (GHRH)+arginine (Arg), femoral neck BMD (g/cm2) by dual energy X-ray absorptiometry, BMI, serum-ionized calcium, parathyroid hormone (PTH) and markers of bone remodelling were evaluated in all patients and controls.Results: Among PHP patients, GH secretion was reduced (8.8 ± 4.2 μg/l, range 1.1–16.5 μg/l) in 34 patients and normal (28.7 ± 11.8 μg/l, range 17.9–55.7 μg/l) in the remaining 16 (P< 0.05), no women in the control group had GHD (peak GH 33.8 ± 10.9 μg/l, range 21.7 ± 63.2 μg/l). Osteoporosis (T-score < − 2.5) and osteopenia (T-score > −2.5 and < −1) were found in 73.5 and 17.6% of GHD patients, in 37.5 and 43.7% of patients with normal GH secretion and 3.1 and 27% of controls. T-score and BMD were not correlated with ionized calcium, age, age at menopause, BMI, GH peak and IGF-I but were correlated with serum PTH levels in both groups. T-score was correlated with serum levels of markers of bone remodelling only in PHP patients with GHD.Conclusions: Concomitant impairment of GH secretion may play a pathogenetic role in the occurrence of changes in bone mass observed in PHP and contribute to make them more severe.

Pharmacological treatment, usually by thionamides (carbimazole, methimazole, propylthiouracil) is, in addition to radioiodine therapy and thyroidectomy, one of the available therapies for Graves’ hyperthyroidism. Thionamides represent the treatment of choice in pregnant women, during lactation, in children and adolescents and in preparation for radioiodine therapy or thyroidectomy. Side effects are relatively frequent but are in general mild and transient. Two main regimens are available: titration method (use of the lowest dose maintaining euthyroidism; duration: 12 – 18 months) and block-and-replace method. Neither one has clear advantages in terms of outcome but the latter method is associated with more frequent side effects. Hyperthyroidism relapses in ∼ 50% of patients, to whom ablative therapy should be offered.

L’amiodarone è un farmaco benzofuranico molto ricco di iodio di largo impiego nel trattamento delle tachiaritmie refrattarie ai comuni farmaci antiaritmici. Questo farmaco spesso causa modificazioni dei test di funzione tiroidea (in genere un aumento dei livelli circolanti di T4e di rT3e la riduzione di quelli di T3) dovuti all’inibizione dell’attività delia 5'-desiodasi, l’enzima che converte la T4in T3. Circa il 14–18% dei pazienti in trattamento cronico con amiodarone sviluppa tireotossicosi (AIT) o ipotiroidismo (AIH). Sia l’AIT sia l’AIH possono insorgere in pazienti con una preesistente tireopatia oppure su una tiroide apparentemente normale. La tiroidite di Hashimoto è un fattore di rischio riconosciuto per lo sviluppo di AIH. La patogenesi dell’AIH consiste nell’incapacità all’escape dal fenomeno di Wolff-Chaikoff, verosimilmente per la presenza di lievi difetti della ormonosintesi oppure per una concomitante tiroidite autoimmune. L’AIT è dovuta all’eccessiva produzione ormonale in conseguenza del carico di iodio nei pazienti con tireopatia di base (AIT tipo 1) o alla tiroidite distruttiva che si verifica in una tiroide apparentemente normale come conseguenza del danno citotossico dell’amiodarone o dei suoi metaboliti (AIT tipo 2); peraltro, non è rara la coesistenza di aumentata sintesi degli ormoni tiroidei e di fenomeni distruttivi (forme miste). La terapia dell’AIH consiste nell’L-T4se non è possibile sospendere l’amiodarone, oppure in brevi cicli ripetuti di basse dosi di perclorato di potassio se non è indispensabile continuare il trattamento con amiodarone e se non sono presenti segni di autoimmunità tiroidea. La terapia medica dell’AIT tipo 1 consiste nella contemporanea somministrazione di tionamidi e perclorato di potassio, mentre nell’AIT tipo 2 i glucocorticoidi rappresentano l’opzione terapeutica più favorevole. Le forme miste possono rispondere alla combinazione di tionamidi, perclorato di potassio e glucocorticoidi. Il trattamento radiometabolico con 131-I non è in genere attuabile per i bassi valori della captazione tiroidea dello iodio; la tiroidectomia rappresenta il trattamento di elezione nei casi resistenti alla terapia medica o quando è necessario ripristinare rapidamente l’eutiroidismo e può essere eseguita dopo un breve ciclo di somministrazione di acido iopanoico capace di normalizzare i livelli circolanti di T3.

Peroxisome proliferator activated receptor (PPAR)γ plays a pivotal role in regulating adipocyte differentiation and metabolism, but also has an antiproliferative effect in several tissues, including colonic mucosa, where it is highly expressed. Loss-of-function mutations have been reported in about 10% of sporadic primary colon cancer. Acromegalic patients have an increased prevalence of colonic neoplasms and lower PPARγ levels in the colonic mucosa. Thus, PPARγ may act as a tumor suppressor gene, and its reduced expression or loss-of-function mutations may contribute to tumorigenesis. In this study the expression and mutations of the PPARγ gene in the colonic polyps and mucosa outside polyps were investigated in 10 acromegalic and 17 non-acromegalic patients. PPARγ expression was evaluated by RT-PCR. PPARγ was expressed in each sample, but expression appeared to be lower in polyps than in mucosa outside polyps from either acromegalic or non-acromegalic patients. All exons of the PPARγ gene were directly sequenced after PCR amplification: no mutations were found either in acromegalic or in non-acromegalic patients. In conclusion, the results of this preliminary study suggest that the lower expression of PPARγ rather than somatic mutations of this gene is involved in colonic tumorigenesis.

C-reactive protein (CRP) levels have not been routinely used to diagnose thyroid disease, although many thyroid conditions involve inflammation. This study was intended to determine whether CRP levels could differentiate between inflammatory and noninflammatory thyroid conditions, especially between type II inflammatory amiodarone-induced thyrotoxicosis (AIT) and type I iodine-induced AIT. Serum high-sensitivity CRP levels were measured in 100 euthyroid controls (7 taking amiodarone) and 353 patients with one of the following thyroid conditions: AIT, subacute thyroiditis, toxic diffuse goiter, nodular goiter, Hashimoto's thyroiditis, shortterm hypothyroidism, or postpartum thyroiditis. No patients with nontoxic multinodular goiter (n= 34), toxic nodular goiter (n= 23), or toxic diffuse goiter, either untreated (n= 49) or euthyroid while taking methimazole (n= 33), had positive CRP levels (>10 mg/L). The occurrence of positive CRP levels among patients with Hashimoto's thyroiditis (n= 35), short-term hypothyroidism (n= 38), and postpartum thyroiditis (n= 70) did not differ significantly from controls. The occurrence of positive CRP values did not differ significantly between patients with type I and type II AIT and controls. Six of 7 patients (86%) with untreated subacute thyroiditis had positive CRP levels (p< 0.00001). These results indicate that there is only a limited role for measurement of CRP levels in the diagnosis of thyroid diseases other than subacute thyroiditis.

Amiodarone, a benzofuranic-derivative iodine-rich drug used mostly for tachyarrhythmias, often causes changes in the peripheral metabolism of thyroid hormones mainly due to the inhibition of 5'-deiodinase activity: an increase in serum thyroxine and reverse triiodothyronine, and a decrease in serum triiodothyronine concentrations. Overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis (AIT) or amiodarone-induced hypothyroidism (AIH), occurring in 14 to 18 of patients receiving long-term treatment, may develop both in apparently normal thyroid glands and in glands with preexisting abnormalities. AIH is mainly due to the failure to escape from the acute Wolff-Chaikoff effect, and, in patients with thyroid autoimmune phenomena, to concomitant Hashimoto's thyroiditis. AIT is due to excess iodine-induced thyroid hormone synthesis (type I AIT) or to amiodarone-related destructive thyroiditis (type II AIT), although mixed forms often occur. Treatment of AIH consists of levothyroxine replacement therapy while continuing amiodarone therapy; alternatively, amiodarone can be discontinued, if possible, and the natural course toward euthyroidism can be accelerated by a short trial of potassium perchlorate. In type I AIT, the simultaneous administration of thionamides and potassium perchlorate is the treatment of choice, while in type II AIT steroids are the most useful therapeutic option. Mixed forms are best treated with a combination of thionamides, potassium perchlorate, and glucocorticoids. The low thyroidal 131I uptake usually makes radioiodine therapy not feasible, while thyroidectomy is a valid alternative in cases resistant to medical therapy.

Particular attention has recently been paid to the relationship between radioiodine administration and the course of thyroid-associated ophthalmopathy (TAO). Conflicting results have been reported in the literature, and radioiodine therapy has been associated either with aggravation, improvement, or no relevant changes of eye disease. Retrospective observations and recent prospective studies suggest that radioiodine can worsen preexisting ophthalmopathy and that these untoward ocular effects can be prevented by concomitant glucocorticoid administration. In the authors' experience, subtotal thyroidectomy can sometimes be associated with an exacerbation of ophthalmopathy; antithyroid drugs per se do not cause relevant changes in eye disease, but drug withdrawal is frequently followed by a relapse of hyperthyroidism which adversely affects the course of ophthalmopathy. Based on these considerations, the authors suggest that in Graves' disease patients with significant eye manifestations, a rapid and permanent control of thyroid hyperfunction should be obtained. Considered that the possible exacerbation of ophthalmopathy can be prevented by short-term glucocorticoid treatment, the authors believe that radioiodine can be effectively and conveniently used to achieve this goal. Indeed, radioiodine therapy provides permanent control of hyperthyroidism, thus avoiding exacerbations from recurrences, and thyroid ablation in the long run may beneficially affect the course of eye disease.

The effects of smoking on the function of endocrine glands have been investigated extensively but still are to be elucidated fully. It is widely recognized that the most important component of the smoke produced from the burning of tobacco, in terms of endocrine effects, is nicotine. Nicotine acts through the interaction with acetylcholine receptors, but it seems likely that others among the numerous smoke products may somehow influence endocrine homeostasis.The present paper will focus on the relationship between smoking and variations in thyroid economy or the occurrence of thyroid dysfunction.

L’intervento chirurgico di adenomectomia rappresenta uno dei capisaldi del trattamento dell’acromegalia; peraltro, la sua efficacia nei tumori ipofisari GH-secernenti di grosse dimensioni e con spiccate caratteristiche invasive è molto limitata. L’obiettivo di questo studio retrospettivo e multicentrico è stato quello di verificare se l’intervento chirurgico di asportazione parziale dell’adenoma ipofisario GH-secernente potesse migliorare la risposta agli analoghi della somatostatina. Sono stati studiati 86 pazienti (42 donne e 44 uomini, età media 42±14 anni). I pazienti erano trattati con octreotide, lanreotide o octreotide a lento rilascio prima e dopo intervento chirurgico di adenomectomia parziale per almeno 6 mesi. Il parametro preso in considerazione per valutare l’andamento della risposta al trattamento con analoghi della somatostatina è stato la determinazione dei livelli di IGF-1 circolanti per classi d’età. Prima dell’intervento neurochirurgico, il trattamento con analoghi della somatostatina riduceva significativamente i livelli circolanti di GH e IGF-1 in tutti i pazienti. I livelli di GH erano <2, 5 µg/litro in 12 pazienti (14%) e quelli di IGF-1 si normalizzavano in 9 pazienti (10%). L’intervento chirurgico riduceva la massa tumorale di oltre il 75% in 50 pazienti (58%), tra il 50 e il 75% in 21 pazienti (24%), tra il 25 e il 50% in 10 pazienti (12%) e di meno del 25% in 5 pazienti (6%). Dopo l’intervento chirurgico, il trattamento con analoghi della somatostatina riduceva i livelli circolanti di GH <2, 5 µg/litro in 49 pazienti (56%) e normalizzava i livelli di IGF-1 in 48 pazienti (55%). Il controllo della malattia con analoghi della somatostatina dopo l’intervento chirurgico era quindi significativamente superiore a quello ottenuto con gli stessi farmaci prima dell’intervento (p<0.0001). I livelli circolanti di GH (r=-0, 48, p<0.0001) e quelli di IGF-1 (r=-0, 38, p=0.0003) erano correlati con la quantità di tessuto adenomatoso rimosso. La funzione ipofisaria prima dell’intervento chirurgico era compromessa nel 14% dei pazienti e dopo l’intervento nel 32, 6%; peraltro, dopo l’intervento chirurgico il 13,9% dei pazienti aveva il recupero della funzione ipofisaria. In conclusione, l’intervento chirurgico di adenomectomia parziale (con rimozione di oltre il 75% della massa tumorale) determina un aumento della risposta agli analoghi della somatostatina senza compromissione significativa della funzione ipofisaria. Per questo motivo l’intervento chirurgico di debulking riveste un ruolo importante nell’algoritmo terapeutico dell’acromegalia.

Pendred’s syndrome is characterized by goiter, sensorineural deafness and impaired iodide organification. It is one of the most frequent causes of congenital deafness accounting for about 10% of hereditary hearing loss. It is caused by mutations in the pendrin (PDS) gene, which was postulated to be a sulfate transporter, because of its homology with other genes. We tested sulfate transport in mammalian COS-7 cells that were transiently transfected with PDS cDNA. 35SO4 uptake increased in a time-dependent manner, but this phenomenon was similar in cells transfected with PDS and in mock-transfected cells (450 and 360 cpm/ß-gal units at 10 min, respectively; 38,250 and 31,000 cpm/ß-gal units, at 12 h, respectively). There was no significant increase in 35SO4 uptake using increasing amounts of PDS-containing plasmid (up to 12 µg per dish). These data indicate that pendrin is not a sulfate transporter. Additional functional studies on this protein are warranted to clarify its role in thyroid pathophysiology and inner ear development.

Therapy with somatostatin analogues (SSAs) may have deleterious effects on glucose metabolism in patients with acromegaly, often leading to the development of diabetes mellitus (DM). The aim of the study was to evaluate whether DM, developed during therapy with SSAs, may revert after drug withdrawal and cure of acromegaly with pituitary adenomectomy. Retrospective cohort study, in a tertiary referral centre. Eighteen acromegalic patients without DMat the diagnosis of acromegaly treated with SSAs as a primary therapy, and then cured by pituitary adenomectomy. Endocrine status and glucose homeostasis were evaluated at diagnosis of acromegaly and at least every 6 months during SSAtherapy. At each visit, patients were classified into one of the following classes: normal glucose tolerance, prediabetes, overt diabetes. Median follow‐up after starting SSAs therapy was 69 months (IQR54.75‐132.25). During SSAtherapy, all patients had controlled acromegaly defined by normal serum IGF1 concentrations for the age. Of the 13 euglycaemic patients at diagnosis, three developed prediabetes and three diabetes, whereas, of the five prediabetic patients at diagnosis, two worsened to overt diabetes and three remained in the prediabetic range (P= 0.04). After curing acromegaly with pituitary adenomectomy and subsequent SSAwithdrawal, prediabetes reverted in five of six patients, and diabetes in all five patients (three reverted to euglycaemia, while two reverted to prediabetes) (P= 0.01). In acromegalic patients with controlled disease, changes in glycaemic status induced by SSAs are not permanent. Therapy with somatostatin analogues in acromegalic patients may lead to the development of diabetes mellitus. Glycaemic alterations that develop during efficacious therapy with somatostatin analogues revert after drug withdrawal and cure of acromegaly with pituitary adenomectomy. In acromegalic patients with controlled disease, changes in glycaemic status induced by somatostatin analogues are not permanent.