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The purpose of this study was to assess prospectively the efficacy and safety of stereotactic body radiation therapy (SBRT) for adrenal gland metastasis, with a focus on the assessment of the irradiated subjects’ endocrinological function. A total of 36 patients were enrolled from 2017 to 2020 in this prospective phase II trial. Patients were treated with Linac-based SBRT, with a dose of 45 Gy in 3 consecutive fractions. Primary end-point was local control (LC) of the treated lesions and secondary end-points included evaluation of acute and late toxicity, progression free survival (PFS), overall survival (OS) and the impact on the hormonal production of adrenal glands. With a median follow-up of 9.5 months, LC rates at 1 and 2 years were 94.7% and 88.4%, respectively. Rates of PFS at 1 and 2 years were 50.5% and 29.8%, with a median PFS of 14.7 months. Rates of OS at 1 and 2 years were 62.9% and 44.1%. At univariate analysis, oligorecurrence was associated with better OS compared to oligoprogressive or synchronous metastatic disease. No grade 3 or greater toxicities were registered and only a minority of patients (22.2%) reported mild treatment-related side effects. Hormonal and electrolytes production was assessed before and after treatment, showing only a slight and transient variation within the reference ranges. SBRT on adrenal metastases has been confirmed to be a feasible and effective treatment. With an excellent disease control and the preservation of the endocrine function, SBRT with ablative dose can be considered a viable alternative to more invasive approaches.

Sommario L’infezione da SARS-CoV-2 è rapidamente diventata una pandemia globale, con più di 100 milioni di persone infettate e 2,3 milioni di morti nel mondo. Particolare attenzione è stata posta all’influenza reciproca tra infezione da SARS-CoV-2 e funzione endocrina. In questa rassegna si discuteranno i risultati dei principali studi ad oggi pubblicati che hanno analizzato le alterazioni della funzione tiroidea, dei livelli di vitamina D e il compenso glicometabolico nei pazienti ospedalizzati per polmonite da SARS-CoV-2 e il loro impatto sull’outcome clinico. Informazioni Supplementari La versione online contiene materiale supplementare disponibile su 10.1007/s40619-021-00949-7.

Purpose “Non thyroidal illness syndrome” (NTIS) or “euthyroid sick syndrome” (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. Methods We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. Results Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. Conclusions COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

L’osteoporosi e le fratture da fragilita scheletrica rappresentano importanti comorbidita nei pazienti con carcinoma differenziato della tiroide (DTC), con potenziale impatto negativo sulla qualita di vita e sulla sopravvivenza. La terapia TSH-soppressiva rappresenta il principale determinante della fragilita scheletrica nei pazienti con DTC, favorendo il riassorbimento osseo e il deterioramento della microstruttura ossea. Tale effetto negativo puo essere amplificato in presenza di metastasi ossee che incrementano ulteriormente il rischio di fratture. L’inquadramento e la gestione della fragilita scheletrica nel DTC sono ancora controverse e i dati sull’efficacia dei farmaci osteo-attivi in questo contesto clinico sono scarsi.

La sindrome da resistenza agli ormoni tiroidei e caratterizzata da una mancata risposta ormonale dei tessuti bersaglio, dovuta nella maggior parte dei casi a un’alterazione recettoriale dell’isoforma $\beta $ . E una patologia rara caratterizzata da valori discordanti di TSH e ormoni tiroidei, che va posta in diagnosi differenziale con altre situazioni, senza escludere interferenze di laboratorio. L’obiettivo terapeutico e ripristinare al meglio l’azione ormonale sui tessuti bersaglio.

The management of pituitary adenomas in the elderly has become a relevant clinical issue, in relationship with improved life expectancy and spreading use of imaging techniques. In this single-center and retrospective study, we investigated the impact of age on peri- and postsurgical outcomes in patients undergoing transnasal sphenoidal (TNS) surgery for pituitary adenomas. One-hundred-sixty-nine patients (62% males) undergoing endoscopic transphenoidal (TNS) surgery for nonfunctioning pituitary adenomas (NFPAs) were enrolled. Patients were subdivided into three groups according to age tertiles: ≤56 (group 1), 57–69 (group 2), and ≥70 (group 3) years. Postsurgical and endocrinological outcomes were evaluated and compared among the three age groups. 37/169 patients (21.9%) developed at least one perisurgical complication, without significant association with the patients’ age (P = 0.838), Charlson co-morbidity score (P = 0.326), and American Society of Anesthesiologist score (P = 0.616). In the multivariate regression analysis, the adenoma size resulted the only determinant of perisurgical complication (odds ratio [OR] 1.07, 95% confidence interval [C.I.] 1.00–1.13; P = 0.044). The development and the recovery of at least one pituitary hormone deficiency were observed in 12.2% and 14.2% of patients, respectively. The risk of developing new pituitary hormone deficiencies was correlated with cavernous sinus invasion as evaluated by magnetic resonance imaging (hazard ratio [HR] 4.19, 95% C.I. 1.39–12.66; P = 0.010), whereas the probability to normalize at least one pituitary hormone deficiency was significantly correlated with younger age of patients (HR 0.27, 95% CI 0.12–0.61; P = 0.002). The results of this study reinforce the concept that endoscopic TNS surgery is a safe therapeutic option in the elderly patients with NFPA, even in presence of comorbidities and high anesthetic risk.

La terapia radio-recettoriale (Peptide Radio-Receptor Therapy, PRRT) nei tumori neuroendocrini (NET) e un trattamento molecolare basato sull’infusione sistemica di radiofarmaci specificamente Disegnati per legare i recettori della somatostatina, generalmente sovra-espressi nei NET. La lunga tradizione in ambito medico-nucleare, la nota efficacia, la buona tollerabilita e bassa incidenza di effetti collaterali (generalmente moderati e transitori) e il recente inserimento di questa terapia nell’ambito dei trattamenti innovativi in oncologia, hanno richiamato una rinnovata attenzione da parte dei clinici. Nella complessa gestione dei pazienti affetti da NET, la PRRT aggiunge un’opzione terapeutica importante.

La gravidanza influisce su morfologia e funzione ipofisarie e tali modificazioni possono rendere complessa non solo la diagnosi di patologie ipofisarie di nuova insorgenza, ma anche il follow-up e la gestione di adenomi ipofisari, secernenti e non, diagnosticati prima della gravidanza. I dati attualmente disponibili su andamento, gestione e esito della gravidanza sono prevalentemente concentrati sulle pazienti con adenomi ipofisari PRL e GH-secernenti. La gestione di queste pazienti durante la gravidanza dipende da tipologia, dimensioni ed estensione dell’adenoma e andrebbe preferibilmente affidata a Centri dedicati alla diagnosi e cura delle patologie ipofisarie. In questa Rassegna si descriveranno in breve sia le modificazioni morfo-funzionali della ghiandola ipofisaria in corso di gravidanza sia le modalita di gestione per ciascuna tipologia di adenoma ipofisario.

Testicular adrenal rest tumors (TARTs) are benign masses deemed to originate from pluripotent testicular steroidogenic cells that grow under chronic ACTH stimulation. These lesions, occasionally misdiagnosed as Leydig cell tumors (LCTs), are typically described in patients with congenital adrenal hyperplasia (CAH). X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of beta-oxidation with accumulation of very long chain fatty acids (VLCFAs) in various tissues, and a rare cause of primary adrenal insufficiency (PAI). TARTs have never been associated with X-ALD. CASE 1 DESCRIPTION: A 19-year old male, who had previously undergone bilateral enucleation of presumed LCTs, was referred to our unit. Follow-up scans showed persistent bilateral lesions compatible with TARTs. Biochemical exams revealed PAI but excluded CAH. A serum VLCFAs panel was consistent with X-ALD, with gene testing confirming the diagnosis. Histological revision of the previously resected testicular lesions was compatible with TARTs. Start of glucocorticoid replacement therapy was associated with a reduction of testicular masses. CASE 2 DESCRIPTION: A 26-year old X-ALD male was diagnosed with bilateral testicular lesions compatible with TARTs. These lesions increased after ACTH elevation following switch to modified-release hydrocortisone. Clinical and sonographic findings allowed for a "watchful-waiting" approach, avoiding unnecessary surgery.These are the first cases reported of TARTs in patients with X-ALD-associated PAI. Testicular lesions in patients with an early onset of ACTH elevation, regardless of the cause, should always be thoughtfully investigated, as they may reveal themselves as TARTs. We suggest that all patients affected from chronic ACTH elevation of a young age of onset should undergo testicular ultrasound in order to evaluate the presence of these lesions. GRT in these patients might also help preserving fertility.

The evaluation of skeletal fragility in Cushing’s syndrome (CS) is a clinical challenge, since dual-energy X-ray absorptiometry (DXA) does not capture abnormalities in bone microstructure induced by glucocorticoid excess. Hypercortisolism was shown to increase bone marrow adiposity, but it is still unknown whether high bone marrow fat (BMF) as measured by vertebral magnetic resonance spectroscopy may predict fracture risk in this clinical setting. In this cross-sectional study, we evaluated the association between BMF and vertebral fractures (VFs) in patients with CS. Twenty patients (5 M, age 44 ± 13 years) with active CS were evaluated for morphometric VFs, lumbar spine BMF, and bone mineral density (BMD). Fifteen healthy volunteers (4 M, age 43 ± 12 years) acted as control group for BMF evaluation. BMF was significantly higher in CS patients vs. controls (52.0% vs. 27.0%, p

Con il termine ipotiroidismo centrale (IC) si indica un difetto della secrezione di ormoni tiroidei secondario a un’insufficiente azione stimolatoria del TSH su di una ghiandola altrimenti normofunzionante. E una patologia rara ed eterogenea causata da alterazioni anatomiche/funzionali ipofisarie (ipotiroidismo secondario) o ipotalamiche (ipotiroidismo terziario). Le manifestazioni cliniche sono in genere lievi e la diagnosi si fonda sul riscontro di ridotti livelli circolanti di FT4 in presenza di livelli ridotti o inappropriatamente normali di TSH. Come nel caso dell’ipotiroidismo primario, la terapia dell’IC prevede la somministrazione di L-tiroxina (L-T4). Poiche la secrezione di TSH e soppressa anche in corso di trattamento con L-T4 a bassi dosaggi, l’adeguatezza della terapia sostitutiva viene monitorata misurando i livelli circolanti di FT4.

Thyrotropin-secreting pituitary adenomas (TSH-omas) present with signs and symptoms of hyperthyroidism and they are characterized by elevated serum levels of free thyroid hormones with measurable TSH levels. TSH-omas are very infrequent, accounting for less than 1% of all pituitary adenomas, thus representing a very rare cause of hyperthyroidism. For this reason, data collected on these rare disorders are relatively few, but some new researches shed new light on the etiopathogenesis, the diagnosis and the treatment of such a remarkable disease. Since the same biochemical picture is present in the syndromes of thyroid hormone resistance (RTH), in particular in the form of pituitary RTH, failure in distinguishing these clinical entities may lead to improper patient management. Conversely, early diagnosis and correct treatment of TSH-omas may prevent the occurrence of neurological and endocrinological complications, thus leading to a better rate of cure. In the present short review article, the most relevant recent advances in the pathophysiology of TSH-omas are described.

Gli adenomi ipofisari TSH-secernenti (TSHomi) rappresentano una rara causa di ipertiroidismo, in cui la secrezione di TSH e svincolata dal normale feedback degli ormoni tiroidei. I segni, sintomi e i dati biochimici nei pazienti con TSHoma sono in gran parte sovrapponibili a quelli osservati nella sindrome da resistenza agli ormoni tiroidei (RTH). La terapia di prima linea dei TSHomi e quella chirurgica, mentre gli analoghi della somatostatina sono efficaci nel normalizzare la secrezione ormonale nei pazienti non guariti dopo chirurgia o non candidabili all’approccio chirurgico.

I tumori neuroendocrini (NET) sono un gruppo eterogeneo di neoplasie che originano dal sistema neuroendocrino diffuso e che si caratterizzano per un relativo ridotto tasso di crescita e per la possibile secrezione di ormoni o di peptidi vasoattivi. I NET, la cui prevalenza e significativamente aumentata negli ultimi decenni, rappresentano il 2% di tutte le neoplasie del polmone e la seconda piu frequente forma di neoplasia maligna del trattato gastroenterico, seconda sola al carcinoma del colon. Quella chirurgica e la terapia di scelta nei pazienti con NET ben localizzati. Tuttavia, il 40% dei pazienti con NET si presenta alla diagnosi con malattia metastatica che richiede, pertanto, ulteriori terapie sia locoregionali che sistemiche. A tale proposito, negli ultimi anni sono state approvate terapie a bersaglio molecolare (quali everolimus e sunitinib) per l’utilizzo nei pazienti con NET in progressione. Si e inoltre osservato un progressivo ampliamento del ruolo degli analoghi della somatostatina nel trattamento dei NET. Se gli analoghi della somatostatina trovavano inizialmente spazio nel controllo della sintomatologia legata alla secrezione di ormoni o peptidi vasoattivi (come nel caso della sindrome da carcinoide), studi recenti hanno dimostrato come tali farmaci siano efficaci nel controllo della progressione di malattia nel caso di NET non funzionanti avanzati.

In western countries, the process of "ageing of the population" is increasingly forcing clinical medicine to find answers for pathologies affecting the elder segments of our community. In this respect, pituitary adenomas often raise difficult questions on surgical indications, since little is known about postoperative morbidity and mortality in elderly patients. The transsphenoidal endonasal approach (TNS), which is considered the gold standard for surgical resection of the majority of functioning and non-functioning pituitary adenomas, is supposed to be a low morbidity and mortality procedure in adult patients. However, only a few contradicting data are available in the literature about elderly patients. In this paper we retrospectively analyze a cohort of 43 consecutive patients aged more than 65 years, operated on for pituitary adenomas at our Institution in the years 1998-2007. These patients were treated by transsphenoidal endonasal approach (TNS) for resection of non-functioning pituitary adenomas (n = 31), GH-secreting adenomas (n = 4) and ACTH-secreting adenomas (n = 8). Clinical records reported a macroadenoma with tumour-related mass symptoms in about 80 % of patients; single or multiple pituitary deficits were present in 44 % of patients. Regarding comorbidities, cardiac disease was the most frequently observed (86 %); assessment of anaesthesiological risk indicated a moderate to severe ASA score in most patients, 11 % showing a 4-5 score. On the basis of current criteria, our retrospective analysis revealed that cure was achieved in 54 % of patients. The outcome was similar to that observed in the general population of patients undergoing transphenoidal surgery in our centre, without differences in the rate of surgical and endocrinological cure, minor and major surgical complications and hospitalization duration. In particular, no significant anaesthesiological complications were observed and no patient developed either permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. In conclusion, in specialized centres the surgical treatment of pituitary adenomas via the transsphenoidal route can be a safe and effective procedure even in elderly patients.

Il riscontro incidentale di un processo espansivo a livello della sella turcica durante indagini neuroradiologiche (risonanza magnetica o tomografia computerizzata) richieste per motivi non correlati al sospetto di malattie ipotalamo-ipofisarie (traumi, vertigine, epilessia, ecc.) e evenienza alquanto frequente nella pratica clinica quotidiana, potendosi verificare in circa il 10% della popolazione. Non v’e dubbio che gli adenomi ipofisari clinicamente non-funzionanti ne siano la causa piu frequente; tuttavia, occorre ricordare che anche lesioni sellari piu rare (cisti della tasca di Rathke, craniofaringioma, metastasi, ecc.) possono talora mostrarsi con le modalita dell’incidentaloma ipofisario. Nel caso in cui il processo espansivo ha dimensioni inferiori al centimetro, esso e indicato con il termine di “microincidentaloma”; viceversa, nel caso di lesioni superiori al centimetro si utilizza il termine di “macroincidentaloma”. La storia naturale dell’incidentaloma ipofisario e poco nota e cid condiziona le reali difficolta nel delineare principi generali d’inquadramento iniziale e di successivo follow-up. In questo scenario, le recenti linee guida proposte dall’Endocrine Society costituiscono indubbiamente un aiuto rilevante nella gestione clinica dei pazienti che giungono all’attenzione dei clinici per il riscontro incidentale di una massa sellare, pur persistendo aree d’incertezza che solamente studi prospettici su ampie coorti potranno chiarire.

Unfortunately, the fourth author's middle name was missed out in the original publication of this article. The complete correct name should read as follows.

Gli adenomi ipofisari non funzionanti (NFPA) sono caratterizzati dall’assenza di ipersecrezione ormonale e quindi di una presentazione clinica specifica. Per questo motivo la diagnosi viene solitamente posta quando il tumore ha raggiunto grandi dimensioni; in questi casi, i segni e i sintomi riscontrabili sono legati all’effetto massa del tumore. Il trattamento di prima scelta degli NFPA e l’asportazione chirurgica della lesione per via transnasosfenoidale (TNS), soprattutto in caso di lesioni che determinino un significativo effetto massa e che coinvolgano in particolare la regione del chiasma ottico. Nel caso si riesca a ottenere la guarigione chirurgica, ossia l’assenza di residuo tumorale al primo controllo neuroradiologico post-intervento, la recidiva di malattia e poco probabile e un follow-up neuradiologico, oftalmologico ed endocrinologico e sufficiente. In presenza di un residuo lesionale, invece, data l’alta probabilita di ricrescita nel tempo, andranno attentamente considerate le opzioni di un reintervento chirurgico oppure di una radioterapia adiuvante, che garantisce un’ottima efficacia in termini di controllo di malattia, sebbene sia gravata da una potenziale tossicita a lungo termine. In casi selezionati, infine, si potra considerare l’ipotesi di una terapia medica. Indipendentemente dall’approccio scelto, il paziente con NFPA necessita di una periodica ma costante rivalutazione del quadro neuroradiologico, oftalmologico e della funzione anteroipofisaria, con la correzione ove necessario di eventuali deficit tropinici associati.

Central hypothyroidism (CH) is a rare cause of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland and it is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects. The diagnosis of CH is usually suggested by the finding of lowered thyroid hormone concentrations, associated with inappropriately low/ normal TSH levels. Restoration and maintenance of euthyroidism represent the therapeutic goals in all forms of CH. On these basis, the vast majority of patients with CH is treated with standard levo-thyroxine (L-T4) therapy which is tailored according to FT4 circulating levels that should be maintained in the normal range.

The cAMP-protein kinase A (PKA) pathway is the major signal transduction pathway involved in melanocyte-stimulating hormone receptor-mediated signaling and melanin production, whereas its role in the control of melanocyte proliferation is still controversial. In this study, we evaluated the effects of selective activation of the different PKA regulatory subunits type 1A (R1A) and type 2B (R2B) on melanocyte proliferation. Immunohistochemistry demonstrated that normal melanocytes lacked R1A protein whereas this subunit was highly expressed in all human melanomas studied (N=20) and in six human melanoma cell lines. Pharmacological activation of the R2 subunits by the cAMP analogue 8-Cl-cAMP inhibited proliferation and increased caspase-3 activity by 68.77+/-10.5 and 72+/-9% respectively, in all cell lines with the exception of the only p53-mutated one. Similar effects were obtained by activating R2 subunits with other analogues and by silencing R1A expression. The antiproliferative and proapoptotic effects of 8-Cl-cAMP were comparable to those observed with commonly used antitumoral drugs. Moreover, 8-Cl-cAMP potentiated the effects of these drugs on both cell proliferation and caspase-3 activity. In conclusion, this study first reports that human melanomas are characterized by a high R1/R2 ratio and that pharmacological and genetic manipulations able to revert this unbalanced expression cause significant antiproliferative and proapoptotic effects in melanoma cells.

G proteins and G-protein-coupled receptors (GPCRs) mediate the effects of a number of hormones. Genes that encode these molecules are subject to loss-of function or gain-of-function mutations that result in endocrine disorders. Loss-of-function mutations prevent signaling in response to the corresponding agonist and cause resistance to hormone actions, which mimics hormone deficiency. Gain-of-function mutations lead to constitutive, agonist-independent activation of signaling, which mimics hormone excess. Disease-causing mutations of GPCRs have been identified in patients with various disorders of the pituitary-thyroid, pituitary-gonadal and pituitary-adrenal axes, and in those with abnormalities in food intake, growth, water balance and mineral-ion turnover. The only mutational changes in G proteins unequivocally associated with endocrine disorders occur in GNAS (guanine nucleotide-binding protein G-stimulatory subunit alpha, or G(s)alpha). Heterozygous loss-of-function mutations of GNAS in the active, maternal allele cause resistance to hormones that act through G(s)alpha-coupled GPCRs, whereas somatic gain-of-function mutations cause proliferation of endocrine cells that recognize cyclic AMP as a mitogen. The study of mutations in G proteins and GPCRs has already had major implications for understanding the molecular basis of rare endocrine diseases, as well as susceptibility to multifactorial disorders that are associated with polymorphisms in these genes.

Abnormal GH responses to GnRH test, observed in about 15% of patients with acromegaly, have been reported exclusively in patients bearing tumors without gsp mutation. The absence of responsiveness to GnRH in gsp+ tumors was not predicted on the basis of the mechanism of GnRH action that mainly involves the activation of calcium and protein kinase C dependent pathways. The aim of the present study was to investigate in detail the transduction of GnRH signaling in these tumors. GH-secreting adenomas removed from patients in vivo responsive to GnRH test were studied. Tumor DNA was screened for Gsalpha and GnRH receptor gene sequences. Intracellular calcium ([Ca2+]i) and cAMP levels were measured in dispersed cells and adenylyl cyclase (AC) activity in membrane preparations. DNA analysis showed wild sequence of both Gsalpha and GnRH receptor genes. GnRH caused a significant increase in intracellular Ca2+ that was associated with a significant stimulation of cAMP accumulation. In these cells neither TRH nor GHRP-6 were effective in causing significant modifications of cAMP levels, despite their ability to increase [Ca2+]i. Finally, GnRH was able to directly stimulate AC from 11.1 +/- 3.3 pmol/mg prot/min to 26.9 +/- 5.4 (p

The effect of TRH on cytosolic free calcium concentrations, [Ca2+]i, was evaluated on cell suspensions obtained from 6 human PRL secreting pituitary adenomas. In these cells resting [Ca2+]i levels were variable (mean ±SE; 103.8 ± 6.5, n=25); the addition of 100 nM TRH caused a marked [Ca2+]i rise within 20 sec, the peak values ranging from 200 to 437 nM (285 ± 10.8 nM, n=10). The transients induced by TRH were composed by a rapid increase, due to mobilization of calcium from intracellular stores, followed within a few seconds by a lower plateau which was due to stimulated influx from the extracellular space. In fact, when EGTA and verapamil were applied after TRH they caused the Ca2+ plateau to dissipate rapidly. The addition of 1uM dopamine (DA) caused a substantial decrease of resting [Ca2+]i (about 10–30% ) as well as an inhibition of the plateau phase induced by TRH. The effect of DA completely depended on extracellular Ca2+. The TRH-induced transients observed in adenomatous cells were quite similar in size and time course to those recorded in normal rat lactotrophs. As previously observed in rat lactotrophs, in adenomatous cells treatment with pertussis toxin (PTx, 1 μg/ml for 4 h) was unable to affect the [Ca2+]i transients induced by TRH while completely abolished the effect of DA. The effects of TRH on in vivo and in vitro PRL secretion were also evaluated. Before surgery, no patient showed a positive response to the iv administration of 200 μg TRH ( serum PRL levels: 95 ± 62 ng/ml in basal conditions vs 124 ± 92 after TRH, P=NS). In in vitro secretion study, 100 nM TRH caused a slight stimulation (about 30–40%) of PRL release in 3 out of 4 adenomas and no effect in 1. By contrast, in the same experimental conditions TRH caused a marked increase of PRL release from rat lac-totrophs. In conclusion, adenomatous lactotrophs possess receptors for TRH which are coupled with the intracellular effectors operating in normal cells. Modifications of processes other than TRH signal transduction might account for the poor sensitivity to the peptide observed in prolactinomas both in vivo and in vitro.

guata copertura steroidea e di profilassi anti-trombotica. L’esame istologico mostrava un carcinoma neuroendocrino ben differenziato del timo con positivita diffusa per ACTH all’immunoistochimica. Nei giorni successivi all’intervento si osservava un progressivo miglioramento del quadro clinico generale con normalizzazione del quadro pressorio, del metabolismo glicidico e scomparsa della poliuria/polidipsia. I successivi esami evidenziavano la presenza di iposurrenalismo per il quale il paziente e tutt’ora in terapia sostitutiva con Cortone acetato. Un uomo di 39 anni veniva ricoverato per multiple fratture vertebrali sospette per lesioni secondarie. Alla tomografia computerizzata (TC) total-body veniva riscontrata una massa espansiva del mediastino anteriore di 80x31 mm, compatibile all’agobiopsia con carcinoma neuroendocrino. Gli esami ormonali evidenziavano un ipercortisolismo ACTH-dipendente (ACTH 185 pg/ml, cortisolo ore 08.00: 50 μg/dl, cortisolo ore 23.00: 38,78 μg/dl, cortisolo libero urinario 2.500 μg/24 h) associato a ipopotassiemia grave, diabete mellito scompensato e ipertensione arteriosa resistente alla terapia farmacologica. All’esame obiettivo il paziente presentava distribuzione centripeta dell’adipe, marcata ipotrofia muscolare degli arti e facies lunare. La risonanza magnetica nucleare (RMN) della colonna vertebrale escludeva la natura sostitutiva degli schiacciamenti a favore di un’origine osteoporotica. Veniva iniziata terapia con ketoconazolo 400 mg 3 volte al giorno ed octreotide 0,5 mg 3 volte al giorno, con miglioramento del quadro clinico. Il paziente veniva sottoposto a intervento chirurgico di asportazione della massa mediastinica con resezione polmonare