Marina Caputo

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.

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.

Progression of pituitary tumours: impact of GH secretory status and long-term GH replacement therapy

BackgroundMost patients treated for hypothalamic–pituitary tumours develop GH deficiency. Long-term GH replacement treatment in adults with a previous history of hypothalamic–pituitary tumour could represent a concern about increasing the risk of tumour enlargement or recurrence.PurposeTo assess the progression risk of hypothalamic–pituitary tumours according to the GH secretory status (normal GH secretion, non-treated and treated GH deficiency). and determine the predictors of neoplasm recurrence.MethodsWe retrospectively reviewed 309 patients with tumours of the hypothalamic–pituitary region (294 subjects underwent neurosurgery while 81 radiotherapy) who were followed for 9.9 ± 8.3 years.ResultsOut of 309 patients, 200 were affected by severe GH deficiency; 90 of these underwent GH therapy. The tumour progression rate did not differ among GH-sufficient, not-treated and treated GH-deficient patients (16.5%, 16.4%. and 10.0%, respectively). In a multivariate analysis, previous radiotherapy (HR 0.12, CI 0.03–0.52, p < 0.005) and residual tumour (HR 8.20, CI 2.38–28.29, p < 0.001) were independent predictors of recurrence. After controlling for multiple covariates, the tumour recurrence risk in GH-sufficient and GH-treated patients was similar to that observed in not-treated GH-deficient patients.ConclusionsWith limitations of retrospective analysis, GH therapy is not associated with an increased progression rate of tumours of the hypotalamic–pituitary region during long follow-up, thus supporting the long-term safety of GH treatment. The only predictors of tumour recurrence appear to be the presence of residual disease and the lack of radiotherapy.

Diabetes in Growth Hormone Deficiency

Growth hormone (GH) deficiency (GHD) is a complex disease with a constellation of symptoms and signs which involve metabolism at several levels. Particular attention has been paid to glucose and insul

Ghrelin Regulation in Epilepsy

Epilepsy is one of the most common neurological problems worldwide affecting approximately 1% of the population (Browne & Holmes, 2000; Chang & Lowenstein, 2003). It is characterized by recurrent unprovoked behavioural seizures (Beck & Elger, 2008). In recent decades, the relationship between epilepsy and the neuroendocrine system has gained a great deal of interest and many researchers as neurologists, endocrinologists and basic scientists have investigated it. The main issue is whether hormonal changes in relation to epilepsy are due to seizures activity per se or to consequential effects of antiepileptic drugs. To understand the far-reaching effects of epilepsy and antiepileptic medications on hormonal system and vice versa, several studies have been recently performed. Their results are interesting but still controversial and the neuroendocrine regulation of epilepsy is far to be clearly explained. However, considering that a role of hormones in epilepsy is known and in part well described, this chapter would firstly review the endocrine regulation mediated by sex hormones, prolactin (PRL), growth hormone (GH), thyrotropin-releasing hormone (TRH), adrenocortical axis and neuropeptide Y (NPY). More recently, also other new hormones have been investigated in this field, bringing to light ghrelin. Ghrelin is a 28 amino acid peptide predominantly produced by the stomach (Kojima et al., 1999). It was discovered as the first natural ligand of the orphan growth hormone segretagogues receptor 1a (GHS-R1a), which exerts, through its activation, a strong GH-releasing activity (Arvat et al., 2001; Howard et al., 1996; Kojima et al., 1999; Kojima & Kangawa, 2005; van der Lely et al., 2004). It also influences glucose and insulin metabolism and controls food and energy intake through many neuroendocrine systems (van der Lely et al., 2004). Furthermore, several evidences suggest that ghrelin not only plays a metabolic role but it is also involved in sleepwake regulation, affective status, learning and memory processes (Steiger et al., 2011; van der Lely et al., 2004). Besides, the recent discovery of ghrelin has also provided an important insight to the neuroendocrine knowledge in epilepsy. In fact, a relationship between ghrelin and epilepsy has been already shown in animal and human models, although the results are sometimes conflicting. Thus, this chapter would secondly describe the intriguing ghrelin role in relation to seizures activity and discuss open questions and future perspectives.

Il trattamento a lungo termine con GH del deficit di GH dell’adulto: sicurezza (safety)

RiassuntoLa terapia sostitutiva con ormone somatotropo (rhGH) del paziente adulto con deficit di GH (GHD) rappresenta ancora oggi una sfida per l’endocrinologo clinico e la sua realizzazione costante nella pratica quotidiana presenta ancora numerose difficoltà e incertezze. Essa va iniziata con dosi assai basse di GH ricombinante e monitorata sulla base dei livelli di IGF-I e sulla risposta clinica. La sensibilità al GH biosintetico presenta una spiccata variabilità inter-individuale e ciÒ spiega perché le dosi di mantenimento dell’ormone siano assai variabili. In accordo con le linee guida è consigliabile iniziare il trattamento con dosi basse di rhGH pari a 0,15–0,30 mg/die. La terapia deve essere intrapresa solo quando i concomitanti trattamenti sostitutivi di eventuali altri deficit endocrini siano già stati ottimizzati. Raggiunti i livelli normali di IGF-I, il trattamento andrà controllato a intervalli semestrali. Deve essere sottolineato che un dosaggio eccessivo di rhGH determina frequentemente effetti collaterali che ricordano i sintomi riscontrabili nei pazienti con ipersecrezione di GH (in particolare artralgie ed edemi declivi), mentre un trattamento sostitutivo adeguato assai raramente presenta effetti collaterali. La presenza di residui di neoplasia ipofisaria stabili nel tempo non costituisce una controindicazione al trattamento sostitutivo con rhGH, anche se, in queste condizioni, è raccomandato un controllo con esami appropriati di imaging della regione ipofisaria, a intervalli inizialmente semestrali e successivamente annuali. È infatti provato che il trattamento sostitutivo con rhGH non determina un aumento della massa tumorale ipofisaria, né induce un’insorgenza significativamente maggiore di neoplasie de novo rispetto alla popolazione generale. Le evidenze derivanti dagli studi rivelano che il rischio di sviluppare iperglicemia o diabete mellito nella popolazione di GHD trattati non è differente da quello della popolazione generale e maggior rischio potrebbe essere presente nei pazienti obesi. Sebbene non esistano prove certe che il trattamento con rhGH possa indurre o favorire la progressione del diabete o delle sue complicanze oculari (retinopatia diabetica), questo trattamento viene sconsigliato nei pazienti con diabete mellito scompensato e con retinopatia diabetica proliferante già in atto.