Antonio Ciccarelli

The Epidemiology of Prolactinomas

Prolactin-secreting tumors (prolactinomas), the most frequently occurring pituitary tumor, have a frequency that varies with age and sex. They occur most frequently in females aged 20 to 50 years old, at which time the female-to-male ratio is approximately 10:1. In the pediatric-adolescent age group, prolactinomas have a prevalence of 100/million population, and account for less than 2% of all intracranial tumors. Prolactinomas occur in approximately 30% of patients with multiple endocrine neoplasia type 1 and in this setting, they may be more aggressive than their sporadic counterparts. Patients with Carney complex or McCune-Albright syndrome may exhibit hyperprolactinemia due to a pituitary tumor derived from somatomammotropic cells that secrete both growth hormone and prolactin. Few familial cases of prolactinoma unrelated to MEN-1 are reported in literature.

Pamidronate improves the quality of life and induces clinical remission of bone metastases in patients with thyroid cancer

Skeletal metastases from thyroid cancer are poorly responsive to medical or radioiodine treatment. Bone destruction in skeletal metastases results from osteoclast-induced bone resorption. Therefore, a new approach in the therapy of bone metastases consists in using aminobisphosphonates, such as pamidronate, which are potent inhibitors of osteoclastic activity. In the present study, 10 thyroid cancer patients with painful osteolytic bone metastases were administered pamidronate (90 mg, as a 2 hour intravenous infusion) monthly for 12 consecutive cycles. Bone pain, quality of life, performance status, analgesic consumption and disease staging were evaluated before and during the trial. The patients who had been administered pamidronate showed a significant decrease in bone pain (P = 0.0052). Performance status improved nearly significantly (P = 0.051), while the quality of life showed a remarkable amelioration. However, no significant decrease in analgesic consumption was recorded. Partial radiographic response of bone lesions was observed in 2/10 patients. The side effects of pamidronate were mild and transient. In conclusion, monthly infusion of pamidronate is a well-tolerated treatment that induces significant relief from bone pain and improves the quality of life of thyroid cancer patients with symptomatic and osteolytic bone metastases.

Ultrasound-Guided Laser Thermal Ablation in the Treatment of Autonomous Hyperfunctioning Thyroid Nodules and Compressive Nontoxic Nodular Goiter

OBJECTIVE Percutaneous laser thermal ablation (LTA) has been applied in several tumors. In this study we evaluated the safety and long-term efficacy of LTA in the treatment of benign thyroid nodules. DESIGN AND PATIENTS Seven patients with autonomous hyperfunctioning thyroid nodule (group A) and five patients with compressive nodular goiter (group B) were treated with LTA. Up to three needles were positioned centrally in the thyroid nodule and laser fiber was placed in the lumen of the needle. Laser illumination was performed reaching a maximal energy deposition of 1800 J per fiber. MEASUREMENTS Thyroid nodule volume, endocrinologic, and clinical evaluation were performed at baseline, 3, and 12 months after the treatment. Scintigraphy was performed at diagnosis and 12 months after the first session in group A. RESULTS In group A, mean thyroid volume decreased from 3.15 +/- 1.26 mL to 0.83 +/- 0.49 mL (p < 0.001) after 12 months. The treatment induced disappearance of clinical signs and symptoms related to hyperthyroidism; normalization of free triiodothyronine (FT(3)), free thyroxine (FT(4)), and thyrotropin (TSH) serum levels and recovery of extranodular uptake at scintiscan. In group B, mean thyroid volume decreased from 11.14 +/- 4.99 mL to 3.73 +/- 1.47 mL (p < 0.01) after 12 months. Pressure symptoms in the neck, difficulty in swallowing and tracheal displacement improved in all patients. The treatment was well tolerated in both groups of patients. CONCLUSIONS LTA appears to be a valid and safe alternative approach in the treatment of benign thyroid nodules.

PRL Secreting Adenomas in Male Patients

Prolactinomas are the most frequent pituitary tumors and their frequency varies with age and sex, occurring most frequently in females between 20–50 yr-old. In men, hyperprolactinaemia is often present for many years without symptoms, as generally the most important symptoms are the decrease in libido and/or sexual potency both underestimated by the majority of the patients. Prolactin (PRL) plays a role in the process of spermatogenesis, and normal serum PRL levels are required for normal testicular function. On the other hand, hyperprolactinaemia has multiple negative effects on the gonadal axis. As a consequences hyperprolactinemic males show alteration of sexual potency and seminal fluid quality. Cabergoline treatments is able to induce normalization of PRL levels and a reduction of tumor mass in the majority of patients and consequently restoring the normal semen quality and ameliorating the quality of life of men with pituitary PRL-secreting adenoma.

Prevalence and determinants of left ventricular hypertrophy in acromegaly: impact of different methods of indexing left ventricular mass

background  Left ventricular hypertrophy (LVH) is the most common cardiac abnormality in acromegaly. Left ventricular mass (LVM) is an important parameter measured to detect LVH, but the relationship with body size should be considered by correcting LVM to body surface area (BSA), height or height2·7. All trials concerning acromegaly have detected LVH on the basis of LVM indexed for BSA, but have been criticized for disregarding the effects of obesity.

The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males

Background  Alterations of sperm number and motility are found in hyperprolactinaemic men. Cabergoline treatment reverses alterations in semen. No information is currently available on the quality of seminal tests in hyperprolactinemia in response to cabergoline treatment.

Lanreotide Autogel for acromegaly: a new addition to the treatment armamentarium.

Since their introduction into clinical practice, somatostatin analogs have been the pharmacological therapy of choice for the treatment of acromegaly. The first preparations of somatostatin analogs available for clinical use were administered subcutaneously two or three times daily, which was not optimal with respect to patient compliance. The introduction of long-acting formulations of somatostatin analogs has overcome this inconvenience.Lanreotide Autogel®, a new viscous, supersaturated, aqueous solution of lanreotide, is available in a prefilled syringe and administered by deep subcutaneous injection every 28 days. Lanreotide Autogel® has different pharmacokinetic properties from the earlier lanreotide slow-release (SR) formulation, which may account for its better tolerability. Furthermore, lanreotide Autogel® is at least as efficacious as the other somatostatin analogs in lowering growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in the majority and in restoring safe GH and age-normalized IGF-1 levels in about 50–60% of patients with acromegaly.In conclusion, lanreotide Autogel® is a valuable new addition to the acromegaly treatment armamentarium. Patients receiving intramuscular lanreotide SR injections every 7–14 days can be switched to an appropriate dose of deep subcutaneous lanreotide Autogel® every 28 days, without any impact on safety or loss of efficacy.

Tensegrity and type 1 dermal dendrocytes in acromegaly

Background  Skin is enlarged and doughy in acromegaly. Alterations have been reported in the structure of the extracellular matrix (ECM) and in the mechanical properties of the dermis. It is recognized that internal tensions in the dermis give rise to active cell‐ECM and cell–cell mechanical interactions. This mechanobiological aspect can lead to functional and conformational changes in the cells. Such alterations in connective tissue cells have not been explored so far in acromegaly. The aim of the study was to assess structural changes in the dermal ECM, and in the number and shape of factor XIIIa‐positive type I dermal dendrocytes (DDs) in acromegaly.

Gonadotropin secreting tumors

Most clinically nonfunctioning pituitary adenomas are gonadotropin-secreting adenomas, also termed gonadotropinomas.

Trattamento a lungo termine dell’acromegalia mediante pegvisomant, un antagonista del recettore dell’ormone della crescita

RiassuntoGli attuali approcci terapeutici nella cura dell’acromegalia comprendono: la chirurgia, la radioterapia e la terapia farmacologica. Il pegvisomant è un nuovo antagonista recettoriale del GH che migliora la sintomatologia e i livelli sierici di IGF-1 in un’alta percentuale di pazienti trattati per 12 settimane. In tale studio si è valutata l’efficacia del farmaco in 160 pazienti con acromegalia trattati per circa 18 mesi. I soggetti hanno ricevuto il pegvisomant tramite iniezione sottocutanea giornaliera con una dose iniziale di 10 mg/die e con dose massima raggiungibile di 40 mg/die. La dose di farmaco da somministrare è stata valutata mediante dosaggio bisettimanale o mensile dell’IGF-1.Trenta dei 160 pazienti arruolati hanno abbandonato prematuramente il protocollo di studio. Dopo 12 mesi di trattamento il 97% dei pazienti mostrava normali livelli di IGF-1. Effetti collaterali si sono verificati nel 10% dei soggetti, generalmente di lieve entità. Solo in 2 pazienti si è avuto un incremento delle transaminasi rientrate nella norma alla sospensione del farmaco. In altri 2 pazienti si è evidenziato un incremento volumetrico della massa tumorale. Il pegvisomant sembra essere, quindi, un ulteriore efficace arma nella cura della patologia acromegalica, soprattutto per i soggetti resistenti o scarsamente responsivi alla terapia con analogni della somatostatina.