Renata S Auriemma, Mariano Galdiero, Ludovica F S Grasso, Pasquale Vitale, Alessia Cozzolino, Gaetano Lombardi, Annamaria Colao and Rosario Pivonello
Somatostatin analogs (SA) are the cornerstone in the medical treatment of acromegaly, used as either primary or adjunctive therapy. In particular, SA are effective in inducing the biochemical remission of the disease and tumor shrinkage, although only few cases of complete disappearance of the pituitary tumor in patients treated with SA as long-acting formulations have been reported. SA withdrawal has been demonstrated to keep safe levels of GH and IGF1 at least in a small subset of patients well responsive to SA, although it is generally followed by disease recurrence after several months.
A 61-year-old female patient bearing a very large GH-secreting pituitary macroadenoma was treated with 12-month lanreotide Autogel (ATG), at the initial dose of 120 mg/28 days. After 3 months, GH and IGF1 levels were fully normalized, to prolong the administration interval from 28 to 56 days. After 6 months of treatment, a significant tumor shrinkage (90% of baseline size) was observed, whereas GH and IGF1 excess was still well controlled. After 12-month therapy, a complete disappearance of the pituitary tumor was observed, and the hormonal evaluation confirmed the complete biochemical remission of acromegaly. Lanreotide ATG treatment was withdrawn. The clinical, biochemical, and radiological remission of acromegaly was maintained 24 months after lanreotide ATG treatment discontinuation, without evidence of disease recurrence.
This report represents an exemplary case of the potentiality of treatment with lanreotide ATG in inducing a complete remission of acromegalic disease, persistent after a long period of time from treatment withdrawal.
Annamaria Colao, Carolina Di Somma, Teresa Cascella, Rosario Pivonello, Giovanni Vitale, Ludovica F S Grasso, Gaetano Lombardi and Silvia Savastano
In the general population, low IGF1 has been associated with higher prevalence of cardiovascular disease and mortality.
To investigate the relationships between IGF1 levels, blood pressure (BP), and glucose tolerance (GT).
Four-hundred and four subjects (200 men aged 18–80 years). Exclusion criteria: personal history of pituitary or cardiovascular diseases; previous or current treatments with drugs interfering with BP, GT, or lipids, corticosteroids (>2 weeks), estrogens, or testosterone (>12 weeks); smoking of >15 cigarettes/day and alcohol abuse (>3 glasses of wine/day).
Two hundred and ninety-six had normal BP (73.3%), 86 had mild (21.3%), and 22 had severe (5.4%) hypertension; 322 had normal GT (NGT (79.7%)), 53 had impaired glucose tolerance (IGT (13.1%)), 29 had diabetes mellitus (7.2%). Normotensive subjects had significantly higher IGF1 levels (0.11±0.94 SDS) than those with mild (−0.62±1.16 SDS, P<0.0001) or severe (−1.01±1.07 SDS, P<0.0001) hypertension. IGF1 SDS (t=−3.41, P=0.001) independently predicted systolic and diastolic BP (t=−2.77, P=0.006) values. NGT subjects had significantly higher IGF1 levels (0.13±0.90 SDS) than those with IGT (−0.86±1.14 SDS, P<0.0001) or diabetes mellitus (−1.31±1.13 SDS, P<0.0001). IGF1 SDS independently predicted fasting glucose (t=−3.49, P=0.0005) and homeostatic model assessment (HOMA)-R (t=−2.15, P=0.033) but not insulin (t=−1.92, P=0.055) and HOMA-β (t=−0.19, P=0.85).
IGF1 levels in the low normal range are associated with hypertension and diabetes in subjects without pituitary and cardiovascular diseases.
Renata S Auriemma, Rosario Pivonello, Ylenia Perone, Ludovica F S Grasso, Lucia Ferreri, Chiara Simeoli, Davide Iacuaniello, Maurizio Gasperi and Annamaria Colao
Cabergoline (CAB) has been found to be associated with increased risk of cardiac valve regurgitation in Parkinson's disease, whereas several retrospective analyses failed to detect a similar relation in hyperprolactinemic patients. The current study aimed at investigating cardiac valve disease before and after 24 and 60 months of continuous treatment with CAB only in patients with hyperprolactinemia.
Subjects and methods
Forty patients (11 men and 29 women, aged 38.7±12.5 years) newly diagnosed with hyperprolactinemia entered the study. Cumulative CAB dose ranged from 12 to 588 mg (median 48 mg) at 24 months and 48–1260 mg (median 149 mg) at 60 months. All patients underwent a complete trans-thoracic echocardiographic examination. Valve regurgitation was assessed according to the American Society of Echocardiography.
At baseline, the prevalence of trace mitral, aortic, pulmonic, and tricuspid regurgitations was 20, 2.5, 10, and 40% respectively, with no patient showing clinically relevant valvulopathy. After 24 months, no change in the prevalence of trace mitral (P=0.78) and pulmonic (P=0.89) regurgitations and of mild aortic (P=0.89) and tricuspid (P=0.89) regurgitations was found when compared with baseline. After 60 months, the prevalence of trace tricuspid regurgitation was only slightly increased when compared with that after 24 months (37.5%; P=0.82), but none of the patients developed significant valvulopathy. No correlation was found between cumulative dose and prevalence or grade of valve regurgitation at both evaluations. Prolactin levels normalized in all patients but one.
CAB does not increase the risk of significant cardiac valve regurgitation in prolactinomas after the first 5 years of treatment.
Renata S Auriemma, Rosario Pivonello, Maria Cristina De Martino, Giuseppe Cudemo, Ludovica F S Grasso, Mariano Galdiero, Ylenia Perone and Annamaria Colao
To evaluate the effects of short- and long-term treatment with pegvisomant (PEG) on arrhythmias in acromegalic patients resistant to long-term, high-dose therapy with somatostatin analogs (SA).
Materials and methods
Thirteen patients entered the study. All patients started PEG at initial dose of 10 mg daily and then titrated to 5 mg every 6 weeks on the basis of IGF1. A standard 24-h electrocardiography registration was performed in all patients at baseline and after 6 and 18 months of PEG to evaluate: mean (HR), maximum (MHR), and minimum (mHR) heart rate; pauses number (P) and duration (PD); supraventricular episodes (SEs) number and duration (SED); and ventricular ectopic beats (EB) number and duration (EBD). Left ventricular mass (LVM) was also evaluated by standard echocardiography.
A slight but not significant decrease in HR, MHR, and mHR was observed after 6-month PEG, whereas a significant decrease in HR (P=0.03), MHR (P=0.05), and mHR (P=0.05) was found after 18-month PEG compared with baseline. LVM significantly (P=0.05) correlated with MRH (r=−0.50) after short-term treatment, and with HR (r=−0.54) and mHR (r=−0.55) after long-term treatment. Long-term PEG induced the complete recovery of arrhythmias recorded at baseline in one patient and the improvement of rhythm disorders developed after 6-month therapy in another patient. The prevalence of conduction disturbances passed from 15 to 7.7% after long-term PEG.
Long-term treatment with PEG reduces HR, MHR, and mHR and improves rhythm abnormalities in acromegaly.
Renata S Auriemma, Mariano Galdiero, Maria C De Martino, Monica De Leo, Ludovica F S Grasso, Pasquale Vitale, Alessia Cozzolino, Gaetano Lombardi, Annamaria Colao and Rosario Pivonello
The GH/insulin-like growth factor 1 axis is physiologically involved in the regulation of electrolytes and water homeostasis by kidneys, and influences glomerular filtration and tubular re-absorption processes. The aim of the study was to investigate renal structure and function in acromegalic patients during active disease and disease remission.
Thirty acromegalic patients (15 males and 15 females), aged 32–70 years, were enrolled for the study. Ten de novo patients had active disease, whereas 20 patients showed disease remission 1 year after medical treatment with somatostatin analogs (SA) (ten patients) or surgery (ten patients). Thirty healthy subjects matched for age, gender, and body surface area were enrolled as controls.
In both active (A) and controlled (C) patients, creatinine clearance (P<0.001) and citrate (P<0.05) and oxalate levels (P<0.001) were higher, whereas filtered Na (P<0.001) and K (P<0.001) fractional excretions were lower than those in the controls. Urinary Ca (P<0.001) and Ph (P<0.05) levels were significantly increased compared with the controls, and in patients with disease control, urinary Ca (P<0.001) levels were significantly reduced compared with active patients. Microalbuminuria was significantly increased in active patients (P<0.05) compared with controlled patients and healthy control subjects. The longitudinal (P<0.05) and transverse (P<0.05) diameters of kidneys were significantly higher than those in the controls. In all patients, the prevalence of micronephrolithiasis was higher than that in the controls (P<0.001), and was significantly correlated to disease duration (r=0.871, P<0.001) and hydroxyproline values (r=0.639, P<0.001).
The results of the current study demonstrated that acromegaly affects both renal structure and function. The observed changes are not completely reversible after disease remission.