Oral and maxillofacial manifestations of Gardner's syndrome associated with growth hormone deficiency: case report and literature review.

Gardner's syndrome (GS) is a hereditary disorder inherited as autosomal dominant with complete penetrance and variable expression. GS is a variant of familial adenomatous polyposis characterized by extracolonic manifestations including osteomas, dental anomalies, and epidermoid cysts. The association between GS and endocrine abnormalities has been well documented but a direct pituitary involvement has never been reported. We present a case of oral and maxillofacial manifestations in an adult patient affected by GS associated with growth hormone deficiency, a hitherto unreported association. The possible pathogenic mechanisms are discussed.     

Oral and maxillofacial manifestations of Gardner's syndrome associated with growth hormone deficiency: case report and literature review

Gardner's syndrome (GS) is a hereditary disorder inherited as autosomal dominant with complete penetrance and variable expression. GS is a variant of familial adenomatous polyposis characterized by extracolonic manifestations including osteomas, dental anomalies, and epidermoid cysts. The association between GS and endocrine abnormalities has been well documented but a direct pituitary involvement has never been reported. We present a case of oral and maxillofacial manifestations in an adult patient affected by GS associated with growth hormone deficiency, a hitherto unreported association. The possible pathogenic mechanisms are discussed.     

Efficacy of Combined Treatment with Lanreotide and Cabergoline in Selected Therapy-Resistant Acromegalic Patients

The aim of this study was to evaluate the efficacy of a 6-month treatment with lanreotide (LAN) (60–90 mg/month) alone and combined with cabergoline (CAB) (1.5-3 mg/week) in 10 acromegalic patients previously demonstrated to be poor responders to octreotide (OCT) (0.6 mg/day) alone and combined with quinagolide (CV) (0.6 mg/day).All patients had previously undergone unsuccessful surgery and none of them received radiotherapy. Immunohistochemistry showed intense positive GH staining in all adenomas, positive PRL staining in 5 adenomas and faint ACTH or FSH/LH positive staining in other 2 adenomas. Moderately elevated serum PRL levels (35 and 47 ng/ml) were recorded in two patients. Fasting plasma IGF-I and serum GH levels were assayed at baseline and 30, 60, 90 and 120 days after each treatment. Gallbladder ultrasonography and sellar MRI were performed before and after 6 months of OCT and LAN treatments.After OCT treatment circulating GH and IGF-I levels remained elevated in all patients, while after 3 months of combined OCT+CV treatment, serum GH levels were suppressed (below 2.5 ng/ml) in only 1 patient. Significant increase of the percent GH (83.9±4.3 vs. 70.3±5.6%, p<0.01) and IGF-I suppression (54±4.4 vs. 45.3±5.7, p<0.01) and decrease of the nadir of GH (8.5±1.2 vs. 14.6±1.9 ng/ml, p<0.01) and IGF-I (400.9±32.8 vs. 462.1±45.1 ng/ml) were obtained with the combined treatment when compared to OCT treatment alone. After a 15–30 days wash-out, circulating GH and IGF-I levels significantly increased up to pretreatment level in all patients. After 6 months of treatment with LAN, suppression of serum GH was achieved in 1 patient, but no difference in GH (66.3±6.3%) and IGF-I (43.9±4.6%) suppression was recorded in comparison to OCT treatment. After 3 months of treatment with LAN combined with CAB, suppression of serum GH and normalization of plasma IGF-I levels was achieved in 4 and 5 patients, respectively. Percent suppression of GH (88.1±2.1%) and IGF-I (57.5±2.8%) was significantly greater with the combined treatment than with LAN treatment alone. In the 7 patients with evident residual mass no change was documented by magnetic resonance imaging (MRI). None of the patients withdrew LAN+CAB treatment for poor tolerance, one patient had mild hypotension. Sludge was shown after 6 months of LAN treatment in one patient without notable change after 3 months of LAN+CAB treatment.In conclusion, the treatment with dopaminergic drugs such as CV and CAB, significantly increased the efficacy of somatostatin analogs, and can be used in combined therapy in poorly responsive patients.     

Effect of growth hormone (GH) and/or testosterone replacement on the prostate in GH-deficient adult patients

The prostate is a target organ of the GH and IGF-I axis because prostate hypertrophy is found in acromegaly, reduced prostate size is found in GH deficiency (GHD) patients, and additionally, IGF-I is reported to be a positive predictor factor of prostate cancer. To investigate whether GH replacement therapy in adult patients with GHD has adverse effects on the prostate, we studied the effect of 12-month GH or GH plus testosterone replacement on prostate pathophysiology in 24 adult patients with GHD (11 euandrogenemic and 13 hypoandrogenemic), compared with 24 age-matched healthy controls. At study entry, GHD patients had lower prostate volume than controls (19.4 +/- 1.7 vs. 24.9 +/- 1.7 ml; P = 0.03). After 12 months of treatment, all hypoandrogenemic patients achieved normal testosterone levels, and prostate volume increased in the patients to the same level as controls (25.0 +/- 1.9 ml). The percentage increase in prostate volume was greater in hypoandrogenemic patients receiving both GH and testosterone replacement (51 +/- 11%) than in those receiving GH replacement alone (15 +/- 3%; P < 0.0009). At baseline, prostate volume was similar in GHD patients below or above 60 yr of age (16.8 +/- 1.3 vs. 23 +/- 3.6 ml; P = 0.08), whereas after treatment it was higher in the latter patients (21.8 +/- 1.2 vs. 29.5 +/- 3.9 ml; P = 0.04). Prostate-specific antigen (PSA) and free PSA did not change, whereas PSA density was significantly reduced after treatment in hypoandrogenemic patients; there was also no change in calcifications, cysts, or nodules. In conclusion, GH replacement restores prostate size to normal in both young and elderly patients, with no increase in prostate abnormalities. Because the simultaneous treatment with GH and testosterone induces an increase of prostate size by 50% of baseline on average, care is suggested in elderly patients with prostate hyperplasia to avoid any risk of prostate symptoms. In these cases, GH replacement might be performed sequentially to reduce the hypertrophic effect of combining GH and testosterone.     

Uncommon Clinical Course of Multiple Osteochondromatosis in a Patient with a Long-Term History of Cushing's Disease

Cushing's disease (CD), the chronic endogenous hypercortisolism derived from an ACTH-secreting pituitary adenoma, and multiple osteochondromatosis (MO), a congenital mesoderm dyschondroplasia, represent two distinct rare neoplastic diseases. Clinical appearance of MO usually occurs during the first-second decade of life. In fact, the growth of osteochondromas parallels the patient's growth, then becoming quiescent after the closure of the epiphyses and the achievement of final stature. Here we describe an uncommon case of a patient with a long-term history of childhood-onset CD, who surprisingly developed MO during the third decade of life, after the remission of CD. Indeed, a female patient had been followed for CD from the age of 12 to the age of 24 years, when CD definitively remitted. At the age of 26 the patient complained progressively worsening backache and pain at level of hips and feet. Standard radiography of skeleton showed multiple bone dysmorphisms at level of the four limbs, spine and pelvis consistent with multiple osteochondromas and exostoses. A diagnosis of MO was performed. Total body bone scintigraphy with ^99mTc-MDP revealed an increased uptake of the radioligand, suggesting an increased metabolic turnover in correspondence of the majority of the osteochondromas. However, the negativity of the majority of the lesions at ^99mTc-DMSA scintigraphy and the histological diagnosis of benign osteochondroma of the only positive lesion at ^99mTc-DMSA evidenced that the high metabolic activity of the osteochondromas was not due to malignant transformation. However, the activity of the lesions was highly surprising considering that they usually become quiescent after the achievement of the final stature. In last analysis, the uncommon characteristics of MO and, particularly, its occurrence after stable remission of hypercortisolism, suggests a possible role of glucocorticoids in influencing the clinical course of the skeletal disease. The inhibitory effect of hypercortisolism on bone growth and maturation could explain the block in the proliferation of skeletal lesions during the developmental age, where CD was in the active phase, and the opposite effect of stimulation of the ostochondromas growth during stable normalization of cortisol secretion, after CD remission.     

Vertebral artery dissection complicated by basilar artery occlusion successfully treated with intra-arterial thrombolysis: three case reports

Cervical artery dissection is an important cause of stroke in young patients and accounts of 10%–20% of stroke or TIA in patients aged less than 50 years. Basilar artery occlusion (BAO) is an infrequent cause of acute stroke, which invariably leads to death or long-term disability if not recanalized. We describe three patients with BAO caused by vertebral dissection, successfully treated with intra-arterial thrombolysis. The lysis of the occluding embolus was obtained by injection of the thrombolytic drug directly or near the thrombus without haemor-rhagic complications. Our cases confirm the safety and efficacy of intra-arterial thrombolysis in patients with BAO due to a vertebral artery dissection.     

Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours

Pituitary tumours express both somatostatin and dopamine receptors. Medical treatment with somatostatin analogues is a cornerstone of GH- and TSH-secreting tumours, while treatment with dopamine agonists is a cornerstone of prolactin-secreting tumours. Dopamine agonists have also demonstrated some efficacy in patients with GH- and TSH-secreting adenomas. Neither ACTH-secreting nor clinically non-functioning tumours have a well-established medical treatment. Nevertheless, some recent results have indicated a potential usefulness of the dopamine agonist cabergoline in patients with pituitary-dependent Cushing's disease. Combination treatment with both somatostatin analogues and dopamine agonists has been poorly investigated. Some studies conducted in small series have documented an additive effect of both drugs in patients with GH-secreting adenomas. Of mention is that none of the studies were randomised and cross-sectional so that the results should be confirmed by other well-designed studies. No data are available in other pituitary tumour histotypes. Preliminary observations in patients with clinically non-functioning adenomas are very promising.     

Sulfur amino acids in Cushing's disease: insight in homocysteine and taurine levels in patients with active and cured disease

BACKGROUND: Cushing's syndrome is associated with an increased cardiovascular risk. Although a series of cardiovascular risk factors have been identified, sulfur amino acids (SAAs), recently indicated as independent cardiovascular risk factors, have been poorly investigated in patients with Cushing's syndrome. AIM: The aim of this cross-sectional controlled study was to evaluate serum and urinary levels and urinary excretion rate (ER) of SAAs in patients with Cushing's disease (CD) during the active disease and after long-term disease remission. SUBJECTS AND METHODS: Forty patients with CD (20 with active disease and 20 with cured disease for at least 5 yr) and 40 controls entered the study. Serum and urinary concentrations and urinary ER of SAAs, namely methionine, cystine, homocysteine, and taurine, were measured by means of cationic exchange HPLC. Serum folic acid and vitamin B12 levels were also evaluated in patients and controls and correlated to SAA levels. RESULTS: CD patients with active disease had higher serum and urinary concentrations of cystine and homocysteine, and lower serum and higher urinary concentrations and ER of taurine than cured patients and controls. Vitamin B12 levels were significantly decreased in patients with active disease compared with cured patients and controls, whereas folic acid levels were slightly decreased in patients than in controls. In patients with active CD, urinary cortisol concentrations were significantly and inversely correlated to serum taurine and directly correlated to taurine urinary ER, and fasting serum glucose levels were significantly correlated to taurine urinary ER. At the multiple regression analysis, urinary cortisol concentrations were the best predictors of taurine ER. CONCLUSIONS: CD is associated with hyperhomocysteinemia and hypotaurinemia. Glucocorticoid excess, acting directly or indirectly, seems to be the most responsible for this imbalance in SAA levels. The long-term disease remission is accompanied by normalization of SAA levels. Hyperhomocysteinemia and hypotaurinemia might contribute to the increased cardiovascular risk of CD.     

Immunohistochemistry and differential diagnosis of a solitary flat laryngeal xanthoma: a case report

A 35-year-old woman presented with dyspnea, recurrent laryngitis and gastroesophageal reflux disease. Laryngoscopic examination revealed a yellow lesion on the anterior site of the left true vocal cord. No abnormal lesions were found in other portions of the larynx. The lesion was biopsied and a histological examination showed numerous foamy cells diffusely presented in the stroma of the specimen. Overlying squamous epithelium did not show cellular atypia. On the basis of histological appearance, the possible differential diagnosis included xanthomatous lesion, granular cell tumor or epithelial neoplasia. CD68, S-100 protein and cytokeratin immunoreactivities were investigated. Immuno-histochemically, foamy cells were positive for CD68, indicating a histiocytic origin.     

Body composition changes and cardiometabolic benefits of a balanced Italian Mediterranean Diet in obese patients with metabolic syndrome

Metabolic syndrome (MS) is a cluster of metabolic alteration associated with a higher risk of cardiovascular disease and overall mortality than the single alterations alone. The Italian Mediterranean Diet (IMD) can exert a positive effect on cardiovascular risk and related morbidity and mortality. The aim was to evaluate the benefits of dietary intervention based on a typical IMD on body composition, cardiometabolic changes and reduction in cardiovascular disease in patients with MS. Eighty White Italian subjects with MS were prescribed a balanced hypocaloric IMD. We investigated dietary habits and impact of the diet on health status, blood biochemical markers, anthropometric measurements and body composition during a 6-month follow-up period. Body composition, fat mass and distribution were assessed by Dual X-ray absorptiometry. Adherence to the IMD led to a decrease in body weight (102.59 ± 16.82 to 92.39 ± 15.94 kg, p < 0.001), body mass index (BMI) (38.57 ± 6.94 to 35.10 ± 6.76, <0.001) and waist circumference (112.23 ± 12.55 vs 92.42 ± 18.17 cm, p < 0.001). A significant loss of total body fat especially in waist region was observed. The MS was resolved in 52 % of the patients. Significant improvements in systolic and diastolic blood pressure and fasting glucose occurred. Low-density lipoprotein cholesterol was reduced from 128.74 ± 33.18 to 108.76 ± 38.61 mg/dl (p < 0.001), triglycerides from 169.81 ± 80.80 to 131.02 ± 63.88 mg/dl (p < 0.001). The present results suggest that a dietary intervention based on a typical IMD effectively promotes weight loss and reduces the growing burden of cardiovascular risk factors that typifies patients with MS.