Testosterone deficiency in non-cancer opioid-treated patients.

PURPOSE: The use of opioids in patients with chronic non-cancer pain is common and can be associated with opioid-induced androgen deficiency (OPIAD) in men. This review aims to evaluate the current literature regarding the prevalence, clinical consequence and management of OPIAD. METHODS: A database search was performed in Medline, Embase and Cochrane using terms such as "analgesics", "opioids" and "testosterone". Relevant literature from January 1969 to March 2018 was evaluated. RESULTS: The prevalence of patients with OPIAD ranges from 19 to 86%, depending on the criteria for diagnosis of hypogonadism. The opioid-induced suppression of gonadotropin-releasing and luteinizing hormones represents the main important pathogenetic mechanisms. OPIAD has significant negative clinical consequences on sexual function, mood, bone density and body composition. In addition, OPIAD can also impair pain control leading to hyperalgesia, which can contribute to sexual dysfunction and mood impairment. CONCLUSIONS: OPIAD is a common adverse effect of opioid treatment and contributes to sexual dysfunction, impairs pain relief and reduces overall quality of life. The evaluation of serum testosterone levels should be considered in male chronic opioid users and the decision to initiate testosterone treatment should be based on the clinical profile of individuals, in consultation with the patient.

Therapeutic indications in upper cervical spine instability. Considerations on 58 cases.

BACKGROUND: The particular biomechanics of the upper cervical spine require, when trauma occurs, careful evaluation of the stability of the lesions, in order to guarantee the best possible therapeutic and prognostic approach. To date, there has been no uniformity of opinion in merit, especially with reference to treatment of odontoid fractures. It is necessary for this reason as much as for the opportune standardisation of the patients' classification parameters to establish what is meant by stability and which lesions are to be held as being unstable in the upper cervical spine. METHODS: All the cases of upper cervical spine instability treated in our Unit from '94 to date have been reviewed. Four fractures to the first cervical vertebra, 29 to the odontoid process, 9 isolated fractures in the C2 body, 12 hangman fractures, 7 fractures of the articular processes, 2 to the occipital condyles and 4 C1-C2 dislocations without fractures were localised. Using precise prognostic indexes as our classification criteria, 56 of the 58 patients observed were addressed towards either conservative treatment or directly towards surgical treatment. In particular, 29 patients were conservatively treated with a collar or Halo-Vest. Twenty-seven surgical operations were carried out: 14 screw fixations, 6 anterior fixations using plates and screws, 4 rear ones using metal wire or wire with bone graft, 3 odontectomy operations associated with posterior fixation. RESULTS: In the follow-up, using a range of between three months to six years, good fusion with spine stabilisation was achieved in all the patients treated. In particular, surgery was carried out as the first therapeutic indication in 25 cases, obtaining excellent results. Surgery was necessary in only 2 cases after the failure of external stabilisation. CONCLUSIONS: The judgement passed on instability in traumatic lesions in the upper cervical spine represents the decisive factor in the choice of the therapeutic option. Instead of always opting for conservative treatment, in the case of C1-C2 fractures-luxations, and going ahead with surgery only when there is instability or non-fusion of the segments resulting after successive monitoring, we believe that the definition and standardisation of the prognostic factors is opportune, in order to provide patients with a specific solution, in such a way as to reduce the failure percentage of the first treatment and optimise the healing time.

Transnasal endoscopic repair of cerebrospinal fluid fistulas and encephaloceles: surgical indications and complications.

INTRODUCTION: Transnasal endoscopic repair of cerebrospinal fluid (CSF) fistulas is recommended for patients with CSF leaks who do not respond to conservative treatment. It is a safer and more successful alternative to transcranial surgery. PATIENTS AND METHODS: We present our experience on using transnasal endoscopy for the repair of anterior skull base cerebrospinal fluid fistulas. Between 1999 and 2003 we observed 20 patients with CSF rhinorrhea. The etiology was heterogeneous: post-traumatic in 6 cases, iatrogenic in 6 cases (one interesting case of meningioma of the sphenoethmoid plate), dysembryogenetic - due to encephaloceles - in 4 patients (one with Cruzon syndrome and one with Down syndrome) and idiopathic in the other 4 patients. Use of a rigid transnasal endoscope allowed the localization and repair of all fistulas, with the use of fluorescein in 6 cases. Different grafts were used, in particular fat, bone or chondral septum with mucoperiosteum or perichondral mucosa. Generally the graft was inserted with the underlay or the sandwich technique. Lumbar drainage was used in the postoperative period only in 6 cases. No antibiotic prophylactic therapy was used. RESULTS: Endoscopy was successful in 90 % of patients at the first attempt, and in 95 % of patients at the second approach. We had two late complications such as infections. In one child with a post-traumatic fistula and shunt for hydrocephalus, we observed meningitis 2 years after the first endoscopic surgery and he underwent both transnasal endoscopic surgery and transcranial surgery. The second patient was a woman with a spontaneous fistula, who had rhinoliquorrhea three years after the first surgical treatment. During surgery a strange similar purulent material filling the submucous space of the ethmoid roof was found, suggestive for an intranasal abscess that was removed. We did not see any complications such as hematomas or seizures. The follow-up (range: 6 months to 3 years) made both with MRI and rhinoscopy has not shown any relapse until now in 19 of 20 patients treated only with endoscopy. CONCLUSIONS: The endoscopic approach is highly effective and safe in the treatment of CSF fistulas, with great visualization and minimal invasiveness, for which it is associated to a very low morbidity. The fluorescein technique is extremely helpful for the diagnosis and surgery of CSF leaks.

[Prospective pharmacologic treatments for subarachnoid hemorrhage]. / Prospettive farmacologiche del trattamento nell'ESA.

The aim of pharmacological therapy in subarachnoid haemorrhage (SAH) is to prevent cerebral ischemia and consequent events. Vasospasm, energy decrease, altered Ca++ homeostasis, lactic acidosis and free radicals are responsible for cerebral ischemic damage. Drug therapy in SAH is necessary before, during and after surgical treatment. Nimodipine is the only drug used today and supported by many clinical trials; scientific trials, on using known and new substances in SAH drug therapy, are in progress.

111Indium-pentetreotide pituitary scintigraphy and hormonal responses to octreotide in acromegalic patients.

GH secreting pituitary adenomas are frequently visualized by scintigraphy with the somatostatin analogue 111Indium-pentetreotide. We studied 111Indium-pentetreotide scintigraphy and hormonal responses to octreotide in 12 acromegalic patients. Nine patients with active acromegaly were studied before pituitary adenomectomy; 6 of these and 3 other patients were studied after operation. GH was measured after a single s.c. dose of 100 micrograms of octreotide (acute test). The patients were preoperatively treated with 100 micrograms s.c. tid octreotide for 3 months as were patients who had been unsuccessfully operated; GH and IGF-I were measured at the end of this period (chronic treatment). A decrease of the hormones higher than 50% of basal values was considered a positive response in both acute test and chronic treatment. Eight/nine unoperated patients had a pituitary adenoma visualized by scintigraphy and a positive response to both the acute test and chronic treatment; one patient had no evidence of tumor at scintigraphy and he did not respond to octreotide. Scintigraphy was negative in all of the three patients cured by surgery. Six patients still had active disease after adenomectomy: scintigraphy was positive only in one case, although GH responded to octreotide treatment in all patients. Conclusions. 111In-pentetreotide scintigraphy frequently visualizes pituitary adenomas and predicts GH responses to octreotide in unoperated acromegalic patients. In unsuccessfully operated patients scintigraphy is infrequently positive and does not predict which patients will respond to octreotide. These data and the cost of 111In-pentetreotide scintigraphy do not warrant its extensive clinical use in acromegaly.

Pituitary microadenomas: surgical results and morphological findings.

The results of transsphenoidal microsurgery in treating 22 patients with pituitary microadenomas are reported. Histological and ultrastructural comparative studies were performed in attempting to obtain a more accurate morphological classification of pituitary microadenomas.

Clinical presentation and outcome of pituitary adenomas in teenagers.

OBJECTIVE: Pituitary adenomas rarely occur in childhood and adolescence, but their mass effect and endocrine abnormalities can compromise both quality and length of life. In this study we evaluated the symptoms at onset and the long-term consequences induced in teenagers by functioning or nonfunctioning pituitary adenomas. DESIGN AND PATIENTS: Clinical, biochemical and neuroradiological data of 44 young patients (12 males and 32 females, aged 16.3 +/- 1.9 years at diagnosis) with pituitary adenomas were evaluated retrospectively at baseline and after therapy. Patients underwent surgery, radiotherapy and/or medical treatment depending on clinical history and endocrine secretion of the tumour. Follow-up ranged from 8 to 252 months (median 55 months). MEASUREMENTS: Baseline and dynamic pituitary function were evaluated in all cases at diagnosis and after treatments. Magnetic resonance imaging (MRI) or computed tomography (CT) scan were performed before therapy and during follow-up. Hormone levels were measured using commercial radioimmunologic or immunoradiometric methods. RESULTS: Pituitary macroadenomas (group 1) or microadenomas (group 2) were found in 61% and 39% of cases, respectively. Overall, 68% were PRL-secreting, 7% GH-secreting, 5% ACTH-secreting and 20% nonfunctioning. The most frequent symptoms at onset were oligoamenorrhoea (62%) and galactorrhoea (59%) in the girls, and headache (58%) in the boys. Pubertal development was delayed in 12/27 (44%) cases with macroadenoma. Growth failure was observed in 4/44 (9%) patients (3 in group 1 and 1 in group 2). At diagnosis, hypopituitarism was detected in 10/27 (37%) patients with macroadenoma. Surgery alone cured 4/18 (22%) and 4/9 (44%) patients in group 1 and group 2, respectively. Adjuvant therapies (second surgery and/or radiotherapy and/or medical treatment) cured the disease in 2/13 (15%) patients with macroadenoma and allowed a persistent normalization in other 4/13 (31%) and 2/4 (50%) cases in group 1 and group 2, respectively. Medical treatment alone cured 2/9 (22%) patients with PRL-secreting macroadenoma and normalized PRL levels in another six (66%) with macroprolactinoma and in 2/7 (28%) patients with microprolactinoma. CONCLUSION: Delay of growth was rarely observed in teenagers with pituitary adenomas. At the onset of the disease, many girls complained of oligoamenorrhoea and galactorrhoea, while headache and delay of pubertal development were the symptoms more frequently referred by boys. Surgery alone was effective in a minority of patients and adjuvant therapies were helpful to obtain the remission of the disease in many cases. In patients with PRL-secreting pituitary adenoma, medical treatment, both as first choice or as adjuvant therapy, normalizes serum PRL levels in 14/27 (52%) cases.

Long-term effects of octreotide on markers of bone metabolism in acromegaly: evidence of increased serum parathormone concentrations.

The effects of octreotide on biochemical markers of bone turnover were evaluated in patients with active acromegaly. Serum GH, IGF-I and serum and urinary markers of bone metabolism were measured before and after 4 months of treatment in 27 patients (short-term treatment) and after 12 and 24 months of treatment in 15 patients (long-term treatment). In the short-term, octreotide significantly decreased the levels of serum GH, IGF-I, calcium, osteocalcin, carboxyterminal propeptide of type I collagen and alkaline phosphatase plus urinary excretion of calcium. Short-term treatment significantly increased serum parathormone levels (before treatment 30.1 +/- 9.57 and at 4 months 46.1 +/- 24.98 ng/L, p < 0.001) and urinary excretion of phosphate; urinary excretion of hydroxyproline was unchanged. The same results were observed during long-term treatment, except that there was no significant difference of serum calcium and alkaline phosphatase levels before and after treatment. Parathormone concentrations were still higher at 24 months compared with those prior to treatment (before treatment 31.9 +/- 9.74 and at 24 months 44.9 +/- 21.18 ng/L, p < 0.05). The changes of most bone markers during octreotide therapy can be explained by the decrease of serum GH and IGF-I concentrations. On the other hand, the rise of parathormone concentrations suggests that octreotide has ulterior and long-standing actions on calcium homeostasis: intestinal malabsorption of calcium due to the octreotide could contribute to this secondary hyperparathyroidism. The clinical consequences of these alterations of bone metabolism need to be further clarified.

Pituitary adenomas in childhood and adolescence. Clinical analysis of 10 cases.

Pituitary adenomas in childhood and adolescence constitute 2-6% of all operated pituitary adenomas. We report the clinical features, treatment and follow-up of 10 pediatric patients affected by pituitary adenomas. All patients underwent clinical evaluation, endocrine tests, magnetic resonance imaging and visual field assessment. Follow-up ranged from 8 to 132 months (median 52.6). All patients were older than 10 years of age; 60% were males. In 50% the initial complaints were headache and/or visual impairment, all except one had clear evidence of endocrine dysfunction. Ninety percent were macroadenomas. According to hormone measurements and immunostaining 50% were prolactinomas, 20% were pure GH-secreting and 30% were non-functioning adenomas. Prolactinomas in two females were successfully treated with cabergoline. The other patients underwent surgery: three prolactinomas are still being treated with dopamine agonists and a GH-secreting adenoma is being treated with octreotide LAR and cabergoline. Two patients were also treated with conventional radiotherapy. Treatments were completely successful in 50% of patients: these have normal hormone secretion, full pubertal development, no significant tumor mass and normal visual field. Hypersecretion of prolactin persists in two cases; partial or complete hypopituitarism is present in four, relevant tumor remnant in another four and impairment of visual field is present in two cases. In conclusion, pediatric adenomas occur mostly in pubertal age, are prevalently macroadenomas and clinically functioning. Medical therapy should be preferred for secreting adenomas, but in some cases, notably prolactinomas in males, surgery and eventual radiotherapy may be needed.

Development of a meningioma in a patient with acromegaly during octreotide treatment: are there any causal relationships?

Somatostatin receptors are highly expressed in almost all meningiomas but in this setting their functional role is not clear. A 59-yr-old woman had been treated with octreotide after an unsuccessful operation for a GH-secreting pituitary adenoma. After 8 yr of treatment, a nuclear magnetic resonance (NMR) scan disclosed a 3 cm meningioma of the tentorium. Mean GH was 2.2 ng/ml and IGF-I 325 ng/ml. Meningioma was resected and tissue was digested to obtain tumor cell suspension. Aim of the study was to measure epidermal growth factor (EGF)-induced proliferation of cultured meningioma cells in the presence of either somatostatin or octreotide. Cells were grown to semiconfluency in Dolbecco's modified eagle medium (D-MEM) supplemented with 10% fetal calf serum (FCS). After 48 h in D-MEM without serum, the medium was replaced by fresh medium plus recombinant EGF (10 ng/ml) and somatostatin or octreotide were added in the final concentrations of 1, 10 and 100 nM. 20 h later 1 microcgCi of 3H-thymidine was added to each well. After 4 h, incorporated radioactivity was measured. While octreotide did not influence significantly cell growth at the three dose tested, somatostatin increased thymidine incorporation dose-dependently (peak 100 nM: 150% +/- 27% vs medium plus EGF, p<0.05). Octreotide effectively suppressed GH secretion in our acromegalic patient but is unlikely that its long-term use could have stimulated the growth of meningioma since it did not significantly influence the in vitro proliferation of the meningioma cells. These results suggest that somatostatin-mediated proliferative effect on meningioma cells is not mediated by the subtype 2 of the somatostatin receptor.