Characteristics of different mesh types for abdominal wall repair in an experimental model of peritonitis.

BACKGROUND: The use of synthetic mesh to repair a potentially contaminated incisional hernia may lead to higher failure rates. A biological mesh might be considered, but little is known about long-term results. Both biological and synthetic meshes were investigated in an experimental model of peritonitis to assess their characteristics in vivo. METHODS: Male Wistar rats were randomized into five groups and peritonitis was induced. A mesh was implanted after 24 h. Five meshes were investigated: Permacol™ (cross-linked collagen), Strattice™ (non-cross-linked collagen), XCM Biologic® (non-cross-linked collagen), Omyra® Mesh (condensed polytetrafluoroethylene) and Parietene™ (polypropylene). The rats were killed after either 30, 90 or 180 days. Incorporation and shrinkage of the mesh, adhesion coverage, strength of adhesions and histology were analysed. RESULTS: Of 135 rats randomized, 18 died from peritonitis. Some 180 days after implantation, both XCM Biologic® and Permacol™ had significantly better incorporation than Strattice™ (P = 0·003 and P = 0·009 respectively). Strattice™ had significantly fewer adhesions than XCM Biologic® (P = 0·001) and Permacol™ (P = 0·020). Thirty days after implantation, Permacol™ had significantly stronger adhesions than Strattice™ (P < 0·001). Shrinkage was most prominent in XCM Biologic® , but no significant difference was found compared with the other meshes. Histological analysis revealed marked differences in foreign body response among all meshes. CONCLUSION: This experimental study suggested that XCM Biologic® was superior in terms of incorporation, macroscopic mesh infection, and histological parameters such as collagen deposition and neovascularization. There must be sufficient overlap of mesh during placement, as XCM Biologic® showed a high rate of shrinkage. Surgical relevance The use of synthetic mesh to repair a potentially contaminated incisional hernia is not supported unequivocally, and may lead to a higher failure rate. A biological mesh might be considered as an alternative. There are few long-term studies, as these meshes are expensive and rarely used. This study evaluated the use of biological mesh in a contaminated environment, and investigated whether there is an ideal mesh. A new non-cross-linked biological mesh (XCM Biologic® ) was evaluated in this experiment. The new non-cross-linked biological mesh XCM Biologic® performed best and may be useful in patients with a potentially contaminated incisional hernia.

Wegener's granulomatosis presenting as a thyroid mass.

A 71-year-old patient was referred for suspected hyperthyroidism because of a 15-kg weight loss, suppressed thyroid stimulating hormone (TSH), and a 4-cm nodule in the left thyroid lobe. Both free T4 and T3 were normal. Antithyroglobulin, anti-TSH receptor and antimicrosomal antibodies were absent. Thyroid scintigraphy showed a cold nodule in the left thyroid lobe. CAT scan of the neck revealed a 4-cm inhomogeneous nodule at the left side. An elevated sedimentation rate suggested bacterial thyroiditis, localized Quervain thyroiditis, malignancy, and the fibrosing variant of Hashimoto's thyroiditis or Riedel's thyroiditis. A fine needle biopsy of the thyroid nodule showed no malignant cells but was inconclusive. A true cut biopsy demonstrated atypical inflammation and also failed to reveal the diagnosis. Therefore, the patient was admitted to the hospital for further work-up and was unexpectedly found to have nodular lesions in the lung on a chest X-ray. Additional blood analysis revealed a positive cytoplasmic ANCA-titer. After inconclusive peripheral lung biopsies, a left hemithyroidectomy and a very large video-assisted thoracoscopic lung biopsy were performed, both revealing extensive zones of necrosis surrounded by granulomatous foci pointing to the diagnosis of Wegener's granulomatosis (WG) disease. To our knowledge, this is the first report of a well-documented WG of the thyroid gland. Although extremely rare, WG should be included in differential diagnosis of inflammatory lesions of the thyroid gland.

The 'AbdoMAN': an artificial abdominal wall simulator for biomechanical studies on laparotomy closure techniques.

PURPOSE: Incisional hernia remains a frequent complication after abdominal surgery associated with significant morbidity and high costs. Animal and clinical studies have exhibited some limitations. The purpose of this study was to develop an artificial human abdominal wall (AW) simulator in order to enable investigations on closure modalities. We hypothesized that a physical model of the human AW would give new insight into commonly used suture techniques representing a substantial complement or alternative to clinical and animal studies. METHODS: The 'AbdoMAN' was developed to simulate human AW biomechanics. The 'AbdoMAN' capacities include measurement and regulation of intra-abdominal pressure (IAP), generation of IAP peaks as a result of muscle contraction and measurements of AW strain patterns analyzed with 3D image stereo correlation software. Intact synthetic samples were used to test repeatability. A laparotomy closure was then performed on five samples to analyze strain patterns. RESULTS: The 'AbdoMAN' was capable of simulating physiological conditions. AbdoMAN lateral muscles contract at 660 N, leading the IAP to increase up to 74.9 mmHg (range 65.3-88.3). Two strain criteria were used to assess test repeatability. A test with laparotomy closure demonstrated closure testing repeatability. CONCLUSIONS: The 'AbdoMAN' reveals as a promising enabling tool for investigating AW surgery-related biomechanics and could become an alternative to animal and clinical studies. 3D image correlation analysis should bring new insights on laparotomy closure research. The next step will consist in evaluating different closure modalities on synthetic, porcine and human AW.

Frozen section in thyroid surgery.

OBJECTIVE: We studied the use of frozen section in the detection of malignancy in thyroid surgery in a large teaching hospital. MATERIALS AND METHODS: We reviewed all case notes of patients operated on for thyroid disease between January 1st 1997 and December 31st 2004. We identified 420 operations in 408 patients. Data were available for 417 operations. RESULTS: In patients with a solitary thyroid nodule, a frozen section is sometimes performed. Frozen section was done in 128 of 417 operations. The specificity for malignancy was 98.16%. The positive predictive value was 81.81% and the negative predictive value 93.85%. However the sensitivity was 56.25%. Frozen section is a time-consuming investigation. With follicular lesions it is very difficult to distinguish between benign disease and malignancy since the diagnosis of malignancy depends on capsular and/or blood vessel invasion. Also it costs about 100 Euro (approximately 125 dollars). CONCLUSION: This study confirms that adequate histopathologic diagnosis of thyroid disease is based on extensive subsampling of the specimen which is not possible during a peroperatory frozen section procedure.

Mesh expansion as the cause of bulging after abdominal wall hernia repair.

BACKGROUND: Recurrence is the most important complication of abdominal wall reconstruction. It is possible the repair itself is intact, but bulging or expansion of mesh causes recurrent swelling's of the abdominal wall. CASE SUMMARY: In this report, we present bulging of a polyester mesh due to central pore expansion. DISCUSSION: Repetitive stress and variations in intra-abdominal pressure can change tensile strength and stretches mesh materials. CONCLUSION: A swelling after abdominal wall repair can be caused by bulging of the mesh. A progressive bulging might be the result of failure of the mesh implant due to elongation. Mesh characteristics should be considered when choosing a feasible and suitable mesh for abdominal wall reconstruction. Clinical distinction between recurrent hernia and mesh bulging is difficult but therapeutically irrelevant in symptomatic patients.

Emergency repair of inguinal hernia in the premature infant is associated with high direct medical costs.

PURPOSE: Inguinal hernia repair is frequently performed in premature infants. Evidence on optimal management and timing of repair, as well as related medical costs is still lacking. The objective of this study was to determine the direct medical costs of inguinal hernia, distinguishing between premature infants who had to undergo an emergency procedure and those who underwent elective inguinal hernia repair. METHODS: This cohort study based on medical records concerned premature infants with inguinal hernia who underwent surgical repair within 3 months after birth in a tertiary academic children's hospital between January 2010 and December 2013. Two groups were distinguished: patients with incarcerated inguinal hernia requiring emergency repair and patients who underwent elective repair. Real medical costs were calculated by multiplying the volumes of healthcare use with corresponding unit prices. Nonparametric bootstrap techniques were used to derive a 95 % confidence interval (CI) for the difference in mean costs. RESULTS: A total of 132 premature infants were included in the analysis. Emergency surgery was performed in 29 %. Costs of hospitalization comprised 65 % of all costs. The total direct medical costs amounted to €7418 per premature infant in the emergency repair group versus €4693 in the elective repair group. Multivariate analysis showed a difference in costs of €1183 (95 % CI -1196; 3044) in favor of elective repair after correction for potential risk factors. CONCLUSION: Emergency repair of inguinal hernia in premature infants is more expensive than elective repair, even after correction for multiple confounders. This deserves to be taken into account in the debate on timing of inguinal hernia repair in premature infants.

Glomerular filtration rate in patients with Cushing's disease: a matched case-control study.

BACKGROUND: Patients with Cushing's disease have a high prevalence of atherosclerosis and maintain an increased cardiovascular risk even after cure of the disease. However, the impact of Cushing's disease on renal function remains to be quantified. OBJECTIVES: To evaluate glomerular filtration rate (GFR) and to identify predictors of GFR in patients with Cushing's disease. DESIGN AND METHODS: We conducted a matched case-control study: 18 patients with active or cured Cushing's disease were compared with healthy population controls matched for age and sex. The main outcome measures were GFR and micro-albuminuria. RESULTS: Patients with Cushing's disease had a lower GFR, as measured by 24-h creatinine clearance (79 versus 95 ml/min per 1.73 m2, P = 0.005) and estimated by the MDRD2 formula (75 versus 88 ml/min per 1.73 m2, P = 0.008). Multiple regression analyses indicated that disease duration was the strongest predictor for a worse GFR. The prevalence of micro-albuminuria was low (5.5% in both groups). CONCLUSIONS: Patients with Cushing's disease have a decreased GFR. Even if they are cured, close follow-up with strict control of cardiovascular risk factors and monitoring of GFR seems mandatory. Furthermore, the dosage of certain drugs should be adapted to the individual GFR.

Open incisional hernia repair with a self-gripping retromuscular Parietex mesh: a retrospective cohort study.

INTRODUCTION: The Rives-Stoppa and component separation technique are considered to be favourable techniques in the treatment of complex incisional hernias. However, mesh-related complications like chronic pain are still a common problem after mesh repair. As a result, a new self-gripping mesh to omit suture fixation has been developed. This study aimed to evaluate the safety and feasibility of the Parietex™ Progrip self-gripping mesh in retromuscular position for the treatment of incisional hernias. METHODS: Patients with incisional hernia who underwent repair between June 2012 and June 2014, using a self-gripping mesh in retromuscular position, were included in the study. All patients visited the outpatient clinic to identify postoperative complications and early recurrence. RESULTS: A total of 28 consecutive patients with a median age of 48 years were included in the study. Twenty-two patients (79%) were diagnosed with an incisional hernia, of whom nine (32%) had a recurrence. Six patients (21%) had an incisional hernia combined with another abdominal wall hernia. The median follow-up was 12 weeks (IQR: 8-20 weeks). Twenty-three patients (82%) did not report any pain at their final outpatient clinic visit; two patients (7%) reported mild abdominal pain, and three patients (11%) had moderate abdominal pain. None of the 28 patients developed a recurrence during follow-up. CONCLUSION: This is the first study concerning the use of a Parietex™ Progrip mesh placed in retromuscular position. The study shows that it is a safe and feasible prosthesis in incisional hernias repair, as short-term recurrence did not occur and adverse events were limited.

Endocrine consequences of long-term intrathecal administration of opioids.

Intrathecal administration of opioids is a very efficient tool in the long-term control of intractable nonmalignant pain. However, despite the well known role of opioids in endocrine regulation, few data are available about possible effects on hypothalamic-pituitary function during this treatment. Seventy-three patients (29 men and 44 women; mean age, 49.2 +/- 11.7 yr) receiving opioids intrathecally for nonmalignant pain were enrolled for extensive endocrine investigation. At the time of hormonal determination, the mean duration of opioid treatment was 26.6 +/- 16.3 months; the mean daily dose of morphine was 4.8 +/- 3.2 mg. The control group consisted of 20 patients (11 men and 9 women; mean age, 54.2 +/- 14.0 yr) with a comparable pain syndrome but not treated with opioids. Decreased libido or impotency was present in 23 of 24 men receiving opioids. The serum testosterone level was below 9 nmol/L in 25 of 29 men and was significantly lower than that in the control group (P < 0.001). The free androgen index was below normal in 18 of 29 men and was significantly lower than that in the control group (P < 0.001). The serum LH level was less than 2 U/L in 20 of 29 men and was significantly lower than that in the control group (P < 0.001). Serum FSH was comparable in both groups. Decreased libido was present in 22 of 32 women receiving opioids. All 21 premenopausal females developed either amenorrhea or an irregular menstrual cycle, with ovulation in only 1. Serum LH, estradiol, and progesterone levels were lower in the opioid group. In all 18 postmenopausal females significantly decreased serum LH (P < 0.001) and FSH (P = 0.012) levels were found. The 24-h urinary free cortisol excretion was below 20 microg/day in 14 of 71 opioid patients and was significantly lower than that in the control group (P = 0.003). The peak cortisol response to insulin-induced hypoglycemia was below 180 microg/L in 9 of 61 opioid patients and was significantly lower than that in the nonopioid group (P = 0.002). The insulin-like growth factor I SD score was below -2 SD in 12 of 73 opioid patients and was significantly lower than that in the control group (P = 0.002). The peak GH response to hypoglycemia was below 3 microg/L in 9 of 62 subjects and was significantly lower than that in the control group (P = 0.010). Thyroid function tests and PRL levels were considered normal. No metabolic disturbances were recorded, apart from significantly decreased high density lipoprotein cholesterol levels (P = 0.041) and elevated total/high density lipoprotein cholesterol ratio (P = 0.008) in the opioid group compared to the control group. Supplementation with gonadal steroids improved sexual function in most patients. In conclusion, of all patients receiving intrathecal opioids, the large majority of men and all women developed hypogonadotropic hypogonadism, about 15% developed central hypocorticism, and about 15% developed GH deficiency. These findings suggest that further investigations are required to determine the need for systematic endocrine work-up in these patients and the necessity for substitutive therapy.

Cabergoline in the treatment of acromegaly: a study in 64 patients.

Cabergoline is a new, long acting, dopamine agonist that is more effective and better tolerated than bromocriptine in patients with hyperprolactinemia. Because dopamine agonists still have a place in the medical management of acromegaly, cabergoline might be a useful treatment. We, therefore, evaluated the effect of long term administration of cabergoline in a large group of unselected acromegalic patients. Sixty-four patients were included in a multicenter, prospective, open labeled study. A subgroup of 16 patients had GH-/PRL-cosecreting pituitary adenomas. Cabergoline was started at a dose of 1.0 mg/week and was gradually increased until normalization of plasma insulin-like growth factor I (IGF-I) levels, occurrence of unacceptable side-effects, or a maximal weekly dose of 3.5 mg (7.0 mg in 1 case) was reached. Treatment with cabergoline suppressed plasma IGF-I below 300 micrograms/L in 39% of cases and between 300-450 micrograms/L in another 28%. With pretreatment plasma IGF-I concentrations less than 750 micrograms/L, a suppression of IGF-I below 300 micrograms/L was obtained in 53% of cases, and a suppression between 300-450 micrograms/L was obtained in another 32%. By contrast, with pretreatment plasma IGF-I concentrations above 750 micrograms/L, only 17% of cases showed a suppression of IGF-I below 300 micrograms/L, and there was IGF-I suppression between 300-450 micrograms/L in another 21%. In GH-/PRL-cosecreting adenomas, 50% of cases suppressed plasma IGF-I levels below 300 micrograms/L, and another 31% did so between 300-450 micrograms/L, in contrast to only 35% and 27%, respectively in GH-secreting adenomas. Similar results were obtained concerning the secretion of GH. Tumor shrinkage was demonstrated in 13 of 21 patients, with a mass reduction by more than half in 5 GH-/PRL-cosecreting adenomas. Except for slight gastrointestinal discomfort and orthostatic hypotension in a few patients at the beginning of therapy, cabergoline treatment was well tolerated. Only 2 patients stopped medication because of nausea. The weekly dose of cabergoline ranged between 1.0-1.75 mg. A further increase in the dose was only effective in 1 GH-/PRL-cosecreting adenoma. The results of this study suggest that cabergoline is an effective, well tolerated therapy that should be considered in the management of acromegaly, especially if the pituitary adenoma cosecretes GH and PRL or if pretreatment plasma IGF-I levels are below 750 micrograms/L.

Cabergoline in the treatment of hyperprolactinemia: a study in 455 patients.

Cabergoline is a new long-acting dopamine agonist that is very effective and well tolerated in patients with pathological hyperprolactinemia. The aim of this study was to examine, in a very large number of hyperprolactinemic patients, the ability to normalize PRL levels with cabergoline, to determine the effective dose and tolerance, and to assess the effect on clinical symptoms, tumor shrinkage, and visual field abnormalities. We also evaluated the effects of cabergoline in a large subgroup of patients with bromocriptine intolerance or -resistance. We retrospectively reviewed the files of 455 patients (102 males and 353 females) with pathological hyperprolactinemia treated with cabergoline in 9 Belgian centers. Among these patients, 41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic hyperprolactinemia; and 1%, an empty sella. The median pretreatment serum PRL level was 124 microg/L (range, 16-26,250 microg/L). A subgroup of 292 patients had previously been treated with bromocriptine, of which 140 showed bromocriptine intolerance and 58 showed bromocriptine resistance. Treatment with cabergoline normalized serum PRL levels in 86% of all patients: in 92% of 244 patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 macroadenomas. Pretreatment visual field abnormalities normalized in 70% of patients, and tumor shrinkage was seen in 67% of cases. Side effects were noted in 13% of patients, but only 3.9% discontinued therapy because of side effects. The median dose of cabergoline at the start of therapy was 1.0 mg/week but could be reduced to 0.5 mg/week once control was achieved. Patients with a macroprolactinoma needed a higher median cabergoline dose, compared with those with idiopathic hyperprolactinemia or a microprolactinoma: 1.0 mg/week vs. 0.5 mg/week, although a large overlap existed between these groups. Twenty-seven women treated with cabergoline became pregnant, and 25 delivered a healthy child. One patient had an intended abortion and another a miscarriage. In the patients with bromocriptine intolerance, normalization of PRL was reached in 84% of cases, whereas in the bromocriptine-resistant patients, PRL could be normalized in 70%. We confirmed, in a large-scale retrospective study, the high efficacy and tolerability of cabergoline in the treatment of pathological hyperprolactinemia, leaving few patients with unacceptable side effects or inadequate clinical response. Patients with idiopathic hyperprolactinemia or a microprolactinoma, on average, needed only half the dose of cabergoline as those with macroprolactinomas and have a higher chance of obtaining PRL normalization. Cabergoline also normalized PRL in the majority of patients with known bromocriptine intolerance or -resistance. Once PRL secretion was adequately controlled, the dose of cabergoline could often be significantly decreased, which further reduced costs of therapy.

Clinical pharmacokinetics of the antiandrogens and their efficacy in prostate cancer.

Prostatic cancer is the second most common cause of cancer death in males. Treatment by radical prostatectomy and radiotherapy is useful in the early stages of the disease. Whenever metastases occur, patients are usually treated by surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH) analogue] castration. This form of treatment is, however, associated with unwanted adverse effects, such as flushing, loss of libido and potency and all patients ultimately escape therapy after a delay of 1 to 2 years. For this reason antiandrogens have been developed as another means of endocrine ablation therapy. Antiandrogens fall in 2 groups of which the first group, the steroidal antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at the cellular level but also inhibit testosterone production by their additional gestagenic properties blocking gonadotropin secretion. Except in preventing the flare-up associated with the start of GnRH analogue therapy and in reducing flushing, no evidence exist of any superiority for CPA over classical therapy in terms of adverse effects and survival. The second group, the nonsteroidal or 'pure' antiandrogens, only block androgens at the cellular level without any central effects. In contrast with other forms of castration, patients on pure antiandrogens as monotherapy preserve their sexual function and potency, at the expense of a slightly inferior androgen blockade and gynecomastia. These latter effects are explained by a compensatory rise in androgens as a result of the blockade at the central level, which weakens the androgen blockade, and by peripheral aromatisation of the increased androgens to oestrogens. In addition, some evidence exist that pure antiandrogens improve survival if combined with other forms of castration as they also inhibit the adrenal androgens, the so-called maximal androgen blockade (MAB). If patients escape control under MAB, a trial of stopping the antiandrogen must always be considered, as some tumours have 'learned' to be activated by these drugs. At the moment it is not yet clear if antiandrogens are of any benefit in downstaging the extent of disease before prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens, bicalutamide offers some advantages over flutamide as it possesses a much longer half-life, allowing a once daily regimen, and has advantages over nilutamide in terms of fewer adverse effects.

Efficacy and tolerability of lanreotide Autogel therapy in acromegalic patients previously treated with octreotide LAR.

OBJECTIVE: This open label, multicentre study was designed to evaluate the efficacy and tolerability of lanreotide Autogel (L-Autogel) in acromegalic patients over a 24-week period. The outcome of treatment with this new, long-acting, aqueous formulation of lanreotide was also compared with the patients' previous treatment with octreotide long acting repeatable (LAR). DESIGN AND METHODS: Twenty-five acromegalic patients (13 males, mean age 51+/-12 years) were switched from octreotide LAR (20-40 mg/4 weeks for at least 6 months) to L-Autogel, given deep subcutaneously at a fixed dose of 90 mg/4 weeks. After 12 weeks, the dose of L-Autogel was titrated according to patients' mean GH and IGF-I levels at week 8. It was increased to 120 mg/4 weeks if GH>2.5 microg/l or if IGF-I was above the age-adjusted normal range. It was reduced to 60 mg/4 weeks if mean GH<1 microg/l and IGF-I was within the normal range. If the values did not fall within these ranges, the dose remained unchanged at 90 mg. RESULTS: After 24 weeks of treatment with L-Autogel (final doses 60 mg in 3 patients, 90 mg in 4 patients and 120 mg in 18 patients), mean serum GH (2.9+/-2.4 microg/l) and IGF-I concentrations (332+/-193 microg/l) remained statistically unchanged when compared with baseline values under octreotide LAR (GH 2.4+/-1.8 microg/l and IGF-I 337+/-201 microg/l, non significant (NS)). There was a significant improvement of the acromegalic symptom score over the study period, from 4.8+/-3.4 to 2.8+/-2.5 (P<0.001) and a small but significant reduction in the residual pituitary tumour volume (P<0.05). Local side-effects were observed less frequently and no technical problems were encountered with the L-Autogel injections, as opposed to treatment with octreotide LAR (60 difficult injections/150 (P<0.001)). CONCLUSIONS: L-Autogel appears to be as effective as octreotide LAR in lowering GH and IGF-I concentrations in acromegalic patients. This treatment was also well tolerated by the patients, giving fewer local side-effects and technical problems with injections. These advantages may improve the long-term acceptability of medical treatment in acromegaly.

Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients.

OBJECTIVE: Slow-release (SR) lanreotide is a long-acting somatostatin analog that has been developed in order to overcome the inconvenience of multiple daily subcutaneous injections of octreotide, required for metabolic control in acromegaly. Lanreotide SR has been found to be well tolerated and effective in reducing GH and IGF-I levels but clinical data are still limited compared with those with subcutaneous octreotide treatment. DESIGN: Sixty-six unselected patients with active acromegaly were therefore evaluated in a multi-center, prospective, open label study. Lanreotide SR was given at a dose of 30mg intramuscular every 7-14 days. METHODS: At baseline and after 2, 4, 8, 12, 24, 36 and 48 weeks patients underwent a clinical examination with assessment of acromegaly related symptoms, and blood was sampled for serum GH, IGF-I, prolactin, glycosylated hemoglobin, fasting glucose, hematology, kidney function and liver function tests. Biliary ultrasonography and pituitary magnetic resonance imaging were performed at baseline and after one year. RESULTS: Treatment resulted in a significant improvement in the symptom score from 2.69+/-0.27 to 1.06+/-0.17 (P<0.0001). Serum IGF-I levels fell from 699+/-38microg/l at baseline to 399+/-26microg/l (P<0.0001, n=60) after one month, after which levels remained stable: 480+/-37microg/l after 6 months (n=54) and 363+/-32microg/l after one year (n=46). GH levels dropped from 13.8+/-3.2microg/l to 4.3+/-0.7microg/l after one month (P<0.0001, n=60) and remained stable thereafter: 3.9+/-0.4microg/l (n=54) after 6 months and 3.5+/-1.1microg/l after one year (n=46). Twenty-nine out of 66 patients (44%) attained a normal age-corrected IGF-I level and 30 patients (45%) attained a GH level below 2.5microg/l. Pituitary adenoma shrinkage of at least 25% was found in 5 of 14 patients (36%) after one year. Side effects were mainly transient gastrointestinal symptoms and pain at the injection site, resulting in drug discontinuation in only 6 patients (9%). Two patients developed new gall stones. No difference was found between subcutaneous octreotide and lanreotide SR in efficacy and almost all patients preferred the easier dose administration of lanreotide SR. CONCLUSIONS: Long-term treatment of acromegaly with SR-lanreotide is effective in controlling GH and IGF-I levels and symptoms and is well tolerated in the majority of patients. Compared with subcutaneous octreotide, lanreotide SR considerably improves patient's acceptance of therapy while having the same overall efficacy.

Corticotropin-dependent Cushing's syndrome in older people: presentation of five cases and therapeutical use of ketoconazole.

BACKGROUND: Cushing's syndrome is a rare disorder. The corticotropin (ACTH)-dependent form of this syndrome generally results either from excessive ACTH secretion by a pituitary adenoma or ectopic secretion by a malignant tumor. Theoretically, the latter type can be assumed to occur more frequently in old age as the incidence of malignancy increases. METHODS: Diagnostic procedures for these five cases of Cushing's syndrome consisted of 24-hour urinary cortisol excretion, plasma ACTH and serum cortisol levels, oCRH stimulatory test, low-dose and high-dose dexamethasone suppression tests, CT scan or MR imaging of the pituitary region, and bilateral inferior petrosal sinus sampling. Patients were treated with ketoconazole, if possible, and evaluated according to clinical response and 24-hour urinary cortisol excretion. PATIENTS: The five cases presented were selected on the basis of age--75 years or older--from a total of about 100 patients presenting with Cushing's syndrome. In only three cases were signs of hypercorticism found on clinical examination. The other two patients were evaluated for adrenocortical excess because of severe hypokalemia and the fortuitous finding of enlarged adrenal glands on CT scan, respectively. RESULTS: As a result of endocrine testing, pituitary-dependent Cushing's disease was suspected in three patients and ectopic Cushing's syndrome in two patients. Imaging techniques demonstrated only one pituitary adenoma in the first three patients and a lung tumor in one of the latter two patients. Inferior petrosal sinus sampling confirmed the suspected origin of the Cushing's syndrome in the three patients in which this procedure was performed. All three patients with pituitary-dependent Cushing's disease underwent successful clinical and biochemical treatment with ketoconazole. CONCLUSION: Pituitary-dependent Cushing's disease may occur more frequently in patients older than 75 years of age than has previously been assumed. Because surgical treatment is not always easily tolerated by older patients, the steroidogenesis inhibitor, ketoconazole, can be a valuable alternative for the control of hypercorticism.

125I-Tyr0-hCRH labelling characteristics of corticotropin-releasing hormone receptors: differences between normal and adenomatous corticotrophs.

The presence of corticotropin-releasing hormone (CRH) receptors has been previously demonstrated in corticotrophs from normal pituitaries using a method combining immunocytochemistry and liquid emulsion autoradiography. The aim of this study was to compare the characteristics of the 125I-Tyr0-hCRH binding in corticotrophs from normal pituitaries (three obtained at autopsy and one obtained at surgery) with corticotrophs from pituitary adenomas (six corticotroph adenomas responsible for Cushing's disease and two silent corticotroph adenomas secreting a biologically inactive ACTH molecule). In normal corticotrophs, the larger part of the 125I-Tyr0-hCRH binding was localised in patchy conglomerates at the centre of the cell and, to a much lesser degree, in a diffuse pattern at the cell periphery. In adenomatous corticotrophs, CRH receptor expression is disturbed both quantitatively and qualitatively. Except for a minority of cells in one adenoma, all adenomatous corticotrophs showed only peripherally bound 125I-Tyr0-hCRH and no centrally localised binding. Furthermore, adenomatous corticotrophs revealed a statistically significant lower signal intensity when compared to normal corticotrophs and a strongly negative correlation was found between the labelling area in adenomatous corticotrophs and both the basal and CRH-stimulated plasma ACTH levels. These findings suggest defective processing of CRH receptors and could be relevant to the sustained ACTH secretion by adenomatous corticotrophs in Cushing's disease and, more generally, provide an explanation to its pathology. The silent corticotrophs secreting a biologically inactive ACTH molecule were characterised by a very faint signal intensity, although present on almost every cell.

Serum creatine, creatinine, and other guanidino compounds in patients with thyroid dysfunction.

Serum levels of creatine (CT), creatinine (CTN), urea, guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), arginine (Arg), homoarginine (Harg), argininic acid (ArgA), and alpha-keto-delta-guanidinovaleric acid (alpha-K-delta-GVA) were measured in 54 patients with hyperthyroidism, 56 with subclinical hyperthyroidism, 28 with subclinical hypothyroidism, and 51 with hypothyroidism compared with 62 euthyroid controls. In agreement with previous reports, serum CT increased (+35%) and CTN decreased (-17.6%) in hyperthyroidism as compared with normal thyroid function, whereas the opposite was seen in hypothyroidism (-17.7% and +11%, P < .0001). Original findings from this study are a highly significant decrease in GSA (-41.7%) and GAA (-36.8%) in hyperthyroidism and an increase in GSA (+36%) in hypothyroidism (P < .0001). In addition, a slight decrease in hyperthyroidism and hypothyroidism was noted for Arg (-6.2% and -13.2%, P = .001) and Harg (-14.8% and -18.1%, P = .05). By contrast, no significant change was seen in levels of urea, G, ArgA, and alpha-K-delta-GVA. No major differences were found for any of the compounds between subclinical hypothyroidism, euthyroidism, and subclinical hyperthyroidism. There was a highly significant positive linear correlation between urea and GSA levels in hyperthyroidism, euthyroidism, and hypothyroidism (r = .68, r = .77, and r = .75, P < .0001), taking into account that for the same increase in urea, GSA increased threefold more in hypothyroid versus hyperthyroid patients. In conclusion, apart from CT and CTN, significant changes can be found in serum levels of GSA, GAA, Arg, and Harg in patients with thyroid dysfunction. Subclinical thyroid dysfunction does not seem to induce changes in serum levels of guanidino compounds. Decreased serum GSA and GAA levels might be an additional indicator of hyperthyroidism.

The effect of naloxone and metoclopramide on the secretion of luteinizing hormone in a hyperprolactinemic hypogonadotropic postmenopausal woman.

OBJECTIVE: To determine the role of opioidergic and dopaminergic activity in the suppression of GnRH0LH in a hyperprolactinemic state. DESIGN: Case report. SETTING: University hospital. PATIENT: A 68-year-old woman with a macroprolactinoma. INTERVENTIONS: Serial 10-hour IV infusions of naloxone and metoclopramide. MAIN OUTCOME MEASURE: Serum LH concentration. RESULTS: Naloxone induced a small but significant rise of serum LH levels, which displayed a pulsatile pattern. By contrast, metoclopramide elicited no significant response in LH secretion. CONCLUSION: Opioidergic but not dopaminergic neurotransmission plays a direct role in the suppression of LH secondary to hyperprolactinemia.

Cushing's disease and hyperprolactinemia due to a mixed ACTH- and prolactin-secreting pituitary macroadenoma.

A 36-year-old man with depression, Cushingoid features and hypogonadism was found to have simultaneous pituitary-dependent Cushing's disease and marked elevation of serum prolactin (PRL). CT-scan revealed a macroadenoma with suprasellar extension. Transphenoidal surgery cured the patient's Cushing's disease, but failed to correct his hyperprolactinemia, which was controlled by subsequent bromocriptine therapy. Immunostaining of the pituitary tumor was positive for PRL as well as for ACTH, and ACTH-related peptides beta-lipotropin and beta-endorphin in two distinct tumor cell lines. This pituitary tumor is one of the few mixed PRL- and ACTH-secreting tumors documented by immunostaining. It is the second reported in a macroadenoma, in which PRL-secreting tumoral cells are much more abundant than ACTH-secreting cells.

Thyrotoxic periodic paralysis, an unusual cause of hypokalemic periodic paralysis.

Over a two-year period two patients were admitted to the hospital with episodes of paralysis and hypokalemia. In the first patient, familial hypokalemic periodic paralysis was initially suspected. Only several months later was Graves' disease diagnosed and this diagnosis linked to thyrotoxic periodic paralysis. The second patient came to notice after treatment with thyreostatic drugs was stopped prematurely and paralysis together with hypokalemia developed. Thyrotoxic periodic paralysis, being rare outside Asia, closely mimics the clinical presentation of familial hypokalemic periodic paralysis. Mainly men in the third decade with a negative family history are affected. Graves' disease is the most common cause of hyperthyroidism. This disorder is not always clinically apparent since signs of hyperthyroidism may be easily missed. Therefore thyroid function tests are part of the diagnostic workup of hypokalemic periodic paralysis. Correction of thyroid function is essential to treatment. The pathophysiology is still controversial.