Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE).

PURPOSE: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). METHODS: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018-2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. RESULTS: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. CONCLUSIONS: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed.

Pilot study to define criteria for Pituitary Tumors Centers of Excellence (PTCOE): results of an audit of leading international centers.

PURPOSE: The Pituitary Society established the concept and mostly qualitative parameters for defining uniform criteria for Pituitary Tumor Centers of Excellence (PTCOEs) based on expert consensus. Aim of the study was to validate those previously proposed criteria through collection and evaluation of self-reported activity of several internationally-recognized tertiary pituitary centers, thereby transforming the qualitative 2017 definition into a validated quantitative one, which could serve as the basis for future objective PTCOE accreditation. METHODS: An ad hoc prepared database was distributed to nine Pituitary Centers chosen by the Project Scientific Committee and comprising Centers of worldwide repute, which agreed to provide activity information derived from registries related to the years 2018-2020 and completing the database within 60 days. The database, provided by each center and composed of Excel® spreadsheets with requested specific information on leading and supporting teams, was reviewed by two blinded referees and all 9 candidate centers satisfied the overall PTCOE definition, according to referees' evaluations. To obtain objective numerical criteria, median values for each activity/parameter were considered as the preferred PTCOE definition target, whereas the low limit of the range was selected as the acceptable target for each respective parameter. RESULTS: Three dedicated pituitary neurosurgeons are preferred, whereas one dedicated surgeon is acceptable. Moreover, 100 surgical procedures per center per year are preferred, while the results indicated that 50 surgeries per year are acceptable. Acute post-surgery complications, including mortality and readmission rates, should preferably be negligible or nonexistent, but acceptable criterion is a rate lower than 10% of patients with complications requiring readmission within 30 days after surgery. Four endocrinologists devoted to pituitary diseases are requested in a PTCOE and the total population of patients followed in a PTCOE should not be less than 850. It appears acceptable that at least one dedicated/expert in pituitary diseases is present in neuroradiology, pathology, and ophthalmology groups, whereas at least two expert radiation oncologists are needed. CONCLUSION: This is, to our knowledge, the first study to survey and evaluate the activity of a relevant number of high-volume centers in the pituitary field. This effort, internally validated by ad hoc reviewers, allowed for transformation of previously formulated theoretical criteria for the definition of a PTCOE to precise numerical definitions based on real-life evidence. The application of a derived synopsis of criteria could be used by independent bodies for accreditation of pituitary centers as PTCOEs.

Low serm Fibroblast Growth Factor-21 levels is not associated with Carotid intima-media thickness in acromegaly patients.

INTRODUCTION: Elevated fibroblast growth factor-21 (FGF-21) levels are related to carotid intima-media thickness (CIMT), a well-established marker of atherosclerosis. Acromegaly has also been linked to increased CIMT. There has been no data considering the association between FGF-21 levels and atherosclerosis in acromegaly patients. This study aimed to evaluate FGF-21 levels and CIMT in acromegalic patients in relation to atherosclerotic complications. DESIGN: Case-control study. MATERIALS AND METHODS: The study group included 70 acromegaly patients and 72 healthy volunteers from the Department of Endocrinology and Metabolism Disease, Marmara University Medical School. FGF-21, growth hormone, insulin-like growth factor I, lipids, glucose, insulin levels were assessed. CIMT was measured from the common carotid artery wall on B-mode ultrasound. RESULTS: Median FGF-21 levels were significantly lower in the acromegaly group than in the control group. CIMT was higher in acromegaly patients compared to controls. Although there was no correlation between FGF-21 levels and CIMT in patients with acromegaly, a positive correlation was found between high-density lipoprotein-cholesterol and FGF-21 levels. Glucose metabolic markers were the determining factors of the FGF-21 levels in acromegaly patients. CONCLUSION: Our study is the first to examine the relationship between serum FGF-21 levels and atherosclerosis in acromegaly patients. The lower serum FGF-21 levels in acromegaly subjects might be associated with the improving effects of growth hormone on liver fat. Acromegaly was linked to higher CIMT, but there was no correlation between FGF-21 levels and CIMT. The role of FGF-21 in acromegaly as a marker of atherosclerosis requires additional research.

Thyroid disease in the perimenopause and postmenopause period.

The interpretation of thyroid function tests should be cautiously made during the perimenopause and postmenopause period bearing in mind that physiologic changes do exist in this group of women in terms of secretion and metabolism of thyrotropin and thyroid hormones. Moreover the incidence of thyroid disorders increases in postmenopausal and elderly women. There is no consensus for screening postmenopausal women even though there is well-known evidence about the effect of thyroid status on cognitive function, cardiovascular risk, bone turnover, and longevity. The diagnosis of any thyroid disorder is challenging in these patients because the symptoms are more subtle and attributed to menopausal symptoms. Management requires more attention in this population than that of younger groups, because high doses of L-thyroxine can lead to cardiac complications and increased bone turnover. Furthermore radio-iodine is preferred in treatment of hyperthyroidism in older patients. The risk of nodular thyroid disease and thyroid cancers increases in this group. Although the diagnostic approach is the same as for young patients, the risk of surgery is high and disease prognosis is worse. Women with any form of thyroid disease should be treated according to the current guidelines. Decision for menopausal hormonal therapy should be individualized regardless of the concomitant presence of thyroid disorders.

Evaluation of depressive mood and cognitive functions in patients with acromegaly under somatostatin analogue therapy.

AIMS: Acromegaly is caused by a pituitary adenoma that releases excess growth hormone (GH) and a concomitant increase in insulin-like growth factor 1 (IGF-1). Acromegaly results not only in phenotypic changes, but also in neurologic complications as peripheral neuropathy and cognitive dysfunction. This study aimed to compare depressive mood and cognitive function in patients with acromegaly and in healthy controls as well as to determine the factors underlying cognitive dysfunction in the acromegalic patients. MATERIALS AND METHODS: This study included 42 patients with acromegaly that were receiving somatostatin analogue therapy and 44 healthy controls. Memory, attention, visuospatial function, inhibitory function, abstract thinking, verbal fluency, and depressive mood were measured in the patients and controls. RESULTS: Patients with acromegaly had lower learning (p = 0.01), planning (p = 0.03), complex attention and inhibitory function (p = 0.04) scores than the controls. There was no significant difference in depressive mood between the patients and controls (p > 0.05). Gamma knife radiosurgery did not negatively affect cognitive function (p > 0.05). CONCLUSION: The present findings show that acromegaly negatively affects learning, attention, and planning.

Peripheral nervous system assessment in acromegaly patients under somatostatin analogue therapy.

PURPOSE: Acromegaly is known to affect peripheral nervous system (PNS) causing carpal tunnel syndrome (CTS) and polyneuropathy. The frequency of these disorders and the evaluation methods vary among studies. In the present study, we aimed to examine PNS of acromegaly patients under somatostatin analogue (SSA) therapy. METHODS: Forty-eight acromegaly patients (26 F/22 M, 45.58 ± 11.6 years) under SSA treatment and 44 healthy controls (25 F/19 M, 47.46 ± 8.7 years) were assessed by symptom questionnaires, neurologic examination and electrophysiological studies. RESULTS: 87.5 % of the acromegaly patients had at least one abnormal finding regarding PNS. With the incorporation of palm-wrist median nerve conduction velocity method, we detected CTS in 50 % of patients. Polyneuropathy was less frequent (29.2 %). Both conditions were independent from the coexisting diabetes mellitus (p = 0.22 for CTS, p = 0.71 for polyneuropathy). Polyneuropathy but not CTS was more common among biochemically uncontrolled acromegaly patients rather than those under control (p = 0.03; p = 0.68, respectively). CONCLUSION: Our findings emphasize the high prevalence of peripheral nervous system involvement in acromegaly patients under SSA therapy and importance of neurological evaluation of these patients. Early diagnosis and treatment of the disease may reduce the PNS involvement.

Urinary incontinence in a young girl due to ectopic ureter: the importance of history in a diagnostic challenge.

In girls who are otherwise well and whose history is that of continuous wetting day and night, despite successful toilet training, for a lifelong history, an extravesical infrasphincteric ectopic ureteral orifice should be strongly suspected and imaging should be vigorously pursued. Here, delayed diagnosis of vaginal ectopic ureter in a young girl with a lifelong history of urinary incontinence is presented. The importance of history and imaging procedures are also discussed.

A new technique for the diagnosis of fallopian tube patency by using hysteroscopy with ultrasound compared with hysterosalpingography in infertile women.

PURPOSE: To evaluate the effectiveness of hysteroscopy as a method for the diagnosis of tubal patency using saline distention media. METHODS: In this prospective study, 62 women between 21 and 38 years with a history of at least 1 year of infertility who underwent hysteroscopy and hysterosalpingography (HSG) on two consecutive cycles were studied. Transvaginal ultrasonography carried out before and after hysteroscopy in order to measure the abdominal fluid (in ml) in the peritoneal cavity of the cul-de-sac. The difference between the two results was calculated. A next cycle HSG was performed and patients were divided into three groups according to whether there was no tubal occlusion (group 1), a unilateral occlusion (group 2) or a bilateral occlusion (group 3): Peritoneal fluid measurements were compared among the three groups. Finally, pain and discomfort were recorded at the end of the process. RESULTS: According to the HSG, 34 women were in group 1, 13 in group 2 and 9 in group 3. Peritoneal fluid measurements were 6.88 +/- 2.7 ml in group 1, 4.21 +/- 0.9 ml in group 2 and 1.08 +/- 0.7 ml in group 3. Statistical differences were found between groups 1 and 3 and between groups 2 and 3 (P < 0.05). All of the patients reported significantly less pain during hysteroscopy in response to HSG. CONCLUSIONS: Using saline distension media during hysteroscopic evaluation was effective to allow measurement of the accumulating fluid in the peritoneal cavity and to confirm at least one patent tube with minimal pain.

A prospective study of the efficacy of Serenoa repens, tamsulosin, and Serenoa repens plus tamsulosin treatment for patients with benign prostate hyperplasia.

INTRODUCTION: Increasing attention has been focused on the use of phytotherapeutic agents to alleviate the symptoms of benign prostatic hyperplasia (BPH) in recent times. The best described and studied phytotherapeutic agent is Serenoa repens (SR). MATERIALS AND METHODS: This prospective study was designed to have 3 arms including SR 320 mg per day (N = 20), Tamsulosin (TAM) 0.4 mg per day (N = 20) and SR + TAM (N = 20) to reveal the superiority or equivalence between these treatment regimens in BPH. RESULTS: The groups were not statistically different with regard to increase in maximal urinary flow rate (Q (max)) and decrease in International Prostate Symptom Score (I-PSS) (P > 0.05). No adverse effect was detected in SR therapy group. CONCLUSION: Treatment of BPH by both SR and TAM seems to be effective alone. None of them had superiority to another and additionally, combined therapy (SR + TAM) does not provide extra benefits. Furthermore SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS due to BPH.

Effect of stanford pouch and ileal conduit urinary diversions on bone mineral density and metabolism.

After urinary-intestinal diversions metabolic complications may occur in long term follow up. We aimed to evaluate bone metabolism changes in urinary diverted patients. Nineteen patients with urinary diversions (11 Stanford pouch and 8 ileal conduit) performed with diagnosis of locally invasive bladder cancer and 19 age-sex matched healthy subjects were enrolled in the study. Bone mineral density (BMD), arterial blood pH, bicarbonate and base excess as well as bone mineralisation parameters at urine and serum were evaluated for all groups. For statistical evaluation, nonparametric comparisons between groups were used. Comparison of ileal conduit and control groups displayed higher alkaline phosphatase and parathormone levels in the patient group though the difference was not significant. The mean BMD values of ileal conduit group were osteopenic, revealing a significant difference with the control group. Statistically significant differences between alkaline phosphatase, parathormone levels of Stanford pouch and control groups were apparent whereas BMD values were not significantly different. When the two patient groups were compared with each other, no difference in BMD or bone metabolism parameter values could be observed. Patients with urinary diversions are under risk of bone demineralisation and must be followed by BMDs, arterial blood analysis and bone mineral metabolism parameters.

Splenogonadal fusion: report of a case.

A 15-year-old male patient was admitted to our hospital with a left undescended testis. He also suffered from congenital limb defects. Ultrasonography revealed atrophic testicular tissue in the left groin, approximately 2-cm in size. Upon left inguinal exploration, atrophic testicular tissue was found and an orchidectomy was performed. Histopathological examination revealed splenogonadal fusion, which has a known association with congenital limb defects.

Remission of idiopathic retroperitoneal fibrosis after sequential therapy with corticosteroids and tamoxifen.

The most favored therapy for idiopathic retroperitoneal fibrosis is the surgical relief of ureteral obstruction and use of corticosteroids to prevent recurrence. Although effective, long-term corticosteroid treatment could be associated with serious side effects. We would like to present a case of idiopathic retroperitoneal fibrosis treated successfully with intraperitonealization of the ureters and sequential therapy with steroids and tamoxifen to minimize the side effects.

A novel surveillance protocol for stage I nonseminomatous germ cell testicular tumours.

OBJECTIVES: To report the results of a novel surveillance policy for stage I nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: Between 1978 and 2000, 132 patients (median age 28 years, range 16-52) who were regularly followed were included in a new surveillance policy. All pathology specimens were studied retrospectively by the same pathologist for embryonal carcinoma, yolk sac tumour and lymphovascular invasion components. A loose surveillance protocol was designed in which computed tomography (CT) was used only for the first year. RESULTS: The median (range) follow-up was 38 (6-265) months; the relapse rate was 24% and all occurred before 23 months, with 87% diagnosed within the first year. Platinum-based chemotherapy was given to patients with relapse, and surgery used after chemotherapy in seven. Among all the risk factors, an embryonal carcinoma component was the only significant predictor of relapse. The overall survival rate was 99%. CONCLUSION: The presence of embryonal carcinoma in the primary pathology is the only risk factor determining the relapse rate of the present surveillance policy for stage I NSGCTs. The overall survival was no different from those reported for retroperitoneal lymph node dissection and primary chemotherapy. Decreasing the frequency of CT in the first year and totally eliminating it after 1 year reduces the cost of surveillance. The possible compliance problems of patients are also minimized, without changing the overall survival. This surveillance protocol for patients with stage I NSGCT has reduced costs and provided a better quality of life for the patients, without jeopardizing the final outcome.

Serum concentrations of sex hormones in men with severe lower urinary tract symptoms and benign prostatic hyperplasia.

OBJECTIVE: To find out the impact of age-related changes in serum concentrations of sex hormones on the development of severe lower urinary tract symptoms and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study group consisted of 61 consecutive patients subjected to prostatectomy for BPH between 2000-2001 in our clinic. Forty-five randomly assigned, age and socioeconomically matched cases without any lower urinary tract symptoms were taken as the control group. Both clinical BPH and control groups were divided to 3 age groups (namely 50-59, 60-69 and > or = 70 years) and age-related changes in serum concentrations of sex hormones were investigated. RESULTS: Prostate adenoma weight was found to be increased significantly (p = 0.02) with advancing age in clinical BPH group. There was no difference between serum concentrations of measured sex hormones between small and large prostates except for serum estradiol levels, which were found to be significantly higher in patients who had an adenoma weight of > 50 g (p = 0.047). Similar results were obtained in both clinical BPH and control groups with respect to age-related changes in serum concentrations of sex hormones. Briefly there was an age-related decrease in serum free testosterone levels and increase in serum estradiol, prolactin and gonadotropin levels. Serum free testosterone concentration was significantly higher in the control group for ages 60-69 (p = 0.015) while total testosterone was higher in BPH patients for patients older than 70 years of age (p = 0.027). No other significant change was documented between 2 groups. An age-dependent increase in serum E/freeT ratio was documented in both clinical BPH and control patients whereas serum freeT/T ratio was decreased in the BPH group with advancing age (p = 0.008). CONCLUSION: The decrease in serum free testosterone concentrations with a relative rise in serum estradiol levels with advancing age might be an important factor in the development of BPH. However it is likely that serum concentrations of sex hormones play little impact on the clinical severity of BPH.

Factors affecting outcome of one-stage anterior hypospadias repair: analysis of 422 cases.

The repair of hypospadias is among the most difficult problems in urology, as it demands the construction of a well-functioning urethra and a good cosmetic appearance. We performed a retrospective analysis of 422 cases subjected to one-stage anterior hypospadias repair between 1982 and 1999 in our clinic and investigated the effects of factors like degree of hypospadias, surgical technique, and the surgeon's experience on outcome. The operations used were MAGPI (91), urethral advancement (10), Mathieu (260), modified Allen-Spence (50), onlay island flap (5), and double-faced island flap (6) procedures. The early complication rate was 18%, while the final success rate following secondary interventions was 95%. The complications included fistula formation in 49 cases (12%), flap necrosis in 12 (3%), meatal problems in 12 (3%), residual chordee in 4 (1%), and urethral stricture in 1 (<1%). Complication rates were significantly higher if the meatus was proximal or there was severe chordee and in the first 6 years of the study. The flap procedures were associated with a higher complication rate. It is concluded that one-stage procedures are successful in the repair of anterior hypospadias in experienced hands with proper patient selection.

Are clinical characteristics of familial benign prostatic hyperplasia different than in sporadic cases?

OBJECTIVE: Familial benign prostatic hyperplasia (BPH) is a recently popularized entity with yet uncertain clinical and pathological features. In the present study we investigated whether there was any difference between clinical characteristics of familial and sporadic BPH in a series of 148 surgically treated BPH patients. MATERIALS AND METHODS: A retrospective analysis was performed in 148 patients subjected to transvesical or transurethral prostatectomy to determine the clinical features of familial BPH. Patients were categorised as having familial BPH when 3 or more (including the patient) first-degree family members gave a history of BPH. Accordingly 23 cases who fit this criterion were accepted as having familial BPH and the rest of the cases were taken as the control group. The two groups were compared with respect to age, International Prostate Symptom Score (IPSS), quality of life score, prostate specific antigen (PSA), maximum urinary flow rate and the weight of the surgical prostate specimen. RESULTS: The mean age, IPSS, quality of life score, total PSA, maximum urinary flow rate and the weight of the surgical prostate specimen were found as 65.13 +/- 5.51 years, 23.13 +/- 4.82, 4.78 +/- 0.95, 6.0 +/- 4.1 ng/ml, 6.9 +/- 2.7 ml/s and 62.96 +/- 38.76 g, respectively, in the familial BPH group whereas the same parameters were measured as 68.13 +/- 7.68 years, 24.74 +/- 3.73, 4.52 +/- 0.85, 5.93 +/- 4.75 ng/ml, 4.6 +/- 1.71 ml/s and 70.87 +/- 53.21 g, respectively. No significant difference was present between familial and sporadic BPH cases in any of the studied parameters. CONCLUSION: The clinical features of familial BPH did not differ significantly from those of sporadic BPH.

Case report: further upward migration of a misplaced double-J ureteral stent.

A 45-year-old man was referred to our hospital for the removal of a misplaced double-J ureteral stent. The lower end of the stent shortly after insertion was at the level of sacroiliac joint. However one week later the stent was further migrated upwards to the level of 4th lumbar vertebra. Immediate ureterorenoscopy was performed to prevent further migration of the stent to the renal pelvis and the stent was removed by the grasping forceps under direct vision successfully.

Effects of combined androgen blockade on bone metabolism and density in men with locally advanced prostate cancer.

OBJECTIVE: To investigate whether combined androgen blockade (CAB) produces any adverse effects on bone metabolism and mineral density in patients with locally advanced prostate cancer. MATERIALS AND METHODS: The study group consisted of 17 stage T4 prostate cancer patients treated with CAB and had no evidence of bone metastasis on bone scintigraphy. The mean duration of CAB and final total prostate specific antigen (PSA) level at the time of study were found at 28.5 +/- 15.9 (6-58) months and 0.39 +/- 0.5 (0.1-2) ngml, respectively. Twenty age and socioeconomically matched benign prostate hyperplasia (BPH) patients were taken as the control group. Both groups were compared with regard to lumbar bone mineral density (LBD), femur bone mineral density (FBD) and serum parameters of bone metabolism namely calcium (Ca), phosphate (P), magnesium (Mg) and alkaline phosphatase (ALP). Bone mineral density was measured with dual energy x-ray absorptiometry. RESULTS: The mean FBD, LBD and serum Ca, P, Mg and ALP measurement of the patients treated with CAB were 0.85 +/- 0.1 g/cm2, 1.16 +/- 0.2 g/cm2, 9.1 +/- 0.3 mg/dl, 3.6 +/- 0.6 mg/dl, 1.95 +/- 0.14 mg/dl, 187.5 +/- 61 mg/dl, respectively. No significant difference was found between patients subjected to CAB and the age matched controls in any of the studied parameters namely age, FBD, LBD, Ca, Mg and ALP except serum phosphate. Serum phosphate levels were significantly (p = 0.001) higher in patients treated with CAB suggesting a minor effect of CAB on bone metabolism. CONCLUSION: No convincing evidence was found about the detrimental effect of CAB on bone mineral density and metabolism in a highly selected group of patients with advanced prostate cancer without bone metastases.

Repeated transurethral resection and intravesical BCG for extensive superficial bladder tumors.

PURPOSE: We report our experience with repeat transurethral resection (TUR) in a group of patients with superficial bladder tumors in whom complete resection in one session was impossible because of the extensive tumor burden. PATIENTS AND METHODS: Only the patients with such extensive (>10 g of resected tissue) tumors that we were unable to perform complete TUR initially were included in the present study. The patients underwent repeat TUR(s) 4 weeks after the previous one until complete resection of the tumor was achieved. After complete TUR, if the pathology examination confirmed superficial disease, the patients received intracavitery immunotherapy and were followed up thereafter. If pathology examination documented muscle-invasive disease, cystectomy was suggested. RESULTS: Of the 43 patients undergoing repeat TUR, 15 needed a second and 5 needed a third session to achieve complete resection. Of the patients, 28 (65%) had stage T1 and 15 (35%) has stage Ta tumor. Eight patients (19%) otherwise regarded as having superficial tumor were found to have muscle-invasive disease following repeat TURs. The mean follow-up of the remaining 35 patients with superficial disease was 34 months (range 1-126 months). Four of the patients with superficial disease progressed to T2 tumor. However, 16 patients achieved a state of complete response with no tumor recurrences during a mean of 38 months (range 4-126 month). The present protocol achieved bladder sparing in a total of 22 (63%) of the 35 patients with superficial disease. CONCLUSIONS: From the presented series, we suggest that one can use the combination of repeat TUR and intravesical immunotherapy in the management of bulky superficial bladder tumors in an effort to preserve the bladder.