Evaluation of sex hormone profile and semen parameters in acromegalic male patients.

OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

Preoperative Somatostatin Analogue Treatment Might Trigger Apoptosis and Autophagy in Tumor Tissues of Patients with Acromegaly: A Pilot Study.

OBJECTIVE: To evaluate the effect of preoperative somatostatin analog (SRL) treatment on proteins associated with apoptosis and autophagy in patients with acromegaly and to determine factors correlating with these parameters. METHODS: Ex-vivo tumor samples of 11 SRL-treated and 9 SRL-untreated patients were retrospectively included in the study. Apoptotic and autophagic proteins were determined via immunohistochemical staining and apoptosis was evaluated via in situ DNA end labeling (TUNEL). RESULTS: TUNEL, caspase-3, and ATG-5 immunopositivity was significantly increased (p<0.01, p=0.01, p=0.01, respectively), survivin and beclin-1 immunopositivity was significantly decreased (p=0.03, p=0.02, respectively) in SRL-treated patients as compared with SRL-untreated controls. Ki-67 index was decreased significantly in the SRL-treated group (p=0.01). Significant positive correlations were detected between TUNEL and caspase-3 immunopositivity (r=0.577, p<0.01), and between survivin and beclin-1 immunopositivity (r=0.503, p=0.03). Age at diagnosis, preoperative GH, IGF-1 levels, tumor size, and invasion status were not found to affect TUNEL positivity nor did they correlate with caspase-3, survivin, beclin-1, ATG-5 immunopositivity (p>0.05 for all). Preoperative SRL treatment was the only factor that had a significant effect on TUNEL positivity (adjusted R2=0.39, p=0.02). Preoperative treatment duration was positively correlated with TUNEL and caspase-3 immunopositivity (r=0.526, p=0.02; r=0.475, p=0.04, respectively) and negatively correlated with survivin immunopositivity (r=-0.533, p=0.01). CONCLUSIONS: Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after SRL treatment.

Daily life reflections of acromegaly guidelines.

PURPOSE: To determine the differences in acromegaly diagnosis, treatment, and follow-up among Turkish endocrinologists, and to investigate how the published guidelines are applied in clinical practice. METHODS: The questionnaire was formatted as an electronic survey, conducted between November and December 2015, and sent weekly for 6 weeks via e-mail to 528 endocrinologists in Turkey. RESULTS: The questionnaire was answered by 37.4 % of endocrinologists. Insulin-like growth factor-1 and nadir growth hormone level after 75 g oral glucose tolerance test (nadir GH-OGTT) were the most commonly preferred methods for the initial diagnosis. A total of 49.5 % of the participants reported using preoperative medical therapy (MT) either routinely or on a case-to-case basis. Somatostatin analogs were the most commonly used drugs, both in pre- and postoperative MT. Disease activity following surgery was assessed in the 3rd postoperative month using IGF-1 levels. Similarly, IGF-1 monitoring was preferred in the follow-up period. Monitoring nadir GH-OGTT levels was the most commonly used method in the assessment of discordant test results. The dose titration was done at month 3 after the start of MT. Resistance to SRLs was considered after using the maximal dose for at least 6 months. Pegvisomant was generally used in second- and third-line therapy. Similarly, cabergoline was not preferred in monotherapy by the majority of participants. Radiotherapy was considered in patients with incomplete response to surgery and medical treatments. CONCLUSIONS: Although there were subtle differences, clinical practice guidelines were usually followed among Turkish endocrinologists.

The problem of unrecognized acromegaly: surgeries patients undergo prior to diagnosis of acromegaly.

PURPOSE: To reveal the variety of symptoms experienced by patients before acromegaly diagnosis and to emphasize unneeded surgeries that patients undergo related to acromegaly prior to diagnosis of the disease. METHODS: In total, 490 consecutive adult patients with acromegaly who were treated at our institution between 1998 and 2014 were included in this cross-sectional study, of which 313 could be contacted. Participants were questioned about their complaints at initial consultation and at the time of diagnosis, the first medical professional who they consulted, interval between onset and diagnosis, and surgeries they had undergone. RESULTS: This study included 313 participants, of whom 181 were women. The mean age was 48.8 ± 12.0 years. Patients most frequently presented with acral growth of hands and feet (32.6%) and headache (26.2%). Internists were the medical specialists who were most frequently first consulted (29.4%) then neurosurgeons (11.8%). Acromegaly was generally diagnosed by endocrinologists (55%), followed by neurosurgeons (23%). The median elapsed period prior to diagnosis was 24 months, interquartile range 6.0-48.0 months. Some 45.7% had undergone surgery; 35.2% were related to acromegaly symptoms: head and throat surgery (12.8%), nose surgery (9.3%), thyroidectomy (6.4%), carpal tunnel surgery (4.8%). The delay period for patients who had an operation prior to acromegaly diagnosis was significantly longer than for those who had no operations (p < 0.001). CONCLUSIONS: Acromegaly patients mostly present to internal medicine professionals. Surgeries related to acromegaly complications and symptoms before diagnosis cause a long delay period before diagnosis. Medical staff must be more aware of the clinical aspects of acromegaly.