51 male patients with acromegaly were assessed by the International Index of Erectile Function-5 (IIEF-5) and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched non-acromegalic controls.
Among 51 patients analyzed, 32 (62.7%) had erectile dysfunction (ED). Patients with ED showed lower Acro-QoL scores regarding global (69.8±17.7 vs 79.4±11.2, p = 0.035) and personal relationship dimensions (59.6±22.1 vs 76.8±17.6, p = 0.012) than non-ED patients. ED patients were older (44.5±11.2 years vs 33.2±8.5 years, p = 0.04) and showed higher growth hormone (GH) levels (15.5 [9.5-34.5] μg/L vs 5.9 [3.4-13.9] μg/L, p = 0.001) compared to non-ED patients. The cutoff values of identifying ED were 7.9 μg/L for random GH and 5.3 μg/L for GH nadir after oral administration of 75 g glucose, respectively. No significant difference in total testosterone levels between the two groups (6.36±4.24 vs 9.54±5.50, p = 0.299). The NO levels in patients with acromegaly were significantly lower than those in non-acromegalic controls (8.77±1.78 μmol/L vs 19.19±5.02 μmol/L, respectively, p = 0.049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14±0.98 μmol/L vs 12.09±3.44 μmol/L, p = 0.027).
The study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required 1).
The purpose of a study was to investigate body composition, including ectopic lipids, measures of glucose homeostasis, and gonadal steroids in patients with active acromegaly compared to age-, BMI-, and sex-matched controls and to determine changes in those parameters following biochemical control of acromegaly. Design:
Cross-sectional study of 20 patients with active acromegaly matched controls. Prospective study of 16 patients before and after biochemical control of acromegaly. Main outcome measures:
Body composition including ectopic lipids by MRI/1H-MRS; measures of glucose homeostasis by an OGTT; gonadal steroids.
Patients with active acromegaly had lower mean intrahepatic lipids (IHL) and higher mean fasting insulin and insulin AUC compared to controls. Men with acromegaly had lower mean total testosterone, SHBG, and estradiol compared to male controls. Following therapy, HOMA-IR, fasting insulin and insulin AUC decreased despite an increase in IHL, abdominal and thigh adipose tissue and a decrease in muscle mass. Conclusions:
Acromegaly is characterized by insulin resistance and hyperinsulinemia but lower IHL, compared to age-, BMI- and sex-matched healthy controls. Biochemical control of acromegaly improves insulin resistance but leads to a less favorable anthropometric phenotype with increased IHL, abdominal adiposity and decreased muscle mass 2).
Retrospective study of 55 consecutive patients [29 men; median age 47years (interquartile range 38-68)] diagnosed with acromegaly between 2003 and 2014. After treatment serum IGF-I and/or GH was measured according to a standardized protocol. The biochemical remission status was defined according to the clinical guidelines from 2010 and 2014.
Out of 55 patients, 44 patients were primarily operated. Of these, 33 (75%) were evaluated 3-12 months postoperatively by measuring serum IGF-I and GH during an oral glucose tolerance test. According to the 2010 guidelines, 11 patients (33%) were in biochemical remission, 15 patients (46%) were not and 7 patients (21%) had discordant results (normal IGF-I and high GH or vice versa). Applying the 2014 guidelines in the same group, 16 patients (49%) were in biochemical remission, 7 patients (21%) were not and 10 patients (30%) had discordant results. Thus, by using the most recent criteria for biochemical control, more patients were considered to be in remission, or with discordant results, and fewer patients not in remission (P<0.05).
An apparently minor adjustment of the criteria for biochemical control has a significant impact on remission status in patients treated for acromegaly, eventually affecting follow-up and treatment strategies 3).
Babu et al. report all patients undergoing endoscopic transsphenoidal surgery for acromegaly from 2005 to 2013 at Cedars-Sinai Pituitary Center. Hormonal remission was established by normal insulin-like growth factor (IGF)-1, basal serum growth hormone <2.5 ng/mL, and growth hormone suppression to <1 ng/mL following oral glucose tolerance test. Oral glucose tolerance test was performed at 3 months after surgery, and then as indicated. IGF-1 was measured at 3 months and then at least annually. We evaluated tumor granularity, nuclear expression of p21, Ki67 index, and extent of cavernous sinus invasion, and correlated these with remission status.
Fifty-eight patients that underwent surgery had follow-up from 38 to 98 months (mean 64 ± 32.2 months). There were 21 microadenomas and 37 macroadenomas. Three months after surgery 40 of 58 patients (69%) were in biochemical remission. Four additional patients were in remission at 6 months after surgery, and 1 patient had recurrence within the first year after surgery. At last follow-up, 43 of 44 (74.1%) of patients remained in remission. Cavernous sinus invasion by tumor predicted failure to achieve remission.
Prognostic markers of disease aggressiveness other than cavernous sinus invasion did not correlate with surgical outcome. Long-term remission after surgery alone was achieved in 74% of patients, indicating long-term efficacy of endoscopic surgery 4).
Early diagnosis of acromegaly prevents irreversible comorbidities and facilitates surgical cure. Carpal tunnel syndrome (CTS) is common in acromegaly and patients have often undergone surgery for CTS prior to the diagnosis of acromegaly.
Zoicas et al. hypothesized that screening CTS-patients for acromegaly could facilitate active case-finding. They prospectively enrolled 196 patients [135 women, 56.9 (range 23-103) years] who presented with CTS for surgery. Patients were asked about 6 symptoms suggestive of acromegaly using a questionnaire calculating a symptom score (0-6 points), and insulin-like-growth factor 1 (IGF-1) was measured. If IGF-1 was increased, IGF-1 measurement was repeated, and random growth hormone (GH) and/or an oral glucose tolerance test (OGTT) with assessment of GH-suppression were performed. The mean symptom score was 1.7±1.3 points. Three patients reported the maximal symptom score of 6 points, but none of them had an increased IGF-1. There was no correlation between the symptom score and IGF-1-SDS (standard deviation score) (r=0.026; p=0.71). Four patients had an IGF-1>2 SDS. In 2 patients acromegaly was ruled out using random GH and OGTT. One patient had normal IGF-1 and random GH at follow-up. One patient refused further diagnostics. In this prospective cohort of patients with CTS, the observed frequency of acromegaly was at most 0.51% (95% CI 0.03 to 2.83%). In this prospective study, none of the 196 patients with CTS had proven acromegaly. Thus, we see no evidence to justify general screening of patients with CTS for acromegaly 5).