Previous studies have linked persistent elevations in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) to cardiac abnormalities including aortic root dilation. Guidelines in the management of this dilation below the size recommended for surgery have not been well defined but follow-up and intervention when appropriate could be life-saving. We report the case of a man in his 60s who had been living with undiagnosed acromegaly for many years. His initial assessment through point-of-care ultrasound raised concerns about potential cardiac enlargement, prompting further investigation with a formal echocardiogram, which revealed a significant aortic root dilation measuring 4.5 cm. Subsequent blood tests confirmed elevated levels of IGF-1. Brain MRI showed a focal lesion in the pituitary gland, which was surgically resected, confirming the diagnosis of a GH-secreting pituitary adenoma. One year after surgery, a repeat CT angiogram of the chest demonstrated a stable size of the aortic root aneurysm.

OBJECTIVE: Long-term GH/IGF-1 excess could increase risk of cancer in acromegaly, but individual levels of these hormones do not relate to this risk. Therefore, we newly investigated longitudinally-measured IGF-1 levels as a potential predictor of cancer in a large NYC acromegaly cohort.
METHODS: We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA)(140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from SEER data.
RESULTS: Cancer prevalence by last follow up was 22.6% in acromegaly and 12.7% in CNFPAs (OR = 1.99 (95% CI, 1.34, 2.97)(P=0.0005). Overall SIR for cancer was 1.78 (1.51, 1.81) in the acromegaly and 1.26 (0.89, 1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR=1.278 (1.060, 1.541)(P = 0.01), years from acromegaly diagnosis to cancer or last follow up, OR= 1.03 (1.004, 1.057)(P=0.024), and age at follow up, OR =1.064 (1.047, 1.082)(P<0.001), were predictors of cancer.
CONCLUSIONS: Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.

BACKGROUND: Excess growth hormone (GH) secretion in acromegaly has a major impact on mineral balance and serum phosphate levels. However, the clinical utilization of serum phosphate levels as a marker for long-term disease outcomes in acromegaly has not been evaluated.
METHODS: This is a retrospective study of patients with acromegaly who were followed in a tertiary center. Data were retrieved on patient characteristics, endocrine and biochemical evaluation, and tumor parameters. Comparisons were performed by measuring baseline phosphate levels and conducting correlation analysis and multivariable logistic regression.
RESULTS: Sixty-one patients were followed for 4.5 years (range 1-21). Patients with hyperphosphatemia (> 4.5 mg/dl) at baseline had larger adenomas (15.0 mm [8.0, 47.0] vs. 10.0 mm [3.0, 24.0], p = 0.001), a rate chance of invasive adenoma (16 [80.0%] vs. 14 [46.7%], p = 0.02), and lower serum cortisol levels (226.0 nmol/l [27.6, 516.0] vs. 294.0 nmol/l [32.0, 610.0], p = 0.02). Baseline serum phosphate levels positively correlated with IGF-1 levels (r = 0.43, p = 0.003) and negatively correlated with morning plasma cortisol levels (r = -0.46, p = 0.002). Regarding long-term impact, baseline phosphate levels correlated with the number of pituitary axes involved 6 months after diagnosis (r-0.34, p = 0.01). In multivariable analysis, baseline plasma phosphate levels were independently associated with risk for disease progression/recurrence (odds ratio [OR] 9.66, 95% confidence interval [CI] 1.5, 105.9, p = 0.03) and for invasive adenoma (OR 6.21, 95% CI 1.6, 28.7, p = 0.01).
CONCLUSIONS: Elevated pretreatment serum phosphate levels are associated with a greater risk of disease persistence and recurrence and with altered pituitary function in patients with acromegaly.

OBJECTIVE: The impact of GH/IGF-1 levels on skeletal muscle in acromegaly is still controversial. Temporal (TMT) and masseter muscle (MMT) thickness has been recently demonstrated as a reliable measure of muscle mass. We aimed to investigate the relationship between TMT, MMT and clinical/biochemical characteristics in patients with acromegaly.
METHODS: Single center retrospective longitudinal study including 69 patients with at least one available brain/sella turcica MRI and matched clinical data. TMT, MMT, and muscle fatty infiltration (modified Goutallier score) were evaluated in all patients at baseline (first available MRI) and over time (182 MRIs analyzed).
RESULTS: At baseline, both TMT and MMT were higher in males than females (p = 0.001 and p = 0.016, respectively). TMT and MMT were positively associated (β 0.508, p < 0.001), and they were positively correlated with IGF-1 xULN (TMT, p = 0.047; MMT, p = 0.001). MMT had a positive correlation with patients\' weight (p = 0.015) and height (p = 0.006). No correlation was found between TMT, MMT and the presence of hypogonadism. Considering all available MRIs, sex and IGF-1 xULN were significant determinants of TMT and MMT at multivariable analysis (female sex: β -0.345/-0.426, p < 0.001; IGF-1 xULN: β 0.257/0.328, p < 0.001). At longitudinal evaluation, uncontrolled patients at baseline showed a significant reduction of MMT over time (p = 0.044). Remarkable fatty infiltration was observed in 34-37% of MRIs; age was the main determinant (temporal muscle: OR 1.665; p = 0.013; masseter muscle: OR 1.793; p = 0.009).
CONCLUSIONS: Male patients with higher IGF-1 values have thicker temporal and masseter muscles, suggesting that sex and IGF-1 have a significant impact on muscle mass in acromegaly.

Objective  Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods  The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons\' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results  The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p  = 0.166), basal GH level ( p  = 0.001), and nadir GH level ( p  = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p  = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion  The surgeons\' experience is an important factor that can affect the patients\' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Introduction  Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors which can impart significant disability owing to their locally invasive potential. To date, the gamut of PitNET subtypes remains ill-understood at the ligand-receptor (LR) interactome level, potentially limiting therapeutic options. Here, we present findings from in silico analysis of LR complexes formed by PitNETs with clinical presentations of acromegaly, Cushing\'s disease, high prolactin production, and without symptoms of hormone hypersecretion. Methods  Previously published PitNET gene expression data was acquired from ArrayExpress. These data represented all secretion types. LR interactions were analyzed via a crosstalk score approach. Results  Cortisol (CORT) ligand was significantly involved in tumor-to-tumor signaling across all PitNET subtypes but prolactinomas, which evidenced active CORT depletion. Likewise, CCL25 ligand was implicated in 20% of the top LR complex interactions along the tumor-to-stroma signaling axis, but silent PitNETs reported unique depletion of the CCL25 ligand. Along the stroma-to-tumor signaling axis, all clinical PitNET subtypes enriched stromal vasoactive intestinal polypeptide ligand interactions with tumor secretin receptor. All clinical PitNET subtypes enriched stromal DEFB103B (human β-defensin 103B) ligand interactions with stromal chemokine receptors along the stroma-to-stroma signaling axis. In PitNETs causing Cushing\'s disease, immune checkpoint ligand CD274 reported high stromal expression, and prolactinomas reported low stromal expression. Moreover, prolactinomas evidenced distinctly high stromal expression of immune-exhausted T cell response marker IL10RA compared with other clinical subtypes. Conclusion  Relative crosstalk score analysis revealed a great diversity of LR complex interactions across clinical PitNET subtypes and between solid tumor compartments. More data are needed to validate these findings and exact clinical importance.

OBJECTIVE: To evaluate the available evidence regarding the quality of life (QoL) in patients with acromegaly, by synthesizing the psychosocial factors of QoL, QoL measures, and complementary interventions targeting QoL.
METHODS: A scoping review was conducted using the PRISMA-ScR guideline. We searched six English databases (PubMed, Embase, CINAHL, Scopus, Web of Science, and the Cochrane Library) from the inception to August 21, 2023. We included observational studies involving psychosocial factors and complementary interventions targeting QoL (concept) in patients with acromegaly (population) in any setting (context). The design characteristics, psychosocial factors, measures, details of interventions, and outcomes of included studies were described in detail.
RESULTS: Twenty-one studies were identified, including sixteen cross-sectional studies and five interventional studies. Ten categories of psychosocial factors that are associated with QoL in acromegaly. Depression and anxiety were the most frequent psychosocial factors. Seven different validated QoL measures were used. AcroQoL was the most common measure. Two categories of complementary interventions targeting QoL were identified including psychological and exercise interventions.
CONCLUSIONS: Our scoping review provides a reasonably clear picture of the current research status of QoL in acromegaly. However, this review also highlights the need to deepen understanding of QoL and psychosocial factors in the future, as well as conduct longitudinal research and qualitative research to clarify the changing trends of psychosocial factors and specific experiences of patients. Further, more potential clinical complementary interventions are needed to improve QoL for patients with acromegaly.

OBJECTIVE: We previously showed the clinical characteristics of acromegaly with a paradoxical growth hormone (GH) response to oral glucose or thyrotropin-releasing hormone. However, the clinical characteristics of acromegaly with an increased GH response to luteinizing hormone-releasing hormone (LHRH responders) remain unclear. The aim of the present study was to evaluate the clinical characteristics, especially gonadotroph-related characteristics of LHRH responders in acromegaly.
METHODS: The clinical characteristics of 33 LHRH responders and 81 LHRH nonresponders were compared.
RESULTS: No differences in age, sex or basal serum levels of GH, insulin-like growth factor-1 (IGF-1), and gonadotropin were observed between the two groups. Steroidogenic factor 1 (SF-1), gonadotropin-releasing hormone receptor (GnRHR), and LH expression was more frequently observed in LHRH responders (P < 0.05). In addition, a greater increased rate of GH after LHRH loading, and the proportion of GnRHR and gonadotropin expression was observed in pituitary tumor with SF-1 expression than that without the expression (P < 0.01). LHRH responders showed a greater GH decrease in the octreotide test and a greater IGF-1 decrease after first-generation somatostatin ligand than LHRH nonresponders (P < 0.05). Furthermore, the proportion of hypointense pituitary tumors on T2-weighted magnetic resonance imaging and tumors with densely granulated type was higher in LHRH responders than in LHRH nonresponders, respectively (P < 0.05). No difference between the two groups was observed in either somatostatin receptor 2 or 5 expression.
CONCLUSIONS: The increased GH response to LHRH is associated with the gonadotroph-related characteristics. This response may reflect the biological characteristics of somatotroph tumors.

OBJECTIVE: To assess the diagnostic features of acromegaly, and analyse its management outcomes over a 15-year period in a tertiary care setting.
METHODS: The descriptive, cohort, retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of adult patients of either gender diagnosed with acromegaly based on biochemical and radiological evidence between January 2005 and December 2019. Data was retrieved from the medical records. Data was analysed using SPSS 19.
RESULTS: Of the 84 subjects, 54(64.3%) were males and 30(35.7%) were female. The overall mean age was 38.69±13.52 years. The patients presented 5.43±4.3 years after the onset of symptoms, with somatic growth features, such as enlarged hands and feet which was the most common complaint 81(96.4%). Of all the patients, 73(86.9%) underwent trans-sphenoidal surgery for the removal of the pituitary adenoma, while 11(13.1%) opted out of the surgical option. Further, 9(12.3%) patients showed biochemical and radiological remission 6 months post-surgery. Out of the remaining 64(87.7%) patients, 38(59.4%) received radiosurgery or radiotherapy, 15(23.4%) underwent repeat trans-sphenoidal surgery, and 11(17.2%) chose medical treatment.
CONCLUSIONS: Majority of patients failed to achieve remission after trans-sphenoidal surgery, which is the first line of treatment. Radiotherapy/repeat surgery was generally the options taken by those with persistent disease.

Medical treatment of acromegaly is currently performed through a trial-error approach using first generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated.
METHODS: prospective trial (21 university hospitals) comparing the effectiveness and time-to control of two treatment protocols during 12 months: A) A personalized protocol in which first option were fgSRLs as monotherapy or in combination with pegvisomant or, pegvisomant as monotherapy depending on the short Acute Octreotide Test (sAOT) results, tumor T2 Magnetic Resonance (MRI) signal or immunostaining for E-cadherin and, B) A control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control.
RESULTS: Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, p < 0.05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI 1.30-4.80). Patients from personalized arm were controlled in a shorter period of time (p = 0.01).
CONCLUSIONS: Personalized medicine is feasible using a relatively simple protocol and allows a higher number of patients achieving control in a shorter period of time.