Acromegaly in humans and cats: Pathophysiological, clinical and management resemblances and differences.

OBJECTIVE: Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species. DESIGN: A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed. RESULTS: Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine. CONCLUSION: Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.

Growth and Growth Hormone through the Ages: Art and Science.

BACKGROUND: People have long been fascinated with the size and growth of living things, from the giants of classic mythology and art to the little people who also have appeared in classical art, as well as the courts of European monarchs, and were exploited in "shows." Serious medical evaluation began in the late 19th century with the description of acromegaly and its association with pituitary tumors. In the early 20th century, multiple investigators attempted to extract a growth-promoting factor from the anterior pituitary and then, over the decades, to purify it and distinguish it from other anterior pituitary hormones. With relatively pure growth hormone (GH), its biological activity in growth promotion and as a metabolic hormone were studied, and species specificity became apparent: primate GH was the only GH active in man. Human GH was prepared from cadaveric pituitaries and distributed by the NIH to treat children with GH deficiency, but there was never enough pituitary hGH for all of the children who required it. When Creutzfeldt-Jakob disease was found in some patients who received pituitary GH, the production and FDA approval of biosynthetic hGH dramatically accelerated. With a large supply, one could treat those who were GH deficient and test its efficacy in other causes of short stature; longer acting versions of hGH have now been developed, tested, and in a few instances received FDA approval. SUMMARY: It has been a long journey from the description of over- and underproduction of GH in animals to the production and clinical use of the biosynthetic hormones. KEY MESSAGES: The efforts of basic scientists led to the extraction and purification of GH. Clinical scientists have expanded the appropriate use of hGH for short children with conditions in addition to GH deficiency.

Association of different pathologic subtypes of growth hormone producing pituitary adenoma and remission in acromegaly patients: a retrospective cohort study.

BACKGROUND: Regarding the inconclusive results of previous investigations, this study aimed to determine the association between pathology, as a possible predictor, with remission outcomes, to know the role of pathology in the personalized decision making in acromegaly patients. METHODS: A retrospective cohort study was performed on the consecutive surgeries for growth hormone (GH) producing pituitary adenomas from February 2015 to January 2021. Seventy-one patients were assessed for granulation patterns and prolactin co-expression as dual staining adenomas. The role of pathology and some other predictors on surgical remission was evaluated using logistic regression models. RESULTS: Among 71 included patients, 34 (47.9%) patients had densely granulated (DG), 14 (19.7%) had sparsely granulated (SG), 23 (32.4%) had dual staining pituitary adenomas. The remission rate was about 62.5% in the patients with SG and DG adenomas named single staining and 52.2% in dual staining groups. Postoperative remission was 1.53-folds higher in the single staining adenomas than dual staining-one (non-significant). The remission rate was doubled in DG group compared to two other groups (non-significant). By adjusting different predictors, cavernous sinus invasion and one-day postoperative GH levels decreased remission rate by 91% (95% CI: 0.01-0.67; p = 0.015) and 64% (95% CI: 0.19-0.69; p < 0.001), respectively. Responses to the medications were not significantly different among three groups. CONCLUSION: Various pathological subtypes of pituitary adenomas do not appear to have a predictive role in estimating remission outcomes. Cavernous sinus invasion followed by one-day postoperative GH is the strongest parameter to predict biochemical remission.

Incidence of Benign and Malignant Tumors in Patients With Acromegaly Is Increased: A Nationwide Population-based Study.

CONTEXT: Whether cancer risk in acromegaly is increased remains controversial, and the risk of benign tumors has been little studied. OBJECTIVE: To investigate the incidence of benign and malignant tumors in acromegaly in a nationwide population-based study. METHODS: Adult patients diagnosed with acromegaly between 1987 and 2017 were identified in the Swedish National Patient Registry. The diagnoses of benign and malignant tumors were recorded. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for neoplasms with 95% CIs were calculated using the Swedish general population as reference. RESULTS: The study included 1296 patients (52% women). Mean (SD) age at diagnosis was 51.6 (14.7) years. Median (range) follow-up time was 11.7 (0-31) years. Overall, 186 malignancies were identified in acromegalic patients compared with 144 expected in the general population (SIR 1.3; 95% CI 1.1-1.5). The incidence of colorectal and anal cancer (SIR 1.5; 95% CI 1.0-2.2), and renal and ureteral cancer (SIR 4.0; 95% CI 2.3-6.5) was increased, whereas the incidence of malignancies of the respiratory system, brain, prostate, and breast was not. Only 3 cases of thyroid cancer were recorded. Mortality due to malignancies was not increased (SMR 1.1; 95% CI 0.9-1.4). Incidence of benign tumors was increased more than 2-fold (SIR 2.4; 95% CI 2.1-2.7). CONCLUSION: Patients with acromegaly had an increased risk of both benign and malignant tumors, including colorectal and anal cancer, and renal and ureteral cancer. Whether this is associated with acromegaly itself or due to more intensive medical surveillance remains to be shown.

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.

The association between treatment and systemic inflammation in acromegaly.

OBJECTIVE: Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function. DESIGN: Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment. RESULTS: Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment. CONCLUSIONS: Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.

Lacrimal gland enlargement and tear film changes in acromegaly patients: A controlled study.

PURPOSE: Evaluation of the lacrimal gland volume (LGV) and its correlation with tear film functions, serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in acromegaly patients compared to a control group was aimed. METHODS: This prospective case-control study included the eyes of 38 patients with uncontrolled (UA) and 48 patients with controlled acromegaly (CA) and 44 patients with nonfunctioning pituitary adenoma. LGV of the patients was evaluated at the baseline, 3rd, and 6th-month visits with magnetic resonance imaging. Schirmer's test, tear breakup time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at the same visits. Their correlation with serum IGF-1 and GH was investigated. Main outcome measure was the difference in mean LGV. RESULTS: The mean LGV of the acromegaly patients at the baseline visit (116.0 ± 33.2 mm3) and the 3rd-month visit (119.5 ± 36.4 mm3) was higher than the control group (65.2 ± 22.3 mm3 and 63.2 ± 22.3 mm3, respectively; p < 0.001) without any significant difference between the UA and CA patients in the LGV in three consecutive visits (p > 0.05). Among all patients, IGF-1 and GH levels showed a positive correlation with the LGV (p < 0.001; r = 0.52; r = 0.6, respectively). However, Schirmer, TBUT, and OSDI scores did not show any difference among the three groups at each visit (p > 0.05). CONCLUSION: Acromegaly patients may have larger lacrimal glands compared to the controls and this increase correlated with the increased IGF-1 and GH levels. Lacrimal gland volume may have no effect on its tear film related functions.

Complications and Comorbidities of Acromegaly-Retrospective Study in Polish Center.

Introduction: In acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them. Materials and Methods: It was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis. Results: The study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20-78) and 46 for men (range 24-76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent. Conclusions: In our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups.

Prognostic Factors of Acromegalic Patients with Growth Hormone-Secreting Pituitary Adenoma After Transsphenoidal Surgery.

BACKGROUND: Acromegaly is a rare, chronic disorder that mostly results from growth hormone (GH)-secreting pituitary adenoma. Transsphenoidal surgery is the first-line treatment of this adenoma. This study aimed to identify factors associated with remission outcome in patients with GH-secreting pituitary adenomas following transsphenoidal surgery. METHODS: Patients with GH-secreting pituitary adenomas who underwent transsphenoidal surgery for tumor removal at Songklanagarind Hospital between January 2003 and December 2019 were retrospectively reviewed. The primary outcome was the remission of disease at the last follow-up using 2000 and 2010 consensus criteria. Using logistic regression analysis, various factors were analyzed for association with disease remission outcome. RESULTS: This study included 51 patients. The remission rate of GH-secreting pituitary microadenomas and macroadenomas following transsphenoidal surgery were 100% and 43.75%, respectively. Multivariate analysis showed that preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were significantly associated with nonremission outcome (P < 0.001 and P = 0.012, respectively). Patients with both of these factors had poor outcomes and never achieved remission after treatment, while patients with neither of these factors had high remission rates (87.5%) following surgery. Four of 6 (66.7%) patients who underwent repeat surgery gained remission. CONCLUSIONS: Preoperative insulin-like growth factor 1 index ≥2.5 and Knosp classification grade 3-4 were important prognostic factors that determined remission outcome after treatment. Patients who have both of these poor prognostic factors should be aggressively treated with surgery, medication, and probably radiation to optimally control the disease.

Reversibility of Cardiac Involvement in Acromegaly Patients After Surgery: 12-Month Follow-up Using Cardiovascular Magnetic Resonance.

Purpose: Cardiac comorbidity is one of the leading causes of death among acromegaly patients. We aimed to investigate the reversibility of acromegalic cardiac involvement after surgical treatment using the gold standard method, cardiovascular magnetic resonance, and to explore the effects of endocrine remission and gender on reversibility. Methods: In this single-center, prospective cohort study, fifty untreated acromegaly patients were enrolled. Comprehensive cardiac assessments were performed using a 3.0 T magnetic resonance scanner before and 3 and 12 months after transsphenoidal adenomectomy. Results: Preoperatively, left ventricular (LV) enlargement (13.0%), LV systolic dysfunction (6.5%), right ventricular (RV) enlargement (4.3%), RV systolic dysfunction (2.2%) and myocardial fibrosis (12.0%) were identified. On average, the LV and RV ejection fractions of acromegaly patients were higher than the healthy reference values. Male patients had thicker LV myocardia, wider ventricular diameters and more dilated pulmonary artery roots than female patients. After surgery, LV myocardial hypertrophy was reversed, the left atrium was remodeled, and ventricular systolic dysfunction recovered to normal. Cardiac alterations were detected early in the 3rd postoperative month and persisted until the 12th month. The interventricular septum was initially thickened in the 3rd postoperative month and then recovered at the 12th month. Notable postoperative cardiac reversibility was observed in male patients but did not occur in all female patients. Patients achieving endocrine remission with normalized hormone levels had thinner LV myocardia than patients without normalized hormone levels. Conclusion: Our findings demonstrated that some of the cardiac involvement in acromegaly patients is reversible after surgical treatment which lowers hormone levels. Endocrine remission and gender significantly impacted postoperative cardiac reversibility.

Bone densitometry by radiofrequency echographic multi-spectrometry (REMS) in acromegaly patients.

INTRODUCTION: Radiofrequency echographic multi-spectrometry (REMS) is a recently introduced non-ionising technology employed in the evaluation of osteoporosis. The aim of our study was to compare bone mineral density (BMD) in acromegaly patients and healthy controls by performing novel REMS densitometry. The second objective was to analyse the correlation between results of REMS and classical dual-energy X-ray absorptiometry (DXA) in acromegaly patients. MATERIAL AND METHODS: We enrolled 33 patients with acromegaly (AG) and 24 controls (CG). The acromegaly patients were divided into two subgroups: well-controlled acromegaly (WCA) and surgery-cured acromegaly (SCA). REMS was performed in all participants, while DXA was performed only in the acromegaly group. IGF-I and GH levels were measured in acromegaly patients. RESULTS: Bone mineral density of the lumbar spine (LS) and the femoral neck (FN) obtained from REMS did not reveal significant differences between AG, CG, WCA, and SCA. Similarly, there were no significant differences in BMD measured by DXA at the LS and at the FN between WCA and SCA. Significant positive correlations between IGF-I concentrations and BMD obtained from both REMS and DXA were detected in the AG and WCA. In the AG and WCA, there were positive correlations between T-scores and LS BMD obtained from both methods. CONCLUSIONS: Radiofrequency echographic multi-spectrometry is a potential method in assessment of bone status in acromegaly. Further studies with participation of active disease patients are needed.

Emerging drugs for the treatment of acromegaly.

INTRODUCTION: Acromegaly is a disease characterized by elevated growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels. Surgery is the only curative treatment, while medical therapies are administered life-long. To date, almost 30% of patients treated with the currently available medical therapies do not achieve biochemical control. AREAS COVERED: This review focuses on new drugs in development for acromegaly. In detail, we provide an overview of the new molecules designed to improve disease control rate (such as novel somotostatin receptor ligands and antisense oligonucleotides), as well as the new formulations of existing medications aiming to improve patients' compliance (e.g. oral or long-acting subcutaneous octreotide). EXPERT OPINION: The constant progresses in the medical treatment of acromegaly could lead to an individualized therapy based on tumor, as well as patient's characteristics. Besides disease control, patient's need represents a major target of medical treatment in chronic diseases such as acromegaly, in order to improve compliance to therapy and patients' quality of life.

The significance of estrogen receptors in acromegaly: Are they useful as predictors of prognosis and therapy regimen?

OBJECTIVE: In this study, we considered to assess the presence of estrogen receptors (ER) and the expression of estrogen receptor genes (ESR) in the surgical tissue samples of acromegaly patients and the control group patients with nonfunctioning adenoma and their association with disease activity. We also aimed to determine the significance of ER positivity in acromegaly patients and to find out whether it carries a potential to be used as a predictor of prognosis and therapy regimen in the future. DESIGN: This study was conducted on a total of 67 patients over 18 years of age. The study group consisted of 34 patients with acromegaly and 33 patients with nonfunctioning pituitary adenoma. The pre- and post-operative basal pituitary hormone levels and magnetic resonance images (MRI) of all patients, as well as their remission status of all acromegaly patients were evaluated. Immunohistochemical (IHC) staining procedures for ER-α were performed on surgical tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) method was used to determine the levels of ESR1 and ESR2 gene expressions. RESULTS: We found that IHC staining for ER-α was positive in 31.3% and 45.5% of the patients with acromegaly and nonfunctioning adenoma respectively. There was no statistically significant difference of ER-α positivity, ER-α immunoreactivity score and ESR1/ESR2 gene expression levels among the study groups (p > .05). Nevertheless, the expression of ESR1 gene was found to be 0.26 times more, and the ESR2 gene to be 0.11 times less in the acromegaly group compared to those of the nonfunctioning adenoma group. Additionally, we detected the positivity of ER-α only in acromegaly patients who were in remission. An inverse association was found between the pre-operative insulin-like growth factor-1 (IGF-1) levels and the expressions of ESR1/ESR2 gene in acromegaly patients. So these results indicated that the high ESR1 and ESR2 gene expressions in acromegaly patients are associated to the decrease of pre-operative IGF-1 values. Also an inverse association was found between the pre-operative adenoma volume and ESR1 Ct values, means that increase in ESR1 gene expression is associated to the decrease of adenoma volume. CONCLUSIONS: The current results may suggest the use of these parameters as useful prognostic markers because all ER-positive acromegaly patients were in remission and the high ESR1 and ESR2 gene expressions in acromegaly patients is associated to the decrease of pre-operative IGF-1 values. Our results need to be supported by further studies.

Thyroid gland changes in patients with acromegaly.

OBJECTIVE: Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. SUBJECTS AND METHODS: In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. RESULTS: Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. CONCLUSIONS: Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75.

Thyroid gland changes in patients with acromegaly

ABSTRACT Objective Acromegaly is characterized by high neoplastic morbidity as a side effect of growth hormone (GH) hypersecretion. Increased incidence of goiter, thyroid carcinoma, and thyroid dysfunction is also reported. The aim of the present study was to find the prevalence of thyroid dysfunction and goiter in patients with acromegaly and determine its relationship to disease activity, disease duration, and the presence of secondary hypothyroidism. Subjects and methods In a cross-sectional study of the period 2008-2012 were included 146 patients with acromegaly (56 men, 90 women) of mean age 50.3 ± 12.4 years. Acromegaly disease activity and thyroid function were evaluated in all patients. Thyroid ultrasonography was performed to calculate thyroid volume and detect the presence of nodular goiter. Results Ninety-one patients were determined to have an active disease, and 55, a controlled disease. The mean thyroid volume in patients without previous thyroid surgery was 37.6 ± 38.8 mL. According to disease activity, thyroid volume was significantly higher in patients with active disease (38.5 ± 45.4 mL vs. 27.2 ± 18.4 mL, p = 0.036). A weak positive correlation was found between thyroid volume and insulin-like growth factor 1 (IGF-1) in the whole group and in females (R = 0.218; p = 0.013, and R = 0.238; p = 0.037, respectively). There was no significant correlation of thyroid volume with disease duration and GH level in the whole group and in both sexes. The patients with secondary hypothyroidism had twofold smaller thyroid volume, relative to the rest of the group. The prevalence of thyroid dysfunction was 39%, with a female to male percentage ratio of 1.73. Goiter was diagnosed in 87% of patients, including diffuse goiter (17.1%) and nodular (69.9%), with no significant difference between patients with active and controlled disease or the presence of secondary hypothyroidism. Conclusions Thyroid volume in patients with acromegaly depends on disease activity and the presence of secondary hypothyroidism as a complication. The increased prevalence of nodular goiter determines the need of regular ultrasound thyroid evaluation in the follow-up of patients with acromegaly. Arch Endocrinol Metab. 2020;64(3):269-75

Clinical features and therapeutic outcomes of patients with acromegaly in Saudi Arabia: a retrospective analysis.

BACKGROUND: Acromegaly is a rare disease resulting in clinical sequelae with significant morbidity and mortality due to the central tumor mass effect and prolonged growth hormone (GH) hypersecretion. OBJECTIVES: The goal is to describe the epidemiology, clinical features, presence of comorbidities, and treatment outcomes of acromegaly in Saudi Arabia. METHODS: Data was collected through a retrospective review of the charts of all patients diagnosed with acromegaly from nine major hospitals in Saudi Arabia over a period of more than 25 years. RESULTS: A total of 195 patients (116 males and 79 females), with a mean age at diagnosis of 43 ± 12 (males) and 46 ± 14 years (females), from nine major hospitals were identified and included in the analysis. All cases were caused by pituitary adenomas, of which 92.4% were macroadenomas. Headache, coarse facial features, acral growth, and sweating/oily skin were by far the most frequent presenting complaints. The most common comorbidities were diabetes mellitus (51.7%), followed by hypertension (50%) and visual field defect (30.5%). The vast majority (95%) of patients were treated surgically (98%). Twenty-four percent also received radiotherapy, and 74.4% received medical therapy. When stringent criteria were applied for assessment of outcomes of therapy, 28.7% of the patients were cured and 30.1% had their disease under control, while 28.7% were found to have active disease despite receiving multimodal therapy. CONCLUSIONS: Our findings highlight the need for a national acromegaly registry to enable early identification, evaluation, and selection of the best therapeutic approaches to improve the outcome and remission rate of the disease.

Active acromegaly is associated with enhanced left ventricular contractility: Results from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

INTRODUCTION: Acromegaly is a relatively rare chronic hormonal disease resulting in disfigurement. In 90% of cases, acromegaly is caused by a benign pituitary monoclonal human growth hormone-secreting tumor. The aim of the present study was to determine the presence of left ventricular (LV) deformation abnormalities using three-dimensional speckle-tracking echocardiography in a group of acromegalic patients. METHODS: Thirty-eight acromegalic patients were involved in the study. Thirteen patients were excluded due to inadequate image quality. The mean age of the remaining patients was 57.2±13.6 years and seven were male. Their data were compared to an age- and gender-matched control population, which consisted of 34 healthy volunteers (mean age: 52.7±4.9 years, 15 male). RESULTS: Global and mean segmental LV radial strain (RS) (33.2±13.4% vs. 25.2±10.8%, p=0.01 and 36.0±12.1% vs. 28.2±10.0%, p=0.009, respectively) proved to be significantly higher in acromegaly compared to controls. Active acromegalic patients had significantly higher global and mean segmental LV-RS (35.5±14.4% vs. 25.2±10.8%, p=0.03 and 37.9±13.3% vs. 28.2±10.0%, p=0.03, respectively) compared to controls. Between the active and inactive acromegaly groups, only basal LV circumferential strain (-30.2±4.8% vs. -26.7±4.1%, p=0.02) was found to be significantly different. CONCLUSION: The presented clinical, demographic, therapeutic and echocardiographic features demonstrate that active acromegaly is associated with enhanced LV RS as compared to healthy controls and those with inactive acromegaly.

Lung function and blood gas abnormalities in patients with acromegaly.

OBJECTIVE: Respiratory disorders are common complications of acromegaly patients. We conducted a large-scale survey in the patients with acromegaly and demonstrated the characteristics of their lung function and blood gas. METHODS: A prospective cohort study was conducted with 115 patients with active acromegaly and 56 patients with nonfunctioning pituitary adenomas. All patients underwent clinical, biological, radiological, lung functional and blood gas assessments. RESULTS: Acromegaly patients had a higher lung volume than those with nonfunctioning adenomas (forced vital capacity value (FVC) and FVC% predicted: p < 0.001). The small airway was less obstructive in acromegaly patients (higher FEV1% predicted, PEF% predicted, MEF75% predicted, MEF50% predicted, MEF25% predicted: p ≤ 0.001 for all analyses, FEV1/FVC: p = 0.151). The average partial pressure of carbon dioxide in acromegaly patients was higher (p < 0.001), but there was no significant difference in the average partial pressure of oxygen or oxygen saturation between the two groups (p > 0.05). In acromegaly patients, the average age of patients with small airway obstruction was higher than that of patients with normal lung function (p < 0.05), but no significant difference in GH or IGF-1 levels between the two groups were found (p > 0.05). CONCLUSION: The acromegaly patients in this cohort had increased lung volume. However, there was no evidence demonstrating hypoxemia in acromegaly patients. The small airway was less obstructive in acromegaly patents. Small airway obstruction was observed in elderly patients with acromegaly.

Risk for Acromegaly-related Comorbidities by Sex in Korean Acromegaly.

CONTEXT: Reports on the incidence, characteristics, and comorbidity in Asian patients with acromegaly are scarce. OBJECTIVE: To evaluate the incidence of acromegaly and the risk of comorbidities in East Asia, especially South Korea. DESIGN: This nationwide population-based cohort study using the Korean Health Insurance Review and Assessment claims database evaluated the incidence of acromegaly, initially diagnosed from 2010 to 2013. We identified comorbidities during, before, and 2 years after diagnosis. Acromegaly and control cases (718 and 7180, respectively) were included in the analysis. SETTING: A longitudinal case-control study using a nationwide population cohort. RESULTS: The mean annual incidence rate of acromegaly was 3.57 cases per 1 000 000. Malignancies occurred in 61 patients with acromegaly (8.5%) during the study period and thyroid cancer was the most common malignancy (n = 38). In the acromegaly group, the overall risk of malignancy was higher: hazard ratio (HR), 2.82 (95% confidence interval [CI]: 2.12-3.74). Malignancy risk was more pronounced in females, with increased risk from the prediagnosis period that is sustained until the postdiagnosis period. Prevalence of diabetes mellitus (DM) and heart failure increased significantly in acromegalic patients. Over the entire period, DM developed in 51.1% and 57.0% of male and female acromegalic patients, respectively. Mortality risk was higher (HR 1.65, 95%; CI: 1.13-2.41) and statistically significant in females (HR 1.75, 95%; CI: 1.07-2.84). CONCLUSION: Comorbidities associated with acromegaly differed by sex in Korean subjects. High malignancy and mortality risk should be considered in female patients when managing acromegaly in Korea.

Somatostatin receptors in normal and acromegalic somatotroph cells: the U-turn of the clinician to immunohistochemistry report - a review.

This is a narrative review of literature introducing somatostatin receptors (SSTRs) as part of understanding the somatotroph cells since they are positive in normal cells but also in tumoral cells as seen in somatotropinoma, a growth hormone (GH)-producing neoplasia, which causes acromegaly. They are five subtypes of SSTRs (1 to 5), which are immunohistochemically positive in different proportions in somatotropinomas. SSTR types 2 and 5 are most frequent in GH-secreting adenomas and they are both targeted by medical therapy with somatostatin analogues (SSTAs) like first generation Octreotide and Lanreotide (mainly targeting SSTR2) and second generation Pasireotide (with highest affinity for SSTR5), thus heterogeneous SSTRs configuration into the tumor explains different pattern of response to treatment and it might predict it once the SSTRs immunostaining is performed. Monoclonal antibodies are used for immunohistochemical detection of SSTRs; currently, a lack of standardization is presented, and scoring systems, such as Volante, H-score or human epidermal growth factor receptor 2 (HER2)-score, are applied. Immunoreactive markers like SSTRs are the U-turn in clinical practice regarding somatotropinomas since the configuration of subtypes 2 and 5 explains the responsiveness to medical therapy like SSTA. Further achievement of disease control is imperiously necessary because acromegaly has an increased rate of morbidity and mortality.