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Pituitary Jun 2024Skeletal fragility is a clinically relevant and not-reversible complication of acromegaly, involving around 30-40% of patients since the disease diagnosis. Few studies...
INTRODUCTION
Skeletal fragility is a clinically relevant and not-reversible complication of acromegaly, involving around 30-40% of patients since the disease diagnosis. Few studies have investigated the effects on skeletal health of medical therapies for acromegaly. In this retrospective longitudinal monocentre study, we investigated the outcome of skeletal fragility in patients treated with Pasireotide Lar in combination with Pegvisomant (Pasi-Lar + Peg-V), also comparing those observed in patients treated with conventional therapies.
RESULTS
We included 6 patients treated with Pasi-Lar + Peg-V, 5 patients treated with Peg-V in monotherapy (m-Peg-V), 16 patients treated with Peg-V plus first-generation somatostatin receptor ligands (fg-SRLs + Peg-V), 9 patients treated with Pasi-Lar. None of the patients treated with Pasi-Lar + Peg-V experienced worsening of spine and femoral bone mineral density (BMD) and incident vertebral fractures (i-VFs). Eight patients experienced i-VFs. The frequency of i-VFs was significantly lower in patients treated with the Pasi-Lar + Peg-V (0/8; 0%), as compared to those observed in m-Peg-V treated patients (4/8; 50%, p = 0.02). The frequency of i-VFs was slightly but not significantly higher in Pasi-Lar treated patients (1/8; 12.5% p = 0.6) and in fg-SRLs + Peg-V treated patients (3/8; 37.5% p = 0.364), concerning those treated with Pasi-Lar + Peg-V (0/8; 0%). I-VFs occurred more frequently in patients with higher GH levels at acromegaly diagnosis (p < 0.001), and in patients who experienced a BMD worsening (p = 0.005).
CONCLUSION
Our preliminary data suggested that in conventional and multi-drug resistant acromegaly, the combination therapy Pasi-Lar + Peg-V may prevent the worsening of BMD and the occurrence of i-VFs. Prospective and translational studies should further validate these results and ascertain underlying physiopathology mechanisms.
Topics: Humans; Acromegaly; Bone Density; Middle Aged; Female; Male; Retrospective Studies; Adult; Somatostatin; Human Growth Hormone; Pilot Projects; Aged; Longitudinal Studies
PubMed: 38713317
DOI: 10.1007/s11102-024-01398-9 -
Endocrine-related Cancer Jul 2024The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL)...
The objective of the study was to evaluate the efficacy of second-line therapies in patients with acromegaly caused by a growth hormone (GH) and prolactin (PRL) co-secreting pituitary neuroendocrine tumor (GH&PRL-Pit-NET) compared to their efficacy in patients with acromegaly caused by a GH-secreting pituitary neuroendocrine tumor (GH-Pit-NET). This is a multicenter retrospective study of patients with acromegaly on treatment with pasireotide and/or pegvisomant. Patients were classified in two groups: GH&PRL-Pit-NETs when evidence of hyperprolactinemia and immunohistochemistry (IHC) for GH and PRL was positive or if PRL were >200 ng/dL regardless of the PRL-IHC and GH-Pit-NETs when the previously mentioned criteria were not met. A total of 28 cases with GH&PRL-Pit-NETs and 122 with GH-Pit-NETs met the inclusion criteria. GH&PRL-Pit-NETs presented at a younger age, caused hypopituitarism, and were invasive more frequently than GH-Pit-NETs. There were 124 patients treated with pegvisomant and 49 with pasireotide at any time. The efficacy of pegvisomant for IGF-1 normalization was of 81.5% and of pasireotide of 71.4%. No differences in IGF-1 control with pasireotide and with pegvisomant were observed between GH&PRL-Pit-NETs and GH-Pit-NETs. All GH&PRL-Pit-NET cases treated with pasireotide (n = 6) and 82.6% (n = 19/23) of the cases treated with pegvisomant normalized PRL levels. No differences in the rate of IGF-1 control between pegvisomant and pasireotide were detected in patients with GH&PRL-Pit-NETs (84.9% vs 66.7%, P = 0.178). We conclude that despite the more aggressive behavior of GH&PRL-Pit-NETs than GH-Pit-NETs, no differences in the rate of IGF-1 control with pegvisomant and pasireotide were observed between both groups, and both drugs have shown to be effective treatments to control IGF-1 and PRL hypersecretion in these tumors.
Topics: Humans; Somatostatin; Male; Female; Human Growth Hormone; Middle Aged; Adult; Prolactin; Retrospective Studies; Neuroendocrine Tumors; Acromegaly; Pituitary Neoplasms; Aged; Young Adult
PubMed: 38713182
DOI: 10.1530/ERC-24-0043 -
Clinical Endocrinology May 2024Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In...
OBJECTIVES
Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies.
DESIGN, PATIENTS, AND MEASUREMENTS
In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated.
RESULTS
The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035).
CONCLUSIONS
Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier.
PubMed: 38712950
DOI: 10.1111/cen.15071 -
The Journal of Craniofacial Surgery May 2024A 40-year-old man presented with acromegaly, reduction of visual acuity and visual field, and elevated blood sugar. Imaging examinations demonstrated a large sellar...
A 40-year-old man presented with acromegaly, reduction of visual acuity and visual field, and elevated blood sugar. Imaging examinations demonstrated a large sellar adenoma with suprasellar extension that compresses the optic chiasma upward, spreads downward to the sphenoid sinus, and invades the cavernous sinus bilaterally. Random prolactin and growth hormone were beyond the scope of normal. The patient achieved complete shrinking of the adenoma by taking bromocriptine orally. For some kinds of giant mixed growth hormone-prolactin adenomas, surgical treatment is not necessary, and drug treatment can also achieve good results.
PubMed: 38710062
DOI: 10.1097/SCS.0000000000010227 -
Journal of Endocrinological... May 2024The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7)...
PURPOSE
The liver is known to be protected from steatosis under the influence of high GH/IGF-1. Cytokeratin 18 (CK18) and insulin-like growth factor binding protein 7 (IGFBP7) increase in liver steatosis and fibrosis. The aim of this study was to use quantitative ultrasound techniques and biochemical markers to assess liver steatosis and liver fibrosis in newly diagnosed acromegaly.
METHODS
This single-center, cross-sectional study included 23 patients with newly diagnosed acromegaly and 46 age, sex, body mass index (BMI) and waist circumference (WC)-matched controls. Liver steatosis was assessed using tissue attenuation imaging (TAI), and stiffness, indicative of fibrosis, was assessed by shear wave elastography (SWE). Serum IGFBP7 and CK18 were studied by ELISA.
RESULTS
The acromegaly group had significantly lower liver steatosis (p = 0.006) and higher liver stiffness (p = 0.004), serum IGFBP7 (p = 0.048) and CK18 (p = 0.005) levels than the control group. The presence of fibrosis (p = 0.012) was significantly higher in the acromegaly group than in the control group. Moreover, CK18 was positively correlated with liver stiffness, WC, HOMA-IR, HbA1c, and triglyceride. In the acromegaly group, liver steatosis was negatively correlated with GH level. Stepwise multiple linear regression analysis revealed that BMI (p = 0.008) and CK18 (p = 0.015) were independent risk factors for increased liver stiffness.
CONCLUSION
This study showed that there was an increased presence of liver fibrosis independent of liver steatosis in newly diagnosed acromegaly. Serum CK18 appears to be a potential marker of increased liver fibrosis in acromegaly.
PubMed: 38709454
DOI: 10.1007/s40618-024-02384-5 -
European Journal of Endocrinology Jun 2024Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display...
INTRODUCTION
Growth hormone (GH)-secreting pituitary tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarker assessment associated with tumor growth and invasion is important to optimize their management.
OBJECTIVES
The study aims to identify clinical/hormonal/molecular biomarkers associated with tumor size and invasiveness in GHomas and to analyze the influence of pre-treatment with somatostatin analogs (SSAs) or dopamine agonists (DAs) in key molecular biomarker expression.
METHODS
Clinical/analytical/radiological variables were evaluated in 192 patients from the REMAH study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). The expression of somatostatin/ghrelin/dopamine system components and key pituitary/proliferation markers was evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables.
RESULTS
Eighty percent of patients harbor macroadenomas (63.8% with extrasellar growth). Associations between larger and more invasive GHomas with younger age, visual abnormalities, higher IGF1 levels, extrasellar/suprasellar growth, and/or cavernous sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (P < .05) were associated with tumor invasiveness. Least Absolute Shrinkage and Selection Operator's penalized regression identified combinations of clinical and molecular features with areas under the curve between 0.67 and 0.82. Pre-operative therapy with DA or SSAs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with DA) and FSHB/CRHR1 (down-regulated with SSAs).
CONCLUSIONS
A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.
Topics: Humans; Male; Female; Acromegaly; Middle Aged; Adult; Growth Hormone-Secreting Pituitary Adenoma; Neoplasm Invasiveness; Adenoma; Aged; Dopamine Agonists; Biomarkers, Tumor; Somatostatin; Human Growth Hormone
PubMed: 38701338
DOI: 10.1093/ejendo/lvae045 -
World Neurosurgery Apr 2024This study aims to evaluate the impact of surgical intervention on anxiety levels in patients with various types of pituitary adenoma (PA). (Review)
Review
OBJECTIVE
This study aims to evaluate the impact of surgical intervention on anxiety levels in patients with various types of pituitary adenoma (PA).
METHOD
A systematic review was conducted following PRISMA guidelines until October 2022, searching Embase, PubMed, Web of Sciences, and Scopus.
RESULTS
A total of 32 studies were included, encompassing 2,681 patients with the mean age of 53.33 ± 6.48 years (43.4% male). Among all subtypes, 664 diagnosed with Cushing's disease (25.8%), 612 with acromegaly (23.8%), 282 with prolactinoma (10.9%), and 969 with nonfunctional pituitary adenomas (37.6%). Pituitary insufficiency was the most common complication. Considering therapeutic modalities, 515 patients (29.8%) underwent endoscopic trans-sphenoidal surgery, while 222 (12.9%) underwent microscopic trans-sphenoidal surgery. The type of trans-sphenoidal surgery was not specified in 977 (56.6%) patients. A total of 17 studies including 1510 patients which mostly assessed anxiety using the Hospital Anxiety and Depression Scale (HADS) and Zung Self-Rating Anxiety Scale (SAS) were included in the meta-analysis. Preoperative evaluation using Hospital Anxiety and Depression Scale (HADS) questionnaire showed a pooled score of 8.27 (95%CI 4.54-12.01), while postoperative evaluation yielded a pooled score of 6.49 (95%CI 5.35-7.63), indicating no significant difference. Preoperative SAS assessment resulted in a pooled score of 50.43 (95%CI 37.40-63.45), with postoperative pooled score of 55.91 (95%CI 49.40-62.41), showing no significant difference.
CONCLUSIONS
Our analysis revealed no significant difference in anxiety scores pre- and postoperatively. While our findings suggest stability in anxiety levels following surgical intervention, it is imperative to recognize the limitations of the current evidence base. The observed lack of consensus may be influenced by factors such as the heterogeneous nature of the patient population, variations in the characteristics of pituitary adenomas, diverse therapeutic approaches, and potential confounding variables such as pre-existing mental health conditions and coping mechanisms. Further research is warranted to elucidate the nuanced relationship between surgical intervention for PA and anxiety outcomes, considering these complex interactions and employing rigorous methodologies to address potential sources of bias.
PubMed: 38697260
DOI: 10.1016/j.wneu.2024.04.154 -
The International Journal of... Apr 2024
PubMed: 38683445
DOI: 10.1007/s10554-024-03110-1 -
Best Practice & Research. Clinical... May 2024
Topics: Humans; Acromegaly; Human Growth Hormone
PubMed: 38677954
DOI: 10.1016/j.beem.2024.101897 -
Reviews in Endocrine & Metabolic... Apr 2024The review discusses the relationship between acromegaly and uterine fibroids. It highlights variations in research methodologies and inconsistent findings, emphasizing... (Review)
Review
The review discusses the relationship between acromegaly and uterine fibroids. It highlights variations in research methodologies and inconsistent findings, emphasizing the complex nature of fibroid development and the role of the somatotropic axis. Additionally, it addresses demographic factors and examines the potential impact of therapies on the risk and prevalence of uterine fibroids in individuals with acromegaly. We conducted an analysis of previously published literature that examined the repercussions of acromegaly on gynecological health in female cohorts, with specific attention directed towards elucidating the prevalence of uterine fibroids. We suggest that larger, more focused studies are needed to understand the specific impact of different treatments on the occurrence of gynecological issues in acromegaly patients. Additionally, our study emphasizes the importance of factors such as disease duration and treatment effectiveness. We hypothesize that a relationship between acromegaly and uterine fibroids may occur. However, it remains an area of ongoing research, with the need for larger, multi-center studies to draw more definitive conclusions.
PubMed: 38668933
DOI: 10.1007/s11154-024-09883-z