GH-secreting Pituitary Adenomas Research Articles

Differences between GH and PRL co-secreting and GH-secreting pituitary adenomas. A series of 604 cases.

To evaluate differences in clinical presentation and in surgical outcomes between growth hormone-secreting pituitary adenomas (GH-PAs) and GH and prolactin co-secreting pituitary adenomas (GH&PRL-PAs). Multicenter retrospective study of 604 patients with acromegaly submitted to pituitary surgery. Patients were classified into two groups according to serum PRL levels at diagnosis and immunohistochemistry (IHC) for PRL: a) GH&PRL-PAs when PRL levels were above the upper limit of normal and IHC for GH and PRL was positive or PRL levels were >100ng/and PRL IHC was not available (n=130) and b) GH-PAs who did not meet the previously mentioned criteria (n=474). GH&PRL-PAs represented 21.5% (n=130) of patients with acromegaly. The mean age at diagnosis was lower in GH&PRL-PAs than in GH-PAs (P<0.001). GH&PRL-PAs were more frequently macroadenomas (90.6% vs. 77.4%, P=0.001) and tended to be more invasive (33.6% vs. 24.7%, P=0.057) than GH-PAs. Furthermore, they had presurgical hypopituitarism more frequently (OR 2.8, 95% CI 1.83-4.38). IGF-1 upper limit of normality (ULN) levels at diagnosis were lower in patients with GH&PRL-PAs (median 2.4 [IQR 1.73-3.29] vs. 2.7 [IQR 1.91-3.67], P=0.023). There were no differences in the immediate (41.1% vs 43.3%, P=0.659) or long-term post-surgical acromegaly biochemical cure rate (53.5% vs. 53.1%, P=0.936) between groups. However, there was a higher incidence of permanent arginine-vasopressin deficiency (AVP-D) (7.3% vs. 2.4%, P=0.011) in GH&PRL-PAs patients. GH&PRL-PAs are responsible for 20% of acromegaly cases. These tumors are more invasive, larger and cause hypopituitarism more frequently than GH-PAs and are diagnosed at an earlier age. The biochemical cure rate is similar between both groups, but patients with GH&PRL-PAs tend to develop permanent postsurgical AVP-D more frequently.

Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

Surgical and non-surgical interventions for primary and salvage treatment of growth hormone-secreting pituitary adenomas in adults.

A novel somatostatin receptor ligand for human ACTH - and GH -secreting pituitary adenomas.

Somatostatin receptor ligands have come to play a pivotal role in the treatment of both ACTH- and GH-secreting pituitary adenomas. Clinical efficacy averages 30-50%, thus a considerable number of patients with Cushing's disease or acromegaly remain unresponsive to this therapeutic approach. HTL0030310 is a new somatostatin receptor ligand selective for subtype 5 over subtype 2, thus with a different receptor profile compared to clinical somatostatin receptor ligands. Assessment of the effect of HTL0030310 on hormone secretion in human ACTH- and GH-secreting pituitary adenomas in vitro. Primary cultures from 3 ACTH-secreting and 5 GH-secreting pituitary adenomas were treated with 1, 10 and 100 nM HTL0030310 alone or with 10 nM CRH or GHRH, respectively. Parallel incubations with 10 nM pasireotide were also carried out. ACTH and GH secretion were assessed after 4 and 24 hour incubation; SSTR2, SSTR3, SSTR5, GH and POMC expression were evaluated after 24 hours. HTL0030310 reduced unchallenged ACTH and POMC levels up to 50% in 2 ACTH-secreting adenomas and blunted CRH-stimulated ACTH/POMC by 20-70% in all 3 specimens. A reduction in spontaneous GH secretion was observed in 4 GH-secreting adenomas and in 2 specimens during GHRH co-incubation. SSTRs expression was detected in all specimens. This first study on a novel somatostatin receptor 5-preferring ligand indicates that HTL0030310 can inhibit hormonal secretion in human ACTH- and GH-secreting pituitary adenomas. These findings suggest a potential new avenue for somatostatin ligands in the treatment of Cushing's disease and acromegaly.

A Novel Preoperative Score to Predict Long-Term Biochemical Remission in Patients with Growth-Hormone Secreting Pituitary Adenomas

Transsphenoidal surgery (TSS) is considered the treatment of choice in most patients with growth hormone (GH)-secreting pituitary adenomas. Several preoperative factors have been studied to predict postsurgical remission. Our objective was to design a score that could be used in the preoperative setting to identify patients that will achieve long-term biochemical remission after TSS. A retrospective analysis of consecutive patients with GH-secreting pituitary adenomas that underwent TSS in our institution from 2000 to 2015 who fulfilled prespecified criteria were included. Logistic regression methods were used to evaluate independent preoperative variables predicting long-term remission. Beta coefficients were used to create a scoring system for clinical practice. Sixty-eight patients were included, with a mean follow-up time of 87months. Twenty (29%) patients had tumors with a Knosp grade ≥ 3A. Gross-total resection was achieved in 43 (63%) patients. Thirty-three (48%) patients had long-term biochemical remission after TSS. In a multivariate analysis, the following variables were statistically significantly associated with long-term biochemical remission: age, adenoma size (diameter), Knosp grade, GH level, and insulin growth-factor 1index 1 at diagnosis. A score of <3 out of 8 total points was identified as a cutoff associated with long-term remission, with a sensitivity of 91.4% and specificity of 72.7% (AUC 0.867, OR 28.44, 95% CI 6.94-116.47, P=<0.001). A novel, simple, easy-to-use scoring system was created to identify patients with the highest chances of long-term biochemical remission following TSS. This scale should be prospectively validated in a multicenter study before widespread adoption.

THU078 The Definition And Epidemiology Of Giant Pituitary GH-Secreting Adenomas Based On Clinical, Imaging, And Hormonal Parameters: A Pilot Study

Abstract Disclosure: L.M. Del Corso: None. M.C. Silva: None. S.Z. Fidalski: None. C.L. Boguszewski: None. Acromegaly is a chronic disease, caused by a GH-secreting pituitary adenoma in most cases. At diagnosis, around 75% of patients have a macroadenoma, which constitute a heterogeneous group with variable biological behavior, therapeutic response, and prognosis. Giant adenomas (GA) have been defined as those which are more than 40 mm at their largest in diameter, but this is an arbitrary definition lacking comparative studies to investigate tumor size at diagnosis with clinical presentation, response to treatment and the evolution of acromegaly patients. Thus, the aim of our study was to compare the aforementioned variables according to the tumor size at diagnosis and review the diagnostic criteria for giant GH-secreting adenomas. In this observational, retrospective, single-centre pilot study, we have retrieved data from 161 medical records and evaluated age, sex, duration of symptoms, GH levels, presence of type 2 diabetes mellitus (T2DM), hypertension and hypopituitarism, imaging characteristics, and the need for adjuvant therapy with somatostatin receptor ligands (SRL) or other drugs. Study population was classified into four groups according to tumor size at diagnosis: (I) &amp;lt;10 mm (microadenomas; n=14); (II) 10-29 mm (n=84); (III) 30-39 mm (n=10); (IV) 40 mm or more (n=9). The final study group consisted of 117 individuals (49% men; mean age 43 ± 13 yrs). Hypopituitarism was significantly more frequent in groups III and IV compared to groups I and II (p=0.004), with no difference between groups III and IV (p=0,3). There was a higher proportion of invasive adenomas when the lesions ≥ 30 mm were compared to groups I and II (p=0.008), but with no difference between groups III and IV (p=0.62). Sixty percent of patients in group III (n=6) and 44% of patients in group IV (n=4) needed other drug therapy than SRL (cabergoline and/or pegvisomant), a higher proportion compared to those of groups I (n=1; 7%) and II (n=25; 30%) (p=0.04), again without difference between groups III and IV (p=0,7). Regarding the initial levels of GH, a significant difference was observed between groups I and IV (p=0.04), but this difference was not observed in the other groups. There were no statistical differences in relation to sex, duration of symptoms, need for SRL therapy, prevalence of hypertension and T2DM between study groups. Our study raises the hypothesis that giant adenomas should be defined as tumors larger than 30 mm, as the clinical behavior of tumors above this cutoff point seems to be similar in comparison with tumors larger than 40 mm but different from those of smaller sizes. Presentation: Thursday, June 15, 2023

Long-term control of acromegaly after pituitary surgery in South-Eastern Norway

PurposeSustained cure of acromegaly can only be achieved by surgery. Most growth hormone (GH) secreting pituitary adenomas are macroadenomas (≥ 10 mm) at diagnosis, with reported surgical cure rates of approximately 50%. Long-term data on disease control rates after surgery are limited. Our aim was to estimate short- and long-term rates of biochemical control after pituitary surgery in acromegaly and identify predictive factors.MethodsPatients operated for GH-secreting pituitary adenomas between 2005–2020 were included from the local pituitary registry (n = 178). Disease activity and treatment data were recorded at one-year (short-term) and five-year (long-term) postoperative follow-up. Biochemical control was defined as insulin-like growth factor 1 (IGF-1) ≤ 1.2 × upper limit of normal value. Multivariate regression models were used to identify factors potentially predicting biochemical control.ResultsA total of 178 patients with acromegaly (median age at diagnosis 49 (IQR: 38–59) years, 46% women) were operated for a pituitary adenoma. Biochemical control was achieved by surgery in 53% at short-term and 41% at long-term follow-up, without additional treatment for acromegaly. Biochemical control rates by surgery were of same magnitude in paired samples (45% vs. 41%, p = 0.213) for short- and long-term follow-up, respectively. At short-term, 62% of patients with microadenomas and 51% with macroadenomas, achieved biochemical control. At long-term, the biochemical control rate was 58% for microadenomas and 37% for macroadenomas (p = 0.058). With adjunctive treatment, 82% achieved biochemical control at long-term. Baseline IGF-1 levels significantly predicted biochemical control by surgery at short-term (OR: 0.98 (95% CI: 0.96–0.99), p = 0.011), but not at long-term (OR: 0.76 (95% CI: 0.57–1.00), p = 0.053).ConclusionIn unselected patients with acromegaly, the long-term biochemical control rate remains modest. Our findings indicate a need to identify patients at an earlier stage and improve therapeutic methods and surgical outcomes.

The potential link between acromegaly and risk of acute ischemic stroke in patients with pituitary adenoma: a new perspective.

Acromegaly is an endocrine disorder due to the excess production of growth hormone (GH) from the anterior pituitary gland after closed epiphyseal growth plates. Acromegaly is mainly caused by benign GH-secreting pituitary adenoma. Acute ischemic stroke (AIS) is one of the most common cardiovascular complications. It ranks second after ischemic heart disease (IHD) as a cause of disability and death in high-income countries globally. Thus, this review aimed to elucidate the possible link between acromegaly and the development of AIS. The local effects of acromegaly in the development of AIS are related to the development of pituitary adenoma and associated surgical and radiotherapies. Pituitary adenoma triggers the development of AIS through different mechanisms, particularly aneurysmal formation, associated thrombosis, and alteration of cerebral microcirculation. Cardiovascular complications and mortality were higher in patients with pituitary adenoma. The systemic effect of acromegaly-induced cardio-metabolic disorders may increase the risk for the development of AIS. Additionally, acromegaly contributes to the development of endothelial dysfunction (ED), inflammatory and oxidative stress, and induction of thrombosis that increases the risk for the development of AIS. Moreover, activated signaling pathways, including activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB), nod-like receptor pyrin 3 (NLRP3) inflammasome, and mitogen-activated protein kinase (MAPK) in acromegaly may induce systemic inflammation with the development of cardiovascular complications mainly AIS. Taken together, acromegaly triggers the development of AIS through local and systemic effects by inducing the formation of a cerebral vessel aneurysm, the release of pro-inflammatory cytokines, the development of oxidative stress, ED, and thrombosis correspondingly.

GH-secreting pituitary adenoma in the course of McCune‑Albright syndrome in a 21-year-old patient complicated by hepatocellular carcinoma.

Not required for Clinical Vignette.

Clinical features and therapeutic outcomes of GH/TSH cosecreting pituitary adenomas: experience of a single pituitary center.

Growth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported. This study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center. We retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital's information system. Based on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P <0.001). In addition, higher occurrence rates of arrhythmia (28.6% vs. 2.4%, P = 0.004), heart enlargement (33.3% vs. 4.8%, P = 0.005) and osteopenia/osteoporosis (33.3% vs. 2.4%, P = 0.001) were observed in the mixed PA group. There are great challenges in the treatment and management of GH/TSH cosecreting PA. Early diagnosis, multidisciplinary therapy and careful follow-up are required to improve the prognosis of this bihormonal PA.

The Methylation Analysis of the Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR) Locus in GH-Secreting Pituitary Adenomas.

The glucose-dependent insulinotropic polypeptide receptor (GIPR) is aberrantly expressed in about one-third of GH-secreting pituitary adenomas (GH-PAs) and has been associated with a paradoxical increase of GH after a glucose load. The reason for such an overexpression has not yet been clarified. In this work, we aimed to evaluate whether locus-specific changes in DNA methylation patterns could contribute to this phenomenon. By cloning bisulfite-sequencing PCR, we compared the methylation pattern of the GIPR locus in GIPR-positive (GIPR+) and GIPR-negative (GIPR-) GH-PAs. Then, to assess the correlation between Gipr expression and locus methylation, we induced global DNA methylation changes by treating the lactosomatotroph GH3 cells with 5-aza-2'-deoxycytidine. Differences in methylation levels were observed between GIPR+ and GIPR- GH-PAs, both within the promoter (31.9% vs. 68.2%, p < 0.05) and at two gene body regions (GB_1 20.7% vs. 9.1%; GB_2 51.2% vs. 65.8%, p < 0.05). GH3 cells treated with 5-aza-2'-deoxycytidine showed a ~75% reduction in Gipr steady-state level, possibly associated with the observed decrease in CpGs methylation. These results indicate that epigenetic regulation affects GIPR expression in GH-PAs, even though this possibly represents only a part of a much more complex regulatory mechanism.

Acromegaly in the differential diagnosis of hearing loss

Acromegaly is a multifactorial neuroendocrine disease caused by hyperproduction of growth hormone (GH). In more than 95% of cases the reason of acromegaly the GH-secreting pituitary adenoma. In patients with this neuroendocrine disease, a slowly developing complex of symptom can manifest with concomitant pathological conditions, including auditory function disordersDiagnostic difficulties of acromegaly at the ambulatory stage determine the importance of doctor`s awareness in different medical specialties.Here we demonstrate a clinical case of the improvement of the auditory function due to combined surgical and medical treatment of a patient with the pituitary macroadenoma, acromegaly and hearing loss.Anamnesis features: a patient with an active stage of acromegaly and a pituitary macroadenoma measuring 57x35x32 mm with ante-, supra-, infra-, parasellar spread, (Knosp III(D), Knosp IV(S) noted a violation of auditory function. She was consulted by an otolaryngologist, sensorineural hearing loss on the right of the 3rd degree was diagnosed, on the left of the 1st degree. The patient underwent surgical treatment of pituitary adenoma, noted a significant improvement in auditory function in the early postoperative period. Six months later, repeated audiometry was performed, marked regression of hearing damage was noted.The case described by us indicates the reversibility of a rare complication of acromegaly - hearing loss and the importance of an interdisciplinary approach in the management of patients with this pathology.

Abstract #1398813: A Rare Case of Acromegaly with Negative Immunohistochemical Staining for Growth Hormone

We are presenting a case of mixed prolactin and growth hormone (GH)-pituitary tumor with negative immunostaining for GH. 81-year-old male with history of type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and colon polyps was found to have a pituitary macroadenoma during evaluation of his visual disturbances. Years before the presentation, he noticed his shoe size had increased and his wife observed his jaw becoming more prominent. Physical exam was notable for enlarged nose, mandibular prognathism, and enlarged hands. Pre-operative laboratory results were remarkable for significantly elevated levels of insulin-like growth factor-1 (IGF-1), GH, and prolactin. He underwent transsphenoidal resection (TSPR) of the mass and pathology demonstrated a lactotroph adenoma, negative for GH immunostaining. After surgery he was started on cabergoline 0.5mg PO twice weekly. Three months afterwards his IGF-1 level remained elevated at 415 ng/mL. Acromegaly was confirmed by an elevated GH level of 13.8 ng/mL 2-hours after oral glucose challenge, then a long-acting somatostatin analogue depot was initiated for treatment. In the first year of therapy, he had weight loss and hypoglycemia that required discontinuation of insulin therapy. His IGF-1 and GH levels decreased to within age-appropriate ranges. His prolactin level returned to normal and cabergoline was stopped after a successful discontinuation trial. Clinical suspicion for acromegaly is confirmed by elevated IGF-1 and GH levels. When a GH-secreting pituitary adenoma is resected, immunocytochemistry with GH staining typically supports the diagnosis. It is not common for these tumors to stain negative for GH in the presence of clinical and biochemical acromegaly. The opposite—termed silent somatotroph— is more common and may represent an early stage in the development of a somatotroph adenoma. Failure to provide adequate diagnostic tissue, histopathology misread, or loss of antigenicity during fixation or embedding may be reasons for false negatives. However, it has been suggested that sparse cytoplasmic stores of GH do not parallel the hypersecretion of GH and may reduce staining capacity. Thus, a diagnosis of acromegaly should be made in patients with clinical and biochemical findings, even in the absence of GH immunostaining.

Predictors of Remission of Acromegaly following Surgical Treatment in Growth Hormone-Secreting Pituitary Adenoma.

Background and Objective Surgery is the treatment of choice for growth hormone (GH)-secreting pituitary adenoma. The remission of random GH depends on various factors. We aimed to evaluate the predictors related to remission of random GH following surgical treatment. Methods We collected the data retrospectively from the chart review from a single unit of neurosurgery. The diagnostic criteria for remission were a random GH < 1 ng/mL or nadir GH < 0.4 ng/mL after an oral glucose tolerance test. Results Data from a total of 110 (females 62 [56.4%]) patients were available for follow-up and were analyzed. The mean age was 36.5 years (14-69 years). Vision impairments were seen in 39 (35.5%) patients. The mean duration of symptoms before surgery was 34 months. The mean volume of the tumor was 7.2 mL (0.44-109.8 mL). Knosp grade 3 and 4 tumors were seen in 41.5% of cases. The mean preoperative random GH level was 68.9 ng/mL. Transsphenoidal surgery was done in 107 (97.3%) cases. The gross total resection could be done in 36 (32.7%) cases. At 3 months, 25 (26%) patients had a biochemical remission. In univariable analysis, lower Knosp grade, preoperative GH level < 40 ng/mL, gross total resection, and male gender were associated with remission at 3 months. In regression analysis, preoperative GH and male gender were related to remission at 3 months. Conclusion The preoperative GH level < 40 ng/mL is associated with higher chances of remission after surgery for GH-secreting pituitary adenoma.

The Role of Soluble α-klotho Protein in Acromegaly

Soluble α-klotho (sαKl) is an isoform of the α-klotho protein that regulates calcium metabolism but also has anti-aging, anti-apoptotic, and tumor suppressor effects. The assumption that sαKl could inhibit the insulin-like growth factor 1 (IGF-1) signaling pathway has increased the interest of its research in acromegaly - a pathology characterized by an excess of growth hormone (GH) and IGF-1. This review aimed to identify the role of sαKl in acromegaly. Most studies have identified higher concentrations of sαKl in acromegaly versus non-GH pituitary adenomas (PAs) or healthy subjects. Also, the sαKl level was higher in active acromegaly versus controlled or cured disease. Moreover, sαKl positively correlated with GH, IGF-1, and GH-secreting PA size. The increased level of sαKl seems to be due to the autonomous secretion of GH, considering their drastic decrease after transsphenoidal surgery. The data regarding the relationship between sαKl, age, and gender in acromegaly are inconsistent. The latest research noted a correlation between sαKl and various parameters for monitoring the quality of life in acromegaly. In conclusion, sαKl could reflect the disease activity. Furthermore, sαKl would represent an alternative for monitoring acromegalic patients with discrepancies between IGF-1 and GH.

Cognitive Dysfunction, an Increasingly Valued Long-Term Impairment in Acromegaly.

Acromegaly is a chronic disease caused by the overproduction of growth hormone (GH) and accompanying insulin-like growth factor-1 (IGF-1), which is often caused by GH-secreting pituitary adenomas. In addition to its somatic burden, a growing number of studies have found that patients suffering from acromegaly exhibit psychosocial and personality changes. Over the past 70 years, there has been increasing interest in the cognitive impairment and neuropsychological issues of patients with acromegaly, and a variety of neuropsychological and neurophysiological tests have been used to measure cognitive changes in patients. The impact of disease progression status, treatment modalities, and various comorbidities on cognitive function and the mechanisms of cognitive impairment in patients with acromegaly are therefore outlined in this review. Multidisciplinary assessment has important implications for the management of acromegaly, particularly in relation to cognitive function. Here, we summarize the relevant literature concerning cognitive-behavioral research on acromegaly to demonstrate the impact of long-term impairment caused by GH and IGF-1 on the cognitive behavior of patients.

Pure Endoscopic Endonasal Treatment of Acromegaly; Classification, Remission Rates, Factors Affecting Remission, and Complications

Aim This study aims to evaluate the effectiveness of the pure endoscopic endonasal transsphenoidal (PEET) approach in treating acromegaly, focusing on remission criteria set by the 2002 and 2010 consensus guidelines. It also seeks to identify variables that affect remission and to analyze early postoperative IGF-1 levels 24 hours after surgery to determine their predictive value for remission. Material and Methods The study retrospectively reviewed the medical records of 129 acromegaly patients who underwent the PEET (Pure Endoscopic Endonasal Transsphenoidal) surgical approach between November 2010 and March 2016 at Ankara Numune Training and Research Hospital. Out of these, 124 patients with complete follow-up and laboratory data were included in the analysis. The study evaluated a range of variables including patients' symptoms, pre- and postoperative GH and IGF-1 levels, imaging results, and remission statuses based on the 2002 and 2010 consensus guidelines. Inclusion criteria for the study required patients to have specific preoperative and postoperative data and a minimum follow-up duration of at least 6 months. Results The study found statistically significant differences between the remission rates based on the 2002 and 2010 consensus criteria for acromegaly, with a 73.4% remission rate under the 2002 criteria and a 65.3% remission rate under the 2010 criteria (p=0.002). Multivariate logistic regression analysis indicated that the atypical nature of the adenoma (p=0.018) and surgical intervention due to recurrence (p=0.028) were significant negative factors affecting cure rates. The study also identified that advanced stages in Hardy Wilson (p=0.008) and Knosp (p&lt;0.001) classifications had a statistically significant negative impact on achieving a cure. No statistically significant predictive value was found for early postoperative IGF-1 levels in relation to cure (p=0.612). Conclusion: PEET is currently the preferred treatment option for GH-secreting pituitary adenomas and has high remission rates.

Presence of cerebral microbleeds is associated with cognitive decline in acromegaly.

Cognitive decline in acromegaly has gained increasing attention. Cerebral microbleeds (CMBs) as radiographic markers for microvascular injury have been linked to various types of cognitive decline. However, the association between CMB formation and acromegaly has not yet been quantified. This study is designed to investigate the prevalence and the radiographic patterns of CMBs and the association between cognitive function and acromegaly-related CMBs in growth hormone (GH)-secreting pituitary adenoma, which is characterized by acromegaly. In a cohort of 55 patients with GH-secreting pituitary adenoma (acromegaly) and 70 healthy control (HC) patients, we determined the presence of CMBs using a 3.0-T MRI scanner. The numbers, locations, and grades of CMBs were determined via susceptibility-weighted imaging (SWI) and the Microbleed Anatomical Rating Scale. Obstructive sleep apnea (OSA) was assessed using the criteria of the American Academy of Sleep Medicine (AASM) Scoring Manual Version 2.2. The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance within 3days of admission. The association between CMBs and cognitive function as well as clinical characteristics was explored. The incidence of CMBs was 29.1%, whereas that of OSA was 65.5% in acromegaly. There was a statistically significant difference in the prevalence of CMBs between subjects with and without acromegaly (29.1% and 5.3%, respectively) (p<0.01). The age of acromegaly patients with CMBs was much younger compared with HCs with CMBs. Compared with HCs, a significant cognitive decline and the occurrence of OSA were demonstrated in patients with acromegaly (p<0.01). Binary logistic regression analysis adjusted for age, education, and body mass index (BMI) revealed that CMB was an independent risk factor for cognitive impairment in patients with acromegaly (OR=3.19, 95% CI 1.51-6.76, p=0.002). Furthermore, in the logistic regression models adjusted for age, BMI, diabetes, and hypertension, OSA was independently associated with the occurrence of CMBs in patients with acromegaly (OR=13.34, 95% CI 3.09-57.51, p=0.001). A significant increase of CMBs was demonstrated in patients with acromegaly, which may be a result of OSA in acromegaly. The present study indicated that increasing CMBs are responsible for cognitive decline in patients with acromegaly.

Giant growth hormone-secreting pituitary adenomas from the endocrinologist's perspective.

Since giant (≥40 mm) GH-secreting pituitary adenomas are rarely encountered, data on their characteristics and treatment outcomes are limited. We aimed to investigate the characteristics of giant GH-secreting pituitary adenomas and to compare their clinical, biochemical, imaging and histopathological features with non-giant macroadenomas. We have evaluated 15 (six female/nine male) and 57 (29 female/28 male) patients with acromegaly in giant and <40 mm adenoma groups, respectively. Patients with <40 mm adenoma were further divided into subgroups with adenoma size 20-29 mm and 30-39 mm. In giant adenoma group, median (IQR) preoperative maximal diameter of adenoma was 40 mm (5 mm), median preoperative GH level was 40 (153.4) ng/mL and median baseline IGF-1 level was 2.19 (1.88) × ULN for age and sex. The number of surgeries was significantly higher in giant adenoma group (median 2, IQR 2) in which 66.7% of patients underwent repeated surgeries (p = 0.014). Residual tumor was detected after last operation in all patients with giant adenoma. Total number of treatment modalities administered postoperatively increased as adenoma size increased (p = 0.043). After a median follow-up duration of 10 years (IQR 10), hormonal remission was achieved in six patients (40%) of giant adenoma group, while the rate of hormonal remission in non-giant adenoma group was 37%. Although preoperative GH and IGF-1 levels and Ki-67 index tended to be higher with increasing adenoma size, there was no statistically significant difference between groups in terms of these variables, as well as age, sex and invasion status. Hormonal remission rates of acromegaly patients with ≥20 mm pituitary macroadenoma were comparable. However, giant GH-secreting pituitary adenomas require an aggressive multimodal treatment approach.

Frequency of CSF Rhinorrhoea in Patients Undergoing Endoscopic Transsphenoidal Surgery (ETSS) for Pituitary Macroadenoma

Introduction: Pituitary adenoma resection via the transsphenoidal approach (TSS)is a safe and common neurosurgical procedure that can be done both through microscopic and endoscopic methods. Objectives: The main objective of the study is to find the frequency of CSF rhinorrhoea in patients undergoing endoscopic transsphenoidal surgery (ETSS) for pituitary macroadenoma. Material and methods: The study data was collected from 1st Oct to 1st Nov 2022, in the departments of Neurosurgery of Hayatabad Medical complex, Khyber Teaching Hospital, Lady Reading Hospital, Peshawar. The data was collected through non-probability consecutive sampling technique. There were 315 patients which were included in the study. The surgical procedure is done under general anesthesia. All patient data was collected and a standardized form was filled by the attending surgeon caring for the patient. Importantly, the primary end points to be recorded were: (1) techniques of intraoperative cranium base reconstruction used, and (2) postoperative CSF rhinorrhoea biochemically confirmed and/or requiring intervention (CSF diversion and/or operative restoration). Results: Of the 315 consecutive patients diagnosed with pituitary adenomas, a total of 250 patients met the inclusion criteria and were included. The pathology included 187 (74.8%) non-functioning adenomas, 40 (16.0%) GH-secreting pituitary adenomas, 3 (1.2%) PRL-secreting pituitary adenomas, and 20 (8.0%) ACTH-secreting pituitary adenomas. There were 30 (12.0%) cases of microadenomas, 205 (82.0%) cases of macroadenomas, and 15 (6.0%) cases of giant adenomas. Intraoperative CSF leakages were determined throughout surgical procedure in eighty patients (32.0%). Postoperative CSF leaks occurred in 9 patients (3.6%), including seven patients with intraoperative CSF leaks. Practical implication: Practical implications of this study is: (1) easily find the CSF leakage (2) frequency of CSF rhinorrhoea in patients undergoing endoscopic transsphenoidal surgery Conclusion: It is concluded that macroadenoma ETSS surgery should be strictly monitored for post-operative CSF leakage and lumber drain is an effective prophylactic strategy. Keywords: Postoperative CSF Leakage, Pituitary Adenomas, ETSS, Surgery, Lumber

Development and testing of diagnostic algorithms to identify patients with acromegaly in Southern Italian claims databases

Acromegaly is a rare disease characterized by an excessive production of growth-hormone and insulin-like growth factor 1, typically resulting from a GH-secreting pituitary adenoma. This study was aimed at comparing and measuring accuracy of newly and previously developed coding algorithms for the identification of acromegaly using Italian claims databases. This study was conducted between January 2015 and December 2018, using data from the claims databases of Caserta Local Health Unit (LHU) and Sicily Region in Southern Italy. To detect acromegaly cases from the general target population, four algorithms were developed using combinations of diagnostic, surgical procedure and co-payment exemption codes, pharmacy claims and specialist’s visits. Algorithm accuracy was assessed by measuring the Youden Index, sensitivity, specificity, positive and negative predictive values. The percentage of positive cases for each algorithm ranged from 7.9 (95% CI 6.4–9.8) to 13.8 (95% CI 11.7–16.2) per 100,000 inhabitants in Caserta LHU and from 7.8 (95% CI 7.1–8.6) to 16.4 (95% CI 15.3–17.5) in Sicily Region. Sensitivity of the different algorithms ranged from 71.1% (95% CI 54.1–84.6%) to 84.2% (95% CI 68.8–94.0%), while specificity was always higher than 99.9%. The algorithm based on the presence of claims suggestive of acromegaly in ≥ 2 different databases (i.e., hospital discharge records, copayment exemptions registry, pharmacy claims and specialist visits registry) achieved the highest Youden Index (84.2) and the highest positive predictive value (34.8; 95% CI 28.6–41.6). We tested four algorithms to identify acromegaly cases using claims databases with high sensitivity and Youden Index. Despite identifying rare diseases using real-world data is challenging, this study showed that robust validity testing may yield the identification of accurate coding algorithms.