High mortality risk among women with acromegaly still persists.

Introduction: The mortality ratio in patients with acromegaly has improved over the last few decades. We aimed to determine the mortality rate and correlated factors in patients with acromegaly before and after the introduction of national protocols for treatment. In addition, we determined whether there are sex-related differences in mortality of patients with acromegaly. Methods: This observational retrospective study included 399 consecutive patients with acromegaly between January 2001-December 2022. Paraclinical data included random growth hormone (GH) and insulin-like growth factor-I (IGF1) levels, maximal pituitary tumor diameter at diagnosis, first visit, and last evaluation. Standardized mortality ratio (SMR) was calculated by dividing the observed and expected mortality rates. Cox regression analysis revealed the independent factors associated with mortality. Results: At the last visit, 31.07% (124) of patients were cured, 22.05% (88) had controlled acromegaly with medication, and 45.31% (181) had not controlled acromegaly. During follow-up (13.03 ± 5.65 years, 5216.62 person-years), 89 patients died (0.017%), resulting in an SMR of 1.18 [95% CI 0.95-1.45]. The independent factors associated with mortality were the last IGF1 level/last random GH level, absence of surgery, gonadotropin deficiency, and age. Patients with normal IGF1 after treatment showed an SMR of 0.71, whereas patients with IGF1 ratio > 1 showed SMR=1.51. Patients diagnosed between 1975-2007 and 2008-2022 had SMR = 1.25 [95% CI 0.97-1.58] and SMR = 1.09 [95% CI 0.68-1.65], respectively. In females with acromegaly, SMR was 1.63 [95% CI 1.24-2.11]; 1.76 [95% CI 1.30-2.34] in women diagnosed before 2008 and 1.33 [95% CI 0.69-2.33] in those diagnosed after 2008. Males with acromegaly had a mortality ratio similar to males from the general population (SMR = 0.99, [95% CI 0.66-1.41]). Conclusion: Patients diagnosed with acromegaly in the last 15 years had lower mortality rates than those diagnosed before 2008, due to the availability of new medications, primarily somatostatin receptor analogs and to a higher proportion of patients undergoing surgery. Females still have a high mortality ratio owing to older age at diagnosis and higher risk of metabolic complications. Therefore, efforts should be made for early diagnosis of acromegaly in women.

Acromegaly versus hypogonadism: Bone fragility and evaluation.

INTRODUCTION: Osteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender. METHODOLOGY: We performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine. RESULTS: Vertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS. CONCLUSIONS: Vertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly.

Clinicopathological Features of Growth Hormone-producing Pituitary Adenomas and Correlation With Preoperative Laboratory Findings.

BACKGROUND/AIM: The histopathological variability of each type of pituitary adenoma (PA) that causes growth hormone (GH) excess influences the phenotype, radiological characteristics and therapy response of acromegaly patients. We correlated the immunohistochemical (IHC) features of GH-secreting PAs with their clinical, laboratory and imaging data. PATIENTS AND METHODS: We included 32 patients with documented acromegaly; tumour specimens were histologically and IHC examined: anterior pituitary hormones, pituitary-specific transcription factor-1 (PIT-1), Ki-67 labelling index were evaluated. RESULTS: Macroadenomas represented 93.75%. Post-surgery disease control negatively correlated with the maximum initial tumour diameter (p=0.04). Ki-67 did not predict remission. No correlation was found between GH serum levels and IHC expression (p=0.45). PIT-1 was positive in all specimens, two had a weak expression. Four were considered PIT-1 positive plurihormonal adenomas and several had unusual IHC combinations. CONCLUSION: PIT-1 accurately classifies GH-secreting PAs. The IHC classification as well as radiological dimensions and extent influence disease control, probably being the best prognosis factors.

Improvement of acromegaly control with multimodal therapy in Romania.

INTRODUCTION: In Romania, there is no acromegaly national register and there are no nationwide data available. However, some studies have reported the control rates in the country's main referral centres. Our aim was to assess the overall control rate in our tertiary referral centre. Also, we assessed the control rate in the last three years, and we compared the results with our previous reports. MATERIAL AND METHODS: We reviewed the charts of 186 patients with acromegaly assessed in our department between January 1st, 2012 and May 31st, 2019. We also compared the control rates for patients treated between April 1st, 2016 and May 31st, 2019 with historical controls (assessed between January 1st, 2012 and March 31st, 2016). RESULTS: Primary analysis: There were 19 untreated and 167 treated patients, mean age 52.46 years, surgery being the most commonly used treatment. The surgical cure rate was 14.8%, and disease control with medical treatment was 35.3%. Secondary analysis: In the first group there were 45 patients, surgery also being the most commonly used treatment. The surgical cure rate was 26.9%, and disease control was 30.4%. In the second group (historical controls) there were 42 patients, surgery being the most commonly used treatment. The surgical cure rate was 9.7%, and disease control with medical treatment was 15.4%. Random GH and IGF-1 after surgery were lower in the first group (p < 0.05) CONCLUSIONS: Changes in the Romanian protocol and highly specialised pituitary centres has improved the cure rate and disease control in patients with acromegaly.

Acromegaly treatment in Romania. How close are we to disease control?

INTRODUCTION: In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly. MATERIALS AND METHODS: We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients. RESULTS: There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I. CONCLUSIONS: In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.

Conventional examination versus immunohistochemistry in the prediction of hormone profile of pituitary adenomas. An analysis on 142 cases.

The large majority of neoplasms located in the sella turcica are benign pituitary adenomas derived from cells of the adenohypophysis. Pituitary adenomas represent the third most common primary intracranial tumor in neurosurgical practice, outnumbered only by gliomas and meningiomas. Their biology of pituitary adenomas is complex and they can cause a variety of endocrine syndromes and disorders, based on hormone profile secreted by proliferating cells. The aim of this study was to evaluate the routine conventional methods and highly specific immunohistochemical methods in order to accurately predict the type of hormone secretion. Our study was investigated 142 cases admitted with pituitary adenomas and treated by open surgery. Sections from each case were stained with routine Hematoxylin and Eosin method for histopathologic evaluation. Immunohistochemistry was performed on additional slides in order to detect specific pituitary adenomas. Based on the immunohistochemical profile of pituitary adenomas we found following results: 37 growth hormone (GH)-secreting adenomas, 23 prolactin (PRL)-secreting adenomas, 15 mixed GH-cell/PRL-cell adenomas, three mammosomatotroph cell adenomas, two adrenocorticotrophic hormone (ACTH)-secreting adenomas, one thyrotrophic cell adenoma, 18 gonadotroph adenomas, 30 null cell adenomas and 13 plurihormonal adenomas. No correlation was found between conventional features and the immunohistochemical profile. The immunohistochemical profile of functional pituitary adenomas is mandatory for a correct diagnosis. We revealed that staining characteristics of the tumor cells, such as acidophilic, basophilic or chromophobe are nowadays outdated as main principle of classification, because they not identify specific adenoma types.