Patients with non-functioning pituitary adenoma (NFPA) often present with a variety of clinical manifestations and comorbidities, mainly determined by the local mass effect of the tumor and by ...hypopituitarism. Whether this has an impact on overall mortality, however, is still unclear.
PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until May 2023 for studies reporting data either about standardized mortality ratios (SMRs) or about predictors of mortality in patients with NFPA. Effect sizes were pooled through a random-effect model. This systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, #CRD42023417782).
Eleven studies were eligible for inclusion in the systematic review; among these, five studies reported data on SMRs, with a total follow-up time of approximately 130,000 person-years. Patients with NFPA showed an increased mortality risk compared to the general population (SMR = 1.57 95%CI: 1.20-1.99, p < 0.01). Age and sex appeared to act as effect modifiers, with a trend towards higher SMRs in females (SMR = 1.57 95%CI: 0.91-2.41, p = 0.10) than in males (SMR = 1.00 95%CI: 0.89-1.11, p = 0.97), and in patients diagnosed at age 40 years or younger (SMR = 3.19 95%CI: 2.50-3.97, p < 0.01) compared to those with later onset of the disease (SMR = 1.26 95%CI: 0.93-1.65, p = 0.13). The trend towards excess mortality was similar in patients with normal (SMR = 1.22 95%CI: 0.94-1.53, p = 0.13) or deficient (SMR = 1.26 95%CI: 0.82-1.79, p = 0.27) pituitary function.
Excess mortality is observed in patients with NFPA, regardless of pituitary function, especially in women and in patients with a younger age at diagnosis.
ObjectiveTo describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity ...and mortality in a nationwide survey of Italian acromegalic patients.DesignRetrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months.ResultsA total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 μg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87–1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34–2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality.ConclusionsPretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.
First-line medical therapy for acromegaly management includes first-generation somatostatin receptor ligands (fgSRLs), but resistance limits their use. Despite international guidelines, the choice of ...second-line therapy is debated.
We aim to discuss resistance to fgSRLs, identify second-line therapy determinants and assess glycemia's impact to provide valuable insights for acromegaly management in clinical practice. A group of Italian endocrinologists expert in the pituitary field participated in a two-round Delphi panel between July and September 2023. The Delphi questionnaire encompassed a total of 75 statements categorized into three sections: resistance to fgSRLs therapy and predictors of response; determinants for the selection of second-line therapy; the role of glycemia in the therapeutic management. The statements were rated on a 6-point Likert scale.
Fifty-nine (79%) statements reached a consensus. IGF-1 levels resulted central for evaluating resistance to fgSRLs, that should be defined considering also symptomatic clinical response, degree of tumor shrinkage and complications, using clinician- and patient-reported outcome tools available. Factors to be evaluated for the choice of second-line medical therapy are hyperglycemia-that should be managed as in non-acromegalic patients-tumor remnant, resistant headache and compliance. Costs do not represent a main determinant in the choice of second-line medical treatment.
The experts agreed on a holistic management approach to acromegaly. It is therefore necessary to choose currently available highly effective second-line medical treatment (pegvisomant and pasireotide) based on the characteristics of the patients.
Purpose
Patients with secondary adrenal insufficiency (SAI) have an increased morbidity and an impaired health-related quality of life (HRQoL), which seems to primarily depend on the sub-optimal ...replacement of hypoadrenalism with standard glucocorticoid (GC) therapy, and on the inadequate correction of other associated pituitary deficiencies. A dual-release hydrocortisone (DR-HC) formulation has shown to exert positive effects on morbidity and HRQoL, mainly in patients with primary adrenal insufficiency. We assessed the variations of anthropometric and metabolic parameters and HRQoL in patients with SAI after switching from cortisone acetate (CA) or hydrocortisone (HC) to DR-HC.
Methods
Twenty-one patients (17 M, 4 F) treated with CA (
n
= 16; 25 mg/day twice a day) or HC (
n
= 5; 20 mg/day three times a day), were evaluated for waist circumference, BMI, fasting glucose, HbA1c, insulin, HOMA-IR index, serum lipids, electrolytes, blood pressure and HRQoL at baseline, at 3, 6 and 12 months after switching from CA/HC to DR-HC.
Results
The study showed a significant reduction of waist circumference and BMI (
p
= 0.04, for both), after 3 and 6months of DR-HC treatment, respectively. No significant changes were observed for fasting glucose, insulin, HOMA-IR index, HbA1c, total cholesterol, triglycerides, LDL cholesterol, electrolytes, and blood pressure. However, HDL cholesterol significantly decreased (
p
= 0.003). An improvement of AddiQoL total score was observed during DR-HC treatment (
p
= 0.01), mainly for the category “emotions”. No predictors resulted for these changes.
Conclusion
DR-HC treatment provides some benefits in patients with SAI, reducing central adiposity and improving HRQoL; however, worsening of HDL cholesterol is observed during treatment with DR-HC.
Introduction
Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the ...neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions.
Materials and methods
A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease (QUIP).
Results
Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%,
p
< 0.01), any ICD (46% vs. 24%,
p
< 0.01), any related behavior (31% vs. 17%,
p
< 0.05), compulsive sexual behavior (27% vs. 14%,
p
< 0.04), and punding (20% vs. 7%,
p
< 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior odds ratio (OR) 2.43 and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82).
Discussion
Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.
Purpose
During the Covid-19 pandemic every hospital has had to change its internal organization. Different institutions have highlighted the risks connected with endoscopic endonasal surgery. The ...goal of this paper is to illustrate the feasibility of pituitary region surgery during the SARS-CoV-2 pandemic.
Methods
After two negative Covid tests were obtained, three patients with macro GH-secreting tumors, and two patients with micro ACTH-secreting tumors resistant to medical treatment underwent surgery during the pandemic. During the surgery, every patient was treated as if they were positive.
Results
Neither operator, nor patient have developed Covid symptoms. The two neurosurgeons performing the operations underwent two Covid swab, which resulted negative.
Conclusions
Pituitary surgery is a high risk non-urgent surgery. However, the method described has so far been effective and is safe for both patients and healthcare providers.
Cabergoline (CAB) has shown to have benefic effects on the metabolism in different clinical settings but its metabolic role in acromegaly disease has not been studied yet. Aim of our study was to ...evaluate the impact of CAB on glucose metabolism and weight in patients with acromegaly.
All patients with acromegaly undergoing continuous treatment with CAB for at least 6 months were retrospectively screened. Exclusion criteria were discontinuation of CAB for more than one month, change of antidiabetic or other therapy for acromegaly, concomitant untreated hormonal deficiency, initiation of pregnancy and/or breastfeeding. All patients were evaluated in terms of biochemical disease control, glucose metabolism and weight at baseline (T0) and after the introduction of CAB therapy at 6 (T6) and 12 months (T12).
Twenty-six patients (15 females and 11 males) were evaluated at T0 and T6 and 19 patients (12 females and 7 males) were also evaluated at T12. Insulin-like growth factor I (IGF-I) and prolactin (PRL) levels were significantly lower at T6 and T12 compared to baseline (p < 0.001 for IGF-I, p < 0.05 for PRL) even if no further differences were observed between T12 and T6. Considering the entire cohort, no differences were appreciated regarding the metabolic parameters but a significant reduction in weight and body mass index (BMI) was observed at both T6 (p = 0.009 for weight, p = 0.021 for BMI) and T12 (p = 0.014 for weight, p = 0.017 for BMI) compared to baseline.
Our results confirm the efficacy of CAB in providing a significant improvement in the biochemical disease control but do not demonstrate a marked benefit on glucose metabolism of acromegaly patients. In such patients, CAB appears to have a rapid effect on weight and BMI, with significant changes noticeable as early as 6 months and persisting for at least 12 months.
Purpose
This study aims to compare the accuracy of mean GH profile (GHP) < 2.5 ng/ml and single fasting GH (SGH) < 1 ng/ml in the evaluation of disease control in acromegaly patients during ...somatostatin receptor ligands (SRLs) therapy.
Methods
We retrospectively enrolled 100 acromegaly patients, 68 responder, and 32 partial responder to SRLs. Controlled disease has been defined as IGF-I levels within age-related normal limits, while partial response as pathological IGF-I values despite a reduction ≥ 50%. In all patients, GHP, SGH, IGF-I, and IGFBP-3 were evaluated.
Results
Median GHP levels (1.2 ng/ml, IQR 0.5–2.3 ng/ml) were lower (
p
= 0.001) than SGH (1.9 ng/ml, IQR 1.0–3.6 ng/ml). Accuracy of GHP was 81%, whereas that of SGH was 55%, with a Kappa index of 0.520 and 0.237, respectively. In multivariable analysis GHP (
p
= 0.002) and IGFBP-3 (
p
= 0.004), but not SGH, were independently associated with normal IGF-I levels. At receiver–operator characteristic curve (ROC) analysis GHP cut-off sensitivity and specificity were 94.1% and 50.0%, respectively, while SGH sensitivity and specificity were 35.3% and 93.7%, respectively. Finally, in obese patients the GH cut-off level (both as SGH and GHP) associated to good disease control was significantly different with respect to not obese ones.
Conclusions
GHP associates with IGF-I (and therefore with appropriate control of disease) with higher accuracy than SGH. When GH evaluation is needed, the measurement of mean GHP should be preferred and use of BMI-related cut-offs is suggested.
Background
In patients with suspected acromegaly, evaluation of IGF-I is recommended as first-line test, while the assessment of GH-nadir during oral glucose tolerance test (OGTT) is advised as ...confirmatory test. The procedure of this test generally involves GH measurement every 30 min (30’) from baseline to +120’ or +180’. However, the optimal timing of samplings for the distinction between patients with or without active acromegaly is still a matter of debate.
Methods
Sixty-seven healthy subjects and 46 acromegalic patients who achieved documented and persistent long-term cure were enrolled. A greedy algorithm was used to identify the minimal subset of time-points that sufficed to correctly detect GH suppression.
Results
The sampling at 90’ was the one in which a GH level < 1 μg/L was most frequently achieved (i.e., in 91.3% of cured acromegalic patients and in 91.0% of healthy subjects). Considering the whole cohort, the best combination of 2 time-points was +90’ and +150’ and achieved 95.6% accuracy; the best combination of 3 time-points was +60’, +90’ and +150’ and achieved 99.1% accuracy. The minimal subset of GH determinations that demonstrated perfect accuracy (100%) needed the inclusion of 4 time-points, namely +60’, +90’, +120’ and +150’.
Conclusion
A subset of 4 time-points (60’ – 90’ – 120’ – 150’) was identified as the most relevant to detect GH suppression at OGTT, with a perfect classification of 100% of subjects. This supports the possibility to restrict the blood samplings to these time-points when assessing disease cure, with possible advantages in terms of saving time and lowering costs.
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