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Objective This study aimed to assess the long-term outcome of patients with acromegaly. Design This is a multicenter, retrospective, observational study which extends the mean observation period of a previously reported cohort of Italian patients with acromegaly to 15 years of follow-up. Methods Only patients from the centers that provided information on the life status of at least 95% of their original cohorts were included. Life status information was collected either from clinical records or from the municipal registry offices. Standardized mortality ratios (SMRs) were computed comparing data with those of the general Italian population. Results A total of 811 patients were included. There were 153 deaths, with 90 expected and an SMR of 1.7 (95% CI 1.4–2.0, p  < 0.001). Death occurred after a median of 15 (women) or 16 (men) years from the diagnosis, without gender differences. Mortality remained elevated in the patients with control of disease (SMR 1.3, 95% CI 1.1–1.6). In the multivariable analysis, only older age and high IGF1 concentrations at last available follow-up visit were predictors of mortality. The oncological causes of death outweighed the cardiovascular ones, bordering on statistical significance with respect to the general population. Conclusions Mortality remains significantly high in patients with acromegaly, irrespectively of disease status, as long as the follow-up is sufficiently long with a low rate of patients lost to follow-up. Therapy strategy including radiotherapy does not have an impact on mortality. Oncological causes of death currently outweigh the cardiovascular causes.

Purpose Clinical control of corticotroph tumors is difficult to achieve since they usually persist or relapse after surgery. Pasireotide is approved to treat patients with Cushing’s disease for whom surgical therapy is not an option. However, Pasireotide seems to be effective only in a sub-set of patients, highlighting the importance to find a response marker to this approach. Recent studies demonstrated that the delta isoform of protein kinase C (PRKCD) controls viability and cell cycle progression of an in vitro model of ACTH-secreting pituitary tumor, the AtT-20/D16v-F2 cells. This study aims at exploring the possible PRKCD role in mediating Pasireotide effects. Methods It was assessed cell viability, POMC expression and ACTH secretion in AtT20/D16v-F2 cells over- or under-expressing PRKCD. Results We found that Pasireotide significantly reduces AtT20/D16v-F2 cell viability, POMC expression and ACTH secretion. In addition, Pasireotide reduces miR-26a expression. PRKCD silencing decreases AtT20/D16v-F2 cell sensitivity to Pasireotide treatment; on the contrary, PRKCD overexpression increases the inhibitory effects of Pasireotide on cell viability and ACTH secretion. Conclusion Our results provide new insights into potential PRKCD contribution in Pasireotide mechanism of action and suggest that PRKCD might be a possible marker of therapeutic response in ACTH-secreting pituitary tumors.

Social determinants of health have been related with kidney diseases and their outcomes. Financial toxicity (FT) refers to the negative impact of health care costs on clinical conditions. This scoping review aimed to evaluate the literature linking FT with renal diseases. We Included all studies analyzing FT and renal disease recorded in PubMed, Embase and Google Scholar between 2013 and 2023. The research question was formulated with reference to the acronym PCC (Problem, Concept and Contest). For each included study, we considered the study design, the population and main results from different populations with distinct renal conditions and the results were summarized in four tables. Socioeconomic deprivation was the main cause of FT, and the majority of studies on the relationship between FT and chronic kidney disease (CKD) were conducted in the USA (4 studies evaluated the pediatric population and 6 studies included adults). Three studies reported the impact of FT on nephrolithiasis, and 3 studies analyzed the link between FT and renal tumors. The methods used for detecting FT differed and were based on consultations, questionnaires, expenditures and database records analysis. The COmprehensive Score for financial Toxicity (COST) questionnaire was used in 7 studies (43%), and the prevalence of FT was reported to be high in children and adults. Although the quality of the selected study is limited, due to different populations investigated and heterogeneity in detecting FT, the latter seems to be a frequent finding in people with renal disease. Health care professionals should recognize socioeconomic deprivation as the major cause of FT. Detecting FT could help in prioritizing patient-centered care in populations with renal diseases through the development of strategies aimed at improving care for people with kidney diseases.

The use of recombinant human thyroid-stimulating hormone (rhTSH) has recently become available as an alternative diagnostic tool to assess the persistence and recurrence of differentiated thyroid carcinoma (DTC) in patients on thyroid hormone-suppressive therapy (THST) after near-total or total thyroidectomy and ablative doses of (131)I. We report the results of rhTSH administration in patients who were monitored for DTC. Thirty-three adult DTC patients (13 men, 20 women; mean age +/- SE, 45.6 +/- 2.31 y; age range, 21-65 y) underwent diagnostic follow-up after rhTSH administration at a dose of 0.9 mg once a day for 2 d. Whole-body scanning and serum thyroglobulin (Tg) measurement were performed after rhTSH administration. Patients were divided into 2 groups depending on serum Tg concentrations on THST: 29 patients had Tg concentrations of <2 ng/mL (group A) and 4 patients had Tg values of >2 ng/mL (group B). In group A, Tg values remained at <2 ng/mL in 25 patients and increased from 1.1 +/- 0.14 ng/mL to 22.0 +/- 5.75 ng/mL (mean +/- SE) in 4 patients after rhTSH administration. Whole-body scanning did not reveal any uptake of (131)I in the 25 patients without an increase in Tg, whereas (131)I uptake was evident in 2 of the 4 patients with a rise in Tg. In group B, Tg values increased in all 4 patients from 17.3 +/- 6.35 ng/mL to 55.3 +/- 12.75 ng/mL, and (131)I uptake was evident in 3 of the 4 patients. No major adverse effects were reported after rhTSH administration. Our results show that the measurement of serum Tg concentrations after rhTSH has a higher diagnostic value than whole-body scanning in detecting the persistence of thyroid tissue. Therefore, rhTSH should be administered in TSH-suppressed patients with basal serum Tg concentrations of <2 ng/mL because the increment in serum Tg concentrations may reveal the persistence of thyroid tissue in these patients.

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency(GHD) in 50 patients (mean age 37.6 ± 2.4 years; 40 males, age 20–60 years; 10 females, age 23–87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor–I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly(p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 ± 0.5 vs. 10.2 ± 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.

Testosterone (T) is known to affect the growth hormone (GH) axis. However, the mechanisms underlying the activation of GH secretion by T still remain to be clarified. Available data in animals and humans have shown that withdrawal of somatostatin (SRIH) infusion induces a GH-releasing hormone (GHRH)-mediated rebound release of GH, and there is accumulating evidence that SRIH infusion withdrawal may be a useful test to probe the GHRH function in vivo. With the aim of investigating whether the stimulatory effect of androgens on GH release in man could be accounted for by activation of the hypothalamic GHRH tone, we evaluated the plasma GH response to SRIH withdrawal in 10 patients aged 29.6 ± 2.4 years (mean ± SEM), diagnosed with hypergonadotropic hypogonadism, before and after a 6-month replacement therapy with T enanthate (250 mg every 3 weeks, i.m.), and in 10 healthy men, aged 26.7 ± 2.8 years. To verify whether the modulation of GH secretion by T could also be mediated through changes in SRIH tone and/or pituitary releasable pool, we examined GH secretory responses to combined GHRH and L-arginine (ARG) in the same individuals. Basal plasma concentrations of GH (0.48 ± 0.11 µg/l) and IGF-I (23.79 ± 1.83 nmol/l) were significantly lower in untreated hypogonadal patients than in healthy men, and significantly increased after T replacement therapy (GH 1.13 ± 0.28 µg/l; IGF-I 28.71 ± 1.46 nmol/l). The mean ΔGH peak after SRIH withdrawal recorded in untreated hypogonadal men (2.65 ± 0.86 µg/l) was significantly (p < 0.05) lower than that observed in healthy men (6.53 ± 1.33 µg/l) and significantly increased after T replacement therapy (5.52 ± 1.25 µg/l). The GH responses to GHRH combined with ARG (a functional SRIH antagonist) were not significantly different between healthy men and untreated hypogonadal patients, and were not significantly affected by T treatment. Plasma T and estradiol (E 2 ) levels significantly correlated with ΔGH peak after SRIH withdrawal in healthy men and in T-treated hypogonadal patients, whereas in untreated patients they did not. No significant correlation was found between GH areas under the curve after GHRH + ARG test and T and E 2 plasma levels in either healthy men or in hypogonadal patients (both before and after T replacement). These findings are consistent with the view that in humans the stimulatory action of T on the GH axis appears to be mediated at the hypothalamic level primarily by promoting GHRH function.

The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems where it often coexists with catecholamines and acetylcholine. Recently we have reported that human GAL (hGAL) in man depresses the release of norepinephrine (NE) and the responses to both assumption of upright posture and insulin-induced hypoglycemia. To gain an insight into the action of hGAL on sympathetic nervous system activity in man, we investigated the effects of a 60-min infusion (80 pmol/kg/min) of hGAL or saline on the release of NE, epinephrine (E) and pancreatic polypeptide (PP) induced by an acetylcholinesterase inhibitor, pyridostigmine bromide (PD), in nine healthy volunteers. PD (120 mg orally) induced a significant rise in plasma concentrations of NE (1.6 +/- 0.04 vs. 1.08 +/- 0.06 nmol/l), E (0.34 +/ 0.05 vs. 0.12 +/- 0.04 nmol/l) and PP (178.06 +/- 33 vs. 37.57 +/- 7.35 pmol/l), whilst it significantly reduced heart rate (HR; 61 +/- 2 vs. 71 +/- 4 beats/min). Changes in plasma levels of PP were determined as an indirect measure of amplification of endogenous cholinergic activity produced by PD. Administration of hGAL blunted the release of NE and PP evoked by PD. The mean (+/- SEM) area under the curve produced by PD of NE (50.05 +/- 3.97 nmol/l.90 min) and PP (8,692.87 +/- 1,724 pmol/l.90 min) was significantly (p < 0.001) reduced by hGAL infusion (2.65 +/- 1.57 nmol/l.90 min and 248.1 +/- 148 pmol/l.90 min, for NE and PP, respectively). hGAL failed to affect significantly the E release evoked by PD. hGAL was able to enhance HR significantly (104 +/- 5 vs. 69 +/- 3 beats/min), and completely prevented the PD-induced slowing of HR. Both PD and hGAL did not alter supine systolic and diastolic blood pressure. We conclude that hGAL significantly reduces the release of NE and PP stimulated by PD-induced enhancement of cholinergic activity. These findings are consistent with a functional interrelationship between GAL and the cholinergic system in man, and may suggest the participation of a cholinergic pathway in the galaninergic modulation of the autonomic nervous system.

Hypertension is an important complication of acromegaly, contributing to the increased morbidity and mortality of this condition. Prevalence of hypertension in acromegalic patients is about 35%, ranging from 18 to 60% in different clinical series, and the incidence is higher than in the general population. The lowering of blood pressure observed concomitantly with the reduction in GH levels after successful therapy for acromegaly suggests a relationship between GH and/or IGF-I excess and hypertension. The exact mechanisms underlying the development of hypertension in acromegaly are still not clear but may include several factors depending on the chronic exposure to GH and/or IGF-I excess. Experimental and clinical studies suggest that the anti-natriuretic action of GH (due to direct renal action of GH or IGF-I and/or to indirect, systemic GH or IGF-I-mediated mechanisms) may play a role in the pathogenesis of hypertension. Acromegaly is frequently associated with insulin resistance and hyperinsulinaemia which may induce hypertension by stimulating renal sodium absorption and sympathetic nervous activity. Whether sympathetic tone is altered in acromegalic hypertensive patients remains a matter of debate. Recent studies indicate that an increased sympathetic tone and/or abnormalities in the circadian activity of sympathetic system could play an important role in development and/or maintenance of elevated blood pressure in acromegaly, and may partially account for the increased risk of cardiovascular complications. Acromegalic cardiomiopathy may also concur to elevate blood pressure and can be aggravated by the coexistence of hypertension. Finally, a role of GH and IGF-I as vascular growth factors cannot be excluded. In conclusion, acromegaly is associated with hypertension, but there is still no real consensus in the literature on the mechanisms behind the development of the high blood pressure.

The genetic relationships among 9 taxa of Anisakis Dujardin, 1845 (A. simplex (sensu stricto), A. pegreffii, A. simplex C., A. typica, A. ziphidarum, A. physeteris, A. brevispiculata, A. paggiae, and Anisakis sp.) were inferred from sequence analysis (629 bp) of the mitochondrial cox2 gene. Genetic divergence among the considered taxa, estimated by p-distance, ranged from p = 0.055, between sibling species of the A. simplex complex, to p = 0.12, between morphologically differentiated species, i.e., A. ziphidarum and A. typica. The highest level was detected when comparing A. physeteris, A. brevispiculata, and A. paggiae versus A. simplex complex (on average p = 0.13) or versus A. typica (on average p = 0.14). Sequence data from the newly identified Anisakis sp. poorly aligned with other Anisakis species but was most similar to A. ziphidarum (p = 0.08). Phylogenetic analyses based upon Parsimony and Bayesian Inference, as well as phenetic analysis based upon Neighbor-Joining p-distance values, generated similar tree topologies, each well supported at major nodes. All analyses delineated two main claides, the first encompassing A. physeteris, A. brevispiculata, and A. paggiae as a sister group to all the remaining species, and the second comprising the species of the A. simplex complex (A. simplex (s.s.), A. pegreffii and A. simplex C), A. typica, A. ziphidarum, and Anisakis sp. In general, mtDNA-based tree topologies showed high congruence with those generated from nuclear data sets (19 enzyme-loci) and with morphological data delineating adult and larval stages of the Anisakis spp.; however, precise positioning of A. typica and A. ziphidarum remain poorly resolved, though they consistently clustered in the same clade as Anisakis sp. and the A. simplex complex. Comparison of anisakid data with those currently available for their cetacean-definitive hosts suggests parallelism between host and parasite phylogenetic tree topologies.