Recurrence in acromegaly: two tertiary centers experience and review of the literature.

BACKGROUND: Recurrence of acromegaly after successful surgery is a rare event, but no clear data are reported in the literature about its recurrence rates. This study aimed to evaluate the recurrence rate in a series of acromegalic patients treated by transsphenoidal surgery (TSS) with a long follow-up. METHODS: We retrospectively analyzed data from 283 acromegalic patients who underwent TSS at two pituitary units in Milan (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and IRCCS Humanitas Research Hospital). The diagnosis and recurrence of acromegaly were defined by both elevated IGF-1 levels and a lack of GH suppression based on appropriate criteria for the assay used at the time of diagnosis. RESULTS: After surgery, 143 patients (50%) were defined as not cured, 132 (47%) as cured and 8 (3%) as partially cured because of normalization of only one parameter, either IGF1 or GH. In the cured group, at the last follow-up (median time 86.8 months after surgery), only 1 patient (0.7%) showed full recurrence (IGF-1 + 5.61 SDS, GH nadir 1.27 µg/l), while 4 patients (3%) showed only increased IGF1. In the partially cured group at the last follow-up, 2/8 (25%) patients showed active acromegaly (IGF-1 SDS + 2.75 and + 3.62; GH nadir 0.6 and 0.5 µg/l, respectively). CONCLUSIONS: In the literature, recurrence rates range widely, from 0 to 18%. In our series, recurrence occurred in 3.7% of patients, and in fewer than 1%, recurrence occurred with elevation of both IGF-1 and the GH nadir. More frequently (25%), recurrence came in the form of incomplete normalization of either IGF-1 or GH after surgery.

GH/IGF-1 axis in a large cohort of ß-thalassemia major adult patients: a cross-sectional study.

PURPOSE: GH deficit (GHD) could represent an endocrine issue in ß-Thalassemia Major (ßTM) patients. GH/IGF-1 axis has not been extensively explored in ßTM adults, so far. We aim to assess GHD and IGF-1 deficiency prevalence in ßTM adult population, focusing on the relationship with liver disease. METHODS: Cross-sectional multi-centre study conducted on 81 adult ßTM patients (44 males, mean age 41 ± 8 years) on transfusion and chelation therapy. GHD was investigated by GHRH + arginine test. IGF-1 levels, routine biochemical exams, Fibroscan, Hepatic Magnetic Resonance Imaging (MRI) and pituitary MRI were collected. RESULTS: Eighteen patients were affected by GHD and 63 were not (nGHD) according to GHRH + arginine test, while basal GH levels did not differ. GHD was associated with a higher BMI and a worse lipid profile (p < 0.05). No significant differences were observed regarding liver function between the two groups. Pituitary MRI scan was normal except for one case of empty sella. The 94.4% and 93.6% of GHD and nGHD, respectively, presented lower IGF-1 levels than the reference range, and mean IGF-1 SDS was significantly lower in GHD patients. CONCLUSION: GHD is frequent in adult ßTM patients and is associated with higher BMI and worse lipid profile. nGHD patients present lower IGF-1 levels as well. There was no relationship between IGF-1 levels and liver disease. Further, multicentric studies with larger cohorts and standardized diagnostic protocols are needed.

Long-term remission of acromegaly after somatostatin analogues withdrawal: a single-centre experience.

PURPOSE: A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. METHODS: We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008-2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. RESULTS: In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24-84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3-12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66-150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. CONCLUSION: A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.

First Report of Plum pox virus on Plum in New York State.

Plum pox, also known as Sharka, is one of the more significant viral diseases of stone fruit trees such as plum, peach, and apricot. It was first reported in Europe in the early 1900s and more recently in Chile in 1992, the United States (Pennsylvania) in 1999, Canada (Ontario and Nova Scotia) in 2000, China in 2001, and Argentina in 2004. Plum pox virus (PPV) was recently detected in two plum (Prunus domestica) trees in an orchard in Niagara County, NY, located within 5 miles from a Canadian plum pox eradication zone. Typical symptoms of chlorotic rings and spots were observed on some of the leaves from these trees. No symptoms were reported prior to the survey collection in July 2006. Survey samples were screened for the presence of PPV by ELISA using the Agdia PPV (Agdia, Elkhart, IN) specific kit that recognizes all strains but C of PPV. Approximately 5% of the survey samples were additionally analyzed by a validated immunocapture reverse transcription (IC-RT)-PCR TaqMan assay in a Cepheid SmartCycler (Cepheid, Sunnyvale, CA). Both replicates of the two New York plum trees produced a positive ELISA reaction in two consecutive tests. The ELISA-positive samples also produced positive results when subjected to the real-time IC-RT-PCR test. The PPV-positive trees were sampled again and an additional 53 samples were collected from trees in the surrounding area. Suspect trees again tested positive, while all the trees in the surrounding area tested negative. The methods used for confirmation included two ELISA tests (Durviz [Valencia, Spain] DAS indirect monoclonal ELISA and Agdia DAS polyclonal ELISA). Confirmatory real-time IC-RT-PCR was performed using universal 3' nontranslated region (NTR) primers (2,3) in a SYBR Green assay format and a coat protein (CP) primers/probe TaqMan assay (3,4). Further, the New York PPV isolate was identified as PPV D group using a subgroup specific conventional IC-RT-PCR (1). A 1.4-kb sequence fragment from the 3' end of the New York PPV was sequenced (GenBank Accession No. DG 883816). Comparison of the sequence with the database confirmed this isolate as subgroup D and exhibited a high degree of identity with other PPV D accessions (PPV D Teycheney [Accession No. X16415]; Penn4 [Accession No. DQ465243] Cnd 123-1 [Accession No. AY9553267]; and Cnd 3 [Accession No. AY953262]). To our knowledge, this is the first report of PPV in New York. References: (1) T. Candresse et al. Phytopathology. 88:198, 1998. (2) L. Levy et al. J. Virol. Methods. 49:295, 1994. (3) V. Mavrodieva and L. Levy. Acta Hortic. 657:141, 2004. (4) T. Wetzel et al. J.Virol. Methods 33:355, 1991.