Abstract
Background
Pseudohypoparathyroidism (PHP) and related disorders newly referred to as inactivating PTH/PTHrP signaling disorders (iPPSD) are rare endocrine diseases. Many clinical features ...including obesity, neurocognitive impairment, brachydactyly, short stature, parathyroid hormone (PTH) resistance, and resistance to other hormones such as thyroid-stimulating hormone (TSH) have been well described, yet they refer mainly to the full development of the disease during late childhood and adulthood.
Objective
A significant delay in diagnosis has been reported; therefore, our objective is to increase awareness on neonatal and early infancy presentation of the diseases. To do so, we analyzed a large cohort of iPPSD/PHP patients.
Methods
We included 136 patients diagnosed with iPPSD/PHP. We retrospectively collected data on birth and investigated the rate of neonatal complications occurring in each iPPSD/PHP category within the first month of life.
Results
Overall 36% of patients presented at least one neonatal complication, far more than the general population; when considering only the patients with iPPSD2/PHP1A, it reached 47% of the patients. Neonatal hypoglycemia and transient respiratory distress appeared significantly frequent in this latter group, ie, 10.5% and 18.4%, respectively. The presence of neonatal features was associated with earlier resistance to TSH (P < 0.001) and with the development of neurocognitive impairment (P = 0.02) or constipation (P = 0.04) later in life.
Conclusion
Our findings suggest that iPPSD/PHP and especially iPPSD2/PHP1A newborns require specific care at birth because of an increased risk of neonatal complications. These complications may predict a more severe course of the disease; however, they are unspecific which likely explains the diagnostic delay.
Abstract
Context
Coronavirus disease 2019 (COVID-19) represents a global health emergency, and infected patients with chronic diseases often present with a severe impairment. Adrenal insufficiency ...(AI) is supposed to be associated with an increased infection risk, which could trigger an adrenal crisis.
Objective
Our primary aim was to evaluate the incidence of COVID-19 symptoms and complications in AI patients.
Design and Setting
We conducted a retrospective case-control study. All patients were on active follow-up and lived in Lombardy, Italy, one of the most affected areas.
Patients
We enrolled 279 patients with primary and secondary AI and 112 controls (patients with benign pituitary lesions without hormonal alterations). All AI patients had been previously trained to modify their replacement therapy on stress doses.
Intervention
By administering a standardized questionnaire by phone, we collected data on COVID-19 suggestive symptoms and consequences.
Results
In February through April 2020, the prevalence of symptomatic patients (complaining at least 1 symptom of viral infection) was similar between the 2 groups (24% in AI and 22.3% in controls, P = 0.79). Highly suggestive COVID-19 symptoms (at least 2 including fever and/or cough) also occurred equally in AI and controls (12.5% in both groups). No patient required hospitalization and no adrenal crisis was reported. Few nasopharyngeal swabs were performed (n = 12), as indicated by sanitary regulations, limiting conclusions on the exact infection rate (2 positive results in AI and none in controls, P = 0.52).
Conclusions
AI patients who are adequately treated and trained seem to display the same incidence of COVID-19-suggestive symptoms and disease severity as controls.
Vertebral fractures (VFs) are a frequent complication of acromegaly, but no studies have been so far published on effectiveness of antiosteoporotic drugs in this clinical setting.
To evaluate whether ...in real-life clinical practice bone active drugs may reduce the risk of VFs in patients with active or controlled acromegaly.
Retrospective, longitudinal study including 9 tertiary care endocrine units.
Two hundred and forty-eight patients with acromegaly (104 males; mean age 56.00 ± 13.60 years) were evaluated for prevalent and incident VFs by quantitative morphometric approach. Bone active agents were used in 52 patients (20.97%) and the median period of follow-up was 48 months (range 12-132).
During the follow-up, 65 patients (26.21%) developed incident VFs in relationship with pre-existing VFs (odds ratio OR 3.75; P < .001), duration of active acromegaly (OR 1.01; P = .04), active acromegaly at the study entry (OR 2.48; P = .007), and treated hypoadrenalism (OR 2.50; P = .005). In the entire population, treatment with bone active drugs did not have a significant effect on incident VFs (P = .82). However, in a sensitive analysis restricted to patients with active acromegaly at study entry (111 cases), treatment with bone active drugs was associated with a lower risk of incident VFs (OR 0.11; P = .004), independently of prevalent VFs (OR 7.65; P < .001) and treated hypoadrenalism (OR 3.86; P = .007).
Bone active drugs may prevent VFs in patients with active acromegaly.
A comprehensive worldwide literature review of blood levels of dioxins and dioxin-like compounds in non-exposed adult general populations was performed. The studies published in 1989–2010 reporting ...information on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), non-ortho-PCBs (nPCBs), mono-ortho-PCBs (mPCBs) levels and Toxic Equivalencies (TEQs, a summary weighted measure of their combined toxicity) were reviewed. TEQs were calculated using as standard the most recent WHO 2005 reevaluation of Toxic Equivalency Factors (TEFs). Weighted multiple regression analyses adjusted for year, subject's age, type of sample analyzed, method used for values below detection limit, and central tendency measure used were performed for each congener and standardized TEQs (log-transformed). We identified 187 studies regarding 29,687 subjects of 26 countries. Year of blood collection ranged from 1985 to 2008. The studies reporting congener levels 161. In adjusted analyses, European countries showed higher levels of most dioxin-like congeners and TEQs. A strong positive association of subjects' age with most congeners and with TEQ values was found, confirming previous findings. Significant decreases over time (1985–2008) were documented for PCCDs, PCDFs, and TEQs including their contributions. No significant decrease was found for non-ortho-PCBs, notably PCB 126. Only some mono-ortho-PCBs showed clear significant declines. Accordingly, TEQs including only PCB contribution did not decrease over time. In interpreting these findings, it should be considered that for dioxin-like PCBs the analysis period was shorter (17years), since these compounds were first measured in 1992.
The analysis of biogeographical structure and patterns of endemism are central topics of biogeography, but require exhaustive distribution data. A lack of accurate broad-scale information on the ...distribution of reptiles has so far limited the analyses of biogeographical structure. Here we analysed the distribution of reptiles within the broad-sense Western Palearctic to assess biogeographical regionalization using phylogenetic and non-phylogenetic approaches, identified areas of endemism and evaluated the environmental factors promoting community uniqueness and endemism. We gathered distributional records from the literature and from the field, mapping the distribution of all the Western Palearctic reptiles on a 1-degree resolution grid. βsim dissimilarity and hierarchical clustering was used to identify bioregions, analysing data both at the species and at the genus level, and considering phylogenetic dissimilarity. Consensus areas of endemism were identified on the basis of the optimality criterion. We then assessed whether biogeographical structure is related to present-day climate, insularity, orography and velocity of climate change during the Late Quaternary. The genus-level analysis identified five main biogeographical regions within the Western Palearctic, in partial agreement with previous proposals, while the species-level analysis identified more bioregions, largely by dividing the ones identified by genera. Phylogenetic bioregions were generally consistent with the non-phylogenetic ones. The strongest community uniqueness was observed in subtropical warm climates with seasonal precipitation and low productivity. We found nine consensus areas of endemism, mostly in regions with limited velocity of Quaternary climate change and warm subtropical climates. The biogeographical structure of Western Palearctic reptiles is comparable to what has been observed in other vertebrates, with a clear distinction between the Saharo-Arabian-Sindian and Euro-Mediterranean herpetofaunas. Unlike other vertebrates, in reptiles the highest uniqueness and endemism is observed in dry climates, but the velocity of climate change during the Quaternary remains a major driver of endemism across all the vertebrates.
The Seveso accident in 1976 caused a large, populated area north of Milan, Italy, to be contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study, the authors followed up the exposed ...population for chronic effects; this paper reports the results of the mortality follow-up extension for 1997–2001. The study cohort includes 278,108 subjects resident at the time of the accident or immigrating/born in the 10 years thereafter in three contaminated zones with decreasing TCDD soil levels (zone A, very high; zone B, high; zone R, low) and in a reference territory comprising surrounding, noncontaminated municipalities. Vital status and cause-of-death ascertainment were 99% complete. Adjusted rate ratios and 95% confidence intervals were calculated by using Poisson regression. Results confirmed previous findings of excesses of lymphatic and hematopoietic tissue neoplasms in zones A (six deaths; rate ratio = 2.23, 95% confidence interval: 1.00, 4.97) and B (28 deaths; rate ratio = 1.59, 95% confidence interval: 1.09, 2.33). These zones also showed increased mortality from circulatory diseases in the first years after the accident, from chronic obstructive pulmonary disease, and from diabetes mellitus among females. A toxic and carcinogenic risk to humans after high TCDD exposure is supported by the results of this study.
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.
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