Calcitonin levels in autoimmune atrophic gastritis-related hypergastrinemia.

PURPOSE: Calcitonin (Ct) is currently the most sensitive biochemical marker of C-cell disease (medullary thyroid cancer [MTC] and C-cell hyperplasia), but its specificity is relatively low. Our aim was to examine whether autoimmune atrophic gastritis (AAG) and chronic hypergastrinemia, with or without chronic autoimmune thyroiditis (AT), are conditions associated with increased Ct levels. METHODS: Three groups of patients were consecutively enrolled in this  multicentric study: group A consisted of patients with histologically-proven AAG (n = 13; 2 males, 11 females); group B fulfilled the criteria for group A but also had AT (n = 92; 15 males, 77 females); and group C included patients with AT and without AAG (n = 37; 6 males, 31 females). RESULTS: Median Ct levels did not differ between the three groups. Ct levels were undetectable in: 8/13 cases (61.5%) in group A, 70/92 (76.1%) in group B, and 27/37 (73.0%) in group C. They were detectable but ≤ 10 ng/L in 4/13 (30.8%), 20/92 (21.7%) and 7/37 (18.9%) cases, respectively; and they were > 10 ng/L in 1/13 (7.7%), 2/92 (2.2%) and 3/37 (8.1%) cases, respectively (P = 0.5). Only three patients had high Ct levels (> 10 ng/L) and high gastrin levels and had an MTC. There was no correlation between Ct and gastrin levels (P = 0.353, r = 0.0785). CONCLUSIONS: High gastrin levels in patients with AAG do not explain any hypercalcitoninemia, regardless of whether patients have AT or not. This makes it mandatory to complete the diagnostic process to rule out MTC in patients with high Ct levels and AAG.

Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy.

BACKGROUND: The number of recognised distinct autoimmune diseases (AIDs) has progressively increased over the years with more than 100 being reported today. The natural history of AIDs is characterized by progression from latent and subclinical to clinical stages and is associated with the presence of the specific circulating autoantibodies. Once presented, AIDs are generally chronic conditions. AIDs have the tendency to cluster and co-occur in a single patient. Autoimmune thyroid diseases (AITD) are the most prevalent of AIDs in the world population, and about one-third of the AITD patients also present with a non-thyroid AID during their life-span. Furthermore, patient with non-thyroid AIDs often presents with a form of AITD as a concurrent condition. Many of the clusters of AIDs are well characterized as distinctive syndromes, while some are infrequent and only described in case reports. PURPOSE: In this review, we describe the wide spectrum of the combinations and the intricate relationships between AITD and the other AIDs, excluding Addison's disease. These combinations are collectively termed type 3 Autoimmune Polyglandular Syndrome (APS-3), also called type 3 Multiple Autoimmune Syndrome (MAS-3), and represent the most frequent APS in the world populations. CONCLUSIONS: Numerous associations of AITD with various AIDs could be viewed as if the other AIDs were gravitating like satellites around AITD located in the center of a progressively expanding galaxy of autoimmunity.

Renin and electrolytes indicate the mineralocorticoid activity of fludrocortisone: a 6 year study in primary adrenal insufficiency.

CONTEXT: Fludrocortisone (FC) is the mineralocorticoid (MC) replacement treatment for patients with primary adrenal insufficiency (PAI). OBJECTIVE: To explore the dose of FC treatment and its relationship with glucocorticoid therapy, sodium, potassium, renin and clinical parameters. SETTING: Monocentric cohort. PATIENTS: Data of 193 patients with PAI (130 autoimmune) were collected during baseline (T0), intermediate (T1) and last follow-up visit (T2, respectively, after a mean of 38 and 72 months). MAIN OUTCOME MEASURE: Utility of endocrine and clinical parameters to titrate FC dose. RESULTS: FC dose (50-75 µg/daily) was stable in the follow-up in half patients. The MC activity of FC was dose-dependent: we observed a reduced but significant positive linear correlation between FC dose and sodium (r = 0.132) and negative linear correlation between FC and potassium (r = - 0.162) or renin (r = - 0.131, all p < 0.01). An overall reduction in the FC dose was observed at T2 in the group with longer follow-up (> 60 months, p < 0.05). Higher doses of FC were observed in patients with low-normal renin, especially in autoimmune PAI (86 vs 65 µg/daily, p < 0.05). On the contrary, reduced sodium and increased potassium levels were observed in patients with high renin at T2. The number of cardiovascular events (15 in the whole cohort) was similar in patients sorted by renin levels or FC dose. CONCLUSIONS: Renin and electrolytes can indicate the MC activity of FC treatment: they should be routinely evaluated and used to titrate its dose that can be reduced in the long-term follow-up.

Tele-medicine versus face-to-face consultation in Endocrine Outpatients Clinic during COVID-19 outbreak: a single-center experience during the lockdown period.

CONTEXT: The COVID-19 outbreak in Italy is the major concern of Public Health in 2020: measures of containment were progressively expanded, limiting Outpatients' visit. OBJECTIVE: We have developed and applied an emergency plan, tailored for Outpatients with endocrine diseases. DESIGN: Cross-sectional study from March to May 2020. SETTING: Referral University-Hospital center. PATIENTS: 1262 patients in 8 weeks. INTERVENTIONS: The emergency plan is based upon the endocrine triage, the stay-safe procedures and the tele-Endo. During endocrine triage every patient was contacted by phone to assess health status and define if the visit will be performed face-to-face (F2F) or by tele-Medicine (tele-Endo). In case of F2F, targeted stay-safe procedures have been adopted. Tele-Endo, performed by phone and email, is dedicated to COVID-19-infected patients, to elderly or frail people, or to those with a stable disease. MAIN OUTCOME MEASURE: To assess efficacy of the emergency plan to continue the follow-up of Outpatients. RESULTS: The number of visits cancelled after endocrine triage (9%) is lower than that cancelled independently by the patients (37%, p < 0.001); the latter reduced from 47 to 19% during the weeks of lockdown (p = 0.032). 86% of patients contacted by endocrine-triage received a clinical response (F2F and tele-Endo visits). F2F visit was offered especially to young patients; tele-Endo was applied to 63% of geriatric patients (p < 0.001), visits' outcome was similar between young and aged patients. CONCLUSIONS: The emergency plan respects the WHO recommendations to limit viral spread and is useful to continue follow-up for outpatients with endocrine diseases.

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients.

BACKGROUND: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison's disease (AD). METHODS: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined. RESULTS: The prevalence of APS-1 was 2.6 cases/million (range 0.5-17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. CONCLUSIONS: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

Proinflammatory/profibrotic effects of aldosterone in Gitelman's syndrome, a human model opposite to hypertension.

PURPOSE: Aldosterone proinflammatory/profibrotic effects are mediated by the induction of mononuclear leucocytes (MNL) to express oxidative stress (OxSt)-related proteins, such as p22phox, and by the activation of RhoA/Rho kinase pathway. Gitelman's syndrome (GS), an autosomal recessive tubulopathy, is an interesting opposite model to hypertension, being characterized by hypokalemia, activation of renin-angiotensin-aldosterone system yet normo/hypotension and lack of cardiovascular-renal remodeling. We aimed to evaluate the proinflammatory/profibrotic effect of aldosterone in MNL of 6 GS patients compared with 6 healthy subjects (HS). METHODS: p22phox expression and MYPT-1 phosphorylation status, a marker of RhoA/Rho kinase pathway activation, were evaluated in MNL of GS patients and HS at baseline and after incubation with aldosterone (1 × 10-8 M) alone or with canrenone (1 × 10-6 M). RESULTS: At basal condition, p22phox expression was significantly higher in HS than in GS patients (1.02 ± 0.05 densitometric unit (du) vs 0.40 ± 0.1 du, respectively). Aldosterone significantly increased p22phox expression in HS and this effect was reversed by coincubation with canrenone (1.4 ± 0.05 du and 1.09 ± 0.03 du, respectively). No significant change was reported in GS after incubation of MNL with aldosterone and/or canrenone compared with basaline. Even MYPT-1 phosphorylation was significantly higher in HS compared with GS patients at basal condition (1.16 ± 0.1 du vs 0.69 ± 0.07, respectively). Aldosterone significantly increased MYPT-1 phosphorylation only in HS (1.37 ± 0.1 du vs 0.83 ± 0.12 du in GS). CONCLUSIONS: GS patients seem to be protected by the OxSt status induced by aldosterone and revealed in HS. This human model could provide additional clues to highlight the proinflammatory/cardiovascular remodeling effects of aldosterone.

Is corifollitropin alfa effective in controlled ovarian stimulation among all poor ovarian responders? A retrospective comparative study.

Several studies have compared the effectiveness of corifollitropin alfa versus daily gonadotropins in poor ovarian responders (PORs) undergoing controlled ovarian stimulation (COS), showing conflicting results in terms of IVF outcomes. Given the heterogeneity of patients included in the classification of POR according to 'Bologna criteria', the aim of this study was to evaluate the impact of corifollitropin alfa in two different categories of POR distinguished according to patients' antral follicle count (AFC). We retrospectively evaluated 104 infertile POR, split into two groups according to AFC (Group A ≤ 5; Group B > 5) and subgroups according to the ovarian stimulation regimen (corifollitropin alfa plus daily gonadotropins (Subgroup 1) versus daily gonadotropins alone (Subgroup 2)). Outcome measures were total oocytes, MII oocytes, total embryos, follicular output rate (FORT), implantation rate (IR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR). Subgroup A1 experienced a lower number of total oocytes, MII oocytes, total embryos, and FORT (p < .05) in comparison to Subgroup A2, while no difference was found when comparing Subgroups B1 and B2. No difference was found between subgroups even in terms of IR, CPR, MR, and LBR. In conclusion, corifollitropin alfa may be as effective as daily gonadotropins in POR with AFC > 5 undergoing COS, while it might be inferior to daily gonadotropins in POR with AFC ≤ 5.

The influence of thyroid autoimmunity on embryo quality in women undergoing assisted reproductive technology.

The influence of thyroid autoimmunity in assisted reproductive technology (ART) outcome in euthyroid women is still controversial. In this study, we retrospectively evaluated embryo quality in 123 euthyroid women undergoing ART with or without thyroid autoantibodies (TAA). Embryo quality was assessed in 119 embryos of 29 infertile patients with TAA and in 394 embryos of 94 infertile patients without TAA. Our results showed not statistically significant differences in age, body mass index, anti-Müllerian hormone, follicle stimulating hormone, free triiodothyronine, and free thyroxine levels between cases and controls. Thyroid stimulating hormone was within the normal range, but significantly higher in TAA patients compared with the controls (2.4 ± 0.8 vs. 2 ± 0.9 mIU/L, respectively, p < .01). The number of oocytes picked up and fertilized was comparable between the two groups. Embryo quality was significantly impaired in women with at least one autoantibody (p < .001). Implantation rate, pregnancy rate, and ongoing pregnancy rate were comparable in the two groups. These results suggest a negative impact of thyroid autoimmunity in embryo quality in women undergoing ART even when thyroid function is normal.

Spironolactone and intermenstrual bleeding in polycystic ovary syndrome with normal BMI.

PURPOSE: Spironolactone (SP) is an effective treatment for polycystic ovary syndrome (PCOS), but it is often associated with menstrual abnormalities whose mechanism is still under investigation. In this study, we investigated the serum sex steroids and endometrial thickness in 30 PCOS patients, before and after one-month 100 mg SP treatment. METHODS: Serum FSH, LH, estradiol, progesterone and endometrial thickness were evaluated at the 14th and 16th day of the menstrual cycle, before and during short-term SP treatment. According to the presence (15 cases) or absence (15 cases) of menstrual bleeding at the 14th day during SP, the patients were divided into two groups, which were then compared using a two-tailed Student's t test. RESULTS: Serum estradiol and endometrial thickness were lower than pretreatment at both determinations in all patients, but patients with bleeding had significantly lower estradiol values than non-bleeding ones, both before and after therapy. Endometrial thickness was significantly lower in the bleeding group compared with non-bleeding group only at the 16th day of the cycle. These differences were significant, even though the values of estradiol and endometrial thickness remained in the normal range. CONCLUSIONS: SP therapy can reduce the values of estradiol and the endometrial thickness in patients with PCOS compared with pretreatment, but PCOS patients with bleeding had pretreatment estradiol values lower than the patients who did not complain of this side effect. Intermenstrual abnormalities may represent the low estrogen impregnation of endometrium due to SP, whose mechanism is complex, involving several factors, such as the effects of some metabolites of SP on estradiol and progesterone production, on their receptors, and the individual metabolism of SP in vivo.