Context Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly. Objective To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs). Methods This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had insulin-like growth factor I (IGF-I) ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0×ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary (ASD) score, and maintenance of mean 5-sample growth hormone (GH) <1.0 ng/mL. Results The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0×ULN (odds ratio: 126.53; 95% CI: 13.73, >999.99; P<.0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (±SE) change in IGF-I of 0.04±0.09×ULN versus 0.83±0.1×ULN (P<.0001); mean (±SE) change in ASD score of –0.6±1.5 versus 4.6±1.6 (P=.02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) versus 5/18 (27.8%) patients (odds ratio: 16.61; 95% CI: 2.86, 181.36; P=.0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs. Conclusion Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.

Context: Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). Objective: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. Design: Open-label, phase 2 study. Participants: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16). Intervention: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). Main outcomes: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs). Results: After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. Conclusion: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover.

Purpose: Polyglandular autoimmune syndromes (PAS) are complex, heterogeneous disorders in which various autoimmune diseases can occur, affecting both endocrine and non-endocrine organs. In this meta-analysis, the prevalence of associated autoimmune disorders was investigated in PAS II and III. Methods: A comprehensive search in MEDLINE and Embase databases identified 479 studies with the keywords of PAS II and PAS III. 18 records containing a total of 1312 patients fulfilled our inclusion criteria (original studies reporting at least 10 cases and containing the combination of other autoimmune disorders) and were selected for further analysis. A meta-analysis of prevalence was performed using the random-effects model with the calculation of 95% confidence intervals (CI). Results of each meta-analysis were displayed graphically using forest plots. Results: Distinction between PAS II and PAS III was made in 842 cases, of which 177 and 665 were PAS II and III (21.1 vs 78.9%), respectively. The prevalence of Hashimoto’s thyroiditis was significantly higher than that of Graves’s disease (39% [95% CI 17–65%] vs. 4% [95% CI 0–10%], respectively; p = 0.001). In PAS II, Addison’s disease (AD) coexisted with AITDs, T1DM or the combination of these conditions in 65, 18 and 10% of cases, respectively. In addition, one other endocrine and five non-endocrine organ-specific autoimmune disorders were reported. In PAS III, two other autoimmune endocrinopathies, six non-endocrine organ-specific, and four systemic autoimmune disorders were found in combination with AITDs. Conclusions: AITDs, T1DM and AD are the most common combinations in PAS, thus screening for these conditions seems to be reasonable.

The function of natural autoantibodies (nAAbs) in maintaining immunological tolerance has been comprehensively explained; however, their function in pregnant patients dealing with autoimmune diseases has not been thoroughly investigated. As Hashimoto’s thyroiditis (HT) is the predominant organ-specific autoimmune condition of women of childbearing age, this study’s objective was to evaluate IgM and IgG nAAbs targeting mitochondrial citrate synthase (CS) and heat shock proteins (Hsp60 and Hsp70) in women diagnosed with HT who were pregnant (HTP). Serum samples collected from HTP and healthy pregnant (HP) women in the first and third trimesters were tested using in-house-developed enzyme-linked immunosorbent assays (ELISAs). Our findings indicate the stability of nAAbs against CS and Hsps throughout the pregnancies of both healthy women and those with HT. However, during both trimesters, HTP patients displayed elevated levels of IgM isotype nAAbs against Hsp60 and Hsp70 compared to HP women, suggesting a regulatory role of IgM nAAbs during the pregnancies of patients with HT. Nonetheless, levels of IgG isotype nAAbs against Hsps were lower solely in the third trimester among HTP patients, resulting in a higher IgM/IgG ratio, which indicates their importance in alterations of the nAAb network during pregnancy in patients with HT.

Thyroglobulin (Tg) is the most important tumor marker in differentiated thyroid cancer (DTC). The aim of this study was to assess the diagnostic and prognostic roles of postoperative stimulated and postablative lowest, highest, and one-year non-stimulated Tg values obtained during the follow-up of patients with DTC. In this retrospective study, 222 radioiodine-treated, anti-thyroglobulin antibody (TgAb)-negative DTC patients having at least 9 months’ follow-up time were included (172 papillary and 50 follicular cancers; median age: 48 (from 15 to 91) years; female–male ratio: 158/64; median (quartiles) follow-up time: 54 (22–97) months). The 2015 American Thyroid Association guidelines were applied as criteria of the therapeutic response. Postoperative stimulated Tg values had significantly lower diagnostic accuracy than any of the non-stimulated postablative Tg values. One-year non-stimulated Tg had excellent prognostic value for structural disease: a cut-off value of 0.85 ng/mL had an 88.1% diagnostic accuracy. If the Tg value did not decrease below 0.75 ng/mL at any time during follow-up, the risk of residual disease was 25 times higher. The highest non-stimulated Tg during follow-up was the best predictor of residual disease (e.g., a Tg value exceeding 7.7 ng/mL indicated a 30-fold increase in risk). Non-stimulated Tg values measured during follow-up have excellent diagnostic accuracy to predict structural disease in DTC patients. The risk classification of a patient can safely be modified based on even a single Tg measurement.

The impact of post-radioiodine therapy SPECT/CT on early risk stratification in differentiated thyroid cancer; a bi-institutional study The impact of post-radioiodine therapy SPECT/CT on early risk stratification in differentiated thyroid cancer; a bi-institutional study