Kenji Yamashiro

Non-classic P450 oxidoreductase deficiency (NC-PORD) is a rare form of congenital adrenal hyperplasia that may remain unrecognized until adulthood. While infertility in patients already diagnosed with P450 oxidoreductase deficiency (PORD) has been described, cases in which unexplained infertility directly leads to the diagnosis of NC-PORD are rare. We report 2 women who presented with unexplained infertility and persistent elevation of progesterone levels. Rapid adrenocorticotropic hormone stimulation testing showed marked increases in progesterone and 17α-hydroxyprogesterone with suboptimal cortisol response, suggesting impaired steroidogenesis. Genetic analysis identified P450 oxidoreductase variants previously reported in PORD, supporting the diagnosis of NC-PORD. These cases suggest that persistent progesterone elevation may serve as an important clinical clue for NC-PORD in patients with infertility. In contrast to non-classic 21-hydroxylase deficiency, the broader impairment of steroidogenesis in NC-PORD may result in a more complex reproductive phenotype. Recognition of this endocrine pattern may facilitate timely diagnosis and enable mechanism-based management strategies in reproductive medicine.

Background: Adult growth hormone deficiency (AGHD) is often diagnosed after surgery for nonfunctioning pituitary neuroendocrine tumor (NF‐PitNET). While a growth hormone stimulation test (GHST) is required to establish its diagnosis, it is associated with a large burden on patients and healthcare providers alike. Currently, the recommended indicators for the diagnosis of AGHD include the IGF‐1 standard deviation score (IGF‐1SDS) from a random blood sample and the number of deficiencies in pituitary hormones other than GH; however, there are also some challenges associated with these indicators. Therefore, to predict the need for GHST, this study focused on the interrelationship between GH and pituitary hormones to investigate whether postoperative thyroid‐stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels measured before GHST could represent novel predictors of AGHD. Methods: Among 166 patients who underwent GHST following surgical treatment for NF‐PitNET, 60 patients who were diagnosed with NF‐PitNET based on clinical and pathological criteria were included in this analysis. Exclusion criteria were as follows: missing data ( n = 16), data collection outside the specified timeframe ( n = 4), positive thyroid autoantibodies ( n = 2), and oral levothyroxine administration during GHST ( n = 3). Clinical parameters of the 35 patients were compared between the AGHD group ( n = 11) and the non‐AGHD group ( n = 24) using Fisher’s exact test and Mann–Whitney U test. Results: Patients with AGHD showed significantly lower postoperative levels of FT3 and FT4 prior to GHST, with median values of 2.10 pg/mL (1.97–2.34) and 0.98 ng/dL (0.77–1.19), respectively, than those without postoperative AGHD, who showed median levels of 2.45 pg/mL (2.28–2.67) and 1.18 ng/dL (1.03–1.26) ( p < 0.001 and p = 0.008, respectively). In contrast, no significant difference in TSH levels was observed between the two groups. Receiver operating characteristic (ROC) analysis identified the optimal cutoff values for predicting AGHD as 2.125 pg/mL for FT3 and 1.010 ng/dL for FT4. Conclusion: These findings suggest the potential utility of FT3 and FT4 as novel predictors for the diagnosis of postoperative AGHD.

In the large-scale, prospective, observational JDCP study, a total of 5944 people with type 2 diabetes (mean age at baseline, 61.4 years old; women, 39.9%; and duration of diabetes, 10.8 years) were followed up for incidence of malignancy. During a mean 5.38 ± 2.92 years of follow-up, malignancies occurred in 322 individuals, accounting for a crude incidence of 10.35/1000 person-years. The 3 most frequently reported malignancies included colorectal cancers (20.4%), breast cancer (16.5%) and lung cancers (13.6%) in women, and gastric cancers (18.3%), colorectal cancers (15.7%) and lung/prostate cancers (12.7%) in men. During follow-up, men had a significantly higher relative risk for malignancy than women. In contrast, women had a significantly shorter time to the first diagnosis of malignancy following a diagnosis of diabetes than men (13.79 ± 7.90 and 17.11 ± 8.50 years, respectively), although there was no marked difference in the age at the diagnosis of malignancy (67.39 ± 7.27 and 68.44 ± 6.62 years, respectively). Cox proportional hazard models revealed that increasing age, a history of drinking and a history of acute myocardial infarction were significantly associated with an increased risk of malignancy. This report may be of interest in that it provides valuable insight into which malignancies Japanese people with type 2 diabetes are likely to be at risk of developing over time.