An Early Association between X-Linked Adrenoleukodystrophy and Type 1 Diabetes Mellitus - A Case Report

X-linked Adrenoleukodystrophy (X-ALD) is a rare genetic disorder of peroxisomal metabolism and is one of the causes of primary adrenal insufficiency. X-ALD is also associated with various neurological manifestations, however the endocrine features may precede neurological symptoms. As it is rare to have two endocrinological conditions with X-ALD, here we present a unique case of a child with confirmed X-ALD and concurrent Type 1 Diabetes Mellitus (T1DM).

Associations between blood cadmium and endocrine features related to PCOS-phenotypes in healthy women of reproductive age: a prospective cohort study

Background Cadmium is an endocrine disrupting chemical that affects the hypothalamic-pituitary-gonadal axis. Though evidence suggests its potential role in altering androgen synthesis and metabolic pathways that are characteristic of polycystic ovary syndrome (PCOS), its relation in healthy women of reproductive age is largely unknown. As women with mild sub-clinical features of PCOS who do not meet the diagnostic criteria of PCOS may still experience reduced fecundability, investigating associations between cadmium and PCOS-phenotypes among healthy women may provide unique insight into the reproductive implications for many on the PCOS spectrum. Therefore, the objective of this study was to evaluate associations between cadmium and androgens, anti-Müllerian hormone (AMH), and metabolic markers in women of reproductive age. Methods This was a prospective cohort study of 251 healthy premenopausal women without self-reported PCOS (mean age 27.3 years and BMI 24.1 kg/m2). Cadmium was measured in blood collected at baseline. Reproductive hormones and metabolic markers were measured in fasting serum 8 times per menstrual cycle for 2 cycles. Linear mixed models and Poisson regression with a robust error variance were used to examine associations between cadmium and reproductive hormones and metabolic markers and anovulation, respectively. Results Median (interquartile range) blood cadmium concentrations at baseline were 0.30 (0.19–0.43) µg/L. Higher levels of testosterone (2.2 %, 95 % confidence interval [CI] 0.4, 4.1), sex hormone-binding globulin (2.9 %, 95 % CI 0.5, 5.5), and AMH (7.7 %, 95 % CI 1.1, 14.9) were observed per 0.1 µg/L increase in cadmium concentrations. An 18 % higher probability of a mild PCOS-phenotype (95 % CI 1.06, 1.31), defined by a menstrual cycle being in the highest quartile of cycle-averaged testosterone and AMH levels, was also found per 0.1 µg/L increase in cadmium levels. No associations were observed for insulin and glucose. These findings were consistent even after analyses were restricted to non-smokers or further adjusted for dietary factors to account for potential sources of exposure. Conclusions Overall, among healthy reproductive-aged women, cadmium was associated with endocrine features central to PCOS, but not with metabolic markers. These suggest its potential role in the hormonal milieu associated with PCOS even at low levels of exposure.

Timely diagnosis of multiple endocrine neoplasia 2B by identification of intestinal ganglioneuromatosis: a case series

Background Medullary thyroid carcinoma (MTC) in childhood is rare and has an unfavorable prognosis. To improve outcome, early diagnosis is essential. In patients with multiple endocrine neoplasia type 2B (MEN2B), MTC can occur already before the age of 1 year. Recognition of non-endocrine features of MEN2B may lead to timely diagnosis. Purpose To describe how early recognition of non-endocrine features can lead to a timely diagnosis of MEN2B as well as the effect of recognition of premonitory symptoms on prognosis. Methods A retrospective case series from the University Medical Center Utrecht/Wilhelmina Children’s Hospital, a Dutch national expertise center for MEN patients. All eight MEN2B patients in follow-up between 1976 and 2020 were included and medical records reviewed. Results Intestinal ganglioneuromatosis (IGN) as the cause of gastrointestinal (GI) symptoms was detected in seven patients. In three of them within months after birth. This led to early diagnosis of MEN2B, which allowed subsequent curative thyroid surgery. On the contrary, a MEN2B diagnosis later in childhood—in three patients (also) triggered by oral neuromas/neurofibromas—led to recurrent, persistent, and/or progressive MTC in five patients. Conclusions Neonatal GI manifestations offer the most important window of opportunity for early detection of MEN2B. By accurate evaluation of rectal biopsies in patients with early onset severe constipation, IGN can be timely detected, while ruling out Hirschsprung’s disease. MEN2B gene analysis should follow detection of IGN and—when confirmed—should prompt possibly still curative thyroid surgery.

Case report: potential treatment of metastatic amphicrine carcinoma of the rectum with FOLFOXIRI chemotherapy

ABSTRACT Amphicrine carcinoma (AmC) is a unique epithelial tumor displaying exocrine and endocrine features in the same cell. It shows an adenocarcinoma-like cellular form and has endocrine granules. There are few reports describing chemotherapy for AmC. Here, we describe a case with metastatic AmC from the rectum that was treated with FOLFOXIRI chemotherapy. A 64-year-old man was diagnosed with a submucosal lesion on the scar produced after an endoscopic mucosal resection, which had been performed for adenocarcinoma of the rectum 2 years before. The endoscopic submucosal dissection revealed AmC. The abdominoperineal resection including lymph nodes dissection was performed. Thereafter, computed tomography showed multiple liver metastases, and FOLFOXIRI was administered. The best overall response was partial response, and progression-free survival was 8.7 months. After 16.0 months since first-line chemotherapy the patient died. We can therefore conclude that FOLFOXIRI may be effective for AmC of the rectum.