Pubertal development and premature ovarian insufficiency in patients with APECED

Abstract

Objective: To determine the natural course of pubertal development, growth during puberty, and development of POI in females with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also called autoimmune polyendocrine syndrome type I. Design: Longitudinal follow-up study. Methods: A national cohort of females with APECED aged 12 years were followed during 1965-2018. Attainment of adult height was defined when patients’ height increased less than 1 cm per year. Diagnosis of POI was based on delayed puberty or POI symptoms with amenorrhea, and/or FSH ≥40 IU/l. Results: Altogether 40 women with APECED were followed up to the average age of 37.3 (range, 14.6–61.9) years; 16 females (40%) were ≥40 years. Pubertal development started spontaneously in 34 patients and 29 had spontaneous menarche. POI developed in 28 patients (70%) at the median age of 16.0 years (range, 11.3–36.5), and in 20 of them (71%) before attaining adult height. In 11 cases puberty was induced or completed by hormonal therapy. Patients with POI were significantly shorter at menarche, but adult heights did not differ from non-POI females. Patients with POI had more often primary adrenocortical insufficiency (93% vs. 58%, p=0.017) and ovarian antibodies (81% vs. 30%, p=0.003) compared to those with normal ovarian function (n=12). Conclusions: POI developed in the majority of patients with APECED, often before or shortly after menarche. Timely commencement of hormonal replacement therapy is important to ensure optimal pubertal development and growth. The possibility of fertility preservation before development of POI in APECED patients should be further studied.

Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy in Two Siblings: Same Mutations but Very Different Phenotypes

“…Premature ovarian insufficiency develops in most patients with APECED, often before or shortly after menarche. In a recent study, it developed in 70% of patients at a median age of 16.0 years and in 71% of them before reaching adult height; therefore, timely initiation of hormone replacement therapy is important to ensure optimal pubertal development and growth [20].…”

Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy

“…All patients with adrenal insufficiency should have access to parenteral hydrocortisone for acute stress dosing and a medical alert bracelet and/or Addison's disease emergency card and should be educated by their treating physicians on the appropriate clinical indications that warrant increasing their hydrocortisone dose (e.g., febrile illness). Furthermore, prompt initiation of hormone replacement is critical to achieve optimal pubertal development and growth in patients with hypogonadism; sperm and oocyte cryopreservation could be considered, when feasible, in adolescent patients before the development of gonadal failure ( 164 ).…”

Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence

“…APS1 women have been included in APOI studies (198,199), and APS1 has become a well-known condition causing this disease (200)(201)(202)(203)(204)(205)(206)(207)(208)(209)(210)(211)(212)(213)(214)(215)(216)(217)(218). Recently, the clinical and immunological features of APS1associated APOI have been detailed in the Finnish cohort of APS1 women (219).…”