Adrenal insufficiency in patients with Prader-Willi syndrome

Abstract

The generalized dysfunction of the hypothalamic-pituitary axis in patients with Prader-Willi syndrome (PWS) is the most likely cause of hypogonadism, inadequate growth hormone secretion, excessive appetite and associated obesity, impaired body temperature regulation, and hypothyroidism. The syndrome is also related to an increased risk of central adrenal insufficiency, although its prevalence remains unknown. The results of the studies in which different methods of pharmacological stimulation were used do not provide conclusive outcomes. As a result, there are no clear guidelines with regard to diagnosis, prevention, or long-term care when adrenal insufficiency is suspected in patients with PWS. Currently, most patients with PWS are treated with recombinant human growth hormone (rhGH). It has been confirmed that rhGH therapy has a positive effect on growth, body composition, body mass index (BMI), and potentially on psychomotor development in children with PWS. Additionally, rhGH may reduce the conversion of cortisone to cortisol through inhibition of 11β-hydroxysteroid dehydrogenase type 1. However, its influence on basal adrenal function and adrenal stress response remains unexplained in children with PWS. This paper reviews the literature related to the hypothalamic-pituitary-adrenal axis dysfunction in the PWS patient population with a focus on children.

Roles of SNORD115 and SNORD116 ncRNA clusters in neuronal differentiation

“…In contrast, the H116 phenotype was associated with neuronal activity: synapses, calcium signaling and hippocampal long-term potentiation. We note that several terms enriched for H116 correlate with PWS phenotypes; including hormonal regulation [(GnRH (Miller et al , 2009), parathyroid hormone (Iughetti et al , 2019), aldosterone (Kusz & Gawlik, 2022)], insulin secretion (Lautala et al , 1986), salivary secretion (Hart, 1998), circadian entrainment (Powell et al ., 2013) and addictive behavior (Salles et al , 2021).…”

Prenatal diagnosis of paternal uniparental disomy for chromosome 2 in two fetuses with intrauterine growth restriction

“…For example, UPD15 leads to gene imprinting abnormalities in the 15q11q13 region, resulting in Prader-Willi/Angelman syndrome. Prader-Willi syndrome is a rare genetic disorder, characterized by clinical features including hypotonia and weakness, severe obesity, hypogonadism, and intellectual disability [ 6 ]. Patients with Angelman syndrome have clinical manifestations such as intellectual defects, microcephaly, ataxia, and seizures [ 7 ].…”

Acute stress response of the HPA-axis in children with Prader-Willi syndrome: new insights and consequences for clinical practice

“…In literature, there is no agreement on the prevalence of CAI during acute stress in PWS ( 12 ). Several studies, in children and adults, using different test methods and definitions of CAI, have shown contradictory results.…”

“…Underdiagnosing can lead to potentially life-threatening situations such as an adrenal crisis during acute stress, and over diagnosing can lead to overuse of hydrocortisone, which might lead to unnecessary side effects. It is, therefore, important to expand the knowledge about acute stress-related adrenal insufficiency in PWS and to create recommendations on the necessity, frequency and repeating the diagnostic procedures for CAI in PWS ( 12 ). It has been reported that there is a negative correlation between age and the HPA-axis ( 18 , 21 ), which suggest that the response of the HPA-axis during acute stress could change with age.…”