Adult Height Following Prepubertal Treatment With Antiandrogen, Aromatase Inhibitor, and Reduced Hydrocortisone in CAH.

Context: Height outcome in patients with classic congenital adrenal hyperplasia (CAH) is suboptimal due to glucocorticoid and androgen excess.

Methods: In an open, randomized, controlled trial, children with classic CAH were randomized to receive a combination regimen of antiandrogen, aromatase inhibitor, reduced hydrocortisone, and fludrocortisone prior to puberty or standard therapy (hydrocortisone, fludrocortisone). Females continued on antiandrogen during puberty.

Younger age and early puberty are associated with cognitive function decline in children with Cushing disease.

Objective: To investigate the effect of hypercortisolism on the developing brain we performed clinical, cognitive, and psychological evaluation of children with Cushing disease (CD) at diagnosis and 1 year after remission.

Study Design: Prospective study of 41 children with CD. Children completed diverse sets of cognitive measures before and 1 year after remission.

Family environment and development in children adopted from institutionalized care.

Background: After adoption, children exposed to institutionalized care show significant improvement, but incomplete recovery of growth and developmental milestones. There is a paucity of data regarding risk and protective factors in children adopted from institutionalized care. This prospective study followed children recently adopted from institutionalized care to investigate the relationship between family environment, executive function, and behavioral outcomes.

Rare Germline Variants in Pediatric Patients With Cushing's Disease: What Is Their Role?

The DICER1 syndrome is a multiple neoplasia disorder caused by germline mutations in the gene. In DICER1 patients, aggressive congenital pituitary tumors lead to neonatal Cushing's disease (CD). The role of in other corticotropinomas, however, remains unknown.

Germline CDKN1B Loss-of-Function Variants Cause Pediatric Cushing's Disease With or Without an MEN4 Phenotype.

Context: Germline loss-of-function CDKN1B gene variants cause the autosomal dominant syndrome of multiple endocrine neoplasia type 4 (MEN4). Even though pituitary neuroendocrine tumors are a well-known component of the syndrome, only 2 cases of Cushing's disease (CD) have so far been described in this setting.

Aim: To screen a large cohort of CD patients for CDKN1B gene defects and to determine their functional effects.

Germline USP8 Mutation Associated With Pediatric Cushing Disease and Other Clinical Features: A New Syndrome.

Background: Somatic mutations in the ubiquitin-specific peptidase 8 (USP8) gene are common in corticotropinomas of children with Cushing disease (CD). We report a unique patient with a germline USP8 mutation who presented with CD and a constellation of other findings that constitute an intriguing genetic syndrome.

Case Description: We describe a 16-year-old female with CD, developmental delay, dysmorphic features, ichthyosiform hyperkeratosis, chronic lung disease, chronic kidney disease, hyperglycemia, dilated cardiomyopathy with congestive heart failure, and previous history of hyperinsulinism and partial GH deficiency.

Aortic pulse wave velocity in children with Cushing syndrome: A window into a marker of early cardiovascular disease.

Objective: To investigate early signs of cardiovascular arterial remodelling in paediatric patients with Cushing syndrome (CS) in comparison with normative values from healthy children.

Study Design: The metrics used to assess cardiac health were from thoracic aorta and carotid MRI. Scans were performed on 18 children with CS (mean: 12.

Large Genomic Aberrations in Corticotropinomas Are Associated With Greater Aggressiveness.

Context: Genomic losses/gains are associated with cancer progression and prognosis. In pituitary adenomas, analyses of copy number variations (CNVs) have shown that a subset of adenomas have higher genomic variability. However, whether CNVs are associated with tumor aggressiveness and prognosis has not been determined.

Children with MEN1 gene mutations may present first (and at a young age) with Cushing disease.

Objective: Cushing disease (CD) is a rare entity caused by ACTH-secreting pituitary tumours, leading to prolonged hypercortisolism. Most cases are sporadic but can rarely occur in the context of familial predisposition, due to germline mutations in genes such as MEN1, leading to multiple endocrine neoplasia type 1, MEN1. We have reported previously that CD can be the first and only presenting manifestation of MEN1.

Cushing's Syndrome in Pediatrics: An Update.

Cushing syndrome (CS) is a multisystem disorder resulting from the prolonged exposure to excess glucocorticoids. In children, CS most commonly results from the exogenous administration of steroids and the typical presentation is height deceleration concomitant with weight gain. Endogenous and ectopic causes are rare.

Mice deficient in AKAP13 (BRX) develop compulsive-like behavior and increased body weight.

Objective: Hormonal contributions to the sex-dependent development of both obsessive-compulsive disorder (OCD) and obesity have been described, but the underlying mechanisms are incompletely understood. A-kinase anchoring protein 13 (AKAP13) significantly augments ligand-dependent activation of estrogen receptors alpha and beta. The hypothalamus and pituitary gland are implicated in the development and exacerbation of OCD and obesity and have strong AKAP13 expression.

Anxiety-like behavior and other consequences of early life stress in mice with increased protein kinase A activity.

Anxiety disorders are associated with abnormalities in fear-learning and bias to threat; early life experiences are influential to the development of an anxiety-like phenotype in adulthood. We recently reported that adult mice (Prkar1a+/-) with haploinsufficiency for the main regulatory subunit of the protein kinase A (PKA) exhibit an anxiety-like phenotype associated with increased PKA activity in the amygdala. PKA is the main effector of cyclic adenosine mono-phosphate signaling, a key pathway involved in the regulation of fear learning.

Postoperative Diabetes Insipidus and Hyponatremia in Children after Transsphenoidal Surgery for Adrenocorticotropin Hormone and Growth Hormone Secreting Adenomas.

Objectives: To define the incidence and risk factors of postoperative sodium alterations in pediatric patients undergoing transsphenoidal surgery (TSS) for adrenocorticotropic hormone and growth hormone secreting pituitary adenomas.

Study Design: We retrospectively reviewed 160 patients ≤18 years of age who had TSS for pituitary adenomas at our institution from 1999 to 2017. Variables included daily serum sodium through postoperative day 10, urine specific gravity, and medications administered.

The Key to Adrenal Insufficiency Education: Repetition, Repetition, Repetition.

Described more than 150 years ago by Thomas Addison, adrenal gland dysfunction, while treatable, remains a clinically significant and potentially fatal disease. Vague and non-specific symptomatology can delay diagnosis of adrenal insufficiency and lead to adrenal crisis. Affected individuals may delay self-management due to knowledge deficits or lack of required therapies.

Dietary Isoflavone-Dependent and Estradiol Replacement Effects on Body Weight in the Ovariectomized (OVX) Rat.

17β-Estradiol is known to regulate energy metabolism and body weight. Ovariectomy results in body weight gain while estradiol administration results in a reversal of weight gain. Isoflavones, found in rodent chow, can mimic estrogenic effects making it crucial to understand the role of these compounds on metabolic regulation.

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics.

The interaction of dietary isoflavones and estradiol replacement on behavior and brain-derived neurotrophic factor in the ovariectomized rat.

Phytoestrogens are plant derived, non-steroidal compounds naturally found in rodent chows that potentially have endocrine-disrupting effects. Isoflavones, the most common phytoestrogens, have a similar structure and molecular weight to 17β-estradiol (E2) and have the ability to bind and activate both isoforms of the estrogen receptor (ER). Most isoflavones have a higher affinity for ERβ, which is involved in sexually dimorphic behavioral regulation.

Protein Kinase A and Anxiety-Related Behaviors: A Mini-Review.

This review focuses on the anxiety related to cyclic AMP/protein kinase A (PKA) signaling pathway that regulates stress responses. PKA regulates an array of diverse signals that interact with various neurotransmitter systems associated with alertness, mood, and acute and social anxiety-like states. Recent mouse studies support the involvement of the PKA pathway in common neuropsychiatric disorders characterized by heightened activation of the amygdala.

Cases of Psychiatric Morbidity in Pediatric Patients After Remission of Cushing Syndrome.

Endogenous Cushing syndrome (CS) may have different effects in children than what has been described in adults. Previous studies of children and adolescents with CS have identified cognitive decline despite reversal of brain atrophy after remission of CS. Although the observations of parents of children and adolescents with CS support personality changes, significant psychopathology has not been described in the literature.

Studies of mice with cyclic AMP-dependent protein kinase (PKA) defects reveal the critical role of PKA's catalytic subunits in anxiety.

Cyclic adenosine mono-phosphate-dependent protein kinase (PKA) is critically involved in the regulation of behavioral responses. Previous studies showed that PKA's main regulatory subunit, R1α, is involved in anxiety-like behaviors. The purpose of this study was to determine how the catalytic subunit, Cα, might affect R1α's function and determine its effects on anxiety-related behaviors.

The Role of Protein Kinase A in Anxiety Behaviors.

This review focuses on the genetic and other evidence supporting the notion that the cyclic AMP (cAMP) signaling pathway and its mediator, the protein kinase A (PKA) enzyme, which respond to environmental stressors and regulate stress responses, are central to the pathogenesis of disorders related to anxiety. We describe the PKA pathway and review in vitro animal studies (mouse) and other evidence that support the importance of PKA in regulating behaviors that lead to anxiety. Since cAMP signaling and PKA have been pharmacologically exploited since the 1940s (even before the identification of cAMP as a second messenger with PKA as its mediator) for a number of disorders from asthma to cardiovascular diseases, there is ample opportunity to develop therapies using this new knowledge about cAMP, PKA, and anxiety disorders.

Kidney Stones as an Underrecognized Clinical Sign in Pediatric Cushing Disease.

Objective: To investigate the prevalence of kidney stones in a population of children with Cushing disease (CD) and to compare it with the prevalence of kidney stones in healthy children.

Study Design: Clinical and biochemical data from 139 pediatric patients with CD (68 females, 71 males) were analyzed retrospectively. Computed tomography scans were reviewed for kidney stones.