Cushing Syndrome

Abstract

Cushing syndrome (CS) is a state of glucocorticoid excess in which there is loss of the normal hypothalamic-pituitary-adrenal feedback axis. First described in 1912 by American neurosurgeon Dr Harvey Williams Cushing in reference to a 23-yearold patient with obesity, hirsutism, and amenorrhea, CS has since been recognized as a rare, yet serious and significant, condition in the pediatric population. Under normal circumstances, hypothalamic corticotropin-releasing hormone (CRH) is delivered to the anterior pituitary via the portal circulation, resulting in adrenocorticotropin hormone (ACTH) release from the anterior pituitary into the systemic circulation. ACTH acts on the zona fasciculata of the adrenal cortex to stimulate release of cortisol. The secretion of cortisol results in negative feedback, downregulating production of both ACTH and CRH. Cortisol has metabolic and cardiovascular effects. It plays an important role in hepatic glucose metabolism by increasing gluconeogenesis and glycogenolysis, as well as affecting proteolysis and lipolysis. In addition, it influences myocardial contractility, cardiac output, and blood pressure. It also has a variety of effects on the immunologic and inflammatory systems, musculoskeletal and connective tissue, and fluid and electrolyte homeostasis, as well as neuropsychiatric, behavioral, gastrointestinal, and developmental effects. In the general population, there are approximately 2 to 5 new cases per million per year of CS; only approximately 10% of these cases occur in the pediatric population. Although adolescents with CS, similar to adults, have a slight female to male predominance, this predilection goes away in younger patients and may even be reversed in infants with CS. Pediatric CS can be divided into 2 distinct categories: ACTH dependent and ACTH independent (Table 1). The most common cause of CS is exogenous administration of corticosteroids, which have become the first-line treatment of multiple pediatric disorders. Although oral corticosteroids are generally implicated in the development of CS, long-term use of inhaled and topical corticosteroids, commonly used as treatment for asthma and atopic dermatitis, respectively, can also result in CS. In addition, ACTH, used as treatment in certain seizure disorders, can stimulate adrenal cortisol release, resulting in CS. When exogenous causes of CS have been ruled out based on a careful history, endogenous causes should be sought. In children older than 5 years, Cushing disease (hypercortisolism resulting from oversecretion of pituitary ACTH from a corticotroph adenoma) is the most common cause of CS. In contrast, infants are most likely to have a primary adrenal condition, such as an adrenocortical tumor (adenoma or carcinoma). Although adrenocortical tumors are fairly rare in the pediatric age group, comprising only approximately 0.6% of childhood tumors, upward of one-third manifest with signs and symptoms of CS. Nearly all are unilateral (90% to 98%) and more than 70% are malignant. Most unilateral adrenal tumo...

A Pediatric Patient With Type 1 Diabetes Mellitus With Poor Glycemic Control, Medication-Resistant Hypertension, and New-Onset Headache Diagnosed With Adrenocorticotropic Hormone (ACTH)-Secreting Pituitary Macroadenoma

“…Unlike patients with type 1 diabetes who often present in DKA, patients with Cushing disease often present with non-specific signs and symptoms that manifest themselves over a prolonged period of time, making it difficult from a diagnostic perspective. Initial presentation commonly includes weight gain (90% of patients at presentation), growth failure (83%), hirsutism or acne (78%), amenorrhea and delayed puberty (78%), centripetal obesity such as buffalo hump or moon facies (75%), osteopenia (70%), violaceous striae (60%), hypertension (50%), headaches (25%), easy bruising (25%), compulsive behaviors and emotional lability (20%), and muscle weakness (12%) [ 5 ]. When presented separately, each of these problems has a broad differential diagnosis, but when considered together, they point toward a single etiology: hypercortisolism.…”

Pediatric Cushing syndrome: An early sign of an underling cancer predisposition syndrome

“…Additional later signs include striae, obesity, emotional lability, hypertension, fatigue, and virilization (Savage & Storr, 2012). The most common cause of CS is iatrogenic because of chronic treatment with glucocorticoids for neuroendocrine diseases (Klein et al, 2014). The overall incidence of endogenous CS is 0.7-2.4 per million people per year with 10% being pediatric cases (Stratakis, 2012).…”

Determinación de los niveles de cortisol salival en niños escolares y adolescentes sanos

“…elevados durante la media noche, horario en la que normalmente los niveles están bajos (8,9). Actualmente los protocolos están diseñados en mediciones de cortisol a las 8 a.m. y 4 p.m., por lo que no se refleja la fisiología normal del cortisol; sin embargo, estos son los horarios disponibles en la mayoría de laboratorios ambulatorios.…”

“…Actualmente los protocolos están diseñados en mediciones de cortisol a las 8 a.m. y 4 p.m., por lo que no se refleja la fisiología normal del cortisol; sin embargo, estos son los horarios disponibles en la mayoría de laboratorios ambulatorios. Ante la dificultad de tomar una muestra de cortisol sanguínea durante este horario, el cortisol salival se convierte en una buena alternativa para realizar su diagnóstico, con una excelente sensibilidad (100 %) y especificidad (96 %) (8,9). Por otra parte, su medición en la mañana puede ser útil en combinación con la prueba de estímulo de ACTH para detectar insuficiencia adrenal, como también para monitorear el tratamiento con glucocorticoides de pacientes con hiperplasia adrenal congénita (10,11).…”