Cushing Syndrome in Pediatrics

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Epidemiology and etiology

Cushing syndrome is a rare entity, especially in children.1 The overall incidence of Cushing syndrome is approximately 2 to 5 new cases per million people per year. Only approximately 10% of the new cases each year occur in children. As in adult patients, in children with Cushing syndrome there is a female-to-male predominance, which decreases with younger age. There might even be a male-to-female predominance in infants and young toddlers with Cushing syndrome.1, 3, 4 The most common cause of

Clinical presentation

In most children, the onset of Cushing syndrome is insidious.1, 3, 4, 14 The most common presenting symptom is weight gain; in childhood, lack of height gain consistent with the weight gain is the most common presentation of Cushing syndrome. A typical growth chart for a child with Cushing syndrome is shown in Fig. 1. Other common problems reported in children include facial plethora, headaches, hypertension, hirsutism, amenorrhea, and delayed sexual development. Pubertal children may present

Diagnostic guidelines

The appropriate therapeutic interventions in Cushing syndrome depend on accurate diagnosis and classification of the disease. The medical history and clinical evaluation, including review of growth data, are important to make the initial diagnosis of Cushing syndrome. Upon suspicion of Cushing syndrome, laboratory and imaging confirmations are necessary. An algorithm of the diagnostic process is presented in Fig. 2.

The first step in the diagnosis of Cushing syndrome is to document

Treatment

The treatment of choice for almost all patients with an ACTH-secreting pituitary adenoma (Cushing disease) is transsphenoidal surgery (TSS). In most specialized centers with experienced neurosurgeons, the success rate of the first TSS is 90%25 or higher. Treatment failures are most commonly the result of a macroadenoma or a small tumor invading the cavernous sinus. The success rate of repeat TSS is lower, closer to 60%. Postoperative complications include transient diabetes insipidus (DI) and,

Glucocorticoid replacement

After the completion of successful TSS in Cushing disease or excision of an autonomously functioning adrenal adenoma, there will be a period of adrenal insufficiency while the hypothalamic pituitary adrenal axis is recovering. During this period, glucocorticoids should be replaced at the suggested physiologic replacement dose (12–15 mg/m2/day 2 or 3 times daily), as we have recently published.27 In the immediate postoperative period, stress doses of cortisol should be initiated. These should be

Psychosocial implications

Cushing syndrome has been associated with multiple psychiatric and psychological disturbances, most commonly emotional lability, depression, and/or anxiety. Other abnormalities have included mania, panic disorder, suicidal ideation, schizophrenia, obsessive–compulsive symptomatology, psychosis, impaired self-esteem, and distorted body image. Significant psychopathology can even remain after remission of hypercortisolism and even after recovery of the HPA axis. Up to 70% of patients will have

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      Germline and tumor DNA samples were extracted as previously described.13 The diagnosis of CD was integrated following established guidelines and our previously published protocol.14 Some individuals have been previously screened for germline defects in AIP, CDKN2C, MEN1, and PRKAR1A (n = 59), CABLES1 (n = 140), CDKN1B (n = 211), DICER1 (n = 182), somatic and/or germline GPR101 variants (n = 34), and somatic CDKN1B (n = 27) and USP8 variants (n = 44) using Sanger sequencing (and multiplex ligation dependent probe amplification for AIP and MEN1).6,13,15-18

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      Periodic or cyclic Cushing's syndrome is frequent in children and adolescents with PPNAD [257]. Ectopic Cushing's syndrome in children accounts for less than 1% of Cushing’ syndromes, and is 80 times less frequent than Cushing's disease [262]. Onset can be at any age, but presentation is age-dependent.

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    This work was completed with support by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892–1862.

    The author has nothing to disclose.

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