Can Cushing's syndrome cause a growth spurt in adolescence?

From the Guidelines

No, Cushing's syndrome typically does not cause a growth spurt in adolescence, but rather leads to growth inhibition and short stature in children and adolescents. Cushing's syndrome is characterized by excessive cortisol production, which interferes with normal growth hormone secretion and action, as noted in a recent consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence 1. The high cortisol levels suppress growth hormone release and impair the growth of long bones, resulting in slowed rather than accelerated growth. Additionally, Cushing's syndrome causes other distinctive features including weight gain with central obesity, rounded "moon" face, purple stretch marks, muscle weakness, and thinning skin.

In adolescents with unexplained growth failure combined with weight gain and other cushingoid features, medical evaluation is warranted. Treatment depends on the underlying cause, which may include surgical removal of tumors, medication to reduce cortisol production, such as metyrapone or ketoconazole 1, or addressing exogenous steroid use. Once the excess cortisol is controlled, some catch-up growth may occur, especially if treated before puberty is complete. It is essential to consider dynamic testing for GH deficiency soon after definitive therapy in all children and adolescents (CYP) in remission from Cushing disease who have not completed linear growth, and closely monitor pubertal progression to identify hypogonadotrophic hypogonadism, as recommended in the consensus guideline 1.

Key considerations in the management of Cushing's syndrome in adolescents include:

• Evaluating for GH deficiency and considering early GH replacement therapy to promote catch-up growth and attain normal adult height 1
• Monitoring for hypogonadotrophic hypogonadism and considering gonadotrophin-releasing hormone analogue therapy to delay puberty and epiphyseal closure 1
• Assessing bone density prior to adult transition in patients at high risk for bone fragility 1
• Using medical therapies, such as metyrapone or ketoconazole, to reduce cortisol levels in preparation for surgery or while awaiting a biochemical response to radiotherapy, while being aware of their potential adverse effects 1.

From the Research

Cushing's Syndrome and Growth in Adolescence

• Cushing's syndrome is characterized by a range of symptoms, including weight gain, hirsutism, obesity, striae, acne, and hypertension 2, 3.
• The most common cause of Cushing's syndrome in children and adolescents is exogenous administration of glucocorticoids 2.
• Linear growth is often severely diminished in patients with Cushing's syndrome, which can be useful in differentiating between childhood obesity and Cushing's syndrome 2.

Growth Patterns in Adolescent Patients with Cushing's Syndrome

• A study analyzing the clinical data of 19 patients with Cushing's syndrome under the age of 18 found that short stature is common in adolescent patients with Cushing's syndrome 4.
• The study found that the disease course of Cushing's syndrome was significantly longer in patients with short stature compared to those without short stature 4.
• However, there is no evidence to suggest that Cushing's syndrome causes a growth spurt in adolescence; instead, it is associated with growth retardation 2, 4.

Treatment and Management of Cushing's Syndrome

• The treatment of choice for Cushing's syndrome remains surgical, with medical therapy used to control hypercortisolaemia prior to surgery or where surgery has failed 5, 6.
• Steroidogenesis inhibitors, such as ketoconazole and metyrapone, can be used to control hypercortisolism in patients with Cushing's syndrome 5, 6.
• However, the management of hypercortisolism with these drugs can be challenging, requiring close monitoring of efficacy and side effects 6.