Endocrine Biochemistry: Cushing Syndrome in Children

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Questions and Answers

What is Cushing syndrome?

A condition that happens when there is too much cortisol in the body.

What hormone is primarily associated with Cushing syndrome?

Adrenaline

ACTH

Cortisol (correct)

Insulin

Cushing syndrome in children is common.

False

What is the estimated incidence of Cushing disease in children per year?

One to two cases per million children. Signup and view all the answers

What is the most frequent cause of endogenous Cushing syndrome in children?

ACTH overproduction from pituitary adenomas Signup and view all the answers

What is the main role of cortisol in the body?

To regulate the body's stress response. Signup and view all the answers

Cushing syndrome represents about _ to _ percent of all cases of endogenous Cushing syndrome.

five to ten Signup and view all the answers

At what age does Cushing disease reportedly occur in children?

7 years and older Signup and view all the answers

What are the two types of endogenous Cushing syndrome?

ACTH-dependent and ACTH-independent. Signup and view all the answers

What is the primary challenge in diagnosing Cushing syndrome in patients?

Symptoms have a slow onset, complicating early diagnosis. Signup and view all the answers

Which factor is most significantly associated with ACTH-dependent Cushing syndrome?

ACTH-secreting pituitary microadenoma Signup and view all the answers

Which of the following conditions is considered a differential diagnosis for adolescents presenting with symptoms of Cushing syndrome?

Neuroendocrine tumors Signup and view all the answers

In treating Cushing syndrome, which of the following is commonly used as a treatment approach for non-endocrine diseases?

Corticosteroids Signup and view all the answers

What is a distinguishing feature of ACTH-independent Cushing syndrome in infants?

Caused by unilateral or bilateral adrenal factors. Signup and view all the answers

What anomaly is present in adolescent patients with ectopic Cushing syndrome (ECS)?

Presence of ACTH-secreting neuroendocrine tumors. Signup and view all the answers

Which of the following best describes the incidence of endogenous Cushing syndrome in pediatric patients?

Rare but significant in the presence of pituitary adenomas. Signup and view all the answers

What is a common symptom that could indicate the presence of Cushing syndrome?

Increased hair growth and virilization. Signup and view all the answers

Which diagnostic method is commonly used as an initial step for diagnosing Cushing syndrome?

24-hour urinary free cortisol (UFC) test Signup and view all the answers

What factor can cause a falsely high result in a 24-hour urinary free cortisol test?

Malnutrition Signup and view all the answers

What is the advantage of using midnight serum cortisol tests in diagnosing Cushing syndrome?

It identifies loss of normal diurnal variation in cortisol levels. Signup and view all the answers

Which method is preferred for analyzing urine samples in the diagnosis of Cushing syndrome?

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) Signup and view all the answers

What limitation might affect the collection of urine samples for the 24-hour urinary free cortisol test?

Difficulties due to patient compliance. Signup and view all the answers

What is the main purpose of the dexamethasone suppression test (DST) in evaluating Cushing syndrome?

To suppress normal cortisol response. Signup and view all the answers

What non-invasive method is used to test cortisol levels outside of a clinical environment?

Salivary cortisol test Signup and view all the answers

Which of the following is NOT a potential issue with obtaining reliable 24-hour urinary free cortisol results?

Low exercise levels Signup and view all the answers

What is the significance of a serum cortisol level of ≥20 µg/dL in relation to Cushing syndrome?

It has 99% sensitivity and 100% specificity for diagnosing Cushing syndrome. Signup and view all the answers

Which diagnostic test is characterized by a failure of serum cortisol to decrease to 3 after administration?

Low-dose dexamethasone suppression test (DST) Signup and view all the answers

What is the recommended first-line treatment for all types of Cushing syndrome?

Surgical interventions Signup and view all the answers

What is the success rate for transsphenoidal resection of pituitary tumors in treating Cushing disease?

Greater than 90% Signup and view all the answers

What complication is NOT typically associated with surgical intervention for Cushing syndrome?

Thyroid dysfunction Signup and view all the answers

How does the success rate of transsphenoidal surgery change over time after the initial procedure?

It decreases to approximately 60% Signup and view all the answers

What is the implication of a saliva cortisol level greater than 0.13 µg/dL?

It is highly indicative of Cushing syndrome. Signup and view all the answers

What does an increased observation after stimulation in the low-dose DST suggest?

It confirms the presence of hypercortisolism. Signup and view all the answers

Study Notes

Background

Cushing syndrome in children, also called hypercortisolism, results from excessive cortisol hormone production.
Cortisol, synthesized from cholesterol, is mainly produced by the zona fasciculata of the adrenal cortex and serves as the primary stress hormone.
Plays a vital role in the stress response, aiding in gluconeogenesis, tissue repair, regulation of blood pressure, and inflammation reduction.
Overproduction of cortisol can disrupt puberty and lead to symptoms like growth deceleration, weight gain, and facial plethora.

Epidemiology

Cushing syndrome is rare in the pediatric population, accounting for 5-10% of all endogenous Cushing syndrome cases.
Incidence of Cushing disease, driven by ACTH-secreting pituitary adenomas, is estimated at 1-2 cases per million children annually.
Most affected children are aged 5-15, with a slight female predominance.
Pediatric cases present distinct characteristics compared to adults; primarily, ACTH overproduction from pituitary adenomas is the most common cause.
Cortisol action occurs through the glucocorticoid receptor (GR), which regulates genes related to metabolism and immune function when bound by cortisol.
ACTH production is controlled by corticotropin-releasing hormone (CRH) from the hypothalamus, with pituitary adenomas causing excessive ACTH and subsequent cortisol overproduction.
Genetic mutations may play a role in Cushing syndrome, particularly in familial syndromes like multiple endocrine neoplasia (MEN) and Carney complex.

Etiology

Both endogenous and exogenous types of Cushing syndrome are uncommon in pediatric patients, with a roughly even distribution between genders.
Exogenous or iatrogenic causes, largely due to chronic glucocorticoid or ACTH administration, are the more prevalent triggers.
Pediatric cases of endogenous Cushing syndrome stem from pituitary adenomas (Cushing disease), adrenal tumors, or ectopic ACTH production.
Endogenous Cushing syndrome can be categorized into:
- ACTH-dependent: Primarily due to Cushing disease from ACTH-secreting pituitary microadenoma, typically occurs in children aged 7 and older.
- ACTH-independent: Often the cause in infants, associated with adrenal gland issues.

Diagnosis of Cushing Syndrome

Salivary cortisol is typically measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for accuracy in detecting small changes.
Serum cortisol levels ≥20 µg/dL indicate Cushing syndrome, boasting 99% sensitivity and 100% specificity.
Salivary levels >0.13 µg/dL are indicative of Cushing syndrome due to abnormalities.
Low-dose overnight dexamethasone suppression test (DST) assesses serum cortisol failure to decrease to 3, suggesting pituitary ACTH secretion.
Initial sensitivity of the DST is lower than in adults, but stimulation increases its diagnostic efficacy.

Treatment and Intervention

Surgical intervention is the first-line treatment for all types of Cushing syndrome.
For pediatric patients, transsphenoidal resection of pituitary tumors (TSS) is preferred, with a success rate of over 90%.
Success rates of TSS decrease over time, approximately to 60%, with potential complications including infection, growth hormone deficiency, and hypogonadism.
Mortality rates within the Cushing syndrome population are low.

Initial Diagnosis in Children

Accurate classification of Cushing syndrome is vital for effective treatment.
Evaluation of physical development and medical history informs diagnosis.
Hypercortisolism is documented through:
- 24-hour urinary free cortisol (UFC)
- Midnight cortisol tests (serum or saliva)
- Dexamethasone suppression test (DST)
24-hour UFC tests are usually performed at least two to three consecutive times for accuracy but are hampered by difficulties in urine collection.
Urine samples are analyzed using LC-MS/MS for their accuracy and ability to minimize interference from medications.

Hormonal Testing

Midnight serum/salivary cortisol tests evaluate diurnal variations and are obtained through non-invasive methods for saliva and intravenous blood draws for serum.
Serum cortisol is analyzed using immunoassays like chemiluminescent immunoassay (CLIA) or enzyme-linked immunosorbent assay (ELISA) for high specificity and sensitivity.

Causative Factors and Types

Common causes of Cushing syndrome include exogenous factors like chronic glucocorticoid administration or ACTH-related disorders.
Endogenous Cushing syndrome can be subdivided into ACTH-dependent and ACTH-independent types:
- ACTH-dependent typically refers to Cushing disease characterized by overproduction of ACTH due to pituitary microadenomas, prevalent in children ≥7 years old.
- ACTH-independent variations usually arise from adrenal factors in infants, presenting challenges in diagnosis and treatment due to gradual onset.

Ectopic Cushing Syndrome

Ectopic Cushing syndrome is rare in adolescents, mainly due to ACTH overproduction from neuroendocrine tumors like bronchial carcinoids or thymic tumors.
Accurate diagnosis often requires ruling out ECS sources to avoid misleading conclusions related to CRH-induced ACTH oversecretion.

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Description

This quiz focuses on Cushing syndrome in children, a critical topic in endocrine biochemistry. It examines the causes, symptoms, diagnosis, and treatment associated with this condition. Students will deepen their understanding of endocrine disorders within the context of children's health.