Paediatrics chapters
Cushing syndrome in children
Cortisol excess in childhood: why steroid treatment is the usual cause, how growth failure with weight gain gives it away, which tests prove and localise it, and how each cause is treated and followed up.
- Cushing syndrome is any state of cortisol excess; Cushing disease is the form caused by an ACTH-secreting pituitary adenoma. In children the commonest cause is long-term glucocorticoid treatment.
- Hallmark in a child: weight gain with growth arrest (falling height velocity, delayed bone age), plus moon face, buffalo hump, purple striae, hypertension, plethora, acne, hirsutism.
- Under 7 years endogenous disease is usually adrenal (adenoma or carcinoma); over 7 it is usually ACTH-dependent (Cushing disease). Prove excess with 24-hour urinary cortisol, late-night salivary cortisol, low-dose dexamethasone test, localise with ACTH, high-dose dexamethasone, imaging; treat the cause and cover surgery with steroids.
On this page
Overview
Cushing syndrome is the clinical picture produced by prolonged excess glucocorticoid (cortisol), from any source. Cushing disease is one cause: an ACTH-secreting pituitary adenoma driving both adrenals. In children, exogenous steroids given long term in anti-inflammatory or immunosuppressive doses are by far the commonest cause. Endogenous Cushing syndrome is rare, but it must be recognised because tumours are curable and the effect on growth is severe.
Normal control of cortisol
- Hypothalamic CRH → pituitary ACTH → adrenal cortex (zona fasciculata) → cortisol.
- Cortisol feeds back to suppress CRH and ACTH.
- Cortisol and ACTH are highest in the early morning and lowest around midnight (diurnal rhythm). Loss of this rhythm is an early sign of Cushing syndrome.
Aetiology
| Group | Causes | ACTH level |
|---|---|---|
| ACTH-independent | Iatrogenic glucocorticoids (commonest overall); adrenal adenoma; adrenal carcinoma; nodular adrenal hyperplasia | Low (suppressed) |
| ACTH-dependent | Pituitary ACTH-secreting adenoma (Cushing disease); ectopic ACTH-secreting tumour (lung, bronchus, gut, pancreas); CRH-secreting tumour; iatrogenic ACTH treatment | Normal to high |
Age rule (Akbar): in children under 7 years, endogenous hypercortisolism is most likely from a primary adrenal cause (adenoma or carcinoma); in children over 7 years, it is more likely ACTH-dependent (pituitary Cushing disease).
Cushing disease is ACTH-dependent and typically in older children; an adrenocortical tumour is ACTH-independent and typically in younger children.
Pathophysiology of cortisol excess
| Effect of cortisol | Clinical result |
|---|---|
| Fat redistribution | Truncal obesity, moon face, buffalo hump (dorsocervical fat), supraclavicular pads |
| Protein breakdown | Muscle wasting, proximal weakness, thin skin, purple striae, easy bruising, poor wound healing |
| Growth plate inhibition, reduced GH effect | Growth arrest, delayed bone age, short stature |
| Bone loss, high urinary calcium | Osteoporosis, fractures, renal stones |
| Gluconeogenesis, insulin resistance | Glucose intolerance, diabetes |
| Mineralocorticoid effect at high levels | Salt and water retention, hypertension, oedema, hypokalaemia |
| Immune suppression | Infections; lymphopenia, eosinopenia, neutrophilia |
| Red cell stimulation | Plethora (raised haemoglobin and haematocrit) |
| Adrenal androgens (ACTH-driven or tumour) | Acne, hirsutism, virilisation, menstrual irregularity |
| ACTH excess (pituitary or ectopic) | Hyperpigmentation |
| CNS | Depression, mood change |
Clinical features
- Obesity: generalised in infants; central (truncal) in older children, with moon face and buffalo hump.
- Decreased height velocity: the child becomes short, with delayed bone age.
- Violaceous (purple) striae, plethora, easy bruising.
- Hypertension; oedema.
- Acne, hirsutism, virilisation, menstrual irregularity; puberty may be disturbed.
- Weakness, muscle wasting, osteoporosis.
- Glucose intolerance; frequent infections; poor wound healing.
- Depression, behaviour change.
- Hyperpigmentation when ACTH is high.
The key clue in a child is weight gain together with slowing growth. A child with simple (exogenous) obesity is usually tall for age with advanced bone age; a child with Cushing syndrome is short with delayed bone age.
"Fat and short = cortisol (or thyroid); fat and tall = food."
Investigations
Step 1: confirm cortisol excess (in a child not on steroids)
| Test | Finding in Cushing syndrome |
|---|---|
| 24-hour urinary cortisol excretion | Raised |
| Late-night (midnight) salivary cortisol | Raised; highly sensitive and specific |
| Midnight plasma cortisol | Raised, with loss of diurnal variation (between midnight and 2 am is a sensitive time) |
| Low-dose dexamethasone suppression test (Akbar: 0.5 mg dose) | Cortisol fails to suppress |
Step 2: find the cause
| Test | Pituitary Cushing disease | Adrenal tumour |
|---|---|---|
| Plasma ACTH | Normal to mildly raised | Low (suppressed) |
| High-dose dexamethasone suppression | Suppresses cortisol | No suppression |
| Imaging | MRI pituitary (microadenoma) | CT/MRI adrenals |
- Ectopic ACTH-secreting tumours give a greatly raised ACTH; the CRH stimulation test helps separate pituitary from ectopic sources (Akbar), and chest and abdominal imaging look for the tumour.
- Radionuclide adrenal scanning in difficult cases.
- Supporting blood tests: low potassium and chloride, mild high sodium, hyperglycaemia, neutrophil leucocytosis with lymphopenia and low eosinophils, raised haemoglobin.
- Bone age (delayed), bone density, blood pressure, glucose.
The high-dose dexamethasone test separates pituitary (suppresses) from adrenal tumour (does not suppress) disease; the low-dose test only shows that cortisol excess exists.
Aetiology-specific management
| Cause | Treatment |
|---|---|
| Iatrogenic (steroid therapy) | Use the lowest effective dose and taper slowly; never stop suddenly |
| Adrenal adenoma | Adrenalectomy (treatment of choice) |
| Adrenal carcinoma | Surgical removal if possible (outlook poor) |
| Pituitary adenoma (Cushing disease) | Pituitary surgery (microadenoma excision) or pituitary irradiation; drugs (Akbar: cyproheptadine, bromocriptine) can lower ACTH |
| Ectopic ACTH tumour | Remove the tumour |
| Adrenal hyperplasia | Partial or rarely bilateral adrenalectomy to control symptoms |
Peri-operative care
- After removal of a cortisol-producing tumour, the remaining adrenal tissue is suppressed. Give parenteral glucocorticoid during and after surgery to prevent acute adrenal insufficiency, then taper slowly while the axis recovers.
Stopping long-term steroids safely
- Sudden withdrawal of high-dose steroids is the commonest cause of secondary adrenal insufficiency.
- Akbar: taper quickly down to about physiological replacement (about 10 mg/m2/day of hydrocortisone or equivalent), then taper further over several weeks so the adrenal can recover.
- During this time, extra steroid cover is needed for illness or surgery.
After long-term steroids or removal of an adrenal tumour, an ill child may go into adrenal crisis. Always think of steroid cover.
Complications
- Short adult stature and delayed or disordered puberty.
- Hypertension; diabetes; osteoporosis and fractures; renal stones.
- Serious infections.
- Psychological problems.
- After treatment: adrenal insufficiency, hypopituitarism (especially after pituitary irradiation), tumour recurrence.
Prognosis and follow-up
- Adrenal and pituitary adenomas: good prognosis after complete resection.
- Adrenal carcinoma and ectopic ACTH tumours: poor prognosis.
- Follow-up: height velocity and bone age (catch-up growth may be incomplete), pubertal staging, blood pressure, glucose, bone health, and tests of the adrenal axis; watch for recurrence (repeat cortisol tests) and for other pituitary hormone deficiencies after pituitary treatment.
Expect: iatrogenic steroids as the commonest cause; Cushing disease as pituitary ACTH excess compared with Cushing syndrome as any cortisol excess; the age rule (adrenal cause under 7 years, ACTH-dependent over 7); obesity with growth arrest and delayed bone age as the key sign separating it from simple obesity; moon face, buffalo hump, violaceous striae, plethora, hypertension, acne and hirsutism; 24-hour urinary cortisol, midnight salivary cortisol and low-dose dexamethasone for screening; ACTH and high-dose dexamethasone to localise; hypokalaemia, neutrophilia with lymphopenia and eosinopenia; adrenalectomy for adenoma, pituitary surgery or irradiation for Cushing disease; steroid cover around surgery and slow tapering of long-term steroids.
Quick revision
- Commonest cause: long-term steroid treatment.
- Cushing disease = ACTH-secreting pituitary adenoma (ACTH-dependent).
- Under 7 years: adrenal tumour; over 7: usually Cushing disease.
- Fat and short with delayed bone age; simple obesity = fat and tall.
- Moon face, buffalo hump, purple striae, plethora, hypertension, acne, hirsutism.
- Screen: 24-h urinary cortisol, midnight salivary cortisol, low-dose dexamethasone.
- Localise: ACTH (low in adrenal tumour), high-dose dexamethasone (pituitary suppresses), MRI or CT.
- Low K+, neutrophilia, lymphopenia, low eosinophils.
- Treat cause; steroid cover around surgery; taper steroids slowly.
- Adenoma: good prognosis; carcinoma: poor.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
What is the difference between Cushing syndrome and Cushing disease?
Cushing syndrome is any state of cortisol excess; Cushing disease is the specific form caused by an ACTH-secreting pituitary adenoma that drives both adrenal glands.
How do I tell Cushing syndrome from ordinary obesity in a child?
Children with simple obesity tend to be tall with advanced bone age; children with cortisol excess are short with slowing growth and delayed bone age.
Which test separates pituitary from adrenal causes?
Plasma ACTH (low with an adrenal tumour, normal or high with pituitary disease) and the high-dose dexamethasone test, which suppresses cortisol in pituitary disease but not with adrenal tumours.
Why do children need steroid cover after adrenal tumour surgery?
The opposite adrenal has been suppressed by months of high cortisol, so without replacement the child can develop acute adrenal insufficiency.