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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Endocrinology

Symptoms, Mimics, and Getting the Right Diagnosis

At a Glance

Familial glucocorticoid deficiency is suspected when a child has low cortisol with very high ACTH, often alongside hyperpigmentation, low blood sugar, or poor growth. An ACTH stimulation test and tests for related conditions help confirm the diagnosis.

Diagnosing a rare condition like Familial Glucocorticoid Deficiency (FGD) often involves a bit of detective work. Because its symptoms can overlap with other conditions, doctors use specific “biochemical signatures”—patterns in blood tests—to confirm that the adrenal glands are specifically struggling to produce cortisol while evaluating whether other functions remain intact [1][2]. Note: If a child is in a suspected adrenal crisis, emergency treatment must be given immediately and should never be delayed to wait for test results.

Signs That Lead to a Diagnosis

In many cases, the first clue is hyperpigmentation, where a child’s skin looks unusually tanned, even in winter or in areas not exposed to the sun (like the gums or skin folds) [3][4]. This happens because the brain’s “shouting” hormone, ACTH, is so high that it overstimulates the skin’s pigment cells [5].

Other common early signs include:

  • Hypoglycemia (Low Blood Sugar): Cortisol helps maintain blood sugar. Without it, infants may become lethargic, weak, or even have hypoglycemic seizures [3][5].
  • Poor Growth: Infants may struggle with failure to thrive or poor weight gain [6][7].
  • Severe Illness Response: Children may experience severe weakness, vomiting, or lethargy during a routine cold or infection because they lack the cortisol needed to handle physiological stress [4][8].

The Diagnostic Pattern

To confirm FGD, doctors look for a specific pattern in the blood. In a healthy child, cortisol and ACTH balance each other like a see-saw. In FGD, that see-saw is broken.

  1. Paired Cortisol and ACTH: Doctors measure these early in the morning. In classic FGD, the cortisol is inappropriately low, while the ACTH is markedly elevated [2][9]. (Exact numeric thresholds vary by the laboratory assay, age, and clinical situation.)
  2. ACTH Stimulation Test: Used as a confirmatory test, doctors give a synthetic version of ACTH (cosyntropin) and measure how the adrenals respond. In FGD, the adrenal glands typically demonstrate an inadequate cortisol response [10][11].
  3. Checking the Neighbors: The adrenal glands also make aldosterone (a salt-balancing hormone). In “classic” FGD, tests for renin and aldosterone are usually normal, and electrolytes like sodium and potassium stay in the healthy range [1][12].

Differentiating FGD from Mimics

Because other conditions can look like FGD, doctors evaluate specific markers to clarify the diagnosis:

  • Congenital Adrenal Hyperplasia (CAH): This is more common than FGD. Unlike FGD, children with CAH usually have very high levels of a precursor hormone called 17-OHP and may have “salt-wasting” (dangerous salt imbalances) [13]. Note: A normal newborn screen for CAH does not rule out FGD [14], nor does a normal 17-OHP completely exclude every rare form of CAH.
  • Adrenal Hypoplasia Congenita (AHC): This often involves a “salt-wasting” crisis in infancy and can affect puberty later on. Mineralocorticoid deficiency can be variable [15][16].
  • Addison’s Disease: This is an autoimmune condition where the body attacks the adrenals. Doctors check for anti-21-hydroxylase antibodies; a positive result makes an autoimmune cause more likely, but a negative test does not entirely rule it out [17][18].

Typical Pattern in Classic FGD

The table below shows the general pattern seen in classic FGD. Keep in mind that results may change with illness, prior treatment, age, assay type, and the specific genetic subtype. Do not use this table to self-diagnose; always rely on your endocrinologist’s interpretation [19][18].

Test Category What it Checks Typical Pattern in Classic FGD
Glucocorticoid Cortisol & ACTH Low Cortisol / Markedly High ACTH
Mineralocorticoid Renin & Aldosterone Usually Normal (varies by subtype)
Electrolytes Sodium & Potassium Usually Normal (varies by subtype)
Metabolic Blood Glucose May be Low (Hypoglycemia)
Precursors 17-OHP Usually Normal
Autoimmune Adrenal Antibodies Negative

Common questions in this guide

What signs might make a doctor suspect familial glucocorticoid deficiency in a child?
Possible signs include unusually dark skin, low blood sugar, poor growth or weight gain, lethargy, and weakness. Vomiting or marked weakness during an ordinary infection, and seizures related to low blood sugar, can also be warning signs.
What does low cortisol with high ACTH suggest in FGD?
A low cortisol level with a markedly high ACTH level is the typical blood-test pattern in classic FGD. ACTH is the signal hormone that tells the adrenal glands to make cortisol, and an endocrinologist must interpret the results based on the child’s age, illness, treatment, and laboratory method.
How does an ACTH stimulation test help diagnose FGD?
During this test, clinicians give cosyntropin, a synthetic form of ACTH, and measure how much cortisol the adrenal glands produce. An inadequate cortisol rise supports impaired adrenal cortisol production, but the result must be interpreted with the rest of the evaluation.
How do doctors tell FGD apart from CAH, adrenal hypoplasia, or Addison’s disease?
Doctors may compare 17-OHP, electrolytes, renin, aldosterone, and anti-21-hydroxylase antibodies to look for other causes. CAH often has high 17-OHP and dangerous salt loss, while adrenal hypoplasia can also affect salt balance. A positive antibody test makes autoimmune Addison’s disease more likely, but a normal newborn CAH screen does not rule out FGD.
Are aldosterone and electrolytes usually normal in FGD?
In classic FGD, renin, aldosterone, sodium, and potassium are usually in the normal range because mineralocorticoid production is often preserved. Results can vary with the genetic subtype and clinical situation, so ongoing monitoring may be needed.
What should I do if my child may be having an adrenal crisis?
A suspected adrenal crisis requires immediate emergency treatment. Do not wait for blood-test results before getting help, because delaying treatment can be dangerous.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What was my child's exact morning cortisol and ACTH result, and how do they compare to the expected patterns for their age and the lab's assay?
  2. 2.Is my child's 17-OHP result reassuring, and does it help us evaluate the likelihood of Congenital Adrenal Hyperplasia?
  3. 3.How often will we check electrolytes and renin to ensure my child's mineralocorticoid function remains stable?
  4. 4.If the ACTH stimulation test or initial blood work was inconclusive, what is our next step for confirming the diagnosis?
  5. 5.Are there any other specific lab tests we should run based on my child's symptoms or potential genetic subtype?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (19)
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This page explains familial glucocorticoid deficiency symptoms and diagnostic tests for informational purposes only and does not constitute medical advice. A pediatric endocrinologist should interpret your child’s results; suspected adrenal crisis requires immediate emergency care and should not wait for test results.

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