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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Pediatric Endocrinology

Understanding Familial Glucocorticoid Deficiency

At a Glance

Familial glucocorticoid deficiency is an inherited condition in which a child’s adrenal glands do not respond to the brain’s ACTH signal and make too little cortisol. Daily hydrocortisone, growth monitoring, and a sick-day plan help most children stay healthy and active.

Finding out your child has a rare condition like Familial Glucocorticoid Deficiency (FGD) can be overwhelming. It is a very rare disorder, representing less than 1% of children with primary adrenal insufficiency in some specialist centers [1][2], though exact prevalence estimates vary by population. However, once diagnosed, FGD is a condition that can be managed effectively with daily medication, allowing children to live full, healthy lives [3][4].

The Core Problem: A Communication Breakdown

To understand FGD, it helps to think of the body’s hormone system as a thermostat. Normally, a part of the brain called the pituitary gland monitors your child’s cortisol (the “stress hormone”) levels. When cortisol is low, the brain releases a “signal” hormone called ACTH (Adrenocorticotropic Hormone) to tell the adrenal glands to make more [5].

In children with FGD, the “receiver” on the adrenal glands is broken or missing. Even though the brain is “shouting” for more cortisol by sending out massive amounts of ACTH, the adrenal glands cannot hear the message [5][6].

Because of this communication breakdown:

  • Cortisol levels stay very low, which the body needs for energy, maintaining blood sugar, and responding to illness [7].
  • ACTH levels become extremely high, as the brain keeps trying harder and harder to get a response [6].

Why FGD is Unique

The adrenal glands have different layers that produce different hormones. In most cases of FGD, only the layer that makes cortisol is affected.

The layer that produces mineralocorticoids (such as aldosterone) usually continues to work perfectly [3][6]. Aldosterone helps the body balance salt and water. Because this part of the gland is typically healthy in FGD, children usually do not have the dangerous “salt-wasting” or mineral imbalances (like low sodium or high potassium) seen in other types of adrenal insufficiency [3][8].

Note: In some genetic subtypes, such as those involving the NNT gene, mineralocorticoids might eventually be affected, so doctors will still monitor these levels periodically [9][10].

Genetic Causes

FGD is an inherited condition. While there are several genetic types, two are most common:

  • Type 1 (MC2R): This accounts for about 25% of cases. The mutation affects the ACTH receptor itself—the “ear” of the cell [6][11].
  • Type 2 (MRAP): This accounts for about 15–20% of cases. It affects a protein that helps the ACTH receptor get to the surface of the cell so it can work [6][12].

Knowing the specific genetic type can help your doctor tailor your child’s long-term monitoring, as some types are associated with other minor health considerations as your child grows [13][14].

What to Expect Long-Term

The goal of treatment is simple: to replace the cortisol your child’s body cannot make. This is done with a medication called hydrocortisone, usually taken two or three times a day [6][15].

  • Growth and Development: With proper treatment, children with FGD typically grow at a normal rate. Your doctor will watch their growth closely, as too little medication can slow growth, while too much can cause rapid weight gain or other side effects [16][17].
  • A Healthy Future: If the diagnosis is made early and the medication is taken consistently, the risk of serious complications like hypoglycemia (dangerously low blood sugar) is greatly reduced [18][4]. Most children with FGD have typical neurological development and lead active lives, participating in sports and school just like their peers [4].
  • Lifelong Management: FGD is a lifelong condition. As your child grows, they will learn to manage their own medication and recognize when they need “stress doses” during illness—a process your care team will help you navigate [3][15].

Common questions in this guide

What happens in familial glucocorticoid deficiency?
It is an inherited condition in which the adrenal glands do not respond to ACTH, the signal that normally tells them to make cortisol. Cortisol stays low and ACTH becomes very high. Aldosterone, which helps balance salt and water, usually remains normal.
How is familial glucocorticoid deficiency treated?
Treatment replaces missing cortisol with hydrocortisone, usually taken two or three times a day. Children may need extra stress doses during illness, following an individualized plan from their care team. Do not change the dose without medical instructions.
Can children with FGD grow and develop normally?
With early diagnosis and consistent hydrocortisone treatment, most children with FGD grow at a normal rate and have typical neurologic development. The care team tracks height, weight, and development because too little medication can slow growth and too much can cause rapid weight gain or other side effects. Children can usually take part in school, sports, and other activities.
Does FGD cause low sodium or other salt problems?
Aldosterone production is usually preserved in FGD, so dangerous salt-wasting and mineral imbalances are less typical than in some other forms of adrenal insufficiency. Some genetic types, including NNT-related FGD, can affect mineralocorticoid function over time. Clinicians may check sodium, potassium, and aldosterone periodically.
Which genes are linked to familial glucocorticoid deficiency?
MC2R and MRAP are two common genetic causes of FGD. MC2R affects the ACTH receptor, while MRAP affects a protein that helps the receptor reach the cell surface. Identifying the genetic type can help the care team plan long-term monitoring.
What should we do if a child with FGD becomes sick?
Families should have a written sick-day plan that explains when and how to give extra hydrocortisone and when to seek urgent care. Caregivers, teachers, and school nurses should know the plan and where the emergency injection kit is kept. The child's medical team should demonstrate injection use and provide instructions specific to the child.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How will my child's clinical symptoms, growth, and routine labs guide their hydrocortisone treatment, rather than just trying to target a specific ACTH number?
  2. 2.Which specific gene (such as MC2R or MRAP) is responsible for my child's FGD, and does this change our care plan?
  3. 3.Are my child's sodium, potassium, and aldosterone levels being checked to monitor their mineralocorticoid function?
  4. 4.Does our child's specific genetic type of FGD mean we need to watch for other health issues beyond their adrenal glands?
  5. 5.How will we monitor my child's growth and development to ensure their medication dose is balanced correctly?
  6. 6.Can you provide a written, individualized 'sick day' plan and demonstrate how to use the emergency injection kit?

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

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This page is for informational purposes only and does not constitute medical advice. Your child's pediatric endocrinology team should personalize hydrocortisone doses, sick-day instructions, and monitoring for your child.

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