Adrenal Hypoplasia Congenita - Causes, Symptoms, Diagnosis, and Treatment

What Is Adrenal Hypoplasia Congenita?

Adrenal hypoplasia congenita is an X-linked disorder that mainly affects males by causing adrenal insufficiency. Adrenal insufficiency usually starts in infancy or childhood and can lead to vomiting, feeding problems, decreased blood sugar levels (hypoglycemia), dehydration, and shock. If left untreated, these complications can often become life-threatening.

Also, the affected males may depict decreased male sex hormones, which causes underdeveloped reproductive tissues, cryptorchidism, delay in puberty, and infertility. Altogether, it is called hypogonadotropic hypogonadism.

What Is the Prevalence Rate of Adrenal Hypoplasia Congenita?

X-linked adrenal hypoplasia congenita is a rare condition. The exact prevalence of this condition is still unknown. Literature shows that this condition can affect approximately 1 in 12,500 newborns.

What Causes Adrenal Hypoplasia Congenita?

The cause of congenital X-linked adrenal hypoplasia is mutations in the NR0B1 gene, which helps provide instructions to produce a protein called DAX1. The function of the produced protein is mainly observed in the development and functioning of several hormone-producing tissues like the adrenal glands, the hypothalamus and pituitary, and ovaries in females and testes in males. The hormones these glands produce help control many important functions of the body. The pattern of inheritance of this condition is an X-linked recessive pattern. X-linked disorders most commonly affect males more than females. Also, another interesting characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

What Are the Other Names for Adrenal Hypoplasia Congenita?

This condition is also known as X-linked adrenal hypoplasia congenital or X-linked AHC.

What Are the Signs And Symptoms of Adrenal Hypoplasia Congenita?

Congenital adrenal hypoplasia most commonly occurs in the neonatal period but may be observed only in later childhood. In patients with adrenal hypoplasia secondary to retardation of intrauterine growth, congenital adrenal hypoplasia, metaphyseal dysplasia, and genital anomalies may be observed. The patients may often complain of dehydration, hyperkalemia, hyponatremia, hypotension, or hypoglycemia.

Patients may have hyperpigmentation due to increased serum concentration of adrenocorticotropic hormone (ACTH) and signs of dehydration. Hypotension, neuroglycopenia symptoms, and undescended testes may be observed. Cryptorchidism or hypospadias and hearing loss may be associated with this condition. The small size of the penis may be seen in patients with hypogonadotropic hypogonadism.

What Are the Other Conditions Mimicking Adrenal Hypoplasia Congenita?

Following are the conditions that may mimic congenital adrenal hypoplasia:

• 17-Hydroxylase deficiency syndrome.

• 46, XY sex reversal due to gene mutations SRY, SOX9, WT1 (Denys-Drash Syndrome), and SF1.

• 5-Alpha-Reductase deficiency.

• Addison disease.

• Adrenal crisis.

• Adrenal hemorrhage.

• Adrenal hypoplasia.

• Hyperaldosteronism.

• Hyperkalemia in emergency medicine.

• Hypogonadism.

• Hyponatremia in emergency medicine.

• Smith-Lemli-Opitz syndrome.

• Adrenoleukodystrophy.

• Aldosterone synthase deficiency.

• Allgrove (AAA) syndrome.

• Hypopituitarism (panhypopituitarism).

• Pediatric adrenal insufficiency (addison disease).

• Pseudohypoaldosteronism.

• Renal tubular disorders.

• Bilateral adrenal hemorrhage.

• C-17 Hydroxylase Deficiency.

• Congenital Adrenal Hyperplasia.

• Congenital unresponsiveness to adrenocorticotropic hormone (ACTH).

• Dehydration.

• Denys-Drash Syndrome.

• Familial Glucocorticoid Deficiency.

• Genital Anomalies.

How Can Adrenal Hypoplasia Congenita Be Diagnosed?

When you visit your physician, you will be asked about your signs and symptoms, and then a physical examination is done to check for any physical signs and symptoms. Then, laboratory tests may be required to confirm the diagnosis.

Following tests may be required in cases of adrenal insufficiency:

• Electrolytes.

• Serum cortisol.

• Blood sugar.

• Serum adrenocorticotropic hormone (ACTH).

• Aldosterone.

• Plasma-renin activity.

• High-resolution karyotype.

• 17-hydroxyprogesterone.

A 24-hour or spot urine test is done for sodium, potassium, and creatinine. Random serum cortisol concentrations must be evaluated. Adrenal cortical hormones panel and cosyntropin stimulation tests are also done. The standard ovine corticotropin-releasing hormone (CRH) stimulation test (1 mcg/kg over 1 min) can also be used to rule out other conditions of adrenal insufficiency. Karyotyping, fluorescent in situ hybridization (FISH), and/or microarray analysis can be used to reveal the gene deletion involving DAX1. Also, prenatal diagnosis is available.

Abdominal ultrasonography helps identify adrenal glands in infants due to the large fetal zone. Apart from these, certain imaging studies can be utilized, like CT (computed tomography). But, CT cannot exclude congenital adrenal hypoplasia caused due to a DAX1 deletion in an infant as preservation of the fetal adrenal zone happens in this condition.

How Can Adrenal Hypoplasia Congenita Be Managed?

It can be managed by medical care, surgical care, or a combination.

1) Medical Care:

Patients who have adrenal hypoplasia are usually hypovolemic and may be hypoglycemic. Hence, the initial therapy should involve intravenous normal saline and dextrose. If the patient is hypotensive, a bolus dose of 20 mL/kg of isotonic intravenous fluid must be necessary for the first hour to restore the blood pressure. This can be given repeatedly if the blood pressure remains low.

Glucocorticoids can also be given after obtaining the laboratory values. A cosyntropin stimulation test helps in confirming the diagnosis of adrenocortical insufficiency. Dexamethasone can be given before cosyntropin without interfering with the test results, as low-dose or short-term administration of dexamethasone does not interfere with the cortisol or the cortisol assay response. Another alternative is hydrocortisone, as it has mineralocorticoid activity.

2) Surgical Care:

Surgery is usually not required in the management of congenital adrenal hypoplasia. However, if a patient requires surgery, he or she must be given stress doses of glucocorticoids during the perioperative period. The following recommendations can be followed, although they are empiric rather than based on evidence:

• Administration of 50 to 75 mg/m2 hydrocortisone intramuscularly or intravenously before surgery.

• Manage the patient with additional hydrocortisone during the surgery. This can be done with either a hydrocortisone drip of 2-4 mg/m2/h or an additional bolus of 10 to 25 mg/m2, which is given intravenously every 6 hours throughout the procedure.

• Continuation of hydrocortisone in the immediate postoperative period.

• The hydrocortisone dose can be decreased by 50% each day to a minimum of the patient's usual daily requirement during the second and third postoperative days. Ensure that there are no complications present and that the patient has a good recovery.

• The usual daily doses of steroids can be started on the fourth postoperative day if the patient has a good recovery. If complications are present, stress doses of glucocorticoids must be continued in the patient.

• Fludrocortisone can be given on the day of surgery and when the patient is receiving stress doses of hydrocortisone, as this increased dose should provide ample mineralocorticoid effect.

• During the postoperative period, if the patient cannot take Fludrocortisone by mouth, stress doses of hydrocortisone can be continued for a longer duration to provide adequate mineralocorticoid activity.

Conclusion:

Adrenal hypoplasia congenita is a genetic condition that can be managed with proper medical and surgical care. You can consult a specialist online to know more about this condition through an online medical platform.