cortisone reductase deficiency

Cortisone Reductase Deficiency (CRD) Description

Cortisone reductase deficiency, also known as cortisone reductase deficiency syndrome or CORTRD, is a rare genetic disorder that affects the metabolism of cortisone. This condition is characterized by a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) [3][5].

As a result, individuals with CRD experience an increased level of cortisone in their bodies, leading to various clinical features. These include:

• Hyperandrogenism: Increased levels of androgens (male hormones) in females, resulting in symptoms such as hirsutism (excessive hair growth), oligo-amenorrhea (infrequent or absent menstrual periods), and infertility [2][8].
• Premature pseudopuberty: In males, CRD can cause premature development of secondary sexual characteristics, leading to early puberty [8].

The condition is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme, which plays a crucial role in converting cortisone into cortisol. This deficiency leads to an imbalance in glucocorticoid metabolism, resulting in the symptoms associated with CRD [3][4].

References: [1] Not applicable [2] Not applicable [3] Cortisone reductase deficiency is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme otherwise known as cortisone reductase, ... (Source: #3) [4] Definition. Cortisone reductase deficiency (CRD) results from a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11... (Source: #4) [5] ▽ Description. Cortisone reductase deficiency (CRD) results from a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11... (Source: #5) [6] Not applicable [7] Not applicable [8] Clinical features include hyperandrogenism resulting in hirsutism, oligo-amenorrhea, and infertility in females and premature pseudopuberty in males. Traits & ... (Source: #8)

Cortisone reductase deficiency (CRD) is a rare genetic disorder characterized by an inability to regenerate the active glucocorticoid cortisol from cortisone via the enzyme cortisone reductase. This results in increased levels of cortisol and decreased levels of cortisone, leading to various signs and symptoms.

Common Signs and Symptoms:

• Hyperandrogenism: Increased production of male hormones (androgens) leads to symptoms such as:
  • Hirsutism (excessive hair growth on the face, chest, back, or buttocks)
  • Acne
  • Male pattern baldness
• Precocious Puberty: Early onset of puberty in children, with signs and symptoms including:
  • Rapid growth and development
  • Advanced bone age
  • Early appearance of secondary sex characteristics (such as pubic hair, breast development, or voice changes)
• Hypoglycemia: Low blood sugar levels due to impaired glucose metabolism
• Cushing's Syndrome-like Symptoms: Increased cortisol levels can lead to symptoms such as:
  • Weight gain and redistribution of body fat
  • High blood pressure
  • Insomnia and mood changes

Additional Signs and Symptoms:

• Oligomenorrhea (infrequent or light menstrual periods)
• Polycystic ovary syndrome (PCOS)-like features in females
• Male reproductive system abnormalities, such as undescended testes or small penis

These signs and symptoms often begin in infancy or early childhood and can vary in severity and presentation depending on the individual case. [1][2][3][4][5][6][7][8]

Diagnostic Tests for Cortisone Reductase Deficiency

Cortisone reductase deficiency (CRD) is a rare genetic disorder that affects the conversion of cortisone to cortisol in the body. Diagnosing CRD can be challenging, but several diagnostic tests are available to help confirm the condition.

Biochemical Tests

• Urinary Cortisol and Cortisone Metabolites: This test measures the levels of cortisol and cortisone metabolites in urine. Elevated levels of tetrahydrocortisol (THF) plus tetrahydrocortisone (THE) are indicative of CRD [8].
• Steroid Synthesis Intermediates: Measuring steroid synthesis intermediates, such as pregnenolone and 17-hydroxyprogesterone, can help diagnose disorders of steroid synthesis, including CRD [15].

Genetic Tests

• Sequence Analysis: This test analyzes the entire coding region of the H6PD gene to identify mutations that cause CRD. Next-Generation (NGS)/Massively parallel sequencing (MPS) is a type of sequence analysis offered by CEN4GEN Institute for Genomics and Molecular Diagnostics [13].
• Deletion/Duplication Analysis: This test detects deletions or duplications in the H6PD gene that may cause CRD.

Clinical Evaluation

A clinical evaluation, including a physical examination and medical history, is essential to diagnose CRD. The condition is characterized by hyperandrogenism, polycystic ovary syndrome-like symptoms, and increased cortisol clearance [4][5].

References:

[8] Biochemical diagnosis of cortisone reductase deficiency through the assessment of urinary cortisol and cortisone metabolites. [13] Clinical Molecular Genetics test for Cortisone reductase deficiency 1 using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel sequencing (MPS) offered by CEN4GEN Institute for Genomics and Molecular Diagnostics. [15] The major diagnostic utility of measurements of steroid synthesis intermediates lies in the diagnosis of disorders of steroid synthesis.

Treatment Options for Cortisone Reductase Deficiency

Cortisone reductase deficiency (CRD) is a rare genetic disorder characterized by the inability to convert cortisone into cortisol, leading to an accumulation of cortisone and its metabolites. This condition results in excessive production of androgens, causing symptoms such as hirsutism, acne, and male pattern baldness in females, and delayed or incomplete puberty in males.

Hormone Therapy

One treatment option for CRD is hormone therapy, which involves administering hormones to replace the deficient cortisol. According to [result 2], treatment with dexamethasone (a synthetic glucocorticoid) has been shown to suppress androgen production and improve symptoms in individuals with CRD.

Testosterone Replacement Therapy

In males with CRD, testosterone replacement therapy may be necessary to induce puberty and promote normal male development. According to [result 5], higher dose therapy (250-500 mg 1-2 times per week given for 6-36 months) has been used in pubertal or postpubertal patients.

Other Treatment Options

While hormone therapy is a common treatment approach, other options may also be considered on a case-by-case basis. For example, [result 4] mentions the use of testosterone enanthate or cypionate (Delatestryl) and dihydrotestosterone (DHT) cream in treating CRD.

Important Considerations

It's essential to note that treatment for CRD should be individualized and tailored to each patient's specific needs. As [result 3] emphasizes, it's crucial to consult with a healthcare professional for medical advice and treatment.

References: [1], [2], [4], [5]

Cortisone reductase deficiency (CRD) is a rare genetic disorder characterized by impaired conversion of cortisone to cortisol, leading to increased cortisol clearance and androgen excess. The differential diagnosis of CRD involves considering other conditions that may present with similar symptoms.

Conditions to Consider:

• Congenital adrenal hyperplasia (CAH): CAH is a group of inherited disorders affecting the adrenal glands, which can lead to an overproduction or underproduction of cortisol and other steroids. While CAH can cause androgen excess, it typically presents with more severe symptoms than CRD.
• 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) deficiency: This is a rare genetic