cortisone reductase deficiency 1

Cortisone Reductase Deficiency: A Rare Disorder

Cortisone reductase deficiency (CRD) is a rare disorder characterized by the inability to regenerate active glucocorticoid cortisol from cortisone due to a failure of the enzyme cortisone reductase. This leads to increased adrenocorticotropic hormone stimulation of the adrenal gland, resulting in hyperandrogenism [1].

Symptoms and Clinical Features

The clinical features of CRD include:

• Hyperandrogenism, leading to hirsutism (excessive hair growth) in females
• Oligo-amenorrhea (infrequent or absent menstrual periods)
• Infertility in females
• Premature pseudopuberty in males [5]

Causes and Genetics

CRD is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme, also known as cortisone reductase. This enzyme plays a crucial role in regenerating active glucocorticoid cortisol from cortisone [4].

Other Relevant Information

• CRD is a rare disorder with close phenotypic similarities to other abnormalities of cortisone metabolism [8].
• The deficiency of cortisone reductase leads to activation of the Hypothalamic-pituitary-adrenal axis, resulting in hyperandrogenism [7].

References

[1] Failure of cortisone reductase results in increased adrenocorticotropic hormone stimulation of the adrenal gland. [4] Dysregulation of 11β-hydroxysteroid dehydrogenase type 1 enzyme causes CRD. [5] Clinical features include hyperandrogenism, oligo-amenorrhea, and infertility in females, and premature pseudopuberty in males. [7] Activation of the Hypothalamic-pituitary-adrenal axis results in hyperandrogenism. [8] Close phenotypic similarities between cortisone reductase deficiency and other abnormalities of cortisone metabolism.

Hyperandrogenism due to Cortisone Reductase Deficiency

Cortisone reductase deficiency (CRD) is a rare genetic disorder characterized by the inability to regenerate cortisol from cortisone. This leads to an overproduction of androgens, resulting in various signs and symptoms.

• Hyperandrogenism: One of the primary symptoms of CRD is hyperandrogenism, which manifests as excessive hair growth on the face, chest, and back (in males) and acne, hirsutism, and male pattern baldness (in females).
• Precocious Pseudopuberty: In males, CRD can cause precocious pseudopuberty, characterized by early onset of puberty symptoms such as rapid growth, deepening voice, and development of secondary sexual characteristics.
• Increased Adrenocorticotropic Hormone (ACTH) Stimulation: The deficiency in cortisol regeneration stimulates the hypothalamic-pituitary-adrenal axis, leading to increased ACTH production. This, in turn, causes the adrenal gland to produce more androgens, exacerbating hyperandrogenism.
• Other Features: In addition to hyperandrogenism, individuals with CRD may also experience other symptoms such as:
  • Recurrent infections due to impaired immune function [8]
  • Skin coloring darker than that of other family members [8]

These signs and symptoms are a result of the body's inability to regulate cortisol levels properly, leading to an imbalance in hormone production.

References:

[1] Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females ...

[3] One of the symptoms of cortisone reductase deficiency is hyperandrogenism, resulting from activation of the Hypothalamic–pituitary–adrenal axis.

[4] The condition is characterized by hyperandrogenism as a result of increased adrenocorticotropic hormone stimulation of the adrenal gland due to failure of ...

[7] Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females ...

[10] Cortisone reductase deficiency (CRD) is characterized by a failure to regenerate cortisol from cortisone via 11beta-hydroxysteroid dehydrogenase type 1 ...

Diagnostic Tests for Cortisone Reductase Deficiency 1

Cortisone reductase deficiency 1 (CRD1) is a rare genetic disorder that affects the conversion of cortisone to cortisol. Diagnosing CRD1 can be challenging, but several diagnostic tests can help confirm the condition.

• Gas Chromatography/Mass Spectrometry: This test can identify steroid biomarkers that correlate with CRD1 in each case [7].
• Biochemical Diagnosis: Elevated levels of cortisone and decreased levels of cortisol can indicate CRD1. Additionally, increased adrenocorticotropic hormone (ACTH) stimulation of the adrenal gland due to failure of cortisol production can lead to hyperandrogenism [2, 5, 6].
• Genetic Analysis: A homozygous or compound heterozygous mutation in the H6PD gene (138090) on chromosome 1p36 can confirm CRD1 [13].
• Postoperative Urinary Steroid Analysis: This test can show decreased levels of cortisol and increased levels of cortisone after surgical removal of cystic teratomas, indicating CRD1 [13].

Specialist Referrals

If you suspect that someone has cortisone reductase deficiency 1, it is essential to consult a specialist. A pediatrician or an endocrinologist can help diagnose and manage the condition.

• Pediatrician: A pediatrician can evaluate the child's overall health and refer them to a specialist if necessary.
• Endocrinologist: An endocrinologist specializes in hormone-related disorders, including CRD1. They can perform diagnostic tests, interpret results, and develop a treatment plan.

Diagnostic Tests for Children

For children who are referred for investigation of Cushing syndrome, the following diagnostic tests may be performed:

• Diagnostic tests for children who are referred for the investigation of Cushing syndrome: These tests include gas chromatography/mass spectrometry, biochemical diagnosis, genetic analysis, and postoperative urinary steroid analysis [11].

It is essential to consult a specialist for accurate diagnosis and management of cortisone reductase deficiency 1.

Treatment Options for Cortisone Reductase Deficiency

Cortisone reductase deficiency (CRD) is a rare disorder that affects the body's ability to convert cortisone into cortisol, leading to an overproduction of androgens. While there are no specific treatments available for CRD, various medications can help manage its symptoms.

• Antiandrogens: These medications can help reduce androgen levels in the body, thereby alleviating symptoms such as hirsutism (excessive hair growth) and acne [3].
• Dexamethasone: This corticosteroid has been used to treat CRD by suppressing androgen production. A study found that treatment with dexamethasone resulted in significant androgen suppression [4].

It's essential to note that these treatments should only be administered under the guidance of a qualified healthcare professional, as they can have various side effects and interact with other medications.

References:

• [3] Treatment of hyperandrogenism can be done through prescription of antiandrogens.
• [4] by EM Małunowicz · 2003 · Cited by 30 — Treatment with dexamethasone (0.375 mg/daily) resulted in androgen suppression.

Cortisone reductase deficiency (CRD) can be challenging to diagnose, and a differential diagnosis is essential to rule out other conditions that may present with similar symptoms. Here are some key points to consider:

• Polycystic Ovary Syndrome (PCOS): CRD has been linked to PCOS in some studies [7]. Both conditions share similar hormonal profiles, including hyperandrogenism and insulin resistance.
• Adrenal Hyperplasia: This condition can also present with hyperandrogenism and may be considered in the differential diagnosis of CRD [9].
• 11β-Hydroxysteroid Dehydrogenase Type 1 (11βHSD1) Deficiency: A deficiency in this enzyme can lead to decreased cortisol production, resulting in symptoms similar to those seen in CRD [8].
• Hyperandrogenism: This condition is characterized by excessive androgen production and may be a presenting feature of CRD. However, it can also occur in other conditions such as PCOS or adrenal hyperplasia.
• Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: The HPA axis plays a crucial role in regulating cortisol production. Any disruption to this axis can lead to symptoms similar to those seen in CRD.

To differentiate CRD from these conditions, clinicians may consider the following:

• Genetic testing: Genetic mutations in the HSD11B1 gene have been identified as a cause of true cortisone reductase deficiency (CRD) [9].
• Biochemical markers: Measuring cortisol and androgen levels can help differentiate CRD from other conditions.
• Clinical presentation: The age of onset, severity of symptoms, and presence of other associated features can also aid in differential diagnosis.

It's essential to note that a comprehensive diagnostic workup is necessary to accurately diagnose cortisone reductase deficiency. A multidisciplinary approach involving endocrinologists, geneticists, and other specialists may be required to provide an accurate diagnosis and develop an effective treatment plan.

References:

[7] Draper N. Cortisone reductase deficiency: a form of PCOS? [Cited by 483]

[8] Lavery GG. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). [Cited by 42]

[9] Auchus RJ. HEXOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY (APPARENT CORTISONE REDUCTASE DEFICIENCY) [Clinical presentation, Hormonal criteria for diagnosis]