What is the congenital adrenogenital disorder with enzyme deficiency associated with thrombosis (blood clot)?

From the Guidelines

Congenital adrenal hyperplasia (CAH) with 21-hydroxylase deficiency is the congenital adrenogenital disorder associated with an increased risk of thrombosis (blood clot). This condition disrupts cortisol production, leading to excess androgen production, which can create a hypercoagulable state and increase the risk of blood clots. The management of CAH involves glucocorticoid replacement therapy, typically with hydrocortisone, to suppress excess androgen production and normalize hormone levels 1. Key aspects of management include:

• Glucocorticoid replacement: hydrocortisone 15-25 mg/day in divided doses
• Mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) for salt-wasting forms
• Anticoagulation therapy for patients with blood clots, typically starting with heparin or low molecular weight heparin followed by warfarin or direct oral anticoagulants
• Regular monitoring of hormone levels and coagulation parameters
• Stress dosing of glucocorticoids during illness or surgery to prevent adrenal crisis Although the provided study 1 focuses on the management of adults with congenital heart disease, the underlying principle of managing hormonal imbalances to reduce the risk of thrombosis is relevant to CAH. In the context of CAH, proper hormone replacement is vital for reducing the risk of blood clots and managing the condition effectively. It is essential to note that the connection between CAH and thrombosis relates to hormonal effects on coagulation factors and vascular function, making proper hormone replacement crucial for reducing clotting risk.

From the Research

Congenital Adrenogenital Disorder with Enzyme Deficiency

• The congenital adrenogenital disorder with enzyme deficiency associated with various clinical manifestations is Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency 2, 3, 4, 5.

Enzyme Deficiency and Clinical Forms

• The deficiency of the enzyme 21-hydroxylase is responsible for about 90% to 95% of all cases of CAH 2, 4, 5.
• CAH can be presented in two clinical forms: classic and non-classic (or late-onset) 2, 3, 4, 5.

Clinical Manifestations

• The classic form is further subdivided into salt-wasting and simple virilizing forms, with the former being potentially life-threatening if not recognized and treated promptly 2, 3, 5.
• The non-classic form may present with precocious pubarche, polycystic ovaries, hirsutism, oligoamenorrhea, acne, and infertility 4, 5.

Diagnosis and Treatment

• Diagnosis of CAH is made by clinical, biochemical, and molecular genetic evaluation, including measurement of 17-hydroxyprogesterone (17-OHP) levels and adrenocorticotropic hormone (ACTH) stimulation tests 3, 5.
• Treatment of CAH involves lifelong hormonal replacement, with glucocorticoids and mineralocorticoids being administered to prevent salt-wasting crises and reduce excessive corticotropin 2, 3.

Thrombosis Association

• However, there is no direct evidence in the provided studies that links Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency with an increased risk of thrombosis (blood clot) 2, 3, 4, 5, 6.