18-Hydroxycorticosterone

Adrenal disorders are complex conditions that can have significant impacts on health and well-being.  Understanding the role of biomarkers in assessing adrenal function is crucial for accurate diagnosis and effective management of these disorders. 

18-Hydroxycorticosterone is a minor steroid hormone produced in the adrenal cortex that primarily acts as an intermediate in the synthesis of aldosterone, a key regulator of blood pressure and electrolyte balance. 

Measurement of 18-hydroxycorticosterone levels can provide insights into adrenal function, particularly in evaluating the aldosterone synthesis pathway.  Testing for this hormone is often used in diagnosing disorders of adrenal hormone production such as primary hyperaldosteronism or adrenal insufficiency.

In this comprehensive article, we delve into the significance of 18-Hydroxycorticosterone as a biomarker in adrenal physiology and pathology. 

What is 18-Hydroxycorticosterone?

18-Hydroxycorticosterone, also known as 18-OH-B, is a steroid hormone derived from the zona glomerulosa of the adrenal cortex. Structurally it belongs to the corticosterone group and is a precursor to aldosterone, a hormone vital for regulating electrolyte balance and blood pressure.

18-Hydroxycorticosterone is synthesized from progesterone through a series of enzymatic reactions within the adrenal glands.  Progesterone is synthesized from pregnenolone, which is then converted to 11-deoxycorticosterone, then into corticosterone.  [6.] 

Corticosterone is converted to 18-hydroxycorticosterone by the enzyme CYP11B2, a member of the CYP 450 enzyme family that is also known as aldosterone synthase.   [4., 8.]

This process is tightly regulated by various enzymes and hormonal signals to ensure adequate production of mineralocorticoids.

While 18-Hydroxycorticosterone (18OHB) has minimal biological activity, higher levels may indicate increased mineralocorticoid action.  [7.]  Produced by the aldosterone synthase enzyme from corticosterone, 18OHB has a low affinity for mineralocorticoid receptors, suggesting limited direct effects on mineral balance. 

Although it mainly serves as an intermediate in aldosterone production, elevated levels of 18OHB can be indicative of increased aldosterone synthesis, useful in the differential diagnosis of conditions like aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) in primary aldosteronism.  [7.] 

18-Hydroxycorticosterone and Aldosterone-Producing Adenoma (APA) and Bilateral Adrenal Hyperplasia (BAH) in Primary Aldosteronism  [2., 3., 5., 9.]

Primary aldosteronism (PA) is marked by the autonomous secretion of aldosterone and leads to hypertension and hypokalemia.  Diagnosing PA involves differentiating between unilateral adrenal adenoma and bilateral adrenal hyperplasia, which can be challenging. 

Primary aldosteronism typically presents with hypertension and may include hypokalemia, though most patients do not show this symptom. It stems mainly from aldosterone-producing adenomas or bilateral adrenal hyperplasia. 

Diagnosed by a high morning aldosterone-to-renin ratio, treatment options include adrenalectomy for unilateral cases or medical management with mineralocorticoid antagonists for bilateral conditions. 

The precursor steroid 18-hydroxycorticosterone (18-OHB) plays a crucial role in aldosterone synthesis, and it may aid in the differentiation of PA due to unilateral adrenal adenoma vs. bilateral adrenal hyperplasia.  Elevated 18-OHB levels are typically seen in patients with adrenal adenomas, significantly higher compared to those with hyperplasia. 

Assays have established a cutoff of 100 ng/dL after overnight recumbency to indicate an adenoma, with no overlap of values between the two conditions. However, the precise discrimination between these PA subtypes still requires additional biochemical markers, as 18-OHB levels alone do not provide a definitive differentiation. 

This distinction is crucial because the treatment strategies for adenomas and hyperplasia differ significantly, impacting clinical outcomes.

Laboratory Testing for 18-Hydroxycorticosterone

Test Information, Sample Collection and Preparation

Laboratory testing for 18-Hydroxycorticosterone involves the measurement of its levels in biological samples, typically serum or plasma.  Blood samples for 18-Hydroxycorticosterone testing are usually collected via venipuncture.  

Timing of sample collection may vary depending on the specific clinical indication, with fasting samples often preferred for certain tests to minimize potential interference from dietary factors.  

Interpretation of Test Results

Reference Range for 18-Hydroxycorticosterone

Many factors can affect the test results, including the patient’s age, fasting status, and positioning.  It is essential to refer to the laboratory reference ranges reported.  One lab reports reference ranges for 18-hydroxycorticosterone as:  [1.] 

Adults: 9−58 ng/dL

8:00 AM Supine: 4-21 ng/dL

8 AM Supine Upright: 5−46 ng/dL

Clinical Significance of Elevated 18-Hydroxycorticosterone Levels

Elevated 18-hydroxycortisone levels may indicate primary aldosteronism, which requires additional workup, particularly if the patient is symptomatic with high blood pressure and low potassium.  

Clinical Significance of Low 18-Hydroxycorticosterone Levels

Low 18-Hydroxycorticosterone levels are not known to be clinically significant.  While hypoaldosteronism is a recognized clinical condition, low 18-hydroxycorticosterone levels are not typically considered part of the pathophysiology.  [10.] 

Laboratory Testing for Related Biomarkers

Aldosterone

Aldosterone, a key mineralocorticoid hormone synthesized in the adrenal cortex, plays a crucial role in regulating electrolyte balance, blood pressure, and fluid homeostasis. 

Elevated aldosterone levels may indicate primary aldosteronism, whereas low levels may suggest hypoaldosteronism or aldosterone deficiency.

Renin

Renin, an enzyme produced by the kidneys, plays a central role in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and electrolyte balance.  Laboratory assessment of renin activity or concentration provides valuable information about the activity of the RAAS pathway. 

Elevated renin levels may suggest secondary hyperaldosteronism due to conditions such as renal artery stenosis or volume depletion, whereas low renin levels may indicate primary aldosteronism or autonomous aldosterone production.

Cortisol

Cortisol, a glucocorticoid hormone synthesized in the adrenal cortex, plays a crucial role in metabolism, immune function, and stress response.  Laboratory testing for cortisol involves measuring its levels in blood, saliva, or urine samples.  

Abnormal cortisol levels may indicate conditions such as Cushing's syndrome (excess cortisol production) or Addison's disease (adrenal insufficiency).  Understanding cortisol levels alongside 18-Hydroxycorticosterone provides comprehensive insights into adrenal function and HPA axis activity.

Dehydroepiandrosterone (DHEA)

Dehydroepiandrosterone (DHEA) and its sulfate form (DHEA-S) are adrenal androgen precursors with roles in hormone synthesis and metabolism.  Laboratory testing for DHEA or DHEA-S levels can provide additional information about adrenal androgen production and function. 

Abnormal DHEA levels may be associated with conditions such as adrenal insufficiency, adrenal tumors, or polycystic ovary syndrome (PCOS).

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