LabMed

Secondary or Tertiary Adrenal Insufficiency

At a Glance

Secondary and tertiary adrenal insufficiency may present with nonspecific symptoms of fatigue, weakness, and hypoglycemia. Suspicion of secondary adrenal insufficiency may be raised by a low serum cortisol level or a history of long-term steroid therapy, head trauma, head irradiation, pituitary tumors, pituitary surgery, or other processes that may impair the hypothalamic-pituitary-adrenal axis. Secondary adrenal insufficiency results from decreased levels of adrenocorticotropin (ACTH).

Usually, production of aldosterone is partially preserved because its primary regulation is by angiotensin and potassium levels. Therefore, hypotension and electrolyte disturbances are usually absent or less severe than with primary adrenal failure. Hyperpigmentation does not occur with secondary adrenal insufficiency because it is related to melanocytic stimulation factors produced from the same precursor as ACTH. Tertiary adrenal insufficiency refers to impaired hypothalamic release of corticotropin-releasing hormone (CRH) with resulting decreased production of ACTH by the pituitary.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Serum cortisol and, to a lesser extent, aldosterone are decreased. Secondary and tertiary adrenal insufficiency are distinguished from primary adrenal insufficiency by a low plasma ACTH, rather than high plasma ACTH in primary deficiency. Plasma glucose should be checked, as hypoglycemia may occur. Electrolyte levels may be affected by decreased aldosterone, resulting in low serum sodium and high potassium (Table 1).

Table 1.

Test Results Indicative of the Disorder
Serum Cortisol Plasma Aldosterone Plasma ACTH
Low Low or normal Low

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Many factors affect cortisol levels, including physiological and psychological stress, timing of specimen collection related to diurnal rhythm, exogenous steroids, and hypoglycemia. Long-term steroid therapy suppresses ACTH levels and adrenal function, and time for recovery of adrenal function is required after therapy is stopped. For that reason, long-term therapy is usually tapered gradually, rather than stopped abruptly. Physiological requirements for cortisol usually increase with stress and illness, exacerbating deficiency.

What Lab Results Are Confirmatory?

The ACTH stimulation test usually provides some increase in serum cortisol, unlike primary adrenal insufficiency, but the increase is usually blunted relative to individuals with normal adrenal function. The overnight metyrapone test does not show a normal increase in serum cortisol. The CRH stimulation test shows a diminished ACTH increase in secondary adrenal insufficiency but normal or increased response in tertiary adrenal insufficiency.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Other pituitary hormones, thyroid-stimulating hormone, prolactin, growth hormone, follicle-stimulating hormone, and luteinizing hormone, should be assessed if there is consideration of pituitary injury. If exogenous steroids are considered a possibility, analysis of a serum profile of glucocorticoids may detect synthetic steroid hormones.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

A history of therapeutic steroid use needs consideration. Some synthetic steroids are minimally detected in assays for cortisol.

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