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Mitotane and Aminoglutethimide

*Mitotanum*, *Aminoglutethimidum*

For medical students2 min readUpdated 2026-10-10

Mitotane and aminoglutethimide are non-selective steroidogenesis inhibitors. They suppress the early stages of adrenal cortex hormone synthesis, reducing the levels of all biologically active compounds in this class.

Target of ActionBlockade of cholesterol conversion to pregnenolone
Main EffectsReduction in levels of all hormonally active steroids
Main IndicationsCushing's syndrome and adrenocortical tumors
Aminoglutethimide EffectSomnolence at doses exceeding 1 g per day

Mechanism of Action and Pharmacological Profile

These pharmacological agents belong to the group of non-selective inhibitors. Their primary pharmacological action involves targeting the early stages of steroidogenesis. The drugs block the key process of converting cholesterol to pregnenolone. As a result of this blockade, the production of virtually all hormonally active steroids in the body is significantly reduced.

Clinical Application in Adrenal Pathology

The ability to suppress steroid hormone synthesis determines the main areas of their medical application:

These drugs help control excessive hormone production by affected tissue.

Special Considerations for Aminoglutethimide in Oncology

The pharmacological properties of aminoglutethimide have found application in oncology. It is used to treat breast carcinoma. The therapeutic effect is achieved through targeted reduction of estrogen and androgen production, which is critical in hormone-dependent tumors.

Important safety guidelines are observed during therapy:

  1. The drug must be administered in combination with dexamethasone.
  2. Dosages exceeding 1 g per day can cause pronounced somnolence.
  3. A daily dose of up to 1 g is generally well tolerated by patients.

Frequently asked questions

Why is concurrent administration of dexamethasone required when treating with aminoglutethimide?

Concurrent dexamethasone administration is necessitated by the non-selectivity of aminoglutethimide: the drug inhibits the synthesis of adrenal cortex hormones, including glucocorticoids and mineralocorticoids. Therefore, aminoglutethimide is prescribed alongside dexamethasone.

What specific adverse reactions and toxic effects are characteristic of mitotane?

Mitotane is characterized by adverse effects affecting the central nervous system (CNS) and gastrointestinal tract (GI).

Specific adverse events include:

  • Teratogenicity — the drug crosses the placenta and exerts an adrenolytic effect on the fetus.
  • Cumulative toxicity — the intensity and magnitude of adverse events increase as the drug accumulates in the body.

All emerging toxic effects are reversible and completely disappear upon discontinuation of therapy. If steroid replacement therapy is inadequate, mitotane tolerance worsens and side effects become more severe.

What are the absolute contraindications to prescribing mitotane?

Pregnancy occurring during mitotane therapy is contraindicated. The drug crosses the placenta, exerts an adrenolytic effect on the fetus, and possesses potential teratogenic effects. Female patients receiving mitotane require effective contraception, preferably non-estrogen or barrier methods. Pregnancy planning is only permissible after discontinuing mitotane therapy and allowing its blood concentration to drop to undetectable levels, which may take 3–12 months.

What are the pharmacokinetic features of mitotane in the body?

Mitotane pharmacokinetics are distinguished by a narrow therapeutic index and a pronounced tendency toward bioaccumulation.

Key features:

  • Blood levels of mitotane depend less on the daily dose taken than on its accumulation associated with a prolonged half-life.
  • A decrease in mitotane concentration to undetectable levels after cessation of therapy can take 3–12 months.
  • Dosing is constrained by the need to rapidly achieve a therapeutic concentration while accounting for toxicity; the target concentration is greater than 14 mg/L.
What is the shared mechanism of action of mitotane and aminoglutethimide?

Both agents block an early step in steroidogenesis—the conversion of cholesterol to pregnenolone. This leads to a general decrease in the production of all hormonally active steroids.

For which conditions are these drugs prescribed?

The primary indications are Cushing's syndrome and hormonally active adrenal neoplasms.

What are the specific features of aminoglutethimide use in oncology?

It is used in breast carcinoma to lower androgen and estrogen levels. The drug is co-administered with dexamethasone.

What are the dosage limitations of aminoglutethimide?

A dose of up to 1 g per day is well tolerated, but exceeding this threshold frequently leads to somnolence.

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