Primary and secondary insufficiency
Primary hypofunction, or Addison's disease, occurs due to direct damage to the adrenal glands themselves (most commonly autoimmune atrophy in the West, less frequently infections or bilateral hemorrhages). Meanwhile, bilateral metastases rarely lead to clinically significant function loss.
Secondary hypofunction is much more common than primary. Its pathogenesis lies in the fact that the pituitary gland stops producing adrenocorticotropic hormone (ACTH). Causes can vary: tumors, pituitary infarction, consequences of radiation therapy, or simple abrupt withdrawal of exogenous steroids.
Important distinction: hypopituitarism leads to a deficiency of cortisol and dehydroepiandrosterone, but does not lead to aldosterone deficiency. Brain MRI may reveal macroadenomas or pituitary infarction, while the adrenal glands themselves appear normal or atrophic due to the lack of pituitary stimulation.
Acute and chronic lesions: CT and MRI
The chronic form is most often the consequence of autoimmune aggression. On contrast-enhanced CT and MRI, the glands appear atrophic, irregular in shape, without calcifications, and often barely distinguishable.
The acute form usually develops due to acute bilateral hemorrhage. Risk factors include anticoagulant therapy, hemorrhagic diathesis, postoperative hypovolemia, or sepsis (e.g., Waterhouse-Friderichsen syndrome caused by meningococcus or Pseudomonas aeruginosa).
In patients without obvious risk factors, it is necessary to rule out an occult space-occupying lesion (e.g., pheochromocytoma or melanoma metastases) that could have triggered bleeding and an addisonian crisis. Here, performing contrast-enhanced MRI is critical: a regular hematoma does not enhance, whereas hemorrhage into a tumor will show enhancement of the solid component.
MRI semiotics of adrenal hematomas
On imaging, non-traumatic hematomas appear as well-defined areas within the glands. Their MR signal changes depending on the age of the hemorrhage:
- Acute stage (< 7 days): iso- or hypointense signal on T1-weighted images; markedly hypointense on T2-weighted images.
- Subacute stage (7 days – 7 weeks): hyperintense (bright) signal on both weightings (T1-WI and T2-WI).
- Chronic stage (> 7 weeks): a hypointense rim appears on T1-WI and T2-WI.
Over time, hematomas decrease in size, and may transform into cysts or calcify. Calcification itself is non-specific, as it is visually indistinguishable from lesions in granulomatous diseases.
Subacute insufficiency and adrenalitis
Hypofunction lasting less than two years is usually considered subacute and occurs against the background of infectious adrenalitis (adrenalitis). Prior to treatment, the glands are enlarged, show signs of central necrosis, and exhibit peripheral contrast enhancement.
A classic example is acute tuberculosis. In 91% of cases, the glands are bilaterally enlarged and may mimic a tumor. Calcifications (59%) and peripheral enhancement (47%) are common. With successful therapy, the glands return to normal in most cases.
Another variant is cytomegalovirus adrenalitis in HIV patients. Axial fat-suppressed T2-WI show hyperintense edema surrounding the parenchyma. Following gadolinium administration, the parenchyma enhances, while the edematous zone does not.
Briefly: answers to topical questions
What causes primary adrenal hypofunction (Addison's disease)?
Primary adrenal hypofunction is caused by acquired and congenital factors.
- Autoimmune diseases are the most frequent cause (immune autoaggression leading to cortical destruction).
- Infections — tuberculosis (TB), acquired immunodeficiency syndrome (AIDS), cytomegalovirus (CMV), histoplasmosis.
- Vascular catastrophes — adrenal hemorrhage, Waterhouse-Friderichsen syndrome.
- Genetic and congenital defects — congenital adrenal hyperplasia, adrenoleukodystrophy, adrenal hypoplasia.
- Other causes — metastatic disease, sarcoidosis, amyloidosis, hemochromatosis, medications, and primary steroidogenesis disorders.
What risk factors contribute to the development of acute bilateral adrenal hemorrhage?
Acute bilateral adrenal hemorrhage is facilitated by various pathological conditions and iatrogenic factors.
- Medication factors — use of anticoagulants.
- Surgical interventions — postoperative hemorrhage in the setting of hypovolemia (e.g., after coronary artery bypass grafting).
- Hematologic disorders — hemorrhagic diathesis, DIC with hemorrhagic infarction, venous thrombosis, and thromboembolism.
- Infectious-toxic lesions — septicemia, severe meningococcal infection (meningococcemia), septic necrosis.
- Stress states — extensive burns, severe neonatal hypoxia.
Which infectious agents cause Waterhouse-Friderichsen syndrome?
Waterhouse-Friderichsen syndrome classically develops against the background of severe meningococcal infection (meningococcemia), but can also be caused by other bacteria. The main infectious agents include:
- Meningococcus (meningococcus / Neisseria).
- Haemophilus influenzae (Haemophilus influenzae).
- Pseudomonas aeruginosa (Pseudomonas aeruginosa).
- Escherichia coli (Escherichia coli).
- Pneumococcus (Streptococcus pneumoniae).
- Staphylococci.
The syndrome can also occur in diphtheria and other bacterial infections accompanied by septicemia.
What clinical symptoms are characteristic of acute adrenal insufficiency (addisonian crisis)?
Acute adrenal insufficiency is characterized by severe hemodynamic and systemic disorders. The main clinical manifestations include:
- Acute hypotension — a sharp and rapidly progressive drop in blood pressure.
- Dehydration — fluid depletion of the body.
- Systemic circulatory failure — collapse, syncope, and shock.
- Pronounced muscular weakness.
- Nausea and vomiting.
- In Waterhouse-Friderichsen syndrome, a significant temperature spike up to 41.5 °C and rapidly advancing coma are possible.
What genetic disorders can cause primary adrenal insufficiency?
Primary adrenal insufficiency can be caused by the following genetic and congenital disorders:
- Adrenoleukodystrophy (adrenoleukodystrophy / X-linked ALD) — the most common genetic cause, up to 20% of cases in men.
- Familial adrenal hypoplasia.
- Congenital adrenal hyperplasia.
- Congenital adrenal hypoplasia and ACTH insensitivity.
The 90% rule: Addison's symptoms appear only when 90% of the cortex is destroyed. The aldosterone rule: secondary insufficiency reduces cortisol, but spares aldosterone.
Class and exam questions
How to differentiate a routine sporadic hemorrhage from tumor hemorrhage on MRI?
The absence of internal contrast enhancement plays a decisive role. Blood breakdown products in the hematoma do not accumulate gadolinium, whereas the solid tissue of the underlying neoplasm will enhance.
Why is there no aldosterone deficiency in hypopituitarism?
Because the pituitary gland (via ACTH) controls the production of cortisol and androgens. Aldosterone secretion is regulated primarily by the renin-angiotensin system, which is unaffected in pituitary pathologies.
When is MRI preferred over CT for adrenal gland visualization?
CT remains the primary method. MRI is indicated for children, patients with CT contraindications, as well as for screening, dynamic follow-up of incidentalomas, and tumor differentiation.
What else to study on this topic
- CT imaging: evaluation of contrast washout characteristics for adenoma differentiation
- Application of chemical shift MRI in diagnostic imaging
- PET/CT with specific tracers (18F-FDG, [11C]metomidate)
- Conn's syndrome: imaging for surgical versus medical treatment selection
- Histological criteria: Helsinki score and Weiss system for adrenocortical carcinoma
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