Cushing syndrome due to bilateral macronodular adrenocortical disease

What it is

From: Orphanet

A rare adrenal Cushing syndrome characterized by bilateral benign adrenal macronodules (>1 cm) that potentially produce autonomously variable levels of cortisol excess. Although in most cases are ACTH-independent, non-suppressed ACTH levels have been described.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Decreased circulating ACTH level · Very frequent (99-80%)

The concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), is below the lower limit of normal in the blood circulation.

Moon facies · Very frequent (99-80%)

A rounded, puffy face with fat deposits in the temporal fossa and cheeks, a double chin.

Macronodular adrenal hyperplasia · Obligate (100%)

Abdominal obesity · Frequent (79-30%)

Excessive fat around the stomach and abdomen.

Abnormal libido · Frequent (79-30%)

Any deviation from the normal sexual drive or desire for sexual activity.

Abnormal response to corticotropin releasing hormone stimulation test · Frequent (79-30%)

An anomalous response to the corticotropin releasing hormone (CRH) stimulation test. Normally,CRH is released by the hypothalamus to induce adrenocorticotropic hormone (ACTH) release by the anterior pituitary. In the stimulation test, CRH is administered intravenously and ACTH and cortisol are measured at intervals.

Bruising susceptibility · Frequent (79-30%)

An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Depression · Frequent (79-30%)

Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.

Dorsocervical fat pad · Frequent (79-30%)

An area of fat accumulation at the back of the neck in the form of a hump.

Emotional lability · Frequent (79-30%)

Unstable emotional experiences and frequent mood changes; emotions that are easily aroused, intense, and/or disproportionate to events and circumstances.

Glucose intolerance · Frequent (79-30%)

Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).

Hirsutism · Frequent (79-30%)

Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).

Hyperlipidemia · Frequent (79-30%)

The concentration of lipid in the blood circulation is above the upper limit of normal.

Hypertension · Frequent (79-30%)

The presence of chronic increased pressure in the systemic arterial system.

Other findings in the same source

From: Orphanet

Additional reported features include Increased circulating cortisol level (Frequent (79-30%)); Increased urinary cortisol level (Frequent (79-30%)); Irregular menstruation (Frequent (79-30%)); Nephrolithiasis (Frequent (79-30%)); Osteoporosis (Frequent (79-30%)); Proximal amyotrophy (Frequent (79-30%)); Proximal muscle weakness (Frequent (79-30%)); Striae distensae (Frequent (79-30%)); Paradoxical increased cortisol secretion on dexamethasone suppression test (Frequent (79-30%)); Plethora (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

All ages

Inheritance in the source

From: Orphanet

Autosomal dominant; Not applicable

Frequency and the population described

From: Orphanet

Point prevalence: <1 / 1 000 000; Europe; Value and class.

Which doctor should you see?

The suggested department for discussing Cushing syndrome due to bilateral macronodular adrenocortical disease is Endocrinology, with a endocrinologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which hormone or metabolic finding is important in this case?
• How should test timing and current medicines be taken into account?
• What follow-up would show whether the care plan is working?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Cushing syndrome due to bilateral macronodular adrenocortical disease. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.