Generalized glucocorticoid resistance syndrome

What it is

From: Orphanet

A rare, adrenogenital syndrome characterized by generalized, partial tissue insensitivity to glucocorticoids leading to variable phenotype, including asymptomatic individuals with only biochemical alterations or patients with ambiguous genitalia at birth in females, hypertension, acne, hirsutism, precocious puberty, male-pattern hair loss, anxiety and depression in both sexes, menstrual irregularities in women, and oligospermia in men.

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 aldosterone level · Very frequent (99-80%)

Abnormally reduced levels of aldosterone.

Fatigue · Very frequent (99-80%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Hirsutism · Very frequent (99-80%)

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

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

An abnormal increased in the concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), in the blood.

Increased urinary cortisol level · Very frequent (99-80%)

Abnormally increased concentration of cortisol in the urine.

Abnormal testosterone level · Frequent (79-30%)

An anomalous concentration of testosterone in the blood.

Acne · Frequent (79-30%)

A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).

Adrenal hyperplasia · Frequent (79-30%)

Enlargement of the adrenal gland.

Hypertension · Frequent (79-30%)

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

Hypokalemia · Frequent (79-30%)

The concentration of potassium(1+) in the blood circulation is below the lower limit of normal.

Metabolic alkalosis · Frequent (79-30%)

Metabolic alkalosis is defined as a disease state where the pH is elevated to greater than 7.45 secondary to some metabolic process.

Oligomenorrhea · Frequent (79-30%)

Infrequent menses (less than 6 per year or more than 35 days between cycles).

Ambiguous genitalia · Occasional (29-5%)

A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale: Prader 0: Normal female external genitalia. Prader 1: Female external genitalia with clitoromegaly. Prader 2: Clitoromegaly with partial labial fusion forming a funnel-shaped urogenital sinus. Prader 3: Increased phallic enlargement. Complete labioscrotal fusion forming a urogenital sinus with a single opening. Prader 4: Complete scrotal fusion with urogenital opening at the base or on the shaft of the phallus. Prader 5: Normal male external genitalia. The diagnosis of ambiguous genitalia is made for Prader 1-4.

Female pseudohermaphroditism · Occasional (29-5%)

Hermaphroditism refers to a discrepancy between the morphology of the gonads and that of the external genitalia. In female pseudohermaphroditism, the genotype is female (XX) and the gonads are ovaries, but the external genitalia are virilized.

Other findings in the same source

From: Orphanet

Additional reported features include Frontal balding (Occasional (29-5%)); Hypoglycemia (Occasional (29-5%)); Increased circulating cortisol level (Occasional (29-5%)); Oligozoospermia (Occasional (29-5%)); Precocious puberty (Occasional (29-5%)); Infertility (Occasional (29-5%)); Stroke (Very rare (<4-1%)). 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; Autosomal recessive; Not applicable

Frequency and the population described

From: Orphanet

Point prevalence: Unknown; Worldwide; Class only.

Which doctor should you see?

The suggested department for discussing Generalized glucocorticoid resistance syndrome 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 Generalized glucocorticoid resistance syndrome. 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.