Cushing's Syndrome Diagnosis and Testing

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Questions and Answers

What does the late-night salivary cortisol test primarily measure?

Total cortisol production over 24 hours

ACTH levels in serum

Free cortisol levels in the saliva (correct)

Circadian rhythm fluctuations of cortisol

Why is a 24-hour urinary free cortisol collection preferred over a single cortisol measurement?

It requires fewer resources and costs less

It provides an integrated measure over a 24-hour period (correct)

It reflects only the morning cortisol levels

To avoid the need for patient compliance

In which scenario would Cushing's syndrome be considered more likely based on the 24-hour urinary free cortisol results?

Cortisol levels above the normal range but less than double

Cortisol levels greater than 3 times the upper limit of normal (correct)

Cortisol levels consistently within normal limits

Cortisol levels show significant day-to-day variation

What is a potential limitation of the 24-hour urine collection method?

It does not account for circadian rhythm fluctuations (C) Signup and view all the answers

What should be taken into consideration regarding the late-night salivary cortisol test?

It should be performed on multiple consecutive nights (B) Signup and view all the answers

What is one of the primary investigations to confirm a diagnosis of Cushing's Syndrome?

24-hour urine free cortisol (A) Signup and view all the answers

Which of the following is a less common sign associated with Cushing's Syndrome?

Proximal muscle weakness (B) Signup and view all the answers

What pathophysiologic change occurs in the hypothalamic-pituitary-adrenal axis in Cushing's Syndrome?

Autonomy from central ACTH control (C) Signup and view all the answers

What clinical feature should always be ruled out when suspecting Cushing's Syndrome?

Exogenous steroid use (B) Signup and view all the answers

Which of the following is NOT a common symptom of Cushing's Syndrome?

Increased libido (C) Signup and view all the answers

What was the main concern for Ms. F related to her lifestyle prior to her referral?

Sedentary lifestyle (C) Signup and view all the answers

Which physical exam finding is characterized by purple striae on the abdomen?

Cushing's syndrome (C) Signup and view all the answers

Which of the following symptoms is indicative of Cushing's syndrome in Ms. F?

Easy bruising (B) Signup and view all the answers

What is Ms. F's BMI classification based on her height and weight?

Class I Obesity (C) Signup and view all the answers

What is the significance of facial plethora in a physical exam?

Points to possible Cushing's syndrome (C) Signup and view all the answers

Which condition is NOT listed as a differential diagnosis for Cushing's syndrome?

Addison’s disease (B) Signup and view all the answers

How has Ms. F's menstrual cycle been affected?

Irregular menstrual cycles (B) Signup and view all the answers

Which medication is NOT mentioned in Ms. F's history for managing hypertension?

Lisinopril (D) Signup and view all the answers

What physical exam finding is characterized by an accumulation of fat at the back of the neck?

Dorsocervical fat pad (D) Signup and view all the answers

What significant change in physical appearance was observed in Ms. F when comparing her current state to two years ago?

Moon facies (B) Signup and view all the answers

Which one of these symptoms is NOT typically associated with Cushing's syndrome?

Cold intolerance (D) Signup and view all the answers

Which of the following defines Cushing's syndrome?

Exposure to high levels of glucocorticoids (C) Signup and view all the answers

In Ms. F's family history, what condition does her father have?

High blood pressure (C) Signup and view all the answers

Which condition is characterized by acne on the chest, back, and face?

Cushing's syndrome (D) Signup and view all the answers

Which factor is least likely to contribute to Ms. F's current health issues?

Family history of obesity (A) Signup and view all the answers

Which of the following describes the type of fat accumulation typically seen in Cushing's syndrome?

Central obesity (D) Signup and view all the answers

What does an elevated cortisol result indicate in the context of the dexamethasone suppression test?

Loss of diurnal variation (D) Signup and view all the answers

What is the primary function of dexamethasone in the suppression test?

To bind to glucocorticoid receptors (A) Signup and view all the answers

If the HPA axis is functioning normally, what should occur after administration of dexamethasone?

Suppression of cortisol production (A) Signup and view all the answers

What does a positive 1 mg low dose dexamethasone suppression test (>50 nmol/L cortisol) indicate?

Inappropriate cortisol secretion (A) Signup and view all the answers

What does normal adrenal function result in after ACTH suppression by dexamethasone?

Shut off cortisol production (C) Signup and view all the answers

Which of the following could lead to a positive dexamethasone suppression test despite normal adrenal function?

Autonomous adrenal tissue production (D) Signup and view all the answers

What is an abnormal result for cortisol measured at 8 AM after taking dexamethasone at 11 PM?

331 nmol/L (B) Signup and view all the answers

What is the relationship between dexamethasone and endogenous cortisol?

Dexamethasone substitutes cortisol in certain functions (A) Signup and view all the answers

What is one of the pathophysiologic changes observed in the HPA axis in Cushing's syndrome?

Loss of feedback inhibition (B) Signup and view all the answers

Which of the following symptoms is typically more common in Cushing's syndrome?

Striae (A) Signup and view all the answers

What is the rationale for always ruling out exogenous steroid use when suspecting Cushing's syndrome?

To establish the likely etiology of excess cortisol (B) Signup and view all the answers

Which investigation is typically performed first to confirm the diagnosis of Cushing's syndrome?

24-hour urine free cortisol test (B) Signup and view all the answers

Which of the following would indicate a more severe form of Cushing's syndrome based on clinical features?

Hypertension and abnormal glucose tolerance (D) Signup and view all the answers

What does the late-night salivary cortisol test primarily indicate regarding cortisol secretion patterns?

A loss of normal diurnal variation in cortisol levels (C) Signup and view all the answers

Why is a 24-hour urinary free cortisol test more informative than a single cortisol measurement?

It captures fluctuations in cortisol levels throughout the day (A) Signup and view all the answers

What is a significant limitation of using the late-night salivary cortisol test?

It may be affected by patients with a disturbed sleep-wake cycle (D) Signup and view all the answers

What interpretation can be made if the cortisol level from a 24-hour urinary free cortisol collection is more than three times the upper limit of normal?

Indicates Cushing’s syndrome is more likely (B) Signup and view all the answers

What does the presence of elevated late-night salivary cortisol levels signify?

A potential endocrine disorder related to cortisol regulation (A) Signup and view all the answers

What is a common psychosocial factor affecting Ms. F's health?

Sedentary lifestyle (B) Signup and view all the answers

Which characteristic physical exam manifestation is typically associated with Cushing's syndrome?

Moon facies (C) Signup and view all the answers

Which physical exam finding is characterized by an increased fat accumulation at the back of the neck?

Dorsocervical Fat Pad (C) Signup and view all the answers

What should be the primary consideration for managing Ms. F's hypertension associated with her obesity?

Increase physical activity (B) Signup and view all the answers

What is the primary hormone involved in the development of Cushing's syndrome?

Cortisol (B) Signup and view all the answers

In evaluating Ms. F's lifestyle choices, which factor is most likely contributing to her health issues?

Her sedentary work environment (D) Signup and view all the answers

Which symptom related to hormonal imbalance in Ms. F might indicate a need for closer evaluation?

Irregular menstrual cycles (B) Signup and view all the answers

Which symptom is least likely to be associated with Cushing's syndrome based on common physical exam findings?

Joint pain (B) Signup and view all the answers

What is the significance of Ms. F’s family history of hypertension?

It indicates a higher risk for developing hypertension (A) Signup and view all the answers

Which of the following conditions is generally considered a differential diagnosis for Cushing's syndrome?

Metabolic Syndrome (C) Signup and view all the answers

Which physical exam sign is typically represented by purple striae observed on the abdomen?

Cushing's Sign (A) Signup and view all the answers

Considering Ms. F's obesity, which factor potentially complicates her clinical management?

Sedentary lifestyle (B) Signup and view all the answers

What role could the medications listed in Ms. F's history play in her clinical picture?

They can control her blood pressure but may impact weight (D) Signup and view all the answers

In what year was the index case of Cushing's syndrome, Minnie G, first presented to a physician?

1910 (A) Signup and view all the answers

Which physical characteristic is NOT typically described in individuals with Cushing's syndrome?

Facial moisture (A) Signup and view all the answers

Which condition is commonly associated with hirsutism as a physical exam finding?

Cushing's Syndrome (B) Signup and view all the answers

What is the primary effect of dexamethasone on the hypothalamic-pituitary-adrenal (HPA) axis?

It suppresses ACTH release (B) Signup and view all the answers

In a scenario where elevated cortisol is observed, what could be a potential cause if the patient has undergone a low dose dexamethasone suppression test?

Autonomous adrenal tissue (C) Signup and view all the answers

What does a positive 1 mg low dose dexamethasone suppression test (>50 nmol/L cortisol) indicate regarding cortisol secretion?

Inappropriate cortisol secretion (D) Signup and view all the answers

What role does dexamethasone play in the context of the HPA axis?

Substitutes for endogenous cortisol to suppress ACTH (B) Signup and view all the answers

What physiological mechanism is disrupted if an exogenous adrenal cortisol level is persistently high despite dexamethasone administration?

ACTH feedback regulation (C) Signup and view all the answers

After administering dexamethasone, what is expected from normal adrenal tissue regarding cortisol production?

Cortisol production should cease (D) Signup and view all the answers

What does an elevated cortisol level in a low dose dexamethasone suppression test suggest about the adrenal tissues?

The adrenal tissues are functioning independently of ACTH (B) Signup and view all the answers

If the HPA axis is functioning normally, what should happen to ACTH levels after administration of dexamethasone?

ACTH levels should decrease (C) Signup and view all the answers

Study Notes

Case-Based Teaching: Cushing's Syndrome

Cushing's syndrome is characterized by excess cortisol secretion, stemming from either endogenous or exogenous glucocorticoid steroid exposure.

New Referral to the Endocrine Clinic

Patient: 37-year-old female
Referral reason: 10-month history of 12 kg weight gain (attributed to inactivity), easy bruising, muscle weakness and fatigue, and irregular menstrual cycles.

Further History

Past medical history: Hypertension (diagnosed 3 years prior) and Class I Obesity (BMI 31 kg/m²).
Family history: Father with high blood pressure (diagnosed in his 60s).
Social history: Works as an engineer, sedentary lifestyle, smokes 10 cigarettes a day for 10 years, drinks 2 glasses of wine on the weekend.

Vital Signs

Blood Pressure (BP): 150/90 mmHg
Heart Rate (HR): 87 BPM
Oxygen saturation (O2 sat): 99% on room air
Body Temperature: Apyrexial
Height: 162 cm
Weight: 83.2 kg
BMI: 31 kg/m²

Comparing Pictures (2 years ago & now)

Visual comparison of patient photos reveals noticeable changes, such as facial features and body shape.

Physical Exam Signs

Striae: Stretch marks, often on the abdomen.
Dorsocervical fat pad (Buffalo Hump): A fat deposit at the back of the neck.
Ecchymoses: Bruising.
Facial plethora: Reddish discoloration of the face.
Hirsutism: Excessive hair growth.
Acne: Skin blemishes.

On Physical Examination

Facial plethora
Hirsutism (on the sides of the face and lower back)
Acne (on the chest, back, and face)
Thyroid examination: unremarkable
Purple striae on the abdomen
Central obesity, increased fat accumulation in the face and trunk
Dorsocervical fat pad
Proximal muscle weakness

Differential Diagnoses

Obesity
Metabolic syndrome
Type II diabetes
Cushing's syndrome

Cushing's Syndrome Definition

A syndrome resulting from consistent exposure to high levels of glucocorticoid steroids, whether from within the body (endogenous) or from outside the body (exogenous).

Some History About Cushing's

Minnie G (the index case) presented to Harvey Cushing in 1910 with symptoms of obesity, hirsutism, and amenorrhea.
Cushing's interest was sparked and resulted in research on pituitary gland adenomas.

Cushing's Syndrome - Signs & Symptoms

More Common: Decreased libido, obesity, plethora, round face, menstrual changes, hirsutism, hypertension, ecchymoses, lethargy, depression, dorsal fat pad, abnormal glucose tolerance.
Less Common: ECG abnormalities, striae, edema, proximal muscle weakness, osteopenia/fractures, headache, backache, recurrent infections, abdominal pain, acne, female balding, emotional disturbance, enlarged sella turcica, moon facies, osteoporosis, cardiac hypertrophy, buffalo hump, adrenal tumor, thin/wrinkled skin, abdominal striae, amenorrhea, muscle weakness, purpura, skin ulcers.

Hypothalamic-Pituitary-Adrenal Axis

The diagram illustrates the pathway by which cortisol is regulated within the body, involving the Hypothalamus, Pituitary gland, and Adrenal glands. Cortisol levels are elevated in Cushing's Syndrome.

Pathophysiologic Cushing's Syndrome

Excess cortisol secretion: An increase in cortisol production.
Loss of diurnal variation of cortisol secretion: A failure of cortisol production to follow a daily pattern.

Investigation: What investigations?

24-hour urine free cortisol
Late-night salivary cortisol
1 mg overnight dexamethasone suppression test

Excess Cortisol: 24-Hour Urinary Free Cortisol

Integrates cortisol over time: Measures free cortisol over a 24-hour period.
Frequency of measurements is needed.
More accurate than single cortisol measurement.
Practical for cortisol amount calculation.

Investigation: Late Night Salivary Cortisol

Measures free cortisol in saliva; easily collected.
Stable, thus can be measured at home at 11 pm.

Investigation: 1 mg Overnight Dexamethasone Suppression Test

Inhibition of excessive cortisol secretion.
A dexamethasone dose is given to a patient at 11 pm, and cortisol is measured at 8 am.
Indicates failure of suppression (> 50 nmol/L or > 1.8 µg/dL).

Results: Confirming Elevated Cortisol

24-hour urine free cortisol: 658 µg/24 hrs (Elevated)
Low dose Dexamethasone suppression test: 331 nmol/L, elevated cortisol
Late Night Salivary cortisol: Elevated

Cushing's Syndrome Confirmed

The elevated results of the investigations confirm Cushing's syndrome.

Next Step?

Excluding exogenous steroid use is the first step.
Sources of excess cortisol: pituitary, adrenal, and ectopic.

Cushing's Disease

High ACTH levels resulting in overproduction of cortisol from a pituitary adenoma.

Determine If ACTH Dependent or Independent

ACTH-dependent Cushing's: Bilateral adrenal hyperplasia, high ACTH levels, due to excessive production of ACTH which causes the adrenals to overproduce cortisol.
ACTH-independent Cushing's: Low ACTH levels, adrenal glands malfunction independently of the pituitary.

Investigation: 8mg High Dose Dexamethasone Suppression Test

For differentiating the source (pituitary vs. ectopic).
If cortisol suppression is present, pituitary is the cause.
If no suppression, the source is ectopic

What is the best modality to image a pituitary gland?

MRI of the pituitary is the modality that should be used.

Radiologic Test

Adrenal CT in case of non-ACTH dependent Cushing's disease.
Pituitary MRI if ACTH dependent Cushing’s is suspected.
CT chest/abdomen/pelvic if ectopic ACTH is suspected.

Pituitary MRI

Standard imaging for the pituitary gland and potential adenomas.
Visualizes the pituitary gland, optic chiasm, and hypothalamus.

MS. F's MRI Findings

MRI shows pituitary adenoma.

Treatment Algorithm for Cushing's Disease

Diagnosis, transsphenoidal surgery, follow-up monitoring.
Treatment for recurrent disease: surgery, radiation, or medical therapy.
Consider bilateral adrenalectomy in cases of recurrence.

MS. F was referred to neurosurgery

She underwent transsphenoidal surgery.

Pathology of Pituitary Adenoma

Corticotroph microadenomas: Microscopic nodules differenciating from a normal pituitary gland.
Identification is crucial for corticotroph hyperplasia/adenomas.

Management: Post-Surgical

Referral to neurosurgeon is part of the ongoing evaluation.
Transsphenoidal resection; postoperative glucocorticoid replacement to normalize HPA feedback.
Serial hormonal assays, long-term monitoring for hypopituitarism.

Post-Operative MRI (3 Months)

Comparison of pre-operative and 3-month post-operative MRI scans.

Features of Cushing's Post-op

Set of photos 1, 2, 3, and 16 months post-op is a visual representation of the patient's recovery.

Our Patient...

Successful resection of the adenoma.
Resolution of her symptoms and normalized hormonal assays.

Cushing's Investigation Algorithm

A flowchart demonstrating the different scenarios of Cushing's syndrome and investigation pathway in relation to ACTH levels and high- vs. low-dose Dexamethasone suppression tests.

Take Home Message

Cushing's syndrome is a set of signs/symptoms from high cortisol levels; causes include steroid use, pituitary tumors, adrenal tumors, and ectopic tumors.
Symptoms include truncal obesity, moon face, hump, muscle loss, easy bruising/thinning of skin and bones.

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Description

This quiz evaluates knowledge on the testing and diagnosis of Cushing's Syndrome, including the late-night salivary cortisol test and 24-hour urinary free cortisol collection. Participants will explore the implications of test results and the pathological changes in the hypothalamic-pituitary-adrenal axis. Brush up on your understanding of the clinical features, common symptoms, and related scenarios of this endocrine disorder.