Adrenal Hormone Disorders: Key Concepts and Diagnostic Algorithms

What are the two major functional regions of the adrenal gland?

Adrenal medulla and adrenal cortex

What hormones are produced by the adrenal medulla?

Catecholamines: dopamine, norepinephrine, epinephrine

What is the primary mineralocorticoid produced by the adrenal cortex?

Aldosterone

Which glucocorticoid is emphasized in the adrenal cortex?

Cortisol

What are the adrenal androgens produced by the adrenal cortex?

DHEA-S, DHEA, and androstenedione

What is the precursor pathway for catecholamines?

Phenylalanine -> Tyrosine -> Dopamine -> Norepinephrine -> Epinephrine

What is the control pathway for cortisol production?

Hypothalamus (CRH) -> anterior pituitary (ACTH) -> adrenal cortex -> cortisol

What specimen is used to measure end products of catecholamine catabolism?

Urine

What are the major metabolites measured for pheochromocytoma?

Urinary metanephrines

What are the urinary metabolites used to diagnose neuroblastoma?

Urinary VMA and HVA

What are common symptoms of pheochromocytoma?

Headaches, palpitations, diaphoresis, paleness, nausea, anxiety, generalized weakness

What signs may indicate pheochromocytoma?

Hypertension, adrenal mass on imaging, increased urinary metanephrines

What is neuroblastoma?

A neoplasm derived from primordial neural crest cells of the sympathetic nervous system, primarily affecting children

What are the first signs of neuroblastoma?

An abdominal mass or effects of bone marrow involvement

What causes increased catecholamine metabolites in pheochromocytoma?

Catecholamine-producing tumor leading to increased urinary metanephrines

What laboratory results are expected in hyperaldosteronism?

Hypernatremia, hypokalemia, metabolic alkalosis, hypertension

What laboratory results are expected in hypoaldosteronism?

Hyponatremia, hyperkalemia, hypotension, metabolic acidosis

What are primary causes of hyperaldosteronism?

Adrenal adenoma, bilateral hyperplasia, aldosterone-producing carcinoma

What is Conn syndrome?

Primary hyperaldosteronism due to adrenal gland overproduction of aldosterone

What are the effects of aldosterone on sodium and potassium?

Promotes sodium retention and potassium/H+ loss

What is the role of MAO and COMT in catecholamine metabolism?

MAO (monoamine oxidase) and COMT (catechol-O-methyl transferase) are enzymes that metabolize catecholamines

What is the significance of VMA in diagnosing neuroblastoma?

VMA detects around 70% of neuroblastoma tumors

What is the relationship between cortisol and ACTH?

Cortisol provides negative feedback to decrease CRH and ACTH levels

What are common causes of adrenal insufficiency?

Autoimmune conditions, congenital adrenal hyperplasia, metastatic tumors, HIV infection

What is the clinical presentation of hyperaldosteronism?

Hypertension, hypokalemia, metabolic alkalosis, increased blood volume

What is the clinical presentation of Addison's disease?

Hyponatremia, hyperkalemia, hypotension, metabolic acidosis

What is the effect of hyperaldosteronism on renin activity?

Renin activity is decreased due to negative feedback

What is the role of catecholamines in the sympathetic nervous system?

Catecholamines increase sympathetic nervous system effects

What are common clinical features of hyperaldosteronism?

Headaches, muscle cramps, excessive thirst, frequent urination, hypertension, hypernatremia, hypokalemia, expanded extracellular fluid volume, metabolic alkalosis.

What is the best screening test for hyperaldosteronism?

The ratio of plasma aldosterone concentration to plasma renin activity.

What distinguishes primary hyperaldosteronism (Conn's syndrome) from secondary?

In primary, aldosterone is high and renin activity is decreased; in secondary, both are high.

What is Addison's disease?

Primary adrenal insufficiency characterized by low aldosterone and low cortisol due to adrenal gland destruction.

What are the clinical features of Addison's disease?

Fatigue, weakness, weight loss, hypotension, hypoglycemia, hyponatremia, hyperkalemia, metabolic acidosis, and skin hyperpigmentation.

What is the initial lab clue for diagnosing Addison's disease?

Low 8 AM cortisol.

What is the significance of elevated ACTH in Addison's disease?

It indicates primary adrenal insufficiency.

What is congenital adrenal hyperplasia (CAH)?

A condition caused by a genetic mutation affecting adrenal hormone production, commonly due to 21-hydroxylase deficiency.

What are the clinical features of CAH?

Virilization, ambiguous genitalia, and precocious puberty.

What is the most common cause of Cushing syndrome?

Excessive glucocorticoid therapy (iatrogenic).

What are key symptoms of Cushing syndrome?

Weight gain, fatigue, headaches, hirsutism, truncal obesity, moon face, purple striae, hypertension.

How is primary adrenal insufficiency differentiated from secondary?

By measuring ACTH levels; low ACTH indicates primary adrenal insufficiency.

What does a blunted cortisol response to ACTH stimulation indicate?

Primary adrenal failure.

What is the purpose of the CRH stimulation test?

To distinguish between secondary and tertiary causes of adrenal insufficiency.

What is the expected finding in the metyrapone test?

It assesses HPA-axis function by blocking cortisol synthesis and observing precursor response.

What are the expected lab findings in Addison's disease?

Increased ACTH, decreased aldosterone, decreased cortisol, increased 17-hydroxyprogesterone.

What is the significance of skin hyperpigmentation in Addison's disease?

It is noted in primary adrenal insufficiency but absent in secondary adrenal insufficiency.

What are the diagnostic criteria for Cushing disease?

High cortisol levels with loss of normal diurnal variation and elevated ACTH.

What does high-dose dexamethasone suppression test help differentiate?

It differentiates pituitary Cushing disease from ectopic ACTH production.

What are common causes of secondary adrenal insufficiency?

Exogenous glucocorticoid administration and dysregulation of stimulating hormones.

What is the role of autoantibodies in diagnosing adrenal disorders?

They help in further etiologic workup for adrenal insufficiency.

What are the expected metabolic changes in Addison's disease?

Metabolic acidosis, hyponatremia, hyperkalemia.

What is the main genetic mutation associated with CAH?

Mutation affecting 21-hydroxylase.

What is the typical presentation of an Addisonian crisis?

Altered mental status, hypotension, hypoglycemia, hyponatremia, hyperkalemia, metabolic acidosis.

What is the expected outcome of a low-dose dexamethasone suppression test in patients with Cushing syndrome?

Patients with cortisol excess do not suppress cortisol production.

What is the impact of adrenal adenoma on cortisol production?

It causes high cortisol production independent of ACTH.

What populations are most affected by congenital adrenal hyperplasia?

Native Americans and Yupik Indigenous Peoples in the Southwest Alaskan region.

What does a CRH stimulation variation with an inferior petrosal sinus/peripheral ACTH ratio >2 indicate?

Cushing disease

What does a CRH stimulation variation with an inferior petrosal sinus/peripheral ACTH ratio

Ectopic ACTH syndrome

What is the purpose of the ACTH stimulation test?

To assess the adrenal glands' functional capacity to synthesize cortisol and identify primary adrenal failure.

What does the CRH stimulation test evaluate?

The ACTH/cortisol response to distinguish secondary vs tertiary causes in hypo- and hypercortisolism.

What is the purpose of metyrapone stimulation?

To indirectly assess hypothalamic-pituitary-adrenal axis function by blocking cortisol synthesis.

What does low-dose dexamethasone suppression test determine?

Whether cortisol/ACTH production can be suppressed; screens for cortisol excess.

What is the purpose of high-dose dexamethasone suppression?

To differentiate pituitary Cushing disease from ectopic ACTH production.

What indicates primary adrenal insufficiency in the ACTH stimulation test?

A low or blunted cortisol response.

What does a normal response in the CRH stimulation test indicate?

Cortisol rises ~20% and ACTH ~50%.

What does an IPS:peripheral ACTH ratio >2 indicate in CRH stimulation variation?

Cushing disease (pituitary origin).

What does an IPS:peripheral ACTH ratio

Ectopic ACTH syndrome.

What is the expected result of metyrapone stimulation in normal/non-pituitary disease?

11-deoxycortisol increases.

What does low-dose dexamethasone suppression indicate if cortisol/UFC decreases?

Normal adrenal function.

What does high-dose dexamethasone suppression indicate in pituitary Cushing disease?

It may suppress cortisol production.

What is the cortisol pattern in Conn syndrome?

Aldosterone high; renin low.

What clinical clues are associated with Addison disease?

Fatigue, weakness, weight loss, postural hypotension, hyperpigmentation.

What is the key hormone pattern in Cushing syndrome?

Cortisol high; ACTH low if primary adrenal, high if ACTH-dependent.

What is the lab pattern for primary hyperaldosteronism?

Aldosterone high, renin low, hypertension, hypernatremia, hypokalemia.

What does a low cortisol response with elevated ACTH suggest?

Primary Addison disease.

What does a high ACTH with high cortisol indicate?

ACTH-dependent Cushing syndrome.

What is the normal diurnal variation of cortisol?

Peaks around 8 AM and troughs around 4 PM.

What is the method used for cortisol analysis?

Electrochemiluminescence immunoassay (ECLIA).

What is the major lab pattern for congenital adrenal hyperplasia (CAH)?

ACTH high, cortisol low, aldosterone low, high 17-hydroxyprogesterone.

What are the urinary markers for neuroblastoma?

VMA and HVA.

What does an elevated urinary metanephrines indicate?

Pheochromocytoma.

What are the clinical clues for Cushing syndrome?

Truncal obesity, moon face, buffalo hump, purple striae.

What does the presence of hyperkalemia and hyponatremia suggest in adrenal disorders?

Addison disease.

What does the term 'Cushing disease' refer to?

A pituitary ACTH-producing tumor leading to cortisol excess.