ACTH Set 13

What does ACTH do?

Controls cortisol synthesis by adrenal gland

ACTH negative feedback

* Endogenous cortisol
* Exogenous steroids with prednisone effect

Circadian rhythm

ACTH and cortisol

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Highest early morning (4 AM)

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Lowest late evening

Diagnosis?

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Cortisol: Up

ACTH: Down

Primary hyperadrenalism

Diagnosis?

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Cortisol: Down

ACTH: Up

Primary adrenal failure

Diagnosis?

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Cortisol: Up

ACTH: Up

Secondary hyperadrenal

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(pituitary adenoma, ectopic ACTH)

Diagnosis?

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Cortisol: Down

ACTH: Down

Secondary adrenal failure

Where does **Adrenal steroid synthesis** take place?

Outer cortex

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**The major steroids produced are cortisol and aldosterone**

Cortisol

* glucocorticoid
* major effect on glucose metabolism

Aldosterone

* mineralocorticoid
* major effect on sodium retention/excretion by kidney

Transcortin

Cortisol bound to protein

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99% metabolized by liver

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1% excreted as free cortisol

24 hr urinary free cortisol

__Excellent test__ to assess daily cortisol production

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* synthesis is regulated by ACTH
* Exceptions: Adenomas, carcinoma, hyperplasia

High cortisol =

Low/suppressed ACTH

Cushing’s syndrome

High cortisol state caused by:

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* ACTH pituitary adenoma source
* ACTH non pituitary malignancy source
* primary adrenal tumors

Symptoms of Cushing’s syndrome

* nonspecific
* weight gain
* glucose intolerance
* hirsutism
* hypertension

Pseudo - Cushing’s Syndrome

* physiologic hypercortisolism with certain conditions:​
* Stress​
* obesity​
* malnutrition

Evaluation of Cushing’s Syndrome

==2 abnormal 1st line tests==

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1st line tests

* late night salivary cortisol (< 145 ng/dL)
* 24 hr urinary free cortisol
* 1 mg dexamethasone suppression test

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Abnormal cortisol: > 1.8 mcg/dL

Renin - Angiotensin - Aldosterone System

1. Blood pressure falls

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2. Kidneys release enzyme renin

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3. Renin splits angiotensinogen to form angiotensin I

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4. Angiotensin - converting enzyme splits I to form II

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5. Angiotensin II stimulates aldosterone production

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6. Aldosterone stimulates sodium retention

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Net effect of the Renin - Angiotensin - Aldosterone System

Water retention and increased blood pressure

Aldosterone effect

Increase Na+ reabsorption

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* increase water reabsorption​
* increased excretion of H+ and K+

Hyperaldosteronism

Primary = Conn’s syndrome

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* aldosterone-producing adrenal adenoma, or​
* bilateral adrenal hyperplasia

Symptoms/ Signs of Hyperaldosteronism

* Hypernatremia (increased Na+ conc)​
* Hypertension​
* Hypokalemia (decreased K+ conc)​
* Metabolic alkalosis​
* increased HCO3-​
* increased pH

How is Hyperaldosteronism diagnosed?

Aldosterone concentration (immunoassay)

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Renin concentration

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*In most patients renin levels are undetectable, ALDOSTERONE IS > 15 ng/dL*

4 tests to confirm Hyperaldosteronism

1. Oral sodium
2. IV saline
3. Fludrocortisone
4. Captopril

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*All 4 tests suppress aldosterone secretion in normal individuals*

Treatment of Hyperaldosteronism

Surgery - adrenalectomy for unilateral disease

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Medication - mineralocorticoid receptor antagonist

* for those who can’t have surgery
* bilateral disease

Adrenocortical carcinoma

* rapidly progressing Cushing’s syndrome
* Androgen - secreting in women
* Estrogen secreting less frequent
* Aldosterone producing rare

Adrenal insufficiency Signs and Symptoms

fatigue, anorexia, and weight loss

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* Hyponatremia (decreased Na+ conc)​
* Hypotension (decreased blood pressure)​
* Hyperkalemia (increased K+ conc)
* Metabolic adidosis​
* decreased HCO3-​
* decreased pH

Evalutation and treatment of Adrenal insufficiency

* Evaluate both cortisol and aldosterone levels​
* Treatment – replacement of hormones

High dose synthetic ACTH stimulation test

* IV (or intramuscular) 250 mcg of cosyntropin​
* Measure serum cortisol 0, 30 and 60 minutes

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Normal minimum values​

18 mcg/dL (any value) - IV injection​

16 mcg/dL (any value) – intramuscular

Low dose synthetic ACTH stimulation test

* IV 1mcg of cosyntropin​
* Measure serum cortisol 0, 30 minutes​

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Normal minimum values​

* 18 mcg/dL (any value)