Cushings/adrenal insufficiency Flashcards
know the top two zones and their hormones.
Hypothalamic-pituitary-adrenal (HPA)axis
Hypothalamussecretes CRH →releaseof ACTH from the anteriorpituitary gland
ACTH release:
Like CRH, therelease of ACTH follows the circadian rhythm
Increased in the early morning hours (before awakening), with peak levels in the morning (~8:00 a.m.) and ↓ in the evening
Adrenal gland (cortex):
ACTH mainly stimulates thezona fasciculata (cortisol) andzona reticularis (androgens)
Zona glomerulosa (aldosterone) is primarily regulated by the renin-angiotensin system andpotassium levels
peaks in the morning, peaks off during day
Cushing Syndrome
general
umbrella term
Constellation of clinical abnormalities caused by chronic high blood levels of cortisol
cushing syndrome
Primary hypercortisolism
↑Production of glucocorticoids by adrenal glands (tumor - adrenal adenoma or adrenal carcinoma)
Cushing syndrome
Secondary hypercortisolism
Cushing’s disease – a subtype of Cushing Syndrome
↑Pituitary ACTH production leading to adrenal gland hyperplasia (most likely due to a pituitary adenoma)
Ectopic ACTH syndrome
↑ ACTH production outside the pituitary andadrenal glands (paraneoplastic syndromes – small cell lung cancer)
Exogenous Cushing syndrome
general
Most common form of hypercortisolism
Medical use ofglucocorticoids
Exogenous cortisol causes negative feedback at the level of the hypothalamus and anterior pituitary → (decreased CRH and ACTH)
Long-term exogenous glucocorticoid use
Cortisol will not be released by the body
Atrophy of the zona fasciculata
Abrupt discontinuation of exogenous glucocorticoid use
Body cannot produce enough cortisol and adrenal insufficiency will occur → adrenal crisis
ACTH-dependent means the body makes too much ACTH which in turn increases the production of cortisol
ACTH-independent means the adrenal glands produce cortisol without stimulation from ACTH
ACTH-dependent causes account for 80% of cases
ACTH-independent causes account for 20% of cases
cushings syndrome
clin man
Moon face
Truncal (central) obesity
Prominent supraclavicular and dorsal cervical fat pads (buffalo hump)
Thin distal extremities and fingers
Proximal muscle wasting
Weakness
Osteopenia/osteoporosis
Glucose intolerance or diabetes mellitus
Hypertension
Recurrent opportunistic or bacterial infections
Cryptococcus neoformans, Candida species
Easy bruising
Thin and atrophic skin
Facial acne
Poor wound healing
Violaceous striae wider than 1 cm (abdomen)
cushings syndrome
24 hour urine
Exclude use of exogenous glucocorticoids
24-hour urine for free cortisol level (> 4 times the upper limit of normal)
Serum or saliva cortisol measurement at midnight to assess the normal fall
cushings syndrom
Dexamethasone suppression test
1-2 mg of dexamethasone is given orally at 11 p.m. (normally should ↓ ACTH) and serum cortisol is measured at 8 a.m. the next morning (normally should ↓ serum cortisol)
↑ cortisol levels = positive test and further testing is needed
cushings syndrome
Plasma ACTH levels
Primary vs secondary
Measured to determine the cause of Cushing syndrome
High levels → secondary pituitary (Cushing disease) or ectopic source
Low levels → primary adrenal cause (adenoma, carcinoma, exogenous glucocorticoids)
might need additinal imaging for tumors
cushings syndrome
CRH Stimulation Test
For secondary
Patient is given synthetic CRH
No ↑ in ACTH and cortisol – ectopic ACTH secretion → order a CT scan of the chest, abdomen, and pelvis
↑ in ACTH and cortisol – Cushing disease → order an MRI of the brain with contrast
cushings syndrome
Tx
Stop exogenous glucocorticoids – gradual withdrawal
Pituitary, adrenal, or ectopic ACTH-producing tumors
Surgical removal
Radiation therapy
Adrenalectomy
Patients will require glucocorticoid replacement therapy
Nonresectable tumors
Glucocorticoid-receptor antagonists
Mifepristone - blocks the effects of cortisol in tissues
Adrenal enzyme inhibitors
Ketoconazole and metopirone - decrease cortisol production
Dopamine agonists
Inhibit ACTH secretion
Pheochromocytoma
general (location ) and Tx
Catecholamine-secreting tumor that mimics over-activity of the sympathetic nervous system
Majority of tumors originate in the adrenal medulla (90%)
Treatment:
Surgical resection
Pheochromocytoma
Clin Man
Clinical Presentation:
Headache
Sweating
Tachycardia/Palpitations
Hypertension (sustained or paroxysmal) – most common symptom
Elevated metabolic rate
Hyperglycemia
Nervousness
Adrenal Glands
general
Sit at the superior poles of the kidneys
Consists of:
Adrenal medulla and cortex
adrenal medulla
inner portion
Responds to sympathetic stimulation by secreting catecholamines (epinephrine and norepinephrine)
adrenal glands
Adrenal cortex
Thicker outer portion
Synthesizes 25 steroid hormones that are collectively known as corticosteroids
Consisting of 3 layers
Zona glomerulosa (outer)
Zona fasciculata (middle)
Zona reticularis (inner)
adrenal glands
mineralcorticoids
Mineralocorticoids
Secreted by the zona glomerulosa
Control electrolyte balance by acting on the kidneys
Main mineralocorticoid is aldosterone
adrenal glands
Glucocorticoids
Secreted by the zona fasciculata
Stimulate fat and protein catabolism
Gluconeogenesis (the synthesis of glucose from non-carbohydrate sources) in the liver
Release of fatty acids and glucose into the blood
Help the body adapt to stress
Main glucocorticoid is cortisol
adrenal glands
sex hormones
Sex steroids
Secreted by the zona reticularis
Androgens and estrogens
Main androgen is dehydroepiandrosterone (DHEA)
adrenals
aldosterone
Wren is it secreted
Part of a hormone family with renin and angiotensin
Secreted directly in response to hyperkalemia and via the RAA system in response to low blood volume/low blood pressure
Actions of Aldosterone
aldosterone acts on collecting ducts and DCTs
Adrenal Insufficiency (AI)
general
Inadequate production of adrenocortical hormones: glucocorticoids (cortisol), mineralocorticoids (aldosterone), and adrenal androgens
Types of adrenal insufficiency
Primary
Secondary
Tertiary
AI
Primary
(Addison’s disease)
Dysfunction or destruction of theadrenal cortex
AI
secondary
Conditions that cause deficiency inpituitary adrenocorticotropic hormone (ACTH)secretion
Most common form
AI
Tertiary
Conditions that cause deficiency in the hypothalamic secretion ofcorticotropin-releasing hormone (CRH)
Primary disease – Addison’s Disease
etiology
Autoimmune
Most common cause – 70% of cases
Adrenal cortex is gradually destroyed → loss of mineralocorticoids, glucocorticoids, and adrenal androgen hormone production
Infection (tuberculosis)
Hemorrhage (rupture of the adrenal cortex blood vessels due to ↑ BP leading to tissue ischemia)
Metastatic cancer
secondary AI
etiology
Hypopituitarism - ↓ ACTH
Pituitarytumors and surgery
tertiary AI
etiology
Prolonged high-dose glucocorticoid use suppresses thehypothalamus–pituitary–adrenalaxis
Effects of Cushing’s syndrome treatment
AI
hormonal regulation
Hypothalamic–pituitary–adrenal (HPA)axis:
Hypothalamus secretes CRH →releaseof ACTH from the anteriorpituitary gland
ACTHrelease:
Like CRH,the releaseis pulsatile, following thecircadian rhythm
↑ in the early morning hours (before awakening), with peak levels in the morning (approximately 8:30 a.m.) and ↓ in the evening
Adrenal gland (cortex):
ACTH mainly stimulates thezona fasciculata (cortisol) andzona reticularis (androgens)
Thezona glomerulosa(aldosterone) is primarily regulated by therenin–angiotensin system andpotassiumlevels
Addison’s Disease
Clin man
Symptoms relate to the degree of hormonal deficiency – ≥ 90% destruction of adrenal tissue by the time symptoms appear
Hyperpigmentation from ↑ ACTH
Most characteristic symptom
addisons
↓ Glucocorticoids Sx
Fatigue
Weakness
Weight loss/anorexia
Myalgia/jointpain
Abdominalpain/diarrhea
Hypoglycemia
addisons
↓Mineralocorticoids Sx
Hypotension, dizziness
Hyperkalemia,hyponatremia (salt craving)
Metabolic acidosis
addisons
↓Androgens:
↓ Axillary and pubic hair
Loss of libido
Amenorrhea in women
AI
Morning serum cortisol test value that suggests Adrenal Insufficiency
Morning serum cortisol
Normal: 10–20 µg/dL
↓ serum cortisol levels (≤ 3 µg/dL): strongly suggests AI
AI
ACTH levels for primary, secondary, tertiary
Obtain baseline level simultaneously with morning cortisol
↑ ACTH: suggests primary AI
↓ or normal ACTH: suggests secondary/tertiary AI
Adrenal insufficiency
High-dose ACTH stimulation test
Measure a baseline serum cortisol and plasma ACTH
Administer 250 mcg of cosyntropin (synthetic ACTH) IV or IM
Measure serum cortisol at 30 and 60 minutes
↓ cortisol level; ↑ ACTH = primary adrenal insufficiency
↓ cortisol level; ↓ or low normal ACTH = secondary adrenal insufficiency
Addisons
Tx
Glucocorticoid replacement
Use the lowest tolerated dose to control symptoms
Oral hydrocortisone in 2-3 divided doses
Stress dosing
Used for illnesses and before surgery
Dose is 3x the maintenance dose x 3 days
Addisons
Tx
Mineralocorticoid replacement
Fludrocortisone (Florinef)
Mineralocorticoid agonist, but also stimulates glucocorticoid receptors
Increase sodium and water reabsorption
Duration of action 8-12 hours
Side effects: fluid retention, hypertension, edema, hypokalemia, hyperglycemia
Adrenal Crisis
general
Medical emergency
More likely to occur in primary disease than secondary disease
Usually precipitated by severe stress (infection, trauma, surgery
Adrenal crisis
Clin man
Profound weakness
Abdominal pain – mimics an abdominal emergency
Hypotension
Orthostasis
Shock
Fever – when precipitated by infection
Adrenal crisis
Tx with dosing
IV fluid resuscitation
Hydrocortisone phosphate or hydrocortisone sodium 100-300 mg IV over 30 seconds, then 50 mg every 6 hours
Treat any electrolyte imbalances and hypoglycemia
Search for the underlying condition and treat accordingly
