Adrenal gland Flashcards
Adrenal gland: structure & what each part makes?
o Cortex: 3 zones “GFR” from outside to inside
o Glomerulosa: mineralocorticoids i.e. aldosterone
o Fasciculata: glucocorticoids
o Reticularis: androgens
o Medulla: catecholamines
o Inside
Normal physiology of adrenal steroid secretion?
o All steroids are made from cholesterol
o Lipoprotein A brings cholesterol to the adrenal gland
o Side chains get cut off to give you pregnenolone
o Pregnenolone →
• Aldo
• Cortisol
• DHEA → Androstenedione → testosterone in adrenals, testis, ovary
• Testosterone → dihydrotestosterone (sexual hair, normal development of prostate/seminal vesicles)
• Testosterone → estrogens (estradiol) in both men/women = aromatization reaction
o ACTH: primary signal for cortisol; also signals to aldo and androgens
What controls ACTH release?
CRH from hypothalamus –> ACTH secretion in pituitary
- Diurnal periodicity: bursts during sleep; lowest at 11 pm, highest at 8 am
- Negative feedback
- Stress increases it i.e. higher during open heart surgery v. hernia repair
What are the sx of hypoadrenalism?
o Glucocorticoids: hypoglycemia, fatigue, anorexia, weight loss, hypotension
o Mineralocorticoids: hyponatremia, hyperkalemia, hypotension, dizziness
o Androgens: reduced pubic & axillary hair in women
Which major symptom can you use to distinguish primary v secondary hypoadrenalism?
Skin hyperpigmentation
o Primary → hypersecretion of ACTH = MSH-like effect → hyperpigmentation (adrenal problem)
o Secondary → no hyperpigmentation bc you have ACTH deficiency (pituitary problem)
How can you get primary hypoadrenalism? acute & chronic
Acute: = Water-house Friederichsen Syndrome
Also- bilateral acute adrenal hemorrhage associated with pregnancy
Chronic = Addison’s Disease
Waterhouse-Friederichsen Syndrome
Acute hemorrhage/necrosis of adrenals
Septicemia with meningococci –> massive adrenal hemorrhage → hypotension, purpura, cyanosis
Treat with antibiotics & steroids
Addison’s disease- causes?
- Autoimmune adrenalitis = JFK had this
- Small glands, cortices thinned; diffuse atrophy of all cortical zones, lymphoplasmacytic infiltrate, medulla unaffected
- Infetions i.e. TB, fungi – would affect cortex & medulla
- Metastatic tumors
- Amyloidosis
- Hemochromatosis
• Clinical findings involves all 3 parts of the cortex: mineralocorticoid deficiency, glucocorticoid deficiency, & adrogenic deficiency
How do you treat Addison’s disease?
o Glucocorticoids
o High Salt diet
o Florinef (mineralocorticoid), if necessary
o Stress response – if they get a viral infx, triple the dose of the glucocorticoids for a few days to help fight the infx
o ID bracelet
How can you get secondary hypoadrenalism?
o Any disorder of the hypothalamus or pituitary leading to diminished ACTH e.g. infection, pituitary tumors, including metastatic carcinoma, irradiation
Whta’s the appropriate diagnostic testing for hypoadrenalism?
o Serum ACTH: for diagnosing primary hypoadrenalism: high in primary
o ACTH (cortrosyn) stimulation test: give ACTH →
• normal will respond by having increased cortisol levels
• Addison’s don’t respond bc they are already high in ACTH
• Secondary adrenal failure will have a partial response bc they have ACTH failure; how much they respond depends on how long ago was their hypopituitarism
o To diagnose central hypoadrenalism: ACTH failure
• 8 am cortisol, ACTH
• Cortrosyn (ACTH) stimulation test
• Insuilin tolerance test – but has risk of seizure
• Response to physiologic dose of glucocorticoids – watch out for placebo
o Once you have a dx, define the causes of adrenal failure:
• Adults: autoimmune, TB, hemorrhage, metastasis, AIDS, adrenoleukodystrophy, drugs, pituitary-hypothalamic disorders
• Children: same as adults + genetic causes
Hyperadrenalism: 3 distinctive clinical syndromes
o Excess cortisol= Cushing’s
o Excess aldosterone = primary hyperaldosteronism
o Excess androges = adrenogenital or virilizing syndrome
o Cushing’s Syndrome: 4 causes
1 Adrenal neoplasm: ACTH independent
2 Cushing’s disease: pituitary adenoma; ACTH dependent
• Causes adrenal cortical hyperplasia: in response to the excess ACTH, you get excess growth of the adrenal cortex
3 ACTH producing tumor/paraneoplastic syndreom: i.e. carcinoma of lung, thyroid can make ACTH = ACTH dependent
• Causes adrenal cortical hyperplasia also!
4 Exogenous = from drugs, most common!
Cushing’s dz v. syndrome:
o Syndrome includes all 4 causes & is all the things that happen to you when you have cortisol secretion for too long
o Disease is just the ACTH secreting pituitary adenoma
Signs and Symptoms of Cushing’s syndrome
Excess cortisol –>
o Abnormal fat distribution:
• Dorsal fat pad
• Moon face
• Thin arms & legs
• Pendulous abdomen
o Increased protein catabolism:
• Ecchymoses (bruises)
• Thin skin
• Striae
• Poor wound healing
• Osteoporosis
• Muscle wasting
• Suppressed resonse to infx
o Also: diabetes, psych sx
o In Cushing’s syndrome, when its ACTH-dependent, you can also get:
o Adrenal androgen excess
• Hirsuitism/deep voice/abnormal menses/acne in women
o Mineralocorticoid excess:
• Hypokalemia with alkalosis
How do you diagnose Cushing’s syndrome?
o (1) Screen: see if they respond to dexamethasone: give 1 mg at night & see if their cortisol levels are low in the morning (normal); if high, possible Cushing’s syndrome
• False positive: acute viral infection/stress, obese so it didn’t distribute properly, didn’t take the pill, taking other meds that interfered
o (2) Confirm the dx: 24 h urine free cortisol
• Will be high in Cushing’s, also in prolonged ACTH, acutely ill
o (3) 11 pm salivary cortisol in Cushing’s: should be low in normal, high in Cushing’s bc they don’t have normal diurnal variation
How do you determine the underlying cause of Cushing’s once you confirmed the dx?
(1) measure ACTH: if low, you know it’s an adrenal tumor
(2) 8 mg dexamethasone test at 11pm: won’t suppress morning cortisol = pituitary dependent or ectopic; those who suppress have adrenal Cushing’s
(3) CRH test: distinguish ectopic from pituitary
• Normal will have a normal response to CRH (not too big, not too small)
• Pituitary dependent Cushing’s = exaggerated response
• Ectopic Cushings = no response
• Remember that CRH is the hypothalamic hormone that stimulates ACTH
(4) Petrosal sinus sampling study: invasive, expensive, but helps distinguish pituitary from nonpituitary
• Catheter into petrosal sinus to drain pituitary & measure blood from here + peripheral vein
• If ectopic, values will be the same
• If pituitary dependent, ACTH will be at least 3x as in peripheral vein
o Unusual causes of Cushing’s?
o Ectopic CRH secretion by tumor
o Alcoholic pseudoCushing’s
o Adrenal adenomas with ectopic receptors to LH, vasopression, GIP, etc
o Bilateral adrenal nodular hyperplasia
o Munchhausen’s syndrome
o Excessive topical exposure (skin, lungs, etc)
Primary hyperaldosteronism: causes? Sx?
o Conn syndrome: aldo-secreting tumor
o Bilateral adrenal hyperplasia
o Sx of both: hypertension, polydipsia (thirst), polyuria (lots of urine), hypernatrima (due to volume depletion), hypokalemia
Cortical neoplasms: adenomas v. carcinomas
o Can be functioning (produce hormones) or non-functioning (most commonly)
• Functioning includes Cushings, Conn, sex-steroid producing
o Adenomas: benign
• Discrete, small (<2.5 cm, <30 gm), yellow-orange, usually without necrosis or hemorrhage; lipid rich & lipid poor cells with little size variation; looks like normal cortex but loses its architecture
o Carcinomas: malignant
• Unencapsulated, large (>20 cm, >200gm), yellow w/ hemorrhagic, cystic & necrotic areas; micro: ranges from mild atypia to wildly anaplastic- cells can be big, small, and mitotic!
o How do you diagnose primary hyperaldosteronism?
o Plasma aldo/renin ratio: if high >25, primary hyperaldo
o Abdominal CT for tumor (but many times it’s too small)
o Adrenal vein sampling to confirm presence of unilateral source of aldo
• If they lateralize= need surgery
• If doesn’t lateralize, suggests hyperplasia; treat with spironolactone = aldo antagonist
Glucocorticoids biological effects
- Increase gluconeogenesis
- Redistribute adipose tissue
- Muscle atrophy & weakness
- Skin fragility, bruising, poor wound healing
- Osteoporosis
- Suppression of immunity & inflammation
Desirable & undesirable effects of administering glucocorticoids?
- Desirable pharm actions of them? Anti-inflammatory, immunosuppressive, hypocalcemic, reduced CSF pressure, enhanced lung maturation in prematurity
- Undesirable pharm actions of glucocorticoids? Immunosuppression, osteoporosis, avascular necrosis of the hip/humerus, reduced muscle mass, poor wound healing, skin fragility, insomnia, depression, anxiety, psychosis, htn, diabetes
Androgens biological effects
- Sexual hair growth
- Penile and clitoral enlargement
- Scrotal and labial pigmentation
- Increased muscle size & strength
- Acne, seborrhea
- Reduced subcutaneous fat
- Linear bone growth
