Adrenal Flashcards
What are the layers that secrete the adrenal hormones?
- Zona Glomerulosa -> mineralcorticoids -> aldosterone
- Zona Fasiculata -> glucocorticoids -> Cortisol
- Zona Reticularis -> androgens -> sex hormones (dihydrotestosterone & estradiol)
- Medulla -> epinephrine & norepinephrine
Which enzyme is responsible for the formation of the sex hormones & cortisol?
17a -> for both
21 & 11B -> cortisol only
Which enzymes are responsible for the formation of aldosterone?
21 & 11B
if there is a deficiency in enzyme 17a, what will be affected?
- NO cortisol & NO sex hormones
- aldosterone will increases -> Conn’s disease
if there is a deficiency in enzyme 21, what will be affected?
- NO aldosterone & NO cortisol
- increase in sex hormones -> adrenogenital syndrome
if there is a deficiency in enzyme 11B, what will be affected?
- NO aldosterone & NO cortisol but their precursors are present
- so there is an increase in sex hormones but no syndrome
What will occur in case of any adrenal hormone deficiency?
- positive feedback to the pituitary gland to secrete more ACTH -> which will cause hyperplasia in the adrenal gland -> leading to an increase in the only normal pathway while the rest are still deficient
What is the function of aldosterone?
- Na & H20 retention
- K excretion
- increases blood volume -> increases blood pressure
- vasoconstriction
What are the factors that increase aldosterone?
- dehydration
- hypovolemia
- hyponatremia (decreased sodium)
- hypotension
- renin from the kidney -> increases angiotensinogen (liver) -> increases angiotensin I -> ACE (lungs) -> ANGIOTENSIN II -> increases aldosterone
What are the metabolic effects of cortisol?
1- on fat: mobilization
- if excess -> deposition in abnormal sites (face, neck, & abdomen)
2- on proteins -> anabolism
- if excess -> catabolism (muscle wasting & osteoporosis)
3- on carbs -> increase gluconeogenesis
- in excess -> decreased glucose uptake by muscles & hyperglycemia
4- on electrolytes -> Na & H20 retention & K excretion
5- on blood -> increases RBCs & decreases eosinophils & lymphocytes
6- androgenic
7- anti-allergic -> decreases Ag-Ab reaction
8- anti-inflammatory
- in excess -> decreases fibrous tissue formation (collagen) & destroys elastic fiber & decreases inflammatory cells
What are the functions of the Zona Reticularis hormones?
androgens & small amounts of estrogen & progesterone
- dehydro-epiandrosterone -> enhances protein anabolism & promotes development of secondary sexual characters
- end product (ketosteroids) are excreted in the urine (used for diagnosis)
What are the causes of Conn’s syndrome?
Primary hyperaldosteronism
- adenoma
- hyperplasia of Zona glomerulosa
- carcinoma
What is the clinical picture of Conn’s syndrome?
1- hypertension: due to sodium retention
2- hypokalemia
- apathy, paresthesia
- arrhythmias (extrasystoles)
- atony of the intestines (constipation & paralytic ileus)
- muscle weakness & episodic paralysis (dyspnea)
- impaired glucose tolerance test
3- alkalosis (metabolic)
- due to heavy loss of H+ with K in urine -> tetany due to decreased ionized calcium
4- NO EDEMA
- K diuresis -> polyuria
- impaired tubular reabsorption of water
What investigations are done in Conn’s disease?
1- BIOCHEMICAL
- hypokalemia (N = 3.5 - 5)
- hypernatremia (N=140)
- alkalosis (increased serum HC03) (N= 22 - 30)
2- URINARY
- polyuria -> due to K diuresis
- increased K & decreased sodium
- increased aldosterone excretion (N= 12-50 ug/24h)
3- MEASURE PLASMA LEVELS
- decreased Renin
- increased aldosterone despite high Na load
4- US & adrenal CT -> for adenoma & carcinoma
How is Conn’s syndrome treated?
- Surgical removal of adenoma
- MEDICAL in bilateral & hyperplasia -> Amiloride (K-sparing diuretics)
What are the causes of Cushing’s syndrome?
ENDOGENOUS tumors
1- pituitary adenoma -> secondary hypercortisol
2- adrenal -> primary Cushing’s syndrome
3- paramalignant -> increases ACTH -> increases cortisol
EXOGENOUS -> corticosteroids (most imp)
What are the general clinical features of Cushing’s syndrome?
1- abnormal fat deposition
- face -> moon face
- neck -> buffalo hump
- abdomen -> trunkal obesity (Samboxa shooed obesity)
2- protein catabolism
- Muscle wasting & weakness
- osteoporosis
3- hyperglycemia -> steroid diabetes (one of the most imp causes of secondary diabetes)
4- Hypertension (sodium & water retention) & hypokalemia (polyuria & alkalosis)
5- plethoric face due to polycythemia (increase RBCs)
6- in females -> amenorrhea, acne, & hirsutism
- in males -> decreased libido, impotence
7- decreases collagen & fibrous tissue formation (delayed wound closure)
- bruises & purpura
- STRIA RUBRA (rupture of weakened s.c tissue due to collagen deficiency)
8- decreases WBCs (eosinophils & lymphocytes) -> more prone to infection
8-
What are the clinical features that will help us identify the etiology?
- virilization -> adrenal carcinoma (increase cortisol & androgens)
- hypokalemic alkalosis, myopathy, & hyperpigmentation -> ectopic (paramalignant)
- in children -> adrenal carcinoma
- in males -> ectopic
- in women -> pituitary
What are the investigations that suggest Cushing syndrome?
1- hypokalemic alkalosis & hypernatremia
2- increased RBCs & decreased lymphocytes & eosinophils
3- impaired glucose tolerance or DM
4- osteoporosis or unexpected fractures (in young patients too young for osteoporosis)
Which investigations confirm the diagnosis of Cushing syndrome?
1- plasma cortisol level (N= 5 - 20) -> taken at 8am then 4pm
- should be higher in the morning & 50% less in the afternoon
- loss of diurnal variation suggests persistent elevation
2- urinary steroid excretion (24hr collection)
- measure hydroxycorticosteroids or free urinary cortisol
- if found in excess overnight
- > do LOW DOSE dexamethasone suppression test (1mg ORAL at night)
- after suppression test take a sample at 8am it SHOULD BE <7 (if not then Cushing’s)
What are the investigations that will help us differentiate between the 3 types of Cushing syndrome?
1- measure plasma ACTH
- very high -> Ectopic
- High -> pituitary
- low or absent -> adrenal
2- HIGH DOSE dexamethasone suppression test
- 2mg every 6hrs IV for 2 days
- if pituitary Cushing’s -> plasma cortisol decreased
- if ectopic or adrenal -> NO EFFECT
3- localization imaging
- abdominal US, CT, retrograde venography -> adrenal tumors
- sellar x-ray -> brain tumors (pituitary)
- chest x-ray -> bronchogenic carcinoma (ectopic)
What are the causes of pseudo-Cushing syndrome?
- chronic alcoholism
- severe illness
- obesity
- depression
increase in cortisol levels & absent diurnal variation
What is the treatment for pituitary Cushing syndrome?
Surgical removal
What is the treatment of adrenal cushing?
REMOVAL
- pre-op -> give metyrapone to decrease cortisol levels
- post-op -> give mitotane for residual disease
What is the treatment for ectopic cushing’s?
- treat original tumor
- surgical removal
- metyrapone +- mitotane
How is exogenous Cushing’s treated?
STOP using corticosteroids
What are the causes of Addison’s disease?
1- autoimmune adrenalitis (most common)
- can occur with other auto-immune diseases
2- miliary TB
3- following bilateral adrenalectomy & congenital enzymatic defects
4- amyloidosis, sarcoidosis, hemochromatosis
5- secondary to hypopituitarism (Simmonds disease)
What are the clinical features of Addison’s disease?
deficiency in all hormones of the adrenal gland
ADDISONS TRIAD: hypotension + hypoglycemia + hyperpigmentation
1- asthenia: weakness of muscles & weight loss
2- hypotension: systolic BP <110mmg & postural hypotension (hypovolemia)
3- hypoglycemia
4- hyperpigmentation
5- loss of adrenal androgen: infertility & amenorrhea in females
6- GIT disturbances: nausea, vomiting, diarrhea
7- polyuria -> Na diuresis (could lead to severe dehydration)
What is the cause of Asthenia in Addison’s disease?
- lack of cortisol -> decreases RBCs -> anemia
- hyperkalemia -> arrhythmia & muscle weakness
- hypoglycemia
- muscle cramps -> hyponatremia
What is the cause of postural hypotension in Addison’s disease?
- NO sodium -> NO vasoconstrictrion -> rapid drop of BP
& - hypovolemia & dehydration
What is the cause of hyperpigmentation in Addison’s disease?
1- hypocorticism -> increases ACTH -> increase melanocyte stimulating hormone -> increases pigmentation (primary hypoadrinalism)
2- destruction of adrenal medulla -> accumulation of tyrosine -> shifted to form melanin instead of epinephrine & norepinephrine
What are the investigations preformed to diagnose Addison’s disease?
1- plasma cortisol level decreased
2- decreased 24hr urinary cortisol or ketosteroids
3- ACTH stimulation test
- normal response -> increase plasma cortisol by 6ug above basal value
- in primary adrenal insufficiency -> no response
- in secondary adrenal insufficiency -> normal response (increased cortisol)
4- biochemical changes: hyponatremia, hyperkalemia, acidosis, hypoglycemia
5- urine -> increased volume (Na diuresis) & decreased K excretion
6- blood
- normochromic anemia
- haemoconcentration
- eosinophilia & lymphocytosis
What is the treatment of Addison’s disease?
1- replacement therapy -> prednisolone (cortisol)
-> fludrocortisone (aldosterone)
2- treat the cause
3- management during stressful conditions
- MINOR illness -> double the dose until condition is resolved
- MAJOR elective surgery -> 100mg (high dose) hydrocortisone the night before & 100mg every 8 hours after surgery -> taper it to reach the previous dose within the next 3 - 5 days
- MAJOR emergencies (treated like addisonian crises) -> fluids, hydrocortisone & fludrocortisone, treat the cause
What are the causes of Addisonian crises?
1- after sudden corticosteroid withdrawal (most imp)
2- previously undiagnosed patient
3- patient on treatment that underwent a major catastrophe without increasing their dose
4- Sheehan sydrome
5- after bilateral adrenalectomy
6- acute meningococcal septicemia (waterhouse friderichsen syndrome) -> hemorrhage -> acute adrenal failure
7- medical treatment for adrenal carcinoma (metyrapone or mitotane)
8- massive thrombosis of adrenal veins (during pregnancy, puerperium & burns)
What are the clinical features of Addisonian crises?
sudden onset of
- severe weakness
- mental confusion
- anorexia, nausea, vomiting, diarrhea
- dehydration -> shock
- coma & death within 24 hours if untreated (from severe hypoglycemia, hypotension, dehydration)
What investigations are done to confirm addisonian crises?
- severe hyponatremia
- hyperkalemia
- severe decrease in serum cortisol
What is the treatment method for addisonian crises?
1- IV normal saline & glucose
2- hydrocortisone 100mg IV then every 8 hours 100mg-> taper until reaching the previous dose
3- fludrocortisone
4- treat cause
What is the adrenogenital syndrome?
inherited enzymatic defects in the enzymes necessary for the synthesis of cortisol -> increased ACTH adrenal hyperplasia & synthesis of the other hormones
What are the clinical features of enzyme 17 oH ase deficiency?
NO cortisol NO sex hormones INCREASED aldosterone
- Hypertension
- in females -> sexual infantilism
- in males -> pseudohermaphroditism
What are the clinical features of enzyme 21 oH ase deficiency?
most common
NO aldosterone NO cortisol INCREASED sex hormones
- hypotension
- hyperkalemia
- female pseudohermaphroditism (big clit, small vagina, libra majora are big & fused)
- male precocious puberty (macrojenitosmia praecox) but no spermatogenesis & dwarfism
What are the clinical features of enzyme 11B oH ase deficiency?
NO cortisol NO aldosterone but deoxycorticosterone & deoxycortsol & androgens are present
- hypertension
- virilization in females pseudohermaphroditism
- precocious puberty
What is the treatment of adrenogenital syndrome?
1- replacement therapy -> prednisone (7.5mg/day) & fludrocortisone (o.1mg/day)
2- surgical correction -> female pseudohermaphroditism
What is pheochromocytoma?
catecholamine releasing tumor (commonly benign) rule of 90% - unilateral 90%- bilateral 10% - benign 90% - malignant 10% - adrenal 90% - extra adrenal 10% - adults 90% - children 10%
Familial types -> MEN II
What are the clinical manifestations of pheochromocytoma?
sympathetic overactivity
1- attacks of one or more times/week for < 1 hr
- vasoconstriction -> cold hands & feet & pallor
- hypertension
2- complications of hypertension on CVS & CNS
3- constipation & ischemic enterocolitis
4- diabetogenic (anti-insulin)
What are the investigations done for pheochromocytoma?
1- urine examination
- 24hr metanephrine (for diagnosis)
- free urinary catecholamines
- VMA 24hrs (only for screening)
2- plasma catecholamine
3- stimulation test is very dangerous
4- clonidine suppression test
- in normal hypertension -> plasma NA decreases to normal rage 3 hours after taking clonidine
- inn pheochromocytoma -> no response
5- localization of tumor
How is pheochromocytoma treated?
1- MEDICAL
- acute therapy for patients with severe hypertension: Phentolamine (a blocker) THEN propranolol
- prolonged medical therapy -> if surgery is delayed
2- SURGICAL
- PRE-OP -> Na nitroprusside or phentolamine to stabilize blood pressure
- surgical removal of tumor
What is the difference between MENI & MENII syndromes?
MEN I (Wermer’s syndrome)
- parathyroid
- pituitary
- pancreas
MEN II (Simple’s syndrome)
- pheochromocytoma
- medullary thyroid carcinoma
- parathyroid adenoma
How do we diagnose hypogonadism?
- decrease in LH & FSH -> pituitary cause (hypogonadotrophic gonadism)
- increase LH & FSH but decreased testosterone -> primary testicular disease
- normal or elevated LH & FSH & testosterone -> end organ resistance
- decreased testosterone with no features of hypogonadism -> decreased sex hormone binding globulin (SHBG)
How do we treat hypogonadism?
- androgen replacement -> IM
- pituitary causes -> like before
- hypothalamic causes -> LHRH
What are the types of hair?
- Lanugo -> in fetus & newborn
- Vellus -> fine adult hair covering body
- Terminal hair -> thick pigmented hair on scalp & pubic area
What are the causes of Hirsutism?
ANDROGEN INDEPENDENT
- constitutional, familial, racial
- starvation & anorexia
- drugs: minoxidil, phenytoin, diazoxide
ANDROGEN DEPENDENT
- ovarian -> arrenoblastoma, idiopathic hirsutism, PCO
- adrenal -> virilizing adrenal tumor, congenital adrenal hyperplasia, Cushing’s
- drugs -> androgens
drugs that hinder action of androgen on hair follicles
- ketoconazol
- spironolactone
- cyproterone acetate
