Adrenal Gland Disorders And Physiology Flashcards
Cushing syndrome causes
Hyper secretion of cortisol in the system
Can be either:
- a mass in the adrenal cortex
- anterior pituitary issues
- hypothalamus issues
If mass on adrenal cortex = decreased ACTH in blood
If anterior pituitary issue = increased ACTH in blood
If hypothalamus issue = increased CRH and ACTH
Cortisol effects on the body
Upregulate gluconeogenesis
Upregulates protein catabolism
Upregulates lipolysis
- these lead to hyperglycemia, muscle wasting (especially in extremities)
Decreases synthesis of collagen proteins
- leads to striae in the trunk/abdomen
Increases appetite and weight gain
Increases fat deposition*
- seems counterintuitive but the body doesn’t take fat away from the neck and also upregulates appetite . Leads to “buffalo hump”.
What is the purpose of the dexamethasone suppression test
Dexamethasone = synthetic glucocorticoid hormone that acts like cortisol
Healthy patients = ACTH and cortisol decrease since dexamethasone induces negative feedback
- this is a positive dexamethasone test
In primary and secondary adrenal issues = ACTH stays low but cortisol DOESN’T CHANGE
- **this is a negative dexamethasone test*
How does hypercortisolism produce hypertension?
Cortisol = upregulates B1 receptors on vascular smooth muscles
Also hypercortisolism casues hyperaldosteronism as a side effect
- hyperaldosteronism = increased salt and water retention and leads to high blood pressure via increased preload and cardiac output from water retention
- this also causes hypokalemia since hypercortisolism casues sodium retention but potassium secretion in CD and DCT cells
What are effects of cushings disease that is only seen in women
Cushing syndrome caused by adrenal cortex tumors leads to excess DHEA and androstenedione are secreted
Masculinization effects (hirsutism, decreased breast size and masculine facial features. Also amenorrhea)
In males it does this also, but the testies already produce a lot of androgens such as DHEA and androstenedione. So this increases doesnt really productable notable sex androgen sideffects
What are treatments for Cushing syndrome
1) surgery of adrenal masses is usually #1
2) can also give ketoconazole initially before surgery
- this drug inhibits cholesterol desmolase which is the enzyme used to synthesize adrenal cortical steroids
Addison’s disease
Primary adrenocortical insufficiency
Hypocortisolism usually due to either TB infections or autoimmune destruction (most common)
Symptoms:
- weight loss
- extreme fatigue
- decreased hair in axiallary and pubic regions*
- hyperpigmented skin*
- amenorrhea
- orthostatic hypotension
- tachycardia*
Tachycardia seems counterintuitive but the decrease in BP and orthostatic HTN causes baroreceptor reflex activation
- this leads to increased sympathetic outflow to heart which stimulates the SA node to increase pulse/heart rates. This gets even faster when a patient stands up (orthostatic exaggerates this)
Electrolyte abnormalities (all are caused by decreased aldosterone effects on principalcells)
- hyponatremia
- hyperkalemia
- decreased serum osmolarity
Difference between primary and secondary adrenal insufficiency
Primary = cortex is disabled itself
- ACTH test will show THE SAME levels of cortisol and aldosterone production (since it is already really high and the adrenal gland is not responding to ACTH)
Secondary = pituitary or hypothalamus is dysfunctional
- ACTH test will show DECREASES in cortisol and aldosterone (since the adrenal cortex still works)
How does orthostatic hypotension occur in hypocortisolism?
Decreases in levels of cortisol and aldosterone causes down-regulation B1-adrenergic receptors
- this leads to decreases Total peripheral resistance and arterial pressure. As well as venous return, cardiac output
Also decreased aldosterone results in hypovolemia which further complicates BP, arterial pressure
What is the actual reason behind why hyponatremia occurs in Addison’s disease?
Two fold
1) decreased aldosterone leads to less sodium reabsorption
2) decreased aldosterone leads to uninhibited ADH levels in the body which works to keep water in the body since it senses hypovolemia (it also senses hyperosmolarity, but ADH is more sensitive to hypovolemia) . However the ADH inadvertently causes worse hyponatremia by diluting it
Why does Addison’s disease result in metabolic acidosis?
Aldosterone deficiency also leads to less excretion of H+ ions and less “new’ bicarbonate production via carbonic anhydrase enzymes
- this is done in the intercalated cells of the CD
- this is a type 4 renal tubular acidosis**
Also because Addison’s disease results in hyperkalemia, hyperkalemia also inhibits renal NH3 synthesis which causes decreased H+ secretion
How does Addison’s disease result in hyperpigmentation
Primary Decreased cortisol results in elevated ACTH. On top of working on the adrenal cortex, ACTH also works on stimulating pro-opiomelanocortin (POMC) synthesis in the anterior pituitary. (Because POMC is precursor for ACTH)
POMC level increases results in melanocyte-stimulating hormone upregulation which increases melanocyte levels.
Why does Addison’s disease result in decreased axillary and pubic hairs
Adrenal cortex deficiency, on top of aldosterone and cortisol decreases, also decreases the levels of androgens in the body (DHEA and androstenedione)
This leads to loss of hair in these areas and libido overall
What is the treatment of Addison disease?
Hydrocortisone (glucocorticoids) and fludrocortisone (mineralcorticoids)
- both are oral and act as synthetic hrormones produced by the adrenal cortex
NOTE: glucocorticoids need to be broken into two doses with a larger dose in the morning and smaller in the afternoon.
- this is because the adrenal cortex secretes cortisol in a Pulsatile fashion with most occurring when waking up and slight amounts in the evening/afternoon
21-hydroxylase deficiency
Congenital adrenal hyperplasia
Deficiency in an enzyme that is required to catalyze 2 conversion pathways.
1) progesterone -> to 11-deoxycorticosterone required for aldosterone
2) 17-hydroxyprogestrone -> 11-deoxycortisol required for cortisol
this prevents synthesis of aldosterone and cortisol and also causes a build up of progesterone, pregneolone (androgens)
- however its worth noting that most CAH cases results in only 20% of enzyme activity. Not a complete loss of enzyme
Also excess ACTH in response to lower cortisol levels produces adrenal hyperplasia which limits the Addison disease symptoms
Symptoms from loss of aldosterone and cortisol
- very mild Addison’s disease symptoms especially
- hypotension
- Hypoglycemia
- hyperkalemia
- metabolic acidosis
Symptoms from excess adrogens
- ambiguous genitalia
- masculinization
Treatment = same as addisons but may not require mineral corticoid therapy unless aldosterone symptoms are bad
Primary hyperparathyroidism
Excess PTH hormone release which causes elevated calcium levels in blood
- normal total calcium = 10 mg/dL
PTH action = works with active vitamin D to stimulate osteoclasts to break down bone and add calcium and phosphate to the blood
- however, phosphate is excreted out via PTH binding to PCT Gs-protein Na/Phosphate cotransporter and inhibits this protein. Also PTH stimulates calcium reabsorption
- this loss of phosphate in urine causes serum calcium to remain high but low phosphate levels in blood
Symptoms
- hypercalciuria and calcium kidney stones*
(this seems strange but the excess calcium increase calcium excretion AND reabsorption)
- severe constipation
- weakened bones and increased risk of bone fractures
- severe back pain similar to kidney stone symptoms
NOTE: often times hyperparathyroidism is asymptomatic until eventually levels get high enough. Classic case shows a patient who has had this for a while and then takes calcium or vitamin D supplements and then gets symptoms
Why is albumin concentration importaint in diagnosing primary parathryodism?
Free calcium is the only active calcium. It also is the only type of calcium that can actually cause side effects.
However, total calcium includes free and bound calcium and it is the only calcium level measured
- therefore it is important to know if calcium levels are high due to hyperalbuminemia (bound calcium and incidental) or free calcium being high (free calcium caused by excess PTH)
Primary hyperparathyroidism = NORMAL or LOW serum albumin
Humoral hypercalcemia of malignancy
Most often seen with lung and breast cancer cells which can secrete PTH-related peptides (this acts as analog PTH).
Causes hypercalcemia symptoms but LOW PTH**
- still shows normal albumin, hypercalcemia and hypophosphatemia
- Shows low PTH since the body assumes it has PTH floating (due to hypercalcemia) around so therefore there is negative feedback on the parathyroid glands which’s top secreting PTH
**Can cause nephrogenic DI due to calcium deposits in the inner medulla of the kidney
Treatment = loop diuretics (furosemide) to correct serum calcium
- loop diuretics block sodium reabsorption which also secondarily prevent calcium reabsorption due to no positive potential difference
Also pamidronate (bisphosphonate analog that inhibits osteoclasts)
Diabetes mellitus type 1
Caused by insufficiency of pancreatic B-cells to make insulin
Causes hyperglycemia in two ways:
- decreases glucose uptakes in cells (no insertion of GLUT4 receptors in muscle and adipose cells)
- increases gluconeogenesis in liver cells
Classic initial triad of symptoms
- weight loss with high appetite
- polydipsia
- polyuria
Also causes:
- neuropathy
- urinary incontinence
- orthostatic nephropathy
End stages:
- renal failure via nephrotic syndrome
- loss of neuronal actions
Urine will show elevated glucose and ketones
Blood shows elevated plasma ketones and fasting plasma glucose
Treatment:
- insulin injections
- if microalbuminemia is present = also give ACE to slow down nephrotic syndrome
Why is polydipsia and polyuria occur in diabetes
Polydipsia
- high glucose in blood causes osmoreceptors to trigger thirst due to hyperosmolarity
Polyuria
- high glucose in tubular fluid causes glucose to be secreted in uterine and promote osmotic diuresis
Androgen insensitivity syndrome
Primary amenorrhea/ 46XY syndrome
Casued by a lack of androgen receptors on target tissues
Results on female phenotypes but intrabdominal testicles and male genotype
- the testies still produce anti-mullarian and testosterone hormones but the tissues don’t respond so the tissues develop into female
Until week 6, the gonads are bipotential
- male s= Y chromsome differentiates gonads into testies at week 6. Testes produce anti-mullarian hormone and testosterone from testies which produces male phenotypes
Symptoms:
- no period, but normal female growth in breasts and body tissue
- blind end vagina with no cervix
- stupid high levels of testosterone in blood*
(Happens because the testies chronically secrete large amounts of testosterone and cant shoes negative feedback since the hypothalamus has no receptors)
Treatment = removal of testies and estrogen replacement therapy
What do anti-mullarian and testosterone do specifically in neonate?
Anti-mullarian = produced by serotonin cells to induce atrophy of the mullarian ducts (this is the primordial female genital tract)
Testosterone = produced by leydig cells to stimulate differentiation and growth of wolffian ducts (male genital tract)
if these aren’t produced, leads to development of ovaries at week 9 and stimulation of
Kalimann syndrome
Male hypogonadism
Only found in males and is caused by the inability of the hypothalamus to secrete proper levels of GnRH. However the hypothalamus will secrete all hormones normally
- shows tonically low testosterone and LH in blood
- WILL however show normal testosterone and LH if given GnRH injection test** (diagnostic)
- results in extremely long puberty
Symptoms:
- always looks young than actual age
- very long arms for body
- erectile dysfunction and loss of libido
- little to no body or facial hair
- poor sense of smell or complete absence*
*normally GnRH producing neurons migrate from olfactory tissues to hypothalmus during growth. However in kallmann syndrome this doesnt happen so olfactory neurons dont have space to grow properly. Results in serious smell deficences or complete loss of smell (anosmia)
How do you treat kallmann syndrome?
Pulsitile GnRH
- initiates correct puberty instead of over stimulating and desensitizing the anterior pituitary to GnRH (would result in no changes)
5a-reductase Deficency
Loss of 5a-reductase enzyme which is required in target tissues to testosterone to turn it into dihydrotestosterone to induce actual action
Produces male muscles and genitalia while producing no body hair and head hair of a girl. Also male with testies but with a blind end vagina
tissue that require dihydrotestosterone
- external male genitalia differentiation
- male hair patterns
- sebaceous glands
- prostate growth
