Adrenal Gland Disorders And Physiology

Question 1

Cushing syndrome causes

Answer 1

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

Question 2

Cortisol effects on the body

Answer 2

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”.

Question 3

What is the purpose of the dexamethasone suppression test

Answer 3

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*

Question 4

How does hypercortisolism produce hypertension?

Answer 4

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

Question 5

What are effects of cushings disease that is only seen in women

Answer 5

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

Question 6

What are treatments for Cushing syndrome

Answer 6

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

Question 7

Addison’s disease

Primary adrenocortical insufficiency

Answer 7

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

Question 8

Difference between primary and secondary adrenal insufficiency

Answer 8

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)

Question 9

How does orthostatic hypotension occur in hypocortisolism?

Answer 9

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

Question 10

What is the actual reason behind why hyponatremia occurs in Addison’s disease?

Answer 10

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

Question 11

Why does Addison’s disease result in metabolic acidosis?

Answer 11

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

Question 12

How does Addison’s disease result in hyperpigmentation

Answer 12

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.

Question 13

Why does Addison’s disease result in decreased axillary and pubic hairs

Answer 13

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

Question 14

What is the treatment of Addison disease?

Answer 14

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

Question 15

21-hydroxylase deficiency

Congenital adrenal hyperplasia

Answer 15

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

Question 16

Primary hyperparathyroidism

Answer 16

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

Question 17

Why is albumin concentration importaint in diagnosing primary parathryodism?

Answer 17

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

Question 18

Humoral hypercalcemia of malignancy

Answer 18

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)

Question 19

Diabetes mellitus type 1

Answer 19

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

Question 20

Why is polydipsia and polyuria occur in diabetes

Answer 20

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

Question 21

Androgen insensitivity syndrome

Primary amenorrhea/ 46XY syndrome

Answer 21

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

Question 22

What do anti-mullarian and testosterone do specifically in neonate?

Answer 22

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

Question 23

Kalimann syndrome

Male hypogonadism

Answer 23

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)

Question 24

How do you treat kallmann syndrome?

Answer 24

Pulsitile GnRH
- initiates correct puberty instead of over stimulating and desensitizing the anterior pituitary to GnRH (would result in no changes)

Question 25

5a-reductase Deficency

Answer 25

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