• zona glomerulosa: mineralocorticoids (ex; aldosterone)
• zona fasciculata: glucocorticoids (ex; cortisol)
• zona reticularis: DHEA (converted to androgens)

• low renal af. art. HP
• SNS
• hyperkalemia
• ACTH

• increases blood sugar: promotes liver gluconeo., inhibits glc uptake by musc and fat (COUNTER REGULATORY HORMONE TO INSULIN!)
• stimulates lipolysis, appetite
• supresses infla and immune func, bone formation, C.T. and musc growth as well as linear growth, kids
• alters mood, behavior and cognition
• can increase BP if in excess due to mineralocorticoid activity

• not much in males
• cause hirsuitism/masc in females or pre-pubertal males if in excess
• normally imp. for maintenance of female axillary, pubic hair and maybe libido

What are the diagnostic steps we take when we evaluate someone for high cortisol?

Screening
- salivary cortisol at 11PM (should be lowest) or a 24 hour urine cortisol
Diagnostic:
- 1mg or 2mg O/N dexmethasone supression test which should bring down the cortisol level. If the cortisol remains high then most likely a pituitary adenoma, but could also be an adrenal or ectopic cortisol overproduction

- If there is too much cortisol confirmed, do a morning ACTH level (should be less than 10 pg/ml). If it is low then you know that it's an adrenal tumor probably (you would have to image the adrenals). If it's still high then you're thinking pituitary source or ectopic source

- 8mg O/N dex suppression test should bring down the cortisol level EVEN if it's a pituitary adenoma (you should now image the pituitary), and this should be done to rule out malignancy which is most likely at an ectopic site. A non-pituitary tumor would also be unresponsice to CRH, so you could stimulate with CRH to investigate for that.

How could you assess someone who you suspect is secreting too much aldosterone?

• Hypertension is usually the main clinical sign here (they also get hypokalemia)
• Serum K, aldosterone and renin are measured. Renin should be supressed by the high aldosterone level causing high plasma volume.
• Do an aldosterone supression test by infusing saline which should bring down their aldosterone
• Abdominal CT scan can see if there's an adrenal ademona

How would you treat someone who has an adrenal adenoma that is overproducing aldosterone?

• Surgical removal of tumor if possible
• If not, use spirinolactone or eplerenone to to treat the hypertension and hypokalemia
• One reason surgery may be impossible would be bilateral adrenal involvement

What are the signs and symptoms of Addison's disease?

- Most common cause is now autoimmune

- Presents with fatigue, weakness, unexplained weight loss (remember cortisol stimulates appetite!), nausea, anorexia, abdominal pain, amenorrhea. Hyperpigmentation occurs frequently (Addison loves tanning!)

- hypoglycemia, hyponatremia and hyperkalemia may be accompanied by hypotension and associated electrolyte imbalance symptoms.

What are the most common causes of Addison's disease?

-autoimmune adrenalitis

- TB

-cytomegalovirus infection due to AIDS

-anti-fungal drugs

-adrenal hemorrgage

-metastatic carcinoma

- surgical removal of adrenals

How would you treat Addison's disease?

- hydrocortisone

- fludrocortisone (mineralocorticoid)

- DHEA for women (well being and libido)

What should be considered in any patient who presents with severe hypoglycemia and hyponatremia?

• ACTH deficiency (which would be a cause of an acute adrenal crisis)
• Symptoms of acute adrenal crisis are:
• fever, hypotension and shock, nausea and vomitting, weakness, hypoglycemia
• This happens when there is not enough cortisol to respond to a stressor

How would you diagnose Addison's disease?

• By clinical findings as well as lab values
• labs should show low cortisol
• can show high or low ACTH
• a metyrapone test will block the final step in cortisol synthesis and should show a hypo-pit response with a rise in CRH and ACTH (if there is no rise, you know it's a problem at that level)
• you can do a CRH stimulation test to make sure that the pituitary is able to respond by making ACTH

Talk for a sec about secondary adrenal insufficiency

• This is when the pituitary does not make ACTH properly
• Can be due to tumors, post-partum infarction, withdrawl from exogenous GCs, irradiation, trauma
• Patients present with pallor and not hyperpigmentation
• RAS system intact
• other hormone deficiencies commonly associated.

What would a patient with Cushings syndrome look like?

- weight gain, round "moon" face, truncal obesity

- weakness

- increased BP

- hirsuitism

- amennorhea

- purple cutaneous striae

How would you diagnose Conn syndrome?

- Patient would present with incrased BP, hypokalemia

- their renin plasma levels would be low

- their aldosterone levels would be really high

*GO BACK MAKE SURE THIS IS RIGHT

- you treat with surgery (cause it's due to adrenaladenoma or hyperplasia) or spirinolactone

How do you diagnose the malignancy potential for a pheo?

• You can't unless it spreads.
• You cannot assess malignancy when considering it's morphologic features alone.

·      ↑ hepatic glucose output and glycogen stores

·      ↑ insulin resistance, permissive effect on catecholamines and glugacon

·      ↓ glucose uptake and utilization in peripheral tissues

steroid xs → hyperglycemia (eg. When on predisone, a patient’s blood sugars may increase substantially and look like diabetes, but this effect is due to steroids!)

steroid deficiency → hypoglycemia

Describe theeffect of glucocorticoids on lipid and protein metabolism:

Lipids:

·      more lipolysis leading to increased release of fatty acids

·      fat redist. - ↓ in extremities, ↑ in trunk, neck and face

steroid xs→ moon face, buffalo hump, central obesity

(eg. Person with skinny arms and legs, but a big tummy – think Cushings!)

 Proteins:

·      Catabolic effects leading to atrophy of skeletal muscle and decreased muscle protein synthesis

Steroid xs → muscle wasting and weakness, thin extremities

·      Catabolic effects leading to ↓ collagen synthesis and inhibition of fibroblasts (decreased/delayed healing)

Steroid xs → thin skin, easy bruising, purple/red striae (the red colour is because you’re seeing the vascular area just underneath where the connective tissue is torn)

·      Immunosuppression

Steroid xs → ↓ bradykinin and histamine causing ↓ vascular permeability

            -↓ delayed sensitivity - ↓ monocytes, eosinophils and antibody production

            -stabilizes lysosomes causing ↓ phagocytosis

            -↑ PMN release causing demargination and chemotaxis

(demargination refers to PMNs that are sitting inside blood vessels, but are released by steroids – they don’t do anything, but if you were to take a blood test, it would look like you have and infection because of the PMNs)

-RESULTS IN ↓ inflammation and increased susceptibility to viral, fungal and parasitic infections

·      ↓ osteoblast and osteoclast functions

·      ↓ bone formation and bone mass

·      ↓ serum calcium leading to ↓ calcium absorption and therefore ↓ activation of Vitamin D

·      ↑ renal excretion of calcium

All of this causes increased levels of PTH, which returns calcium levels to normal by activation osteoclasts in the bone (so despite all of this, patients on corticosteroids will still have normal serum calcium levels, but just weak bones)

·      ↑ BP – sodium retention, potassium loss, increased free water clearance, positive inotropic effects

Steroid xs → HTN, hypernatremia, hypokalemia, metabolic alkalosis

Steroid deficiency → hypotension, hyponatremia, shock, hyperkalemia, metabolic                                    acidosis

CNS:

Steroid xs → increased appetite (leads to weight gain), insomnia, irritability, euphoria, decreased libido, decreased memory

Steroid deficiency → depression, psychosis

growth:

Steroid xs → epiphyseal fusion and stunted growth

            -↓ bone effects of IgF1 and GH

Describe some of the effects of cortisol on other endocrine processes including the HPG axis and HPT axis

– induces cataract formation and glaucoma

            -matures lung surfactant (give to women who will deliver prematurely)

            -decreases LH/FSH secretion and therefore inhibits gonadal function

            -decreases TSH, T ₄ to T₃ conversion (therefore use in thyroid storm)

            -increases episodes of peptic ulcers and pancreatitis (b/c of affect on TGs)

What would you think of in a patient who presents with headache, palpitations and sweating?

• For endocrine, think of Pheo as this is the classic "triad"
• I would also think stuff like MI, panic attack, shock, cerebral event... there could be lots of things I would think.

What are the two major causes of adrenal hypertension?

• Pheo
• Conn's *remember with Conns you also get hypokalemia

Even though you may have already done this, explain Conn's syndrome a bit.

Conn’s Syndrome – primary aldosteronism – due to oversecretion of aldosterone by unilateral aldosterone-producing adrenal adenoma or bilateral adrenal hyperplasia
  -presents with triad of hypertension, unexplained hypokalemia andmetabolic alkalosis
  -note the lack of edema – initially there is Na and water retention, but it is followed within a few days by spontaneous diuresis (aldosterone escape) due to the secretion of atrial natruretic peptide and increased renal perfusion pressure
tx – restrict Na, surgery to remove tumor, give spironolactone, may also give Amiloride, Nefidipine or an ACE inhibior

Describe the investigations of

Primary hyperaldosteronism:

   1. 24 hour urine collection of potassium

            -inappropriate potassium wasting >30mEq/day

            -an inappropriately low potassium excretion suggests extrarenal losses (diuretics)

            -sodium induced hypokalemia strongly suggests Conn’s syndrome

      2. Plasma renin activity – is typically low (<1mg/ml/hr)

            -elevated value is due to renovascular hypertension or diuretic use

      3. Plasma aldosterone level

            >30ng/L is considered high

      4. Plasma aldosterone to renin ratio

            normal is 4-5; Conn’s syndrome would have a ratio of 30-50

      5. CT/MRI – to distinguish between unilateral adenoma/carcinoma from bilateral                                  hyperplasia

      6. Nuclear medicine – scan to detect unilateral adenoma

How would you diagnose a pheochromocytoma?

      1. History

      2. 24 hour urine looking for metabolites of epinephrine or free catecholamine

Clonidine suppression test: Will differentiate tumour from central neurogenic stimulation. Clonidine is a central α₂ agonist that will suppress catecholamine release if the cause of the excess is neurogenic.

      3. CT/MRI to look for tumrs

      4. nuclear medicine scan

How would you manage someone with a pheo?

§  Surgical resection

§  Have to pre-operatively α and β-block to control BP and reduce risk of postoperative hypotension

§  CCBs also used to control BP before surgery

§  Postoperative hypotension requires volume reexpansion

§  Check 24 hour urine catecholamines and metanephrines 2 weeks post-op and annually for 10 years

Inhibin

• Inhibits FSH

Somatostatin

• inhibits TRH and TSH
• inhibits pituitary release of GH (IGF-1 activates that by negative feedback)

Prolactin: what stimulates it, what inhibits is and what does it do?

1.)   Prolactin (PRL)

·      Stimulated by oxytocin, TRH, VIP, and estrogen and inhibited by dopamine

·      Function: lactation, increased maternal behaviour, antagonizes gonadotropin action in gonads (decreased steroidogenesis)