Disorders Of Adrenal Glands 1/2 Flashcards
What are the secretory products from the adrenal medulla?
Peptides:
- Somatostatin and substance P
Catecholamines:
- epinephrine and norepinephrine
What are all the functions that adrenal gland hormones play a part in?
BP regulation
Salt and water balance
Control blood sugar levels
Energy production
Sex organ development
Stress response
Heart rate
Attention
Inflammation
Fetal development
How do catecholamines axis and CRH-ACTH axis differ?
Catecholamines
1) nerve impulses from hypothalamus -> middle horn of the spinal cord and synapse
2) middle horn of the spinal cord -> directly on adrenal medulla and synapse on the ganglion.
- this is the preganglionic sympathetic nerves.
3) postganglionic sympathetic goes directly to adrenal medulla cells and releases catecholamines into blood stream
CRH-ACTH
1) hypothalamus releases CRH in response to circadian rhythms and stressors which moves down the infundibulum the corticotroph cells in the anterior pituitary/ adenohypophysis.
2) cells release ACTH into blood and go to adrenal cortex to bind to cells in the Zona fasiculata. These cells release glucocorticoids (primarily cortisol/sortisone) into blood
Cushing syndrome/adrenal excess/hyperadrenalism/hypercortisolism
Excessive levels of adrenocortical hormones (specifically cortisol)
Effects 13 in 1 million
- more common in women and occurs primarily between ages 25-40 (endogenous)
- more common in males who use high levels of exogenous steroids and then cease (exogenous)
Common symptoms from excess Mineralcorticoids
Hypertension
Hypernatremia
Hypokalemia
Expanded blood volume
Edema
Common symptoms from excess cortisol
Symptoms:
- weight gain
- deposition of adipose tissue in abnormal areas
- proximal muscle weakness
- osteoporosis
- mental disturbances
- thin skin and bruises with “striae”
- “moon-facies”
Common symptoms from excess androgens
Hirsutism
Atrophy of breasts
Amenorrhea
Masculinization of voice and virilization of body
Why does hyperpigmentation appear in both excess cortisol and deficiency of cortisol
Hyperpigmentation is caused by excess ACTH
- this is more common in Addison disease but is possible in cushings since it could be a secondary issue releasing too much ACTH and leads to excess cortisol
When is work up for cushings needed?
Specific features to cushings gets worse
Adrenal masses are noted on imaging or physical exam
Diagnosis of cushings
Low dose dexamethasone suppression
- inject dexamethasone 1mg at evening and wait until morning, then pull levels of cortisol
- if cortisol is low = normal (the dexamethasone will suppress the ACTH)
- if cortisol is high = cushing syndrome)
Can also use imaging studies (CT or MRI (MRI is better)
Can also measure a 24hr urine free cortisol count
- a level >140 mmol/d it’s suggestive of cushing syndrome
Difference between Cushing syndrome and disease
Syndrome = primary (adrenal cortex is the issue)
Disease = secondary (pituitary gland is the issue)
How to tell difference between ACTH secreting pituitary tumor (adenoma) and ectopic ACTH secretion with only labs?
1 = dexamethasone suppression high dose
- if cortisol stays high = ectopic ACTH secretion
- if cortisol stays low = ACTH pituitary tumor
Can check Serum hypokalemia
- if serum potassium is low it is more likely ectopic (75%) chance vis pituitary
Surgical management for cushing disease and syndrome
Cushing disease = transsphenoidal hypophysectomy
Cushing syndrome = adrenalectomy via adrenal adenoma
Prognosis of Cushing
Without treatment = 50% mortality at 5 years
- usually CV risks and HTN
Addison disease
Deficiencies of cortisol/ glucocorticoids
Most common affects people between ages 30-50
- more common in women than men
Primary = inability of the adrenal cortex to secrete sufficient cortisol
- will show hyperkalemia, high ACTH and eosinophila
Secondary = inability of pituitary to secrete adequate ACTH
- will show normal potassium, low ACTH, and no eosinophila
Etiology of Addison disease
Most common overall = autoimmune adrenalitis
- can also be idiopathic
- genes associated are HLA-DR3 and CTLA-4
Other casues
- TB , Funchal, viral infections with AIDS patinets
- metastatic cancers
- CAH’s
- surgical/iatrogenic
- drug induced
- Waterhouse-friedrichson syndrome or anti phospholipid syndrome
- Sheehan syndrome (traumatic blood loss casues infarctions most common = pregnancy)
Symptoms of Addison disease
Fatigue
Weight loss/anorexia**
Fever
Myalgia
Hyperpigmentation of skin and mucous membranes**
Normochromic anemia/lymphocytosis and eosinophils
Orthostatic hypotension**
Hyponatremia And hypoglycemia**
Hyperkalemia**
Osteoporosis**
Abdominal pain and nausea/vomiting**
Adrenal crisis
Acute Addison disease
Most commonly caused by steroid withdrawal or intense stress with underlying Addison disease present
Symptoms:
- profound fatigue
- dehydration
- super low hypotension
- hyperkalemia
- severe hyponatremia
- sudden extreme back/leg cramps
- cyanosis
- refractory fluid treatment without hydrocortisone therapy ;
looks a lot like sepsis
How to diagnosis Addison disease
Serum levels of glucose, electrolytes
- hypoglycemia
- hyponatremia
- hyperkalemia
Blood levels of hormones
- primary = high ACTH and renin. Low aldosterone
- secondary = low ACTH/renin and normal aldosterone
CBC
- shows eosinophil and Normocytic anemia
Presence of adrenal autoantibodies = autoimmune adrenalitis
- if these aren’t there get a chest xray and CT to look for masses of TB infection
Management for adrenal crisis
Give IVs and glucose as needed to replace
Also needs to replace steroids with hydrocortisone in order tor place
After stablizing = corticosteroids and Mineralcorticoid replacement therapy for life
Congenital adrenal hyperplasia (CAH)
A group of 5 different enzyme disorders that result in varying effects
ALWAYS shows cortisol Deficiency
VARIES with Mineralcorticoids and androgen excess of Deficiencies
21a-deficiency is the most common (90%)
Treatments = glucocorticoid replacement
- if salt wasting is present = Mineralcorticoid as well
21-hydroxylase deficiency
Gene mutation in CYP21A2
Causes glucocorticoids and Mineralcorticoid deficiency. Androgen excess
Diagnostic markers: all in blood and are high
- 17-hydroxyprogesterone ***
- 21-deoxtcortisol
- 17-hydroxyurea a loose
Should suspect in both true/pseudo hermaphroditism
Simple virilizing form = 25%
- shows ambiguous genitalia and virilization of females and males
- linear growth is accelerated by plates fuse shut eagerly = short stature
Salt wasting form = 75%
- presents with adrenal crisis at 1-4 wks old
- may present with some charactistics of virilization but is less pronounce compared to the simple virilization form
11B-hydroxylase deficiency
Gene mutation in CYP11B1
Causes glucocorticoid deficiency
Mineralcorticoid and androgen excess
Diagnostic markers: all high in blood
- 11-deoxycortisol
- 11-deoxycorticosterone
17a-hydroxylase deficiency
Gene mutation in CYP17A1
Glucorticoid and androgen deficiency
Mineralcorticoid excess
Diagnostic markers: all high in blood
- 11-deoxycorticosterone
- pregnenolone
- progesterone
Hyperaldosteronism
Most common cause is bilateral adrenal hyperplasia
- most common = adrenal adenoma (conn-syndrome)
Other causes of primary (shows elevation of aldosterone)
- over use of glucocorticoid and then acute withdrawal
- carcinomas
- CAH (17a and 11b only)
- cushing syndrome
- Liddell syndrome (mutant ENaC channels which increases ENaC function)
Other causes of secondary (shows elevation of aldosterone and renin)
- Bilateral renal stenosis
- cirrhosis of liver
- CHF
- nephrotic syndrome
What the easiest way to differentiate primary hyperaldosteronism from secondary hyperaldosteronism
Check renin levels
Secondary = high Primary = low
Symptoms of hyperaldosteronism
Often asymptomatic but is most commonly suspected with unexplained HTN/edema, hyperkalemia and hypokalemia***
Labs
- hypokalemia
- hypernatremia
- metabolic alkalosis
Treatment of hyperaldosteronism
If surgery = laparoscopic adrenalectomy
If medical drug therapy = spironolactone/amiloride or eplernone
- spironolactone is #1
Definition of orthostatic hypotension
Decrease of 20 systolic and/or 10 diastolic BP after laying/sitting down to standing up quickly
What is primary, secondary and tertiary adrenal insufficiency etiology
Primary = adrenal gland hypoproduction of cortisol
- injection of ACTH = NO CHANGE cortisol
Secondary = pituitary gland hypoproduction of ACTH
- injection of ACTH = INCREASED cortisol
Tertiary = hypothalamus hypoproduction of CRH
- injection of ACTH = INCREASED cortisol
How to differentiate 21b/17a/11b CAH from each other based on symptoms
21b-hydroxylase (most common)
- HYPOTENSION*
- HYPERKALEMIA*
- HYPONATREMIA*
- INCREASED PLASMA RENIN*
- virilization and hermaphroditism
- precocious puberty
17a-hydroxylase
- HYPERTENSION*
- HYPOKALMEIA*
- NORMAL OR HYPERNATREMIA*
- NO VIRULIZATION*
- NORMAL PLASMA RENIN*
- NO PRECOCIOUS PUBERTY*
11b-hydroxylase
- HYPERTENSION*
- HYPONATREMIA*
- HYPERKALEMIA*
- VIRULIZATION*
- NORMAL PLASMA RENIN*
- precocious puberty
How does 11B cause hypertension
11-deoxycortisol even though it is not cortisol it does have weak Mineralcorticoid actions
- therefore excess 11-deoxycortisol acts like excess aldosteronism and leads to HTN, Hypernatremia and hypokalmeia
Medications used to treat cushings (excess cortisol levels)
Ketoconazole = inhibits glucocorticoid production via 17-20 desmolase inhibition.
Metyrapone = reversibly inhibits 11B-hydroxylase in steroid synthesis pathway
Aminoglutethimide = inhibits p450scc which prevents cholesterol eating -> pregnenolone
Review how aldosterone is regulated
Via the RAAS axis and ACTH levels
- angiotensin 2 is a potent stimulator of aldosterone synthase enzymes
Causes of secondary HTN
Renal artery stenosis
- more commonly seen between 25-50yrs
- causes are usually atherosclerosis or fibromuscular dysplasia
Pheochromocytoma
- adrenal medulla tumor that secretes excess catecholamines
- will present with episodic intensive headaches/sweating and tachycardia
Conn syndrome
- unilateral adrenal cortex tumor that secretes aldosterone excess
- will present with HTN, hypokalemia and metabolic alkalosis
Cushing syndrome: excess ACTH that causes excess cortisol
Primary renal disease:
- typically unilateral renal parenchyma disease
What is the most common ECG finding in hyperaldosteronism
Prominent flattening of U waves
Flattened T waves
ST-segment depression
**this is because of the hypokalmeia
Sheehan syndrome
Caused by some sort of massive blood loss which leads to ischemia and necrosis of the pituitary gland
this is most common in pregnancy because during pregnancy, other factors promote hyperplasia of both the anterior and posterior pituitary. However during pregnancy, extreme blood loss occurs which causes ischemia due to focal volume loss
Symptoms:
- inability to breast feed after pregnancy**
- intense fatigue
- mental sluggishness
- tachycardia and orthostatic HTN
- symptoms related to loss of pituitary hormones
