1 - Endocrine Patho Flashcards
Target cells may fail to respond to a hormone due to abnormalities in two places:
The cell surface receptors (most for water soluble hormones)
Inside the cell (abnormal second messengers
What types of medications may cause SIADH, especially in the elderly?
hypoglycemics
antidepressants
antipsychotics
narcotics
general anesthetics
cehmo
NSAIDs
synthetic ADH
Why is transient SIADH common after pituitary surgery?
All the stored ADH is released in an unregulated fashion
SIADH manifests as:
- hypoosmolar plasma (<280) with hyponatremia (<135)
- hyperosmolar urine
- urine sodium excretion equal to sodium intake
- normal adrenal/renal/thyroid function
- absence of other causatives (heart failure etc)
Treatment of SIADH includes:
- Underlying cause
- fluid restriction of 800-1000ml
- emergency correction of hyponatremia if symptomatic
How long does it usually take for SIADH to resolve?
3 days
What renal disorders can lead to nephrogenic DI?
pyelonephritis
amyloidosis
destructive uropathies
PKD
intrinsic renal disease
What drugs can result in a reversible nephrogenic DI?
lithium carbonate
colchicines
Ampho B
loop diuretics
general anesthesia
demeclocycline
What is gestational DI?
Rare pregnancy complication
level of vasopressinase is elevated
usually mild and doesn’t require treatment
Which has a more gradual onset: central or nephrogenic DI?
nephrogenic
Diagnostic criteria for DI are:
urine SG < 1.010
Urine Os < 200
Serum Os > 300
Hypernatremia
What is dipsogenic DI?
DI cause by excessive thirst and drinking
__________ is an ADH precusor molecule that can be used to measure ADH secretion
copeptin
What causes hypopituitarism? (3)
- Problem with the hypothalamus’ production of HRH
- Problem with the pituitary stalk cuts off comms
- AP gland can’t produce hormones
What is Sheehan Syndrome?
Postpartum hypopituitarism caused by a severe hemorrhage resulting in a pituitary infarction
Very rare
What is panhypopituitarism?
All the hormones of the AP are deficient
lack of cortisol from ACTH
lack of thyroid from TSH
lack of FSH AND LH
stunted growth from lack of GH
What are the s/s of ACTH deficiency?
- N/V, anorexia
- Fatigue and weakness
- Hypoglycemia d/t insulin sensitivity, decreased glycogen reserves and decreased gluconeogenesis
- Decreased aldosterone secretion
- Decreased GFR and urine output
What is myxedema
the characteristic sign of hypothyroidism
nonpitting, boggy edem in around the eyes, hands, and fett and supraclaviular fossae
Tongue and laryngeal and pharyngeal mucous membranes thicken
thick, slurred speech and hoarseness
Which is usually worse: primary hypothyroidism or TSH deficiency?
Primary
reduced TSH usually results in mild myxedema
What does a deficiency of LH and FSH cause?
amenorrhea
atrophy of the vagina, uterus, and breasts
How does GH deficiency manifest in children?
Hypopituitary dwarfism
Fasting hypoglycemia
How does GH deficiency manifest in adults?
increased body fat
decreased muscle
osteoporosis
reduced sweating, dry skin
psuch issues
MI from dyslipidemia and atherosclerosis
Hyperpituitarism is often caused by a ______
primary adenoma
What causes acromegaly?
Exces GH and IGF-1
Acromegaly is almost always caused by increased GH from:
a GH secreting pituitary adenoma
Almost never from ectopic production of GHRH
Why does elevated GH often lead to diabetes?
GH prevents peripheral glucose uptake, increases hepatic glucose production, and causes insulin resistance
The pancreas produces more insulin, but eventually insulin resistance and pancreatic exhaustion cause DM
What cardiac defects are seen in nearly 50% of patients with acromegaly?
HTN and L heart failure
Pituitary tumors that secrete _______ are the most common pituitary adenomas
prolactin
What kind of medications can increase prolactin?
Anything that decreases dopamine levels
risperidone
metoclopramide
TCAs
Methyldopa
How does excess prolactin manifest in men and women?
Hypogonadism
What causes postpartum thyroiditis?
pathologically related to Hashimoto disease
occurs 6-12 months after delivery
hyperthyroid phase precedes a hypothyroid phase
recover spontaneously 95% of the time
If there is a primary elevation in Thyroid Hormone, what will happen to TSH levels?
They will decrease
If there is a secondary elevation in Thyroid hormone, TSH levels will be:
elevated
Which is more common: primary hyperthyroidism or secondary hyperthyroidism?
Primary
the problem is usually with the thyroid, not the hypothalamus
50-80% of hyperthyroidism is caused by:
Grave’s Disease
Grave’s disease results from a type ______ hypersensitivity
Type II
Thyroid-Stimulating Immunoglobulins override normal negative feedback mechnaisms and cuase hyperplasia of the gland
The TSH in a patient with Grave’s disease would most likely be:
Low
What is pretibial myxedema?
lumpy and swollen red rash over the tibia from GRAVES DISEASE
What usually causes thyroid storm?
when people who have undiagnosed or uncontrolled hyperthyroidism are exposed to extreme stress from other causes (infection, trauma, burns, seizure, surgery, emotioanl distress, dialysis)
Describe the TSH levels for patients with:
primary hypothyroidism
secondary hypothyroidism
high
low
The most common cause of primary hypothyroidism is:
Hashimoto disease
(autoimmune thyroiditis)
How would the levels of TSH and TH appear in a patient with subclinical hypothyroidism?
TH would be normal
TSH would be elevated
Describe the difference between the following types of hyperparathyroidism:
Primary
Secondary
Tertiary
- primary*: increased PTH secretion, usually from parathyroid adenoma. Hypercalcemia, hypophosphatemia
- Secondary:* incrased PTH in response to chronic hypocalcemia, usually due to CKD or Vitamin D deficiency
- Tertiary*: develops after longstanding hypocalcemia d/t dialysis or GI malabsorption. Problematic after renal transplant, because the body is suddenly producing way more PTH than it actually needs
Describe the effects of hyperparathyroidism on renal function
Causes hypercalcuria and hyperphosphaturia
Causes alkaline urine
Prediposed to calcium stones
impairs the concentraing ability of the renal tubule by decreasing its response to ADH
The most common cause of hypoparathyroidism is:
surgical removal of the thyroid
Hypo_______ inhibits PTH secretion
magnesemia
What are the s/s of hypocalcemia?
perioral numbness, parasthesias, tingling, tetany
hyperreflexia
Chvostek’s (cheek) and Trousseau (BP cuff)
What is the most common pediatrics chronic disease?
Type 1 DM
When is DM1 usually diagnosed?
12 years old
Both a lack of ______ and an excess of ______ contribute to DM1
insulin
glucagon
Alpha and beta cell functions are both abnormal. Amylin, which ordinarily inhibits glucagon, is also not produced
Is the onset of Type 1 DM gradual or acute?
gradual
The later in life it starts, the longer the latent period usually is, so people who are near-adult are sometimes misdiagnosed with DM2
Why is glucagon elevated in DM2?
pancreatic alpha cells become less responsive to glucose inhibition
For a patient in DKA, describe the following labs:
BG
Bicarb
Anion Gap
>250
low
increased
What is the most common precipitating factor for DKA?
Intercurrent illness: infection, trauma, surgery, MI
What are the pathophysiology mechanisms for DKA?
Insulin deficiency is further antagonized by cortisol, glucagon, and GH released d/t stress
These hormones make insulin deficiency even worse
Results in decreased glucose uptake, increased fat mobilization, accelerated gluconeogenesis, glycogenesis, and ketogenesis
Why does DKA cause a metabolic acidosis?
Everytime a ketone is formed, bicarb is lost
Normally the body uses ketones in tissues for energy, releasing that bicarb
But in the total absence of insulin, the liver produces ketones at a rate that exceeds peripheral use
these ketones eat up bicarb and accumulate
The ketones form strong organic acids that aren’t buffered by bicarb
What are the criteria for diagnosis of DKA?
- serum glucose > 250
- Bicarb < 18
- pH <7.3
- anion gap
- presence of urine and serum ketones
Why is ketoacidosis only present in DM1?
Insulin has an anti-lipolytic effect
It moderates the rate at which the liver produces ketones in a high stress state
Without any insulin present, the lipolytic effect is completely unchecked, resulting in waaaay more ketones than the body could possibly use for energy
Hyperglycemia likely induces mitochondrial:
overproduction of oxygen free radicals, leading to activation of the metabolic pathways known to cause atherosclerosis etc
Why is hyperglycemia particularly hard on the kidneys, blood vessels, eyes, and nerves?
All these tissues don’t require insulin for glucose transport
That means in the setting of hyperglycemia, they can’t just downregulate the cellular uptake of glucose
Instead, it gets shunted into the polyol pathway for metabolism
Overactivation of polyol causes excess sorbitol (swelling) and reduced glutathione (an antioxidant)
Many of the microvascular complications of hyperglycemia are likely due to inappropriate activation of which signalling pathway?
Why?
DAG - Protein Kinase C
Once activated, PKC may cause insulin resistance, cytokine production, vascular proliferation, enhanced contractility, angiogenesis, and increased permeability
What is glycation?
the nonenzymatic, reversible binding of glucose to proteins, lipids, and nucleic acids
How is glycation altered in recurrent/persistent hyperglycemia?
glucose becomes irreversibly bound to collagen and other proteins in RBCs, vessels, interstitial tissue, and within cells
These glucose-protein complexes are called AGEs (advanced glycation end products)
Why are AGEs problematic?
proteins, including albumin, LDLs, immunoglobulin, and complement get bound and trapped in the basement membrane
AGEs bidn to cell receptors of macrophages and glomerular mesangial cells, causing inflammation, cytokines, fibrosis
Can inactivate nitric oxide, leading to vasodilation
bound endothelial cells are procoagulant
What percentage of individuals with DM develop kidney disease?
50%!
Which tubule is particularly vulnerable to damage from hyperglycemia?
Proximal tubule (high level of aerobic metabolism and energy requirements, doesn’t tolerate hypoxia well)
What is the first manifestation of diabetic kidney disease?
microalbuminuria (30-300 mg/day)
Sometimes, as patient with DM related nephropathy gets worsening kidney disease, their insulin requirements go down.
Why?
The kidney isn’t metabolizing insulin
Diabetic neuropathy targets which nerve fibers preferentially?
Sensory fibers, specifically Polymodal C and A delta
Which is related to the severity of diabetes:
microvascular or macrovascular
microvascular
Macrovascular is not related to the severity of the diabetes, and may be present with very mild disease symptoms
How many diabetics end up dying of cardiovascular disease?
68%
Why are diabetics so prone to infection?
- Poor sense (decreased vision and sensation)
- glycosylated RBCs impede release of O2, causing hypoxia in most tissues
- pathogens proliferate rapidly thanks to all the glucose
- Decrease blood supply from capillary disfunction
- supressed immune response
- delayed wound healing d/t slower collagen synethies and decreased angiogenesis
Hyperfunction of the adrenal cortex leads to _____ disease
Hypofunction of the adrenal cortex leads to _____ disease
Cushing Syndrome
Addison Disease
Is cushing syndrome more common in men or women?
Women
What’s the difference between
cushing syndrome
cushing disease
cushingoid syndrome
syndrome refers to the effects of excess endogenous cortisol
disease refers specifically to excess endogenous secretion of ACTH (corticotropin), which leads to excess cortisol or (more rarely) from an adrenal adenoma
side effect of prolonoged glucocorticoid drug therapy
If someone has Cushing syndrome caused by excess ACTH, their ACTH levels will always have three characteristics regardless of the root cause:
- Non-diurnal or circadian secretion pattern
- No increase in ACTH in response to a stressor
- Depressed levels of CRH
In patients with Cushing syndrome who do NOT have elevated levels of ACTH or CRH, the problem must be:
Excess cortisol secretion from a tumor in the adrenal cortex
Patients with ACTH-independent Cushing’s often have an atrophied adrenal cortex. Why?
When the tumor produces massive amounts of cortisol, ACTH release is suppressed
This means the normal cells of the adrenal cortex aren’t being stimulated by ACTH at all, and they begin to atrophy
What are the two reasons people gain weight with cushing syndrome?
- Truncal obesity (trunk, face, cervical area)
- Weight gain from sodium and water retention 2/2 the mineralocorticoid effect of cortisol at high levels
Why do patients with elevated cortisol have hyperglycemia?
cortisol causes:
insulin resistance
gluconeogenesis
Why does excess cortisol cause fatty deposits?
cortisol stimulates lipolysis by stimulating the production of lipases in adipocytes, which chomp the adipocyte into glycerol and fatty acids
glycerol is then used by the liver to make glycogen/glucose
BUT the fatty acids are left free to roam, and wind up depositing in weird places throughout the body
What does the liver use to create glucose from non-carb products?
Amino Acids + glycerol = glucose
(proteins + lipids = glucose)
It can ALSO use lactic acid
Why does excess cortisol cause high blood pressure and glycogenolysis?
It sensitizes the adrenergic receptors, making them more responsive to NE
in the blood vessels, this leads to vasoconstriction
in the liver, it leads to glycogenolysis
Why do 20% of Cushing patients get renal stones?
increased osteoclasts activity results in bone resportion and hyperciurea
What causes congenital adrenal hyperplasia?
deficiency of an enzyme that synthesizes cortisol results in low cortisol production (usually 21-hydroxylase)
ACTH increases, causing hyperplasia of the adrenal gland
What causes Conn Syndrome?
Hypersecretion of aldosterone from the adrenal cortex
Usually caused by a unilateral benign adrenal adenoma
Primary Hyperaldosterism has very different effects that secondary. Why?
Primary occurs in the absence of Angiotensin II, so it has effects that are out of balance with the perceived needs of the body:
Hypokalemia
insulin resistance
inflammation
LV remodeling
What are some causes of secondary aldosteronism?
Anything that’s increasing Angiotensin II production:
hypovolemia
hypoperfusion
Bartter Syndrome
What are the hallmarks of excess aldosterone?
hypertension
hypokalemia
hypervolemia
alkalosis
DOES NOT CAUSE EDEMA (pressure natriuresis - which worsens hypokalemia)
Hypersecretion of estrogen causes:
Hypersecretion of androgens causes:
feminization
virilization
Primary hypocortisolism is better known as:
Addison Disease
Need to “Add” Aldosterone
What is the most common cause of Addison Disease?
autoimmune destruction of the adrenal cortex
Addison Disease is characterized by: (3)
inadequate corticosteroid and mineralocorticoid synthesis
elevated serum ACTH
90 % loss of adrenocortical tissue
Which enzyme is targeted in autoimmune destruction of the adrenal cortex?
21-Hydroxylase!
People with Addison disease will have low levels of _____ AND ______
cortisol
aldosterone
What happens in adrenal crisis?
Severe hypovolemia caused by Addison disease
Sparked by undiagnosed disease, acute withdrawal from steroids, or a concurrent infection/stressful event
Patients with Addison disease exhibit ____ glucose levels and ____blood pressure
low
low
What causes secondary hypocortisolism?
decreased ACTH 2/2 long term steroid therapy means adrenal glands atrophy and shrink
when steroid therapy is stopped, glands can’t produce enough cortisol on their own
Secreting tumors of the adrenal medulla are rare. They include which two tumors?
pheochromocytomas
sympathetic paragongliomas
Pheochromocytomas and sympathetic paragangliomas cause uncontrolled production of __________
Primarily norepinephrine
Really big ones will also secrete epinephrine
Ingestion of what kinds of foods can spark a hypertensive crisis in a patient with an adrenal medulla mass?
Tyrosine-containing foods:
Aged cheese
red wine
beer
yogurt
AND caffeine
What is usually the first sign of a pheochromocytoma?
hypertension that is unresponsive to drug therapy
Why do patients with pheochromocytomas have glucose intolerance?
Catecholamines inhibit insulin release from the pancreas
