Conditions Flashcards
1
Q
Occurs in growing bone
A
rickets
2
Q
enlargement of cartilage at growth plates of costochondral junctions (rachitic rosary in ribcage) and long of long bones
bowing of long bones of legs
A
rickets
3
Q
Same thing as rickets except in mature bone
A
osteomalacia
4
Q
almost all filtered calcium is?
A
reabsorbed
5
Q
Calcium handling in the kidney: PTH independent
A
*Most (passively in the proximal tubule *
some in the thick ascending limb driven by a voltage gradient created by NA/K/Cl reabsorption
6
Q
Normal Calcium Handling in the kidney: PTH dependent
A
PTH dependent calcium reabsoption occurs in the *distal convuluted tubule *
7
Q
what upregulates the mediators of Ca reabsorption in the DCT
A
PTH
8
Q
low bone mass and/or microarchitectural changes that lead to bone fragility and increased risk of fracture
A
osteoporosis
9
Q
what is sthe most common cause of osteoporosis?
A
most causes of osteoporosis occur because bone remodeling becomes “uncoupled” with bone resorption outpacing bone formation
10
Q
What are two mechanisms that can treat osteoporosis?
A
decrease bone resorption- inhibit osteoclasts (these are call antiresoptive agents)
stimulate bone formation- stimulate osteblasts (these are called anabolic agents)
11
Q
what stimulates the maturation of osteoblasts and prolongs their lifespan?
what inhibits the matruation of osteoclasts and shortens their lifespan?
A
estrogen!
12
Q
what is the net effect of estrogen
A
supporting bone formation and suppressing bone resorption
13
Q
what does estrogen inhibit the expression of?
A
RANK-L (decreasing osteclast activity)
14
Q
parathyroid has this receptor on their surfaces which detects the level of free calcium in the blood
A
calcium sensing
15
Q
a decline in calcium levels would cause PTH to?
increased levls of calcium would lead PTH to?
A
- declince in calcium levels lead to release of PTH
- Elevated levels leads to suppression of PTH
16
Q
other than parathyroid, where else are CaSR cells present?
A
in the thick ascending loop of henle
when Ca bind to renal CaSR, leads to calcium excretion in the kidney
17
Q
what is the primary stimulus for PTH secretion
A
hypocalcemia
18
Q
what is necessary for proper PTH secretion
A
Magnesium
19
Q
decreases PTH levels?
A
Vitamin D (supresses PTH gene transcription)
Magnesium
20
Q
increases PTH levels?
A
Calcium
phosphate
21
Q
what is PTH action at the kidney?
A
PTH increases calcium reabsorption
inhibits renal phosphate reabsorption- promotes phosphaturia
PTH increases the transcription of 1alpha-hydroxylase, the enzyme that activates vitamin D
22
Q
PTH receptors are found where?
A
osteoblasts (bone building cells)
23
Q
what do osteoblasts do?
A
signal osteoclast precursors to develop mature, active osteoclasts. RANKL is one of these signals
24
Q
what can mimic excess PTH? How?
A
PTH- related protein (PTHrp)
it is structurally similar to PTH and shares a receptor
25
why can't excess sun not cause vitamin D toxicity?
Prolonged UV light exposure also breaks down vitamin D to inactive forms
26
what is the predominant form of Vitamin D in the body, and considered the storage form?
Vitamin is converted in the liver by hydroxylation to 25-hydroxy vitamin D(25-(OH) vitamin D
27
what serum level is the best marker of vitamin D status in an individual? Why?
25-(OH) Vitamin D
it reflects the total amount of Vitamin D entering the system; it is also the predominant storage form
28
what is the active form of vitamin D? how does it become active? what induces the active form? what suppresses it?
25-(OH) vitamin D is hydroxylated in the kidney by 1alpha-hydroxylase to **1,25-dihydroxy vitamin D**
enzyme is *induced by PTH and hypophosphatemia*
suppressed by *calcium and by its product 1,25-(OH)2 vitamin D*
29
What does vitamin D do in the GI tract, in the Parathyroid, in the bone?
GI: stimulates calcium absorption in the intestine
Parathyroid: decreases the transcription of PTH
Bone: main role is to maintain (via GI absorption) the availability of adequate calcium and phosphate for bone mineralization
30
what is the most common cause of primary hyperparathyroidism? what is an occasional cause? what do you see left often? very rarely?
* most commonly caused by a parathyroid adenoma in one gland
* occasionally more than one adenoma can occur simultaneously
* less often: diffuse hyperplasia of all glands can occur
* very rare: parathyroid carcinoma
31
main clinical concerns in primary hyperparathyroidism?
detrimental effect on bone density and the risk of kidney stones
32
treatment of primary hyperparathyroidism?
surgical removal of the abnormal glands (usually curative)
33
* rare disorder caused by loss of function mutation of the CaSR (i.e, it is less sensitive to calcium)
* it is transmitted in an autosomal dominant fashion
* the mutation leads to requirement for higher than usual serum calcium levels before PTH secretion is supressed
familial hypcalciuric hyperplasia
34
clinical manifestation: mild hypercalcemia, high-normal or mildly elevated PTH, and low urinary calcium levels.
familial hypocalciuric hypercalcemia
35
treatment for familial hypocalciuric hypercalcemia?
no treatment needed
parathyroidectomy would not solve because the problem lies in all cells
36
mechanisms of hypercalcemia of malignancy?
* **invasion/destruction of bone by tumor**- appears that tumor cells secrete signals that stimulate osteoclast activity and cause release of calcium from bone
* **production of PTHrP by tumor-** buinds to the same receptor as PTH increasing serum calcium levels
* **production of Vitamin D by tumor-** certain hematologic malignancies can produce hypercalcemia related overproduction of 1,25(OH)2 vitamin D
37
when does vitamin D cause hypercalcemia?
Very high doses of oral vitamin D (vitamin D intoxication) - the hypercalcemia is due to vitamin D-mediated increases intestinal calcium absorption and increase resorption of bone
38
how does sarcoidosis and granulomatous lead to hypercalcemia?
granulomatous cells can have unregulated 1alpha-hydroxylase activity, leading to excess active Vitamin D
39
how does hyperthyroidism (severe) cause hypercalcemia
Excess thyroid hormone stimulates bone resoption directly
40
how does immobilization lead to hypercalcemia?
can be seen in the setting of prolonged immobilization related to elevated bone resorption
41
disorder of inadequate PTH secretion. In the absence of PTH the following are impaired
* activation of Vitamin D/GI absorption of calcium
* mobilization of calcium from bone
* resorption of filtered calcium at the kidney
Primary hypoparathyroidism
42
characterized by low calcium and low PTH
hypoparathyroidism
43
what factors can cause primary hypoparathyroidism?
absence or destruction of the parathyroid glands
* congenital
* post surgical
* autoimmue
Impaired PTH secretion from intact glands
* hypomagnesemia
44
Hypocalcemia can be caused by?
vitamin D deficiency
45
hypocalcemia caused by Vitamin D deficiency would show?
mildly low or normal calcium level, low phosphate, low urinary calcium, elevated PTH, low 25-(OH) Vitamin D
normal 1,25-(OH)2 Vitamin D
46
Other than Vitamin D deficiency, what is another cause of secondary hyperparathyroidism?
chronic kidney disease
47
how are secondary hyperparathyroidism and chronic kidney disease related?
renal clearance of phosphate is impaired
renal 1aphla-hydroxylase activity is impaired
* both are triggers for PTH secretion
48
bone modeling occurs when?
bone remodeling occurs when?
bone modeling occurs during growth
bone remodeling occurs throughout life
49
denser outer portion of bone, most shafts of long bones. 80% of all bone
cortical bone
50
"spongy" inner area of bone spicules. 20% of bone but most surface area so it is an active site of bone remodeling
trabecular bone
51
secrete matrix proteins & faciliate mineraliztion- contian most receptors for hormones affecting bone remodeling- communicates these signals to osteoclasts, which keeps bone buidling and breakdown coupled
osteoblasts
52
osteoblast that has been completely surrounded by bone
involved in sensing mechanical stresses and communicating this information to osteoblasts on the bone surface
osteocytes
53
derived from hematopoietic precursors
create small cavities during bone remodeling which are filled with new bone by osteoblasts
osteoclasts
54
low bone mass and/or microarchitectural changes that lead to bone fragility and increased risk of fracture
osteoporosis
55
osteoporosis can be due to?
failure to achieve peak bone mass
* related to genetics, childhood calcium intake, vitamin D status, physical activity
bone loss
* related to accelerated bone resorption or decreased formation
56
most common type of osteoporosis?
postmenopausal osteoporosis
57
when is bone loss the most rapid in postmenopausal women? why?
in the first few years after menopause
bone resorption outpaces bone formation
58
risk factors for osteoporosis
* female gender (men get osteoporosis too, only later)
* increasing age
* postmenopausal status (or testosterone deficiancy in men)
* low weight
* smoking
* family history of osteoporosis
* risk factors for falls/fractures: poor muscle strength, impaired balance or vision
59
STRONGEST risk factor for future fragility fracture
is previous fragility fracture, these patients are at high risk of more fractures and aggressive risk reduction should be implemented
60
most common osteoporotic fracture
vertebral compression fractures
61
have high morbidity and mortality
hip fractures
62
fracture that often occurs in younger women?
distal radius fracture (colles fracture)
63
osteoporosis due to identifiable risk factors (other than age and menopause)
osteporosis
64
what are examples of secondary osteoporosis?
glucocorticoid-induced: meds or endogenous cushings syndrome
endocrine issue: low testosterone, hyperparathyroidsm, hyperthyroidism
malignancies: multiple myeloma, other lymphoproliferative malignanicies
65
how are steroids bad for bones? when would you see a increased fracture risk?
decrease intestinal calcium absorption
increase expression of RANKL on osteoblasts
suppress maturation and increase apoptosis of osteoblasts
increase renal Ca and Phos losses
* increased fracture risk within a few months of therapy and with low doses*
66
What is whipple's triad?
* decreased plasma glucose
* symptoms consistent with hypoglycemia
* relief of symptoms by correction of hypoglycemia
67
why do we care about the insulin level?
the normal response to hypoglycemia is feedback inhibition of insulin secretion
* therefore, an elevated insulin level in the context of hypoglycemia is suggestive of **Endogenous Hyperinsulism **
68
what is C-peptide? what does it measure?
C-peptide is a fragment of endogenously produced proinsulin that is split from proinsulin as insulin if formed.
*As a result C-peptide level can only increase if endogenous insulin production is increased*
69
what are adrenergic mediated symptoms of hypoglycemia?
Sweating
pallor
tachycardia
palpatiations
tremor/shaking
nervousness/anxiety
tingling, parasthesias (mouth and fingers)
70
Neuroglycopenic
Headache
drowsiness
lightheadedness/syncope
mental dullness/confusion
amnesia
seizures
coma
71
often misdiagnosed as post-partum anxiety and depression
usually self-limited
postpartum thyroiditis
72
what is postpartum thyroiditis?
a postpartum patient that may experience hyperthyroid phase followed by hypothyroid phase before returning to euthryoid state
73
may be present with thyrotoxicosis, hypothyroidism, euthyroid states.
can be due to benign or malignant disease
Goiter
74
when do you treat low TSH with normal free T4 and Free T3?
Symptomatic
arrthymia
bone loss
consider if desires pregnancy
75
what are pharmacological causes of hypothyroidism?
* lithium (impaires release of T4 and T3)
* amiodarone
* methimazole
* PTU
* interferon (cuases hashimoto's thyroiditis like presentation, resovles after drug stopped)
* Rifampin (increased levothyroxine metabolism- concern for comprised function of baseline
76
Treament options of hypothyroidism?
Levothyroxine(drug of choice)
liothyronine (may use for faster onset)
dessicated thyroid
77
Treament options of hypothyroidism?
Levothyroxine(drug of choice)
liothyronine (may use for faster onset)
dessicated thyroid
| [](http://)
78
the zona glomerulosa makes
aldosterone
79
Zona fasciulata makes
cortisol and adrenal androgens
80
Zona reticularis makes?
Cortisol and adrenal androgens
81
what is the major regulator of cortisol?
ACTH
82
Cortisol exerts what type of feedback on ACTH and CRH secretion
negative feedback
83
what regulates ACTH?
CRH
84
what are actions of corticosteroids?
* Mobilization of energy stores
* lipolysis and increased delivery of FFA
* increased hepatic glucose production by gluconeogenesis
* inhibits glucose uptake in muscle, fat and lymphoid tissue
* protein degredation etc.
* anti-inflammatory effects
* stimulates bone resorption and inhibits new bone formulation
85
a constellation of symptoms due to excess glucocortioids (exogenous glucorticoids, ectopic ACTH, ETC)
Cushing's syndrome
86
disease due to excess pituitary secretion of ACTH (about 70% of cases are endogenous)
Cushing's disease
87
What are common causes of ACTH dependent cushing's disease? (80% of cases)
Pituitary adenoma (cushing's adenoma)
Ectopic ACTH syndrome (oat cell ca, carcinoid tumor)
Medullary ca or the thyroid, pheocromocytomas
88
causes of ACTH independent (20% of cases- much higher in kids)
iatrogenic- exogenous glucocorticoids (very common)
adrenal adenomas
adrenal cancer
micor and macronondular hyperplasia
89
Common symptoms of cushing's syndrome
moon facies
facial plethora
supraclavicular fat pads
buffalo hump
truncal obesity
weight gain
purple striae
90
common cause of iotrogenic cushing's disease
Glucorticoid therapy
91
when would you use radiation therapy for cushing's syndrome
for larger pituitory tumors and/or persistent hormonal hyperfunction despite surgical intervention
92
what is aldosterone under the control of?
renin-angiotensin system
Na/k levels
93
what stimuli causes release of aldosterone?
decrease in vascular volume
sympathetic nervous system stimulation of renin
rise in serum potassium concentrations
94
signs and symptoms of primary aldosterone?
hypertension
hypokalemia
metabolic alkalosis
muscle weakness/cramps
95
what causes primary aldosternism?
aldosterone-producing adrenal adenoma
bilateral hyperplasia of the zona glomerulosa (idiopathic hyperaldosteronism)
primary adrenal hyperplasia
adrenal carcinoma
96
usually small (<2cm)
more commonly occur in L adrenal gland
produce more aldosterone than in any other conditions
aldosterone producing adenoma
97
what do levels look like in APA?
demonstrate normal or semi-normal response to ACTH- because of that plasma aldosterone is highest in A.M, lowest in late afternoon
98
PTH Low, Calcium Normal
PTH independent
malignancy
granulomatous disease
milk-alkali
99
Calcium High, PTH normal/High
PTH dependent
primary hyperparathyroidism
Familial hypercalciuric hypercalcemia
lithium
100
Calcium Low, PTH Low/normal
primary hypoparathyroidism
autoimmune hypoparathyroidsim
post surgical
congenital/genetic
hypomagnesemia
101
PTH high, calcium low
Vitamin D deficiency
chronic kidney disease
102
what are scenarios where the parathyroid is responding normally?
PTH independent
secondary hyperparathyroidsim
PTH normal, calcium normal
103
PTH high, calcium normal
secondary Hyperparathyroidism
104
High BP
low K
adrenal adenoma on CT
primary aldosteronism- Conn's syndrome
105
what medication inhibits thyroid hormone release?
Lithium
106
What is the initial screening test for thyroid?
TSH
107
When should you obtain a free T4 and Free T3?
If the TSH is abnormal
*reverse T3 only in critical illness
* total T4 monitored in pregnancy
108
if evaluating antibodies for thyroid- which would you evaluate for hypothyroidism? Which for hyperthyroidism
TPO and TG antibodies in hypothyroidism
TSI and TRab in hyperthyroidism
109
What level is used as a tumor marker for thyroid cancers?
Thryroglobulin
110
Elevated levels of: TSH
Free T4, Free T3:
Anitbodies:
Thyroglobulin:
Elevated TSH: Hypothyroidism
Elevated T4, T3: Hyperthyroid
Antibodies: either
Thyroglobulin- thyroid cancer
111
Suppressed levels: TSH
Free T4, T3
Thyroglobulin
Suppressed TSH: Hyperthyroidsim
Free T4, Free T3- hypothyroidism
thyroglobulin- thyroid cancer
112
TSH elevated
Free T4 is normal or low
Free T3 often remains low until late in disease course
Primary hypothyroidism
113
seen with hypothalmic/pituitary failure, pituitary gland abnormality
* TSH is low-normal or low
* Free T4 is low
central hypothyroidsim (secondary disorder)
114
TSH is low
Free T4 is high
Free T3 high
Thyrotoxicosis (hyperthyroidism)
115
TSH is normal or high
Free T4 elevated
Free T3 elevated
TSH secreting tumor or central thyroid hormone resistance syndrome
116
what should you be aware of with thyroid hormone measurements?
* Estrogen increases total T4 and T3 due to increased TBG
* Illness decreases total T4 and T3 due to decreased protein levels
| Can cause the appearance of abnormality, when fx is normal
117
* thyroid enlargement
* may be present with thyrotoxicosis, hypothyroidism or euthyroid states
* can be due to benign or malignant diseae
* size does not dictate function
Goiter
118
signs as symptoms of hyperthyroidism?
increasd metabolic rate: palpitations, tachycardia, arrhythmia
heat intolerance
weight loss
decreased menstrual flow, infertility,
increased spontaneous abortion rate
hyperdefecation
119
can occur due to omission of anti-thyroid therapy, surgery, MI, CVA or infection in patient with underylying thyrotoxicosis
thyroid storm
120
what are some causes of hyperthyroidism?
* High iodine uptake: Grave's disease, toxic multinodular goiter, autoimmune polyglandular syndrome 1&2
* Low iodine uptake: Thyroiditis (subacute, silent, postpartum)
* drug induced (iodine, amiodarone, thyroid hormone)
121
Diseases of hyperthyroidism
grave's disease
toxic multinodular goiter
toxic adenoma
TSH secreting pituitary adenoma
122
often presents after URI
thyrotoxic symptoms
anterior neck pain, thyroid tenderness
results from inflammation of gland
Subacute thyroiditis
123
treatment for subacute thyroiditis?
treat with NSAIDS +/- steroids
use beta blockers for HR (propranolol)
self-limited
124
* similar to subacute thyroiditis but **without** pain
* often a diagnosis of exclusion
* monitor for improvement
* treat hormone excess or deficiency as needed
silent thyroiditis
125
* often misdiagnosed as post-partum anxiety and depression
* usually occurs within 6 months of delivery and is self limited
* tends to recur with subsequent pregnancies
post-partum thyroiditis
126
what is postpartum thyroiditis?
patient may experience hyperthyroid phase followed by hypothyroid phase before returning to euthyroid state
127
Complications of total thyroidectomy or lobectomy?
recurrent laryngeal nerve injury
hypoparathyroidism
permanent hypothyroidism
may precipitate thyroid storm
128
Isolated increased TSH with normal free T4 and free T3
subclinical hypothyroidism
129
when do you treat subclincial hypothyroid
symptomatic
arrhythmia
bone loss
consider if desires pregnancy
if TSH > 10 (levothyroxine therapy)
goiter
family history
TPO antibodies
hypercholesterolemia
130
Symptoms of hypothyroidism
fatigue
cold intolerance
weight gain
dry skin
brittle nails
hyponatremia
etc.
131
pharmacologic causes of hypothyroidism?
**Lithium** (impairs release of T3 and T4)
**amiodarone**
methimazole, pTU
interferon (causes hashimoto's thyroiditis like presentation)
**rifampin** (increased levothyroxine metabolism)
132
* severe hypothyroidism with mental status changes
* usually occurs in longstanding untreated hypothyroidism with an acute precipitating event
* most common in older women
* may have history of lithium or amiodarone treatment
myxedmea coma
133
Presentation: hypotension, hypothermia, hyponatremia, hypoglycemia, hypoventilation, bradycardia
myexedma coma
134
most common thyroid cancer
excellent prognosis
treatement: thyroidectomy(may be curative or radioactive iodine +/- TSH supression
metastasizes via lymphatics
papillary thyroid cancer
135
10-15% of thyroid cancers
good prognosis depending on extent of extra-thyroidal extension and vascular invasion
*hurthle cell variant may be aggressive
follicular carcinoma
136
uncommon 5-10% of cases
sporadic (75%) or familial (24%)
calcitonin is a serum marker
can diagnose with FNA
tends to metastasize early, even before tumor is palpable
medullary carcinoma
137
uncommon 5-10% of cases
sporadic (75%) or familial (24%)
calcitonin is a serum marker
can diagnose with FNA
tends to metastasize early, even before tumor is palpable
medullary carcinoma
138
rare <5% of cases
more common in elderly
very poor prognonsis 100% mortality
treatment: palliative
presents as rapidly expanding, fixed, hard thyroid mass
may be seen as late differentiation of papillary TCA
anaplastic carcinoma
