endocrine- thyroid/parathyroid Flashcards
1
Q
thyroid is composed of what two types of cells?
A
follicular & parafollicular (C-cells)
2
Q
what do parafollicular cells produce?
A
calcitonin (osteoclast inhibitor)
3
Q
thyroid hormones require ____ for synthesis, coupled to ______.
A
iodine, coupled to tyrosine.
4
Q
what are the two forms of thyroid hormone?
A
Triiodothyronine (T3): Biologically active
Tetraiodothyronine (T4, aka thyroxine): Most secretion
Converted to T3 in periphery (5’-iodinase)
*either have 3 or 4 iodines attached to tyrosine molecule
5
Q
what is the only gland that stores appreciable amounts of hormone?
A
thyroid gland: stores premade thyroid hormone in “colloid”
6
Q
thyroid hormone is synergistic with the SNS : what are the 3 effects of this?
A
- Increase metabolic rate (cell rxn rate) & heat production (ATP production)
- Promote catabolism
- Increase HR & contractility
7
Q
what is the “jod-basedow phenomenon”?
A
low levels of iodine - thyroid is hungry to iodine - if you give them iodine it will grab onto everything it can (iodine transport into follicular cell) and pump out all of its hormones
—> create a thyroid storm
- gland under heavy TSH stimulation
8
Q
what can cause the “jod-basedow phenomenon”? why is this significant?
A
Treating iodine-deficient patients with heavy iodine can produce acute hyperthyroidism or even thyroid storm
takehome message: txt iodine deficiency in a slow controlled manner
9
Q
what is the Wolff-Chaikoff effect? (kinds weeds)
A
High levels of I- inhibit coupling of I2 to TG & coupling of MIT/DIT
10
Q
txt for hyperthyroidism (and jod-basedow phenom) ?
A
- methimazole (inhibits TPO)
- PTU (inhibits TPO + conversion of T4 to T3)
*TPO = thyroperozidase - catalyst for T4 and T3 production
11
Q
what is thyroglobulin?
A
thyroglobulin - carrier proteinmolecule - most abundant thyroid binding hormone
12
Q
what are the steps of thyroid hormone synthesis? (3)
A
- Thyroglobulin secreted into follicles
- Active transport & oxidation of iodine by Thyroid peroxidase (TPO)
- MIT and DIT coupled to form thyroid hormones…
2 of the DIT (diiodotyrosin) - T4
DIT + MIT (mono iidotyrosin) = T3
13
Q
what is the ratio of T4 to T3 in plasma?
A
T4 > T3 secreted into plasma (9:1 ratio)
14
Q
99% of thyroid hormones, are bound to plasma protiens… what are the three proteins thyroid hormone can be bound to? what is the most prevalent?
A
Thyroid-binding globulin (TBG)-most
Transthyretin
Albumin
15
Q
what type of thyroid hormone is “free”?
A
Only “free” hormone is active (free to bind to target receptors)
16
Q
how can hepatic failure and pregnancy each effect the amount of TBG (thyroid binding hormone)?
A
Hepatic failure (liver produces most plasma proteins- so failure = lower levels of thyroid binding hormones)- more free thyroid hormone
pregnancy - increase in estrogen increase level of binding protein - less free thyroid hormone
17
Q
best way to increase thyroid binding hormone
A
give estrogen
18
Q
how likely is Clinical hyper-/hypo-thyroidism due to binding hormones?
A
rare due to negative feedback
19
Q
what are the hypothalamus/pituitary axis for thyroid hormone secretion?
A
Hypothalamic TRH stimulates TSH secretion
TSH stimulates thyroid growth & hormone secretion
–> T3 and T4 secretion
*negative feedback to anterior pituitary
20
Q
What is TRAb?
A
Thyroid-stimulating antibodies
-they bind & stimulate TSH receptors (in this case, antibodies don’t destroy but actually stimulate)
21
Q
why is measuring thyroid hormone levels easier than measuring any other hormone level?
A
secretion is constant (not pulsatile) so a “spot” level is possible
22
Q
what is “cretinism”?
A
congenital hypothyroidism
- screened for at birth
- check TSH +/- T4
- untreated can lead to mental retardation, deafness, spasticity
23
Q
what is a “goiter”?
A
enlarged thyroid- can be from anything- hyper, hypo or normal thyroid
24
Q
3 types of acquired hypothyroidism
A
Primary: under functioning thyroid despite normal stimulation
Secondary (central hypothyroidism): under stimulation from too little TSH (pituitary problem)
Tertiary (the other central hypothyroidism): too little TSH from too little TRH (hypothalamic abnormality)
25
which type of acquired hypothyroidism is most common? least common?
most: primary
least: tertiary
26
txt for all three types of acquired hypothyroidism?
thyroid hormone replacement (synthroid)
27
6 causes of acquired hypothyroidism?
1. Lack/loss of thyroid tissue
*2. Iodine deficiency (ultra rare in US)
*3. Excess iodine (Wolff-Chaikoff)
**4. Hashimoto’s (chronic autoimmune) thyroiditis (MOST COMMON)
*5. Amiodarone - can induce wolff-chaikoff effect
(High iodine content)
6. Valproic acid
28
8 manifestations of hypothyroidism
1. Slowing of body & mind: Mistaken for “depression”
2. Decreased HR & contractility
3. Increased LDL cholesterol
4. Constipation, weight gain
5. Coarse, brittle hair
6. Cold intolerance
7. Delayed “hung” DTRs (deep tendon reflexes)
8. Myxedema
29
what is myxedema?
```
accumulation of ground substance in connective tissues
Thick tongue
Periorbital edema
Coarse voice
(seen in hypothyroidism)
```
30
what is hashimoto's thyroiditis?
"chronic autoimmune thyroiditis"
- Autoimmune reaction to thyroglobulin &/or TPO ( the immune system attacks these)
- lymphocyte infiltration of thyroid gland ( goiter common)
- Usually euthyroid, many hypothyroid, few transiently hyperthyroid
31
what is schmidt's syndrome? (kinda weeds)
a triad:
hypothyroidism
autoimmune adrenalitis - adrenal insufficeincy (addisonism)
DM type 1
32
txt of schmidt's syndrome, what do you need to be careful to do? (kinda weeds)
cover with steroids THEN add synthroid
(if you don't do this first you can kill them)
... not sure why ..
33
what is DeQuervain’s Subacute Thyroiditis?
viral infection of the thyroid (i.e. coxsackie)
| Spotty destruction of follicular cells with release of colloid
34
presentation of DeQuervain's Subacute thyroiditis? what can it lead to (short term and long term)?
- Neck pain, fever
- Increased ESR
* May cause transient hyperthyroidism, may lead to hypothyroidism (longterm)
35
3 types of hyperthyroidism
Primary-hyper functioning thyroid despite normal stimulation
Secondary-hyper functioning thyroid due to overstimulation from excess TSH (pituitary) . Usually ectopic
Tertiary-too much TSH from too much TRH (hypothalamus)
36
what are the most and least common types of hyperthyroidism?
most: primary
least: tertiary
37
5 important causes of hyperthyroidism (and which are the two most common) ?
1. Graves’s disease (most common)
2. Plummer’s disease (2nd most common)
3. Jod-Basedow (rare in US)
4. DeQuervain’s (transient) (with initialy destruction of gland- get hypo)
5. amiodarone
38
presentation of hyperthyroidism (5)
1. increased mentation - labile, anxious
2. hypermetabolic
3. enhanced epinephrine effect
4. ***Osteoporosis
5. Lid lag/exophthalmos
39
what do the hypermetabolic effects of hyperthyroidism cause? (3)
Increased appetite & weight loss
Muscle atrophy
Heat intolerance
40
what does the enhanced epinephrine effect cause? (3)
Tremors
Bounding pulse
Atrial fibrillation
41
what is Grave's disease ?
Idiopathic autoimmune production of anti-TSH receptor antibodies (TRAb)
- TRAb stimulate TSH receptor
- increase T4
42
what is the "classic triad" of grave's disease?
1. Goiter (diffuse toxic) (hot on throid scan)
2. Ophthalmopathy-proptosis/exophthalmos - lid lag
3. Pretibial myxedema-connective tissue nodules on anterior leg - tissue deposits on anterior leg
43
labs for grave's disease
High T4 & low TSH
| +TRAb
44
3 pharm. Txt options for Grave's disease
1. Antithyroid drugs: PTU, methimazole
2. Propranolol (blocks some of the SNS effect- HR, tachycardia, etc)
3. Radioactive iodine (I131) - ablation of thryoid- usually most common option. (produces Hypothyroidism)
45
surgical txt for grave's disease?
Near-total thyroidectomy (avoid post-op hypothyroidism)
46
what is plummer's disease?
“Toxic adenoma” Benign functional tumor
Hyperfunctioning tumors-mutated TSH receptor stuck in the “on” position
“Hot” nodule on thyroid scan
- rarely turn malignant
47
txt for plummer's disease?
surgical removal
surgical dilemma: *difficult to differentiate from malignant follicular carcinoma
- both benign and malign. tumors here can be functional- produce hormones
48
what is the most common endocrine cancer overall ?
thyroid cancer
49
4 types of thyroid cancer?
Papillary-most common, least deadly
Follicular-modestly aggressive
Medullary-aggressive
Anaplastic-least common, ultra aggressive
50
overall, thyroid disorders more common in men or women?
women
51
60-85% percent of thyroid cancers are what kind?
papillary
52
while most don't die from papillary carcinoma (thyroid cancer)- what manifestation can cause death?
Asphyxiation - invasion into trachea - can cause death
53
where does papillary carcinoma metastasize?
metastasizes to cervical lymph nodes (lymphatic route of metastasis as opposed to blood)
54
can you "just watch" thyroid cancers?
NO! all have the potential to become the ultra aggressive anaplastic kind
55
what cancer is "orphan annies tumor" associated with?
papillary carcinoma
56
what are the characteristics of "orphan annies" tumor? (5)
1. Most often affects young women
2. Stays around for years without getting bigger (comic strip around for years without her getting older)
3. Well-behaved & doesn’t kill people
4. Nuclei have marginated chromatin-”Orphan Annie’s eyes” (she had just whites as eyes)
5. Psammoma bodies in cytoplasm-calcifications (Greek for sand, “Sandy” was orphan annies dog)
57
prognosis of follicular carcinoma? (kinda weeds) - (% that will die if metastatic, survival, biggest risk)
50% will eventually die from it if metastatic
Survival commonly >> 5 years
Iodine deficiency is greatest risk
58
how does follicular carcinoma (thyroid cancer) metastisize?
hematogenous route of metastasis (Lungs, bone)
59
what type of thyroid cancer notoriously creates the "surgical dilemma"?
follicular carcinoma: difficult to distinguish from follicular adenoma on frozen section
-lobectomy or total thyroidectomy? ..
60
txt for follicular carcinoma
- Many take up I131- (radioactive iodine) useful for detecting metastases or
- treatment (if you dont want surgery)
61
describe medullary carcinoma
- cancer of C-cells (calcitonin)
-Mutation in RET proto-oncogene on chromosome 10
Multiple Endocrine Neoplasia type II syndrome-familial
(more during “adrenal”)
More often (80%) sporadic
62
which thyroid cancer may you do genetic testing for? why?
medullary carcinoma
| - Test for gene available (MEN gene) : Prophylactic thyroidectomy
63
how can you tell if you got the entire tumor for medullary carcinoma surgical removal?
Tumors typically produce calcitonin (differentiated enough to act like normal cells) -marker for adequate surgical resection
- if calcitonin negative = you got the tumor completely
64
prognosis of aplastic carcinoma (what % of thyroid cancers? arise from what?, txt?)
5% of thyroid cancers
Virtually all will die from it within months
Most arise from a previous papillary carcinoma
Usually offered hospice over chemotherapy
65
what are the two ways we can measure T4?
Serum T4- total (bound + unbound) hormone
| Serum free T4- unbound (active) hormone: More expensive
66
which thyroid hormone do we care about measuring?
T3
| but serum T3 and free T3 is only available at some institutions
67
explain the T3RU test results (kinda weeds)
T3 resin uptake: inversely proportional to free sites on thyroid binding proteins
- T3RU if high- low # free binding sites on TBG b/c they were already filled up - more bind to resin
- if T3RU low - high # free binding sites on TBG - less bind to resin
68
how does the T3RU test work? (weeds)
* resin has lower affinity for T3 than natural TBG
- dump plasma (w/ T3 bound to TBG) on resin
- add radioactive T3: preferentially binds TBG free sites
- leftover radioactive T3 will bind resin
- dump mix, measure radioactive levels
69
what is used to "correct for the binding abnormalities" of the T3RU test?
Free thyroxine index (FTI)=T4 * T3RU
70
what TSH levels correlate with hypo-/hyperthyroid? (kinda weeds)
hypothyroid- high TSH
hyperthyroid- low TSH
*normal TSH about 0.35-5.0
71
do we treat patients based on the T3/T4 levels or the symptoms?
TSH levels & symptoms > T3/T4 levels in guiding therapy
| Treat the patient, not the numbers
72
what are "hot" vs "cold" on thyroid scans?
Hyperfunctional tissue looks “hot” (dark)
| Nonfunctional/suppressed tissue looks “cold” (white)
73
thyroid scan interpretation: hot nodules most likely produce ______ while cold nodules most likely to be _____
Hot nodules most likely to produce hyperthyroidism
| Cold nodules most likely to be malignant
74
thyroid scan interpretation: diffusely hot =? diffusely cold =?
Diffusely hot in Graves
| Diffusely cold in DeQuervain’s, factitious
75
what 3 thyroid autoantibodies can we test for, what does each indicate?
TRAb-TSH receptor antibody (Graves’s)
TPOAb-anti-peroxidase/anti-microsomal antibody (Hashimoto’s)
TgAb-anti-thyroglobulin antibody (Hashimoto’s)
76
FNA result interpretation, what do you do if result is " nondiagnostic" ?
repeat with ultrasound (need another sample with better FNA- guided)
77
FNA result interpretation, what do you do if result is "benign"?
follow clinically
78
FNA result interpretation, what do you do if result is "atypia of uncertain significance"?
repeat FNA
79
FNA result interpretation, what do you do if result is "suspicion of follicular neoplasm"?
lobectomy (where the “surgical dilemma” comes in.
| - Benign/malignant distinction difficult
80
FNA result interpretation, what do you do if result is "suspicion of malignant" or "malignant" ?
Suspicious for malignancy-lobectomy/thyroidectomy
| Malignant-thyroidectomy
81
what is the major regulator of calcium homeostasis?
parathyroid glands
82
parathyroids contain what type of cells?
hormone-secreting cheif cells
83
parathyroid effect on kidney
1. Promotes conversion of 25-OH-D3 to active 1,25-(OH)2-D3 that increases calcium absorption from the gut
2. Promotes reabsorption of calcium & loss of phosphate
84
parathyroid effect on bone
Promotes resorption of calcium by osteoclasts
| Promotes proliferation of osteoclasts
85
parathyroid effect on gut
Promotes calcium absorption (INDIRECT via vitamin D activation)
86
parathyroid is a rapid strong secretory response to Ca2+ < ____ mg/dL
Ca+2 < 10 mg/dL
87
Chronic _________ impairs PTH secretion
hypomagnesia
88
what induces feedback inhibition of PTH?
Normalization of Ca+2 induces feedback inhibition
89
primary hyperparathyroidism is due to what? (and 3 biggest causes)
Primary hyperparathyroidism-due to parathyroid disease
1. parathyroid adenoma (single gland)
2. parathyroid hyperplasia (all glands)
3. parathyroid carcinoma
90
what is the most and least common cause of primary hyperparathyroidism?
```
parathyroid adenoma (single gland) - MOST 85%
parathyroid carcinoma - LEAST
```
91
85% of people with hyperparathyroidism have what genetic abnormality?
MEN-I
92
Incidental hypercalcemia is usual presentation of what?
hyperparathyroidism
93
"Stones, bones, abdominal moans, & psychiatric overtones" - indicates what?
hyperparathyroidism
94
Dx labs of hyperparathyroidism
High serum Ca+2, low serum P, elevated PTH
95
what level defines hypercalcemia?
Total serum Ca+2 > 10.5 mg/dL
96
two major causes of hypercalcemia?
1. hyperparathyroidism
| 2. hypercalcemia of malignancy
97
what are the general signs of hypercalcemia?
Polyuria, polydipsia, renal calculi
Bone demineralization, pathologic fractures
Constipation, nausea, vomiting
Fatigue, personality changes, frank psychosis
Pancreatitis
98
hypercalcemic crisis causes what?
-hypovolemia, depressed LOC, fever, cardiac dysrhythmias/arrest
99
parathyroid adenoma
Autonomous production of PTH
- Other glands suppressed/atrophic
- 10% are “ectopic” (variable location)
100
4 part txt of parathyroid adenoma
1. Preoperative sestamibi scan can localize
2. surgical removal
3. Intraoperative PTH levels determine effectiveness (if it drops near zero after you removed hot gland - tells you that you got the adenoma)
4. post-op Ca+ supplement
101
what post-operative supplement do people need after removal of parathyroid adenoma?
Postoperative calcium supplementation (500-100 mg /day)
102
if you have a functional parathyroid adenoma, why is it hard to find the other parathyroid glands? what happens to these when you remove the cancerous one?
its hard to find the other parathyroid glands b/c they are atrophied. These will grow and recover when we remove the oppressive PTH - producing parathyroid.
- So the pt will not be hypoparathyroid after some time.
103
parathyroid hyperplasia
All glands hyperplastic & autonomous
- “4 gland adenoma”
Raise suspicion for MEN I or IIa
104
2nd most common cause of hyperparathyroidism?
parathyroid hyperplasia
105
txt of parathyroid hyperplasia
Requires excision of majority of parathyroid tissue (take all 4)
Slithers of gland transplanted to forearm muscle to prevent hypoparathyroidism (so their calcium doesnt go very low) - if calcium still high, take a few of these implanted ones out - easier to get there than the throat)
106
secondary hyperparathyroidism causes
```
Parathyroid hyperplasia due to chronic hypocalcemia
- Renal failure (hypocalc, hyperphos.)
- Vitamin D deficiency
= serum Ca+ high
= bone Dz (osterodystrophy)
```
107
txt for secondary hyperparathyroidism
Treated with cinacalcet or transplantation
108
tertiary causes of hyperparathyroidism
Hyperplastic gland in renal failure becomes autonomous
| - Overproduces PTH, Serum Ca+2 high
109
txt of tertiary hyperparathyroidism: may regress after what? may require what?
May regress after renal transplantation
| May require removal of adenoma
