Thyroid and Parathyroid- Usera Flashcards
1
Q
What are the diverse cellular effects of the thyroid hormone?
A
- up regulation of carbs and lipid catabolism
- protein synthesis
- increase basal metabolic rate (upregulate Na/K atpase pump on cell surface)
2
Q
What is thryotoxicosis?
A
hypermetabolic state due to elevated T3 and T4
3
Q
What are the primary ways you can get hyperthyroidism?
A
- diffuse hyperplasia (due to grave’s disease)
- hyperfunctional multinodular goiter
- hyperfunctional adenoma of the thyroid
4
Q
What are the seondary (extrinsic) ways you can get hyperthyroidism?
A
-TSH secreting adenoma of pituitary
5
Q
What are the signs and symptoms of hyperthyroidism?
What are these caused by?
A
- warm, flushed skin
- heat intolerance
- weight loss, skeletal muscle atrophy
- tachycardia, palpitations, cardiomegaly, arrhythmias, thyroid myopathy
- GI hypermotility, malabsorption, diarrhea
- osteoporosis
Increased sympathetic tone
6
Q
What are the 2 mechanisms behind the ocular changes due to hyperthyroidism?
A
- increased muscle tone of levator palpebrae superioris
- antibody-mediated hyperplasia of periorbital soft tissue (only in grave’s disease)
7
Q
What is a thyroid storm?
A
-abrupt onset of severe hyperthyroidism (MEDICAL EMERGENCY)
8
Q
What causes a thyroid storms?
A
-acute infection, surgery, cessation of anti-thyroid meds, any major stress
9
Q
How do patients die of a thyroid storm?
A
die of a cardiac arrhythmia
10
Q
How do you diagnose hyperthyroidism?
A
Labs:
-serum TSH levels (MOST USEFUL SINGLE SCREENING TEST)
-Low TSH value confirmed by elevated T4
Clinical findings
11
Q
What are the derangements like in hypothyroidism? What percentage are overt? What percent are subclinical?
A
structural or functional
0.3% overt
4% subclinical
12
Q
THe prevalence of hypothyroidism increases with (blank). What gender is it more common in?
A
age
10 fold more common in women
13
Q
Are the vast majority of causes of hypothyroidism intrinisc or extrinisc?
A
intrinsic (i.e defect in thyroid itself)
14
Q
Intrinisc hypothyroidism can be accompanied by a (blank). How can you get intrinic hypothyroiism?
A
goiter
congenital, acquired, or autoimmune (hashimoto)
15
Q
What are the extrinsic/secondary causes of hypothyroidism?
A
hypothalamic/pituitary axis
16
Q
What are the clinical findings of hypothyroidism?
A
- proximal muscle myopathy
- mental sluggishness
- weight gain
- dry brittle hair
- loss of outer third of eyebrow
- coarse yellow skin
- periorbital puffiness
- fatigue, cold intolerance, constipation
17
Q
Congenital hypothyroidism is usually due to (blank) deficiency
A
endemic iodine deficiency
18
Q
How can you get a dishormonogenic goiter?
What are these steps?
A
defect in any step of T3 or T4 synthesis
- iodide transport into thyrocytes
- iodide organifications (binding to tyrosine residues on TGB)
- Iodotyrosine coupling to form T3 and T4
- Most commonly effected step:: thyroid peroxidase deficiency
19
Q
What is pendred syndrome?
What is the pathophysiology of this?
A
hypothyroidsm and sensorineural deafness
Autosomal recessive disorder with a deficiency in th SLC26A4 gene that results in reduced pendrin which is an anion transporter
20
Q
What is thyroid resistance syndrome?
A
rare AD disease where you have an inactivating mutation in the TSH receptor that causes high T3, T4, and TSH.
21
Q
What are all the congenital causes of hypothyroidism?
A
- iodine dieficiency
- Pendred syndrome
- Thyroid hypoplasia/agenesis
- Thyroid horomone resistance syndrome (inactivating mutations in TSH receptor)
22
Q
How can you get acquired hypothyroidism?
A
- surgical or radiation inducd
- drugs (methimazole and proprylthiouracil, lithium)
- hypothalamic or pituitary trauma
23
Q
How does methimaxole and propylthiouracil cause hypothyroidism?
A
-they inhibit thyroid peroxidase
24
Q
A (blank) is a specific type of ectopic thyroid, and results from lack of normal caudal migration of the thyroid gland.
A
lingual thyroid
25
What is this:
a midline cyst line by ciliated mucosa (oropharyngeal mucosa)
When does this present and in what gender does it present most?
Thyroglossal duct cyst
| -adolescents, more common in males
26
What is struma ovarii?
rare ovarian tumor with the presence of thyroid tissue compromising more than 50% of the overall mass. It occurs as part of a teratoma.
27
What is cretinism?
congenital hypothyroidism resulting in severe mental retardation and skeletal and CNS impairment
28
Why does cretinism result in menta retardation?
because T3 and T4 are critical to fetal brain development-> if maternal deficiency exists prior to fetal thyroid development-you get mental retardation
29
What will children with cretinism look like?
- short stature
- coarse facial features
- large tongue
- umbilical hernia
- mental retardation
30
What is Myxedma (gull disease)?
| What does it present like clinically?
hypothyroidism in older child or adult
| -general slowing of physical and mental activity (intermediate b/w cretinism and adult hypothyroidism)
31
What does myxedma (gull disease) look like histologically?
-accumulation of matrix substances in skin, soft tissue and viscera (hyaluronic acid, glycosaminoglycans)
32
Thyroiditis can present in what 2 ways? How is it spread? Is it painful? What causes this?
- chronic or acute
- hematogenous spread or direct seeding
- autoimmune
33
What is the most common cause of hypothyroidism in iodine sufficient areas?
Hashimoto thyroiditis
34
How can you tell someone has hashimoto thyroiditis histologically?
the goiter has an intense lymphocytic infilitrate
35
What is the disease progression of hashimoto thyroiditis?
-gradual onset of thyroid failure
36
When is the peak incidence of hashimoto thyroiditis and is it more common in females or males? Is it genetic? Is it painful?
-45-65 years
females (20:1)
-40% concordance in monozygotic twins
-Painless!
37
What is this:
presents as painless enlargement of thyroid
May be diffusely enlarged or focal, raising suspicion of a neoplasm.
Hashimoto thyroiditis
38
How does hashimoto thyroiditis present clinically? What can it be preceded by?
- lethargy, mental sluggishness etc.
i. e sign and symptoms of hypothyroidism.
- hyperthyroidism (hoshitoxicosis)
39
Individuals who have hashimoto thyroiditis may be at increased for other autoimmune diseases such as...?
- DM
- SLE
- Myasthenia Gravis
- Sjogren syndrome
- Non-hodgkin B cell lymphoma
40
What is the pathology behind hashimoto thyroiditis?
- failed self tolerance to thyroid auto-antigens
- circulating antibodies; Anti-microsomal, anti-TPO, anti-TBG
- associated with polymorphisms in immune regulating genes.
41
What are the circulating antibodies found in Hashimoto thyroiditis?
- Anti-microsomal
- Anti-TPO
- Anti-TBG
42
What are the polymorphisms associated with Hashimoto thyroiditis?
- CTLA4-negative regulator of T-cell function
| - PTPN22-lymphoid tyrosine phosphatase, also a negative regulator
43
What are the three types of injury caused by the auto antibodies created in hashimoto thyroiditis?
- T cell mediated cytotoxicity
- Thyrocyte injury
- Antibody-dependent cell mediated cytotoxicity
44
What causes the T- cell mediated cytotoxicty found in hashimoto thyroiditis?
-CD8 and cytotoxic t cells
45
What causes thyrocyte injury in hashimoto thyroiditis?
-CD4+ and TH1 cell activate macrophages via IFN-gamma
46
What causes antibody-dependent cell-mediated cytotoxicity?
-plasma cells create antibodies which activate NK cells
47
What will hashimoto thyroiditis look like histologically?
- lymphocytic infiltrate (diffuse large infiltrate)
- hyperplastic germinal centers
- atrophic thyroid follicles
- fibrosis
- hurthle cell change
48
What kind of cancer can hashimoto thyroiditis develop into?
B cell lymphoma
49
What is this:
Folicuar cells with large, acidophilic cytoplasm (metaplastic chang)
Characterized as enlarged epithelial cells with abundant eosinophilic granular cytoplasm as a result of altered mitochondria.[2] They generally stain pink and are prominently found in histological sections of thyroid glands affected with Hashimoto's.
Hürthle cells
50
What is this:
| PAINUL, variably enlarged thyroid gland, transient HYPERthyroidism (2-6 weeks)
Subacute granulomatous thyroiditis (de quervan)
51
What causes subacute granulomatous thyroiditis (De quervan)?
virally mediated- coxsackie, adenovirus, mumps, measles etc (virus-initated immune response, thus self-limited)
52
What is subactue granulomatous thyroiditis (de quervan) usually preceded by? When does it occur? What age is peak incidence and what gender is it more common in?
URTI
Seasonal incidence
40-50 years old
F: M 4:1
53
What does subacute granulomatous thyroiditis look like histologically?
giant cells, destruction of thyroid follicles, non caseating granulomas
54
What is subacute lymphocytic thyroiditis (variant of hashimotos)?
a painless thyroiditis resulting in mild hyperthyroidism, goitrous enlargement or both
55
Who commonly gets subacute lymphocytic thyroiditis?
middle aged females
56
(blank) resembles post partum thyroiditis
subacute lymphocytic thyroiditis
57
What are the similiarities between subacute lymphocytic thyroiditis and hashimotos?
- Anti-TPO antibodies
- Other autoimmune diseases
- 1/3 of cases evolve to hypothyroifism
- similiar histology but without Hurthle cell change or fibrosis
58
What is Reidel's thyroiditis?
fibrous replacement of thyroid gland, extending to surrounding soft tisues resulting in a hypothyroid state
59
What is the major worry in reidels thyroiditis?
tracheal obstruction
60
What is reidels thyroiditis associated with?
sclerosing diseases e.g sclerosing mediastinits
61
How do you treat reidels thyroiditis?
corticosteroids or surgery
62
What is the most common cause of intrinsic hyperthyroidism?
| Who most commonly gets this?
Grave's disease
| females 20-40 y/o
63
Is graves disease genetic?
40% concordance in monozygotic twins and linked to polymorphisms in CTLA4 and PTPN22 and HLA-DR3 allele
64
What is the clinical triad of Grave's disease?
- hyperthyroidism
- exopthalmos
- pretibial myexedema
65
What are the lab findings of graves disease?
-low TSH, elevated T3 and T4
66
What causes Graves's disease?
- thyroid-stimulating immunoglobulin
- thyroid growth-stimulating immunoglobulin
- TSH-binding inhibitor immunoglobulin
67
WHat does thyroid stimulating immunoglobulin do?
anti-TSH receptor IgG that stimulates thyroxine synthesis
| MOST SPECIFIC FOR GRAVES
68
What does thyroid growth-stimulating immunoglobulin do?
Anti-TSH receptor, but induces proliferation of follicular epitheliums
69
What does TSH-binding inhibitor immunoglobulin do?
anti-TSH receptor IgG, but inhibitos thyroid cell function
70
In graves disease you get exopthlamos, why do you get this?
because orbital fibroblasts express TSH receptors that results in adipocyte proliferation, accumulation of ECM (glycosaminoglycans, hyaluronic acid), inflammatory edema, infiltrate of lymphocytes
71
What is the tx for grave's disease?
Beta blockers-symptoms
Propothiourcil-decreased thyroxine synthesis
Radioiodine ablation
Surgery
72
WHat is this:
diffuse enlargment of thyroid without nodularity
caused by deficiency in thyroid hormone synthesis (iodine def. biosynthetic disorder) with a compensatory increase in TSH secretion, often euthyroid (normal functioning thyroid)
Diffuse non-toxic goiter
73
What is this:
- geographic areas with low iodine salt content
- goitrogenic substances containing thiocyanate
Endemic goiter
74
What are goitrogenic substances and what do they cause goiters?
cruciferae family: cabbage, brussel sprouts, cauiflower, cassave
Have thiocyanate: inhibits iodide transport within thyroid
75
What are the causes of a multinodular goiter?
endemic or sporadic
-recurrent episodes of hyperplasia and involutions
-trophic hormones causing variable follicular epithelial responses
-alterations in TSH-signaling pathway
(males and females get this equally)
76
What are the clinical consequences of a goiter and what are they related to?
related to mass effect
- airway obstruction
- dysphagia
- compression of vessels (e.g SVC syndrome)
- cosmetic
77
The inferior Parathyroid gland comes from (blank) pharyngeal pouch
third
78
The superior parathyroid gland comes from (blank) pharyngeal pouch
fourth
79
What are the general functions of the parathyroid gland?
- increase renal tubular resorption of calcium
- increase conversion of 25 OH vit D to 1,25 Vit D in kidneys
- increase urinary phosphate excretion
- augements GI calcium absoprtion (mediated by activated vit D)
80
the parathyroid gland will have a progressive increasse in (Blank) with age, up to 30%
stromal fat
81
What are the 2 cell types found in the parathyroid gland and what do they do?
- Chief cells-functional cells that secrete PTH
| - oxyphil cells- mystery
82
What are the three types of hyperparathyroidism?
- primary
- secondary
- tertiary (AKA Pseudo)
83
What causes primary hyperparathyroidism?
| Who common gets this?
Spontaneous, autonomous overproduction
1. Adenoma (usually one gland involved)
2. Primary hyperplasia (usually all glands involved)
3. Parathyroid carcinoma (veyr rare)
-females 4:1
84
What will primary hyperparathyroidism lead to?
hypercalcemia, often diagnosed incidentally
85
What is primary hyperparathyroidism MOST COMMONLY caused by?
solitary parathyroid adenoma
86
What causes sporadic adenomas?
monoclonal neoplasms
87
What are the genetic syndromes associated with primary hyperparathyroidism?
- MEN-1: inactivation of 11q13 tumor suppressor
- MEN:2 activating mutation of Ret GENE, 10q
- Familial hypocalciuric hypercalcemia
88
What is familal hypocalciuric hypercalcemia?
- autosomal dominant
| - decreased sensitivity to extracellular calcium
89
What are the clinical findings of primary hyperparathyroidism (hypercalcemia)?
```
calcium stones
PUD
pancreatitis
osteolitis fibrosa cystica
Diastolic HTN
Metastatic calcification
Psychosis, confusion, anxiety
```
90
What are the lab findings of primary hyperparathyroidism (hypercalcemia)?
What is the anion gap like?
What is the chloride: phosphorus ratio?
increased PTH, calcium, 1,25 OH vit D (increased synthesis of 1 alpha hydroxylase)
Decreased phosphorus,
normal anion gap metabolic acidosis->Decreased renal resorption of bicarb (pee out bicarb)
chloride: phosphorous> 33
91
What is this:
arises from any condition causing chronic hypocalcemia
What are some examples of this?
Secondary hyperparathyroidism
| -inadequate calcium intake, steatorrhea, vit D deficiency
92
What is tertiary hyperparathyroidism? What can often cause this? It is essentially the same as primary hyperparathyroidism without the increased (blank).
- autonomous hypersecretion regardless of calcium levels.
- often post-renal transplant
-size
93
What are the causes of hypoparathyroidism?
- inadvertent consequence of surgery
- autoimmune hypoparathyroidism
- autosomal dominant hypoparathyroidism
- familial isolated hypoparathyroidism
- congenital absence
94
What is autoimmune hypoparathyroidism assocaited with?
mucocutaneous candidiasis due to polyendocrine syndrome type 1
95
What causes autosomal dominant hypoparathyroidism?
a gain of function mutation in calcium sensing receptor (CASR) gene
96
What can cause a congenital absence in a parathyroid gland?
DiGeorge (w/ thymic dysplasia)
97
What are the clinical findings of hypoparathyroidism (hypocalcemia)?
- tetany (chovostek and trousseau signs)
- mental status changes
- metastatic calcification of basal ganglia, lens of they eye and cataract
- prolongation of QT interval
- Dental hypoplasia (early onset)
98
What are the lab findings of hypoparathyroidism (hypocalcemia)?
decreased PTH, decreased Calcium, Increased Phosphate
99
What are 2 tests used to elicit signs of calcium deficiency and please describe them
Trouseaus sign and chovosteks sign
- Chovstek you tap around the facial nerve and your eye muscles will go into tetany
- Trousseaus-take blood pressure and you will get wrist flexion and spasm of fingers
100
What is pseudohypoparathyroidism?
What are the PTH levels like?
What can causes this?
What are the calcium levels like? phoshate levels?
- end organ resistance to PTH
- normal or elevated
- genetic defect in GPPCRs (also affecting TSH, FSH, and LH signaling)
Decreased calcium
Increased phosphate
