Pathology Flashcards
1
Q
Lack of most or all of the hormones from the anterior pituitary gland CC: “I don’t feel good.” – Growth hormone “My love life ”–FSH/LH “ .” – ACTH, TSH
A
Hypopituitarism (“Simmond’s disease”)
2
Q
Simmond’s due to watershed infarction of the adenohypophysis during an obstetrical catastrophe.
A perennial point of confusion.
A
Sheehan’s
3
Q
You have a tired, mousy, scrawny, unhappy patient. Spot morning cortisol (the screen) is less than 13 mcg/mL (as for many normals).
What test do you order?
A
ACTH stimulation test to rule ACTH insufficiency / adrenal insufficiency in / out
NOTE:
Please do NOT ask for a “spot ACTH” assay. And don’t kill your severely addisonian patient – the testing is stressful.
4
Q
Too little cortisol produced after ACTH administration. Doesn’t get better no matter how often
you do it.
A
Adrenal insufficiency
5
Q
The cortisol response is still low after an ACTH stimulation test, but it gets better each day.
A
Pituitary insufficiency
6
Q
Your patient is thirsty and peeing a lot. The urine probably isn’t concentrated (SG
A
Give an injection of ADH (ADH stimulation test).
If the urine becomes concentrated, the diagnosis is pituitary (“central”) diabetes insipidus.
If the urine still won’t become concentrated, there’s a renal medullary problem (“nephrogenic diabetes insipidus”)
7
Q
Your patient complains of failing libido and the history and ancillary testing indicate an organic cause.
Spot serum hormone levels as appropriate. What do you consider?
A
Serum prolactin level
8
Q
- You have a short kid, or an older adult who “just doesn’t feel well.”
- Consider a screen for what? ex: spot IGF-I assays. Think about doing some stimulation test or other.
- Give this make a kid who’s short grow taller regardless of the cause.
- Caution: “Failure to thrive” from not being cuddled may also feature lowish levels
A
growth hormone
9
Q
- Our patient is slowing down and you suspect hypothyroidism
- What do you screen with?
A
Free T4, free T3, and sensitive TSH.
10
Q
Your patient is fat and/or hypertensive and/or diabetic and/or sad and/or crazy.
1st: 24 hour urine cortisol is one good screen for Cushing’s. Then use a dexamethasone suppression test.
Given at midnight, 2 mg of dexamethasone (the synthetic glucocorticoid) will suppress ACTH and hence blood cortisol levels measured in the morning.
Dx if…?
Suppressed by 8 mg but not by 2 mg?
Not suppressed by 8 mg?
A
Suppressed by 8 mg but not by 2 mg:
Pituitary adenoma
Not suppressed by 8 mg:
Some other cause of inappropriate ACTH / inappropriate cortisol production.
11
Q
Your patient is sick and found to be hyponatremic. The urine sodium is higher than you’d expect.
Ask the patient to drink as little water as they can and see if things normalize
A
Note:
Don’t overdiagnose the syndrome of inappropriate ADH, especially in the presence of cachexia.
12
Q
Galactorrhea-amenorrhea or something else that makes you think we have a pituitary problem.
Order what?

A
Spot FSH and LH
13
Q
Looking at this diabetic / ugly adult / too-tall kid makes you wonder, “Could this be a growth-hormone producing pituitary tumor?”
What do you order?
A
Spot IGF-1
Note:
A serum GH itself is best used as a suppression test – if a glucose load fails to suppress=acromegaly / gigantism
14
Q
Declining libido, menstrual irregularities?
What do you order?
A
Spot serum prolactin.
If it’s a prolactinoma, the concentration will usually be >100 ng/mL.
Most other entities will not give such a high prolactin.
15
Q
High TSH and high T4?
A
Hyperthyroidism due to a TSH-producing pituitary lesion
16
Q
T/F
Pressure on the optic chiasm from a mass (pituitary) can lead to bitemporal hemianopsia
A
TRUE
17
Q
Pt presents with papilledema, HA, N/V…
A
Signs of incr intracranial pressure!
Can happen in pituitary adenoma patients.
18
Q
Hemorrhage into the tumor --> Necrotic--> Swells--> Midbrain compressed--> Cavernous sinus syndrome
A
Pituitary apoplexy from hemorrhage into the tumor
19
Q
Difference b/t normal ant. pituitary and adenoma on a slide?
A
The normal anterior pituitary has a variety of cells while the adenoma has a uniform population
20
Q
Reticulin staining of the pituitary:
If it surrounds groups instead of individual cells=_______.
If really scrambled=_______.
A
hyperplasia
adenoma (reticulin also around BV)
21
Q
TQ
In pituitary adenomas, what often mutates and loses self-feedback control?
A
G-protein signaling
may lead to proliferation, hormone syn and secretion
22
Q
TQ
Pituitary adenoma genetics – ONCOGENES (gain-of-function mutations):
- Activating mutation
- GH-omas
A
GNAS
23
Q
TQ
Pituitary adenoma genetics – ONCOGENES (gain-of-function mutations):
- Carney complex/germline mutation
- GH-omas
- Prolactinomas
A
PRKAR1A
24
Q
TQ
Pituitary adenoma genetics – ONCOGENES (gain-of-function mutations):
- Amplified
- Marker for aggressive adenoma
A
Cyclin D1 (CCND1)
25
TQ
Pituitary adenoma genetics – ONCOGENES (gain-of-function mutations):
- Point mutation
- Pituitary carcinoma warning
HRAS
26
TQ
Pituitary adenoma genetics – ANTI-ONCOGENES (loss-of-function mutations):
- Germline
- Prolactinoma (less often GH or ACTH-omas)
MEN-1
27
TQ
Pituitary adenoma genetics – ANTI-ONCOGENES (loss-of-function mutations):
- Germline
- ACTH-omas
CDKN18
28
TQ
Pituitary adenoma genetics – ANTI-ONCOGENES (loss-of-function mutations):
- Germline
- Familial GH-omas
- Irish giants
AIP
29
TQ
Pituitary adenoma genetics – ANTI-ONCOGENES (loss-of-function mutations):
-If this promoter is methylated, an adenoma is more likely to be aggressive
RB
30
TQ
| What are the two markers that correlate with tumor aggressiveness?
p53
Ki67/MIB-1
31
TQ
- Lights up the golgi
- Tends to be comprised of acidophils
- May only have a few granules
- Fibrotic post-tx
Prolactinoma
32
What is a pituitary stone?
calcifying prolactinoma
33
How do we take out a prolactinoma?
trans-sphenoidal resection
34
TQ
| What are a few health problems faced by acromegalics?
-Big bones, famously the jaw (prognathism)
-Overdense (hyperostotic) or
osteoporotic bone
-Glucose intolerance / diabetes
-Gonadal dysfunction
-Myopathy / muscle weakness; congestive heart failure
-Hypertension
-Arthritis
-Goiter
-Sleep apnea
-Carpal tunnel
-High blood phosphate (IGF-1 promotes reabsorption)
-Clearly increased risk of some cancers, most notably colon
35
T/F:
| The amount of stainable hormone in an HGH acidophil adenoma does not correlate with blood levels
True!
| Densely granulated adenomas tend to be less aggressive than sparsely granulated adenomas.
36
Cushing's syndrome vs. disease?
Cushing’s SYNDROME: Too much cortisol.
Cushing’s DISEASE: Too much cortisol as a result of an ACTH- producing pituitary adenoma.
37
-smallish “basophilic” tumors
ACTH-producing adenomas
38
TQ
- Old-time pt w/ Cushing’s disease had his adrenals removed instead of his pituitary adenoma :(
- The little bit of feedback that the high cortisol levels once gave is now gone.
- The pituitary ACTH-oma is now growing out of all control. He’s turned brown and is losing his eyesight (optic chiasm)
Dx?
Nelson's syndrome
39
Carcinoma of the pituitary:
What is the real criterion for malignancy in an anterior epithelial pituitary tumor?
Metastases
40
```
TQ
Pt presents w/:
-weakness
-lost libido/amenorrhea
-wt loss
-personality changes
-muscle wasting
-failure of lactation, diabetes insipidus, growth failure may also presents
```
Hypopituitarism
| adenoma, infarct, empty sella
41
TQ
| What are a few causes of hypopituitarism?
-Tumors (adenomas, craniopharyngiomas)
-Big Rathke cyst
-Brain trauma / subarachnoid bleeds
-After surgery / radiation
-“Pituitary apoplexy” (bleed into an adenoma)
-Ischemic necrosis / Sheehan’s
Empty sella syndrome:
-Primary (arachnoid & CSF herniate into the sella)
-Secondary (after damage from any cause)
-Hypothalamic lesions (rare, arcane)
-Sarcoidosis (anterior, posterior or both)
-TB meningitis
-Lymphocytic or granulomatous hypophysitis
-Genetic defects (remember PIT-1 – no GH, TSH, prolactin)
42
A large opening in the diaphragm on top of the sella allows arachnoid and CSF to move downward
Empty sella syndrome
43
Which twin has hypopituitarism due to a pituitary adenoma?
Hair loss, skinny
OR
No hair loss and overweight
No hair loss and overweight
44
How can you tell between simmonds or anorexia?
Ask pt if they like the way they look
45
Lymphocytes fill the adenohypophysis and the glandular cells are depleted
Lymphocytic hypophysitis
46
A family with no GH may have a mutation in which gene?
PIT-1 gene
47
What are two surprise causes of diabetes insipidus?
Sarcoidosis and eosinophilic granuloma (histiocytosis X)
48
- benign but locally destructive, and usually surgery is curative
- arise in or near the pituitary gland from Rathke’s pouch remnants
- stain catenin
Craniopharyngiomas
49
TQ
- Mostly children
- Look for calcifications, cell palisades
- Machine-oil cysts, layers of keratin
- Recall oral / tooth histology
Which gene mutation is assoc w/ this pathology?
Dx: Adamantinomatous craniopharyngioma
Gene: CTNNB1 (beta-catenin) mutations
50
TQ
- Mostly older adults
- Papillae lined by stratified squamous cells
Which gene mutation is assoc w/ this pathology?
Dx: Papillary craniopharyngioma
Gene: BRAF V600E mutations
51
Most familiar cause of secondary pituitary insufficiency?
Hypothalamic gangliocytoma (hamartoma)
52
Underworked ACTH-producing cells get a glassy look to their cytoplasm
Crooke's hyaline change
53
Simple cysts in the pituitary region lined by columnar and/or squamous epithelium. Rarely, pressure can damage the pituitary.
Rathke cyst
54
17 yo old boy, HA behind left eye. N w/out vomiting, school performance declined. Growth stopped at 15. Angry outbursts...HA now 2-3 times per week...put on an anti-anxiety drug...HA continued...Not disabled
Bitemoporal hemianopsia, hyper pigmentation on shoulder, strong erections and no gynecomastia.
Labs: Hypothyroid but very high prolactin...so give thyroxine replacement...Has simmons
Imaging: 2 masses-one bone and other cystic in the sella (prolactinoma!)
Next biopsy trans-sphenoidally, lights up with MIB-1 (aggressive)
What gene is most likely altered?
CCND1: amplified if tumor aggressive
55
Gene review:
1. ___: rare...giant families. hGH predominant
2. _______: familial ACTH-omas
-MEN-1: proliferation marker, not mutated (multiple endocrine neoplasia), families
3. ____: genetic pituitary insuff
GNAS: sporadic HGH-omas
HRAS: cancer
1. AIP
2. CDKN1B
3. PIT-1
56
Pituitary adenoma has expanded which direction..?
-______: bitemporal hemianopsia
- _______: hydrocephalus from midbrain compression
- _______: cavernous sinus syn--> opthalmoplegia (III, IV, VI), severe HA, stroke, venous stasis (eyelid swlled, proptosis), blood leakage into CSF
Upward
Posterior
Laterally
57
-Tired, can't eat, feel sick:
lost finger to TB, hypothyroid-->tx, speaks slowly, depressed (endocrine), vomiting (intracrhaial)
- CT (big blob of contrast-->mass in head)...yellow mass, calcium cyst, machine oil
- Dx?
- Meds needed for hypopituitarism because of damage to hypothal, keratin from tumor-->meningitis
- Mutation: BRAF 600E
Papillary craniopharyngioma b/c no palisading
58
How do we stain C-cells?
calcitonin
small groups outside thyroid follicles
59
Black thyroid due to ?
antibiotic minocycline
60
Hyperplastic epithelium-->goiter could result from...(3)
- Graces
- Iodine deficiency
- Goitrogen/PTU effect
61
Colloid-filled follicles-->goiter could result from...(2)
- Idiopathic nodular goiter
| - Extreme iodine excess
62
Anaplastic cells-->goiter could result from...(1)
cancer
63
Lymphocytes-->goiter could result from... (1)
Hashimoto's
64
Foreign-body granulomas-->goiter could result from...(1)
DeQuervain's
| coxsackie virus-->macrophages attack thyroglobulin-->tender
65
Fibrous tissue-->goiter could result from...(1)
Riedel's
66
Because they block oxidation of iodine & thus T4 production, they produce very cellular, colloid-poor thyroid glands
Goitrogens
| cabbage, cassava, iodine def
67
Macrophages clean up a thyroid gland that’s been injured through palpation by lots of physicians
Palpation thyroiditis
68
-common, minor birth defect
-can grow over time and become troublesome
-Especially with the possible passageway to the mouth, they’re prone to get infected
-Removing them is generally a good idea

Thyroglossal duct cysts
69
TQ
- Slowing of mind and body
- Constipation
- Myxedema (increased tissue ground substance)
- Big tongue
- Schizophrenia, irritability, depression
- Weak heartbeat
- high LDL
- Slow reflexess
- Croaky voice
- Dry, cold skin
- Cold intolerance
- Hair thinning
Hypothyroidism
70
What are some causes of hypothyroidism?
- Thyroid agenesis
- Inborn errors of metabolism
- Other genetic mutations: TSH receptor
- After surgery / radiotherapy
- Autoimmuity (Hashimoto’s)
- Iodine deficiency
- Medications (lithium, para-amino salicylic acid)
- Secondary (lack of TSH / TRH, uncommon)
71
-extreme example of hypothyroidism in the young
-In much of the world, this results from maternal hypothyroidism
/ iodine deficiency.
-Diminished learning ability per year, and less brain power overall in the iodine-deficient population
-In the United States, inborn errors of metabolism and
the occasional agenesis of the thyroid get screened for soon after birth.

Cretinism
72
Iodine deficiency and goitrogen (cabbage)-->hyperplasia whereas iodine ______ gives huge, distended, follicles that prevent breakdown of thyroglobulin
toxicity
73
- Coursing of facial features
- Big tongue
- Hard to smile
Myxedema due to hypothyroid
74
Most adult-onset endogenous hypothyroidism in the US is due to what?
hint: brown thyroid from the mitochondria
Autoimmune thyroiditis, usually Hashimoto’s, in which T-cells attack and cause apoptosis of thyroid follicle cells
May see germinal centers and Hurthle cells (mitochondria)...may also see fibrosis
75
When discovered incidentally (workup of goiter), most Hashimoto’s are ______. When damage is rapid, release of thyroglobulin may actually produce hyperthyroidism (“Hashitoxicosis” or “Toximoto’s”).
euthyroid
76
A few percent of Hashimoto patients get an ____________ (probably a vasculitis).
encephalopathy
77
Thyroiditis w/ lymphocytes, but no germinal centers or antibodies seen in hashimoto's is what?
hint: common in Down's pt and may cause hypothyroidism
Non-Hashimoto lymphocytic thyroiditis
78
Lipid-laden macrophages in the colloid
Amiodarone
oily-iodine rich heart medicine
79
Hyperchromatic nuclei and scar.
| 
Radiated thyroid
80
-Sore thyroid gland
-Virus attacks and kills the follicular epithelial cells, setting the thyroglobulin colloid free-->
Granulomatous (giant cells) foreign body reaction to it-->
Breakdown releases thyroxine-->
Briefly causing mild hyperthyroidism
It heals on its own in a few weeks. Simple pain meds (NSAIDS, aspirin) work well.
DeQuervain's subacute granulomatous thyroiditis
Vain=pain
81
- Dense fibrosis that invades surrounding tissue of thyroid
- IgG4 autoimmune fibrosing diseases
- Hard mass
Riedel’s
82
Due to graves, hot adenoma, factitious (meds), rapid Iodine replacement, or ectopic TSH
hyperthyroidism
83
- Lid lag
- Sweating
- Neurotic anxiety
- Fine tremor (paper test)
- Wide pulse pressure
- Strong, rapid pulse
- Brisk reflexes
- Low LDL diarrhea
- Wt loss despite incr appetite
- Osteoporosis
- Afib
- Depression, dementia, apathetic
Hyperthyroidism
84
-Autoimmune disease with auto-antibodies binding to and activating the TSH receptors...TSI (thyroid stimulating immunoglobulni) or TRAB (thyroxine recepteor antibodies).
-Gland gets big (“diffuse toxic goiter”) and
the thyroglobulin colloid is reabsorbed rapidly-->resorption vacuoles
-In the end, the colloid is gone and the gland is very big and cellular.
-There are also TSH receptors on the fibroblasts of the shins (“pretibial myxedema”) and behind the eye (“infiltrative ophthalmopathy”)....excess lymphocytes / ground substance / fat / water edema can accumulate here
Graves disease
85
Happens when iodine is given to someone who’s been deficient for a long time
Overzealous replacement has caused epidemics of catastrophic hyperthyroidism / “thyroid storm” (diarrhea, sick)
Putting iodine in the salt supply and keeping it there is probably a better solution. In “goiter belts”, there will be excess hyperthyroidism only for the first few years
Jod-Basedow
Thyroid has hyperplasia and takes up all the iodine and spits out a bunch of thyroid hormone
86
Results when a single poorly- trained butcher takes thyroid along with strap muscle
Hamburger thyrotoxicosis
87
Follicles emptied, giant cells with oxalate crystals and granulomas
Lithium thyroiditis
88
Clones of altered cells overgrowing their neighbors, but cancer seldom arises there. They may contain one or more “hot spots” causing hyperthyroidism.
Idiopathic nodular goiter
89
Why are these people euthyroid but have low serum total thyroxine levels?
take steroids, have minimal change dz, or have rx dilantin have
All have low levels of thyroid binding proteins
90
Why are all these people euthyroid but have high total serum thyroxine levels?
methadone, birth control, pregnant
All have high levels of thyroid binding proteins (incr T4 but euthyroid)
91
5% of patients with hyperthyroidism have T3 toxicosis. How will you spot this?
Look hyperthyroid,
Low TSH, Low T4, High T3
(T3 producing thyroid adenoma)
92
How can you diagnose factitious hyperthyroidism?
The thyroid gland takes up no iodine on scan. Incr T4, Decr TSH
(Same as in De Quervain’s, Hashitoxicosis, ectopic T4 from an ovarian teratoma).
93
When do you order a serum thyroglobulin?
Suspected metastatic thyroid cancer
Or “baseline”
Or “suspected disease of the thyroid with destruction of follicles.”
94
When do you order up a
| TSI (“thyroid stimulating immunoglobulin”) / TRAB (thyroxine receptor antibody) assay?
Suspected Graves’
95
Anti-TPO (anti-thyroid peroxidase, anti-microsomal antibodies) are markers for what illness?
Hashimoto's
96
T/F:
| “Euthyroid sick” – don’t overtreat “thyroid problems” in the setting of other acute illness
TRUE
Decr T4, T3 but incr rT3
97
T/F:
Reflexology treats all diseases of the thyroid gland

FALSE
98
Anterior midline neck mass that moves during swallowing or protrusion of the tongue
Thyroglossal duct cyst
99
- MC cause of hypothyroidism in iodine-sufficient regions
- Autoimmune disorder (anti-TPO, anti-microsomal, and anti-thyroglobulin Abs)
- Females 10:1
- Age 45-65
- Assoc with HLA-DR5
- Increased risk of non-Hodgkin lymphoma
- Histo: Hurthle cells, lymphoid aggregate with germinal centers
- Moderately enlarged, NONTENDER thyroid
Hashimoto's thyroiditis
100
- Self-limited dz often following a flu-like illness (stimulates cytotoxic T cells)
- Females 4:1
- Age 40-50
- May be hyperthyroid early in course, followed by hypothyroidism
- Histo: granulomatous inflammation, giant cells present
- Increased ESR, jaw pain, very TENDER thyroid
Granulomatous (Subacute or de Quervain) thyroiditis
101
- PAINLESS lymphocytic thyroiditis
- Mild hyperthyroidism, goitrous enlargement of the gland
- MC middle-aged women
- Asymmetric enlargement of thyroid gland
- Histo: lymphocytic infiltrate composed of large germinal centers, focal areas of collapsed follicles
- Difference from Hashimoto's: lacks significant fibrosis and Hurthle cell metaplasia
Subacute lymphocytic thyroiditis
102
- Diffuse enlargement and/or nodularity, may have cystic degeneration
- May be assoc with impaired hormone production and increased TSH
- Females >>> Males
- Enlarged thyroid gland, pink to red, multiple nodules +/– cystic degeneration
- Iodine-deficient regions, sporadic
Diffuse and nodular goiter
103
- Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor
- Increase release of T3 and T4
- Rarely malignant
Toxic multinodular goiter
104
- Gross: solitary spherical encapsulated, well-demarcated
- Gray-white to red-brown in color
- May see fibrosis, hemorrhage, cystic change
- Histo: derived from follicular epithelium
- Functional vs. non-functional
Adenoma
105
Gain-of-function mutations
- RET or NTRK1 (tyrosine kinase)
- BRAF
- RET 10q11
Papillary carcinoma
106
Possible mutations:
- RAS or PI3K/AKT (tyrosine kinase pathway)
- Loss-of-function PTEN
- T(2;3)(q13;p25) translocation PAX8-PPARG fusion gene
Follicular carcinoma
107
Mutations:
| -RAS, PI3K, TP53, PTEN, or ß-catenin
Anaplastic carcinoma
108
- Palpable mass in neck with lymph node involvement (lymphatic invasion common)
- Empty-appearing nuclei with central clearing ("Orphan Annie eyes") ***
- Psammoma bodies
- Nuclear grooves
- Increased risk with RET and BRAF mutations, childhood irradiation
Papillary carcinoma
109
- Malignant epithelial neoplasm
- Females, age 40-50
- Solid or cystic mass that may extend into adjacent structures
- Usually asymptomatic and painless
- Stained by thyroglobulin and TTF-1
- Tumor invades capsule or vessels ***
Follicular carcinoma
110
- Highly malignant neoplasm composed of undifferentiated cells of epithelial derivation, very poor prognosis
- T4 by definition
- Most die within 6 months
- Female > Male, mostly over age 60
- Gross: large, flashy masses with necrosis and hemorrhage
- Histo: poor architecture, rudimentary follicles to sheets of cells
- Cyto: bizarre cells with atypical mitosis, profound pleomorphism, may see osteoclast-like giant cells
- Stains with keratin, EMA+
- Thyroglobulin(–), TTF-1(–)
Anaplastic undifferentiated carcinoma of thyroid
111
- From parafollicular "C cells"
- Produces calcitonin
- Assoc with MEN 2A or 2B (RET mutations)
- Spindle-shaped cells ***
- Sheets of cells in amyloid stroma ***
Medullary thyroid carcinoma
112
- Thymoma subtype
- Epithelial cells
- Spindling
Thymoma, A
113
- Thymoma subtype
- Epithelial cells
- Lymphocytes
Thymoma, AB
114
- Thymoma subtype
| - Both cortex and medulla seen on histo
Thymoma, B1
115
- Thymoma subtype
| - Epithelial cells easy to see, big pale nuclei
Thymoma, B2
116
- Thymoma subtype
| - Epithelial cells in sheets, almost no lymphocytes
Thymoma, B3
117
- Thymoma subtype
| - Serious anaplasia, lights up with chromogranin
Thymoma, C
118
- Gross: firm to hard, unencapsulated, lack septations, and have areas of necrosis/hemorrhage
- Mets to lung
- Keratinizing and non-keratinizing
- Cytologic atypia, large epithelial cells in nest or cords, broad bands of fibrosis
- Large polyhedral cells with atypia fibrohyaline stroma and/or keratin
- Gain = 1q
- Loss = 6 and 16q
Thymic carcinoma, squamous cell carcinomas
119
Paraneoplastic syndromes to know that are assoc with thymoma: (3)
- Myasthenia gravis
- Hypogammaglobulinemia
- Anemia
120
5 T's for anterior mediastinal masses:
```
Thymoma
Teratoma
Testicular type tumor
T-cell lymphoma
Thyroid substernal goiter
```
121
Pineal tumors famously cause:
Precocious puberty
122
- Usually due to parathyroid adenoma or hyperplasia
- Increased PTH
- Hypercalcemia
- Hypophosphatemia
- Increased ALP
- Abdominal/flank pain (kidney stones, acute pancreatitis)
- Depression
- Osteitis fibrosa cystica
"Stones, bones, groans, and psychiatric overtones."
1º hyperparathyroidism
123
What scan revolutionized the search for parathyroid adenomas / hyperplasia detected on lab screening?
Tc99-sestamibi
| actually lights up mitochondria, and it stays longer in parathyroids for some reason
124
A large minority of parathyroid adenomas are driven by one or both of following mutations:
- Cyclin D1, as an inversion within chromosome 11, over-activating it.
- MEN-1, the multiple endocrine neoplasia locus.
125
Necrosis, hemorrhage, invasion of the capsule, mitotic figures all suggest:
Cancer
126
Adenoma nuclei usually light up with ____________, while carcinoma nuclei usually do not.
parafibromin
127
- Parathyroid bone dz
- Thinning and loss of trabeculae
- In hyperparathyroidism, the fingertips are involved most severely ***
Osteoporosis
128
- Parathyroid bone dz
| - Masses of osteoclasts and loose connective tissue replacing bone
"Brown tumors"
129
- Parathyroid bone dz
- Enlarged cutting cones of osteoblasts with their connective tissue, often passing right through the centers of trabecular bone
- Consists of hemosiderin from hemorrhages; causes bone pain
Osteitis fibrosa cystica
130
Calciphylaxis (metastatic calcification) often due to:
Parathyroid dz
131
Water clear cell hyperplasia is assoc with:
Blood group O
132
```
Causes of 2º hyperparathyroidism:
Tips:
-High serum phosphate. Think...
-Low serum phosphate. Think...
-Eucalcemic pt with extreme calcitonin overproduction. Think...
```
High serum phosphate. Think renal failure.
Low serum phosphate. Think vitamin D deficiency.
Eucalcemic pt with extreme calcitonin overproduction. Think medullary thyroid cancer.
133
- Defective Ca2+-sensing receptor on parathyroid cells
| - PTH cannot be suppressed by an increase in Ca2+ level >> mild hypercalcemia with normal to increased PTH levels
Familial hypocalciuric hypercalcemia
134
- PTH1R receptors stuck in the "on" position
| - Serum PTH = 0
Jansen's metaphyseal chondroplasia
135
- Due to accidental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome
- Findings: hypocalcemia, tetany
- Chvostek sign
- Trousseau sign
- Long QT interval on EKG
- Calcification in basal ganglia
- Calcification of the lens of the eye
- Abnormal tooth formation in children
Hypoparathyroidism
136
- Unresponsiveness of kidney to PTH
- Hypocalcemia
- Shortened 4th/5th digits (short thumbs, short metacarpals)
- Short stature
- Most often mutant GNAS / Gs(a)
Pseudohypoparathyroidism
| "Albright hereditary osteodystrophy"
137
Lymphocytes attacking an islet of Langerhans.
| Think...
Type 1 diabetes
138
- HLA DR3/DR5 (and/or either with a DQ8 haplotype)
- Insulin gene promoter
- CTLA4
- PTPN22
- AIRE
All are linked to autoimmune endocrinopathies, such as:
Type 1 diabetes
139
2 specific auto-antibodies in type 1 diabetes:
- Anti-insulin
| - Anti-glutamic acid decarboxylase
140
What virus is a molecular mimic of glutamic acid decarboxylase?
Coxsackie B4
141
- Genetic (identical twin gets dz 90% of the time)
- More likely to announce itself as hyperosmolar nonketotic coma (hyperosmotic syndrome or as complications of nerve / vessel dz
Type 2 diabetes
142
- No evidence of autoimmunity
- Increased resistance to insulin
- Inadequate (but not absent) insulin secretion (ß-cell dysfxn)
- 90% concordance in identical twins
- > 30 loci contributing to what is usually a polygenic illness
Type 2 diabetes
143
Which proinflammatory cytokine is infamously described in how obesity might cause insulin resistance?
Hint: released from macrophage inflammasomes in obesity / lack of exercise.
IL-1ß
144
Amyloid is present in maybe half of which type of diabetes?
| Often the islets are actually engorged and hypercellular from have to work against insulin resistance.
Type 2 diabetes
145
"Secondary diabetes": due to another dz or Rx...
Damage to pancreas itself: (4)
Insulin resistance: (3)
Both:
-Pancreatic cancer
"Secondary diabetes": due to another dz or Rx...
Damage to pancreas itself:
- Cystic fibrosis *
- Chronic pancreatitis
- Hemochromatosis *
- After pancreatectomy
- Others
Insulin resistance:
- Acromegaly *
- Cushing's *
- Glucagonoma
- Rx's: glucocorticoids, thiazides, anti-HIV protease inhibitors *
Both:
-Pancreatic cancer
146
Which is the most common acute metabolic disturbance in both type 1 and type 2 diabetes?
HypOglycemia
147
Prolonged hyperglycemia ("glucotoxicity") has five known effects, all of which probably contribute.
List 3 of the most important effects.
- Formation of advanced glycation end products (AGE's) *
- Activation of protein kinase C *
- Disturbing polyol pathways / "oxidative stress"
148
Which cytokine causes thick basement membranes and proliferation of small-artery smooth muscle?
TGF-ß
149
What accumulates in the lens in the setting of glucose excess, causing the snowflake cataracts of diabetes?
Sorbitol
150
The macroangiopathy assoc with long-term hyperglycemia and long-term complications of diabetes is recognized as:
Atherosclerosis
151
Hyalinization of both the afferent and efferent arterioles of the kidney is a known complication of:
Hyperglycemia due to diabetes
152
Diabetics are susceptible to infection of various causes, but which bug likes glucose in particular?
Candida
153
Proliferative retinopathy is attributed to local production of:
VEGF
154
Autonomic neuropathy is common in ________ and unusual in any other common illness.
diabetes
155
Joints without good sensory nerve supply become deformed (pts hit their joints on things, and they don't know they do it)...
Charcot's neuropathic arthropathy
156
The familiar queezy feeling during hypoglycemia in healthy people is due to an epinephrine upsurge when blood sugar is dropping. The real name of this is:
Postprandial syndrome
157
Whipple's triad:
- Measured low blood glucose
- Mental symptoms induced by fasting and/or exercise
- Symptoms relieved by intravenous glucose
Insulinoma
158
Whenever you see sudden weight gain and/or "emotional illness" ...
Insulinoma
159
If leucine induces hypoglycemia, think...
Insulinoma
160
If the serum C-peptide is high, think...
Insulinoma
161
If you light up an insulinoma with MLH1, it's a sign of (good/bad) behavior.
MLH1+ = GOOD behavior
162
In addition to diabetes, this may present as necrolytic migratory erythema with necrosis of the epidermis about 3/4 of the way up...
Glucagonoma
163
- Causes Zollinger-Ellison syndrome
| - Multiple endocrine neoplasia type 1
Gastrinoma
164
Insulin resistance and malabsorption. Think...
Somatostatinoma (delta cell tumor)
165
- Extreme watery diarrhea
- Hypokalemia
- Achlorhydria
Think...
VIPoma
166
Deficiency of aldosterone and cortisol production due to loss of gland function, leading to:
- Hypotension (hyponatremic volume contraction)
- Hyperkalemia
- Metabolic acidosis
- Skin and mucosal hyperpigmentation (due to high ACTH)
Addison's disease
| Primary adrenal insufficiency
167
MC cause of primary adrenal insufficiency in the US:
Autoimmune, as part of:
- AIRE1 (polyendocrinopathy I)
- Polyendocrinopathy II (Schmidt's)
- Some other pattern of by itself
168
Autoimmune Addison's has autoantibodies against:
21-hydroxylase
169
Autoimmune Addison's +
Hashimoto's autoimmune thyroiditis +
Autoimmune (type 1) diabetes +
Autoimmune vitiligo
What syndrome encompasses features of all this dz's?
Autoimmune polyendocrine syndrome type II
| "Schmidt's syndrome"
170
-Due to autoantibodies against tryptophan hydroxylase (serotonin-making pathway)
Pts have:
- Autoimmune Addison's
- Autoimmune hypoparathyroidism
- Candida on mucosal surfaces
Autoimmune polyendocrine syndrome type I
171
Which cancer spreads to the adrenals more than any other organ?
Lung cancer
172
Acute 1º adrenal insufficiency due to adrenal hemorrhage and necrosis assoc with septicemia (usually Neisseria meningitidis), DIC, endotoxic shock.
"Bloody adrenal necrosis in sepsis."
Waterhouse-Friderichsen syndrome
173
Increased cortisol due to a variety of causes:
- Exogenous corticosteroids
- Primary adrenal adenoma, hyperplasia, or carcinoma
- ACTH-secreting pituitary adenoma (Cushing disease)
Findings: hypertension, weight gain, moon facies, truncal obesity, buffalo hump, skin changes (thinning, striae), osteoporosis, hyperglycemia (insulin resistance), amenorrhea, immunosuppression.
Cushing's syndrome
174
Primary pigmented micronodular adrenal hyperplasia.
Think...
Runs with atrial myxomas.
Carney complex syndrome (PRKAR1A)
175
2 risk factors assoc with adrenal cortical carcinoma:
- Li-Fraumeni (TP53)
| - Beckwith-Weideman (imprinting)
176
4 cancers that spread via veins:
- Adrenal
- Renal cell CA
- Hepatocellular cell CA
- Follicular cell of thyroid
177
Rx for hyperaldosteronism:
Spironolactone
178
- MC congenital adrenal hyperplasia
- Present in infancy (*salt wasting*) or children (precocious puberty)
- XX: virilization
- Gene CYP21A2
21-hydroxylase deficiency
179
- "The other common adrenal cortical mass."
| - A hamartoma made of red bone marrow and fat
Myelolipoma
180
- MC tumor of the adrenal medulla in adults
- Derived from chromaffin cells (arise from neural crest)
- Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension
- Assoc with von Hippel-Lindau dz, MEN 2A and 2B
- Symptoms occur in "spells" – relapse and remit.
- Increased catecholamines and metanephrines in urine and plasma
- "Rule of 10's"
Pathologic features:
- Red-brown variegated color
- Rim of preserved adrenal cortex
- Abundant cytoplasm
- "Zellballen" clusters of cells
Pheochromocytoma
181
Rx for pheochromocytoma:
Irreversible alpha-antagonists
| E.g., phenoxybenzamine
182
Mutated succinic acid dehydrogenase.
| Think...
Pheochromocytoma
183
Pheochromocytoma genetics: (4)
RET: MEN2A and 2B
NF1: Neurofibromatosis
VNL: Von Hippel-Lindau
Familial paraganglioma 1, 3 and 4 (SDHD, SDHC, SHDB)
184
- Pheochromocytoma
- Medullary thyroid cancer (secretes calcitonin)
- Oral/intestinal ganglioneuromatosis (mucosal neuromas)
- Assoc with marfanoid habitus
- Mutation in RET gene
MEN 2B
185
-MC tumor of the adrenal medulla in children, usually
Neuroblastoma
186
Favorable prognosis factors in neuroblastoma: (6)
-Under 18 months of age
-Stage 1, 2, 4S
-Schwann cells
-MKI index < 200 / 5000 cells
-Hyperdiploid / gains of whole chromosomes
TRKA neurotrophin expression
187
Along with age, the most important bad prognostic sign of neuroblastoma is:
MYCN / N-myc amplification
188
- Neuroblastoma with stroma and some maturation
| - Most are neuroblastomas that self-cure in infancy
Ganglioneuroblastoma
189
- Parathyroid hyperplasias / adenomas
- Pancreatic endocrine tumors – Zollinger-Ellison syndrome (gastrinoma), insulinomas, VIPomas, glucagonomas (rare)
- Pituitary tumors – prolactinoma or GH (gigantism / acromegaly)
- Mutation of MEN1 suppressor gene, which produces MENIN
MEN 1
190
- Parathyroid hyperplasia
- Pheochromocytoma
- Medullary thyroid carcinoma (secretes calcitonin)
- Assoc with marfanoid habitus
- Mutation in RET gene (codes for receptor tyrosine kinase)
MEN 2A
