Pathology Flashcards
1
Q
What is the mechanism of Cushing syndrome?
A
Increased cortisol due to a variety of causes
2
Q
What causes bilateral adrenal atrophy and is the most common cause of Cushing syndrome?
A
Exogenous steroid use
3
Q
Atrophy of uninvolved adrenal gland in Cushing syndrome points to what cause?
A
Primary adrenal adenoma, hyperplasia or carcinoma
4
Q
What is Cushing disease?
A
An ACTH-secreting pituitary adenoma
5
Q
What are some paraneoplastic causes of increased ACTH?
A
Small cell lung cancer or bronchial carcinoids
6
Q
What is the affect of increased endogenous ACTH on adrenal glands?
A
Adrenal hyperplasia
7
Q
What is the affect of increased exogenous ACTH on adrenal glands?
A
Adrenal atrophy
8
Q
What is responsible for the majority of endogenous cases of Cushing syndrome?
A
Cushing disease
9
Q
What is suspected if ACTH levels are suppressed on low-dose dexamethasone test?
A
Exogenous glucocorticoids or adrenal tumor
10
Q
What needs to be done if adrenal tumor is suspected?
A
Adrenal CT to confirm
11
Q
What is next step if ACTH levels are elevated on low-dose dexamethasone test?
A
High-dose dexamethasone test and CRH stimulation test
12
Q
What test results are consistent with Cushing disease?
A
Adequate suppression with high-dose dexamethasone and increased ACTH and cortisol with CRH stimulation
13
Q
What test results are consistent with ectopic ACTH secretion?
A
No suppression with high-dose dexamethasone and no increase in ACTH and cortisol with CRH stimulation
14
Q
What is next step with adequate suppression with high-dose dexamethasone and increased ACTH and cortisol with CRH stimulation?
A
MRI of pituitary
15
Q
What is next step with no suppression with high-dose dexamethasone and no increase in ACTH and cortisol with CRH stimulation?
A
CT of the chest/abdomen/pelvis
16
Q
Inability of the adrenal glands to generate enough glucocorticoids
A
Adrenal insufficiency
17
Q
Acute primary adrenal insufficiency due to hemorrhage associated with septicemia form N. meningitidis, DIC or endotoxic shock
A
Waterhouse-Friderichsen syndrome
18
Q
Hypotension, hyperkalemia, metabolic acidosis with skin and mucosal hyperpigmentation points to what disease?
A
Primary adrenal insufficiency
19
Q
Shock or hemorrhage causing hypovolemia leading to ischemia of the adrenal glands causes what type of adrenal insufficiency
A
Acute primary adrenal insufficiency
20
Q
What is the most common cause of chronic primary adrenal insufficiency in the Western world?
A
Autoimmune destruction
21
Q
What is the most common cause of chronic primary adrenal insufficiency in the developing world?
A
TB
22
Q
Adrenal atrophy or destruction by disease either from autoimmune or TB is called what?
A
Chronic primary adrenal insufficiency or Addison disease
23
Q
What cortisol and ADH levels are seen in primary adrenal insufficiency?
A
Decreased cortisol
Increased ACTH
24
Q
What cortisol and ADH levels are seen in secondary adrenal insufficiency?
A
Decreased cortisol and ACTH
25
What are findings in secondary adrenal insufficiency?
Intact renin-angiotensin-aldosterone axis
No hyperkalemia
No skin/mucosal hyperpigmentation
26
What is a common cause of tertiary adrenal insufficiency?
Exogenous steroid use
27
How is aldosterone synthesis affected in tertiary adrenal insufficiency?
Not affected
28
What prevents edema in hyperaldosteronism?
Aldosterone escape mechanism
29
Increased secretion of aldosterone from the adrenal glands
Hyperaldosteronism
30
Findings in hyperaldosteronism
HTN, decreased or normal potassium, metabolic alkalosis
31
What are lab findings in primary hyperaldosteronism?
Increased aldosterone, sodium reabsorption and potassium excretion
Decreased renin
Metabolic alkalosis
32
What is the cause of primary hyperaldosteronism?
Adrenal adenoma
33
What is the cause of 2ndary hyperaldosteronism?
Renovascular HTN, juxtaglomerular cell tumors and edema
34
What are lab findings in 2ndary hyperaldosteronism?
Increased renin, aldosterone
35
What is the most common tumor of the adrenal medulla in children?
Neuroblastoma
36
Neuroblastomas originate from what cell line?
Neural crest cells
37
What type of tumors can occur anywhere along the sympathetic chain?
Neuroblastomas
38
Abdominal distention and a firm, irregular mass that can cross the midline points to what disease?
Neuroblastoma
39
Abdominal distention with a smooth mass that is unilateral, points to what disease?
Wilms tumor
40
Child with history of "dancing eyes-dancing feet" and an abdominal mass that crosses the midline with normal BP points to what disease?
Neuroblastoma
41
What are common findings in urine in someone with Neuroblastoma?
Increased catecholamines (homovanillic and vanillylmandelic acid)
42
Histology with Homer-Wright rosettes and Bombesin and NSE positive indicates to what disease?
Neuroblastoma
43
What oncogene is associated with neuroblastomas?
N-myc oncogene
44
Most common tumor of the adrenal medulla in adults?
Pheochromocytoma
45
Pheochromocytoma is derived from what cells?
Chromaffin cells of the adrenal medulla
46
What germline mutations are associated with pheochromocytoma?
NF-1, VHL, RET (MEN2A and MEN2B)
47
What is the rule for pheochromocytomas?
```
Rule of 10s:
10% malignant
10% bilateral
10% extra-adrenal (bladder wall, organ of Zuckerandl)
10% calcify
10% kids
```
48
What are common symptoms of pheochromocytomas?
Relapsing and remitting symptoms of 5 Ps:
Pressure (increased BP) - increased catecholamines
Pain (headache)
Perspiration
Palpitations
Pallor
49
What are common findings in pheochromocytomas?
Increased catecholamines: Epi, NE, dopamine in urine and plasma
50
What is a worry in someone with history of chronic exogenous steroid use who stops using immediately?
Tertiary adrenal insufficiency
51
What is the treatment for pheochromocytoma?
Irreversible a-antagonists (phenoxybenzamine) and B-blockers prior to tumor resection
52
Why is a-blockade needed before giving B-blockers?
To avoid a hypertensive crisis
53
What are the cholesterol levels in hypothyroidism?
Hypercholesterolemia due to decreased LDL receptor expression
54
What are the CK levels in hypothyroidism?
Increased CK levels
55
What are the TSH levels in hypothyroidism?
Increased TSH levels if primary
56
What are the T3 and T4 levels in hypothyroidism?
Decreased T3 and T4
57
What are the CK levels in hyperthyroidism?
Normal CK levels
58
What type of receptors are upregulated leading to palpitations, arrhythmias and CP?
B-adrenergic receptors
59
What is the TSH level in hyperthyroidism?
Decreased TSH levels
60
What are the free T3 and T4 levels in hyperthyroidism?
Increased T3 and T4 levels
61
What are the cholesterol levels in hyperthyroidism?
Hypocholesterolemia due to increased LDL receptor expression
62
Causes of nodular thyroid goiters
Toxic multi-nodular goiter
Thyroid adenoma
Thyroid cancer
Thyroid cyst
63
Causes of smooth/diffuse thyroid goiters
Graves disease
Hashimoto thyroiditis
Iodine deficiency
TSH-secreting pituitary adenoma
64
What is the most common cause of hypothyroidism in iodine-sufficient regions?
Hashimoto thyroiditis
65
What are antibodies are associated Hashimoto thyroiditis?
Anti-thyroid (anti-microsomal) peroxidase and anti-thyroglobulin antibodies
66
What malignancy is associated with Hashimoto thyroiditis?
Non-Hodgkin lymphoma (B-cell origin)
67
Hashimoto thyroiditis may present as hyperthyroid early in disease course - why?
Thyrotoxicosis during parafollicular rupture
68
Presents as a non-tender, moderately enlarged thyroid with decreased T3 and T4 and Hurthle cells with lymphoid aggregates and germinal centers on histology.
Hashimoto thyroiditis
69
What malignancy can present as an enlarging gland in Hashimoto thyroiditis?
Marginal zone lymphoma
70
What is the most common cause of congenital hypothyroidism in the U.S?
Thyroid dysgenesis
71
What is the cause of congenital hypothyroidism?
Severe fetal hypothyroidism due to maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis, iodine deficiency, dyshormonogenetic goiter
72
What are the findings in congenital hypothyroidism?
6 Ps:
| Pot-bellied, Pale, Puffy, Protruding umbilicus, Protuberant tongue, and Poor brain development
73
Self-limited disease often following a flu-like illness presenting with increased ESR, jaw pain, and very tender thyroid
de Quervain (subacute granulomatous thyroiditis)
74
What is the histology of subacute granulomatous thyroiditis?
Granulomatous inflammation
75
How does subacute granulomatous thyroiditis present early on in disease course?
Hyperthyroid early on, followed by hypothyroid
76
Thyroid replaced by fibrous tissue with inflammatory infiltrate and may extend to surrounding structures mimicking anaplastic carcinoma
Riedel thyroiditis
77
Young female presents with fixed, hard, rock-like painless goiter points to what disease?
Riedel thyroiditis
78
Thyroid gland down-regulation in response to increased iodine seen in hypothyroid diseases - what effect is this?
Wolff-Chaikoff effect
79
What drugs can cause hypothyroidism and presents as goitrogens?
Amiodarone and lithium
80
What is the most common cause of hyperthyroidism?
Graves disease
81
What type of hypersensitivity reaction is Graves disease?
Type II; IgG thyroid stimulating immunoglobulin
82
What HLA subtypes are associated with Graves disease?
HLA-DR3 and HLA-B8
83
What histological findings are seen in Graves disease?
Tall crowded follicular cells and scalloped colloid
84
What lymphocytes are associated with Graves disease?
T-cells
85
Increased osmotic swelling, muscle inflammation and adipocyte count in retro-orbital space causes what in Graves disease?
Exophthalmos
86
What symptoms are seen in Graves disease?
Exophthalmos, pretibial myxedema
87
What causes pretibial myxedema in Graves disease?
Dermal fibroblasts
88
What mediates exophthalmos?
Infiltration of activated T-cells in the retro-orbital space leading to increased cytokines like TNF-a and IFN-y
89
Focal patches of hyperfunctioning follicular cells distended with colloid and working independently of each TSH
Toxic multinodular goiter
90
What is the cause of toxic multinodular goiters working independently of TSH?
TSH receptor mutations
91
What are T3 and T4 levels in toxic multinodular goiter?
Increased T3 and T4 levels
92
What is usual cause of toxic multinodular goiters?
Iodine deficiency
93
Uncommon but serious complication that occurs when hyperthyroidism is incompletely treated or undertreated, and then significantly worsens in the setting of acute stress such as infection, trauma or surgery
Thyroid storm
94
Commonly presents with agitation, delirium, fever, diarrhea, coma and tachyarrhythmias from incomplete treatment of hyperthyroidism after acute illness
Thyroid storm
95
What lab findings are typically seen in thyroid storm?
Increased LFTs
96
What is the treatment for thyroid storm?
4 Ps:
| Propranolol, PTU, Prednisone, and Potassium iodine
97
A patient with an autonomous nodule who is iodine deficient is given iodine and develops thyrotoxicosis
Jod-Basedow phenomenon
98
Asymptomatic benign solitary growth of the thyroid that is non-functional rarely causing hyperthyroidism
Thyroid adenoma
99
What is the histology or thyroid adenoma?
Follicular with absence of capsular or vascular invasion
100
What is the treatment for thyroid cancer?
Thyroidectomy
101
How is thyroid cancer diagnosed?
Fine needle aspiration
102
What nerve can be damaged in thyroidectomy?
Recurrent laryngeal nerve
103
Hypocalcemia after thyroidectomy is cause by damage to what structure?
Removal of parathyroid glands
104
What nerve can be damaged during ligation of inferior thyroid artery in thyroidectomy?
Recurrent laryngeal nerve
105
What nerve can be damaged during ligation of superior laryngeal artery in thyroidectomy?
Superior laryngeal nerve
106
What is the most common thyroid cancer?
Papillary carcinoma
107
What is the histology of papillary carcinoma?
Empty-appearing nuclei with central clearing (Orphan Annie eyes), psammoma bodies, and nuclear grooves
108
What mutations increase risk of papillary carcinoma?
RET and BRAF mutations
109
What is a major cause of papillary carcinoma in childhood?
Irradiation
110
What is the prognosis of papillary carcinoma?
Excellent prognosis
111
Presents with uniform follicles on histology, invades thyroid capsule and vasculature with a good prognosis?
Follicular carcinoma of the thyroid
112
What mutation is associated with follicular carcinoma?
RAS mutation
113
How does follicular carcinoma spread?
Hematogenous spread
114
Thyroid cancer from parafollicular cells that produces calcitonin in sheets of cells in an amyloid stroma
Medullary carcinoma
115
What stain is used in Medullary carcinoma?
Congo red stain for amyloid stroma
116
What mutations are associated with medullary carcinoma?
MEN 2A and 2B RET mutations
117
What is done if RET mutations detected in someone with thyroid cancer?
Has medullary carcinoma so prophylactic thyroidectomy
118
Thyroid cancer that is common in older patients presenting with dysphagia and respiratory compromise with invasion of local structures and has a very poor prognosis?
Undifferentiated/anaplastic carcinoma
119
What is lymphoma of the thyroid associated with?
Hashimoto thyroiditis
120
Accidental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome can all cause what condition?
Hypoparathyroidism
121
What are common findings in Hypoparathyroidism?
Tetany, hypocalcemia and hyperphosphatemia
122
Contraction of facial muscles with tapping of facial nerve on the check is called what?
Chvostek sign
123
Occlusion of brachial artery with BP cuff causing carpal spasm is called what?
Trousseau sign
124
Common procedures done to test for Hypoparathyroidism are what?
Chvostek and Trousseau sign
125
Unresponsiveness of kidney to PTH causing hypocalcemia despite increased PTH level is called what?
Pseudohypoparathyroidism type 1A or Albright hereditary osteodystrophy
126
What are common findings in Albright hereditary osteodystrophy?
Shortened 4th/5th digits and short stature
127
What is the inheritance pattern of Albright hereditary osteodystrophy?
Autosomal dominant
128
What is the mechanism of end-organ resistance to PTH in Albright hereditary osteodystrophy?
Defective Gs protein a-subunit
129
How is the defect inherited in Albright hereditary osteodystrophy?
From mother due to imprinting
130
How is the defect inherited in pseudopseudohypoparathryroidism?
Inherited from father due to imprinting
131
What is the mechanism of pseudopseudohypoparathryroidism?
Defective Gs protein without end-organ resistance
132
What are the PTH levels in pseudopseudohypoparathryroidism?
Normal
133
What are the causes of primary hyperparathyroidism?
Carcinoma, adenoma, hyperplasia
134
What are lab findings seen in primary hyperparathyroidism?
Hypercalcemia, hypercalciuria, hypophosphatemia
| Increased PTH, ALP, cAMP in urine
135
Disease that presents with weakness and constipation, abdominal/flank pain, and depression
Primary hyperparathyroidism
136
What is the mnemonic for primary hyperparathyroidism?
Stones, thrones, bones, groans and psychiatric overtones
137
What is the cause of osteitis fibrosa cystica?
Increased PTH
138
Cystic bone spaces filled with brown fibrous tissue with increased PTH levels?
Osteitis fibrosa cystica
139
What is contained in the cysts seen in osteitis fibrosa cystica?
Osteoclasts and deposited hemosiderin from hemorrhages
140
What is the most common cause of 2ndary hyperparathyroidism
Chronic renal disease
141
2ndary hyperplasia due to decreased calcium absorption and/or increased phosphate
2ndary hyperparathyroidism
142
What are common findings in 2ndary hyperparathyroidism?
Hypovitaminosis D, Hypocalcemia, Hypophosphatemia
| Increased ALP, PTH
143
What are common findings in 2ndary hyperparathyroidism due to chronic renal failure?
Hypovitaminosis D, Hypocalcemia
Hyperphosphatemia
Increased ALP, PTH
144
What is the cause of tertiary hyperparathyroidism?
Refractory hyperparathyroidism from chronic renal failure
145
What are common lab findings in tertiary hyperparathyroidism?
Markedly increased PTH and increased calcium
146
What disease is caused by a defective G-coupled sensing receptor in multiple tissues requiring higher than normal calcium levels to suppress PTH
Familial hypocalciuric hypercalcemia
147
What lab findings are seen in familial hypocalciuric hypercalcemia?
Hypercalcemia, low urine calcium, normal to increased PTH
148
What is the cause of hypocalciuria and hypercalcemia seen in familial hypocalciuric hypercalcemia?
Increased renal calcium uptake
