Endocrine - Pathology Flashcards
(130 cards)
1
Q
Symptoms of nonfunctional pituitary adenoma (3)
A
Mass effects
- headache
- bitemporal hemianopsia (compression of optic chiasm)
- hypopituitarism
2
Q
Most common pituitary adenoma
A
prolactinoma
3
Q
Prolactinoma: Presentation
A
Female: galactorrhea, amenorrhea
Males: decreased libido, headache
4
Q
Prolactinoma: Treatment
A
Dopamine agonists (bromocriptine, cabergoline) Surgery for larger lesions
5
Q
Growth hormone cell adenoma: Presentation
A
Children: gigantism (increased linear bone growth because epiphyses are not fused)
Adults: acromegaly
6
Q
Acromegaly: Presentation
A
Enlarged bones of hands, feet, jaw
Coarse facial features
Growth of visceral organs leading to dysfunction (e.g. cardiac failure)
Enlarged tongue
7
Q
What is often present with GH adenoma?
A
Secondary diabetes mellitus (induces liver gluconeogenesis)
8
Q
Growth hormone cell adenoma: Diagnosis
A
Elevated GH/IGF-1
Lack of GH suppression by oral glucose
Pituitary mass on brain MRI
9
Q
Growth hormone cell adenoma: Treatment
A
Octreotide (somatostatin analog)
GH receptor antagonists
surgery
10
Q
Common cause of death in acromegaly
A
Heart failure from cardiomyopathy
11
Q
ACTH cell adenoma: Presentation
A
Cushing syndrome
12
Q
Causes of Hypopituitarism (5)
A
- Mass effect or pituitary apoplexy (bleeding): pituitary adenoma in adults and craniopharyngioma in children
2 Sheehan syndrome
- Empty sella syndrome
- Brain injury, hemorrhage
- Radiation
13
Q
Sheehan syndrome: Presentation
A
Poor lactation, loss of pubic hair, fatigue
14
Q
Sheehan syndrome: Mechanism
A
Pregnancy-related infarction of pituitary gland
Gland doubles in size during pregnancy but blood supply does not -> blood loss during parturition precipitates infarction
15
Q
Empty sella syndrome: Presentation
A
absent (empty sella) pituitary gland on imaging
16
Q
Empty sella syndrome: Mechanism
A
Congenital defect
Herniation of arachnoid and CSF into sella compresses and destroys the pituitary gland
Common in obese women
17
Q
Central diabetes insipidus: Presentation
A
Polyuria, Polydipsia with riks of life-threatening dehydration; intense thirst
ab: urine specific gravity < 1.006; serum osmolality > 290 mOsm/L
hypernatremia and high serum osmolality
18
Q
Central diabetes insipidus: Mechanism
A
ADH deficiency (pituitary tumor, trauma, infection, inflammation)
19
Q
Central diabetes insipidus: Diagnosis
A
Water deprivation test
Urine osmol does not increase, but respond to desmopressin
20
Q
Central diabetes insipidus: Treatmet
A
Intranasal desmopressin (ADH analog) Adequate fluid intake
21
Q
Nephrogenic diabetes insipidus: Treatment
A
HCTZ, indomethacin, amiloride
22
Q
Nephrogenic diabetes insipidus: Mechanism
A
impaired response to ADH
Mutation or drugs (lithium an demeclocycline)
23
Q
Nephrogenic diabetes insipidus: Presentation
A
Similar to central diabetes insipidus, but does not respond to desmopressin
24
Q
SIADH: Presentation
A
Hyponatremia and low serum osmolality
Mental status changes and seizures (neuronal swelling and cerebral edema)
25
SIADH: Causes
Ectopic ADH (small cell lung cancer)
CNS disorder/head trauma
Pulmonary disease
Drugs (cyclophosphamide)
26
SIADH: Treatment
Fluid restriction, IV saline, conivaptan, tolvaptan, demeclocyline
27
Hyperthyroidism: Presentation (12)
1. weight loss despite increased appetite
2. heat intolerance/sweating
3. tachycardia with increased CO
4. arrhythmia (Afib) in elderly
5. tremor, anxiety, insomnia, heightened emotions
6. staring gaze with lid lag
7. diarrhea with malabsorption
8. oligomenorrhea
9. bone resorption with hypercalcemia (osteoporosis)
10. decreased muscle mass with weakness
11. hypocholesterolemia
12. hyperglycemia
28
Graves' disease: Mechanism
Type II hypersensitivity
| Autoantibody (IgG) stimulates TSH receptor -> increase syntehsis and release of thyroid hormone
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Most common cause of hyperthyroidism
Gaves' disease
30
Graves' disease: Risk group
Women of childbearing age (20-40 years)
| Often presents during stress (e.g. childbirth)
31
Graves' disease: Presentation
1. Hyperthyroidism
2. Diffuse goiter (constant TSH stimulation leads to thyroid hyperplasia and hypertrophy)
3. Exophthalmos and pretibial myxedema
32
Mechanism of exopthalmos and pretibial myxedema in Graves' disease?
Fibroblasts behind orbit and overlying shin express TSH receptors
Glycosamnoglycan (chondroitin sulfate and hyaluronic acid) build up, inflammation, fibrosis, and edema
33
Graves' disease: Histology and Lab
Irregular follicles with scalloped colloid and chronic inflammation
Lab: high total and free T4, hypocholesterolemia, increased serum glucose
34
Graves' disease: treatment
Beta-blockers, thioamide, radioiodine ablation
35
Thyroid storm: Mechanism
Elevated catecholamines and massive hormone excess, usually in response to stress (surgery, childbirth)
36
Thyroid storm: Presentation
Arrhythmia, hyperthermia, and vomiting with hypovolemic shock
May also see increased ALP due to increased bone turnover
37
Thyroid storm: Treatment
PTU, beta-blockers, steroids
38
Multinodular goiter: Presentation and Cause
enlarged thyroid gland with multiple nodules, usually nontoxic
Due to relative iodine deficiency
39
Toxic multinodular goiter: Presentation and Malignancy
Focal patches of follicular cells working independently of TSH due to mutation in TSH receptor
Increased T3, T4
Rarely malignant
40
Jod-Basedow phenomenon
Thyrotoxicosis if patient with iodine deficiency goiter is made iodine replete
41
Cretinism: Mechanism and Causes
Hypothyroidism in neonates and infants
Causes: maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter, iodine deficiency
42
What is dyshormonogenetic goiter?
Congenital defect in thyroid hormone production - thyroid peroxidase
43
Cretinism: Presentation
Mental retardation, short stature with skeletal abnormalities, coarse facial features (puffy faced-child), enlarged tongue, umbilical hernia (pot bellied, protruding umbilicus), pale
44
Myxedema: Presentation (9)
Hypothyroidism in older children/adults
1. Myxedema (accumulation of glycosaminoglycans in skin and soft tissue - deepening of voice and large tongue)
2. weight gain despite normal appetite
3. slowing of mental activity
4. muscle weakness
5. cold intolerance with decreased sweating
6. bradycardia with decreased CO; SOB and fatigue
7. oligomenorrhea
8. hypercholesterolemia
9. constipation
45
Most common causes of hypothyroidism
iodine deficiency and hashimoto thyroiditis
| Others: drugs (lithium), surgical removal or radioablation of thyroid
46
Hashimoto thyroiditis: Mechanism
Autoimmune destruction of thyroid gland
| HLA-DR5
47
Hashimoto thyroiditis: Presentation
```
Initial hyperthyroidism (follicle damage)
Progresses to hypothyroidism (low T4 and high TSH)
```
Antithyroglobulin and antimicrosomal antibodies often present (signs of damage)
Moderately enlarged, non-tender, firm thyroid
48
Hashimoto thyroiditis: Histology
Chronic inflammation (lymphocytic infiltrate) with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)
49
Hashimoto thyroiditis: Complications
Increased risk of B-cell (marginal zone) lymphoma (presents as enlarging thyroid gland late in disease course)
50
Subacute granulomatous (de quervain) thyroiditis: Presentation
Granulomatous thyroiditis that follows viral infection
Tender thyroid with transient hyperthyroidism; jaw pain, increased ESR
Self-limited
51
Subacute granulomatous (de quervain) thyroiditis: Histology
multinucleated giant cells, histocytes, and lymphocytes (granulomatous inflammation)
52
Reidel fibrosing thyroiditis: Mechanism
Chronic inflammation with extensive fibrosis of thyroid gland
IgG4-related systemic disease
53
Reidel fibrosing thyroiditis: Presentation
Hypothyroidism with "hard as wood", non-tender thyroid gland
May extend to involve local structures (airways)
Clinically mimic anaplastic carcinoma, but patients are younger (40s) and malignant cells are absent
54
What are cold and hot nodules? Examples of each.
Hot nodule (increased uptake): Graves' disease or nodular goiter
Cold nodules (decreased uptake): adenoma and carcinoma - warrant biopsy
131I radioactive uptake
55
Follicular adenoma: Histology
Benign proliferation of follicles surrounded by fibrous capsule
Usually non-functional
56
Most common type to thyroid carcinoma
Papillary carcinoma
57
Papillary carcinoma: Risk factors
exposure to ionizing radiation in childhood (severe acne)
58
Papillary carcinoma: Histology
Papillae lined by cells with clear 'Orphan Annie eye' nuclei (empty appearing nuclei) and nuclear grooves
Assocated with psammoma bodies
59
Papillary carcinoma: Metastasis and Prognosis
Spread to cervical (neck) lymph nodes, but prognosis is excellent
60
Follicular carcinoma: Histology
Malignant proliferation of follicles surrounded by fibrous capsule with invasion through capsule (FNA cannot make distinction between adenoma and carcinoma)
61
Follicular carcinoma: Metastasis
Hematogenously
62
Medullary carcinoma: Mechanism and Presentation
Malignant proliferation of parafollicular C cells (5% of thyroid carcinoma)
Can lead to hypocalcemia
63
Medullary carcinoma: Histology
Sheets of malignant cells in amyloid stroma (calcitonin deposits within tumor as amyloid)
64
Which hereditary diseases are associated with medullary carcinoma? And what mutation?
MEN2A and 2B
RET oncogene
Detection of RET mutation warrants prophylactic thyroidectomy
65
Anaplastic carcinoma: Histology
undifferentiated malignant tumor of thyroid
66
Anaplastic carcinoma: Presentation
Usually in elderly
Invades local structures, leading to dysphagia or respiratory compromise
Poor prognosis
67
Most common cause of primary hyperparathyroidism
```
Parathyroid adenoma (80%)
Sporadic parathyroid hyperplasia and carcinoma are less common causes
```
68
Parathyroid adenoma: Presentation and Mechanism
Benign neoplasm, usually involving 1 gland
| Results in asymptomatic hypercalcemia or symptomatic
69
What are symptoms of hypercalcemia? (5)
1. Nephrolithiasis (calcium oxalate stones)
2. nephrocalcinosis: metastatic calcification of renal tubules leading to renal insufficiency and polyuria
3. CNS disturbances (depression seizures)
4. Constipation, peptic ulcer, acute pancreatitis
5. Osteitis fibrosa cystica: resoprtion of bone leading to fibrosis and cystic spaces
70
Parathyroid adenoma: Laboratory findings
High PTH, High calcium, Low phosphate
| High urinary cAMP, High serum alkaline phosphatase
71
Parathyroid adenoma: Treatment
Surgical removal
72
Most common secondary hyperparathyroidism
Chronic renal failure
Decreased phosphate excretion -> increase phosphate binding to calcium -> decrease free calcium stimulates all 4 parathyroid glands
73
Secondary hyperparathyroidism: Laboratory findings
High PTH, Low calcium, High phosphate, High alkaline phosphatase
74
Hypoparathyroidism: Mechanism and Causes
Low PTH
| Autoimmune damage, surgical excision, DiGeorge syndrome
75
Hypoparathyroidism: Presentation and Lab
Presentation related to low serum calcium
| Lab: Low PTH levels and low calcium
76
Low serum calcium: Presentation
1. Numbness and tingling (circumoral)
| 2. Muscle spasms (tetany) - Troussea sign (blood pressure cuff) and Chvostek sign (tapping on facial nerve)
77
Pseudohypoparathyroidism: Presentation and Association
Autosomal dominant form: short stature and short 4/5th digits
End-organ resistance to PTH
Hypocalcemia with High PTH level
78
Type 1 Diabetes mellitus: Mechanism
Insulin deficiency leading to hyperglycemia
| Autoimmune destruction of beta ells by T lymphocytes (Type IV hypersensitivity) characterized by inflammation of islets
79
Type 1 Diabetes mellitus: Genetics
HLA-DR3 and DR-4
| Autoantibodies against insulin often present and may be seen years before clinical disease develops
80
Type 1 Diabetes mellitus: Presentation
Age group: children <30
High serum glocuse
Weight loss, muscle loss, polyphagia
Polyuria, polydipsia, lipolysis, glucosuria
81
Type 1 Diabetes mellitus: Treatment
lifelong insulin
82
Diabetic ketoacidosis: Mechanism
Excessive serum ketones
Stress/Infection -> epinephrine stimulates glucagon secretion increasing lipolysis -> increase FFA -> converted to ketones
83
Diabetic ketoacidosis: Presentation
Hyperglycemia (>300), anion gap metabolic acidosis, hyperkalemia
Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, fruity smelling breath (acetone)
Depleted intracellular K+ due to transcellular shift from decreased insulin
84
Diabetic ketoacidosis: Treatment
Fluids (correct dehydration), insulin and potassium
85
Diabetic ketoacidosis: Complications
mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart failure
86
Type 2 Diabetes mellitus: Mechanism and Prevalence
End-organ insulin resistance
| Most common type of diabetes (90%); 5-10% of US population
87
Type 2 Diabetes mellitus: Risk group
```
Middle aged, obese adults
Family history (strong genetic predisposition)
```
88
Progression of Diabetes Mellitus Type 2
Initial rise in insulin early, but later, insulin deficiency due to beta cell exhaustion (amyloid deposits in islets - AIAAP)
89
Type 2 Diabetes mellitus: Presentation and Lab
Polyuria, polydipsia, hyperglycemia
Lab:
random glucose >200
fasting glucose >126
glucose tolerance test >200 2 hours after glucose loading
90
Type 2 Diabetes mellitus: Treatment
```
Weight loss (diet and exercise)
Drug therapy or exogenous insulin after exhaustion of beta cells
```
91
Hyperosmolar non-ketotic coma
```
High glucose (>500) leads to life-threatening diuresis with hypotension and coma
Ketones absent due to circulating insulin
```
92
Type 2 Diabetes mellitus: Complications (Nonenzymati glycosylation)
Nonenzymatic glycosylation of vascular basement membrane
- atherosclerosis (cardiovascular and peripheral vascular disease)
- hyaline arteriolosclerosis of renal (preferentially efferent) progressing to nephrotic syndrome (Kimmelstiel-Wilson nodules)
- glycated hemoglobin (HbA1C) marker of glycemic control
93
Type 2 Diabetes mellitus: Complications (Osmotic damage)
Glucose enter Schwann cells, pericytes of retinal blood vessels and lens
Aldose reductase converts glucose to sorbitol, leading to osmotic damage
Peripheral neuropathy, impotence, blindness and cataracts
94
What is the leading cause of death among diabetics?
Cardiovascular disease
95
What is the leading cause of blindness in the developed world?
Diabetes
96
Cushing syndrome: Mechanism
Excess cortisol
97
Cushing syndrome: Presentation (6)
1. muscle weakness with thin extremities (break down muscle for gluconeogenesis)
2. Moon facies, buffalo hump, truncal obesity
3. Abdominal striae (impaired synthesis of collagen)
4. Hypertension
5. Osteoporosis
6. Immune suppression
98
Cushing syndrome: Diagnosis
Diagnosis by 24-hour urine coritsol levels
99
Cushing syndrome: Causes (4)
1. exogenous corticosteroids (bilateral adrenal atrophy)
2. Primary adrenal adenoma, hyperplasia or carcinoma - 15% (unilateral atrophy)
3. ACTH-secreting pituitary adenoma -70% (bilateral hyperplasia)
4. Paraneoplastic ACTH - 15% (e.g. small cell carcinoma) - bilateral hyperplasia
100
What is the high-dose dexamethasone test?
Dexamethasone is a cortisol analog that suppresses ACTH production in pituitary adenoma but not in ectopic ACTH (cortisol remains high)
101
Conn syndrome: Mechanism
Excess aldosterone, most commonly due to adrenal adenoma
102
Conn syndrome: Presentation
Hypertension with hypernatremia, hypokalemia, metabolic alkalosis
103
How to distinguish between primary and secondary hyperaldosteronism?
Both have high aldosterone, but primary hyperaldosteronism has low renin (high blood pressure downregulates renin)
104
Examples of Secondary Hyperaldosteronism
Activation of renin-angiotensin
| Renovascular hypertension, CHF, renal artery stenosis, nephrotic syndrome
105
Primary Hyperaldosteronism: Treatment
Surgery to remove tumor
| Spironolactone as aldosterone antagonist
106
Secondary Hyperaldosteronism: Treatment
Spironolactone
107
Adrenal insufficiency: Acute and Chronic Causes
Acute: Waterhouse-Friderichsen syndrome
Chronic: autoimmune, TB, metastitic carcinoma (lung)
108
Addison's disease: Presentation
Hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (increased ACTH by-products stimulate melanocytic production of pigment), vomiting, diarrhea
109
Waterhouse-Friderichsen syndrome: Mechanism
Hemorrhagic necrosis of adrenal glands, classically due to DIC in young children with N. meningitidis
Lack of cortisol exacerbates hypotension, often leading to death
110
Addison's disease: Mechanism
Primary adrenal insufficiency
| Adrenal atrophy and absence of hormone production (all 3 cortical divisions)
111
How is primary and secondary adrenal insufficiency differentiated?
Secondary adrenal insufficiency: low pituitary ACTH - no skin hyperpigmentation and no hyperkalemia
112
Pheochromocytoma: Mechanism
Tumor of chromaffin cells
| Increased serum catecholamines
113
Pheochromocytoma: Presentation
Episodic hypertension, headache, palpitations, tachycardia, sweating
114
Pheochromocytoma: Diagnosis
Increased serum metanephrines and increased 24-hour urine metanephrines and vanillymandelic acid
115
Pheochromocytoma: Treatment
Surgical excision
| Phenoxybenzamine (irreversible alpha-blocker) administered perioperatively to prevent hypertensive crisis
116
What is Pheochromocytoma's rule of 10?
10% bilateral
10% familial
10% malignant
10% outside of adrenal medulla (bladder wall or organ of Zuckerkandl at inferior mesenteric artery root)
117
What hereditary conditions are associated with pheochromocytoma?
MEN 2A, 2B
Von hippel-lindau
Neurofibromatosis 1
118
Neuroblastoma: Presentation
Occur anywhere along sympathetic chain
| Elevated homovanillic acid in urine (breakdown product of dopamine)
119
What gene is associated with neuroblastoma and tumor progression?
N-myc
120
Carcinoid tumor: Mechanism
Carcinoid tumors (neuroendocrine cells), especially in small bowel which secretes high levels of serotonin.
No carcinoid syndrome if within GI tract (first-pass metabolism in liver)
121
Carcinoid syndrome: Presentation
Recurrent diarrhea, cutaneous flushing, asthmatic wheezing, R sided valvular disease
Increased 5-HIAA in urine, niacin deficiency
122
Carcinoid syndrome: Treatment
Somatostatin analog (Octreotide)
123
What is the most common tumor fo the appendix?
Carcinoid tumor
124
What is carcinoid tumor/s rule of 1/3
1/3 metastasize
1/3 present with 2nd malignancy
1/3 multiple
125
Zollinger-Ellison syndrome: Mechanism
Gastrin-secreting tumor of pancreas or duodenum
126
Zollinger-Ellison syndrome: Histology
Stomach shows rugal thickening with acid hypersecretion
| Can cause recurrent ulcers
127
What hereditary disorder is associated with Zollinger-Ellison syndrome?
MEN 1
128
MEN 1 (Wermer's syndrome): Presentations
```
Pituitary tumor (prolactin/GH)
Parathyroid tumor
Pancreatic tumor (ZE, insulinoma, VIPoma, glucagonoma)
```
Kidney stones and stomach ulcers
129
MEN 2A (Sipple's syndrome: Presentations
Medullary thyroid carcinoma
Pheochromocytoma
Parathyroid tumors
130
MEN 2B: Presentations
Medullary thyroid carcinoma
Pheochromocytoma
Oral/intestinal ganglioneuromatosis
(associated with marfanoid habitus)
