General Flashcards
(186 cards)
1
Q
What are the major subtypes of pituitary adenomas?
A
- Prolactin-producing
- GH producing
- ACTH-producing
2
Q
What is the most common hormone-producing adenoma?
A
Prolactin-producing
3
Q
T or F: Diabetes insipidus is common in patients with pituitary adenomas.
A
False, check for other sellar lesions
4
Q
What do lactotrophs make?
A
Prolactin
5
Q
What do somatotrophs make?
A
GH
6
Q
What do corticotrophs make?
A
ACTH
7
Q
What do thyrotrophs make?
A
TSH
8
Q
What do gonadotrophs make?
A
FSH/LH
9
Q
What is the most common presentation of a lactotroph adenoma?
A
Amenorrhea/galactorrhea in younger women, mass effects in older
10
Q
Most common presentation of a corticotroph cell adenoma
A
Cushing’s
11
Q
Most common presentation of a thyrothroph cell adenoma
A
Hyperthyroidism
12
Q
Most common manisfestations of a gonadotroph adenoma
A
Mass effect
13
Q
Most null cell adenomas are probably
A
FSH/LH-producing tumors
14
Q
What hormones does the posterior pituitary produce? What nuclei does it use?
A
ADH and oxytoxin from the supraoptic and paraventricular nuclei.
15
Q
What is the normal microscopic appearance of the posterior pituitary?
A
nuclei (pituicites) in a pink (axon) background
16
Q
Adenomas less than ___ are called microadenomas
A
10 mm
17
Q
Adenomas more than ___ are called macroadenomas
A
4 cm
18
Q
Histology of pituitary adenomas
A
Columnar to cuboidal to polygonal, monomorphic round-to-oval nuclei, salt & pepper chromatin
19
Q
What gene is implicated in pituitary adenomas?
A
MEN-1
20
Q
Epidemiology of prolactinomas
A
W, 21-40
21
Q
Prolactinoma symptoms in men
A
Sexual impotence, decreased libido
22
Q
Prolactinoma symptoms in children
A
Mass effect, growth failure
23
Q
Prolactinoma symptoms in adolescents
A
Mass effects, pubertal delay, growth arrest (boys), glactorrhea (girls)
24
Q
Stalk effect will increase serum prolatin up to
A
100 ng/mL
25
A level of prolactin over ___ indicates and adenoma
250 ng/mL
26
Gross imaging prolactinoma
Soft, red-tan
27
Prolactinoma histology
Monomorphic cells, sheet-like architecture, granulated (sparse common or dense), psammoma bodies/amyloid in sparsely granulated
28
T or F: most prolactinomas are caused by MEN-1
False, most are sporadic. Familial cases are usually caused by MEN-1
29
These adenomas account for 25% of operated tumors.
GH adenoma
30
Cilinal symptoms due to GH adenomas are mediated by
GH and IGF-1
31
Tumor that causes sleep apnea
GH adenoma (because of enlargement of tongue and uvula)
32
Tumor that cuases sleep apnea, LVH, arthalgias, and diabetes
GH adenoma
33
How is a GH adenoma diagnosed?
Elevated IGF-1 in the plasma
34
Gross appearance of GH adenomas
Soft, white to grey-red
35
GH adenoma histology
Columnar or cuboidal cells, granules containing GH, keratin filaments (fibrous bodies) if sparsely granulated
36
Pit adenoma associated with Carney's complex and MEN-1
GH adenoma
37
T or F: Most GH adenomas are sporadic
True
38
What do ACTHomas make?
Proopiomelanocortin (POMC), which is cleaved to form ACTH
39
Epidemiology of ATCHomas
W, 30-40
40
Abdominal & neck fat, purple striae, insulin resistance, immunocompromised, neuropsyc?
Cushing's
41
How to diagnose Cushing's
24 hr cortisol urine, demonstrate loss of circadian cortisol secretion
42
Gross ATCH adenoma
Small (usually too small for surgeon to find), red
43
Histology ATCH tumors
Columnar/polygonal cells, small monomorphic nuclei, abundant cytoplasm
44
What gene is implicated in ATCH adenomas?
MEN-1, but most occur sporadically
45
What is a null cell adenoma?
Anterior pituitary tumor with no immunohistochemical demonstration of hormone production
46
Epidemiology of null cell adenomas
Older patients (>40)
47
How do null cell adenomas present
Mass effect, maybe stalk effect, usually very large & cytic on imaging
48
Gross null cell adenomas
Soft, yellow-tan
49
Null cell adenoma histology
Columnar to polygonal, round-oval nuclei, sheet-like
50
What is pituitary apoplexy?
Enlargement of adenoma due to hemmorhage, often with accompanying infarct
51
What are some signs of apoplexy?
Subarachnoid hemorrhage, increased intracranial pressure, headache, visual symptoms (sudden blindness), worsened hypopituitarism
52
What is a pituicytoma?
Neoplasm of pituicites (glial cells of posterior pituitary)
53
Epidemiology pituicytomas
Rare, adults 40-60
54
Signs of pituicytoma
Mass effects
55
Gross pituicytoma
Tan, rubbery, well-curcumscribed
56
Histology pituiccytoma
Elongated bipolar glial cells with elliptical nuclei, intersecting fascicles
57
How to treat pituicytoma
Surgery
58
How to treat GH adenoma
Surgery or somatostatin analogs
59
What are craniopharyngeomas composed of?
Squamous epithelial cells of the sellar region, probably associated with cells in Rathke's pouch
60
What are the 2 variants of craniopharyngiomas?
Adamantinomatous
| Papillary
61
Which craniopharyngioma variant occurs in children 5-15 and adults 45-60?
Adamantinomatous
62
Which craniopharyngioma occurs in adults 40-55 years old?
Papillary
63
Where are most craniopharyngiomas located?
Suprasellar
64
What are some signs of cranipharyngiomas?
Endocrine disturbances (esp in children), diabetes insipidus, elevated intracranial pressure (if 3rd ventricle involved)
65
Gross cranipharyngioma
Ada: cystic, fibrotic, calcified area. Cysts ahev green-brown fluid. Cells may adhere to nearby vessels, nerves, or brain, well-circumscribed
Papillary: no cysts or calcification
66
Histology adamnatinomatous
Basaloid cells resting on loose connective tissue surrounding lobules of well-differentiated squamous epithelial cells. Nodules of keratin and cysts with debri.
67
Histology papillary cranipharyngioma
Well-differentiated squamous, no basaloid layer or nodules of keratin
68
Genetics adamnatinomatous
b-catenin
69
Most common glioma in children
Pilcytic astrocytoma
70
Where are pilocytic astrocytomas found?
Throughout CNS (brain, nerves, hypothal, stem, etc)
71
Signs of pilocytic astrocytoma
Headache, nausea, vomiting, clumsiness (cerebellar), loss of vision (ootic), hemiparesis (thalamic), hypo/pit dysfuncion (hypo)
72
Gross pilocystic astrocytoma
Well-demarcated, soft, tan-gray, sytic, contract-enhancing, slow-growing
73
Packed bipolar astrocytes adjacent to short stellate astrocytes. Rosenthal fibers, eosinophilic granular bodies.
Pilocytic astrocytomas
74
Genetics of pilocytic astrocytomas
NF-1 (esp optic), loss of 17q (sporadic)
75
Rathke's cleft cyst composition
Single layer of columnar epithelium (may be goblet or cilliated) on layer of collagenous connective tissue. Cells produce watery or mucoid material.
76
Treatment of Rathke's cleft cyst
Surgery, but 15% recurrence
77
Signs of Rathke's cyst
Mostly incidental, if in suprasellar (>1 cm) visual, endocrine, diabetes insipidus
78
What is lymphocytic hypophysitis?
Autoimmune disorder that causes pituitary insufficiency
79
Epidemiology lymphocytic hypophysitis
Women in late pregnancy or after delivry
80
Gross & microscopic lymphocytic hypophysitis
Firm, infiltrated by T and B lymphocytes, plasma cells, histiocytes. +/- follicles w/germinal centers.
81
Infiltrates may spread to other endocrine organs liek the thyroid or adrenal glands, antibodies to pituitary tissue and/or hormones
Lymphocytic hypophysitis
82
ADA criteria for DM
Fasting > 126
Random > 200 (w/classic symtoms)
HBA1c >6.5%
Load >200 (2 hrs after 75 g)
83
What can falsely elevate HBA1c levels?
Prolonged RBC life
84
What can falsely lower HBA1c levels?
Decreased RBC life: pregnancy, anemia
85
Pre-diabetes criteria
Fasting - 100-125
Load - 140-199
HBA1c - 5.7-6.4
86
How is glucose sensed by beta cells?
GLUT2
| high Km glucose transporter
87
What is the role of glucokinase?
Traps glucose in beta cells by converting it to G6P
88
Delta cells in the pancreas secrete
Somatostatin
89
Alpha cells in the pancreas secrete ____ and are located in ______
Glucagon
| Periphery
90
Which cells are closest to the arterioles in the center of a pancreatic islet?
Beta cells
91
How is glucagon secretion mediated?
Beta cells sense glucose. High glucose will cause release of insulin, which will spread to alpha cells and inhibit release of glucagon.
92
Describe the pathway of insulin secretion from the beta cell
Glucose enters through GLUT2, glucokinase turns it to G6P, ATP is formed through glycolysis, ATP inhibits ATP-sensitive K channel, membrane is depolarized, voltage-dependent Ca channels open, insulin storage granules released
93
Which enzyme cleaves the insulin preprohormone into alpha and beta chains and c-peptide?
carboxypeptidase
94
Which phase of insulin secretion is first lost in diabetes?
The first phase (10 min after a meal)
95
Amylin
- Co-secreted from beta cell with insulin
- suppreses glucagon, slows gastric emptying, promotes satiety
- reduced or absent in DM
96
Insulin effects on glucose uptake
Increase uptake in muscle and fat (GLUT-1/4) but not liver (insulin-independent, more taken up by liver when insulin-deificient)
97
Insulin effects on glucose storage and release
(-) hepatic gluconeogenesis [PEPCK]
(-) glycogenolysis [glyc phosphorylase]
(+) glycogen synthesis [glyc synthase]
98
Insulin effects on FA synthesis and storage
```
(-) lipolysis in adipocytes [HSL]
(-) FA oxidation [malonyl CoA blocks CPT1]
(+) TG-->FFA [LPL]
(+) FFA-->TG inside fat cells
(+) FA synthesis [FA synthase]
```
99
Insulin effects on protein synthesis and storage
(+) translation factors and elongation factors
| (-) of protein catabolism
100
Which is the onyl hormone that protects against hyperglycemia?
insulin
101
What is the first defense to protect against hypoglycemia?
Reduced insulin secretion.
| Low insulin: + hepatic output, - muscle/fat utilization
102
How does glucagon protect against hypoglycemia?
More hepatic output (+glycogenolysis, +gluconeogenesis)
103
How to catelcholamines protect against hypoglycemia?
Stilumate B2 (+hep output), less utilization in muscle, mobilization of lactate and alanine from muscle & glycerol from fat (gluconeogenic),stimulate a2 receptors to release insulin
104
Which hormone is mainly responsible for symptoms of hypoglycemia?
Epinephrine
105
How does GH protect against hypoglycemia?
ketone production from released of FA, more hepatic output, less important that other hormones
106
How does preganncy affect the HBA1c test?
Underestimates
107
How does low insulin affect glucose levels?
Increase
More uptake in liver, but not make into glycogen for storage. More glucose made and glycogen broken down because of counter-regulatory hormones, since tissues believe there is glucose shortage.
108
How does low insulin affect lipids metabolism?
Increased levels in blood
Less synthesis/storage and more lipolysis and mobilization. Oxidation in mitochondria = ketones. DKA or HHS (high glucose)
109
How does low insulin affect protein?
amino acid production
| Increased gluconeogenesis and urea production, azoturia (protein in urine)
110
Which HLA is associated with T1D?
DR/DQ
111
T1D patients can have autoantibodies to what?
```
AI-2 (insulinoma-associated antigen-2)
AI-2b (AI-2 homologous antigen)
GAD65 (glutamic acid decarboxylase)
ICA (cytoplasmic islet cell)
IAA (insulin)
```
112
Autoimmune destruction of beta cells in T1D is mediated by which cell type?
T cells
113
What is LADA?
Latent autoimmune diabetes of adulthood
| Less severe T1D that won't present until adulthood
114
What is Type 1a diabetes?
Autoimmune type 1 diabetes
115
What is type 1b diabetes?
Idiopathic diabetes
116
What are the typical things associated with idiopathic diabetes?
Mild DKA but no autoimmune markers, obesity with weight loss.
117
How are idiopathic diabetes patients treated?
At first, need high dose insulin, can be switched to oral atgents later on. insulin requirements tend to wax and wane.
118
Why do patients with T2D get polyuria and polydypsia?
Blood glucose exceeds kidney's absorbing capacity (osmotic diuresis), free water loss and increased thrist.
119
What is acanthosis nigricans?
Thickening and hyperpigmentation of skin folds typically associated with insulin resistance
120
What occurs first, macrovesicular complications or microvesicular complications?
Macrovesiclular first (atherosclerosis and peripheral vascualr disease)
121
What is MODY?
Maturity onset diabetes of the young, inherited AD, nonketotic, under 25 yrs, no obeses or resistant, defect in b-cell function (ex: glucokinase)
122
What are some complication of maternal diabetes?
preeclampsia, polyhydramnios, infections, stillbirthm, macrossomia, neonatal hypoglycemia
123
3 microvascular complications of diabetes
- diabetic retinopathy
- renal disease
- neuropathy
124
3 macrovascular complications of diabetes
- Heart disease
- stroke
- ED
125
Risk factors for developing complications of diabetes
Duration, hyperglycemia, HTN, genetics, smoking, compliance
126
HBA1c is an estimate of glucose control for the past _____
3 months
127
T or F: Patients with comorbidities should be on stricter glucose control
False. Those with hypo, age, or heart disease have a goal of 7.5-8% instead of 6-6.5%.
128
Kussmaul respirations are a sign of
DKA
129
What is the teatment for DKA?
Saline and insulin drip
130
DKA is considered resolved if gluc under ____, venous pH ____ and anion gap _____
Gluc 7.3, AG < 12
131
What are the characteristics of non-proliferative diabetic retinopathy?
- microaneurysms (dot & blot)
- exudates (hard & sharp from lipoproteins, edema)
- macular edema (thickening of retina)
- retinal ischemia (cotton-wool spots, venous beading)
132
What is the first finding in diabetic retinopathy?
Microaneurysms
133
What 3 findings suggest pre-proliferative retinopathy>
IRMA (intra=retinal microvascular abnormalities), venous bleeding, intra-retinal hemorrhages
134
What are the characteristics of proliferative retinopathy?
- neovascularization
- fibrosis (contract=detachment)
- Vitreous hemmorhage
- Traction retinal detachment
135
Where is neovascularization retinopathy usually found?
Near optic nerve head and surface (outer layer) of retina
136
2 risk factors apart from glucose control that predisposes to retinopathy
- Duration of disease
| - Ethnic (mexicans)
137
Risk factors for retinopathy
Duration, hyper, genetic, HTN (diastolic over 70), puberty, nephropathy, smoking, pregnancy
138
When should Type 1 diabetics get first eye exam?
3-5 yrs (initial after diagnosis)
139
How often should diabetics get eye exams?
- Annual (children, adult w/out retinopathy)
- Semi (non-proliferative)
- Quarter (Pre-proliferative)
- Individual (Proliferative)
140
What is diagnostic of early stage renal disease?
Microalbuminuria (2/3 samples in 6 mo)
| - 20-200 ug/min or Alb/Cr ratio
141
What are some treatments of early diabetic nephropathy?
- glycemic control
- ACEI or ARB (ALWAYS X pregnancy)
- Low protein diet
- Aldose reductase inh (exp)
- PKC inh (exp)
142
Risk factors for diabetic neuropathy
- genetics
- male
- tall
- alcohol
- hyperlgycemia
143
Vibratory perception measure __ nerves
Large
144
Thermal perception measure __ nerves
Small
145
How can you tell if someone has a pseudocushing state?
Gluccocorticoid excess but diurnal rhythm is intact
146
What is the cosyntropin test used for?
ACTH analog used to stimulate production of cortisol. Diagnosis of primary adrenal insufficiency if no cortisol increase.
147
What is the metyrapone test?
CYP11B1-OHase inhibitor. Give at night, 11-deoxycortisol should be high in morning (loss of feedback inhibition). Checks secondary adrenal insufficiency
148
How can you test for 2ry adrenal insufficiency?
- insulin (cortisol peak normal)
- metyrapone (11-deoxycortisol in morning normal)
- cosyntropin (pass standard but fail low dose)
- DHEA-S (normal excludes acquired deficiency)
149
What is Conn's disease?
Excess aldosterone
150
What are the clinical features of mineralicorticoid excess?
- HTN (resistant, <40 yrs)
- hypokalemia
- met alkalosis
- hypomagnesemia
- no edema
151
What caused apparent mineralicorticoid excess syndrome?
11b-HSD2 deficiency. Cortisol activates MR. Also can occur with licorice and carbenoxolone.
152
Familial hyperaldosteronism is due to what gene?
Fusion protein from linked CYP11B1 and CYP11B2
153
How to diagnose Liddle syndrome
Mineralocorticoid excess responds to amiloride but not spirinolactone. (Apical ENaC constitutively active)
154
What is the mechanism behind pregnancy-induced HTN?
Mutations in MR allow progesterone to act as agonist
155
Which conditions can cause mineralocorticoid excess?
- 1ry or 2ry adosteronism
- DOC excess (tumor)
- 11/17-hydroxylase insuff
- GGI (21-hydroxylase + HTN/hyerK)
- AME
- Liddle's
156
How to screen for aldo excess
- 24 hr Urine: K >30meq and Na >100meq
| - Plasma renin/aldo ratio
157
How to confirm adlo excess
- 24 hr urine @ high salt w/no aldo suppresion
- Saline influsion w/no aldo supp.
- Fludocortisone test w/high urine aldo
158
What are the localizing studies used for hyperaldo?
Adrenal CT (tumors) or adrenal vein sampling (unilateral tumor)
159
What are some signs of primary adrenal insufficiency?
Weakness, weight loss, nausea, hyperpigmentation, hypotension, hyponatremia, hyperkalemia
160
What medications must you stop before screening for hyperaldo?
Discontinue ACEI, ARBs, diuretics, NSAIDS.
| Can use alpha blockers and low dose beta blockers
161
How do you treat mineralocorticoid excess?
Surgery or spirinolactone
162
Which disorder causes salt wasting with normal glucocorticoid activity?
Aldo synthase (CYP11B1) deficiency
163
Why is secondary adrenal insufficiency usually limited to gluccocorticoids?
Mineralocorticoids are not dependent on ACTH
164
Intra-adrenal pheochromocytomas usually make
epinephrine (except VHL)
165
Extra-adrenal pheochromocytomas (apargangliomas) usually make
NE
166
Glomus tumors of head and neck usually make
dopamine
167
What is COMT? Where is it found? Why is it important?
Catechol O-methyl transferase. Present in periphery and convert catelcholamines to metanephrines. Tumors usually contain it (easier to diagnose)
168
What enzyme is needed to amke HVA & VMA from metanephrines?
MAO
169
What are the 5 P's of pheochromocytoma?
| Other symptoms?
- Pressure (spikes & elevation)
- Pain (acute throbbing headache)
- Perspiration (drenching)
- Pallor (minimal exertion)
- Peripheral vasoconstriction
- orthostasis, hyperglyc, hypercal, tremor
170
MEN-2A is susually associated with
MTC, hyperPTH, RET mutations
171
MEN-2B is ususally associated with
MTC, marfanoid habitus, musocsal neuromas, RET mutations
172
How to diagnose pheochromocytoma
- collect 24 hr urine to measure cate & meta & Cr
- positive if excretion 2X above upper limit normal
OR
- collect plasma meta in calm conditions
- elevation in meta positive (slightly elevated normeta is common)
173
Which medications/conditions can cause false positives in pheo diagnossis?
- sleep apnea
- clonidine use/withdrawal
- tricyclic antidepressants
- MEN or VHL presymptomatic states
174
How to prepare for pheo surgery
1. a1 blockade (until stuffy)
2. 2 weeks salt overload
3. Tyrosine hydroxylase inhibitor (block syntehsis of catecholamines)
4. b2 blockers
175
What to do in incidental adrenal nodule is found
1. Check BP and K
2. Screen for Cushings and Pheo if HTN/hypoK
3. If nasty-looking, biopsy if Pheo is neg
4. Hounsfield units 3 cm, monitor (scan 6 mo)
6. >4 cm, remove
176
The pituitary fossa is bound anteriorly and inferiorly by
sphenoid sinus
177
The pituitary fossa is bound posteriorly by
bony dorsum sella
178
The pituitary fossa is bound laterally by
```
Cavernous sinuses
(internal carotid a, CN 3/4/6, 1st two divisions of 5)
```
179
The pituitary fossa is bound superiorly by
Diaphragma sella
| optich chiasma within suprasellar cistern
180
Eosinophilic adenomas secrete
GH
181
Basophilic adenomas secrete
ACTH
182
What is a pituitary apoplexy/
Infarction of a pituitary adenoma causing acute swelling of the tumor and hemorrhage
183
How do you treat a pituitary adenoma that is secreting over 200 ng/mL of prolactin?
Dopamine agonists (bromocriptine and cabergoline)
184
How do you treat a pitoma which is mainly secreting GH?
Surgery
| Radiation or medication if surgery not possible
185
How do you treat a pitoma which is mainly secreting ACTH
Surgery
| radiation or medication if surgery not possible
186
Which surgical method cannot eb used for predominantly suprasellar tumors?
Transphenoidal (need to use transcranial approach)
