Endo Flashcards
1
Q
What is the foramen cecum?
A
- Divot on tongue from obliteration of thyroglossal duct
- Where the thirds of tongue meet
2
Q
What are parafollicular cells?
A
- Cells in between thyroid follicles that secrete calcitonin
- Derived from neural crest cells
3
Q
Where is calcitonin produced?
A
Parafollicular cells of the thyroid
4
Q
What type of cancer does neoplasia of parafollicular cells produce?
A
Medullary thyroid cancer - progress can be tracked by measuring calcitonin levels
5
Q
Where are branchial cleft cysts found? Thyroglossal duct?
A
Branchial: sides of neck
Thyroid: midline, will move with tongue movement as are attached to foramen cecum
6
Q
Venous drainage of adrenals?
A
Left: renal vein, IVC
Right: IVC
7
Q
Layers of adrenal cortex and what is produced?
A
Glomerulosa: Mineralocorticoids - aldosterone
Fasciculata: Corticosteroids - cortisol
Reticularis: Androgens
8
Q
Regulation of adrenal cortex?
A
ACTH (Adrenocorticotropic hormone): regulates reticularis / fasciculata
Renin: Glomerulosa
9
Q
What are the adrenal medulla and cortex derived from?
A
Cortex: Mesoderm
Medulla: ectoderm -> neural crest
10
Q
What does the adrenal medulla secrete? How is it regulated?
A
- Epi and NE into the bloodstream when
- Preganglionic SNS neuron release ACH (acetylcholine) directly onto Nicotinic receptors of the medulla
11
Q
Where is the pituitary gland found?
A
In the sella tursica
12
Q
What is the anterior pituitary derived from?
A
Rathke’s pouch / surface ectoderm
13
Q
Another name for anterior / posterior pituitary?
A
Anterior: adenohypophysis
Posterior: neurohypophysis
14
Q
What is posterior pit derived from?
A
Neuroectoderm, just like the adrenal medulla
15
Q
What do the nueral crest and neuroectoderm become?
A
Crest: PNS
Derm: CNS
16
Q
How does hypothalamus communicate with anterior?
A
Trophic hormones released into portal capillary system causing release of new hormones from anterior
17
Q
How does hypothalamus communicate with posterior?
A
- No portal system, axonal projections form hypo to post
- Hormones made in hypo and moved down axons by neurophysins
18
Q
What do basophils and acidophils of anterior secrete?
A
Acidophils: secrete prolactin and GH
Basophils: everything else
19
Q
Which pituitary hormones share same alpha subunit?
A
- FSH
- LH
- TSH
* ***B-HCG shares this sub unit two so can act as TSH in high enough doses
20
Q
Hormones from posterior pit?
A
Vasopressin: Supraoptic nuclei
Oxytocin: Paraventricular neclei
21
Q
What are the islets of langerhan?
A
Bodies of alpha and beta cells in pancreas:
Beta cells: insulin
Alpha cells: glucagon
Delta: somatostatin
22
Q
3 places glucose can be stored?
A
- Skeletal muscle
- Liver
- Adipose tissue
23
Q
Does insulin control glucose transport at liver?
A
No, but does increase glucose metabolism
24
Q
Does liver prefer to metabolize glucose into glycogen or fatty acids?
A
Glycogen, has small capacity though, so quickly begins making triglycerides to send off in VLDLs
25
Insulin impact on fat and muscle metabolism?
1. Decreased lipolysis
| 2. Increased AA uptake and protein construction
26
How is glucose formed?
- Found in vesicles in B cells as proinsulin
| - Cleaved in vesicle forming C peptide and active insulin
27
How to tell between high endogenous/exogenous insulin?
Endogenous will have CRP high as well
28
Mechanism of insulin release?
1. Glucose enters Beta via GLUT2
2. Converted to ATP
3. ATP deactivates K leak channel increasing [K]
4. Beta cell depolarizes from + charge
5. Ca now enters cell = insulin release
29
What is GLP-1?
- When GI cells sense sugar, release GLP-1 leading to insulin release before sugar hits bloodstream
- This is why oral glucose spikes insulin higher than IV
30
How does insulin signal at cell?
- Binds membrane tyrosine kinase autophosphorylation
- MAPK goes to nucleus
- PI3K works on cytoplasm
31
Where is GLUT4 found?
- Muscle and adipose tissue
| - Insulin causes it to integrate in cell membrane
32
Why does exercise help diabetes?
Exercise induces GLUT4 insertion in skeletal muscle just as insulin does
* Can lead to HYPOglycemia if dont drop insulin levels before exercising
33
How is glucose transported in liver?
- GLUT2 transporter - not dependant on insulin
34
How does GLUT2 work?
- Found in Liver and Beta cells
- By directional allowing liver to release glucose in fasting state
- Maxes out transport later than GLUT4
35
GLUT4 vs. GLUT2 kinetics?
GLUT4: lower Km, ramps up faster
GLUT2: higher vMAX, can handle higher loads
36
Where are gluco/hexokinase found?
Gluco: liver
Hexo: everywhere else
37
Characteristics of GLUT1/3 and where are they found?
High affinity high capacity glucose transport:
1. Brain
2. RBC: no mitochondria so only energy comes from anaerobic glucose metabolism
3. Placenta
4. Cornea
38
What is GLUT5?
- Fructose transporter found in SI allowing fructose to be absorbed and turned into glucose for rest of body to use
- Also found in sperm
39
Glucagon signaling path?
G coupled increase cAMP, increased PkA
40
What is a trophic hormone?
Impact on target leads to release of another hormone: for example TSH leads to TH release from thyroid
41
What is somatostain
AKA: GHIH "Growth hormone inhibiting hormone"
| - Remember that this is same hormone that brings GI activity to a halt
42
How is prolactin regulated?
Dopamine inhibits prolactin
43
What does prolactin regulate?
- Inhibits GNRH shutting down production of sex hormones
44
Which drugs will lead to increased prolactin?
Antipsychotics: if they are inhibiting DE prolactin is no longer being inhibited
45
Impact of TH/TRH on prolactin?
Both increase prolactin
| - Elevated TRH would be see in HYPOthyroid
46
Somatostatin impact on TH?
Decreases it
47
What does prolactin do?
- Stimulates breasts to produce milk
- DOES NOT cause milk to be released
* Let down is they job of oxytocin
48
Why isn't there milk DURING pregnancy?
- Progesterone is inhibiting prolactin
| - Once placenta is delivered, progesterone drops allowing for Milk to be made
49
What is another name for GH?
Somatotropin
50
Functions of GH?
1. Bone lengthening: kids
2. Bone strengthening: adults
3. Protein synthesis
4. Lipolysis / gluconeogenesis `
51
What are some natural factors that stimulate GH?
1. Sleep
2. Exercise
3. Arginine (glucose decreases)
4. Puberty
52
2 hormones causing insulin resistance?
1. GH
| 2. Cortisol
53
What regulates most effects of GH?
IFG-1
54
What is ghrelin?
"Hunger hormone"
- Secreted by stomach when empty
- Acts on lateral hypothalamus
* ****Activity in laterally nuclei makes you hungry = grow laterally
55
What is leptin?
- Secreted by fat cells when full of fat
| - Acts on medial thalamic nuclei
56
What does sleep do to hunger hormones?
- Increases ghrelin = grow laterally
| - Decrease leptin = implicated in congenital obesity
57
Thirst receptors in brain and what are they sensing?
1. Arterial baroreceptors: HYPOvolemia
| 2. OSMOreceptors: HYPERtonicity
58
Is ADH or aldosterone regulating osmolality of blood?
ADH
| ***Since aldosterone brings in Na/H2O it is not changing the tonicity of the water
59
Actions of ADH and receptors?
V2: Free water retention
V1: arterial constriction
**Think Vasopressin as it is a pressor
60
What is the precursor to all steroids? Rate limiting step?
Cholesterol: conversion to pregnenolone is rate limiting
61
What controls entry to steroid synthesis pathway?
ACTH
62
What enzyme is not found in z. glomerulosa?
17-a-hydroxylase which is needed for cortisol
63
What is necessary to enter cortisol pathway?
17-a-hydroxylation of pregnenolone or progesterone
64
2 Enzymes necessary to make aldosterone and Cortisol?
1. 21-hydroxylase
| 2. 11-B-hydroxylase
65
Do precursors to mineralocorticoids of mineral or glucocorticoid activity?
Mineral
66
Final regulation in aldosterone pathway?
Angiotensin II
67
What is happening in CAH?
"Congenital adrenal hyperplasia"
| - Defect in an enzyme necessary for creation of cortisol
68
What feedback happens when cortisol is low?
- ACTH increases increasing amount of cholesterol heading into the adrenal cortex
- ACTH also causes hypertrophy of cells in all layers of cortex
69
Role of androgens?
1. External male genitals in fetus
| 2. Male secondary characteristics in adolescence
70
Most common form of CAH? What happens?
21-a-hydroxylase deficiency
- Needed or production in both reticularis and fascicularis
- Sex steroid path is only one functioning
- Virilization in females
- Precocious puberty in males
- Decreased BP with HYPER K
71
What happens in 11-B-hydroxylase deficiency?
- Female virilization
- Normal or precocious males
- No cortisol
- Increased minerals as all precursors have mineral activity
- High BP with HYPO K
72
What happens in 17-a-hydroxylase deficiency?
- Increased minerals: High BP with HYPO K
| - Decreased androgens: boys with ambiguous genitals, girls may not develop secondary sex characteristics at puberty
73
What does 5-a-reductase do?
DHT creation from androgens
74
What are flutamide and finasteride?
Finasteride: androgen receptor blocker
Flutamide: blocks 5-a-reductase
75
Effects of cortisol?
1. Increased arterial A1: high BP
| 2. Stronger catabolic effects than glucagon
76
Extra effects cortisol has that glucagon does not?
1. Proteolysis
2. Insulin resistance
3. Osteo/fibroblast inhibition leading to bone and connective tissue weakness
4. Immunosuppression
5. Anxiety, depression, psychosis
77
What are some things cortisol shuts down in immune?
1. Phospholipase A: no AA release
2. IL2: no T cell proliferation
3. Neutrophils adhesion: false neutrophilia
4. Decreased EOSs and blocks histamine
78
Breakout of Ca in blood?
1. Free: 45%
2. Bound to albumin: 45%
3. 10%: bound to anions other than albumin
79
What does acidosis do to Ca?
- Causes HYPERcalcemia
| - H+ is competing with Ca to bind to anions so this increases free Ca in blood
80
What is cholecalciferol?
Vitamin D - steroid hormone
81
What is hydroxyapatite?
Combination of Ca / PO4 that makes up majority of bone mineral
82
Vitamin D?
1. Increased absorption of both Ca and PO4
2. Decreased Ca excretion at kidney
3. Increased osteoclast activity for remodeling
83
3 things stimulating 1-a-hydroxylation of vitamin D in kidney?
1. Low Ca
2. Low PO4
3. PTH
84
PTH relation to osteoclasts?
- Osteoclasts have RANK receptor but not PTH
| - PTH receptor on osteoblast leads to rank-L secretion
85
PTH impact on kidney?
1. Increased Ca resorption
2. Increased PO4 excretion
3. Increased vitamin D activation
86
Regulation of PTH?
Increased by:
1. Low Ca
2. High Po4
3. Low Mg
* ***Super low Mg inhibits PTH though
87
Function of calcitonin?
1. Stops osteoclast resorption
2. Stops gut Ca absorption
3. Increased Ca renal excretion
* **CalcitonINNNNN wants to keep Ca innnnnn Bones, not in blood
88
Cancer known to secrete PTH and what will it cause?
Squamous cell lung cancer
1. Decreased bone density
2. Decreased serum phosphate
89
Effects of TH?
1. Increased B receptor activity: Increased HR / contract
- Increased SNS activity
2. Increased energy and alertness
3. Increased metabolism: increased Na/K ATPase synthesis
- Heat generation / weight loss
4. Bone Growth
5. CNS maturation
6. Endometrial development
90
What is increased appetite and weight loss indicative of?
HYPERthryroid
91
Difference between T3/4?
T4: secreted by thyroid but is weaker version
T3: Stronger version with an iodine cleaved by peripheral tissue
92
What happens to TH in liver failure?
- TH is highly lipophilic so needs to be bound by TBG in serum
- TBG decreases in liver failure increasing TH
* ***Free T4 will be high but total will be low because free is inhibiting TSH and TRH
93
What can decrease TBG?
1. Nephrotic syndrome
2. Liver failure
3. Corticosteroids
94
What can increase TBG?
1. Pregnancy
| 2. Exogenous estrogen
95
2 ingredients in TH?
1. Iodine
| 2. Tyrosine
96
What is thyroglobulin?
TH precursor that will be combined with Iodine in lumen to make TH
97
What does thyroid peroxidase do?
1. Oxidizes Iodide -> iodine
2. Iodinates thyroglobulin
3. Makes T3/4 from globulins
98
How does TH increase metabolism?
Increases action of Na/K ATPase
99
Where to lipophilic hormones bind?
Intracellular receptors
100
What are the lipophilic hormones?
1. Vitamin D
2. Sex hormones
3. Adrenal hormones
4. TH
101
How do all vasodilators work? What are they?
Activating guanylyl cyclase increasing cGMP
1. NO
2. ANP
3. BNP
102
How do the FLAT hormones signal?
- Gs receptor increasing cAMP
1. FSH
2. LH
3. ACTH
4. TRH
103
How do the Pig hormones signal?
Receptor associated tyrosine kinases
1. Prolactin
2. GH
104
What molecules signal with tyrosine kinase?
```
Receptor associated:
1. PiG: prolactin and GH
2. Immunomodulators
3. EPO / thrombopoietin
4. GCSF
Intrinsic tyrosine:
1. Insulin
2. IGF-1
```
105
What is Gs/q coupled with?
Gs: cAMP, decreased Ca, vasodilation
Gq: IP3, increased Ca, Constriction
106
Endocrine hormones signaling via cAMP?
```
"FLAT CHAMP"
FSH
LH,
ACTH
TSH
```
```
CRH /calcitonin
hCG
ADH: V2-receptor
MSH
PTH
***GHRH / glucagon
```
107
What signals via IP3?
```
"GOAT HAG"
GnRH
Oxytocin
ADH: V1
TRH
```
Histamine: H1
Angiotensin II
Gastrin
108
Which are the receptor associated tyrosine kinase hormones / JAK / STAT?
```
"PIGG lET"
Prolactin
Immunomodulators
GH
G-CSF
```
Erythropoietin
Thrombopoietin
109
How does non functional pituitary adenoma present?
Mass effect:
1. Bitemporal hemianopsia: adjacent to optic chiasm
2. Headache
3. HYPOpituitarism
110
What is adjacent to sell turcica?
Optic chiasm, this is why pituitary adenoma will cause bitemporal hemianopsia
111
What is bitemporal hemianopsia?
Inability to see objects in peripheral fields of vision
112
Presentation of prolactinoma in men and women?
Men: Headache and decreased libido
- No galactorrhea as men dont have lobules
Women: Galactorrhea and amenorrhea
- This is because prolactin suppresses GNRH
113
What is bromocriptine?
Dopamine agonist: can be used to treat prolactinoma as DE suppresses prolactin
114
Why does GH adenoma lead to gigantism in kids but acromegaly in adults?
Adults have already fused epiphyseal growth plates long bones can no longer grow
115
What often occurs secondary to GH adenoma and why?
- Secondary diabetes as GH decreases glucose uptake
116
How do diagnose GH adenoma?
1. Increased GH
2. Increased IGF-1
3. Oral glucose does not suppress GH
117
Treatment of GH adenoma?
1. Octreotide: somatostatin analog
* **Remember that another name for somatostatin is "Growth hormone inhibiting hormone" and that it is also the thing that slows everything down in the gut
118
What is octreotide?
Somatostatin analog: can be used to treat GH adenoma
119
Causes of hypopituitarism?
1. Pituitary adenoma compression of normal tissue
2. Apoplexy: bleeding of the adenoma
3. Craniopharyngioma: kids
4. Sheehan: infarct during pregnancy
120
Presentation of sheehan?
1. Poor lactation
| 2. Loss of pubic hair
121
Functions of oxytocin?
1. Uterine contraction
| 2. Release of breast milk with suckling
122
What is desmopressin?
ADH analog that can be used to treat diabetes insipidi s
| **Think another name for ADH is vasopressin and desmopressin sounds like vasopressin
123
Drug that causes nephrogenic diabetes insipidus?
Think of all the people at FP who likely should be taking Li waiting in line to used the bathroom because they all have to be so bad
124
Tumor classically secreting ADH?
Small cell lung carcinoma
125
Drug causing SIADH?
Cyclophosphamide
126
Infx causing SIADH?
Pulmonary
127
Treatment of SIADH?
1. Demeclocycline - ADH antagonist
128
What is lingual thyroid?
Thyroid stays at base of tongue and does not descend
129
Which way to lipids and sugars go in HYPERthyroid?
- HYPERglycemia
| - HYPOcholesterolemia
130
Most common cause and pathology of PARAthyroid?
Graves: IgG stimulating TSH receptor
131
Why and when to exophthalmos and pretibial myxedema occur?
- Fibroblasts behind eye and on shin have TSH receptors that IgG is stimulating
- Leads to glycosaminoglycan release
132
What does "scalloping of the colloid" indicated?
Grave's disease
133
Graves treatment?
1. BBs: B1 is being over expressed
2. Thioamide: blocks thyroid peroxidase
3. Radioiodine ablation
134
What happens in organification?
Thyroglobulin combined with I2 in the follicle - this is catalyzed by peroxidase
135
Presentation of thyroid storm?
1. Arrhythmia
2. HYPERthermia - very high fever
3. Vomiting / diarrhea
4. Hypovolemic shock
5. Agitation
6 Diaphoresis
****Most being caused by beta sympathetic stimulation
136
Treatment of thyroid storm?
1. BB
2. PTU
3. Steroids
137
What does PTU do?
1. Inhibits thyroid peroxidase
| 2. Inhibits peripheral conversion of T4 - T3
138
What is and multinodular goiter?
- Enlarged thyroid with many nodules
- Usually from iodine deficiency
- Usually non toxic - "euthyroid" but can become independent of TSH
139
What is cretinism?
CONGENITAL HYPOthyroidism in kids presenting with:
1. Retardation - TH needed from brain / bones
2. Short stature and skeletal abnormal
3. Coarse facial features
4. Enlarged tongue
5. Umbilical hernia "potbelly"
6. Jaundice at birth
140
Cretinism cause?
1. Maternal HYPOthyroid
2. Iodine deficiency
3. Thyroid peroxidase deficiency
141
What is myxedema?
HYPOthyroid in adult:
1. Myxedema of tissues
- Larynx: deepening of voice
- Tongue: enlarged tongue
2. Weakness
3. Hypercholesterol
4. Oligomenorrhea
142
Causes of myxedema?
1. Hashimotos
2. Iodine deficiency
3. Lithium
4. Amiodarone
143
What is Hashimoto's thyroiditis?
- Autoimmune destruction of thyroid gland
- Associated with HLA-DR5
- Starts as HYPER and progresses to HYPO
* **Pernicious anemia seen in DR5 also
144
Markers for hashimoto?
1. Antithyroglobulin Ig
2. Antimicrosomal Ig
3. Hurthle cells
145
What are the following indicative of?
1. Antithyroglobulin Ig
2. Antimicrosomal Ig
Hashimoto
146
When are hurthle cells seen?
Hashimoto
147
Progressive risk for hashimoto?
Marginal zone B cell lymphoma
148
What is subacute / de quervain / granulomatous thyroiditis?
- Granulomatous thyroiditis following viral infx
- Tender HYPERactive thyroid
- Self limited
149
When is thyroid tender?
"De Quervain, brings the pain"
| Subacute / de quervain / granulomatous thyroiditis
150
What is reidel fibrosing thyroiditis?
- Chronic inflammation = fibrosis of thyroid
- HYPOThyroid
- 'Hard as wood' non tender thyroid
- Fibrosis can extend to airway
- Classically seen in younger females
151
What is a thyroid that is hard as wood and non tender indicative of?
Reidel fibrosing thyroiditis
152
Ddx for firm invading locally?
Older: anaplastic carcinoma
| Young women:Reidel fibrosing thyroiditis
153
Iodine uptake study result in thyroid cancer?
Low
154
How is thyroid biopsied?
Fine needle aspiration
155
What is follicular adenoma?
- Benign tumor of thyroid glands
- Surrounded by capsule
- Usually not secreting TH
156
What is thyroid cancer surrounded by dense capsule indicative of?
Follicular adenoma
157
4 types of thyroid carcinoma?
1. Papillary
2. Follicular
3. Medullary
4. Anaplastic
158
Major risk factor for papillary carcinoma of thyroid?
- Ionizing radiation in childhood
159
Characteristics of papillary thyroid carcinoma?
- Orphan annie eye nuclei
- Nuclear grooves
- Psammoma bodies
160
Spread and prognosis of papillary thyroid cancer?
- Spread to cervical nodes with excellent prognosis
161
What is follicular carcinoma?
- Malignant proliferation of thyroid follicles
| - Fibrous capsule with INVASION through capsule
162
Where does follicular carcinoma spread?
Hematogenously
163
What is medullary carcinoma?
- Malignancy of parafollicular C cells
- Produces lots of calcitonin = HYPO Ca
- Calcitonin can deposit in tumor = amyloid `
164
What thyroid tumor has amyloid?
Medullary thyroid carcinoma
165
When is hereditary thyroid carcinoma seen?
Medullary carcinoma of thyroid
- MEN2A and B
- RET mutations: detection warrants thyroidectomy
166
What is anaplastic carcinoma of thyroid?
- Malignant and undifferentiated
- Seen in elderly
- Poor prognosis
- Local invasion: dysphagia and respiratory compromise
167
Cell in parathyroid that releases PTH?
Chief cell
168
What does increased urinary cAMP indicate? How?
- Hyper PTH
- TPH binds GS activating adenylate cyclase
- AC converts ATP to cAMP
169
Not obvious lab findings in hyper PTH?
1. Increased urinary cAMP
| 2. Increased alk phos: bone resorption from PTH turning on the osteoblasts
170
Most common cause of secondary hyper PTH?
- Renal failure increases PO4 in serum
| - Excess P binds Ca increasing PTH
171
Genetic cause of HYPO PTH?
Digeorge from failure to develop 3 and 4th pharyngeal pouch
172
Presentation of HYPO PTH?
1. Low PTH and Ca
2. Muscle spasms: tetany
3. Numbness and tingling
173
What is trousseau sign? Chvostek?
Signs of Hypo Ca:
Chvostek: tap on facial nerve = spasm
Trousseau: Fill BP cuff up = muscle spasms
174
What is pseudo HYPO PTH?
- End organs are not responding to PTH
* **Error in Gs protein
- Ca will be low but PTH will be elevated
175
What is the exocrine pancreas responsible for?
Digestive enzymes
176
Where are beta cells found?
Center of pancreatic islets of langerhorn
177
What type of hypersensitivity is TIDM and what is it associated with?
- Type IV - destruction by T lymphocytes
- HLA DR3 and 4
- Inflammation of islets with anti insulin Ig in blood
178
Presentation of TIDM?
1. Weight loss
2. Low muscle mass
3. Polyphagia
4. Polyuria / dipsia
5. Glucosuria
179
Pathology of DKA?
- Increased stress = epinephrine increasing glucagon
- Glucagon increases lipolysis = increases FFAs
- Liver converts FFAs to ketone bodies
180
Type of acidosis in DKA?
Anion gap metabolic
181
K status in TIDM?
- No insulin so not being driven in cells
| - High in blood put kidney wasting it so overall low
182
When are kussmaul respirations seen?
DKA - function is to blow off acid
183
Why is breath fruity in DKA?
Increased acetone in serum
184
Treatment of DKA?
1. Fluids
2. Insulin
3. K
185
How is insulin resistance being caused in TIIDM?
Decreased # of insulin receptors on cell surfaces
186
Islet histology in TIIDM?
Amyloid
187
What is hyperosmolar nonketotic coma?
- Feared complication of TIIDM
- Glucose > 500 = deadly diuresis
- Leads to hypotension and coma in absence of ketones
188
3 manifestations of non enzymatic glycosylation seen in TIIDM?
1. Large vessels: atherosclerosis
2. Small: hyaline arteriolosclerosis
3. RBC: increased HBA1C
189
Why and in what type of cells is osmotic damage seen in TIIDM?
Occurs in cells that don't need insulin to take up glucose
1. Schwann: neuropathy
2. Pericytes of retinal blood vessels: hemmerhage = blind
3. Lens: cataracts
190
Pathology of osmotic damage from glucose?
- Aldose reductase converts glucose to sorbitol
| - Sorbitol pulls water in causing damage
191
What does gastrin cause in stomach?
"Zollinger ellison syndrome"
- Parietal cell production of Acid
- Multiple and extend to jejunum
192
What is ZE syndrome?
Gastrinoma creating treatment resistant peptic ulcers
193
What occurs in somatostatinoma?
1. Achlorhydria: from gastrin inhibition
| 2. Cholelithiasis / steatorrhea: cck inhibition leading to inhibited gallbladder contraction
194
VIPoma presentation?
1. Achlorhydria
2. Watery diarrhea
3. HYPO K
195
What catecholamines are secreted by the adrenal medulla?
1. Epinephrine
| 2. Norepinephrine
196
Features of cushing's?
1. Muscle weakness and thin extremities
2. Moon face, buffalo hump, truncal obesity
3. Abdominal striae - impaired collagen
4. HTN: upregulated A1
5. Osteoporosis
6. Immunosuppression
7. Psychiatric changes
8. Menstrual irregularities
197
Why does Cushing's cause Muscle weakness and thin extremities?
- Cortisol wants to raise blood sugar and is breaking down muscle for gluconeogenesis
198
Why does cushing's cause buffalo, moon, and central adiposity?
- Cortisol has raised blood sugar which is now being stored as fat in these locations
199
3 mechanisms of cortisol immunosuppression?
1. Phospholipase A2 inhibition = no AA
2. Inhibition of IL2 = T cell growth factor
3. Inhibition of histamine from mast cells
200
Most common cause of cushing's?
Exogenous, prescribed corticosteroids
201
Size of adrenals in exogenous cushing's?
- Bilateral adrenal Atrophy
| - High serum cortisol shuts down ACTH production in anterior pituitary
202
Size of adrenals in primary cushing's?
- Adrenal that is producing will have HYPERplasia
| - Adrenal NOT producing will shrink from diminished ACTH
203
Size of adrenals in secondary cushing's?
"ACTH secreting adenoma"
| - Both are hyperplastic
204
What 2 types of cushing's is dexamethasone suppression test trying to distinguish?
1. Primary pituitary ACTH secreting adenoma
| 2. Paraneoplastic ACTH secretion from another location
205
Cancer classically secreting paraneoplastic ACTH?
Small cell lung carcinoma
206
Interpretation of suppression test?
1. Response seen: ACTH secreting pituitary adenoma
- Decreased cortisol levels will be seen
2. No response seen: Paraneoplastic ACTH
207
Aldosterone's impact on distal collecting duct?
1. Principal cell: grabs Na, dumps D
| 2. Alpha intercalated: dumps H ions
208
Renin levels in primary and secondary hyperaldosteron?
Primary: low, high aldosterone increase BP providing negative feedback to RAAS
209
What does fibromuscular dysplasia often do?
- Thickens renal artery decreasing flow to kidney activating RAAS
210
What is CAH?
"Congenital adrenal hyperplasia"
- Hyperplasia of BOTH adrenals
- Defect in enzyme needed for hormone production
- Cortisol is decreased so ACTH increased = HYPERplasia
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Main fear of abrupt large decrease in cortisol?
- Life threatening HYPOtension from decrease in vascular tone
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2 enzymes needed for mineralocorticoids and result of loss?
21 hydroxylase: zero mineralocorticoid activity
| 11 hydroxylase: If 21 functions, we have weak MCs but cannot be converted to final, STRONGER product
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What cannot be made in 17 deficiency?
Cortisol AND sex steroids
Girls: delayed puberty
Boys: ambiguous genitalia
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What is happening in waterhouse friderichsen?
N. meningitisis infx:
1. DIC - from N. menin
2. Bilateral adrenal necrosis - acute cortisol shortage
- Causes severe HYPOtension
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3 causes of chronic adrenal deficiency?
1. Autoimmune destruction
2. TB
3. Metastatic Cancer: Lung cancer
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Presentation of adrenal insufficiency?
1. HYPOtension and Na, HYPER K
2. Weakness
3. HYPERpigmentation
4. vomit / diarrhea
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Why does adrenal insufficiency cause HYPERpigmentation?
- No cortisol = increased ACTH
- ACTH is derived from POMC which also makes MSH "melanocyte stimulating hormone"
- Since you cannot make cortisol excess MSH is made
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Type of cells in adrenal medulla?
Chromaffin cells derived from adrenal medulla
| - Main source of catecholamines: NE/E
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What is a pheochromocytoma?
- Tumor of chromaffin cells in adrenal medulla
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Presentation of pheochromocytoma?
1. Insane Episodic HTN > 200
- Beta causing heart to crank
- Alpha causing vessels to constrict
2. headaches, palpitations, tachy, sweet
2.
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What are E and NE broken down into?
Epi: Metanephrine
Nor: Normetanephrine
***both metas broken down into HVA/VMA by MAO
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Diagnosis of pheochromocytoma?
1. Increased serum metanephrines
| 2. Increased urine meta and VMA
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What do you need to do before removing pheochromocytoma?
Give phenoxybenzamine and BB: irreversible A blocker
- Want to make sure it is not spilling into blood when you excise tumor
* ***Need to give Phenoxy first as Beta is dilating so blocking first = 2x constriction
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10% rule of pheochromocytoma?
10%:
1. Familial
2. Bilateral
3. Malignant
4. Outside adrenal medulla: bladder wall
* **Would present as HTN on urination
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What is MEN2A?
1. Medullary carcinoma thyroid
2. Pheochromocytoma
3. Parathyroid adenoma
* RET disease
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What is MEN2B?
1. Medullary carcinoma thyroid
2. Pheochromocytoma
3. Mucosol neuroganglioma
* RET disease
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Pheochromocytoma associations?
1. MEN2A
2. MEN2B
3. VHL
4. NF type 1
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What is cushing's disease?
Refers specifically to syndrome caused by excess ACTH
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When should cortisol be measured?
- Midnight, this is when it is lowest: rises and falls throughout day
- With tumor, might remain high at night
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Cortisol levels with exogenous cortisol?
- Will actually show up as decreased as test is not picking them up natural axis is now depressed
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GI symptoms of cortisol loss?
1. Decreased catabolism: low serum nutrients
2. GI distress
3. Anorexia
* **Weight Loss, fatigue, HYPOglycemia
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What is addison's disease?
Chronic adrenal insufficiency
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Another name for chronic adrenal insufficiency?
Addisons
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What is a neuroendocrine cell?
Cell that receives synaptic signals from a neuron and responds by secreting hormones into serum
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What is APUD + indicative of?
Neuroendocrine cells
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What is a neuroblastoma?
- Tumor of adrenal medulla
| - Classically in kid
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What do suspect in 4 yo with abdominal mass crossing midline?
Neuroblastoma
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Signs of neuroblastoma?
- Urine VMA / HVA
- Bombesin +
- Neuro specific enzyme +
- Homer wright rosettes
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What is the following indicative of:
- Bombesin +
- Neuro specific enzyme +
- Homer wright rosettes
Neuroblastoma
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Mutation in neuroblastoma?
nMYC
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DDx for abdominal mass in kids?
1. Wilms: renal tumor in > 10yo
- Smooth and dont cross midline
2. Neuroblastoma: adrenal tumor in
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Different between pheo and neuroblastoma?
Pheo: mature secreting catecholamines
Neuroblastoma: immature, no secretion
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What are VMA and HVA in urine indicative of?
Pheochromocytoma or neuroblastoma
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Myxedema seen in HYPO or HYPER thyroid?
HYPO: it is actually sometimes referred to as myxedema
| ****However it is seen in graves but not other types of HYPER
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Myopathies seen in hyper or HYPO thyroid?
Both
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Best test for HYPO / HYPER?
Serum TSH
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Why do thyroid issues impact menstruation?
TRH also stimulates prolactin which is a GnRH inhibitor
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Why does lack of iodine lead to goiter?
- Without iodine, cannot make T3/4
| - Pituitary over secretes TSH = HYPERplasia
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When are anti TPO Igs seen?
Hashimotos
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Do pretibial myxedema and exophthalmos present in thyroid tumors?
No, only in graves
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Difference between iodine uptake in graves and toxic thyroid tumor?
Graves: diffuse uptake
Tumor: focal
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Cold or hot thyroid nodules usually malignant?
Cold
253
Cancers presenting with psammoma bodies?
```
"PSAMM"
Papillary thyroid
Serous cyst....
Adenoma / carcinoma
Meningioma
Mesothelioma
```
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What do recurrent laryngeal nerves innervated?
Larynx: vocal cords
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What disease process can lead to Vitamin D induced HYPER Ca?
Granulomatous diseases: granulomas often have a-1-hydroxylase in them that is activating vitamin D
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What is familial HYPOcalciuric HYPERcalcemia?
- High Ca is unable to inhibit PTH
- Decreased PO4, is still able to stop PTH
- Urine Ca is low
- Serum Ca is high
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Symptoms of hyper PTH?
Usually Asymptomatic but if there are symptoms:
| "Stones, Bones, abdominal groans (constipation), psychic overtones"
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Kidneys handling of Ca / PO4 normally?
Ca resorber, P waster
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When are shortened 4/5 digit seem?
- Pseudo HYPOparathyroidism
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What does parathyroid adenoma do to PTH?
Increases
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What happens to organs in acromegaly?
Organ hypertrophy
1. Deep voice: laryngeal swelling
2. Large tongue
3. Colorectal polyps and cancer
4. Cardiac hypertrophy
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What happens in oral glucose test in acromegaly?
Normally glucose drops GH, will not happen in acromegaly
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What is pegvisomant?
GH receptor antagonist
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What is larone syndrome and what causes it?
Dwarfism caused by GH receptor malfunction
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Presentation of dwarfism?
1. Short limbs
2. Small heads (achondroplasia is large head)
3. Saddle nose
4. Micropenis
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What would labs be in dwarfism?
Elevated GH
| Decreased IGF1
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Drugs causing diabetes insipidus?
1. Lithium (also causes hypothyroid)
| 2. Demeclocycline
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Electrolyte changes in DI?
1. High ca
| 2. Low K
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Treatment for nephrogenic DI?
1. Thiazide and K sparing diuretic
| 2. NSAIDs to decrease RBF
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Most dangerous effect of hypotonic serum?
- Cerebral edema: fluid wants to move from veins to more hypertonic brain
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What happens if you correct hypotonic serum too fust?
From low to high, the pons will die: "osmotic demyelination syndrome"
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What is glucose converted to in the cells in which is causes osmotic damage?
Sorbitol
- This allows for more glucose to enter cell as [] gradient is not being changed
- Sorbitol is unable to leave cell without help of sorbitol dehydrogenase
- Sorbitol pulls water into cells leading to damage
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Why does stress / illness precipitate DKA?
- These scenarios ramp up cortisol and epinephrine which are anti insulin hormones
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When and why is kussmaul breathing seen?
DKA: deep and rapid breaths
| - Body is acidotic so trying to blow off the extra CO2
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First thing to give patient DKA?
1. Fluids / saline
2. Insulin
3. K
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What do nearly all neuroendocrine tumors respond well too?
Octreotide
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Worst side effect of glucagonoma?
Necrolytic migratory erythema
278
What would a new onset diabetes and skin rash be indicative of?
Glucagonoma
279
Sequelae of insulinoma?
- Brain runs out of energy and shuts down leading to lethargy, coma, and death
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What is carcinoid tumor?
- Neuroendocrine GI tract tumor secreting serotonin
| - Only shows signs if in liver as liver metabolizes serotonin before it has effect if coming from stomach
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Symptoms of carcinoid tumor?
1. Asthma
2. Diarrhea
3. Flushing
4. Right heart murmurs
5. B3 deficiency that can cause pellagra: both are made from tryptophan
- So much Serotonin being made that none is left for B3
282
What is pelagra?
- Vitamin B3 deficiency that can be caused by carcinoid tumor presenting with:
1. Diarrhea
2. Dementia
3. Dermatitis
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What to think if you see jejunal ulcers?
ZE syndrome as peptic ulcers usually dont make it this far down the stomach
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Diagnosis of ZE syndrome?
Secretin test: normally this should decrease gastrin, but in ZE for some reason it increases
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What happens in patient on BB who gets HYPOglycemia?
- Normal symptoms of HYPOglycemia are beta mediated hyper arousal, however BBs block these so they can pass out or get altered mental status as immediately
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What occurs in M1?
3 Ps
1. Pituitary tumors
2. Parathyroid tumors
3. Pancreas tumors
* Mutation in MEN bene
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What occurs in MEN2A?
2Ms, 2Ps
1. Marfanoid habitus
2. Medullary thyroid carcinoma
3. PTH tumors
4. Pheochromocytoma
* RET gene mutation
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What occurs in MEN2B?
3Ms, 1Ps
1. Marfanoid habitus
2. Medullary thyroid carcinoma
3. Mucosal neuromas
4. Pheochromocytoma
* RET gene mutation
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How would addison's disease impact a diabetic?
In addison's, the adrenal is not producing cortisol which usually is insulin resistant. Since there is less cortisol in addison's, this resistance is decreased leading to a lower required insulin load.
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Injury to what causes chronic central DI?
- HYPOTHALAMIC nuclei: do not pick posterior pituitary as the hormones are made in hypo
- If damage is done to pituitary the axons will eventually regenerate allowing ADH secretion to resume
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Signs of hyper Ca?
1. Muscle weakness
2. Constipation
3. Mental status change
4. Impaired urine [ ]
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Treatment of CAH?
Low doses of corticosteroids to suppress the excess ACTH that is being secreted in its absence
293
What is proptosis?
Protrusion of the eyes
294
What medicine can cause syndrome looking like cushings?
HAART
295
Why would low levels of FSH lead to decreased spermatogenesis?
FSH is necessary to made androgen binding protein which keeps levels high in the testitcles and is necessary for sperm developent. If there are issues with FSH androgens will not be high enough for the development
296
Impact of sex hormones on growth places?
Initially encourage growth but will close plates during puberty
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How do OCPs treat hirsutism?
The provide inhibition of LH which decreases androgen as well as increase SHBG which decreases free testosterone
