Endocrinology Flashcards
(162 cards)
1
Q
Where does the thyroid diverticulum arise from?
A
The floor of primitive pharynx and descents into the neck
connected to the tongue by thyroglossal duct which normally disappears.
2
Q
pt presents with a anterior midline neck mass that moves with swallowing and protrusion of the tongue.
A
thyroglossal duct that persists as cysts or the pyramidal lobe of the thyroid
3
Q
What is the most common ectopic thyroid tissue site?
A
tongue (lingual thyroid)
removal can result in hypothyroidism if its the only thyroid tissue present
4
Q
What is the normal remnant of the thyroglossal duct?
A
foramen cecum
5
Q
Follicular cells are derived from? Parafollicular cells like C cells that product calcitonin are derived from?
A
1) endoderm
2) neural crest
6
Q
Adrenal cortex is derived from? medulla?
A
1) mesoderm
2) neural crest
7
Q
Layers of the adrenal cortex?
A
Zona Glomerulosa –> Zona Fasciculata –> Zona Reticularis
8
Q
Layers of the adrenal cortex and what they produce? How are they regulated?
A
think GFR, the deeper you go the sweeter it gets
G-glomerulosa –> salt (mineralocorticoids) –> aldosterone regulated by angiotensin II
F-Fasciculata –> sugar (glucocorticoids) –> cortisol regulated by ACTH,CRH
R-Reticularis –> Sex (androgens) –> DHEA regulated by
ACTH, CRH
9
Q
What are the cells of the medulla (core of adrenal cortex) made of? What do they make? How is it regulated?
A
medulla is made of chromaffin cells which make catecholamines like epinephrine and NE. Regulated by preganglionic sympathetic fibers
10
Q
What is the anterior pit (adenohypophysis) derived from? What is the posterior pit (neurohypophysis) derived from?
A
- oral ectoderm (Rathke pouch)
- neuroectoderm
11
Q
What does the anterior pituitary secrete?
A
FASH,LH,ACTH, TSH,prolactin, GH, beta endorphin, melanotropin (MSH is from intermediate lobe of pit)
alpha subunit - hormone subunit common to TSH,LH,FSH,hCG
Beta subunit-determines hormone specificity
12
Q
Pit hormones that are acidophils? Basophils?
A
B-FLAT : basophils are FSH,LH, ACTH, TH
acidophils are GH and PRL
13
Q
What does the posterior pituitary do?
A
Hypothalamus makes vasopressin (ADH/antidiuretic hormone) and oxytocin via the supraoptic and paraventricular nuclei –> transported via neurophysins carrier proteins –>the posterior pituitary stores and releases
14
Q
Islets of langerhans arise from? cells in them? what they produce?
A
Islet of langerhans arise from pancreatic buds
They have alpha, beta, and delta cells
alpha - glucagon (peripheral)
beta-insulin (Central)
delta - somatostatin (interspersed)
15
Q
Insulin synthesis
A
1) preproinsulin is made by RER
2) Cleavage of presignal form proinsulin which is stored in secretory granules
3) cleavage of prosinulin
4) exocytosis of insulin and c peptide equally
note: insulin receptors have tyrosine kinase activity
note: insulin cannot pass the placenta
16
Q
Pt with an insulinoma or sulfonylurea use will have ____ c peptide and ____ insulin levels
A
increased both
17
Q
Pt taking exogenous insulin will have ____ c peptide and ____ insulin levels
A
increased insulin
low c peptide because exogenous insulin lacks c peptide
18
Q
GLUT4
A
adipose tissues and striated muscles
insulin dependent
19
Q
GLUT1
A
insulin independent transporter
RBCs, brain, cornea, placenta
20
Q
GLUT2
A
insulin independent transporter
transports glucose, fructose, galactose to blood
bidirectional, beta islet cells, liver, kidney, small intestine
21
Q
GLUT3
A
insulin independent transporter
brain placenta
22
Q
GLUT5
A
insulin independent transporter
fructose is taken up by fascillitated diffusion
spermatocytes, GI tract
23
Q
SGLT1/SGLT2
A
insulin independent transporter for glucose and galactose
Na-glucose cotransporters in kidney and small intestine
24
Q
What does the brain use for metabolism when in starvation mode?
A
normally it is glucose but during starvation it is ketone bodies
note: RBCs cant use ketone bodies because lack mitochondria for aerobic metabolism
25
How does glucose cause in increase in insulin response?
via incretins like glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP)
they are released after meals and increase beta cell sensitivity to glucose
Release is decreased by alpha2 and increased by beta 2
26
How does glucose result in increased insulin RELEASE?
1) glucose enters beta cells
2) glucose used to make ATP
3) increased ATP closes K channels
4) Results in depolarized beta cell membrane
5) voltage gated Ca channels open
6) Calcium influx
7) stimulation of insulin exocytosis
27
Glucagon
released in response to hypoglycemia due to alpha cells
inhibited by insulin, hyperglycemia, somatostatin
28
What hormone increases water permeability of distal convoluted tubule and collecting duct cells in kidney in response to increased plasma osmolality? What is the exception?
ADH
exception: SIADH (Syndrome of inappropriate antidiuretic hormone secretion) where ADH is inappropriately elevated despite decrease plasma osmolality
29
Corticotropin-releasing hormone (CRH)
increases ACTH, MSH, beta endorphin
CRH decreases in exogenous steroid use
30
Dopamine function
function to decrease prolactin and TSH
inhibits prolactin via the tuberoinfundibular pathway of the hypothalamus. (prolactin inhibits its own secretion by increasing dopamine from hypothalamus)
dopamine antagonists can cause galactorrhea due to hyperprolactinemia
31
GHRH (growth hormone releasing hormone)
Increases GH
32
GnRH (Gonadotropin-releasing hormone)
Increases FSH and LH
33
MSH (Melanocyte-stimulating hormone)
Increases melanogenesis by melanocytes
34
Why do cushings patients also suffer from hyperpigmentation?
Due to MSH which shares the same precursor molecule as ACTH - proopiomelanocortin
35
What hormone is important for the suckling reflex and uterine contractions?
Oxytocin
36
Prolactin
Causes a drop in GnRH which is important for FSH and LH synthesis.
stimulates milk production
inhibits ovulation and spermatogenesis
Decreased libido
37
The analog of what hormone is used to treat acromegaly?
Somatostatin because it decreases GH and TSH
"somatostatin keeps your growth STATIC"
38
Thyrotropin-releasing hormone (TRH)
Increase TSH and prolactin
excess will cause increased prolactin which will result in galactorrhea
39
Pt presents with amenorrhea, osteoporosis, hypogonadism, galactorrhea, decreased libido. Patient has low GnRH levels, FSH, an LH. What is causing these labs and symptoms?
Pituitary prolactinoma
can treat with a dopamine agonist
40
What is estrogens effect on prolactin?
stimulates prolactin release
41
What hormone stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secreted by the liver?
Growth hormone (somatotropin)
"somatoMEDIN MEDIATES your growth"
42
How does GH impact diabetes?
Secretion increase during hypoglycemia. Secretion inhibited by glucose and somatostatin.
Increases insulin resistance therefore it is diabetogenic
43
What hormone has an orexigenic effect? What is its impact on GH?
Ghrelin increases GH release (makes you hungry and grow)
Increases with sleep deprivation and prader willi syndrome
44
What hormone is important for Satiety? where is it produced?
Leptin "leptin keeps you thin" produced by adipose tissue
Decrease with sleep deprivation
Mutation causes congenital obesity
45
Leptin acts on the _______ area of the _____ to decrease appetite?
Acts via the ventromedial area of hypothalamus to decrease appetite
46
Ghrelin acts on the _____ area of the ______ to increase hunger
Acts via the lateral are of hypothalamus to increase appetite
47
Endocannabinoids act on the _____ in the ________ and ___________, two key brain areas for the homeostatic and hedonic control of food intake. Increases appetite
cannabinoid receptors in the hypothalamus and nucleus accumbens
exogenous cannabinoids cause the munchies
48
Where is ADH/Vasopressin synthesized?
hypothalamus at supraoptic and paraventricular nuclei then stored and secreted by the posterior pituitary. Ultimately increases aquaporin channel insertion in principal cells of renal collecting duct
regulates serum osmolality with V2 receptors and blood pressure with V1 receptors
49
What are ADH levels in central DI? nephrogenic DI?
central it is low (give analog Desmopressin)
| nephrogenic it is normal or hgh but mutation in V2 receptor
50
17 alpha hydroxylase pathway and deficiency
Important in using pregnenolone and progesterone (in zona glomerulosa) to form 17 hydroxypregnenolone and progesterone (zona fasiculata). 17 alpha hydroxylase further takes these and forms DHEA and androstenedione, respectively. These are important for testosterone synthesis.
Because it cant make testoterone. The pathway is shunted within the zona glomerulosa to form more aldosterone.
results: Increased mineralocorticoids, increase BP, decreased sex hormones, decreased K, decreased androstenedione
51
17 alpha hydroxylase in men vs women
In men: ambiguous genitalia, undescended testes
| women: lacks secondary sexual development
52
21- hydroxylase pathway and deficiency
important for taking progesterone in zona glomerulosa to form 11-deoxycorticosterone --> --> aldosterone
Also important for taking 17 hydroxyprogesterone in the zona fasiculata to form 11 deoxycortisol --> cortisone
Deficiency prevents formation of aldosterone and cortisone. Shunted down the 17 alpha hydroxylase pathway to make testosterone.
results: decreased mineralocorticoids, cortisol, BP. Increased sex hormones, K+, renin activity
53
21 hydroxylase deficiency presentation
presents in infancy as salt wasting or childhood as precocious puberty
girls are virilized
most common deficiency
54
11 beta hydroxylase pathway and deficiency
similar to 21 hydroxylase deficiency, blocks the pathways to form aldosterone and cortisone. Difference is that there is still accumulation of 11-deoxycorticosterone in zona glomerulosa. This causes rise in BP eventhough aldosterone is low. Rest shunted towards testosterone pathway
results: low aldosterone, high 11 deoxy, low cortisol, low K+, low renin activity,increased sex hormones, increased BP
55
11 beta hydroxylase deficiency presentation
XX: virilization
56
11 beta hydroxylase
21 hydroxylase
17 alpha hydroxylase
memory tool
if starts with a 1: hypertension
if ends with a 1: virilization
note: any congentital adrenal enzyme deficiency are characterized by skin hyperpigmentation due to increased MSH production which is coproduced with ACTH
57
Why do exogenous corticosteroids cause the reactivation of TB and candidiasis?
blocks IL2 production
58
Cortisol effects on appetite? BP? insuline resistance? glucose utilization? fibroblast activity? inflammatory an immune response? bone?
- increases appetite
- Increases BP via upregulation of alpha 1 receptors and at high concentrations also mineralocorticoid (aldosterone) receptors
- increases insulin resistance
- increases gluconeogenesis, lipolysis, and proteolysis (decreased glucose utilization)
- decreased fibroblast activity causes poor wound healing
- decreased inflammatory and immune responses
- decreased bone formation
59
Effect of pH on calcium homeostasis
increase in pH will increase albumins affinity for Ca which results in hypocalcemia
60
What is the primary regulatory of PTH?
ionized/free Ca
NOT albumin bound
61
PTH pathway
PTH secreted by the chief cells of the four parathyroid glands where they go to the renal tubular cells and have the follow effects:
1) renal effects
Increases 1,25 (OH)2D3 synthesis
Increases reabsorption of Ca and decreases PO4
Urine is low Ca high PO4
2) Bone
(low PO4 and) PTH + stimulate 1alpha hydroxylase to convert 25 OH D3 to 1,25 OH2 D3 --> Increases Ca and PO4 release from bones
3) Intestine
(Low PO4 and) PTH + stimulate 1alpha hydroxylase to convert 25 OH D3 to 1,25 OH2 D3 --> increased absorption of Ca and PO4
OVERALL: increase serum Ca and decrease serum PO4
62
How does PTH cause increase bone resporption?
it increases RANK-L secreted by osteoblasts and osteocytes.
Binds RANK receptor on osteoclasts
increase bone resorption
note: intermittent PTH release can also stimulate boen formation
63
Parafollicular cells (C cells) of the thyroid secrete?
Calcitonin which decreases bone resorption of Ca due to high serum Ca
opposes PTH which increases resorption
64
Source of thyroid hormones (and enzyme)
follicles of thyroid
5'-deiodinase converts T4 to T3 in peripheral tissues
this is inhibited by glucocorticoids, beta blockers, propylthiouracil (PTU)
65
Function of thyroid perioxidase
oxidation, organification, and coupling
DIT + DIT = T4
DIT + MIT = T3
note: only free thyroid hormone is active
66
Wolff chaikoff effect
excess iodine temporarily inhibits thyroid peroxidase which decreases T3 and T4
by prevent DIT + DIT = T4
MIT +DIT = T3
67
Which thyroid hormone binds nuclear receptors with greater affinity? What are its effects?
T3 binds nuclear receptors with greater affinity than T4
6 Bs?
Brain maturation, Bone growth, Beta adrenergic effects, Basal metabolic rate, Blood sugar (increase gluconeogenesis and glycogenolysis), break down lipids
68
How is T3/T4 regulated? What protein binds them?
Hypothalamus --> TRH ---> stimulate Ant. pit --> TSH --> stimulate thyroid follicular cells --> T3/T4
bound by thyroxine-binding globulin (TBG)
69
Sex hormone-binding globulin
in men : can get gynecomastia if increases SHBG because there will be less free active testosterone
In women: can get hirsutism because decrease in SHBG raises free testosterone
OCP and pregnancy cause an increase in SHBG
70
What three things can cause the increase in cortisol thats seen in cushing syndrome?
1) exogenous corticosteroids --> drop in ACTH --> adrenal atrophy
2) primary adrenal adenoma, hyperplasia, or carcinoma --> drop in ACTH --> adrenal atrophy
3) MOST COMMON: Cushings DISEASE or ACTH-secreting pituitary adenoma
71
Characteristic findings in cushings?
- Moon facies
- abdominal striae
- truncal obesity
- buffalo hump
- can have pseudohyperaldosteronism
other: HTN, hirsutismm, osteoporosis, hyperglycemia, amenorrhea, immunosuppression
72
How do you screen for Cushings syndrome?
Increase free cortisol on 24 hr analysis
increase midnight salivary cortisol
no suppression with overnight low dose dexamethasone test
Cushings syndrome!
Then measure ACTH: if low then suspect arenal tumor or exogenous glucocorticoids. If high then think ACTH dependent cushings syndrome
If adequate suppression on high dose dexamethasone test or increase ACTH and cortisol on CRH stimulation test--> cushings
If no suppression and no increase in ACTH and cortisol then ---> ectopic ACTH secretion
73
Patient presents with high ACTH and low cortisol?
primary adrenal insufficiency - loss of gland function causes deficiency in cortisol and aldosterone
classic triad: Hypotension due to hyponatremia, hyperkalemia, metabolis acidosis
skin pigmentation due to MSH production as ACTH is produced (same precursor of proopiomelanocortin)
74
Patient presents with low ACTH and low cortisol
secondary or tertiary adrenal insufficiency
75
metyrapone stimulation test for adrenal insufficiency
metyrapone blocks last step of cortisol synthesis (11-deoxycortisol to cortisol)
normal: decrease cortisol but increase ACTH
primary: ACTH high and 11-deoxycortisol stays low
secondary/tertiary: both low
76
A type of primary adrenal insufficiency, chronic, hypotension, hyponatremia, hyperkalemia, metabolic acidosis.
Autoimmune destruction of adrenal gland
Addisons disease
A=autoimmune
77
A type of primary adrenal insufficiency, chronic, hypotension, hyponatremia, hyperkalemia, metabolic acidosis.
Adrenal hemmorrhage due to septicemia
Waterhouse friderichsen syndrome
waterhouse=hemorraging fills the house with liquid
78
Adrenal insufficiency due to drop in pituitary ACTH production that spares the skin/mucosa
secondary
no skin/mucosa
no hyperkalemia because intact renin angiotensin aldosterone axis
79
Adrenal insufficiency due to chronic exogenous steroid use that is abruptly stopped
tertiary
aldosterone synthesis unaffected
80
Triad for hyperaldosteronism
HTN
decreased or normal K
metabolic alkalosis
81
High aldosterone
Low renin
Causes resistent hypertension
does not directly cause edema
primary hyperaldosteronism due to adrenal adenoma (conn syndrome) or bilateral adrenal hyperplasia
Has aldosterone escape mechanism and therefore does not directly cause edema
82
Seen in patients with renovascular HTN
Juxtaglomerular cell tumors that produce renin
edema due to HF etc.
Secondary hyperaldosteronism
impaired aldosterone escape mechanism and therefore does cause edema
83
Pt is a 4 yo child that presents with abdominal distension and a firm irregular mass that crosses the midline. Pt is normotensive
Neuroblastoma-Most common tumor of the adrenal medulla in children
can also present with opsoclonus-myoclonus syndrome or dancing eyes dancing feet
84
This tumor originates from neural crest cells and can occur anywhere along the sympathetic chain
Neuroblastoma
associated with overexpression of n-myc gene and is classified as an APUC tumor (neuroendocrine tumor cells contain amine precursor uptake decarboxylase)
elevated HVA and VMA which are catecholamine metabolites in urine
histology: see homer wright rosettes, Bombesin and NSE +
85
This tumor of the adrenal medulla causes episodic hypertension and polycythemia
Pheochromocytoma - most common tumor of the adrenal medulla in adults and is derived from chromaffin cells (neural crest)
secretes EPI, NOREPI, Dopamine (increases catecholamines and metabolites)
86
Rule of 10 in pheochromocytoma
```
10% malignant
10% bilateral
10% extraadrenal
10% calcify
10% kids
```
87
Episodic hypertension
spells that relapse and remit
```
Pressure due to increase BP
Pain due to headache
Perspiration
Palpitations due to tachy
Pallor
```
88
Treatment for pheochromocytoma
tx: irreversible alpha antagonist followed by beta blockers prior to tumor resection. alpha antagonist prevents hypertensive crisis
Phenoxybenzamine
89
Patient presents with watery diarrhea, hypokalemia, achlorhydria (absence of hydrochloric acid in the gastric secretions)
VIPoma
secretes vasoactive intestinal peptide (VIP)
usually in pancreas and associated with MEN1
90
In what thyroid disorder do you see proximal mm weakness with increased CK and myoedema
hypothyroid myopathy
also see carpal tunnel syndrome
note :myoedema is having a small lump rise on the surface of a mm when struck with a hammer
91
In what thyroid disease do you see proximal mm wekaness with normal CK and an increased risk of osteoporosis
hyperthyroid
thyrotoxic myopathy
increased risk of fracture due to high T3 and T4
92
Which thyroid disease causes increased reflexes? which causes decreased?
hypo is decreased reflex
| hyper is increased reflex
93
In which thyroid disease do you see hypercholesterolemia due to a drop in LDL receptor expression? In which do you see a decrease in LDL, HDL, and total cholesterol?
1) hypothyroid
| 2) hyperthyroid
94
Thyroid disease with increased number and sensitivity of beta adrenergic receptors, increased expression of cardiac sarcolemmal ATPase, and decrease expression of phospholamban
hyperthyroid
95
Hashimotos thyroiditis
```
hypothyroid
antithyroid peroxidase (antimicrosomal)
antithyroglobulin antibodies
HLA DR3
Increased risk of non hodgkins lymphoma
Histo: hurthle cells, lymphoid aggregates with germinal centers
large nontender thyroid
```
96
Pregnant women present with this thyroid disorder 1 year after delivery
postpartum thyroiditis
transient
97
Baby is pot bellied, pale, ouffy faced, protruding umbilicus, protuberant tongue, poor brain development
Congential hypothyroidism (cretinism)
severe fetal hypothyroid due to antibody mediated maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis (most common in us), iodine deficiency, dyshormonogenetic goiter
98
pt was sick with the flu and now presents with jaw pain and severely tender thyroid
subacute granulomatous thyroiditis aka de quervain "pain"
self limiting
histology shows granulomatous inflammation
high ESR
99
Patient prevents with a fixed hard rock like painless goiter
Riedel thyroiditis
thyroid is replaced by fibrous tissue with inflammatory infiltrate. fibrosis extends to local tissues and resembles anaplastic carcinoma.
IgG4 related systemic dz
100
wolf chaikoff effect
thyroid gland downregulation in response to increased iodide
101
Graves disease pathway
thyroid stimulating immunoglobulin (IgG type II hypersensitivity) stimulates TSH receptors on thyroid and dermal fibroblasts (pretibial myxedema)
HLA DR3 and HLA B8
histology: tall crowded follicular epithelial cells, scalloped colloid
102
Graves disease - exophthalmos disease pathway
Infiltration of retroorbital space by activated T cells causes an increase in cytokines (TNF alpha and IFN gamma etc.) which increase fibroblast secretion of hydrophilic GAGs and increase osmotic swelling, mm inflammation, and adipocyte count
103
What causes lid lag in graves disease
increased sympathetic stimulation of the levator palpebrae superioris
104
Toxic multinodular goiter
focal patches of hyperfunctioning follicular cells distended with colloid and working independently of TSH
hot nodules are rarely malignant
105
Patient presents with agitation, delirium, fever, diarrhea, coma, tachyarrhythmia post thyroid surgery. how do you tx this patient?
thyroid storm. tachyarrhythmias are the main cause of death
tx with a beta blocker, propylthiouracil, corticosteroids, potassium iodide
106
Jod-Basedow phenomenon
thyrotoxicosis
iodine deficient and partially autonomous thyroid tissue is suddenly made iodine replete
can happen after iodine iv contrast
opposite of wolf chaikoff effect
think "job well done"
107
Causes of smooth goiter/diffuse
graves disease
hashimoto thyroiditis
iodine deficiency
TSH-secreting pituitary adenoma
108
Thyroid adenoma
nonfunctional/cold
mostly follicular
absence of capsular or vascular invasion
109
Thyroid cancer complications: hoarseness
recurrent laryngeal nerve damage
110
Thyroid cancer complications: dysphagia and dysphonia
transection of recurrent and superior laryngeal nerves during ligation of inferior thyroid artery and superior laryngeal artery
111
Papillary carcinoma
Most common thyroid cancer
Orphan annie eyes
psammoma bodies
RET/PTC rearrangements and BRAF mutations or childhood irradiation
112
Follicular carcinoma
invades thyroid capsule and vasculature
uniform follicles
hematogenous spread is common
RAS mutation and PAX8-PPARgamma
113
Medullary carcinoma
parafollicular c cells
produce calcitonin
sheets of cells in an amyloid stroma (congo red stain)
MEN2A and 2B (RET mutations)
114
undifferentiated/anaplastic carcinoma
older patients
invades local structures
very poor prognosis
115
Hypoparathyroidism lab findings?
Low Ca
high PO4
tetany
116
Sign that involves tapping of facial nerve (tap the cheek) that causes contraction of facial mm
Chvostek sign for hypoparathyroidism
Ch=Cheek
117
Sign that involves the occlusion of brachial artery with BP cuff (cuff the triceps) --> carpal spasm
Trousseau sign for hypoparathyroidism
T=Triceps
118
Pseudohypoparathyroidism type 1A
unresponsiveness of kidney to PTH. Defective Gs protein alpha subunit causing end organ resistance to PTH
albright hereditary osteodystrophy - shortened 4th/5th digits, short stature, obesity, developmental delay
aut. dominant - defect inherited from MOTHER
119
Pseudopseudohypoparathyroidism
features of albright hereditary osteodystrophy
no end organ PTH resistance (PTH level normal)
defective Gs protein alpha subunit is inherited from FATHER
120
Primary hyperparathyroidism
Parathyroid adenoma or hyperplasia
Hypercalcemia, hypercalciuria (renal stones), polyuria (thrones), hypophosphatemia, increased PTH, increased ALP, increase cAMP in urine
pt has constipation, neuropsychiatric disturbances
classically you see osteitis fibrosa cystica
121
cystic bone spaces filled with brown fibrous tissue (brown tumor) consisting of osteoclasts and deposited hemosiderin for hemorrhages, causes bone pain
osteitis fibrosa cystica
classically seen in primary hyperparathyroidism
122
Secondary hyperparathyroidism
decreased calcium absorption and or increase PO4
chronic renal disease (low vit D and high PO4 --> low Ca)
hypocalcemia, hyperphosphatemia (chronic renal failure), increase ALP, increase PTH
123
_________ is renal disease in secondary and tertiary hyperparathyroidism that leads to bone lesions
Renal osteodystophy
124
Tertiary hyperparathyroidism
Refractory (autonomous)hyperparathyroidism resulting from chronic renal disease
increase in PTH and increase in Ca
Renal osteodystrophy
125
Familial hypocalciuric hypercalcemia
defective G coupled Ca sensing receptors that are less sensitive to Ca levels
more Ca is requried to suppress PTH
therefore there is excessive renal Ca reuptake --> mild hypercalcemia and hypocalciuria with normal to high PTH levels
126
Patient had a bilateral adrenalectomy and now suffers from hyperpigmentation, headaches, and bitemporal hemianopia (blindness over half of vision)
Nelsons syndrome- enlargement of existing ACTH secreting pit adenoma after bilateral adrenalectomy for refractory cushing disease. This is due to removal of cortisol feedback
127
Excess GH in adults due to a pituitary adenoma can cause __? in Children? how is it diagnosed? how to tx?
Acromegaly in adults
Gigantism in children
HF is most common cause of death
dx: increased serum IGF-1, failure to suppress serum GH following oral glucose tolerance test, pituitary mass seen on brain MRI
tx: pit adenoma resection. If not cured then give octreotide (somatostatin analog) or pegvisomany (growth hormone receptor antagonist), dopamine agonist
128
Acromegaly findings
```
large tongue
frontal bossing
coarsening of facial features with aging
insulin resistance
large hands and feet
```
129
pt presents with short height, small head circumference, saddle nose, and prominent forehead, delayed skeletal maturation, and small genitalia
Dwarfism/Laron syndrome- defective GH receptors cause a decrease in linear growth
causes a upreg of GH and down reg of IGF-1
130
Pt presents with intense thirst and polyuria with inability to concentrate urine
Diabetes insipidus
lack of ADH (Central) or failure of response to circulating ADH (nephrogenic)
131
Low ADH levels with increased urine osmolality only after administration of ADH analog (desmopressin)
Central Diabetes insipidus
ADH analog only given if serum osm between 295-300, plasma Na >= 145, or urine osm does not rise despire a rising plasma osm
132
Normal or high ADH levels with minimal change in urine osmolality even after adminisration of ADH analog
Nephrogenic DI
133
Syndrome of inappropriate ADH secretion
- excessive free water retention
- euvolemic hyponatremia with continued urinary Na excretion
- urine osm >serum osm
very low Na levels can lead to cerebral edema and seizures. Correct slowly to prevent osmotic demyelination syndrome
134
First line treatment for syndrome of inappripriate ADH secretion?
fluid restriction
135
What causes the euvolemic hyponatremia seen in syndrome of inappropriate ADH secretion?
Body responds to water retention with decreased aldosterone and increased ANP and BNP
this results in increased urinary Na secretion --> normalization of extracellular fluid volume
136
Pt suffered from significant postpartum bleeding and now has failure to lactate, absent menstruation, and cold intolerance. What syndrome are we worried about?
Sheehan syndrome-ischemic infarct of pituitary following postpartum bleeding
postpartum pituitary gland necrosis
"she hamaraged"
137
Empty sella syndrome
atrophy or compression of pituitary which lies in the sella turcica
common in obese women
idiopathic intracranial HTN
138
Pt presents with a sudden onset severe headache, visual impairment (bitemporal hemianopia, diplopia due to CN III plasy), and features of hypopituitarism
pituitary apoplexy
sudden pit hemorrhage often in presence of existing adenoma
139
Examples of small vessel diseases seen in DM?
retinopathy, glaucome, neuropathy, nephropathy (ACEi are renoprotective, arteriolosclerosis --> HTN
nephropathy: nodular glomerulosclerosis aka Kimmelstiel Wilson nodules which result initially in microalbuminuria and then progressive proteinuria
140
What is the most common cause of death in a diabetic patient?
MI
141
Osmotic damage in DM?
sorbitol accumulation in organs with aldose reductase and decrease or absent sorbitol dehydrogenase
results in neuropathy and cataracts
142
Diagnostic cut offs for DM?
HbA1c?
Fasting plasma glucose?
2 hr oral glucose tolerance test?
>= 6.5%
>= 126
>=200
143
Type 1 diabetes characteristics
autoimmune destruction of beta cells
- weak genetic predisposition
- HLADR4 and HLADR3 (4-3=1)
- Severe glucose intolerance
- Insulin sensitivity high
- Keto acidosis common
- histology shows islet leukocytic infiltrate
144
Type 2 diabetes characteristics
Hyperosmolar hyperglycemic state
Increased resistance to insulin, progressive pancreatic beta cell failure
Strong genetic predisposition
Low insulin sensitivity
histology shows islet amyloid polypeptide (IAPP) deposits
145
Diabetic ketoacidosis is usually due to
insulin noncompliance or increased insulin requirement form stress in a pt with type I DM
ketone bodies: beta-hydroxybutyrate > acetoacetate
146
DKA symptoms and tx
```
Delirium/psychosis
Kussmall respirations (rapid deep breathing)
ab pain nausea and vomiting
dehydration
fruity breathe due to exhaled acetone
```
tx: IV fluid, IV insulin, K+ to replenish intracellular stores, glucose to prevent hypoglycemia
147
DKA labs
High H+
Low bicarb (increase anion gap metabolic acidosis)
leukocytosis
hyperkalemia (intracellular depleted)
osmotic diuresis results in increased K in urine and thus total body K+ depletion
148
Complications of DKA
life threatening mucormycosis (rhizopus infection)
cerebral edema
cardiac arrhythmias
HF
149
Hyperosmolar hyperglycemic state
state of profound hyperglycemia induced dehydration and increased serum osmolality
labs: hyperglycemia >600,serum osm >320,no acidosis,
150
tumor of pancreatic alpha cell that causes hyperglycemia
glucagonoma
overproduced glucagon --> increase glycogen breakdown into glucose
dermatitis- necrolytic migratory erythema
diabetes
DVT
151
tumor of pancreatic beta cells that cause hypoglycemia
Insulinoma
whipple triad: low blood glucose, sx of hypoglycemia, resolution of sx after normalization of glucose levels
10% associated with MEN1 syndrome
152
Tumor of pancreatic delta cells that cause diabetes/glucose intolerance, steatorrhea, gallstones, achlorhydria
somatostatinoma
increase somatostatin causes a drop in secretin, CCK, glucagon, insulin, gastrin, GIP
153
Carcinoid syndrome
syndrome caused by carcinoid tumor (neuroendocrine cells) which secrete high levels of serotonin (5HT).
use neuroendocrine tumor markers chromagranin A and synaptophysin
not seen if tumor is limited to GI tract because 5HT undergoes first pass metabolism in the lvier
154
Rule of 1/3 for carcinoid syndrome
1/3 metastasize
1/3 present with second malignancy
1/3 are multiple
155
what is the most common malignancy in the small intestine?
carcinoid tumours
156
pt presents with recurrent diarrhea, cutaneous flushing, ashtmatic wheezing, right sided valvular heart disease
carcinoid syndrome
R sided valvular disease is due to lung MAO-A enzymatic breakdown of 5HT before left heart return
increase in 5 hydroxyindoleactic acid (5-HIAA) in urine
niacin deficiency --> pellagra
157
Zollinger-Ellison syndrome
Gastrin secreting tumor (gastrinoma) of pancreas or duodenum
acid hypersecretion causes recurrent ulcers in duodenum and jejunum
positive secretin stimulation test : gastrin levels remain elevated after administration of secretin, which normally inhibits gastrin release
158
MEN syndromes
multiple endocrine neoplasias
all are autosomal dominant
MEN are DOMINANT
159
MEN1
3 Ps
pituitary tumors
pancreatic tumors
parathryoid adenoma
mutation in MEN1 (menin, a tumor suppressor, chromosome 11)
160
MEN2
2 Ps
Parathyroid hyperplasia
Medullary thyroid carcinoma
Pheochromocytoma
mutation in RET (codes for tyrosine kinase receptor) in cells of neural crest origin
161
MEN3
1 Ps
Medullary thyroid carcinoma
Pheochomocytoma
mucosal neuromas
associated with marfanoid habitus. mutation in RET gene
162
Medullary thyroid cancer
parafollicular calcitonin secreting c cells
