Endocrine Flashcards
(159 cards)
1
Q
cAMP hormones
A
FSH, LH, ACTH, TSH (all ant. pit) FLAT
and also hcG
MSH
GHRH
CRH
PTH
Calcitonin
Glucagon
V2 vasopressin receptor
2
Q
Gq Inositol triphosphate (IP3) pathway
A
hypothalamic hormones
GnRH
TRH- thyrotropin releasing hormone
post pit:
Oxytocin
Vasopressin at the V1 receptor
3
Q
Tyrosine kinase receptor
A
growth factors growth hormone (GH) prolactin insulin insulin-like growth factor (IGF1) platelet- derived growth factor (PDGF) fibroblast growth factor (FGF) cytokines
4
Q
cGMP
A
nitric oxide (NO) antrial natriuretic peptide (ANP)
these both act to vasodilate
5
Q
steroid receptors
A
estrogens, progesterones, testosterone glucocorticoids aldosterone thyroid hormone vitamin D
- intracellular
- gene transcription
these receptors are found intracellularly. When bound, the receptor undergoes coformational change whereby DNA- binding domain is exposed. This leads to binding of a gene enhancer region
6
Q
stimulates bone and muscle growth
A
growth hormone via insulin like growth factor (IGF1), which stimulates TKR
7
Q
stimulates milk production
A
prolactin
8
Q
stimulates milk secretion during lactation
A
oxytocin
9
Q
responsible for female secondary sex characteristics
A
estradiol
10
Q
stimulates metabolic activity
A
T4, T3
11
Q
increases blood glucose level and decreases protein synthesis
A
glucacorticoids
12
Q
responsible for male secondary sex characteristics
A
testosterone
13
Q
prepares endometrium for implantation/ maintenance of pregnancy
A
progesterone
14
Q
stimulates adrenal cortex to synthesize and secrete cortisol
A
ACTH- adrenocorticotropic hormone
15
Q
stimulates follicle maturation in females and spermatogenesis in males
A
follicle stimulating hormone
16
Q
increases plasma calcium, increases bone resorption
A
parathyroid hormone
17
Q
decreases plasma calcium, increases bone formation
A
calcitonin
18
Q
stimulates ovulation in females and testosterone synthesis in males
A
luteinizing hormone
19
Q
stimulates the thyroid to produce TH and uptake iodine
A
thyroid stimulating hormone
20
Q
where does growth hormone come from?
A
anterior pituitary
21
Q
where does thyroid hormone come from?
A
thyroid
22
Q
glucocorticoids
A
adrenal cortex (zona fasciculata)
23
Q
progesterone
A
ovaries, and placenta if there is one
24
Q
prolactin
A
anterior pituitary
25
oxytocin
hypothalamus (paraventricular nucleus)
26
atrial natriuretic hormone
atria of the heart
27
glucagon
alpha cells of the pancreas
28
testosterone
testes (men) ovaries (women), and in a small amount, in the zona reticularis of the adrenal cortex
29
vasopressin (ADH)
posterior pituitary for storage, ,made in the hypothalamus (supraoptic nucleus)
30
calcitonin
parafollicular cells of the thyroid
31
thyroid stimulating hormone (TSH)
anterior pituitary
32
epinephrine and norepinephrine
chromaffin cells of the adrenal medulla
33
insulin
beta cells of the pancreas
34
estradiol
ovaries
35
estriol
placenta
36
estrone
fat cells
37
estrogen in males
testes
38
PTH
parathyroid glands
39
somatostatin
delta cells of pancreas
40
luteinizing hormone (LH)
anterior pituitary
41
mineralocorticoids (aldosterone)
zona glomerulosa
42
adrenocorticotropic hormone (ACTH)
anterior pituitary
43
androgen binding protein
binds testosterone
44
embryological origins of anterior pituitary
Rathke's pouch (ectodermal diverticulum)
45
embryological origins of posterior pituitary
invagination of hypothalamus (neuroectoderm)
46
2 proteins produced in the hypothalamus and stored in the posterior pituitary
oxytocin, ADH
47
ADH
antidiuresis by increasing water reuptake in the DCT of the kidney
more ADH for concentrate urine in small amounts
ADH promotes vascular constriction
this is why and how vasopressin can be used to stimulate an increase in BP
48
how do nicotine and opiates affect ADH levels?
increase (less urine)
49
how do decreased serum osmolarity, ethanol and atrial natriuretic factor affect ADH?
They decrease ADH, promoting diuresis
50
oxytocin
pregnancy breastfeeding hormone
causes uterine contractions, important for delivering baby as well as for stopping bleeding afterwards.
oxytocin release is stimulated by uterine dilation during labor
stimulates milk ejection from the breast, upon suckling
this is inhibited by alcohol and stress
51
anterior pituitary hormones
stimulated by upstream hormones, and have downstream targets at various glands. middle men
pulsatile release of GnRH-->
pulsatile release of FSH --> gonads
constant GnRH inhibits LH and FSH release
```
GnRH--> LH --> gonads
ACTH
TSH
Prolactin
Intermediate- MSH
GH
```
52
inhibin
inhibits FSH
53
progesterone and testosterone affects on LH
inhibition
54
four hormones that share a common alpha subunit
LH, FSH, TSH, hCG
55
ACTH
stimulated by CRH from the hypothalamus, and stress
ACTH induces cortisol production at the adrenal gland, which has a negative feedback effect on ACTH
56
MSH
anterior pituitary, stimulates melanocytes of skin
57
ACTH, MSH, and proopiomelanocortin (PMC)
ACTH is synthesized as part of a large precursor called POMC.
POMC contains sequences for other hormonal peptides including lipotropin, MSH, beta-endorphin
When ACTH is in excess, it stimulates MSH receptors, leading to hyperpigmentation in for example, Addison disease
58
TSH
stimulated by thyroid releasing hormone from the hypothalamus
it in turn, stimulates thyroid hormone production and secretion from the downstream thyroid gland
T3 and T4 will directly inhibit TSH secretion
59
Growth hormone (somatotropin)
helps grow, decreases glucose uptake, increases protein synthesis, increases organ size and lean body mass
increased by growth hormone releasing hormone (GHRH)
and inhibited by growth hormone inhibiting hormone (GHIH), aka somatostatin
downstream hormone (rather than gland) is IGF1, or insulin growth factor 1, which stimulates growth in peripheral tissues
60
things that stimulate growth hormone release
GHRH, exercise, sleepp, puberty, hypoglycemia, estrogen, stress, endogenous opioids
61
things that inhibit growth hormone release
```
somatostatin
somatomedins
obesity
pregnancy
hyperglycemia
```
62
prolactin functions
```
stimulates breast development
inhibits ovulation (inhibits GnRH, which inhibits release of FSH, LH, and thereby decreases the likeliihood of pregnancy while breast feeding)
```
63
what hormone stimulates prolactin release?
thyrotropin releasing hormone
64
what inhibits prolactin release
DA, which comes from the hypothalamus and is a constant tonic inhibitor of prolactin
65
hyperprolactinemia- causes
pregnancy/ nipple stimulation
stress (physical or psychological)
prolactinoma (associated with bitemporal hemianopia)
dopamine antagonists- antipsychotics (haloperidol, risperidone), domperidone, metoclopramide
66
hyperprolactinemia- symptoms in premenopausal females
hypogonadism
infertility, oligo/amenorrhea, rarely, galactorrhea
postmenopausal females may not have symptoms since they are already hypogonadal
67
symptoms of hyperprolactinemia in males
hypogonadism (low testosterone), decreased libido, impotence, infertility (low sparm counts), gynecomastia, rarely glactorrhea
68
pituitary adenoma
amenorrhea, galactorrhea, low libido, infertility, bitemporal hemianopia
Treat with bromocriptine or cabergoline, which are dopamine agonists
surgical resection if symptoms are severe
69
Acromegaly
large tongue with deep furrows and indentations, increased spacing of teeth, deep voice, large hands and feet, coarse facial features (nose, ears), impaired glucose tolerance (opposite from insulin in some ways)
70
Gigantism
excess bone growth of linear bones, tall/big children
excess growth hormone
71
how to diagnose acromegaly/ gigantism
diagnose by checking IGF1, which is a stable downstream protein. Growth hormone itself is pulsatile, so depending on when you check it you will get different levels (highest at night)
confirm with oral glucose tolerance test (check GH after glucose intake) because insulin usually suppresses growth hormone, but this is not the case in acromegaly
72
hot to treat acromegaly/gigantism
surgical resection/ octreotide
73
somatostatin
produced in several places in the body:
D cells in the GI mucosa
pancreatic islet cells
nervous system
actions:
1. reduced splanchnic flow, reduces GI motility and gallbladder contractions, inhibits secretion of most GI hormones
2. decreases exocrine secretion in the pancreas, which affects digestion
3. decreases hormone secretion in the CNS, PNS, and endocrine organs
74
clinical uses for somatostatin analogs (octreotide, somatostatin LAR, lanreotide-P)
pituitary excesses: acromegaly, thyrotropininoma, ACTH- secreting tumors
GI endocrine excess: SE, carcinoid, VIPoma, glucagonoma, insulinoma
certain diarrheal diseases
need to reduce splanchnic circulation: portal hypertension (bleeding varices), bleeding peptic ulcers
75
Sheehan syndrome
postpartum hemorrhage leading to underperfusion of the pituitary
pituitary necrosis and hypopituitarism
presentation:
- agalactorrhea due to deficient prolactin
- amenorrhea after delivery
- secondary hypothyroidism leading to fatigue, cold intolerance, and weight gain
- hyponatremia (rare)
76
empty sella syndrome
asymptomatic, symptoms of pituitary hormone deficiency of one or more hormone
77
Primary hyperaldosteronism
HTN
Hypokalemia
Metabolic alkalosis due to potassium out, H in
low renin
78
Secondary hyperaldosteronism
high aldosterone secondary to high renin
possibly due to
renal artery stenosis
congestive heart failure (low LV EF leading to poor renal perfusion)
low protein states such as cirrhosis and nephrotic syndrome that lead to low intravascular volume
79
Symptoms of pheochromocytoma
```
pressure (increased BP)
pain (HA)
perspiration
palpitations (tachycardia)
pallor
```
pheo may secrete EPO --> polycythemia
80
tumors that secrete erythropoitin
pheochromocytoma
RCC
HCC
hemangioblastoma
81
treat pheo
phenoxybenzamine, non-selective irreversible alpha blocker.
Alpha blockade must be achieved before giving beta blockers to avoid a hypertensive crisis.
Just giving a beta blocker alone will make the HTN worse since epinephrine stimulates alpha receptors even when beta blockers have been blocked
alpha receptors are vasoconstrictors
follow with surgical resection
82
symptoms of Addison disease
```
hypotension
hyponatremia
hyperkalemia
weakness
malaise
anorexia
weight loss
skin hyperpigmentation
```
83
what causes Addison disease?
autoimmune destruction of adrenal glands leading to decreased production of aldosterone and cortisol
84
MEN1
```
parathyroid tumors
pituitary tumors (prolactin or GH)
pancreatic endocrine tumors- ZE, insulinomas, VIPomas, glucagonomas (Rare)
```
associated with menin tumor suppressor mutation (MEN1 gene)
85
MEN2A
parathyroid hyperplasia
pheochromocytoma
medullary thyroid cancer
associated with RET gene mutation (TKR), marfanoid habitus
86
MEN2B
pheochromocytoma
medullary thyroid carcinoma (secretes calcitonin)
oral/intestinal ganglioneuromatosis (mucosal neuromas)
associated with marfanoid habitus, mutation in RET gene
87
catecholamine metabolites in a pheo patient's plasma and urine
Plasma: metanephrine, normetanephrine
urine: VMA (vanillylmandelic acid)
88
what pancreatic cell type makes glucagon
alpha
89
what pancreatic cell type makes insulin
beta
90
what pancreatic cell type makes somatostatin
delta
91
GLUT 2 receptors are found on which cell types?
beta cells of pancrease
liver
small intestine
renal cells (kidney)
92
GLUT 4 is insulin responsive. What cell types is it found on?
adipose tissue
| skeletal muscle
93
GLUT 1 receptors are found on which cell types
brain
| RBCs
94
what kind of receptor is the insulin receptor?
tyrosine kinase
95
DM initial presentation
hyperglycemia, polyuria, polydipsia, polyphagia, weightloss
96
1DM HLA associations
HLA DR3 DQ2
| HLA DR4 DQ8
97
cell types that don't have sorbitol dehydrogenase
schwann cells
lens
retina
kidney
98
Biguanides (metformin)
```
advantages:
effective
low risk for hypoglycemia
no weight gain
low cost
few side effects
```
can be used in prediabetes to prevent progression as well as in PCOS to prevent diabetes onset
99
lactic acidosis is a rare but worrisome risk with this medication
metformin
100
MC SE is hypoglycemia
insulin
| and sulfonylureas, since these enhance beta cell function in the pancrease
101
recommended first- line treatment for most patients
metformin (2DM), insulin (1DM)
102
not sage in patients with symptoms of CHF or fluid balance problems
TZDs
103
should not be used in patients with abnormal kidney function
SGLT2 inhibitors, metformin (increased risk of lactic acidosis)
sulfonylureas (increased risk of hypoglycemia in renal failure)
104
Not associated with weight gain, may help with weight loss
metformin, DPP4, inhibitors, GLP1 analogs, SGLT inhibitors
105
metabolized by the liver, could be used in patients with renal dysfunction
TZDs
106
MOA: closes + channel on beta cells
leading to depolarization leading to calcium influx
and ultimately, insulin release
sulfonylureas, meglitinides
107
MOA: inhibits alpha- glucosidase ta intestinal brush border
alpha- glucosidase inhibitors (acarbose, miglitol)
108
MOA agonist at PPARgamma receptors leading to improved target cell response to insulin
glitazones/TZDs
109
MOA: decreases hepatic gluconeogenesis
metformin, and also to a lesser extent TZDs
110
MOA: decreases glucose reabsorption at renal tubules
SGLT-2 inhibitors
111
possible non-insulin treatment for patients with organ failure (renal, liver, heart)
DPP4 inhibitors
112
Hypocalcemia causes
```
hypoparathyroidism (parathyroidectomy 2/2 thyroidectomy)
autoimmune destruction of parathyroids
pseudohypoparathyroidism (kidneys unresponsive to PTH due to mutated PTH receptor- Albright hereditary dystrophy)
DiGeorge syndrome (branchial apparatus)
```
Albright:
short stature, obesity, shortened 4th and 5th digits
Osteitis fibrosis cystica
Vitamin D deficiency
nutritional deficiency, paucity of sunlight
chronic renal failure
Acute pancreatitis
calcium precipitates out of the abdomen and forms soaps
113
Chvostek sign
tap the cheek (facial nerve) and get contraction of facial muscles
114
Trousseau sign
tighten BP cuff on arm
| carpopedal spasm
115
What does vitamin D do?
increases dietary absorption of calcium
increases dietary absorption of PO43-
increases bone turnover
116
how does PTH affect calcium?
PTH increases calcium by increasing bone resorption and increasing renal reabsorption at the DCT
117
how does PTH affect phosphate?
PTH pulls phosphate from bone and excretes it in the urine
118
What cells make PTH?
chief cells of parathyroid
119
What cells make calcitonin?
parafollocular C cells of thyroid
120
Obesity causes
cultural habits
food choices
medications: atypical antipsychotics, mirtazapine, insulin, TZDs, sulfonylureas, some progestins
genetics
121
Metabolic syndrome diagnostic criteria
```
Any 3 of the following:
ABD OBESITY:
-waist circumference
> 40 in men or
>35 in women
not all metabolic syndrome patients are overweight
```
ELEVATED TG:
>150mg/dL
LOW HDL:
130/85 mmHg
ELEVATED GLUCOSE:
*FSG > 100mg/dL
(or 2 hour post oral glucose > 140 mg/dL)
122
medical complications of obesity
2DM, HTN, atherosclerotic disease (CAD, MI, PAD, OSA, gout, gallstones, PCOS, fatty liver, which can become NASH, stroke)
osteoarthritis
candidal infections in skin folds
cancer (esophageal, colon, liver, gallbladder, pancreatic)
breast, ovarian, uterine cancer
prostate cancer
non-hodgkin lymphoma
multiple myeloma
123
Non alcoholic steatohepatitis
fat in the liver cells causing inflammation/irritation
LFT increases in inflammation
is a progression from non-alcoholic fatty liver. Suspect NASH if LFTs are chronically elevated
MCC: obesity, 2DM, hyperlipidemia, insulin resistance leading to lipid accumulation in the liver
NAFL to NASH to cirrhosis
diagnosis; image the liver (US, CT, MRI)
Magnetic resonance spectroscopy is gold standard
liver biopsy
124
at what BMI is a pt considered obese?
>30
125
mcc hypercalcemia in outpatients
| p.321
primary hyperthyroidism (solitary parathyroid adenoma 90-95%)
parathyroid hyperplasia (5%)mcc hypercalcemia in inpatients
p.321
malignancy
squamous cell cancer (especially lung, head, and neck, via PTH- related peptide PTHrp)
RCC PTHrp
Breast mets to bone PTHrp
multiple myeloma (via local osteolytic factors)
126
most common location for ectopic thyroid tissue
tongue
127
how would pregnancy affect thyroid hormone levels?
increased thyroid binding globulin (TBG), which increases with estrogen. the body senses this and increases T4 and T3
free T4 and T3 remain constant
TSH may be low due to its similarity to beta HCG
128
hypothyroidism, symptoms
```
cold intolerance
weight gain
constipation
deepening of the voice
menorrhagia
slowed mental/ phyisical function
dry skin
coarse brittle hair
reflexes showing slow return phase
```
129
Levothyroxine
synthetic analog of T4, which gets converted to T3 in the peripheral tissues
```
tachycardia
heat intolerance
tremors
arrhythmias
if dosed too high
```
130
Congenital hypothyroidism- causes
- thyroid- related enzyme deficiency
- dysfunctional hormone production, transport, or function
- TSH resistance
- Transfer of anti-thyroid medication or anti-thyroid antibodies from the mother
- iodine- deficient diet in the mother during pregnancy
131
congenital hypothyroidism- presentation
impaired physical growth
intellectual disability
enlarged tongue
enlarged/distended abdomen
every baby is screened in order to intervene early if needed
132
Hashimoto thyroiditis
autoimmune disorder, HLADR5, HLAB5
more common in women
histology: Hurthle cells, lymphoid aggregate with germinal centers
thyroglobulin and thyroid peroxidase antibodies
painless goiter
hypothyroidism
dense infiltrate of lymphocytes into the thyroid gland that cause eventual destruction of all hormone production, in some
```
Early:
euthyroid
positive antibody
normal TS, TSH
Asymptomatic
possibly with a goiter
```
Inflammation- hyperthyroidism, transient, as T3, and T4 spill into the blood, lasting a few months
Destruction of thyroid: patient becomes hypothyroid, develops a scarred and shrunken gland in the hypothyroid state, resembling a lymph node
133
thyroiditis with granulomatous inflammation
Subacute thyroiditis
134
thyroiditis with lymphocytic inflammation
Hashimoto thyroiditis
135
Riedel's thyroiditis
fixed, hard, rock-like painless goiter
| histologically: fibrosis, macrophages, eosinophils
136
thyroiditis with macrophages and eosinophils
Riedel's thyroiditis, where thyroid is replaced by fibrous tissue, and this fibrosis can extend into adjacent structures, mimicking anaplastic carcinoma (consider cancer if the patient is older)
137
most common type of thyroid cancer
papillary carcinoma
138
second most common type of thyroid cancer
follicular carcinoma
139
activation of receptor tyrosine kinases
papillary and medullary carcinoma
140
hashimoto thyroiditis is a risk factor
for B- cell lymphomacancer arising from parafollicular C cells
141
medullary carcinoma
commonly associated with either a RAS mutation or a PAX8-PPARgamma1 rearrangement
142
follicular carcinoma
commonly assocaited with rearrangements in RET oncogene or NTRK1
143
papillary carcinoma
most common mutation is the BRAF genepapillary carcinoma
144
causes of CAH
iodine deficient diet in mother
thyroid dysgenesis
thyroid developmental defect
failure of thyroid descent during development
transfer of antithyroid antibodies or medication from mother to fetus
145
Thyrotoxicosis
```
tachycardia
palpitations
anxiety
weightloss
heat intolerance
hyperactivity
warm skin
diarrhea
hyperreflexia
hyperactivity
pretibial myxedema (Grave's disease)
periorbital edema
warm, moist, skin, fine hair
increased free or total T3, T4
hypercholesterolemia 2/2 increased LDL receptor expression
decreased or absent menstrual flow
```
phenomenon
146
Graves' disease
autoimmune disorder
TSI binds to TSH receptor and stimulates the thyroid gland to secrete T3 and T4
HLA-DR3, HLA-B8, 4:1 female predominance
increased uptake on radioactive iodine study
exophthalmos due to connective tissue deposition in the orbit and extraocular muscles
pretibial myxedema- thickening of the skin on the front of the shins
147
Jod- Basedow phenomenon
| aka iodine- induced hyperthyroidism
thyrotoxicosis with a patient with iodine deficiency goiter is made iodine replete
148
Propylthyiouracil
block thyroid peroxidase, inhibiting the oxidation of iodide and the organification (coupling) of iodine. This leads to inhibition of thyroid hormone synthesis.
blocks 5'deiodinase, and leads to the decrease of peripheral conversion of T4 to T3
Toxicity: skin rash, agranulocytosis, aplastic anemia, HEPATOTOXICITY
causes fetal goiter and hypothyroidism, preferred over methimazole in the 1st trimester
149
Methimazole
Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification (coupling) of iodine. This leads to inhibition of thyroid hormone synthesis.
causes aplasia cutis (scalp defect) preferred over PTU in 2nd and 3rd trimesters of pregnancy
150
toxic adenoma/ multinodular goiter
Mutation in TSH receptor leading to focal patches of hyper-functioning follicular cells
radioactive iodine uptake and scan, "hot nodules"
reassuring because these are not malignant.
151
subacute thyroiditis
focal destruction of thyroid with granulomatous inflammation
3:1 female predominance
associated with HLA-B35
viral infections
thyrotoxicosis early in the course, which later switches to hypothyroidism
self- limited
152
Thyroid storm
```
increased body temperature
altered mental status
tachycardia
arrhythmias
vomiting
diarrhea
dehydration
coma
death
stress- induced catecholamine surge seen as a serious complication of thyrotoxicosis due to disease and other hyperthyroid disorders
```
Treat with propanolol, PTU, corticosteroids such as Prednisolone
20% mortality
ow
153
Struma ovarii
thyroid tissue teratoma that presents as hyperthyroid
154
hyperthyroid and extremely tender thyroid gland
subacute (de Quervain) thyroiditis
155
hyperthyroid and pretibial myxedema
graves' disease
156
hyperthyroid and pride in recent weightloss, medical professional
thyroid hormone abuse
157
hyperthyroid and palpation of single thyroid nodule
toxic thyroid adenoma
158
hyperthyroid and palpation of multiple thyroid nodules
toxic multinodular goiter
159
hyperthyroid and recent study using IV contrast (iodine)
Jod- Basedow phenomenon
