Endocrine Flashcards
cAMP hormones
FSH, LH, ACTH, TSH (all ant. pit) FLAT
and also hcG
MSH
GHRH
CRH
PTH
Calcitonin
Glucagon
V2 vasopressin receptor
Gq Inositol triphosphate (IP3) pathway
hypothalamic hormones
GnRH
TRH- thyrotropin releasing hormone
post pit:
Oxytocin
Vasopressin at the V1 receptor
Tyrosine kinase receptor
growth factors growth hormone (GH) prolactin insulin insulin-like growth factor (IGF1) platelet- derived growth factor (PDGF) fibroblast growth factor (FGF) cytokines
cGMP
nitric oxide (NO) antrial natriuretic peptide (ANP)
these both act to vasodilate
steroid receptors
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
stimulates bone and muscle growth
growth hormone via insulin like growth factor (IGF1), which stimulates TKR
stimulates milk production
prolactin
stimulates milk secretion during lactation
oxytocin
responsible for female secondary sex characteristics
estradiol
stimulates metabolic activity
T4, T3
increases blood glucose level and decreases protein synthesis
glucacorticoids
responsible for male secondary sex characteristics
testosterone
prepares endometrium for implantation/ maintenance of pregnancy
progesterone
stimulates adrenal cortex to synthesize and secrete cortisol
ACTH- adrenocorticotropic hormone
stimulates follicle maturation in females and spermatogenesis in males
follicle stimulating hormone
increases plasma calcium, increases bone resorption
parathyroid hormone
decreases plasma calcium, increases bone formation
calcitonin
stimulates ovulation in females and testosterone synthesis in males
luteinizing hormone
stimulates the thyroid to produce TH and uptake iodine
thyroid stimulating hormone
where does growth hormone come from?
anterior pituitary
where does thyroid hormone come from?
thyroid
glucocorticoids
adrenal cortex (zona fasciculata)
progesterone
ovaries, and placenta if there is one
prolactin
anterior pituitary
oxytocin
hypothalamus (paraventricular nucleus)
atrial natriuretic hormone
atria of the heart
glucagon
alpha cells of the pancreas
testosterone
testes (men) ovaries (women), and in a small amount, in the zona reticularis of the adrenal cortex
vasopressin (ADH)
posterior pituitary for storage, ,made in the hypothalamus (supraoptic nucleus)
calcitonin
parafollicular cells of the thyroid
thyroid stimulating hormone (TSH)
anterior pituitary
epinephrine and norepinephrine
chromaffin cells of the adrenal medulla
insulin
beta cells of the pancreas
estradiol
ovaries
estriol
placenta
estrone
fat cells
estrogen in males
testes
PTH
parathyroid glands
somatostatin
delta cells of pancreas
luteinizing hormone (LH)
anterior pituitary
mineralocorticoids (aldosterone)
zona glomerulosa
adrenocorticotropic hormone (ACTH)
anterior pituitary
androgen binding protein
binds testosterone
embryological origins of anterior pituitary
Rathke’s pouch (ectodermal diverticulum)
embryological origins of posterior pituitary
invagination of hypothalamus (neuroectoderm)
2 proteins produced in the hypothalamus and stored in the posterior pituitary
oxytocin, ADH
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
how do nicotine and opiates affect ADH levels?
increase (less urine)
how do decreased serum osmolarity, ethanol and atrial natriuretic factor affect ADH?
They decrease ADH, promoting diuresis
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
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
inhibin
inhibits FSH
progesterone and testosterone affects on LH
inhibition
four hormones that share a common alpha subunit
LH, FSH, TSH, hCG
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
MSH
anterior pituitary, stimulates melanocytes of skin
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
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
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
things that stimulate growth hormone release
GHRH, exercise, sleepp, puberty, hypoglycemia, estrogen, stress, endogenous opioids
things that inhibit growth hormone release
somatostatin somatomedins obesity pregnancy hyperglycemia
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)
what hormone stimulates prolactin release?
thyrotropin releasing hormone
what inhibits prolactin release
DA, which comes from the hypothalamus and is a constant tonic inhibitor of prolactin
hyperprolactinemia- causes
pregnancy/ nipple stimulation
stress (physical or psychological)
prolactinoma (associated with bitemporal hemianopia)
dopamine antagonists- antipsychotics (haloperidol, risperidone), domperidone, metoclopramide
hyperprolactinemia- symptoms in premenopausal females
hypogonadism
infertility, oligo/amenorrhea, rarely, galactorrhea
postmenopausal females may not have symptoms since they are already hypogonadal
symptoms of hyperprolactinemia in males
hypogonadism (low testosterone), decreased libido, impotence, infertility (low sparm counts), gynecomastia, rarely glactorrhea
pituitary adenoma
amenorrhea, galactorrhea, low libido, infertility, bitemporal hemianopia
Treat with bromocriptine or cabergoline, which are dopamine agonists
surgical resection if symptoms are severe
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)
Gigantism
excess bone growth of linear bones, tall/big children
excess growth hormone
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
hot to treat acromegaly/gigantism
surgical resection/ octreotide
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
- decreases exocrine secretion in the pancreas, which affects digestion
- decreases hormone secretion in the CNS, PNS, and endocrine organs
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
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)
empty sella syndrome
asymptomatic, symptoms of pituitary hormone deficiency of one or more hormone
Primary hyperaldosteronism
HTN
Hypokalemia
Metabolic alkalosis due to potassium out, H in
low renin
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
Symptoms of pheochromocytoma
pressure (increased BP) pain (HA) perspiration palpitations (tachycardia) pallor
pheo may secrete EPO –> polycythemia
tumors that secrete erythropoitin
pheochromocytoma
RCC
HCC
hemangioblastoma
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
symptoms of Addison disease
hypotension hyponatremia hyperkalemia weakness malaise anorexia weight loss skin hyperpigmentation
what causes Addison disease?
autoimmune destruction of adrenal glands leading to decreased production of aldosterone and cortisol
MEN1
parathyroid tumors pituitary tumors (prolactin or GH) pancreatic endocrine tumors- ZE, insulinomas, VIPomas, glucagonomas (Rare)
associated with menin tumor suppressor mutation (MEN1 gene)
MEN2A
parathyroid hyperplasia
pheochromocytoma
medullary thyroid cancer
associated with RET gene mutation (TKR), marfanoid habitus
MEN2B
pheochromocytoma
medullary thyroid carcinoma (secretes calcitonin)
oral/intestinal ganglioneuromatosis (mucosal neuromas)
associated with marfanoid habitus, mutation in RET gene
catecholamine metabolites in a pheo patient’s plasma and urine
Plasma: metanephrine, normetanephrine
urine: VMA (vanillylmandelic acid)
what pancreatic cell type makes glucagon
alpha
what pancreatic cell type makes insulin
beta
what pancreatic cell type makes somatostatin
delta
GLUT 2 receptors are found on which cell types?
beta cells of pancrease
liver
small intestine
renal cells (kidney)
GLUT 4 is insulin responsive. What cell types is it found on?
adipose tissue
skeletal muscle
GLUT 1 receptors are found on which cell types
brain
RBCs
what kind of receptor is the insulin receptor?
tyrosine kinase
DM initial presentation
hyperglycemia, polyuria, polydipsia, polyphagia, weightloss
1DM HLA associations
HLA DR3 DQ2
HLA DR4 DQ8
cell types that don’t have sorbitol dehydrogenase
schwann cells
lens
retina
kidney
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
lactic acidosis is a rare but worrisome risk with this medication
metformin
MC SE is hypoglycemia
insulin
and sulfonylureas, since these enhance beta cell function in the pancrease
recommended first- line treatment for most patients
metformin (2DM), insulin (1DM)
not sage in patients with symptoms of CHF or fluid balance problems
TZDs
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)
Not associated with weight gain, may help with weight loss
metformin, DPP4, inhibitors, GLP1 analogs, SGLT inhibitors
metabolized by the liver, could be used in patients with renal dysfunction
TZDs
MOA: closes + channel on beta cells
leading to depolarization leading to calcium influx
and ultimately, insulin release
sulfonylureas, meglitinides
MOA: inhibits alpha- glucosidase ta intestinal brush border
alpha- glucosidase inhibitors (acarbose, miglitol)
MOA agonist at PPARgamma receptors leading to improved target cell response to insulin
glitazones/TZDs
MOA: decreases hepatic gluconeogenesis
metformin, and also to a lesser extent TZDs
MOA: decreases glucose reabsorption at renal tubules
SGLT-2 inhibitors
possible non-insulin treatment for patients with organ failure (renal, liver, heart)
DPP4 inhibitors
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
Chvostek sign
tap the cheek (facial nerve) and get contraction of facial muscles
Trousseau sign
tighten BP cuff on arm
carpopedal spasm
What does vitamin D do?
increases dietary absorption of calcium
increases dietary absorption of PO43-
increases bone turnover
how does PTH affect calcium?
PTH increases calcium by increasing bone resorption and increasing renal reabsorption at the DCT
how does PTH affect phosphate?
PTH pulls phosphate from bone and excretes it in the urine
What cells make PTH?
chief cells of parathyroid
What cells make calcitonin?
parafollocular C cells of thyroid
Obesity causes
cultural habits
food choices
medications: atypical antipsychotics, mirtazapine, insulin, TZDs, sulfonylureas, some progestins
genetics
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)
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
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
at what BMI is a pt considered obese?
> 30
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)
most common location for ectopic thyroid tissue
tongue
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
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
Levothyroxine
synthetic analog of T4, which gets converted to T3 in the peripheral tissues
tachycardia heat intolerance tremors arrhythmias if dosed too high
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
congenital hypothyroidism- presentation
impaired physical growth
intellectual disability
enlarged tongue
enlarged/distended abdomen
every baby is screened in order to intervene early if needed
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
thyroiditis with granulomatous inflammation
Subacute thyroiditis
thyroiditis with lymphocytic inflammation
Hashimoto thyroiditis
Riedel’s thyroiditis
fixed, hard, rock-like painless goiter
histologically: fibrosis, macrophages, eosinophils
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)
most common type of thyroid cancer
papillary carcinoma
second most common type of thyroid cancer
follicular carcinoma
activation of receptor tyrosine kinases
papillary and medullary carcinoma
hashimoto thyroiditis is a risk factor
for B- cell lymphomacancer arising from parafollicular C cells
medullary carcinoma
commonly associated with either a RAS mutation or a PAX8-PPARgamma1 rearrangement
follicular carcinoma
commonly assocaited with rearrangements in RET oncogene or NTRK1
papillary carcinoma
most common mutation is the BRAF genepapillary carcinoma
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
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
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
Jod- Basedow phenomenon
aka iodine- induced hyperthyroidism
thyrotoxicosis with a patient with iodine deficiency goiter is made iodine replete
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
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
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.
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
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
Struma ovarii
thyroid tissue teratoma that presents as hyperthyroid
hyperthyroid and extremely tender thyroid gland
subacute (de Quervain) thyroiditis
hyperthyroid and pretibial myxedema
graves’ disease
hyperthyroid and pride in recent weightloss, medical professional
thyroid hormone abuse
hyperthyroid and palpation of single thyroid nodule
toxic thyroid adenoma
hyperthyroid and palpation of multiple thyroid nodules
toxic multinodular goiter
hyperthyroid and recent study using IV contrast (iodine)
Jod- Basedow phenomenon
