Pituitary and Thyroid Flashcards
Which hormones are peptide hormones? Steroid hormones? Amino acid derivatives?
- insulin, glucagon, ACTH, PTH, prolactin
- cortisol, aldosterone, estrogen, testosterone, progesterone
- epi and norepi, thyroid hormones
What is the hypothalamus made of?
paraventricular and supraoptic nuclei, with axons that make up stalk that connects to PPG/
What type of tissue is the APG/? PPG/?
APG/ - glandular tissue
What connects the APG/ to the H/?
hypothalamo-hypophyseal-portal system
What hormones are made by the hypothalamus?
Dopamine (prolactin inhibiting factor), CRH, GHRH, TRH, GnRH, GHIH (somatostatin), ADH, Oxytocin
What hormones are made by the APG/?
GH, ACTH, TSH, FSH, LH, Prolactin
What hormones are secreted by PPG/?
ADH and oxytocin
What type of cells secrete GH? What will this do?
Somatotrophs, stimulate secretion of insulin-like growth factor from liver + effect on long bones etc..
What is somatostatin? What synthesizes it? What does it do?
GH-inhibiting hormone, secreted by hypothalamus and GI tract to decrease GH
How is dopamine secreted? By what?
Continuously secreted to inhibit prolactin by H/
What triggers H/ to stop secreting dopamine?
Suckling of infant
Where are hormones stored in the posterior pituitary?
Herring Bodies (dilations in axons)
When is ADH secreted? What is it’s MOA?
when high blood osmolarity or low blood volume/BP, retains H2O from urine + vasoconstriction of blood vessels
What is the action of oxytocin?
dilates cervix + stimulates uterine contractions during childbirth + makes breast muscle cells contract during breastfeeding + increases during orgasm and pleasant social interactions
Where is the pineal gland? What is it made up of? What does it secrete?
behind H/ and pituitary, made up of pinealocytes which secrete melatonin
What does melatonin do? What secretes it?
regulates circadian rhythm (sleep/wake cycle), secretion by pinealocytes
What cells secrete Calcitonin? What gland is this?
Parafollicular cells (c-cells) of the thyroid
When is aldosterone secreted? By what? MOA?
with low BP or high serum K+ = prevents H2O and Na+ loss, increases K+ elimination, secreted by zona glomerulosa of adrenal gland
What does zona fasciculata secrete? What does this do?
Cortisol, stress hormone secreted during fight or flight + stimulate osteoclasts + increases blood sugar
What does the zona reticulata secrete?
sex hormone precursors/androgens
What is the blood supply to and from the adrenal glands?
afferent = branches of suprarenal arteries Efferent = large medullary veins go to suprarenal veins
What cells secrete PTH?
Chief/principal cells of parathyroid
Where does the pituitary gland sit?
Anteroinferiorly to H/, inferior to optic chiasm, in sella turcica of sphenoid bone of skull
What type of cells of the pituitary gland are chromophils? What does this mean? Which of these are acidophils vs basophils?
Chromophils = cells that produce hormone, are stainable
Acidophils (stain pink): somatotroph (GH), mammotroph (Prolactin)
Basophils (stain blue/purple): gonadotrophs (FSH/LH), corticotroph (ACTH and alpha-MSH), thyrotroph (TSH)
What do corticotrophs secrete?
ACTH and alpha-MSH
What is alpha-MSH? What does it do? Where is it secreted from?
alpha-melanocyte stimulating hormone, leads to secretion of pigment from melanocytes, secreted from corticotrophs
What hormones act on prolactin?
Dopamine (inhibits), TRH (stimulates)
What is another name for ADH?
vasopressin
What cells are found in the PPG?
pituicytes - modified glial cells that help insulate nerve fibers, increase speed of impulse conduction
From what does the PPG arise from?
evagination of diencephalon (neuroectoderm) of the 3rd vesicle
From what does the APG arise from?
outpouching of roof of oral ectoderm/mouth (Rathke pouch) - glandular. Apoptosis at base of pouch
Which pituitary lobe is more vascularized?
Anterior since hormones have to diffuse
What blood vessel feed infundibulum? What about the different pituitary lobes?
Internal carotid artery branches into inferior and superior hypophyseal arteries. Superior supplies infundibulum and anterior lobe, inferior supplies posterior
Where are the capillary plexuses formed in the pituitary? What are they made of?
- Superior hypophyseal artery forms primary capillary plexus around infundibulum, and secondary plexus in anterior lobe
- Inferior hypophyseal artery forms its own capillary plexus in posterior lobe
What causes hyperpituitarism?
Pituitary adenoma (tumor, >99% benign)
How are pituitary adenomas diagnosed?
Headache/visual field deficits –> elevated hormone levels + MRI of pituitary
What is considered a microadenoma? Macroadenoma?
micro <1cm
macro>1cm
What are the sxs associated w/ pit. adenomas? (general)
Visual changes (tumor presses on optic nerve, optic chiasm right above it), acute headaches, hormone changes
What type of visual deficits can be seen w/ pituitary adenomas?
Bitemporal hemianopia (temporal vision loss in both eyes), monocular visual field deficits (loss of vision in specific quadrant), junctional field deficits (partial loss of vision or blind spot)
What are the sxs associated w/ pituitary adenoma that originates within gonadotrophs?
Usually no sxs
What are the sxs associated w/ pituitary adenoma that originates within thyrotrophs?
hyperthyroidism = heat intolerance, weight loss, anxiety, diarrhea, moist skin, heart palpitations
What are the sxs associated w/ pituitary adenoma that originates within somatotrophs in adults? What are complications associated?
Acromegaly = coarsening of facial features, enlarged hands, thickening of skin, and prognathism (jaw protrusion) secondary to pharyngeal soft tissue growth –> obstructive sleep apnea, cardiomyopathy, HTN, osteoarthritis, increased risk of cancers
What are the sxs associated w/ pituitary adenoma that originates within somatotrophs in children?
Gigantism
What are the sxs associated w/ pituitary adenoma that originates within corticotrophs?
Cushing disease (2ndary hypercortisolism) = hyperpigmentation, purple skin striae, HTN, weight gain, moon-shaped face, truncal obesity, skin changes, hyperglycemia
What are the sxs associated w/ pituitary adenoma that originates within lactotrophs?
irregular/ absent menses, infertility, galactorrhea (milky discharge), decreased libido, hypogonadism
Macroadenomas = visual field deficits
What is the tx for pituitary adenomas that show neurological sxs?
surgery (transsphenoidal sinus approach)
What is the tx for pituitary microadenomas?
no surgery unless GH or ACTH hypersecretion
What is the tx for pituitary adenomas when surgery contraindicated?
treat elevated hormone, ex: high GH = give octreotide or lanreotide, high prolactin = treat w/ cabergoline or bromocriptine
If surgery contraindicated and no reponse to meds, what is a possible x for pituitary adenomas?
radiation
What is panhypopituitarism?
Multiple hormones are synthesized less (should see decrease in ACTH)
What are possible causes of hypopituitarism?
tumors (pituitary adenoma, tumor compresses pituitary blood supply), head trauma, pituitary surgery, stroke, granulomatous disease, Sheehan syndrome (infarction of PG/ after postpartum hemorrhage), Empty Sella Syndrome (enlarged sella turcica)
What is Sheehan syndrome? What does it cause? Sxs?
infarction of pit. gland after postpartum hemorrhage, causes hypopituitarism –> hypotension, post-delivery lethargy, anorexia, weight loss, inability to breastfeed
What is Empty Sella Syndrome? What does it cause? Sxs? What is seen on imaging?
enlarged sella turcical due to high CSF pressure causing herniation of subarachnoid space into sella, pit. gland flattened on MRI, asymptomatic
What are symptoms associated with decreased prolactin production?
can’t lactate after delivery, decreased reproductive function
What are symptoms associated with decreased GH production in children? In adults?
Children = short stature Adult = increased fat mass, decreased bone mineral density, dyslipidemia, increased atherosclerosis
What are symptoms associated with decreased ACTH production?
2ndary cortisol deficiency -
Mild cases: postural hypotension and tachycardia
Severe cases: weight loss, fatigue, decreased libido, hypoglycemia
Worst cases: hypotension, shock, death due to vascular collapse (cortisol needed for peripheral vascular tone maintenance)
What are symptoms associated with decreased FSH/LH production?
Hypogonadotropic hypogonadism: sterility, decreased libido
Women only - decreased estradiol secretion = hot flashes, sxs of vaginal atrophy (dryness, bleeding)
Men only - low testosterone causing infertility, decreased energy, low libido
What are symptoms associated with decreased TSH production?
2ndary hypothyroidism - fatigue, cold intolerance, decreases appetite, constipation, facial puffiness, dry skin, bradycardia, depression, anemia
What are symptoms associated with decreased ADH production?
Central diabetes insipidus since K excretes high-volume dilute urine = leads to dehydration, increased thirst, and dizziness
What is pituitary apoplexy? What does it often occur in? What is the tx?
sudden hemorrhage into pituitary gland, often in pit. adenoma, medical emergency so treat w/ fluids and cortisol replacement
What are the sxs of pit. apoplexy?
sudden-onset excruciating headaches, diplopia due to increased pressure on oculomotor nerves, developing hypopituitarism
How is pituitary apoplexy diagnosed?
lab studies: target gland and respective stimulatory pituitary hormone
Stay aware of timing (particularly for cortisol and GH which fluctuate over diurnal cycle)
Which hormones are secreted in different amounts throughout the day?
Cortisol and GH
What is expected with hypopituitarism for GH and FSH/LH? How do you measure GH? What about FSH/LH?
decreased insulin-like growth factor I (IGF-I)
Low estradiol or morning testosterone
What is expected with hypopituitarism for ADH and ACTH? How do you measure ADH? ACTH?
low urine volume and high urine osmolarity after giving synthetic ADH
low ACTH, low cortisol, elevation of cortisol after giving synthetic ACTH
What is the tx for hypopituitarism due to low ACTH?
IV saline + dextrose (hypoglycemic) + IV hydrocortisone (supplement cortisol)
What is the name for T3 and T4? What are their 1/2 lives?
T3 = triiodothyronine, 1-2 days T4 = thyroxine or tetraiodothyronine, 6-8 days
What does basolateral mb of follicular cell contain? What about apical mb?
Na+/I- symporter, brings in I- from blood into cell
Cl-/I- exchanger, brings in CI- into colloid
What happens to I- once it is in colloid?
undergoes oxidation by thyroperoxidase enzymes, becomes Iodine. Attaches to tyrosine a.a. on thyroglobulin (iodination) forming MIT or DIT. These link via thyroperoxidase to form T3 and T4 still bound to thyroglobulin
What are the 2 processes that occur in the colloid?
Iodide oxidation to Iodine
Iodination of thyroglobulin tyrosine a.a. to form MIT and DIT
What is the important enzyme in colloid?
thyroperoxidase
How are T3 and T4 secreted?
follicular cell endocytoses thyroglobulin into vesicle, cleaved by proteases within lysosome, released into bloodstream through MCT
What is MCT?
monocarboxylaste transporter, releases T3 and T4 into bloodstream from follicular cell
How do T3 and T4 circulate in blood? Are they biologically active?
Bind to thyroxine binding globulin (TBG), albumin, and transthyretin, not biologically active when bound, only 0.03% of T4 and 0.3% of T3 active
What enzyme converts T4 to T3
5’-deiodinase
What happens when T3 binds to R inside cell nucleus?
corepressor of thyroid hormone response elements displaced and coactivator attaches, allows gene expression
What do Thyroid hormones do?
Increase metabolic rate, activate SNS, promotes hair growth, long bone growth
What can cause hyperthyroidism?
1ary: abnormal thyroid gland
2ndary; increased APG synthesis of TSH
Exogenous hypeT: OD on thyroid med (used for weight loss)
What sxs can we see w/ hyperthyroidism?
heat intolerance, weight loss, tachy, palpiatations, arrhythmias, chest pain, HTN, warm moist skin, fine hair, increased appetite & gastric motility, diarrhea, muscle weakness (proximal mainly), hand tremors, increased reflexes, lid lag, hyperactivity, anxiety, insomnia, oligomenorrhea/amenorrhea, gynecomastia, decreased libido, infertility, hyperventilation, dyspnea
What are the causes of primary hyperthyroidism?
- Graves Disease
- Toxic multinodular goiter
- thyroiditis
- toxic thyroid adenomas
What is Grave’s disease? What does it cause? What are the sxs?
autoimmune condition, type 2 hypersensitivity, body produces IgG that targets and stimulates TSH R in TG/ –> hyperthyroidism.
Smooth nontender goiter, pretibial myxedema, exophthalmos
What is pretibial myxedema? What is it caused by? Pathophysiology
waxy discoloration of skin w/ nonpitting edema, generally covers shins. Due to inactivation of fibroblasts in skin by IgG stimulated TSH R, deposit collagen in skin = swelling. Seen w/ Grave’s disease
What is exophthalmos? What is it caused by? What is seen w/ it?
bulging eyes, conjunctival irritation, upper lid retraction. T cells activated by TSH R to infiltrate retro-orbital space, release cyk (TNF-a, IFN-g) = secretion of hydrophilic glycosaminoglycans, bind water causes muscle swelling, inflammation, and adipocyte buildup. Seen with Graves disease
Can exothalmos be reversible?
Yes, w/ treatment of hyperthyroidism, though less likely the longer you wait
What is seen on histology for Graves disease? How is this obtained?
diffuse hypertrophy and hyperplasia of follicular cells caused by stimulating autoAb + vascular congestion to keep up w/ overproductive cells. Thyroid biopsy
What is toxic multinodular goiter? What does it cause? What is seen on histology?
irregular goiter w/ multiple nodules that dvp throughout thyroid gland due to differences in hyperplasia rate. Causes hyperthyroidism. Histology = follicular cells distended w/ colloid in uneven manner
How do you dx toxic multinodular goiter? What is it associated w/?
irregular enlargement of thyroid, associated w/ increased risk of thyroid cancer
What is thyroiditis? What are the subtypes? What is seen with them?
inflammation of thyroid, gives rise to hyperthyroidism. Subacute granulomatous (de Quervain) thyroiditis presents w/ painful diffusely tender goiter. Silent lymphocytic thyroiditis
What is a toxic thyroid adenoma? What does it cause? What is the tx?
solitary adenoma, causes hyperthyroidism, requires surgical removal
What are causes of secondary hyperthyroidism?
pituitary disease (adenoma), non-thyroid secretion of thyroid hormone (usually cancer)
What is seen with exogenous hyperthyroidism? Is goiter present ? Labs?
meds used for weight loss or hypoT, no goiter since thyroid repressed = high T3, T4, low TSH
What is thyroid storm? What causes it?
thyrotoxic crisis, emergent severe hyperthyroidism, can occur w/ untreated or inadequately treated hyperT. Acute stressors: MI, infection, trauma, surgery = massive overproduction of thyroid hormones
What are the sxs of thyroid storm?
Agitation, delirium fever, diarrhea, coma, tachyarrhythmias, high-output HF, atrial fib
What is the ability of thyroid hormone on cardiovascular system? Specifically involves receptor
upregulates beta1 adrenergic R, can cause atrial fib
How is hyperthyroidism dx?
labs (T3, T4, TSH), radioactive iodine uptake test, antithyroid Ab
What is seen on radioactive iodine uptake test w/ goiter disease, toxic multinodular goiter, and exogenous HT?
Graves: homogenous distribution
Toxic Multinodular goiter: multiple focal patches of iodine uptake
Exogenous HT: decreased iodine uptake since thyroid gland function suppressed
What does a positive antithyroid ab test indicate? What Ab are used?
Anti-TSH R Ig in blood = Graves disease
What is the tx for hyperthyroid induced tachycardia?
Beta blocker (propranolol)
What is tx for increased T3/T4 in hyperthyroidism?
antithyroid (methimazole or PTU though PTU used for patients in 1st trimester of pregnancy)
What is exophthalmos treated with? What is this associated with?
corticosteroids (prednisone), reduces inflammation and swelling –> Grave’s disease
If medical management of hyperthyroidism not sufficient, what are other treatment modalities?
radioactive iodine ablation, surgical thyroidectomy
When is surgical thyroidectomy done?
Hyperthyroidism, often for children with whom meds (methimazole) didn’t work, or patients w/ compressive goiter
What can radioactive iodine ablation and surgical thyroidectomy result in?
hypothyroidism, will need to take thyroid replacement hormones permanently
What are sxs assocaited w/ hypothyroidism?
cold intolerance, decreased sweating, weight gain, hypercholesterolemia, bradycardia, dyspnea on exertion, decreased cardiac output, dry cool skin, coarse brittle hair, alopecia, brittle nails, facial puffiness, pretibial myxedema, decreased appetite, decreased GI motility, carpal tunnel syndrome, cramping, stiffness, slowed refelxes, hypoactivity, lethargy, fatigue, weakness, depressed modd, hyporeflexia, heavy menses, mild nipple discharge (galactorrhea), impaired fertility
Which pts should be screened for hypothyroidism?
all elderly pts w/ depression
What are the causes of primary hypothyroidism?
Hashimoto thyroiditis, atrophic thyroiditis, iatrogenic causes, iodine deficiency, toxins or drugs, congenital hypothyroidism (cretinism)
What is myxedema coma? What patients are usually affected?
decompensated state of severe hypothyroidism, usually elderly w/ hx of previously stable hypoT triggered by stressful events (MI, stroke, infection…)
What are sxs associated w/ myxedema coma?
diminished mental capcaity, decreased body temp, hypoglycemia, hyponatremia, hypercapnia, hypoxia, bradycardia, hypoventilation
What is the tx for myxedema coma?
high-dose thyroid hormone supplementation, saline, pressors (hemodynamic stability)
What is atrophic thyroiditis? Which pts often affected?
autoimmune thyroiditis, due to anti-TSH R autoAb, often in middle age or older pts
What are the risk factors for hashimoto thyroiditis?
female, personal/family hx of autoimmune disorders (Graves disease), Down and Turner syndrome, HLA DR3 and DR5
What is the histology of Hashimoto thyroiditis?
diffuse infiltration by lymphocytes + Hurthle/Askanazy cells
What is Hashimoto thyroiditis?
most common cause of hypothyroidism in developed countries, autoimmune destruction of gland by antithyroid Ab: antithyroperoxidase (anti-TPO, which converts iodide to iodine), antithyroglobulin, antimicrosomal IgG
What are the sxs associated w/ hashimoto thyroiditis?
hypothyroidism - pretibial myxedema, smooth nontender goiter (not required), insidious onset
What are you at risk for if dx w/ Hashimoto thyroiditis?
other autoimmune diseases like pernicious anemia
What sxs are seen w/ atrophic thyroiditis?
insidious onset, pretibial myxedema (presents similar to Hashimoto but w/o goiter)
What is iatrogenic cause of hypothyroidism?
subtotal thyroidectomy or radioactive ablation of thyroid for tx of hyperT or thyroid cancer –> decreased thyroid function
What is the most common cause of hypothyroidism globally? What labs are seen w/ this? What happens to thyroid gland?
iodine deficiency, see low T3 and T4 resulting in high TSH and TRH –> hypertrophy of gland
Which toxins or drugs result in hypothyroidism?
Amiodarone (antiarrhythmic drug that decreases T4–>T3 conversion + causes inflammatory thyroiditis)
Lithium: bipolar drug, inhibits hormone synthesis, Aspirin and Sulfonamide: can induce thyroiditis
What is congenital hypothyroidism? What is another name for it? Is it reversible? What causes this?
fetal hypothyroidism (cretinism), causes: fetal thyroid agenesis, autoimmune maternal hypothyroidism, iodine deficiency
What are sxs associated with congenital hypothyroidism?
pot belly w/ protruding umbilicus, pale skin, puffy face, protruding tongue, poor neurologic dvpmt
What is seen on cholesterol levels with hypothyroidism?
usually increased
What can be used to test for iodine deficiency? Muscle disease? Hashimoto?
urine or serum iodine levels
CPK (increased w/ muscle disease)
CBC since Hashimoto associated w/ other autoimmune disorders including pernicious anemia
What is the tx for hypothyroidism?
thyroxine supplementation, monitor TSH and T4 every 6 weeks
What can thyroid supplementation cause? What should we look out for?
can cause angina or MI’s, get cardiac evaluation before giving supplements to pts w/ atherosclerosis or heart disease
What is Iodine deficiency treated w/?
K+ iodate and chronically increasing dietary iodine intake w/ foods and iodized table salt
What are risk factors for thyroid neoplasms? How many of them are benign?
older adults and women, radiation exposure, family hx 90% benign
What are the types of thyroid tumors?
thyroid adenomas, papillary thyroid carcinoma, follicular adenoma, medullary carcinoma, anaplastic carcinoma
What is the dx for thyroid tumor? What is seen on imaging?
lump in neck, difficulty swallowing, rapid nodule growth
U/S: calcifications, irregular borders, invasion would show malignancy. Cystic nodules likely benign
What signs would indicate malignant thyroid tumor?
fixed nodules w/ rapid growth, hoarseness (vocal cord paralysis or local invasion of nerves), cervical lymphadenopathy
Can radioactive iodine uptake scanning be used to dx malignancy in thyroid nodules?
Hyperfunctioning nodules more likely benign, lack of uptake = increased odds of malignancy
If pt has solitary nodule, what is used to dx?
Fine needle aspiration
What is the tx for thyroid carcinoma?
total thyroidectomy surgery 1st line for all type of carcinomas
What are potential complications from thyroidectomy?
hypothyroidism, hypoparathyroidism, recurrent laryngeal nerve injury
What should be given after thyroidectomy? In what cases? Why
radioactive iodine when local invasion or distant metastasis to ablate residual thyroid tissue and decrease rate of recurrence
How are papillary and follicular cancer monitored for recurrence after thyroidectomy? What about medullary cancer?
Measure serum thyroglobulin for papillary and follicular
Measure Calcitonin for medullary
What is anaplastic carcinoma? What are risk factors? What is the presentation?
rarest and worst thyroid tumor, metastasize aggressively to nearby tissues, tumor large, painful, histologically undifferentiated. Older pts higher risk
What is medullary cancer? Where does it often metastasize to? What are the risk factors?
derived from parafollicular C cells, secrete Calcitonin. Metastasis to liver, lung, bone at time of dx often. Risk factors: genetic syndromes Multiple endocrine neoplasia (MEN) types 2A and 2B
What does MEN 2A present w/ What is it associated w/?
pheochromocytoma (HTN, tachycardia), hyperparathyroidism (hyperCa2+), possible cutaneous lichen amyloidosis (amyloid deposits in skin) –> assocaited w/ medullary thyroid carcinoma
What does MEN 2B present w/? What is it associated w/?
pheochromocytoma (HTN, tachycardia), neurofibromas, marfanoid features (long limbs, overgrown teeth and gums, spider fingers, double jointedness) –> associated w/ medullary thyroid carcinoma
What is the histology of medullary carcinoma of the thyroid?
nests of tumor cells (purple) separated by amyloid stroma (red/pink) containing Calcitonin deposits
What are thyroid adenomas? Are they nonfunctiong or functioning? Do they invade the capsule?
benign thyroid growths, usually nonfunctional, don’t invade tumor capsule or blood vessels
What is papillary thyroid carcinoma? How does it spread?
most common thyroid cancer with good prognosis, slowest growing, spreads locally to lymphs rather than metastasis
What are the risk factors for papillary carcinoma?
RET or BRAF mutations, childhood radiation
What is the histology of papillary thyroid carcinoma?
papillary architecture w/ fibrovascular core lined by tumor cells, often see psammoma bodies (concentric spherules of calcification) and nuclei look empty (“orphan annie”)
What is follicular carcinom? How common is it? How quickly does it grow, how does it spread? Where does it spread?
2nd most common thyroid cancer, grows faster than papillary carcinoma, spread hematogenously to bone or lung
What are the risk factors for follicular carcinoma?
older pts, associated w/ RAS mutations
What is the histology seen w/ follicular carcinoma?
invades tumor capsule and beyond
