Pregnancy, primary hypothyroidism (incresaed TSH leading to prolactin increase), stress and corticosteroid tx, DA receptor antagonists, chronic renal failure, idiopathic, stalk disconnection, acromegally
What is a bone complication associated with prolactinoma? What is the mechanism?
bone demineralization due to loss of estrogen effect (decreased estrogen due to supression of GnRH
Prolactinomas are made up of what cell type predominately ?
Are endocrine tumors usually malignant or benign?
most of them are benign. Only considered malignant *IF THEY METASTASIZE*. Malignancy cannot be determined by cytology, only by metastasis
WHat is the recommended treatment for a prolactinoma (rx)?
dopamine agonist: bromocriptine or cabergoline. surgical resection or radiotherapy may also be used if warranted
why is hyperglycermia seen with a GH secreting adenoma (somatotroph)
because GH inhibits insuline release.
Upon administration of a glucose tolerance test, a pt's GH levels were found to have no change in response to glucose. dx?
GH secreting adenoma. It would also be noted that glucose levels would spike more, for a longer period of time, as compared to a normal pt. Relationship b/w GH and glucose should inverse, due to insulin response.
What is the tx for a GH secreting adenoma?
somatostatin analogue to shrink tumor in preparation for surgical removal
How are the effects of Growth Hormone mediated?
GH does not act directly on tissues. It is first converted to IGF-1 in the liver, which in turn acts on target tissues.
What is the function of IGF-1?
The active form of GH. GH itself does not act directly on tissue, it acts via IGF-1
List the major metabolic fx of growth hormone
synergize with cortisol and antagonize insuline (insuline resistance), increase lipolysis, increase glycogenolysis and gluconeogenesis, increase GFR leading to increase sodium and H2O retention (HTN!!!). increase BMR and thyroxin (T3)
What are the two types of somatotroph adenoma ? What are the unique features
Densely granulated (SLOW GROWING) - STRONGLY POSITIVE FOR GH. and sparsely granulated (FAST GROWING) MADE OF KERATIN 8. Cells show cellular and nuclear pleomorphism
What is sheehan's syndrome?
postpartum hypopituitarism due to necrosis of the anteriod pituitary, The necrosis is caused by severe bleeding and hypoperfusion during delivery. Presents with fatigue, anorexia, poor lactation, and loss of hair all over body.
Describe the blood supply of the pituitary
There is no direct arterial blood supply to the anterior pituitary, instead there is a low pressure portal vein system. THis prevents large amount of hormones from being leaked out constantly.
What is the treatment for sheehan's syndrome
hormone supplimentation. TSH is replaced by *L-thyroxine*, cortisone is given po, and testosterone must be given to men. IGF-1 is given to replace GH.
Patient complains of loss of libido.... what pituitary hormone may be deficient?
How can GH function be observed?
growth chart, IGF-1, and bone age (X-ray of left hand
What hormone is deficient in DI
SIADH is seen with what conditions?
rarely due to pituitary pathology. Most always due paraneoplastic syndrome, etc
Why is K+ normal and Na+ decreased in SIADH?
dilutional hyponatremia due to excess water resorption. K+ is normal or slightly decreased because the hypokalemia is compensated by a shift of extracellular H+ for intracellualar K+. pH of urine is normal because of the h+ reabsorption
What is the best tx of SIADH?
restricting water intake to normalized the ADH levels
What hormones are secreted by the pituitary?
Post pituitary (neurohypophesis): vasopressin (ADH) and oxytosin (made in the hypothalamus and shipped to the post pit. Ant Pituitary: FSH, LH, ACTH, TSH, Prolactin, GH (FLAT PIG) and MSH
Where is ADH produced?
ADH (AKA vasopressin) is secreted from the hypothalamus into the post. pituitary, where it is secreted.
Acanthosis nigricans: What is it? What disease is it most commonly associtated with?
Thickened, dark, hyperpigmented area of skin seen in area of friction such as the neck, belt lines, or medial aspect of thigh. Common in TYPE II DM (AKA insulin resistant)
What is the reason for the vision problems and glaucoma seen diabetes?
high blood sugar results in higher osmostic pressure within the lens which draws in water, causing swelling of the lens
What is the balancing hormone of insuline ie what is the antagonist of insulin
What are incretins? What do they do?
GLP-1 and GIP Incretins are gastrointestinal hormones that increase insulin released from beta cells of pancrease (islet of langerhans) even before glucose levels increase. They also inhibit glucagon release.
What incretin decrease gastric emptying?
What incretin activates satiety in the brain?
Why are people with type 2 DM always hungry (polyphagia)?
Because they don't produce enough incretins (GLP-1 and GIP) so gastric emptying is too fast (due to asbsence of GLP-1) and satiety is not signalled (Also due to absence go GLP-1). They also have dcreasd B-Betacell funct due to lack of incretin stim.
What is the pancreatic biopsy finding of type II DM?
amyloid deposits in the pancrease. Apple green perfringence on viewing with polarized light... stains red with congo red stain.
What do alpha cells secrete? What stimulates this?
alpha cells secrete glucagon. Stimilated by free fatty acids.
Where is glucagon secreted from?
Alpha cells of pancreas.
What are the diagnostic blood glucose levels for diabetes (list fasting and 2 hr post glucose)
FASTING GLUCOSE: 100-125 = Impaired fasting glucose, 126 and up= diabetic. Normal is under 100. 2 hour post glucose load = normal under 140, diabetic if over 200, impaired tolerance if 141-200.
Fasting blood sugar of ___ , random blood sugar of ___, and Hba1c of ___ is diagnostic of diabetes
FBS 126 and up, RBS 200 and up. ABNORMAL HbA1c cannot be used to diagnosis of DM
Increased risk of what cardiac pathology is increased with DM?
MI. Increased risk by 50%, which is same risk increase as someone who has already had an MI
What is the most important factor in management of type 2 DM?
Diabetic ketoacidosis (metabolic acidosis) is associated with what blood sugar finding?
What cell type mediates islet cell destruction in type 1 DM?
cytotoxic T-cells (CD8+) and Th1 (CD4+) . Antigen is unknown.
What type of diabetes is most associated with infections? with DKA?
type II is asso with infections, type I is asso with DKA
What type of diabetes has higher level of concordance?
type II. Concordance = frequency of occurence in identical twins. Type I is likely to be due to environmental factors in addition to a minor role with genetics.
What is the tx for DKA?
1) IV fluids to rehydrate, correct osmolarity and acidosis (by flushing out ketones). 2) insulin to decrease ketone formation (lipolysis) and correct acidosis. (continue till acidosis is resolved). 3) replace K. Give mannitol to tx cerebral edema
If pt takes too much insulin and passes out, what should be given?
glucose in liquid form. If they are unconscious give glucagon or IV glucose.
What metabolic disorder is seen with CF?
diabetes due to severe exocrine pancrease dysfunction. (cystic fibrosis related diabetes (CFRD)
What is MODY
Maturity Onset Diabetes of Young. type of diabetes seen in non-obese kids due to monogenetic mutation in GLUCOKINASE OR HAPTIC NUCLEAR FACTOR 1 or 2. Presents as nonketotic form of DM w/o islet cell ABs. Often asso with a fam hx of DM over several gens
Diabetes in a young, non-obese child with no antibody causation: dx?
What is the cause of MODY
mutation in glucokinase or hepatic nuclear factor 1 or 2
What is the primary cause of almost all diabetes associated complications?
NON-ENZYMATIC GLYCOSYLATION is athe core of all pathology. Formation of advanced glycosylation products, activation of PKC and angiogenic pathways, IC disturbances in polyol pathway (neoropathy, cateracts, etc) CAUSES MACROANGIOPATHY AND MICROANGIOPATHY
Why is atherosclerosis higher in diabetics?
ALong with high glucose, diabetics also have higher free fatty acids,,, this leads to atherosclerosis and increased risk of MI.
What is the cause of the nephropathy associated with diabetes?
depostion of advanced glycosylation products due to non-enzymatic glycosylation!
What is the cause of diabetic retinopathy?
AGEs cause changes to basement membrane / pericyte degeneration leading to ischemia. This triggers VEGF mediated angiogenesis of leaky vessels which hemorrhage.
At what rate due beta cell die in the presence of prolonged hyperglcyermia
At what BP must a diabetic patient be treated for htn?
Hyperplasia of the beta cells due to transplacental effects of glucose at high levels in mother. Hyperplasia in beta cells leads to higher than normal insulin levels.
What are the symptoms of MEN1?
the "P" organs: pancrease, pituitary, and parathyroid overactivity. AD inheritence. (elevated gastin (from pancrease), calcium and parathyroid hormone elevation.
Elevated gastrin, calcium, and parathyroid with lower phosphorus and chloride. Dx?
What three cells makes up the parathyroid gland?
Chief cells, water clear cells, and oxyphil cells
What is the function of calcitonin? Where is it secreted from?
Calcitonin increased calcium uptake in the bones by lowering serum Ca2+. IT IS SECRETED BY THE THYROID GLAND. This hormone is opposed by PTH which increases osteoclast acitivity, thus increasing serum Ca++ by increasing bone resorption
Describe the major actions of PTH?
Stims osteoclastic resorption/inhibits osteoblastic bone formation.2) increases ca++ reabsorption in the kidney while blocking phosphate reabsorption. 3) INCREASES 1-hydroxylation 25-hydroxy vitamin D in the PCT epith. -> 1,25-dihydroxyvitamine D
What is the active form of vitamin D
1,25-dihydroxyvitamin D (Calcetriol). PTH facilitates its formation by converting 25-hydroxy vitamin D
What is the cause of tertiary hyperparathyroidism?
formation of a neoplasia in the presence of a secondary hyperparathyroidism induced hyperplasia
Contrast primary, secondary, and tertiary hyperparathyroidism.
primary: hypersecretion of PTH by an adenoma or hyperplasia Secondary: Physiologic increase in PTH in response to hypocalcemia. Tertiary: development of autonomatous hypersecreting adenoma in longstanding 2ry hyperparathyroidism
Most cases (80%) of primary hyperparathyroidism is due to:
a primary adenoma.
How is a primary hyperparathyroidism different from tertiary?
Primary is due to a primary adenoma, tertiary is due to an adenoma that arises in a patient with SECONDARY DISEASE.
Hypomagnesemia usually coincides with what other imbalance
hypocalcemia. THe kidney confuses these two ions. so: Hypomagnesemia is a cause of hyperparathyroidism
When Calcium goes up... ___ goes down
Whate are the calcium and phosphate levels seen with hyperparathyroidism?
HYPERCALCEMIA and HYPOPHOSPHATEMIA
What are the clinical findings (pt presentation) of hyperparathyroidism
painful bones, renal stones, abdominal groans (pancreatitis) and mental moans
How is an adenoma differentiated from hyperplasia grossly?
If only one parathyroid gland is enlarged, its an adenoma. If all 4 are enlarged, it is hyperplasia
In a bx, how is a hyperplastic parathyroid gland differentiated from a parathyroid adenoma?
Hyperplastic parathyroid has more areas of fat.
Malignancy of endocrine tumors is always determined by the presence of
What is osteitis fibrosa cystica?
brown tumor of bone caused by hyperparathyroidism
What is the ddc of hypercalcemia?
Hyperparathyroidism, paraneoplastic phenomenon, malignancy with bone mets, and thiazide diuretic use. (lithium use, hypervitiminosis D, etc are rarer causes)
How is primary hyperparathyroidism diagnosed
Increased serum calcium levels and raised PTH levels with decreased plasma phosphate and mild metabolic acidosis. THis is confirmed with a SPECT scan of the parathyroid gland.
How is secondary hyperparathyroidism is diagnosed?
Decreased Ca++ amd increased PTH
What is renal osteodystrophy?
Chronic renal failure leading to decreased levels of calcium and *calcitriol* leads to increased PHT --> increased bone resorption and decreased bone remodeling. Also decreased Vitamin D production --> osteolamalasia.
What ist the cause of the osteomalasia seen with renal osteodystrophy?
decreased vitamin D synthesis
All patients with primary hyperparathyroidism should be screened for:
MEN tumors and RET gene mutations
What is Cvostek sign
Twitching of facial muscles after tapping the facial nerve just in front of the ear. Indicative of hypoparathyroidism.
What are the lab finding of hypoparathyroidism>
Low or absent PTH, hypocalcemia, hyperphosphatemia.
Hyperexcitability of muscles is seen with __calcemia, while hypoexcitability (fatigue, etc) is seen with ____calcemia
High PTH with normal or low Ca++ is characteristic of what dz
pseudohypoparathyroidism (Parathyroid resistance). Urinary cAMP fails to rise in response to PTH administration
What is the presentation of pt with pseudohypoparathyroidism
Obese patient with various skeletal abormalities, bachydactly, potters thumb, and dimples over knuckles when fist is clenched.
Flank pain, hematuria, renal calculus. What hormonal syndrome is this likely to be?
MEN syndrome (Multiple Endocrine Neoplasia)
What is the main protein that bind T3 and T3?
Thyrid Binding Globulin
Describe the TOTAL T4, TOTALT3, and T3-Uptake (increased or decreaesed) in Hyperthyroidism?
T4: increased, T3: Increased, T3RU: Increased
Describe the TOTAL T4, TOTAL T3, and T3-Uptake (increased or decreaesed) in Hypothyroidism?
T4: decreased, T3: decreased, T3RU: decreased
Describe the TOTAL T4, TOTAL T3, and T3-Uptake (increased or decreaesed) in Increased protein-binding state
T4: increased, TOTAL T3: Increased, T3RU: decreased
Describe the TOTAL T4, TOTAL T3, and T3-Uptake (increased or decreaesed) in decreased protein-binding state
T4: decreased, T3: decreased, T3RU: increased
When conducting a thryoid scan usuing Technetium, what can be concluded about nodules that take up the isotope, as opposed to those that dont?
Hyperfunctioning nodules will take up isotope... the are hot nodules. Non-functioning nodules will not take up isotope... these are cold nodules. Cold nodules are more likely to cary malignancy, but overall majority of nodules are benign
What is the most common type of tumor in the thyroid ?
Follicular adenoma. it is composed of follicular adenomas (thyroid follices) It presents as a COLD NODULE. Most common 40-60 yo. Has no potential to turn malignant.