Endocrine Flashcards
Differential: clinical, diagnostic, histo
Subacute granulomatous thyroiditis
vs.
Hashimoto’s
de Quervain - after virus, painful, transient hyperthyroid sx; high ESR/CRP; decreased radio-iodine uptake; infiltrate with macros + giant cells
Hashimoto’s - painless, mostly hypothyroid; anti-TPO, variable radio-iodine uptake; lympho infiltrate with germinal centers + Hurthle cells (eosinophilic follicular epithelium with granular cytoplasm/vesicular nucleus)
Papillary thyroid cancer
histo of NORMAL variant
branching papillary structures with concentric calcification (Psamomma bodies)
Papillary thyroid cancer
histo of TALL CELL variant, differential
follicular hyperplasia lined with tall epithelial cells
Graves can also have follicular hyperplasia, but would have increased radio-iodine uptake (via high TSH stim)
Riedel thyroiditis
histo? clinical?
extensive fibrosis extending into surrounding structures
hard + non-tender thyroid
Neonatal complications of diabetes during pregnancy
6
- premature delivery
- macrosomia
- malformations - NT, CV and “caudal regression syndrome”
- respiratory distress
- transient hypoglycemia
- polycythemia + hyperviscosity
Why does TRANSIENT HYPOGLYCEMIA occur in neonates born to diabetic mothers with poorly controlled glucose?
Glucose passes placenta but insulin does not –> stimulates fetal insulin production –> after birth insulin production is still high but maternal glucose is not being provided
2 mechanisms of diabetic neuropathy
- NEG - affects endoneural arterioles > thickening, hyalinization and luminal narrowing > ischemia
- Intracellular hyperglycemia - glucose converted to fructose and sorbitol by ALDOLASE REDUCTASE > water influx with osmotic damage
3 types of diabetic neuropathy
- Distal symmetric neuropathy
- Autonomic neuropathy
- Mononeuropathy
Distal symmetric diabetic polyneuropathy
s/s?
Mostly SENSORY with paresthesias, burning pain, loss of pain/temp/vibration/position
Motor comes mostly with sensory sx, not on its own > weakness, atrophy, decreased deep tendon reflexes
symmetric, bilateral, stocking and glove pattern
Autonomic Diabetic Neuropathy
effects by organ system
GI - gastroparesis and constipation
CV - orthostatic hypo
Urinary - overflow incontinence, “neurogenic bladder”
Sexual - erectile and ejaculatory issues
Diabetic Mononeuropathy
specific nerves commonly affected
Cranial: oculomotor, facial and optic (ischemic optic neuropathy)
Somatic: commonly bilateral, ULNAR, MEDIAN and COMMON PERONEAL
Medullary thyroid cancer
histo, assoc.
nests / sheets of polygonal or spindle cells and EC amyloid (calcitonin)
amyloid stains red with CONGO
MEN2A/B
GPCR-mediated control of insulin release
4 stimulators, 2 inhibitors
Overall effect of epinephrine?
Stimulators: M3 receptor (Gq) Glucagon (Gq or Gs) Beta2 (Gs) GLP-1 (Gs)
Inhibitors:
Alpha2 (Gi)
Somatostatin 2 receptor (Gi)
Epinephrine stimulates B2 and A2, but overall effect is DECREASED insulin release
Diffuse atrophy of thyroid follicles with decreased colloid is seen on histo
Thyroid is small + non-tender and without palpable nodules
What is the cause?
Excess exogenous thyroid hormone
Can be either by mis-dosing of a hypothyroid patient or EATING DISORDER patient with access to thyroid meds
Histo shows atrophy without signs of inflammation
Gigantism
cause (TWO hormones involved + where they’re from + molecular pathways they effect)
increased GH > GH-R on liver > JAK-STAT activation > increased transcription of IGF-1
IGF-1 binds a receptor tyrosine kinase, affecting mostly bone, cartilage, skeletal muscle + other soft tissues
(note that IGF-1 released by hypothalamus regulates CNS and does not play role in growth)
Gigantism
s/s
rapid linear growth
weight gain excess SWEATING OILY SKIN large hands + feet THICK CALVARIUM PROGNATHISM (large jaw)
Laron dwarfism
cause? effect? labs?
GH-R defect > high GH but low IGF-1
decreased linear growth
Androgen insensitivity syndrome
cause? karyotype? phenotype?
testosterone receptor defect
46, XY
phenotypically FEMALE adolescent with PRIMARY AMENORRHEA due to ABSENT INTERNAL REPRODUCTIVE TRACT and presence of CRYPTORCHID testes
mechanism of infertility in hypothyroidism
low T3/4 > TRH release from hypothalamus > there are TRH RECEPTORS ON LACTOTROPHS in the pituitary > PROLACTIN release
Prolactin inhibits GnRH secretion from the hypothalamus > low FHS/LH
pt may also have galactorrhea
Which commonly deficient steroid synthesis enzyme is responsible for the “DOWNWARD MOVEMENT” on the chart from PROGESTERONE and 17-OH PROGESTERONE to final products?
what results from deficiency?
21 hydroxylase - #1 type of CAH
increased androgens; decreased cortisol + aldosterone
males - normal junk; hyperkalemic/hypotensive
females - male junk; hyperkalemic/hypotensive
Which commonly deficient steroid synthesis enzyme is responsible for FURTHER DOWNWARD MOVEMENT on the chart from slightly active intermediates to the final products?
what results from deficiency?
11B-hydroxylase
decreased cortisol; increased androgens and weak MCs (11-deoxycorticosterone)
males - normal junk; hypokalemic/hypertensive
females - male junk; hypokalemic/hypertensive
may have low renin levels
Which commonly deficient steroid synthesis hormone is responsible for ‘RIGHTWARD MOVEMENT’ on the chart from pregnenolone and progesterone to final products?
what results from deficiency?
17alpha-hydroxylase
decreased cortisol + androgens; increased aldosterone
males - feminine junk; hypokalemic/hypertensive
females - normale junk (but delayed menarche); hypokalemic/hypertensive
low renin levels; do not undergo puberty
What is the triad for confirming symptomatic hypoglycemia?
Whipple’s triad
- Symptoms - tremor, sweating, confusion
- Low blood glucose
- Relief when glucose is admin’d
What role do FREE FATTY ACIDS play in type 2 DM?
why are FFAs elevated and what do elevated FFAS affect?
increased circulating FFAs are both caused by and contribute to insulin resistance
- Insulin resistance > less anti-lipolytic effect on fat cells > release of FFAS
- Chronic FFA elevation > IMPAIRS INSULIN-DEPENDENT GLUCOSE UPTAKE and INCREASES GLUCONEOGENESIS
McCune Albright Syndrome
mutation + result?
a mosaic SOMATIC mutation during embryogenesis of the GNAS gene, encoding ALPHA STIMULATORY SUBUNIT of G protein
constitutive activation of Gs pathway
hormone overproduction etc.
McCune Albright Syndrome
first sign; later signs
complications (think of the results of the mutation)
- Cafe Au Lait Macules - usually UNILATERAL with IRREGULAR borders (melanocyte overstimulation)
- POLYOSTOTIC FIBROUS DYSPLASIA - fibroblast proliferation, high IL-6 and osteoclast activation; typically UNILATERAL
- PERIPHERAL PRECOCIOUS PUBERTY - before 8 in girls
hormone overproduction can also cause a) ACROMEGALY, b) THYROTOXICOSIS, and c) CUSHING
Differentiation of cafe au lait in NF1 and McCune Albright syndrome
MAS - large, unilateral, irregular border
NF1 - small, bilateral, smoother border (plus axillary/inguinal freckles, cutaneous neurofibromas; bone involvement can be tibial bowing and pseudoarthrosis)
what 3 molecules bind thyroid hormones for transport in blood?
- THYROXINE-BINDING GLOBULIN - not to be confused with thyroglobulin which is only in the thyroid; binds 70% of bound T hormones
- ALBUMIN
- TRANSTHYRETIN - binds both T4 and retinol+retinol-binding-protein complexes
What effect does INCREASED ESTROGEN have on THYROID HORMONES?
as in pregnancy, oral contraceptives, postmenopausal hormone therapy
first - INCREASES THYROXINE-BINDING GLOBULIN
this binds free T4 > transient TSH increase > more T4 produced > T4 binds excess TBG
finally - TOTAL T4 is INCREASED (but fT4 remains same and patient is clinically euthyroid)
What effect does TNF-alpha have on carbohydrate metabolism and how?
What other molecules have the same effect via the same mechanism?
induces INSULIN RESISTANCE by activating SERINE KINASES that phosphorylate beta subunits of INSULIN RECEPTOR and IRS-1
this inhibits their phosphorylation on Tyr residues by the insulin receptor itself, and thus inhibits downstream signaling
catecholamines, glucocorticoids and glucagon all have same effect
Maternal to fetal transfer of what causes thyroid aplasia?
T4
Endocrine abnormalities in Klinefelter’s (2 + histo picture involved in one of them)
- SEMINIFEROUS TUBULE DYSGENESIS (don’t see normal lumen in testicular histo) > low inhibin B from Sertolis > HIGH FSH
- Abnormal Leydig cell function > low testo > high LH > HIGH ESTROGEN
Cushing’s DISEASE adrenal histo
cush DISEASE = pituitary ACTH adenoma
increased ACTH causes CORTICAL HYPERPLASIA (not hypertrophy; so number of cells, not size of cells)
Very SPECIFIC dermatological finding of Graves
+ its pathophys mech
“thyroid dermopathy”
PRETIBIAL MYXEDEMA - induration and thickening of shin skin
stimulation of FIBROBLASTS by anti-TSH-R Ab and activated T-cells > produce GAGs
(similar mech for retro-ocular fibroblasts in Graves ophthalmopathy)
2 molecular pathways stim’d by insulin + their effects
PI3K - glycogen, lipid + protein synth; GLUT4 translocation
RAS/MAP kinase - cell growth + DNA synth
biochem mechanism of opposing actions of glucagon and insulin on glycogen metabolism
insulin - activates PROTEIN PHOSPHATASE > DEphosphorylation of glycogen synthase + glycogen phosphorylase promotes glycogen SYNTHESIS
glucagon - activates PKA > PHOSPHORYLATION of glycogen synthase + glycogen phosphorylase promotes glycogenoLYSIS
(glucagon > PKA > glycogen phosphorylase kinase > activated glycogen phosphorylase)
SIADH
how does it affect sodium levels and volume and why?
“Euvolemic Hyponatremia”
high ADH > water resorption in CDs > transient hypovolemia suppresses RAAS and activates ANP + BNP SECRETION > natriuresis
this compensates for the volume overload, but the hyponatremia remains
What is the weak mineralocorticoid that is in excess in one of the forms of CAH?
11-deoxycorticosterone
in 11B-hydroxylase deficiency
(results in increased androgens and mineralocorticoid effects)
What are endogenous fasting serum insulin levels like in someone with long-standing T2DM treated with insulin?
VERY LOW
due to beta cell exhaustion + inhibition of insulin release by control of blood sugar via exogenous insulin
Fasting glucose and random glucose values ABOVE WHICH a diabetes diagnosis can be made
fasting at least 126 mg/dl
random at least 200 mg/dl
