Endocrine Flashcards by Ben Dahlberg

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)

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Papillary thyroid cancer

histo of NORMAL variant

branching papillary structures with concentric calcification (Psamomma bodies)

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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)

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Riedel thyroiditis

histo? clinical?

extensive fibrosis extending into surrounding structures

hard + non-tender thyroid

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Neonatal complications of diabetes during pregnancy

premature delivery
macrosomia
malformations - NT, CV and “caudal regression syndrome”
respiratory distress
transient hypoglycemia
polycythemia + hyperviscosity

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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

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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

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3 types of diabetic neuropathy

Distal symmetric neuropathy
Autonomic neuropathy
Mononeuropathy

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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

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Autonomic Diabetic Neuropathy

effects by organ system

GI - gastroparesis and constipation
CV - orthostatic hypo
Urinary - overflow incontinence, “neurogenic bladder”
Sexual - erectile and ejaculatory issues

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Diabetic Mononeuropathy

specific nerves commonly affected

Cranial: oculomotor, facial and optic (ischemic optic neuropathy)

Somatic: commonly bilateral, ULNAR, MEDIAN and COMMON PERONEAL

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Medullary thyroid cancer

histo, assoc.

nests / sheets of polygonal or spindle cells and EC amyloid (calcitonin)

amyloid stains red with CONGO

MEN2A/B

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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

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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

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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)

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Gigantism

s/s

rapid linear growth

weight gain
excess SWEATING
OILY SKIN
large hands + feet
THICK CALVARIUM
PROGNATHISM (large jaw)

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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)

1. Cafe Au Lait Macules - usually UNILATERAL with IRREGULAR borders (melanocyte overstimulation) 2. POLYOSTOTIC FIBROUS DYSPLASIA - fibroblast proliferation, high IL-6 and osteoclast activation; typically UNILATERAL 3. 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?

1. THYROXINE-BINDING GLOBULIN - not to be confused with thyroglobulin which is only in the thyroid; binds 70% of bound T hormones 2. ALBUMIN 3. 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?

Endocrine abnormalities in Klinefelter's (2 + histo picture involved in one of them)

1. SEMINIFEROUS TUBULE DYSGENESIS (don't see normal lumen in testicular histo) > low inhibin B from Sertolis > HIGH FSH 2. 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