Endocrinology

Sex hormones growth at epiphyseal plate closure; precocious puberty may result in
short stature despite initial growth spurt (excess sex hormone will close plates
prematurely)
Cushing Syndrome can result from (1) exogenous glucocorticoids, most commonly, (2)
ACTH secreting pituitary adenoma, (3) Ectopic production of ACTH (paraneoplastic), (4)
Primary adrenocortical hyperplasia
Pituitary adenomas (Cushing disease) and ectopic ACTH = elevated ACTH levels,
suppression with
high dose dextromethasone
Serine and threonine residue phosphorylation by serine kinase leads to insulin resistance
(TNFa, catecholamines, glucocorticoids, and glucagon (GLUT-4)
Lactic acidosis (gapped) occurs w/ septic shock d/t tissue hypoxia, which results in
impaired oxidative phosphorylation (pyruvate lactate in glycolysis)
Elderly pts w/ dementia or hemiparesis may also have dysphagia = risk factor for
aspiration pneumonia
Lecithin-sphingomyelin ratio marker of fetal lung maturity; Glucocorticoids have
greatest effect on increasing surfactant production
Thyroid peroxidase iodination of thyroglobulin to produce T3 and T4
Glucokinase is first enzyme in glycolytic pathway in the beta cell of pancreas mutations
of this enzyme result in mild hyperglycemia, exacerbated during pregnancy
MEN1: parathyroid, pancreas (hypergastrinemia and ulcer formation) and pituitary
MEN 2A: medullary carcinoma of thyroid, pheochromocytoma, parathyroid
MEN 2B: medullary carcinoma of thyroid, pheochromocytoma, mucosal neuromas
MEN 2 RET proto-oncogene
Chromaffin cells of adrenal medulla and parafollicular cells of thyroid both originate
from neural
crest.
Most common reason for elevated AFP levels is underestimation of gestational age;
Downs syndrome assc w/ decreased AFP levels
Kallmann Syndrome absence of GnRH secretory neurons in the hypothalamus d/t
defective migration from olfactory placode hypogonadism and anosmia w/ delayed
puberty
Flutamide = non steroidal anti-androgen that competes with testosterone and DHT for
testosterone receptors used for prostate cancer tx in combo with GnRH agonists
Finasteride decreased peripheral conversion of testosterone into DHT by inh 5areductase

Endocrinology
Ketoconazole weak antiandrogen, decreases synthesis of steroid hormones in gonads
and adrenals
GnRH agonists leuprolide, goserelin, nafarelin and histrelin bind to receptors in
anterior pituitary and inhibit synthesis of LH and FSH, which leads to decreased Leydig
cell stimulation and diminished testosterone synthesis
Transmembrane domains hydrophobic AAs: valine, alanine, isoleucine, methionine and
phenylalanine; assoc w/ glycoprotein hormones (TSH, LH and FSH)
After 12-18hrs of fasting, gluconeogenesis is primary source of blood glucose initial
step is conversion of pyruvate to OAA and OAA to phosphoenolpyruvate.
Neurophysins = carrier proteins for oxytocin and ADH from paraventricular and
supraoptic nuclei to site of release in posterior pituitary. Point mutations in neurophysin II
diabetes insipidus (insufficient ADH release)
Estrogen effects on thyroid hormone estrogen causes increase in total T4, but function
remains normal (as w/ pregnancy or oral contraceptives) TBG is increased which leads to
increased circulating levels of T4 and T3, free levels of thyroid hormone remain the same
Diabetes Tx:
Metformin intracellular microsomal enzymes to reduce glucose levels by
enhancing glycolysis and inh gluconeogenesis
Acarbose alpha glucosidase inhibitor decreases the activity of membrane bound
disaccharidases on the intestinal brush border (prevent disaccharide breakdown to
allow carbohydrate absorption, which is absorbed as monosaccharide)
Insulin surface tyrosine kinase-coupled receptor
Sulfonylurea membrane bound ion channel
GLP-1 acts on surface adenylate cyclase-coupled receptors; decreases glucose by
inducing satiety, decreasing gastric emptying and increasing insulin release
TZDs act on intracellular nuclear receptors; bind to peroxisome proliferator
activated receptor gamma (PPAR-gamma) which is a transcriptional regulator of
genes involved in glucose and lipid metabolism; decrease insulin resistance and
increase adiponectin levels (which are low in T2DM)
Celiac disease decreased absorption of Vit D and therefore Ca and PO4 from SI low
levels of Vit D and hypocalcemia cause increase in PTH release (secondary
hyperparathyroidism). This causes more PO4 to be excreted and bone mineralization,
leading to signs of osteomalacia.
Decreased serum calcium and phosphorus with increased serum PTH
Non-selective B-blockers exacerbate hypoglycemia and mask adrenergic symptoms
(sweating, tremor, palpitations) by inhibiting epi/NE compensatory reactions. Selective
B1 antagonists should be used instead if a B-blocker is needed

Endocrinology
Graves disease hyperthyroidism w/ infiltrative opthalmopathy and pretibial myxedema
glucocorticoids are used to control opthalmopathy and decrease severity of
inflammation
Anovulation common cause of infertility treat with drugs that act like FSH and LH
(menotropin); ovulation is induced by administration of large dose of hCG which
stimulates LH surge
DKA results from deficiency of insulin and excess of glucagon (coupled with adrenergic
activation and increased levels of growth hormone and cortisol)
DMT1 pt unable to produce insulin to prevent hyperglycemia and inhibit glucagons
effect
Glucagon stimulates ketoacid production in adipose tissue (as well as
glycogenolysis,
gluconeogenesis, lipolysis and urea production)
Insulin acts via tyrosine kinase second messenger to stimulate synthesis of glycogen,
proteins, fatty acids and nucleic acids leads to activation of protein phosphatase which
directly modulates enzyme activity
Medullary carcinoma of thyroid deposits of amyloid formed by calcitonin secreted from
neoplastic parafollicular C cells congo red positive deposits
Papillary thyroid cancer calcifications and psamomma bodies ground glass, grooved
nuclei
Anaplastic thyroid carcinoma large pleomorphic giant cells
21-hydroxylase deficiency salt wasting and virilization (ambiguous genitalia in females)
vomiting, hypotension, hyponatremia and hyperkalemia
Cannot synthesize aldosterone and cortisol, increased production of androgens d/t
diversion of accumulating precursors. Increased serum levels of 17-hydroxyprogesterone
FFA and serum triglycerides are believed to increase insulin resistance in overweight pts
Aldolase B deficiency hereditary fructose intolerance which manifests after
introduction of fructose into diet with vomiting and hypoglycemia, failure to thrive,
jaundice and hepatomegaly
IP3 second messenger system: G protein coupled receptor activates phospholipase C
degradation into DAG and IP3 Protein Kinase C is activated by DAG as well as Ca+
released from SR under the influence of IP3
Pyruvate dehydrogenase deficiency prevents conversion of pyruvate to acetyl coA
leading to lactic acidosis; lysine and leucine are exclusively ketogenic and would not
further increase blood lactate levels in these pts
17-hydroxylase deficiency impairs synthesis of androgens and estrogens and cortisol but
does not inhibit mineralocorticoid production boys appear phenotypically female at
birth but girls develop normal genitalia. Hypogonadism, hypertension, hypokalemia

Endocrinology
21-hydroxylase deficiency is most common type of CAH decreases glucocorticoid and
mineralocorticoid synthesis and increases production of adrenal androgens; male
appears phenotypically normal and develops hypotension and hyperkalemia (salt
wasting)
11B-hydroxylase deficiency causes decreased glucocorticoid synthesis and increased
production of adrenal androgens. Features of mineralocorticoid excess. Male
phenotypically normal and present with hypertension and hypokalemia
5a reductase deficiency results in defective testosterone to DHT, which is responsible for
fusion of labial folds during male fetal development. Affected males have ambiguous
genitalia at birth but develop normal secondary sexual characteristics at puberty
T2DM pancreatic amyloid deposition, increased insulin resistance
T1 DM pancreatic islet infiltration w/ leukocytes, circulation anti-islet antibodies, HLA
class II (DQ and DR 3, DR 4), ketoacidosis with insulin therapy
Klinefelters XXY hypogonadisum, small firm testes, infertile, increased LH and FSH d/t
loss of feedback inhibition w/ decreased testosterone and sperm count
Kallmanns is d/t central hypogonadism decreased LH/FSH/testosterone and
sperm count
Intramuscular glucagon or IV glucose is used to treat severe hypoglycemia
SIADH low plasma sodium and osmolality, inappropriately concentrated urine,
increased urinary sodium and normal body fluid volume paraneoplastic effect
secondary to small cell carcinoma of the lung (EUVOLEMIC HYPONATREMIA)
Thyrotoxicosis labs show decreased TSH and increased free T4 B blockers decrease
effect on sympathetic adrenergic impulses and decrease in rate of peripheral conversion
of T4 to T3
Amino Acid
Amino acids w/ three titratable protons = histidine, arginine, lysine, aspartic acid,
glutamic acid,
cysteine and tyrosine
Histidinemia - Rare autosomal recessive disorder with deficiency of histidase
Basic Amino acids = histidine, arginine and lysine
Insulin DOC for gestational diabetes
McArdles Syndrome myophosphorylase deficiency, type 5 glycogen storage disease;
failure of glycogenolysis w/ decreased exercise tolerance, myoglobinuria, and muscle
pain w/ physical activity
Heavily methylated DNA low transcriptional activity
Histone acetylation euchromatin (loosely arranged), high transcriptional activity

Endocrinology
Destruction of hypothalamus (and dopamine production) would lead to INCREASED levels
of prolactin, which is under constant inhibition by Dopamine
von Willebrands Disease prolonged bleeding. vW factor increases stability of VIII and
important in forming platelet plug treated with Desmopressin which is known to
increase vWF release from endothelial cells
Desmopressin can also be used to treat enuresis
Adrenal crisis = hypotensive, tachycardic and hypoglycemic tx with corticosteroids
Primary mineralocorticoid excess = hypertension, hypokalemia, suppressed renin and
non-suppressible aldosterone (decreased potassium and increased bicarb = metabolic
alkalosis)
Spironolactone anti-androgen properties used for hirsuitism (flutamide and finasteride
can also be used)
Dietary fructose is phosphorylated in liver to F1P and rapidly metabolized, bypasses PFK
rate limiting step of glycolysis
Coronary heart disease is most common cause of death in pts with DMT2
W/ Essential fructosuria, metabolism of fructose by hexokinase to F6P is primary
metabolism; this is not significant pathway for dietary fructose metabolism in normal
individuals
Primary hyperparathyroidism bones, stones, groans and psychic moans
subperiosteal thinning w/ cystic degeneration
Adrenal insufficiency hyponatremia, hyperkalemia, hypochloremia, metabolic acidosis
Menopause elevated FSH, absence of cycle for 6 mos
DM during pregnancy transient hypoglycemia in baby, fetal macrosomia,
Breast ca aromatase inhibitors to decrease estrogen (anastrozole)
Cortisol increases transcription of enzymes in gluconeogenesis
Amiodarone = anti-arrhythmic; induces hypothyroidism; co-administer with levothyroxine
Also assoc w/ thyroid dysfxn, corneal micro-deposits, blue-gray skin discoloration,
hepatitis and pulmonary fibrosis
Smooth ER steroid and phospholipid biosynthesis; all steroid producing cells (adrenals,
gonads, liver) contain a well developed smooth ER which is stimulated by ACTH
Agranulocytosis is rare but serious complication of anti-thyroid drugs WBC count with
differential is necessary in pt receiving methimazole or PTU who present with a fever

Endocrinology
hCG has structural similarity to TSH. Can be produced from teratoma/testicular tumor
and cause hyperthyroidism