Endocrine Flashcards
Xanthelesmas, a type of xanthoma, are yellowish macules/papules found on the medial eyelids; they are dermal accumulations of mo containing cholesterol and triglycerides; an LDL receptor abnormality is the most common cause
Congenital hypothyroidism
TSH resistance due to a mut in a TSH receptor gene; characterized by increased TSH and low thyroxine; thyroid gland is normal in size and location
Sulfonylureas
(glipizide) inhibit the ATP-sensitive K+ ch on the pancreatic beta cell inducing depolarization and L-type Ca2+ ch opening; increased Ca2+ influx stimulates insulin release independent of [blood glucose] increasing the risk of hypoglycemia when meals are missed or during exercise
Pheochromocytoma
a tumor arising from the chromatin cells of the adrenal medulla characterized by excess production of catecholamines; presents w episodic HTN, diaphoresis, and palpitations tumor cells show electron-dense membrane bound secretory granules and immunohisto show (+) synaptophysin, chromogranin and neuron-specific enolase
Postoperative hypoparathyroidism
hypocalcemia is a common complication due to inadvertent injury or removal of the parathyroid gland; postoperative supplementation with oral Ca2+ and vitamin D can be used to prevent postoperative hypocalcemia
SGLT-2 inhibitors
Canagliflozin and Dapagliflozin
decrease renal reabsorption of glucose and Na+ resulting in osmotic diuresis and natriuresis leading to reduced BP and decreased mortality rate in HF pts
long term use of exogenous glucocorticoids
causes suppression of the HPA which leads to b/l adrenocortical atrophy involving the zona fasciculata and reticularis; cessation can lead to adrenal crisis
NE to epi
cortisol increases the conversion of NE to epi in the adrenal medulla by increasing the expression of phenylethanolamine-N-methyltransferase (PNMT)
Primary adrenal insufficiency
autoimmune destruction of the b/l adrenal cortex; reduced aldosterone (renal salt wasting w hypovolemia, hypotension, and hyperkalemia); reduced cortisol causes decreased EPI w a compensatory increase in NE
Smoking cessation
by far the most effective prevention in almost all pts, especially diabetics
ATP-sensitive K+ channels
oxidative metabolism of glucose in pancreatic cells generate ATP; ATP-induced closure of ATP-sensitive K+ ch leads to membrane depolarization and subsequent insulin release
Hyperaldosteronism
results in hypokalemia which causes muscle cramps, muscle weakness and paresthesia
Gynecomastia and tx
development of glandular breast tissue in males and is commonly seen in men receiving androgen deprivation therapy for prostate cancer; tamoxifen inhibits the effect of estrogen on breast tissue and can reduce the risk
Hirsutism
male-pattern hair growth in a women most common cause is PCOS; combination contraceptive pills can tx by suppressing pituitary LH secretion and subsequently decreasing ovarian androgen production
Causes of increased risk of hypoglycemia in DM1
pts w DM1 are at increased risk of hypoglycemia because exogenous insulin will continue to be absorbed from the injection site despite failing glucose levels; long standing diabetes will cause alpha-cell (glucagon) failure leading to decreased glucagon secretion which leads to a greater risk for hypoglycemia
Methimazole
thioamides (methimazole and propylthiouracil) decrease the formation of thyroid hormones via inhibition of thyroid peroxidase enzyme responsible for both iodine organification and coupling of iodotyrosines; PTU also decreases peripheral conversion of T4 to T3
Excess production of ACTH
trophic hormone for zona fasciculata and reticularis; excess ACTH causes increased cortical (Cushing’s) and increased androgens (irregular menses, hirsutism)
Embryology of adrenal medulla
neural crest cells; multipotent, migratory cells that originate in ectoderm; also gives rise to melanocytes and neural ganglia
Gherlin
stimulates appetite and promotes weight gain; caloric restriction leads to increased gherlin levels along w decreased insulin and leptin levels causing an increase in appetite that can make it difficult to maintain weight loss
21-hydroxylase deficiency
most common form of congenital adrenal hyperplasia; excess stimulation of the adrenal cortex by ACTH; presentation of non-salt wasting, early virilization (2-4 yrs), accelerated linear growth and elevated 17-hydroxyprogesterone and androgens
21-hydroxylase deficiency tx
low doses of exogenous corticosteroids to suppress excess ACTH secretion, which reduces production of androgens by the adrenal cortex
physiological insulin secretion
admin of long-acting and rapid-acting insulin analogues; long-acting (ex: glargine) replicate basal insulin and rapid-acting (ex: lispro) replicate meal-related insulin surges
pituitary apoplexy
acute pituitary hemorrhage (pituitary apoplexy) is characterized by severe HA, bitemporal hemianopsia and ophthalmoplegia (CN III); occurs in preexisting adenoma; it is an medical emergency that requires urgent tx w glucocorticoids to prevent adrenal crisis and circulatory collapse
Injectable or intranasal glucagon
severe hypoglycemia causing impaired consciousness can be tx by glucagon which rapidly corrects hypoglycemia by increasing hepatic glycogenolysis, resulting in release of glucose from pre-existing hepatic glycogen storage
Maple syrup urine disease
presents within the first few days of life with irritability, dystonia, poor feeding and sweet-smelling urine; dietary restriction of branched chain amino acids (leucine, isoleucine and valine) is required
brown adipose cells
contain multiple lipid droplets and abundant mitochondria, produce large amounts of heat (thermogenesis) by uncoupling oxidative phosphorylation w the protein thermogenin; preterm infants are at increased risk for hypothermia because they have less brown adipose tissue
Hypothyroidism effects on lipids
causes decreased expression of LDL receptors in the liver leading to decreased clearance of LDL and increased blood LDL levels; also causes hypertriglyceridemia due to decreased expression of lipoprotein lipase; pts are at increased risk for coronary atherosclerosis
hyperthyroid induced bone loss
causes increased bone turnover w net bone loss potentially leading to osteoporosis; bone loss is driven by T3 which stimulates osteoclast differentiation, increased bone resorption and release of Ca2+
hypothyroid myopathy
presents w myalgias, proximal muscle weakness, elevated creatinine kinase, delayed relaxation of DTRs; dx can be confirmed by elevated TSH
Ketones
when glycogen stores are depleted during fasting, ketone bodies are produced in the liver and can be used as an energy source in the mitochondria; preferentially the brain; erythrocytes lack mitochondria and unable to use ketones
thyroid migration
thyroid gland is formed from evagination of the pharyngeal epithelium and descends to the lower neck; due to failure of *migration the thyroid can reside anywhere along the thyroglossal duct’s usual path, including the tongue (lingual thyroid)
tx of prolactinoma
prolactin-secreting pituitary adenoma is tx w dopamine agonist (ex: cabergoline); suppresses prolactin production and reduce tumor size; benefits are typically seen within the first few weeks
hypercalcemia-induced constipation
hypercalcemia inhibits nerve depolarization, leading to impaired smooth muscle contraction and reduced motility; symptoms include constipation, cramps abdominal pain and nausea
Thyroid hormone resistance
thyroid hormone resistance is characterized by decreased sensitivity of peripheral tissues to thyroid hormones due to defect in the thyroid receptor; T3, T4 and TSH will all be elevated; presents as goiter and ADHD
somatostatinoma associated biliary stones
somatostatin inhibits CCK; decreased CCK leads to decreased gallbladder contractility; increased risk for biliary stones
Growth hormone signal transduction
GH binds to cell surface receptors leading to intracellular activation of JAK-STAT pathway; cytokines and hematopoietic GFs also use this pathway
Papillary thyroid carcinoma
most common type of thyroid cancer; large cells w nuclei containing finely dispersed chromatin, giving them an empty or ground-glass appearance (ex: Orphan Annie eye), as well as intranueclear inclusions and nuclear grooves
most common type of thyroid cancer; large cells w nuclei containing finely dispersed chromatin, giving them an empty or ground-glass appearance (ex: Orphan Annie eye), as well as intrnueclear inclusions and nuclear grooves
Canagliflozin and Dapagliflozin MOA
SGLT2 inhibitors decrease renal reabsorption of glucose and Na+ leading to increased urinary glucose excretion and decreased BG levels; increased natriuresis and osmotic diuresis lead to a small decrease in Extracellular fluid volume, total body Na+ content and BP
SGLT2 inhibitors
Canagliflozin and Dapagliflozin; tx for DM2; decrease renal reabsorption of glucose and Na+ leading to increased urinary glucose excretion and decreased BG levels
Insulin-induced weight gain
insulin can cause weight gain due to physiologic and behavioral factors; counseling should elicit the pts perspective on appetite, changes in dietary patterns and hypoglycemic symptoms
neonatal hypoglycemia
common in infants in diabetic mothers; pathophysiology involves maternal hyperglycemia which in turn causes fetal hyperglycemia and compensatory hyperfunctioning of the pancreas (hyperinsulinemia); after birth persistently elevated insulin levels lead to transient hypoglycemia
Testosterone replacement therapy
indicated for men w symptomatic hypogonadism; associated w an increase in serum prostate-specific antigen and may increase risk of prostate cancer; can also cause erythrocytosis (leading to thromboembolism) and hematocrit
CF-related diabetes
cystic fibrosis (CF) causes the accumulation of thick, viscous secretions in ducts throughout the body; CF-related diabetes occurs after the progressive destruction of pancreatic islet cells leads to decreased insulin production
Graves disease drug-induced neutropenia
drug-induced neutropenia is the major side effect of 1st line meds used to tx Graves; initial manifestations usually include fever and oropharyngeal ulcers
Metyrapone stimulation test
admin of metyrapone will cause a decrease in cortisol synthesis via inhibitor of 11B hydroxylase; in pts with an intact HPA axis this will cause a reactive increased in ACTH, 11-deoxycortisol (DOC) and urinary 17-hydroxycorticosteroid
Prolactin-secreting tumors on GnRH HPA axis
elevated prolactin levels suppress the release of GnRH, leading to decreased LH and impaired testosterone production in men
hCG testicular germ cells induced gynecomastia
secretion of hCG by testicular germ cell tumors impairs testosterone production in Leydig cells while increasing aromatase activity and conversion of androgens to estrogens; resulting increase in estrogen/androgen ration can cause gynecomastia
Sorbitol accumulation
in hyperglycemic states, aldose reductase converts glucose to sorbitol at a rate faster than sorbitol can be metabolized; sorbitol accumulates in certain cells, lens, leading to cataracts
Polyol pathway
aldose reductase converts glucose into sorbitol which is slowly metabolized into fructose by sorbitol dehydrogenase
Osteoporosis associated w chronic admin of GnRH agonist
chronic GnRH agonist (ex: leuprolide) suppresses pituitary LH release and leads to reduced production of testosterone; lower levels of circulating testosterone produces a clinical effect similar to orchiectomy and can lead to accelerates bone loss and increased risk for osteoporosis
SERMs
Tamoxifen and Raloxifene
selective estrogen receptor modulator (SERM) has estrogen agonist activity on bone and decreases bone resorption; increase the risk for venous thromboembolisms
Anorexia nervosa on functional hypothalamic amenorrhea
functional hypothalamic amenorrhea is a common cause of secondary amenorrhea and occurs due to decreased amplitude and frequency of pulsatile GnRH leading to low FSH, LH and estrogen; causes are anorexia, excessive strenuous exercise and chronic illness
metformin
metformin
lowers blood glucose by reducing hepatic gluconeogenesis and increasing insulin-dependent peripheral glucose uptake; lactic acidosis is a rare complication of metformin therapy; the risk is increased in pts w underlying renal insufficiency
Postpartum thyroiditis
occurs within 12 months of pregnancy and is characterized by autoimmune destruction of thyroid follicles; typically begins w a hyperthyroid phase due to the release of preformed thyroid hormone, followed by a hypothyroid phase due to depletion of thyroid hormone and an eventual return to a euthyroid state; histo - lymphocytic infiltration w the formation of germinal centers (similar to chronic lymphatic Hashimoto thyroiditis)
pharmacokinetic profiles of common insulin preparations
regular insulin has a rapid onset and short half-life allowing the rapid adjustments needed for DKA; peaks in 2-4 hrs and lasts 5-8 hrs
functional hypothalamic amenorrhea
results from loss of pulsatile GnRH release from the hypothalamus and is caused by weight loss, strenuous exercise, systemic illness or abnormal eating habits
proinsulin: insulin and c-peptide
proinsulin is cleaved into insulin and c-peptide; c-peptide is a marker of endogenous insulin secretion; diabetic meds that increase endogenous insulin secretion (ex: sulfonylureas) elevate the c-peptide levels
thyroid peroxidase (TPO)
TPO catalyzes the oxidation of iodide to iodine, the iodination of thyroglobulin tyrosine residues and the iodotyrosine coupling reaction that forms T3 and T4; antibodies against TPO are present >90% of pts w Hashimoto thyroiditis
primary hyperaldosteronism (Conn syndrome)
caused by excessive aldosterone secretion, typically due to an aldosterone-producing adrenal adenoma or b/l nodular hyperplasia of the zona glomerulosa; presents HTN, low plasma renin, hypokalemia and metabolic alkalosis
Vasopressin and oxytocin release
synthesized and packages w carrier proteins (neurophysins) within neurons found in the hypothalamus; hormones are transported down axonal projections to the posterior pituitary (neurohypophysis) where they are secreted into circulation
Autoimmune insulinitis
progressive beta cell loss; most common cause of DM1
MEN type 2
caused by a gremlin activating mut in RET photo-oncogene and frequently results in both medullary thyroid cancer and pheochromocytoma;
Exercise, insulin & glucose transport
glucose uptake in skeletal muscle occurs primarily via GLUT4; muscle contraction and insulin induce translocation of GLUT4 to the cell surface increasing glucose uptake during exercise and lower BG levels
Stress hyperglycemia
transiently elevated BG levels in context of severe illnesses (sepsis, burns, major hemorrhage) in pts w/o preexisting diabetes cortisol and catecholamines released in response to severe metabolic stress act on the liver to increase glycogenolysis and gluconeogenesis
beta blockers in thyrotoxicosis
beta blockers (ex: propranolol) provide rapid relief of the adrenergic-mediated symptoms of thyrotoxicosis and can be given while awaiting diagnostic evaluation and definitive management
Inhibit B
LH stimulates the release of testosterone from the Leydig cells of the testes; FSH stimulates the release of inhibin B from Sertoli cells in the seminiferous tubules; inhibin B induce negative feedback on FSH
Secondary hyperthyroidism
most common cause is a TSH-secreting pituitary adenoma; elevated TSH, T3 and T4
5-alpha reductase deficiency
converts testosterone to DHT; mediates development of the external genitalia in the male fetus; male neonates with 5-alpha reductase deficiency are born w ambiguous genitalia that typically masculinize at puberty
Klinefelter syndrome
47, XXY causes infertility characterized by primary hypogonadism (elevated FSH and LH and low testosterone) and azoospermia
changes in male hormone levels w age
normal aging in men is associated w slow decline in gonadal testosterone production, compensatory rise in LH and rising serum levels of sex hormone-binding globulin; nonspecific symptoms of decreased ejaculate volume, increased erectile latency and sexual refractory time
Aromatase inhibitors
anastrozole, letrozole, exemestane; aromatase inhibits decrease the synthesis of estrogen from androgens, suppressing estrogen levels and slowing progression of ER (+) tumors
Hormone sensitive lipase
found in adipose tissue where it functions to drive the breakdown of stored triglycerides into FFAs and glycerol; during times of starvation, this enzyme provides substrates for hepatic gluconeogenesis and ketone formation
Familial chylomicronemia syndrome type I
defect in lipoprotein lipase; elevated chylomicrons; major manifestations: acute pancreatitis
hyperosmotic volume contraction
hyperosmotic volume contraction is caused by loss of free water (w retention of electrolytes); can occur in pts w diabetes insipidus or as a result of decreased fluid intake/excessive sweating
Sheehan syndrome
high estrogen levels during pregnancy causes enlargement of the pituitary gland w/o a proportional increase in blood supply; permpartum hypotension can cause ischemic necrosis of the pituitary leading to panhypopituitarism (Sheehan syndrome); pts commonly develop failure of lactation due to deficiency of prolactin
osteoclast differentiation
PTH directly stimulates osteoblasts leading to bone formation; expression of RANKL on osteoblasts indices increased bone resorption via paracrine effect on nearby osteoclast; hyper-PTH causes increased RANKL expression and decreased expression of osteoprotegrin leading to net bone loss
G protein-coupled receptors on pancreatic beta cells
alpha-2 adrenergic receptors inhibit insulin secretion and beta-2 adrenergic receptors stimulate insulin secretion
VitD deficiency caused by anticonvulsants
catabolism of VitD is initiated by CYP24A1 (aka 24-hydroxylase); expression of this enzyme is induced by phenytoin and other anticonvulsants (ex: carbamazepine), which can lead to increased breakdown of VitD and lead to VitD deficiency
thyroid lymphoma
primary lymphoma of the thyroid is characterized by rapidly progressive thyroid enlargement, often w compression of surrounding structures; thyroid lymphoma is uncommon, but the incidence is significantly greater in pts w preexisting chronic autoimmune Hashimoto’s thyroiditis
