Glucocorticoid side effects
Iatrogenic Cushing's syndrome (buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, Acne, adrenocortical atrophy, peptic ulcers, glucose intolerance/ diabetes (if chronic); Immunosuppression, psychosis, Glaucoma, insomnia. Adrenal insufficiency when the drug is stopped after chronic use.
#1 most common location for ectopic thyroid tissue
2 main tests to evaluate thyroid status
next most valuable test is 2 - free T4.
21 α hydroxylase deficiency
Masculinization, hypotension (deion); 11Beta-hydroxylase deficiency - Hypertension, masculinization (drew).
3 toxicities of insulin
Hypoglycemia, Lipodystrophy (where you inject insulin), weight gain.
48 year-old female suffering with progressive lethargy and extreme sensitivity to cold. Most likely diagnosis
hypothyroidism (#1 Hashimoto Thyroiditis)
5 Areas of hypothalamus that regulate food intake
Paraventricular nucleus also regulates food intake. Dorsomedial nuclei and Arcuate nucleus also regulate food intake.
Lateral hypothalamus is inhibited by leptin.
Ventromedial area. Receive many inputs: GI gut distension, nutrient signals from the blood. Hormones ie leptin. Cortex sight, smell, taste.
5 categories for the diagnosis of metabolic syndrome
Waist circumference; TGAs; HDL; fasting blood glucose; BP "X = GB HAT"
50 year old female complains of double vision (bitemporal hemianopia), amenorrhea, low libido, and headaches, Galactorrhea. Most likely diagnosis
Prolactinoma, pressing optic chiasm.
A 35-year-old female presents w/ diffuse goiter and hyperthyroidism. Her relative values of TSH and thyroid hormone show
Graves Disease: ↓TSH, ↑ free T4 (Thyroid hormone) , ↑ total T4, ↑T3 uptake.
Addison's characterized by 3 A's
Adrenal Atrophy and Absence of hormone production (involves All 3 cortial divisions. ADDison's = Cusing's + Conn's
Chronic Primary adrenal insufficiency due to adrenal atrophy or or destruction by disease (autoimmune TB, Metastiasis)
Adipocyte-generated leptin affects the hypothalamus
Inhibits lateral area, stimulates ventromedial area; -> Satiety
modified fibroblasts that use GLUT-4 receptors (insulin dependent) Produce the hormone leptin which stimulates appetite and termogenesis. Store TGAs in cytosol. 80-95% triglycerides. Converted to saturated or unsaturated form. Can Synthesize small amounts of fatty acids and triglycerides from carbohydrates (like the liver). Turnover of Stored Fat (Lipases) Every 2-3 weeks.
most common tumor of the adrenal gland
Adrenal "incidentaloma" - benign,
traps glucose in cell by converting it to sorbitol
Sorbitol is then converted to fructose using sorbitol dehydrogenase (Schwann cells, lens, retina, kidneys don't have!). If ↑ blood levels galactose (AR) will also ® osmotically active alcohol forms.
Affect of aldosterone on potassium?
Aldosterone makes you LOSE POTASSIUM -> HYPOKALEMIA
Increases salt reabsorption and potassium excretion. Acts on Principle cells of collecting tubules. Also at the sweat glands.
- Retention of salt at sweat glands prevents excess leakage of water. Increases sodium reabsorption from the gut. ↑ BP;
- ↓ Heart contractility because of increased serum sodium (opposite of digoxin).
- Pro vascular, prohypertensive, but anticontractility to a certain extent. Thus, in a patient w/ CHF, it is a good idea to give an aldosterone antagonist like spironolactone ® reverse the sodium effect on the heart (XS salt increases gradient to drive calcium out of the myocytes, reducing contractility) and also reduce afterload by reducing blood pressure.
What stimulates aldosterone release? What reduces its release?
Stimulated by: ↑ K+, ANG II,
Reduced by: ↓ Na2+
Leptin; MSH; Serotonin; Norepinephrine; CRH; Insulin; CCK. Signal that you are in a fed or alert state (↓feeding).
When should metformin be avoided?
Avoid metformin if IV contrast needed for imaging (IV contrast toxic to kidney) ® ↑ risk for lactic acidosis. Also avoid if Renal disease, Advanced liver disease or CHF.
BMI that a patient is considered obese
obese > or = 30.
overweight range BMI
BMI: 25-30 is overweight range. 18.5 to 25 is normal
Another term for Bone marrow suppression
Cancers associated with RET gene mutation
Medullary thyroid carcinoma
Papillary thyroid carcinoma
Causes of Lipodystrophy
sites of insulin injections
Cells sensitive to Osmotic damage
because they don't have Sorbitol dehydrogenase (sorbitol -> fructose)
"It's SLeRK out when it Rains (osmotic damage), wish I was in SD (sorbitol dehydrogenase)
Used to treat pain associated with parasthesias in diabetics
Parasthesias (tingling with pain on feet) Treat with
- Gabapentin (Neurontin) or Pregabalin (Lyrica) for pain.
Clinical applications of atropine
↓ airway secretions (anesthesiology);
Pupillary dilation and cycloplegia,
↓ stomach acid secretion;
↓ gut motility;
↓ urgency/bladder spasms;
Antidote for organophosphate poisoning.
Clinical features of acromegaly
large hands/feet; coarse facial features (large nose, ears, tongue); ↑ spacing of teeth; Deep voice; Impaired glucose tolerance.
Clinical manifestations of Addison disease?
Cause of addison disease?
Cause - Autoimmune destruction of adrenals: Adrenal atrophy; ↓ aldosterone ↓ cortisol.
Clinical uses for somatostatin
Pituitary excess: Acromegaly, TSH-secreting tumor (thyrotropinoma), ACTH secreting tumors;
GI endocrine excess: Zollinger-Ellison syndrome, carcinoid syndrome (XS serotonin), VIPoma (AKA pancreatic cholera), gastrinoma, glucagonoma, insulinoma; Certain diarrheal dx (off-label use!);
Need to reduce splanchnic circulation: portal hypertension (bleeding esophageal varices), bleeding peptic ulcers (Off-label use, but fairly common).
Common alpha subunit
TSH, LH, FSH, and β-hCG (not pituitary)
Complications of obesity
Osteoarthritis of hips and knees. Nonalcoholic Steatohepatitis (NASH); Metabolic syndrome; DM; HTN; MI; atherosclerosis; peripheral artery disease; coronary artery stenosis; PCOS; candida in skin folds; don't do prevention ie pap smear. Sometimes the only place an obese patient can get a CT scan is at the Zoo.
What is a nickname for Cortisol? Why?
the brain hormone - more glucose, more blood, more calcium, putting glucose in blood but not letting muscles and fat have it by increasing insulin resistance. It's going to the BRAIN! and RBCs! It's going to all the places that don't need insulin.
Effect of cortisol on bone and immune system
↓bone formation (osteoporosis) and ↓immune system function (high risk for infection).
severe fetal hypothyroidism
1. Endemic lack of dietary iodine;
2. Sporadic = defect in T4 formation; Findings -
- Protruding umbilicus,
- Protuberant tongue. (5 Ps)
Only tumor suppresible by Dexamethasone test on cortisol
he Only Tumor that is Suppressible is an ACTH-Producing Pituitary Tumor (and only with High-Dose Dexamethasone); This is Cushing's Disease.
Diabetes is associated with Acanthosis Nigricans due to insulin resistance. AN also associated with visceral malignancies.
a potassium channel agonist, keeps K+ channels open and prevents beta cells from depolarizing and ↓ insulin secretion. Tx: Insulinoma
Differential diagnosis for DKA
DKA almost always related to state of XS glucagon, catecholamines or corticosteroids) Dfx for DKA = 'How'd you get "UR ACIDS" :
- Undiagnosed DM,
- Reduction or omission in Diabetic medication;
- Alcohol or drug abuse (especially stimulants),
- Corticosteroids (other doctor gave for back pain),
- Infection (pneumonia, gastroenteritis, UTI),
- Severe medical illness (MI, CVA, trauma)
hyperosmolar non-ketotic state
DM (II) - hyperosmolar non-ketotic state = hyperosmolar coma = Hyperosmolar hyperglycemic state (HHS)
DOC anaphylactic shock
DOC anaphylactic shock - epinephrine;
Cardiogenic shock - dobutamine;
Septic shock - NE.
DOC for Atrial fibrillation due to hyperthyroidism
Propranolol will control heart rate and prevent side effects of hyperthyroidism. Atrial fibrillation usually uses Diltiazem or verapamil and a beta-blocker.
Effect of stress on adipocytes
Stress ↑ sympathetic tone ® E and NE released from the adrenal medulla ® Activates lipase in fat cells ® Mobilization of fatty acids. Stress also causes anterior pituitary to release ACTH ® Adrenal cortex secretes glucocorticoids ® Same end result of stimulating lipase in fat cells.
Enlarged Thyroid (Goiter) can mean
Hyperthyroid, Hypothyroid, Euthyroid (no abnormal levels of thyroid hormone).
Exercise/Stress and Sympathetic tone
Epinephrine and norepinephrine ® Activates triglyceride lipase in the fat cells ® Mobilization of fatty acids to be used by muscles.
synthetic aldosterone replacement drug. Give if low aldosterone
Foods that Interfere with Thyroid Hormone Synthesis
Brassica Vegetables, Cruciferous vegetables. (cabbage, cauliflower, brussel sprouts, turnips). These foods are referred to as Goitrigens because they interfere with thyroid hormone synthesis. ↑TSH ® hypertrophy and hyperplasia of thyroid gland, manifest as a diffuse, nontoxic goiter.
Genetic factor for DM-1
Chromosome 6 - HLA-DR3 DQ2 and HLA-DR4 DQ8
Location of GLUT-2
GLUT-2 (bidirectional) receptors are on Beta islet cells, liver, kidney, small intestine.
Type of hypersensitivity for Graves disease
Type II hypersensitivity - Autoantibody (IgG) Stimulates TSH receptor.
Initially can cause thyrotoxicosis (follicular rupture phase); Causes hypothyroidism. Autoimmune - antimicrosomal and antithyroglobulin antibodies;
Histology - Hurthle cells (enlarged epithelial cells w/ excessive eosinophilic granular cytoplasm) lymphocytic infiltrate w/ germinal centers. Lymphocytic = Hashimoto's! Macrophages and eosinophils = Riedel's!
Risk factor in Hashimotos
Hashimoto's thyroiditis - Risk factor for thyroid lymphoma (anytime you accumulate lymphocytes you can have this problem)
Hormones that arise from the anterior pituitary
Where does the AP arise?
FSH, LH, ACTH, TSH, Prolactin, GH, melanotropin (MSH).
- AP is derived from oral surface ectoderm, Rathke's pouch.
group of GI hormones that ↑ insulin release (even before high blood glucose) and ↓ nutrient absorption (gastric emptying).
Example: glucagon-like peptide -1 (GLP-1). Newer DM drugs like Sitagliptin, Saxagliptin (DPP-IV inhibitors) Exenatide and Liraglutide (analogs), Pramlintide (Amylin analog) are based on action of integrins.
hyperthyroidism + Recent study using IV contrast dye (iodine).
inhibits Lateral hypothalamus;
stimulates the ventromedial hypothalamus.
Both result in ↓ appetite
adipocyte deficiency, defective metabolism of fat. Caused by: Leptin deficiency; HIV; HIV medications; Sites of insulin injection.
Liver disease associated with obesity
Nonalcoholic steatohepatitis (NASH)
Long acting glucocorticoids
Medications used to shrink prolactinomas
Dopamine agonists: Bromocriptine; Cabergoline
Pituitary, Parathyroid, Pancreas (3 Ps)
- #1 tumor is Medullary thyroid carcinoma (secretes calcitonin);
- Pheochromocytoma (45%)
- Parathyroid tumors (25%)
- Medullary thyroid carcinoma,
- Intestinal ganglioneuromatosis (mucosal neuromas);
Mneumonic Congenital Adrenal Hyperplasias
"1 in the first digit = hypertension. 1 in the second digit = XS androgens and masculinization"
Most common presentation of hyperprolactinemia in a female patient
if premenopausal, Hypogonadism - infertility, oligomenorrhea or amenorrhea. If postmenopausal, already hypogonadal, so asymptomatic. Rarely you may see galactorrhea in pre or postmenopausal, but NOT most common!
generated from POMC, a precursor to ACTH. Melasma - Estrogens can cause Excess MSH production ® ↑pigmentation, "Mask of pregnancy". A polypeptide hormone secreted by the intermediate lobe of the hypophysis in humans that causes dispersion of melanin by melanophores, resulting in darkening of the skin, presumably by promoting melanin synthesis
What leads to worse prognosis?
#1 tumor adrenal medulla children; anywhere in sympathetic chain (NCC);
- ↑Homovanillic acid ( HVA breakdown product of dopamine) in urine; HTN less likely;
- Overexpression N-myc oncogene ® rapid tumor progression;
- Bombesin is tumor marker;
- Histochemical Stain = neurofilament stain. Homer-Wright Rosette/Homer-Wright pseudorosette (circle of tumor cells around a tangle of fibrils). (NOT a perivascular rosette)
Why aren't there ketones in DMII?
No ketones in DM II because a lot of insulin excess that inhibits lypolysis/Beta-oxidation of fatty acids (that generates the ketone bodies) No ketones = No kussmaul breathing (no acidosis). Usually blood glucose is 800+ in type II diabetics with surging insulin. High osmolarity (340+) in type I diabetics with DKA
causes small vessel disease (diffuse thickening of basement membrane) resulting in nephropathy - nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to hypertension, and Kimmelstiel-Wilson nodules (note the acellular nodules in the glomerulus).
Osmotic damage causes:
Neuropathy (motor, sensory - lose proprioception, can't feel wound on feet, autonomic) and Cataracts.
Nuclear localization signals
4-8 AA sequences that are rich in Lysine, Arginine, Proline are required for a molecule to enter into the nucleus through a nuclear pore
↑ feeding): Endorphins; Endocannabinoids, Cortisol; Neuropeptide Y; Agouti-related protein.
binding of iodine to thyroglobulin
Pancreatic cancer tumor markers
CA 19-9 (more specific) CEA (gastric, colon, GI cancers)
Papillary Carcinoma Features
"Ground-Glass" Nuclei (dispersed chromatin in nucleus , orphan Annie) + Psammoma bodies. If ever irradiated for cancer, always check for thyroid cancer later in life
Breakdown products in urine of a patient with Pheocromocytoma?
Homovanillic acid or HVA (from dopamine),
Vanillylmandelic acid or VMA (from NE),
Metanephrine (from E),
Normetanephrine (from NE)
Patient's MRI reveals replacement of tissue in the sella turcica with CSF. Most likely diagnosis?
empty sella - Subclinical (incidental finding) Usually enough tissue to maintain function.
most common tumor of the medulla
Pheochromocytoma - most common tumor of the medulla, chromaffin cells.
Pheochromocytoma can be associated
↑ EPO ® polycythemia. Associated w/ Diabetes mellitus - catecholamines are counter regulatory hormones like glucagon, cortisol, can cause gluconeogenesis.
Peroxisome proliferator-activated receptor - intracellular receptor that acts as a transcription factor that regulate fatty acid storage and glucose metabolism. Found in adipose tissue, Liver and skeletal muscle. Alpha, Beta, Gamma.
Ligands are: fatty acids, prostaglandins, leukotrienes. TZDs bind to this receptor and turn on transcription factor -> ↓ insulin resistance and ↑ insulin sensitivity
Precursor molecule for synthesis of ACTH
Thyroid hormone levels in pregnancy?
Pregnancy will ↑ thyroid binding globulin (TBG) due to ↑estrogen;
- TBG takes up more free thyroid hormone and body senses this decrease so thyroid gland releases more T4 and T3.
- Total T4 and total T3 are higher.
Primary Adrenal Insufficiency
(Addison disease) Adrenal atrophy or destruction = Deficiency of aldosterone and cortisol causing hypotension, hyperkalemia, acidosis, skin hyperpigmentation. AAA. 80% of time autoimmune and adrenal atrophy, Addison's disease, adrenal atrophy, can't generate aldosterone, cortisol - no upregulation of alpha 1 receptors on vascular tree + no aldosterone = low BP. No potassium is lost, so hyperkalemia. General signs of weakness. Thin b/c no cortisol. Skin pigmentation b/c ACTH is in overdrive. JFK had Addison's.
Propylthiouracil (PTU) MOA
Blocks the iodination of tyrosine groups on thyroglobulin;
- ↓ synthesis of thyroid hormone. Inhibits peroxidase enzyme -> prevent organification of iodide for thyroid hormone synthesis.
- Also blocks 5'-deiodinase, which ↓ peripheral conversion of T4 to T3.
- Methimazole works like PTU but only works in the gland with no block in periphery.
- Toxicities: Skin rash, agranulocytosis, aplastic anemia (bone marrow suppression), hepatotoxicity w/ PTU but PTU has less birth defects than Methimazole.
- Papillary carcinoma of thyroid;
- Serous cystadenocarcinoma of ovary;
- Malignant mesothelioma.
MEN2A; MEN2B; Medullary thyroid carcinoma(#1 cancer MEN2A); Papillary thyroid carcinoma (#1 thyroid).
Thyroid replaced by fibrous tissue (hypothyroid or euthyroid if not severe); Findings: Fixed, hard (rock-like), and PAINLESS goiter. Histology - fibrosis maybe macrophages and eosinophils. Macrophages and eosinophils = Riedel's! Lymphocytic = Hashimoto's!
Secondary Adrenal Insufficiency
↓ Pituitary ACTH production = No hyperpigmentation; No hyperkalemia; Low cortisol; ± Hyponatremia. One level up, the pituitary, doesn't make ACTH so adrenals make no cortisol. Still can make aldosterone. Do not get hyperkalemia. No hyperpigmentation.
After delivery - post partum hemorrhage (oxytocin prevents this by clamping down on uterus) ® ↓ perfusion ® Pituitary gland infarcts ® ↓any of the pituitary hormones, especially prolactin.
Patient presents as being unable to produce milk in post partum period, especially if the patient required a blood transfusion. LH or FSH may not be produced ® patient would not resume menses. Could be growth hormone. Classically, it is ↓↓prolactin.
When is Sibutramine contraindicated?
(sympathomimetic) is contraindicated in SSRIs or MAOIs; CAD; Cerebrovascular disease; CHF; arrhythmia.
Side effects of prednisone use
"COACH PP HII"
- Cushingoid syndrome;
- Peptic ulcer disease;
- Insomnia, Immunosuppresion.
Careful when giving to diabetic! Give kid prednisone for poison ivy and they couldn't sleep all night
Stress Effects and Cortisol
Stimulates triglyceride lipase in the fat cells ® generates free fatty acids to be used by the Muscles. Excessive mobilization ↑ free fatty acids and leads to ketosis. GH may result in mild ketogenic effect; TH results in rapid mobilization of fat.
Subacute (de Quervain's thyroiditis)
hyperthyroidism early + Extremely tender thyroid gland. Hypothyroid late.
Very tender thyroid gland! Self-limited hypothyroidism following flulike illness; Histology - granulomatous inflammation; Findings - ↑ESR, jaw pain, early inflammation, VERY tender thyroid - tips you off. May be hyperthyroid early in course.
Very tender thyroid gland!
Subacute thyroiditis (de Quervain's)
Tertiary Adrenal Insufficiency
Abrupt withdrawal of long term corticosteroids. Negative feedback on hypothalamus ® no more CRH ® pituitary not making ACTH. If you give exogenous corticosteroids for more than 7-10 days, you should not stop them abruptly. Tapper off. No hyperkalemia b/c normal aldosterone production. No hyperpigmentation (suppressing ACTH).
Thyroid Hormone Storage
Stored in 3 different places: Thyroid gland, blood, and cell. Calcium in bone, blood, and SR of cells.
- Follicle - months
- Blood - 1-2 weeks
- Cells - Days or weeks
Thyroid stimulating immunoglobulin (TSI)
elevated in Graves disease; stimulates T3 and T4 release; immune system's way of controlling thyroid hormone.
Thyroxin Binding Globulin alters levels of which hormone?
How long to see the effect of administered Thyroxine?
takes 2-3 days after administration to see effect; Recheck levels > 1 month after administration. (T3's latent period is only 6-12 hours)
Tissues that depend on insulin for glucose uptake have what receptor?
have GLUT-4, Adipose tissue and skeletal muscle
Tissues that uptake glucose in the absence of insulin because they use a GLUT-1 receptor are
BRICK L - Brain, RBCs.
Intestine, Cornea, Kidney, Liver also don't need insulin but don't have GLUT-1 transporters.
Toxic Multinodular goiter
hyperthyroidism + palpation of multiple thyroid nodules
Toxic Thyroid (follicular) Adenoma
hyperthyroidism + palpation of single thyroid nodule
progesterone and cortisol
Tumor Locations in MEN 1, MEN2A, MEN2B
MEN 1 are Parathyroid, Pituitary, Pancreas ;
MEN2A are Parathyroids, Pheochromocytoma (Adrenal medulla), Medullary thyroid cancer;
MEN2B Medullary thyroid cancer, Pheochromocytoma; Mucosal neurons or GI tumors.
Very tan child w/ pale mother presents and is hypotensive: most likely diagnosis
most likely diagnosis is Addison's Disease (Primary Adrenal Insufficiency).
What are the functions of cortisol?
Cortisol is BBIIG:
Maintains Blood pressure (upregulates alpha 1 receptors on arterioles);
↓ Bone formation;
- (Inhibits production of leukotrienes and prostaglandins,
- inhibits leukocyte adhesion (neutrophilia),
- Blocks histamine release from mast cells,
- reduces eosinophils,
- Blocks IL-2);
↑Insulin resistance (diabetogenic); ↑Gluconeogenesis, lipolysis, proteolysis.
Findings in Cushing syndrome
ORD Thin Men Hyp Hir DEGWO
• Obesity or weight gain (95%)
• Rounded face (90%)
• Decreased libido (90%)
• Thin skin (85%)
• Menstrual irregularity (80%)
• Hypertension (75%)
• Hirsutism (75%)
• Depression (70%)
• Easy bruising (65%)
• Glucose intolerance (60%)
• Weakness (60%)
• Osteopenia or fracture (50%)
Adrenal hyperplasia or aldosterone-secreting adrenal adenoma (Conn's syndrome) = HTN, hypokalemia, metabolic alkalosis, LOW plasma renin
Kidney perception of low intravascular volume = overactive RAAS.
- Causes: Renal Artery Stenosis, CRF, CHF, cirrhosis, or nephrotic syndrome.
- HIGH plasma renin