What is acromegaly?
acromegaly and gigantism are usually caused by a pituitary adenoma that secretes excessive amounts of Growth Hormones; rarely, they are caused by non-pituitary tumors that secrete GHRH
- gigantism occurs if growth hormone (GH) hypersecretion begins in childhood, before the closure of the epiphyses
- acromegaly involves growth hormone GH hypersecretion beginning in adulthood; a variety of bony and soft tissue abnormalities develop
What is the presentation of acromegaly?
- large hands, feet, nose, lips, ears, jaw, tongue
- presents as gigantism (excessive height) if occurs before epiphyseal closure
How is acromegaly dx?
- GH test 2 hour after glucose load
- increased IGF-1
- MRI/CT shows a pituitary tumor
What is the tx for acromegaly?
pituitary tumor removal
What is Addison’s disease?
typically autoimmune, may be due to tuberculosis in endemic areas
- destruction of the adrenal cortex resulting in loss of cortisol production (decrease cortisol)
- nonspecific symptoms: hyperpigmentation, hypotension, fatigue, myalgias, GI complaints, weight loss
What are the lab findings for Addison’s disease?
decreased sodium, decreased 8 AM cortisol, increased ACTH (primary), increased potassium (primary), low DHEA
How is Addison’s disease dx?
high dose cosyntropin (synthetic ACTH) stimulation test
- blood or urine cortisol is measured after an IM injection of cosyntropin (synthetic ACTH)
- the normal response is a rise in blood and urine cortisol levels after synthetic ACTH is given
- primary adrenal insufficiency results in little or no increase in cortisol levels (< 20 mcg/dL) after ACTH is given
What is the tx of Addison’s disease?
hydrocortisone/prednisone PO daily
- Crisis: hypotension, altered mental status
- treatment: emergent IV saline, glucose, steroids
What is Cushing’s syndrome?
a collection of signs and symtpoms due to prolonged exposure to excess cortison
- symptoms from increased cortisol secretion
- it doesn’t specify cause or soure of excess
What is Cushing disease?
ACTH secreting pituitary microadenoma usually very small on anterior pituitary, F 3x >M
-secondary - increased cortisol due to ACTH excess, typically caused by pituitary adenoma -ACTH causes adrenals to secrete cortisol
What are the features of Cushing disease?
- hypercortisolism (increased cortisol) = obesity (buffalo hump, moon facies, supreclavicular pads), HTN, thirst, polyuria, hypokalemia
- proximal muscle weakness, pigmented striae; backache, headache, oligomenorrhea/amenorrhea/ED; emotional lability/psychosis
How is Cushing disease dx?
confirming high cortisol with a 24 hr urine free cortisol, late-night serum cortisol, and/or low-dose dexamethasone suppression test
- 24-hr urinary free cortisol is the most reliable index of cortisol secretion
- once confirmed, the source of the high cortisol needs to be determined with an ACTH level
- a high ACTH level indicates an ACTH dependent cause, a low ACTH level indicated an ACTH independent cause (plasma or serum ACTH < 20 pg/mL suggest adrenal tumor
- if it is an ACTH dependent cause, an MRI of the brain should be done to look for a pituitary adenoma (Cushing disease)
- if it is an ACTH independent cause, a CT of adrenals should be done to look for an adrenal mass such as an adenoma
What is low dose dexamethason suppresion test?
- give a steroid (dexamethasone) = failure of steroid to decrease cotisol levels is diagnostic = proceed next to high dose dexamethason suppression test = no suppression = Cushing’s syndrome
- supression < 5 ugs/dL excludes Cushing with some certainty
What is the tx for Cushing disease?
trnasphenodial selective resection of pituitary tumor cures 75-90%
- irradiation provides remission in 50-60%
- 95% 5-year survival
What is diabetes insipidus?
caused by a deficiency of or restance to vasopressin (ADH), which decreases the kidney’s ability to reabsorb water, resulting in massive polyuria
What is central diabetes insipidus?
deficiency of ADH from posterior pituitary/hypothalamus
-no ADH production most common type: idiopathic, autoimmune destruction of posterior pituitary from head trauma, brain tumor, infection, or sarcoidosis
What is nephrogenic diabetes insipidus?
Lack of reaction to ADH
-partial or complete insensitivity to ADH: caused by drugs (lithium, amphoterrible), hypercalcemia and hypokalemia affect the kidney’s ability to concentrate urine, acute tubular necrosis
How is diabetes insipidus dx?
serum osmolality (concentration) is high (unable to stop the secretion of water into the kidneys so blood becomes more concentrates) and urine osmolality is low because it is so dilute
- water deprivation test - simplest/most reliable method - continued production of dilute urine despite water deprivation
- desmopression stimulation test:
- central: reduction in urine output indicating a response to ADH
- nephrogenic: continued production of dilute urine (no response to ADH) because kidenyes can’t respond
How is diabetes insipidus tx?
- central = desmopression/DDAVP
- nephrogenic = sodium and protein restriction, HCTX, indomethacin
What is the etiology of diabetes mellitus type 1?
autoimmune - HLA-DR3/4/O antiboies
-Islet cell antibodies
What is the presentation os Type 1 DM?
- children
- polyuria, polydipsia, polyphagia, fatigue and weight loss
- often first recognized as diabetic ketoacidosis:
- symptoms: fruity breath, nausea, vomintg, dehydration
- treatment: IV regular insuling
What is the the treatment of type I DM?
insulin
What is the dawn phenomenon?
normal glucose until 2-8 am when it rises
- results from decreased insulin sensitivity and a nightly surge of counter-regulatory hormones during nighttime fasting
- treat with bedtime injection of NPH to blunt morning hyperglycemia, avoiding carbohydrate snak late at night
What is the somogyi effect?
nocturnal hypoglycemia followed by rebound hyperglycemia due to a surge in growth hormones
-treat with decreased nighttime NPH dose or give bedtime snack
What is insulin waning?
a progressive rise in glucose from bedtime to morning
-treat with a change of insulting dose to bedtime
What is DKA?
fruity breath, weight loss, rapid respirations, hypotension
- diabetic ketoacidosis (DKA) should always be handled in a hospitalized setting, usually an intensive care unit, and often with an endocrinologist’s consultation, if appropriate
- TREAT WITH FLUIDS! patinets with DKA are always dehydrated and need large-volume IV fluid resucitation, usually isotonic fluids such as normal saline
- if corrected serum sodium level is high, this can be reduced to half-normal saline
- insuling should always be administered by an IV pump to guard against accidental overdose
How is the diagnosis of DM made?
- randoma blood glucose level of > 200 mg/dL + diabetic symptoms
- 2 separate fasting (8 hours) glucose levels of >126 mg/dL
- 2-hour plasma glucose of > 200 on an oral glucose tolerance test (3-hour GTT is the gold standard in GDM)
- hemoglobin A1c of >6.5%
What are the insulin and c-peptide levels with Type I DM?
low or inappropriately normal fasting C-peptide and insulin levels with concomitant hyperglycemia
-high fasting insulin and C-peptide level suggest T2DM
What are insulin, GAD65, and IA-2 antibodies?
if one or more the antibodies are present, and especially if two or more are positive, the patient should be presumed to have type 1 diabetes and should be treated with insulin replacement therapy
How you monitor/evaluate glycemic control?
- hemoglobin A1c
- represents mean glucose level from previous 8-12 weeks (approx lifespan of an RBC)
- useful to gauge the ‘big-picture’ overall efficacy of glucose control in patients (either type 1 or type 2) to assess the need for changes in medication/insulin levels
- treatment goal of A1c <7.0%
- “finger-stick” blood glucose monitoring
- useful for insulin-dependent (either type 1 or type 2) diabetics to monitor their glucose control and adjust insulin doses according to variations in diet or activity
- treatment goals: <130 mg/dL fasting and <180 mg/dL peak postprandial
What is diabetes mellitus type 2?
diagnosis: random glucose > 200 x two or fasting glucsoe >126 x two
What are the characteristics of Metformin?
decreases hepatic glucose production and peripheral glucose utilization, decreases intestinal glucose absorption (these are reasons it leads to weight loss)
- side effects: lactic acidosis, GI side effects, initiation is contrindicated with eGFR <30 mL/min and not recommended with eGFR 30 to 45 mL/min, discontinue 24 hours before contrast and resume 48 hours after with monitoring for creatinine, stop if creatinine is >1.5
- benefits: weight loss, inexpensive
What are the characteristics of sulfonylureas?
stimulates pancreatic beta-cell insulin release (insulin secretagogue)
- Glyburide (diabeta), glipizide (glucotrol), glimepride (amaryl)
- side effects: hypoglycemia
- benefits: cheap, rapidly effective
What are the characteristics of thiazolidinediones?
increases insuling sensitivity in peripheral receptor site adipose and muscle has no effect on pancreatic beta cells
- pioglitazone (Actos), rosiglitazone (avandiaz0
- contraindictions: CHF, liver disease, fluid retention, weight gain, bladder cancer (pioglitazone), a potential increase in MI (rosiglitazone)
What are the characteristics of alpha-glucosidase inhibitors?
delays intestinal glucose absorption
- acarbose (precose), miglitol (glyset)
- GI side effects, three times a day dosing
What are the characteristics of meglitinides?
stimulates pancreatic beta-cell insulin release
- repaglinide (prandin) and nateglinide (starlix)
- side effects: may cause hypoglycemia
What are the characteristics of GLP-1 Agonists?
lowers blood sugar by mimicking incretin - causes insulin secretion and decreased glucagon and delays gastric emptying
- Exenatide (bydureon, Byetta), dulaglutide (trulicity), semaglutide (Ozempic), liraglutide (Victoza, saxenda)
- side effects: requires injection, frequent GI side effects, caution is gastroparesis
- benefits: weight loss, reduced CV mortality (semaglutide, Liraglutide) in patient with CVD
What are the characteristics of DPP-4 Inhibitors?
dipetpidylpetase inhibition - inhibits degradatino of GLP-1 so more circulation GLP-1
- sitagliptin (januvla), saxagliptin (onglyza)
- side effects: expensive, possible increased risk of heart failure with saxagliptin
What are the characteristics of SGLT2 inhibitor?
SGLT2 inhibition lowers renal glucose threshold which results in increased urinary glucose excretion
- canagliflozin (invokana or sulisent)
- side effects: vulvovaginal candidiasis, urinary tract infections, bone fractures, lower limb amputations, acute kidney injury, DKA, long-term safety not established
- benefits: weight loss, reduction in systolic blood pressure, reduced cardiovascular mortality in pateitns with established CVD
When do you add insulin?
add if HbA1C > 9
What is the follow up with DM2?
annual - ophthalmologist visit, urine microalbumin
What are the complications of DM?
neuropathy (most common), retinopathy (a leading cause of blindness), nephropathy
What is normal fasting glucose?
between 70 and 100
What is the diagnostic criteria for prediabetes?
- A1C 5.7 -6.4
- fasting glucose 100-125
- 2-hour oral glucose tolerance test 140-100
What are the glucose goals and basic management?
- A1C <7.0% check every 3 months if not controlled and 2x per year if controlled
- preprandial glucose 80-110 (60-90 if pregnant)
- postprandial blood glucose goal (1.5 - 2 hours after a meal) is <140
- annual dialted eye exams, ACEI if microalbuminuria, annual foot examination
- blood pressure should be maintained at <130/80
- new statin guidelines: recommend statins in persons with diabetes mellitus who are 40 to 75 years of age with LDL-C levels of 70 to 189 mg per dL but without clinical ASCVD
What is hypercalcemia?
- serum total calcium > 10.5 mg/dL
- ionized fraction of calcium > 5.6 mg/dL
What is the presentation of hypercalcemia?
“stones, bones, abdominal groans, psychiatric moans”, EKG: shortened QT interna
- blood: increased PTH, increased calcium, decreased phosphorus
- associated with malignancy and hyperparathyroidism
What is the treatment for hypercalcemia?
IV normal saline and furosemide
What is the definitiion of hypernatremia?
serum sodium of >145 mmol/L
What is the etiology of hypernatremia?
diarrhea, burns, diuretics, hyperglycemia, diabetes insipidus, a deficit of thirst
What are the signs and symptoms of hypernatremia?
poor skin turgor, dry mucous membranes, flat neck veins, hypotension, increased BUN/CR ratio >20:1
-decrease circulating volume = decrease of flow to kidneys means more bound urea in the blood which means increased BUN
What is the tx of hypernatremia?
intravenous (IV) 5% detrose in water (D5W)
-rapid overcorrectio ncaused cerebral edema and pontine herniation
What is hyperparathyroidism?
a condition in which one or more of the parathyroid glands become overactive and secrete too much parathyroid hormone (PTH)
-this causes the levels of calcium in the blood to rise
What are the characteristics of hyperparathyroidism?
- increased PTH = bone breakdown = releases Ca
- kidney holds on Ca and increased Vitamin D3
- the intestine absorbs more Ca = increased Ca in blood levels
What are the causes of hyperparathyroidism?
primary and secondary
- primary: increased PTH usually caused by a PTH secreting parathyroid ADENOMA
- secondary: increased PTH by a physiologic response to hypocalcemia or vitamin D deficiency
- chronic kidney disease is the most common cause of secondary hyperparathyroidism
What is the presentation of hyperparathryoidism?
weakness, fatigue, constipation = stones, bones, abdominal groans, psych moans, and fatigue overtones
- bone loss from increased PTH and Ca absorption from bones = pain in bones
- renal loss of Ca and phosphorus = kidney stone
- increase GI absoprtion of Ca and abdominal cramps = graons
- irritability, psychosis, depression = moans
What are the labs for hyperparathyroidism?
- blood = increased Ca, increased PTH, and decreased phosphorus
- urine = hyperphosphaturia, hypercalciuria (all CA and phosphorus go out through kidneys to urine)
What is the tx of hyperparathryoidism?
- primary = surgical correction to remove the overactive parathyroid gland = if all 4, remove 3.5 glands
- secondary = replace cause (vitamin D/Ca supplementation)
- If Ca very high: IV fluids, lasix, calcitonin; treat osteoporosis with bisphosphonates
What is hyperthyroidism?
the production of too much thyroxine hormone
-it can increase metabolism and accelerate the body’s metabolism, causing unintentional weight loss and a rapid or irregular heartbeat
What is the etiology of hyperthyroidism?
Grave’s disease (autoimmune), toxic adenoma, thyroiditis, pregnancy, amiodarone
What is the presentation of hyperthyroidism?
heat intolerance, palpitations sweating, weight loss, tremor, anxiety, tachycardia
- graves - diffuse goiter with a bruit, exophthalmos, pretibial myxedema
- thyroid storm - fever, tachycardia, delirium
How is hyperthyroidism dx?
- TSH (best test): decreased in primary disease (decreased TSH and increased free T4), elevated in secondary disease (increased TSH and increased free T4)
- T4: elevated although may be normal
- thyroid radioactive iodine uptake:
- graves: diffusely high uptake
- toxic multinodular: discrete areas of high uptake
What are the antibodies of hyperthyroidism?
graves: anti-thyrotropin antibodies
What is the tx for hyperthyroidism?
- beta-blockes (symptomatic), methimazole/propylthiouracil, radioactive iodine, thyroidecotmy
- thyroid storm - prompt beta-blockers, hydrocortisone, methimazole/propylthiouracil, iodine
- thyroidecotmy - most likely complication is injury to the recurrent laryngeal nerve (hoarseness)
What do you do about antithyroid drugs during pregnancy and nursing?
- propylthiouracil used to be the drug of choice during pregnancy because it causes less severe birth defects than methimazole
- experts now recommend that propylthiouracil be given during the first trimester only
- this is because there have been rare cases of liver damage in people taking propylithiouracil
- after the first trimester, women should switch to methimazole for the rest of the pregnancy
- for women who are nursing, methimazole is probably a better choice than propylthiouracil (to avoid liver side effects)
What is thyroiditis?
a general term that refers to “inflammation of the thyroid gland”
- includes a group of individual disorders causing thyroidal inflammation but presenting in different ways
- painful va painless may be hypo or hyperthyroid
What is hashimoto’s thyroiditis?
diffusely enlarged, painless, nodular goiter
What is subacute thyroiditis?
- young women, after a viral infection
- painful enlarged thyroid with dysphagia, mild fever
- aspirin
What is postpartum thyroiditis?
- 1-2 months of hyperthyroidism after delivery
- completely resolves, give propranolol for cardiac symptoms
What is suppurative thyroiditis?
- fever, pain, redness, fluctuant mass, increased WBC
- antibiotic/surgical drainage
What is hypocalcemia?
- serum total calcium <8.4 mg/dL
- ionized fraction of calcium <4.4 mg/dL
What is the presentation of hypocalcemia?
QT prolongation, trousseau’s sign, chvostek’s sign
- labs: decreased Ca, decreased PTH, increased phosphate
- EKG = prolonged QT
What is the tx of hypocalcemia?
IV calcium gluconate or calcium chloride
What is hyponatremia?
serum sodium of <135 mmol/L
-peripheral and presacral edema, pulmonary edema, JVD, hypertension, decreased hematocrit, decreased serum protein, decreased BUN/CR
What is the presentation of hyponatremia?
msucle cramps and seziures
- hypervolemic hyponatreia - CHF, nephrotic syndrome, renal failure, cirrhosis
- euvolemic hyponatremis - SIADH, steroids, hypothyroid
- hypovolemic hyponatremia - sodium loss (renal, non-renal)
What is the tx of hyponatremia?
- asymptomatic: free water restriction
- moderate hyponatremia: IV normal saline and loop diruetics may be added
- severe hyponatremia: hypertonic (3%) saline
-serum Na should be corrected slowly - by <10 mEq/L over 24 h to avoid osmotic demyelination syndrome
What is hypoparathyroidism?
an uncommon condition in which your body secretes abnormally low levels of parathyroid hormone (PTH)
-thic causes calcium levels in the blood to decrease
What is the etiology of hypoparathyroidism?
thyroidectomy
What is the presentation of hypoparathyroidism?
tingling, tetany, cataracts
What is the physical exam of hypoparathyroidism?
- chvostek’s sign - tap facial nerve illicity cheek twitch
- trousseau’s sign - BP cuff inflation illicit carpal spasm
What are the labs for hypoparathyroidism?
hypocalcemia decreased CA, low decreased PTH, hyperphosphatemia, low urinary calcium
What is the tx for hypoparathyroidism?
Vitamin D and calcium
-tetany - secure airway, IV calcium gluconate
What is the etiology of hypothyroidism?
Hashimoto’s (chronic lymphocytic/autoimmune), previous thyroidecotmy/iodien ablation, congential
What is the presentation of hypothyroidism?
- cold intolerance, fatigue, constipation, depression, weight gain, bradycarida
- congenital: round face, large tongue, hernia, delayed milestones, poor feeding
What are the labs for hypothyroidism?
TSH - elevated in primary diease, low T4 (increased TSH and decreased free T4)
-Hashimoto’s antithyroid peroxidase, antithyroglobulin antiboides
What is the tx for hypothyroidism?
levothyroixine, follow up with serial TSH monitoring
What is Paget disease?
bone remodeling disorder that results in the formation of an unorganized mosaic of woven and lamellar bone that is less compact and weaker than the normal bone
What are the characteristics of Paget disease?
- the exact cause is unknown but can be triggered by infections (e.g measles) and linked to genetic mutations
- Paget’s disease of bone most commonly occurs in the pelvis, skull, spine, and legs
- risk factors include increasing age and a family history of the condition
- over time, affected bones may become fragile and misshapen
- this condition can be sympotmless for a long period of time
- when symptoms do occur, they may include bone deformiteis, broken bones, and pain in the affected area
- may lead to osteosarcoma - Paget’s Sarcoma
How is Paget disesse dx?
the x-ray shows lytic lesions and thickened bone cortices, a bone biopsy to exclude malignanices
-labs: increased alkaline phosphatase and bone-specific alkaline phosphatase; increased osteoclast activity and osteoblastic activity
What is the tx of Paget disease?
includes bisphosphonates (which reduce bone resorption and may improve pain and quality of life), and occasionally, calcitonin -surgery can help correct bone deformities, decompress an impinged nerve, and reduce fractures
What is a pheochromocytoma?
catecholamine secreting adrenal tumor - secretes norepinephrine and epinephrine autonomously and intermittently
- 5 P’s: pressure, pain (HA), perspiration, palpitations, pallor
- associated with neurofibromatosis type 1, MEN 2A/B
How is a pheochromocytoma dx?
- 24-hour catecholamines including metabolities (metanephrine and vanillylmandelic acid)
- MRI or CT of the abdomen to visualize the tumor
What is the tx for a pheochromocytoma?
- resect tumor - complete adrenalecotmy
- medical treatment preoperative: Alpha-blocker (phenoxybenzamine) preop, phentolamine (acute HTN crisis), sodium nitroprusside (acute HTN crisis), nicardipine (acute HTN crisis)
- pre-op nonselective alpha blockade: phenoxybenzamine or phentolamine 7-14 days followed by beta-blocker to control HTN (NO solo beta-blockers = prevent unopposed alpha constriction = life-threatening HTN)
What is a pituitary adenoma ?
noncancerous tumors in the pituitary gland that don’t spread beyond the skull
- most common tumors are microadenomas that are functional (hypersecretion of pituitary hormones), nonfunctional or compressive
- microadenomas are less than 1 cm in diameter, whereas adenomas that are 1 cm or more are commonly referred to as macroadenomas
- microadenoma < 10 mm
- macroadenoma > 10 mm
What are the s/s of pituitary adenoma?
diminished temporal vision or bitemporal hemianopsia = MC visual
What are lactotroph adenomas?
(prolactinomas = MC) are pituitary masses = hypersecretion of prolactin
- s/s: amenorrhea, galactorrhea, and headaches
- location of the mass at the sella turcica = tumor applies pressure on the optic chiasm of the optic nerve resulting in loss of vision in the temporal visual fields
What is a growth hormone tumor?
gigantism, acromegly
What is a corticotroph adenoma?
secrete ACTH = present with Cushings syndrome
What is a thyrotroph adenoma?
secrete TSH = presents with hyperthyroidism
How is a pituitary adenoma dx?
MRI is the study of choice to look for sellar lesions/tumors
-endocrine studies: prolactin, GH, ACTH, TSH, FSH, LH
What is the tx of pituitary adenoma?
dopamine agonists cabergoline and bromocrptine; if dopamine agonsts are unsuccessful, transsphenoidal resection of the pituitary tumor should be considered
-in women, estrogen therapy can also be used due to the associated hypogonadism
What is thyroid cancer?
thyroid cancer occurs in the cells of the thyroid
- MC risk is radiation exposure; MC F 40-60 y/o
- hoarse voice, solitary cold nodule on thyroid uptake scan
- most often papillary carcinoma (80%) = papillary = popular
How is thyroid cancer dx?
ultrasound - all lesions >1 cm should be biopsied; smaller lesions can be followed/reevaluated if they grow
- high-risk malignancy on U/S: microcalcifications, hypoechogenicity, a solid cold nodule, irregular nodule margins, chaotic intranodular vasculature, and a nodule that is more tall than wide
- to eval malignancy: thyroid uptake scan - cancerous does not up take iodine (cold); non-cancerous will take up iodine (hot)
- if cold = fine needle aspiration
What is the tx of tyroid cancer?
depends on staging (99% 5-year survival with local confined, <1 cm papillary carcinoma)
- always involves complete/parital thyroidectomy with chemo and radiation for anaplatic thyroid CA
- recommended TSH level for pt: 1-2.0
