2 go Uworld Endocrine & metabolism - Step2
What is the treatment for prolactinoma ?
Dopamine agonist Surgery
What does elevated testosterone with normal DHEAS levels suggest? What about elevated DHEAS?
Elevated testosterone with normal DHEAS suggest ovarian source Elevated DHEAS only suggest adrenal
What can cause increased TBG production ?
Elevation of estrogen: Pregnancy OCP HRT Hepatic dysfunction (acute hepatitis)
What issues do you get with diabetic autonomic neuropathy in the GI track?
Esophageal motility issues (dysphagia) Gastric emptying issues (gastroparesis) Intestinal dysfunction (diarrhea, constipation incontinence)
What are most cases of cushing syndrome due to?
Exogenous glucocorticoid intake Ectopic ACTH production (small cell lung cancer) ACTH producing pituitary Less commonly it's caused by adrenal adenomas
In what thyroid disease do you find hurthle cells?
Follicular thyroid cancer Hashimotos Benign adenomas These cells are not specific to any of these tumors
What is another way to assess for serum calcium levels without having to use the equation for calculation of serum calcium with low albumin?
For ever 1g decreased in serum albumin you will have 0.8 mg decrease calcium
What are other substances that can chelate ionized calcium?
Foscarnet (antiretroviral) EDTA Bisphosphonates Phenytoin
What is the initial testing for suspected CAH?
17 hydroxyprogesterone level
Why do patients with DKA have pseudohyponatremia?
2/2 hyperglycemia. For every 100mg/dl of glucose over 100 you add 2mEq/L. Example: pt's serum level is 128 and glucose is 600 So.. 100 over original base 100 = x5 and if each 100 equates to 2 mEq/L of sodium and you have 5 (100's) over the first 100, then 5x2 = 10 So serum Na = 128+10 = 138 normal
What work up should you perform if hypercortisolism is suspected?
24 hour assay for urine free cortisol Late night salivary cortisol Low-dose dexamethasone supresión test Once establish, measure ACTH to determine whether it is ACTH dependent or ACTH independent If ACHT is extremely high, then perform a HIGH dose dexamethasone suppression to determine whether it is pituitary or ectopic
What is a normal T4 level ?
5-12
What should be the initial work up for suspected PAI (primary adrenal insufficiency)?
8 AM Serum cortisol Plasma ACTH If serum cortisol is relatively normal but plasma ACTH is high, then it suggest aldosterone deficiency
What level of HbA1C have been shown to reduce the occurrence and progression of microalbuminuria in a diabetic patient?
<7.0
Even if the BP is normal and there is somewhat tight glycemic control, if there is microalbuminuria what is the recommended next step?
ACE inhibitors
What test can you use to confirm a diagnosis of primary adrenal insufficiency
ACTH stimulation test. Cosyntropin is a synthetic ACTH analog that causes rapid increase in serum cortisol, but if PAI exist, then no significant rise in cortisol will occur
What can you suspect in patients who have good fasting glucose control based on measurements but high A1C level?
Frequent post-prandial hyperglycemia
How does gastroparesis present like?
Anorexia Nausea EARLY SATIETY Postura dial fullness VOMITING
What antibody is associated with increased risk of miscarriage in both euthyroid and hypothyroid women?
Anti-TPO
What is the most common cause of PAI in developed countries?
Autoimmune adrenalitis
Which antiglycemic allows you to lose weight?
GLP1 inhibitors
What is characteristic of a glucagonoma?
Glossitis Necrotic migratory rash Face, perineum and extremities Elevated glucose levels
What confirm the diagnosis of glucagonoma?
Glucagon level >500
What is the MOA of leuprolide?
GnRH agonist
How long does HHS take to develop VS DKA?
HHS takes days to weeks while DKA takes only a few hours
What is PTU associated with as far as side effects?
Hepatic failure ANCA associated vasculitis Agranulocytosis
What will be the thyroid TSH and free hormones look like in a secondary hyperthyroidism ? Pituitary adenoma?
High TSH (may be high normal) High free T3 and T4
What causes a DECREASE of TBG production ?
Hormonal abnormalities (Cushing or glucocorticoids) Hypoprotenimia states (nephrotic syndrome, malnutrition) High dose androgens
Which medication do you want to avoid and use in pheochromocytomas ?
Avoid BB 2/2 to unopposed alpha activity Use phenozybenzamine alpha blockade
Why is GH alone not helpful for diagnosis of acromegaly?
Because it fluctuates throughout the day. Therefore IGF is the best one to start with
Why does ketosis not occur in HHS? But you do see some ketones, why?
Because there is SOME insulin working, which prevents ketogenesis. The few ketones you do see are 2/2 starvation ketosis primarily due to decreased food intake
Which cells in the pancreas produces insulin?
Beta cells
Hyperaldosteronism is most commonly 2/2 ?
Bilateral adrenal hyperplasia Then aldosterone producing adrenal adenoma
Why can you get Hypocalcemia with blood transfusion ?
Blood contains citrate which will bind ionized calcium. Note that in patients with no liver abnormalities will actually metabolized the citrate of the blood rapidly enough as to prevent any abnormal drop of Ca that will cause symptoms
How does CKD cause secondary hyperparathyroidsm ?
CKD causes inability to activate vitamin D, and high levels of phosphate. The low level of vitamin D will lead to decrease absorption of Ca in the GI, thus decreasing Ca serum levels. Both the low serum Ca and high Phosphate serum levels will lead to increase PTH secretion Phosphate binds to circulating Ca serum and inhibits activation of vitamin D conversion in the kidney Also note that PTH levels increase with decreased GFR (CKD)
how does CKD cause secondary hyperparathyroidism?
CKD leads to both decrease phosphate excretion and conversion of active vitamin D which causes decrease of Ca absorption.
What are 2 dopamine agonists used in prolactinoma ?
Carbegoline Bromocriptine
What is the leading cause of death in acromegaly?
Cardiovascular disease (CHF and arrhythmias secondary to chronic changes of acromegaly)
Why do patients get easy bruisability in Cushing's syndrome?
Catabolic effect of cortisol on connective tissue Note that platelet function and coagulation proteins are normal
How does hypomagnasemia causes Hypocalcemia?
Causes decrease release of PTH Causes PTH resistance
What is the pathophysiology of PCOS
Hyperandrogenism that leads to hyperandrogenism and subsequently leads to annovulation Pt's are obese, hairy and have irregular menses
What is the dawn phenomenon ?
Hyperglycemic surge in the early morning due to diurnal increase in counter regulatory hormones (growth hormone, cortisol)
What additional laboratory abnormalities can hypothyroidism cause?
Hyperlipidemia Hyponatremia CK elevation Serum transaminases Hyperlipidemia is 2/2 decreased receptors of LDL and decrease lipoprotein lipase activity
Potential features of Pan-hypopituitarism?
Central adrenal insufficiency (low cortisol and ACTH) increased hyperpigmentation Hypogonadotropic hypogonadism (low FSH/LH and testosterone) Central hypothyroidsm (low or low normal TSH, low T4) Remember that the aldosterone pathway is affected directly by the kidneys.
What is the presentation of CAH (21 hydroxylate deficiency) aka classic CAH VS nonclassic CAH?
Classic CAH will present at birth with ambiguous genitalia and elevated androgen precursors Nonclassic CAH (partial 21 hydroxylate deficiency) develops hyperandrogenism from late childhood to early adulthood
First line therapy for menstrual regulation in PCOS?
Combined OCP which contains progesterone that stimulates endometrial differentiation (limits its continued proliferation) as PCOS patients have way to much estrogen. Then it also regulates estrogen by stabilizing the uttering lining and restoring normal cycles. In addition it decreases hirturism by blocking androgen secretion Increases sex hormone binding globulins decreasing free testosterone
What changes in the heart will acromegaly cause?
Concentric myocardial hypertrophy Left ventricular dilation Global hypokinesis Enlargement of the heart will have valvular complication such as mitral and aortic regurgitations
Most common electrolyte abnormality in PAI? Why?
Hyponatremia 2/2 pituitary increasing CRH which induces increased production of ADH diluting the Na in the serum. Conversely hyperkalemia arises due to lack of aldosterone production
What are some common metabolic causes of myopathy?
Hypothyroidsm Thyrotoxicosis Cushing syndrome Electrolyte abnormalities (decreased K, Ca, and Phosphorus)
What is the characteristic of necrológica migratory erythema ?
Crusting and scaly borders with central clearing and sometimes blistering
What is the difference between Cushings disease and Cushing's syndrome?
Cushings disease is 2/2 pituitary adenoma ACTH excretion which leads to cushings syndrome Cushing's syndrome can be from any etiology causing high levels of glucocorticoids Ectopic ACTH production Exogenous glucocorticoids intake
What is the indication for discontinuation of an antithyroid drug?
If a constitutional symptom develops likely 2/2 an infectious etiology Fever Sore throat
What is the pathophysiology of G6PD deficiency ?
Inability to reduce NADP to NADPH which is an essential factor to synthesize glutathione which is projective for oxidative stress of RBCs
Effect of alkalosis on calcium levels?
Decreases free ionized calcium due to increased Ca bound to albumin
What is the pathophysiology of osteomalacia?
Defective mineralization of the organic bone matrix 2/2 vitamin D deficiency
MOA of demeclocycline?
Inhibits ADH-mediated aquaporin insertion in cortical collecting tubule and helps dilute the urine
What is specific for biopsy finding of follicular thyroid cancer?
Invasion of the tumor capsule and or blood vessels Note that benign follicular adenomas do NOT invade capsule or vessels
Which is the only physiologic active form of calcium ?
Ionized calcium
What is the effect of graves on the eyes?
It may cause opthalmopathy by decreasing convergence and diplopia. This occur secondary to T cell activation and stimulation of orbital fibroblast and adipocytes causing tissue expansion and lymphocytic infiltration
What is the function of spironolactone in PCOS?
It regulates hirturism by blocking androgen receptors (antagonist)
What will be the C-Peptide protein level be like in an individual who is hypoglycemic 2/2 exogenous insulin use?
It will be low c-peptide as it suppresses endogenous insulin production
Diagnosis of Cushing's syndrome?
Late night salivary cortisol 24 hour urine free cortisol Low - dose dexamethasone suppression test
Mechanism of hypercalcemia in immobilization ?
Likely due to increased osteoclasts bone resorption in pts with preexisting high bone turnover such as young individuals or Paget's.
What will be the ACTH and cortisol level in central adrenal insufficiency ?
Low ACTH and low cortisol
What is euthyroid sick syndrome? What is the pathophysiology ?
Low T3 syndrome (low free and total T3 levels) It is primarily induced by a severe illness, which causes a decrease in peripheral deodination aka T4 —> T3. This is in part by a multifactorial array of reasons, such as: Caloric deprivation Elevated glucocorticoids Inflammatory cytokines levels There is a rough correlation between the severity of the underlying non-thyroidal illness and the fall of T3 levels both total and free. The thyroid levels will show normal TSH and free T4 but a decrease total T3 and free T3
What levels of cortisol and ACTH will you find in primary adrenal insufficiency ?
Low cortisol High ACTH
What syndrome are VIPomas associated with ?
MEN1
Causes of osteomalacia?
Malabsorption Bowel resection CKD Chronic liver disease Celiac spruce Intestinal bypass surgery
Once you have measured the radioactive iodine uptake with a scan and it comes back low, there are different pathways through that fought, thyroiditis/iodine exposure or exogenous hormone intake. How can you distinguish between both of these?
Measure the serum thyroglobulin. If its high then it is thyroiditis If its low then it is exogenous
Describe MEN3 tumors
Medullary thyroid cancer Pheochromocytoma Mucosal neuromas/marphanoid
What is the best pharmacy for gastroparesis treatment?
Metoclopramide which has prokinetic and antiemetic properties Alternatives include erythromycin
Tight glycemic control reduces what risk factors?
Microvascular complications such as retinopathy or nephropathy But It does not have any change in macrovascular complications such as MI or stroke (possible in long term reduction)
Clinical presentation of glucagonomas?
Mild hyperglycemia (not required insulin) Necrolyitic migratory erythema GI symptoms like diarrhea or abdominal pain. Constipation may also occur Weight loss DVT's
What does easily induced hypokalemia signify
Mild primary aldosteronism
What is the hormonal characteristic of non functioning adenomas?
Mildly elevated prolactin Low TSH Low LH both of these due to compression of the dopaminergic pathways
Why can patients w/ hyperthyroidism can develop bone loss?
Direct effect of thyroid hormone on bone is 2/2 increased osteoclasts bone resorption. It can therefore lead to hypercalcemia and hypercalciuria
Are LH:FSH ratios diagnostic for PCOS?
NO! And sometimes are not always seen but if you do, LH will be higher than FSH
Typical symptoms of alkali syndrome?
Nausea vomiting and constipation Polyuria and polydipsia Neuropsychiatric symptoms
Large fiber injuries 2/2 diabetes are characterized by predominance of what symptoms?
Negative symptoms Numbness Propioception loss Vibration sense loss Reflex loss
Does transdermal estrogen patches affect thyroid hormone levels?
No because it bypasses the liver and does not affect the TBG levels
Does subacute lymphocytic thyroiditis require thyroid replacement therapy?
No, it will have a hyperthyroid phase, but it will be self limited. You may want to control hyperthyroid symptoms with beta blockers
How can you categorized hypercalcemia based on etiology?
PTH independent (malignancy, vitamin D tox, granulomatous diseases) vs PTH dependent (primary hyperparathyroidsm)
What will the level of PTH be in primary hyperparathyrodism? What about the level of calcium?
PTH will be elevated even with elevated calcium due to inability for the parathyroid gland to be suppressed by negative feedback
What subtle clue will you find that will allow you to differentiate between PTHrP vs PHPT?
PTHrP does not induce conversion of 25hydroxyvitamin D to 1,25 vitamin D while PTH does
Where is the typical location of VIPomas?
Pancreatic tails 75%
What is the most common epithelial malignancy of the thyroid ?
Papillary
In what type of thyroid cancer will you find psammoma bodies?
Papillary thyroid cancer
Which cells secrete calcitonin?
Parafollicular cells of the thyroid
Most common cause of primary hyperparathyroidism ?
Parathyroid adenoma
Describe MEN2 tumors
Parathyroid hyperplasia Pheochromocytoma Medullary thyroid cancer
Describe MEN1 tumors
Pituitary (prolactinoma) Parathyroid (hypercalcemia) pancreatic (gastrinomas, insulinoma, VIPomas, glucagonoma)
In what thyroid disease would you perform a scintigraphy study?
Plummer disease (multinodular toxic goiter)
What will you see in ovaries with PCOS?
Polycystic ovaries
Small fiber injuries 2/2 diabetes are characterized by predominance of what symptoms?
Positive Pain Paresthesias (sensation) Allodynia
How does a nonfunctional adenoma present?
Presents with low levels of most pituitary hormones due to compression of neighboring pituitary cells.
Etiologies for primary, secondary and tertiary AI?
Primary AI = Addison's disease AI most common, second most common is infection Secondary AI/central = exogenous glucocorticoid suppressing the HPA. Hypopituitarism (rare) Tertiary AI/central = hypothalamic disease
What is the pemberton sign?
Raising the arms causing compression of the subclavian and right internal jugular vein between the clavicles and the enlarged thyroid. This leads to more prominent venous distention and facial redness
What ratio of Aldosterone/Renin is typically suggestive of primary hyperaldosteronism ?
Ratio >20
Name some causes for secondary hyperaldosteronism ?
Renovascular disease RAS Ectopic aldosterone production Diuretic use
What should you do in asymptomatic patients with Hypocalcemia?
Repeat calcium levels
What is the most beneficial therapy to reduce the progression of diabetic nephropathy ?
Right BP control
What is the presentation of thyroid lymphoma and what is a risk factor?
Risk factor is hashimotos therefore will have anti-TPO It presents with B cell symptoms (Fever, night sweats, weight loss) Mild pain to palpation but firm Compressible symptoms due to retrosternal extension. Causing venous compression leading to distended neck veins, facial plethora
What is the best way to monitor for response to the treatment given in DKA patients?
Serum anion gap
What is the characteristic of humoral hypercalcemia of malignancy HHM?
Severe >14 mg/dl Acute onset of symptoms
Explain the mechanism of HHS causing hyperosmolality?
Severe hyperglycemia and high serum osmolality is due to relative insulin deficiency OR elevated glucagon, cortisol (can be exogenous like steroids), and growth hormone. Factors such as infections (most common), traumas, medications or interruption of insulin therapy can cause hyperglycemia. Once hyperglycemia occurs, it leads to osmotic diuresis, causing hypovolemia and worsening the GFR, causing reduced renal glucose excretion and worsening the hyperglycemia and high serum osmolality.
Common causes of secondary adrenal insufficiency s/p partum?
Sheehan syndrome Lymphocytic infiltration of the pituitary gland
What are the meal time short acting insulin's? What is the longest acting basal insulin?
Short acting meal time LAG Lispro Aspart Glulisine Long acting basal insulina Glargine
Effects of thyroid hormones of rhythms of the hearT?
Sinus tachycardia PAC/PVC A-fib/a-flutter
Where are most of carcinoid syndrome tumors located?
Small intestine 70-80% NOT Pancreas
If suspicion of acromegaly, what should be the initial work up?
Start with IGF level because if normal it rules it out F/U w/ oral glucose suppression test. If there is an adequate suppression then it rules out GH but if not then f/u with MRI
What are the different types of thyroiditis?
Subacute thyroiditis (de Quervain thyroiditis) PAINFUL! :( followed by virus infection elevated ESR Subacute lymphocytic thyroiditis (Painless thyroiditis variant) of hashimotos and presents with transient hyperthyroid phase prior to going out. Non-tender elevated TPO Chronic lymphocytic thyroiditis (hashimotos) Most common form oh hypothyroid Elevated TPO
What is the effect of prolactinoma on other hormonal pathways?
Suppresses GnRH this decreasing testosterone LF FSH
Primary treatment for papillary thyroid cancer?
Surgical resection
How does thyroid hormone increases HR and BP?
T3 affects cardiac myocites by Increases myocardial contractility Increases CO Decreases SVR but systolic BP raisins 2/2 ionotripic and chronotropic effects of thyroid T3. Widened pulse pressure
What is the initial eval for thyroid nodules?
TSH level U/S If normal or elevated TSH level proceed to FNA If low TSH then proceed to do a scintigraphy
What is methimazole associated with as Farq s side effects?
Teratogen Cholestasis Agranulocytosis
Testing what hormones can help you delineate the etiology of Virilizaton?
Testosterone and DHEAS
What are the 3 major proteins circulating thyroid binds too?
Thyroid binding globulin TBG Transthyretin Albumin Note that only the free (unbound) thyroid hormones are active Note that changes in any of these proteins can altered the free circulating thyroid pools AND can affect the hypothalamic-pituitary-axis as it may change thyroid [] This being said... For example: in states of increased production of TBG such as OCP use, pregnancy or HRT, the free thyroid hormones will bind to the excess of TBG, decreasing the biologically active free/unbound thyroid but increasing the TOTAL T4 This will create a euthyroid state as the little T4 bound to the new TBG will only cause slight loss of free unbound thyroid which will not affect the axis (total is actually increased)
What hormone does strums ovarii produce?
Thyroid hormone
Where do you find arterial ulcers ?
Tips of the digits
What are the most common causes of hyperthyroidism after graves? What is the pathophysiology for both of these?
Toxic adenoma Toxic Multinodular goiter (Plummer disease) These 2 can be viewed as the same disease with different spectrum of activity, one has a single hot nodule while the latter has multiple Activating mutations in the TSH receptors causes hormone secretion.
What will the radioactive uptake patter be like in Toxic adenoma vs multinodular goiter (Plummer disease)
Toxic adenoma will be localized to one nodule Plummer disease will be patchy in distribution (multiple nodules)
What is clomiphene citrate used for?
Treats infertility in PCOS
What is the most common cause of PAI worldwide?
Tuberculosis
What is the pathophysiology of VIPomas?
Tumor that secretes vasoactive intestinal peptide VIP, which binds to the intestinal epithelium cells and increases fluid and electrolyte secretion. Known as pancreatic cholera with watery diarrhea
What causes primary aldosteronism?
Unilateral adrenal adenoma B/L adrenal hyperplasia
What test can aid in diagnosis of G6PD deficiency ?
Urinary Prussian blue stain. It will indicate presence of hemosiderin found in the urine during hemolytic episodes
Metabolic syndrome criteria
Waist > 40 in men 35 in women Fasting glucose > 100-110 Blood pressure >130/80 Triglycerides > 150 HDL <40 in men or <50 in women Need 3 out of 5
What is diagnostic of VIPomas?
Water diarrhea with VIP level >75 Stool osmolality < 50
Features of VIPomas?
Watery diarrhea due to decrease of gastric acid Intermittent flushing (yes, like carcinoid syndrome) Hypokalemia (diarrhea) Hypercalcemia (bone resorption) Hyperglycemia (increased glycogenolysis)
Where do you find neuropathic ulcers?
Weight bearing sites like sole of foot or below the head of the first metatarsal
What is the first line therapy for PCOS patients that is not pharmacological?
Weight loss
3 primary treatments for hyperthyroidism ?
antithyroid meds RAI Thyrodectomy
What will excessive secretion of growth hormone increase in hepatic production ?
insulin growth factor IGF-1 which causes excessive growth of bones and soft tissues
What is the best screening test for primary aldosteronenism ?
plasma aldosterone concentration to plasma renin activity PAC/PRA If >20 with a plasma Aldo >15 then it suggest primary hyperaldosteronism
How can you distinguish primary hyperthyroidism (graves) from exogenous hormone intake?
radioactive iodine uptake. If its high and diffuse*, it means there is de novo production thus graves has increased production of thyroid hormone. If the uptake is low, then it means the thyroid is not producing new hormones thus it's either releasing preformed thyroid hormone (thyroiditis) or exogenous use.
How do you go about diagnosis of primary adrenal insufficiency ?
serum cortisol level ACTH level Aldosterone and renin
Clinical features of PCOS
Androgen excess causing hirturism, acne, male pattern baldness Anovulation Obesity Polycistic ovaries on U/S
Which medications can exacerbate pheochromocytoma induced HTN?
Anesthetics
Algorithm for treatment of hyperprolactenimia 2/2 prolactinoma
After clinical eval and high suspicion perform MRI of pituitary If a prolactinoma is found then determine the size. If <10 mm and asymptomatic no treatment If >10 or symptomatic you have 2 options Dopamine agonist Resection if increases in size while on treatment Dopamine agonist should normalize prolactin levels and decrease size
Why do patients with primary hyperaldosteronism do not have edema?
Aldosterone escape mechanism
How do you correct calcium based on albumin levels?
Corrected calcium = measured calcium + 0.8x(4-albumin)
Describe the defect, etiology and clinical features as far as serum Na that is found for primary polydipsia, central DI and nephrogenic DI
Primary polydipsia occurs due to drinking too much water. Etiologies include antipsychotics, anxious elderly women and molly. Will have a low serum Na due to dilution effects Central DI occurs due to inability of ADH production from pituitary. Etiologies include trauma, idiopathic, pituitary surgery or ischemic encephalopathy. Serum Na will be high (cannot retain H20) urine Na will be low (diluted) Nephrogenic DI occurs when the kidneys are resistant to ADH. Etiologies include drugs such as lithium, hypercalcemia and AVPR2 mutations. You will have normal serum Na to high, it depends on the degrees of renal ADH resistance
What is the PE presentation of primary vs secondary hyperthyroidism?
Primary you will have exothalmus, pretibial myxedema and may hear a thyroid bruit Secondary you WILL NOT have extrathyroidal manifestations
What is megestrol acetate ?
Progesterone analogs
What is the only level that may be elevated in a non functioning adenoma ?
Prolactin, it will be mildly elevated as supposed to a prolactinoma which will have >200 levels
Which proto-oncogene is associated with MEN 2A/2B syndrome?
RET
What treatment can worsen graves opthalmopathy ?
Radioactive iodine as it can increase titers of TRAB which will worsen the ophthalmoplegia