1. What is the result of elevated prolactin?
    • Decreases the secretion of GnRH, which leads to reduced levels of LH and FSH and their target organ functions:
    • Men -- impotence and hypogonadism
    • Women -- oligomenorrhea or amenorrhea, hirutism, galactorrhea
  2. What drugs can raise prolactin levels?
    • Reglan
    • Antidopaminergics
    • Cimetidine
    • Verapamil
    • Risperidone
    • Haldol
    • Higher doses of estrogen
  3. At what prolactin level do you suspect prolactinoma?
    • PRL > 100
    • If PRL > 20 but < 100, look for other causes of hyperprolactinemia
    • PRL levels are especially elevated with macroadenomas, so suspect another tumor type when > 1 cmm and PRL < 200
  4. What are treatment options for prolactinoma?
    • Transsphenoidal surgery
    • Cabergoline and bromocriptine
  5. What is one side effect of Bromocriptine and cabergoline that you should watch out for?
    • Valvular heart disease
    • -- although unlikely at the doses used to treat hyperprolactinemia, and more likely when used at the higher doses to treat Parkinson's
  6. When is surgery indicated in prolactinoma?
    • If there is marked mass effect or poor response from drugs
    • Elevated PRL levels often return after surgery, so follow for an extended period of time.
  7. Is Radiotherapy effective in prolactinoma?
  8. What do you warn the female patient before initiating medical treatment for prolactinoma?
    She may ovulate during therapy, and thus need to take precaution against pregnancy
  9. What do you do with bromocriptine in patient with prolactinoma who become pregnant?
    • Bromocriptine is not proven safe in pregnancy, not FDA approved, and should be discontinued unless:
    • -- Current evidence of mass effect
    • -- h/o a very large tumor, which greatly shrunk with treatment before pregnancy
  10. How do you follow a patient with prolactinoma during pregnancy?
    • Do not follow prolactin levels (it is always elevated during pregnancy)
    • Follow clinically depending on tumor size
    • -- Microprolactinomas - 3-5% will enlarge significantly during pregnancy. Follow q 3 months and check for symptoms
    • -- Macroprolactinomas - about 20-30% will enlarge during pregnancy. Follow q 1-2 months for symptoms and check visual fields
  11. What happens if prolactinoma symptoms occur during pregnancy?
    • Order MRI without contrast
    • May need surgery if substantial enlargement
    • Otherwise, medical treatment is preferred
    • If medical therapy is reinstated, use bromocriptine at the lowest dose that provides sufficient improvement.
  12. Discuss Prolactinomas and hormones
    • Oral contraceptives are okay in women with microprolactinomas, but remember that estrogen stimulates prolactin secretion so PRL levels may rise a little.
    • Avoid oral contraceptives in any woman with a macroprolactinoma
  13. Give a brief overview of GH
    • Stimulates production of insulin-like growth factors in the liver.
    • Main IGF is IGF-1
    • Stimulates hepatic glucose production and inhibits peripheral action of insulin
  14. What 3 endocrine disorders can cause carpal tunnel syndrome?
    • Acromegaly
    • DM
    • Hypothyroidism
  15. Discuss the normal physiology of GH
    • Low glucose stimulates GH secretion
    • High glucose suppresses GH secretion
    • GH secretion is pulsatile
    • Random level of GH not usually helpful
  16. Screening for acromegaly
    • Order IGF-1.
    • If elevated, must confirm GH. Do not order GH randomly
    • Check GH only while glucose is high -- check 1 hour and 2 hours after 100 g glucose tolerance test
    • While glucose is elevated, GH should be suppressed to < 5 ng/mll.
    • In acromegaly, GH > 5 ng/ml
  17. Acromegaly treatment
    • Resection of pituitary tumor
    • Consider radiation therapy, but this take years to be effective
    • Medical therapy
    • -- somatostatin analogues (ocreotide, lanreotide)
    • -- hGHR blockers (pegvisomant)
  18. Management of small pituitary Incidentaloma
    • If patient is asymptomatic, test for:
    • -- prolactin
    • -- 24-hour urine cortisol or dexamethasone suppression test
    • -- IGF-1
    • If inactive, repeat CT/MRI in 6 months, then annually for several years to watch for growth.
  19. Discuss Empty Sella Syndrome
    • Usually seen in multiparous women
    • Weakened diaphragm at top of sella invaginates and pushes the pituitary tissue to the sides of the sella.
    • Pituitary still functions
    • Ignore
  20. Discuss Sheehan Syndrome
    • Löss of blood flow to the pituitary during or shortly after delivery
    • May cause panhypopituitarism, or may cause loss of only one or a few hormones
    • May also cause loss of posterior function with resultant diabetes insipidus
  21. Discuss Pituitary Apoplexy
    Hemorrhagic infarction of a pituitary tumor
  22. What is the usual presentation of Pituitary Apoplexy
    • Severe HA with variable onset
    • n/v
    • Meningismus
    • Vertigo
    • +/- visual field defects
    • +/- altered consciousness
  23. Workup in patient with suspected Pituitary apoplexy
    • CT/MRI will show high-density mass within the pituitary due to blood
    • Must differentiate from a leaking aneurysm
  24. Risk factor for Pituitary apoplexy
    • DM with microvascular changes
    • Radiotherapy to the pituitary
    • Warfarin use
  25. Intervention in patient with suspected Pituitary Apoplexy
    • Neurosurgical emergency -- may need decompression
    • Mild cases can be treated with steroids
  26. Explain management of Central Diabetes Insipidus
    • Central DI can be caused by trauma or surgery. There are three phases:
    • Phase I -- occur secondary to injury to axons. The nerve axons can be intact or severed. If injured but still intact, ADH may not be secreted and Phase I starts. This is characterized by high volume urine, serum hypernatremia, and increased osmolality. This is treated with fluids and desmopressin. If the axons are not severed, then normal function slowly resume and Phase 2 and 3 will not occur.
    • Phase 2 -- occurs when the severed axons begin to decay. The stored ADH vesicles are released into the circulation. Large volume urine stops, Serum Na decreases. This is treated with fluid restriction and d/c desmopressin.
    • Phase 3 -- occurs after the axons have decayed and all the stored ADH have been released. Large volume urine recur, serum Na again rises. This is treated with lifelong desmopressin, and fluid replacement. Patient now has DI for life.
  27. Describe the test for Diabetes Insipidus
    Testing for diabetes insipidus involves a water deprivation test, as long as the baseline serum osmolality is not substantially elevated. Patient weight and urine and serum osmolalities are obtained every 2 hours until the urine and serum osmolalities have stabilized (serum osmolality >295 mosm/kg) and the patient has lost no more than 3% of body weight. The patient is then given 5 µg of desmopressin intranasally; urine osmolality continues to be measured hourly for the next 2 to 3 hours. During water deprivation and before desmopressin administration, healthy persons will increase their urine osmolality to greater than 800 mosm/kg, but those with diabetes insipidus will not increase theirs above 300 mosm/kg. In response to desmopressin, patients with central diabetes insipidus will increase their urine osmolality by at least 50%, but those with nephrogenic diabetes insipidus will not respond appreciably to desmopressin administration. Patients with partial diabetes insipidus will increase their urine osmolality to 300 to 500 mosm/kg with dehydration and by at least another 9% with desmopressin.
  28. How do you differentiate between polyuria caused by primary polydipsia vs. DI?
    • A low plasma sodium concentration (less than 137 meq/L) with a low urine osmolality (eg, less than one-half the plasma osmolality) is usually indicative of water overload due to primary polydipsia.
    • A high-normal plasma sodium concentration (greater than 142 meq/L, due to water loss) points toward DI, particularly if the urine osmolality is less than the plasma osmolality [1].
    • A normal plasma sodium concentration is not helpful in diagnosis but, if associated with a urine osmolality more than 600 mosmol/kg, excludes a diagnosis of DI.
  29. If an incidentaloma is found in the pituitary, what tests should you send?
    • IGF-1
    • PRL
    • 24-hour urine cortisol
  30. In Thyroid Uptake studies, give examples of low uptake (< 5%), and high uptake (>35%):
    • Low uptake:
    • -- Thryroiditis
    • -- Suppression (iodine, PTU/methimazole, T4/T3)
    • -- Iodine excess (kelp, contrast dye, amiodarone)

    • High uptake:
    • -- Graves disease
    • -- Iodine deficiency
    • -- Really high levels of B-HCG
  31. Describe some of the signs and symptoms of hypothyroidism
    Dementia, CHF, pericardial effusions, pleural effusions, respiratory depression, chronic constipation, ascites, irregular menses, galactorrhea, muscle cramps, weakness, fatigue, hyperlipidemia, anemia, depression, joint discomfort, dry skin, hair loss, HTN, coarse hair, periorbital swelling, hoarse voice, large tongue
  32. Etiologies of hypothyroidism
    • Thyroiditis
    • Loss of gland (surgery or ablation)
    • Antithyroid agents
    • Iodine deficiency
    • Recent Iodine load
    • Pituitary disorders
  33. What is a cautionary note regarding Subclinical Hypothyroidism?
    • it is most often due to aery, mild Hashimoto's disease
    • -- check anti-TPO antibodies
    • -- if elevated
    • -- high risk of overt hypothyroidism
    • -- follow regularly, consider treatment
  34. Treatment of hypothyroidism
    • T4 (levothyroxine)
    • -- if you suspect cardiac disease, start low and titrate low
  35. What can interfere with intestinal absorption of T4?
    • Cholestyramine
    • FeSO4
    • Al(OH)3
    • Sucralfate
    • CaCO3
    • Soy protein dietary supplements

    *Take LT4 several hours before or after
  36. When do you need to increase LT4 (levothyroxine) dose?
    • When taking meds that can accelerate metabolism of T4
    • -- Rifampin and anticonvulsants
  37. Name some uncommon presentation of Hyperthyroidism
    • Any tacharrhythmia (not just a-fib)
    • Chronic diarrhea
    • CHF
    • Depression
    • Osteopenia
    • Increased ALP
    • Irregular menses
    • gynecomastia
    • weakness
    • fatigue
    • hair loss
    • conjunctivitis
    • diplopia
  38. Etiologies of hyperthyroidism
    • Graves disease
    • Exogenous T4/T3
    • Toxic multinodular goiter
    • Autonomous (hot) nodule
    • Excessive iodine
  39. Discuss Graves disease:
    • Classically, goiter and ophthalmopathy
    • Elevated nuclear medicine uptake
  40. Discuss hyperthyroidism due to Exogenous T4/T3
    • No goiter
    • Increased FT4 and/or T3
    • Low uptake
  41. What is another description of toxic multinodular goiter?
    • Lumpy/bumpy, patchy scan
    • Uptake may be high, low, or normal
  42. Discuss treatment of Hyperthyroidism
    • Thionamides
    • -- PTU and menthimazole
    • - inhibit synthesis of thyroid hormone
    • - watch out for fetal malformations
    • Iodine
    • B-blockers
    • Radioablation
  43. In a pregnant patient with hyperthyroidism, which one would you use?
    • PTU preferred in pregnancy (but not FDA approved).
    • Both methimazole and PTU can cause fetal malformations, but methimazole > PTU
  44. What are life-threatening side-effects of the Thionamides(PTU and methimazole)?
    • Hepatic toxicity
    • Aganulocytols
    • -- both are very rare, unpredictable. Do not screen or routinely check LFT or CBC. Follow clinically instead.
  45. Discuss Radioablation in the treatment of hyperthyrodism
    • Delayed effect, so not useful for acute symptoms
    • Transient worsening of hyperthyroidism may occur
    • May initially need to continue antithyroid medication
    • -- resume PTU or methimazole
    • May become hypothyroid later on
    • Goal of treatment is hypothyroid. They may be euthyroid initially
  46. Describe the effect of thyroid radioablation in pregnancy.
    What should you advise female patients of child-bearing age who are going through radioablation?
    What is the effect of hyperthyroidism on contraception?
    • It will destroy the thyroid gland of the fetus resulting in cretinism.
    • Patients undergoing radioablation need to avoid pregnancy for at least 6 months.
    • Oral contraceptives are less effective in hyperthyroidism
    • Use at least two methods of contraception
  47. When is thyroid surgery indicated?
    • If patient with Graves disease also has a cold nodule. Otherwise, radioablation is preferred if problem is only hyperthyroidism.
    • Potential complications for surgery are:
    • -- recurrent laryngeal nerve damage
    • -- temporary or permanent hypoparathyroidism
  48. Describe Euthyroid Sick Syndrome
    • also known as non-thyroidal illness
    • Usual labs: TSH mildly low or low-normal, FT4 mildly low or low normal
    • T3 very low
    • rT3 high (hallmark)
    • Thyroid is not the problem, treat the underlying illness
  49. Discuss Thyroiditis
    • May be hypothyroid because the gland is sick, not making enough thyroid hormone
    • Or hyperthyroid because the gland is inflamed and some thyroid hormone may leak out
    • May even be euthyroid
  50. Subacute thyroditis -- what is it?
    What is a hallmark sign
    What is the result of thyroid uptake?
    • may follow a viral illness, most often URI
    • Usually a diffuse, symmetric goiter
    • Very tender gland ( hallmark sign)
    • Disease is self-limited
    • Sed rate elevated
    • Thyroid uptake is suppressed
    • This is a self-limited disease
    • Treat with ASA and / or glucocorticoids, if at all
  51. What is the test to order if you suspect subacute thyroiditis?
    Thyroid uptake
  52. Discuss Hashimoto's thyroiditis
    • Hashitoxicosis if hyperthyroid
    • May imitate Graves disease
    • -- Both may have goiter plus hyperthyroidism
    • -- Thyroid uptake will differentiate
  53. How do you differentiate Hashimotos from Graves?
    • Thyroid uptake will differentiate:
    • - Grave's disease if the uptake is high
    • - Hashitoxicosis if the uptake is low.
  54. What is the treatment for Hashimoto's?
    • Treat symptomatically
    • -- if hypothyroid, LT4
    • -- if hyperthyroid, thionamide
  55. Evaluation of thyroid nodules
    • Nuclear medicine thyroid scan -- if hot or warm, then it's probably a high functioning thyroid adenoma. If cold, look at cancer risk.
    • If the patient is euthyroid on presentation and has a single palplable nodule, many endocrinologist will bypass the nuclear medicine thyroid scan and proceed diretly to the FNA since this is the most cost-effective workup.
  56. If patient has multiple nodules..
    biopsy the biggest cold nodule
  57. If the FNA result from the thyroid nodule come back malignant, what is the next intervention?
    refer to an endocrinologist
  58. Discuss Papillary thyroid cancer
    • most common
    • Usually grows slowly
    • Lymphatic spread
  59. What are the Thyroid malignancies?
    • Papillary cancer
    • Follicular cancer
    • Anaplastic cancer
    • Medullary
  60. Summarize treatment for thyroid cancer.
    • Thyroidectomy
    • High-dose radioactive iodine while TSH is markedly elevated
  61. What is important during Thyroid cancer testing?
    TSH must be markedly elevated for total body scans and radioablation. TSH should be greater than 30.
  62. Discuss thyroid hormone replacement
    Aim for low TSH (0.2 -- 0.4, not <0.01)
  63. What are the two kinds of thyroid emergencies?
    • Thyroid storm
    • Myxedema coma
  64. What is the classic presentation of Thyroid Storm?
    • Preexisting hyperthyroidism
    • Mental status change
    • Increased temp
  65. Discuss treatment of Thyroid storm:
    • Glucocorticoids -- patient will have high cortisol but this is not enough for what they need.
    • Beta-blockers
    • PTU or methimazole
    • Iodine
  66. How do you treat Myxedema Coma?
    • Clinical presentation is decreased mentation, hypothermia, hyponatremia, hypoventilation.
    • Treat aggressively, but exercise caution if heart disease suspected
    • IV T4 used frequently. Oral drug is poorly absorbed.
    • IV T3 not usually used due to cardiac side effects
  67. Discuss Hyperthyroid preop consult
    • There is risk of underlying cardiac dysfunction
    • Surgery may precipitate thyroid storm
    • If surgery is not urgent, make the patient euthyroid first
    • If surgery is urgent but can be postponed for a few days, start treatment
  68. Discuss preop consultation in patient with Hyperthyroidism needing emergent surgery
    • Load with Beta-blockers and steroids (IV)
    • Start thionamide (PTU, methimazole) as soon as possible after surgery
  69. Discuss hypothyroid Preop consult
    • Risk of underlying cardiac dysfunction plus fluid and electrolyte abnormalities
    • Be suspicious of possible adrenal insufficiency
    • Replace thyroid hormones carefully and slowly if any suspicion of heart problems
    • If surgery is not urgent, make patient euthyroid first
  70. Describe the pregnant patient's thyroid profile
    Increased binding globulins result in increased TT4 even if euthyroid, so always check FT4.
  71. Discuss management of pregnant patient with hyperthyroidism
    • Grave's disease may become symptomatic only during pregnancy, resolve once deliver
    • Don't rush to treat
    • Beta-blocker if necessary
    • PTU if necessary
    • Treatment goal is FT4 and pulse rate that are high-normal or mildly elevated.
  72. Discuss management of pregnant patient with Hypothyroidism
    • Treatment of hypothyroidism during pregnancy may help the child's neuropsychological development
    • May need a higher dose due to greater levels of binding globulins
    • Follow TSH and FT4
    • If they are already on thyroxine before they became pregnant, may have to increase the dose
  73. Discuss Postpartum Thyroiditis
    • Somewhat common
    • Usually early hyperthyroid stage (about 1 month)
    • Followed by a long hypothyroid period (up to a year)
    • Self-limited, but treat the hypothyroidism
  74. What do you do with a pregnant or nursing woman who comes to you with a goiter, or a thyroid complaint?
    Never order a thyroid scan or give radioactive iodine for any reason to a woman who might be pregnant or nursing
  75. What do you check for if you suspect 21-hydroxylase deficiency?
    17-OH progesterone
  76. Discuss 21-Hydorxylase Deficiency
    • Low cortisol
    • Low mineralocrticoids -- hypotension, salt-wasting, hyperkalemia
    • High Androgens -- virilization, hirsutism, menstrual irregularities
  77. If an adrenal incidentaloma is found, what s/s will make you think of adrenal carcinoma vs. adrenal adenoma?
    Adrenal carcinoma usually also secrete DHEA and/or testosterone, may be palpable, much more symptomatic, progress more readily
  78. Discuss the Diagnostic Workup for Cushing's
    • First, verify hypercortisolism
    • 24-hour urine for cortisol
    • Normal: 20-90 ug/day
    • Cushing syndrome: > 150 ug/day
    • Second, check for normal suppression
    • Use low-dose dexamethasone suppression
    • If adequate suppression
    • Normal HPA axis
    • Pseudo-Cushing's
    • Inadequate suppression indicates disorder
    • Third, check for pituitary disease
    • Use high-dose dexamethasone suppression
    • Adequate suppression indicates pituitary source (Cushing disease)
    • Inadequate suppression indicates non-pituitary cause
  79. Discuss Low-dose Dexamethasone Test
    • 1 mg dexamethason suppression test
    • give 1mg of dexamethason at 11:00 pm
    • draw blood at 8:00 am
    • Cortisol
    • -- Normal post-suppression: < 5 ug/dL
    • -- Cushing syndrome: > 10 ug/dL
  80. Discuss High-dose Dexamethasone Test
    • 8 mg dexamethasone suppression test
    • give dose at 2300
    • draw blood at 0800
    • Check cortisol
    • < 50% of baseline suggests pituitary ACTH-dependent (Cushing's) disease
    • > 50% of baseline suggests wither exotic ACTH disease or ACTH-indpendent cause
  81. An adrenal tumor that lights up with T2 weighting suggests:
    • Malignant adrenal tumor
    • Adrenal cyst
    • Pheochromocytoma
  82. Tx of Cushing disease
    • Surgery if it's a tumor
    • Other options are not very good.
  83. Differentiate the symptoms and signs of Primary and Central (secondary) adrenal insufficiency:
    • Primary symptoms: Fatigue, nausea, anorexia, weight loss, abdominal pain, arthralgia, low-grade fever; salt craving, postural dizziness; decreased libido
    • Central symptoms: Same symptoms as primary insufficiency but no salt craving and postural dizziness

    • Primary signs: Hyperpigmentation, Dehydration, Hypotension, Decreased pubic/axillary hair in women
    • Central signs: Normal pigmentation, Normal volume, Slight decrease in blood pressure, Decreased pubic/axillary hair in women
  84. Differentiate between primary and secondary adrenal insufficiency
    • When primary adrenal insufficiency is present, plasma ACTH levels are increased and serum cortisol and aldosterone levels are low. A minimal or no increase in serum cortisol level in response to cosyntropin stimulation confirms the diagnosis. In normal persons, serum cortisol levels increase to 18.5 µg/dL (510.6 nmol/L) or greater 60 minutes after 250 µg of cosyntropin is administered intravenously (mean response, 28 µg/dL [772.8 nmol/L]).
    • Patients with central adrenal insufficiency have low or low-normal plasma ACTH levels and normal plasma aldosterone levels. Although patients with central adrenal insufficiency usually have a subnormal response to cosyntropin, some with partial deficiency display normal responses; in such patients, using a lower dose of cosyntropin (1 µg instead of 250 µg) improves the diagnostic accuracy of the test. Serum levels of DHEA and DHEA-S are low in both primary and central adrenal insufficiency.
  85. What is the standard mineralocorticoid replacement therapy for patients with preimary adrenal insufficiency?
    fludrocortisone, 0.05 to 0.1 mg/d
  86. Is there a difference in the treatment between Primary and Secondary adrenal insufficiency?
    • Patients with primary adrenal insufficiency require corticosteroid therapy and mineralocorticoid replacemen
    • Whereas those with central disease need corticosteroid therapy only
  87. Differentiate the major laboratory findings between Primary and Central Adrenal insufficiency:
    • Primary: Low basal serum cortisol level (<5.0 µg/dL [138 nmol/L]) with a suboptimal response (<18.5 µg/dL [510.6 nmol/L]) to cosyntropin; low serum DHEA and DHEA-S levels but high plasma renin activity and ACTH level
    • Secondary: Same cortisol findings as primary insufficiency except low or inappropriately normal ACTH level; normal aldosterone and plasma renin activity
  88. Symptoms of Adrenal insufficiency
    • Usual findings with low cortisol
    • Weakness and fatigue
    • Sparse body hair
    • Low or low-normal glucose
    • Anorexia
    • Nausea
    • Diarrhea
    • Abdominal pain
  89. Primary causes of Adrenal insufficiency
    • Autoimmune destruction (Addison disease)
    • Surgery or trauma
    • Infectious destruction
    • Hemorrhagic destruction ( i.e., Waterhhouse-Friderichson syndrome of meningococcemia, purpura, and acute adrenal hemorrhage)
  90. Secondary causes of Adrenal Insufficiency
    • Pituitary insufficiency secondary to inadequate ACTH production
    • Withdrawal of exogenous glucocorticoids (common)
  91. When is the best time to give glucocorticoids?
    Giving it in the morning makes it less likely to suppress ACTH, which can happen if dose is given at night.
  92. Discuss ACTH stimulation test
    • Synthetic ACTH (cosyntropin)
    • 1 amp (250 ug) given IM or IV
    • Draw blood before the ACTH is given and 30 to 60 minutes afterwards
    • Measure serum cortisol
    • Normal is any cortisol > 20 ug/dL
  93. What is the hydrocortisone therapy in established Adrenal insufficiency patients with the following conditions?

    Septic shock
    150-200 mg/d IV in four divided doses
  94. What is the hydrocortisone therapy in established Adrenal insufficiency patients with the following conditions?

    Severe stress (major surgical procedure, such as cardiac surgery, hip replacement), sepsis without shock
    100-150 mg/d IV in four divided doses
  95. What is the hydrocortisone therapy in established Adrenal insufficiency patients with the following conditions?

    Minor stress (symptoms of a cold or mild influenza)
    30-50 mg/d PO in three divided doses
  96. What is the hydrocortisone therapy in established Adrenal insufficiency patients with the following conditions?

    Physiologic daily dosing
    15-25 mg PO in three divided doses,a at 8:00 AM (7.5-12.5 mg), 12:00 noon (5.0-7.5 mg), and 6:00 PM (2.5-5.0 mg)

    aFor twice daily dosing, the morning dose is 10-15 mg PO, and the late afternoon dose is 5-10 mg PO.
  97. Discuss treatment of Adrenal insufficiency
    • The only treatment is glucorticoids
    • Typically hydrocortisone BID
    • Hydrocortisone also has some mineralocoticoid effects, which are useful if primary adrenal insufficiency
  98. In a patient with adrenal insufficiency and hypothyroidism (Schmidt syndrome), which do you replace first?
    Replace glucocorticoids before starting on thyroxine replacement
  99. Presentation of Hypoaldosteronism
    • Hyperkalemia
    • Metabolic acidosis
    • Hypotension
  100. Presentation of Hyperaldosteronism
    • Hypokalemia
    • Metabolic alkalosis
    • HTN
    • Often without edema
  101. Diagnosis of hyperaldosteronism
    • First, try to suppress aldosterone
    • Saline load
    • Supine for several hours while fully hydrated
    • Check aldosterone and renin
    • High aldosterone and low renin indicates primary hyperaldosteronism
    • High aldosterone and high renin indicates secondary hyperaldosteronism
  102. Describe "Apparent Mineralocorticoid Excess."
    • Presentation similar to primary hyperaldosteronism
    • - hypokalemia
    • - alkalosis
    • - hypertension
    • - low renin
    • But low aldosterone
    • High levels of deoxycorticosterone (DOC)
    • - can be from DOC-secreting tumor
    • Ingestion of natural licorice
    • - has metabolite which inhibit 11β-hydroxysteroid dehydrogenase type 2 (converts cortisol into cortisone) and raises cortisol levels within the kidney.
  103. Presentation of Pheochromocytoma
    • HTN
    • Sudden, severe throbbing HA
    • Profuse sweating
    • Palpitations
    • Anxiety or a sense of doom
    • Skin pallor
    • Nausea
  104. Diagnostic tests for pheochromocytoma
    • 24-hour urine for catecholamines, metanephrines, VMA
    • Consider serum catecholamines while patient is symptomatic
    • Plasma free metanephrines -- high sensitivity, but has high false positive
  105. What medications are best used for BP control in pheochromocytoma:
    • Diuretics
    • Vasodilators (hydralazine, minoxidil)
    • CCB
    • ACE-I
  106. Treatment of Pheochromocytoma
    • Surgical recetion of tumor, but patient must first be treated with an a-adrenergic receptor blocker (phenoxybenzamine)
    • Never block B-receptores without first blocking a-receptors; otherwise unopposed a-stimulation worsens vasoconstriction
    • Give large volume during surgery
  107. Workup for Adrenal Incidentaloma:
    • Check the ff:
    • - Blood pressure
    • - Serum potassium
    • - 24-hour urine dor catecholamines, metanephrines, and VMA

    • *If you suspect cortisol excess, order 24-hour urine cortisol or overnight dexamethasone suppression test
    • *If suspect mineralocorticoid excess, order supine aldosterone and renin activity
    • *Women with hirsutism, check testosterone
    • *Man with gynecomastia, check testosterone and estradiol
  108. Treatment of Adrenal Incidentaloma
    • If (+) secretion or if tumor is > 5 cm, need surgical resection
    • Otherwise, consider referral for CT-guided biopsy (first rule out pheo)
    • Remaining option is to repeat CT in 3 months and look for evidence of growth
    • If growing, refer for surgical resection
  109. Signs and symptoms of Secondary adrenal insufficiency:
    • Same symptoms as primary insufficiency but no salt craving and postural dizziness
    • Normal pigmentation
    • Normal volume
    • Slight decrease in blood pressure
    • Decreased pubic/axillary hair in women
    • Same cortisol findings as primary insufficiency except low or inappropriately normal ACTH level; normal aldosterone and plasma renin activity
    • Same findings as primary insufficiency but also normal potassium level
  110. Signs and symptoms of Primary Adrenal insufficiency
    • Fatigue, nausea, anorexia, weight loss, abdominal pain, arthralgia, low-grade fever; salt craving, postural dizziness; decreased
    • libido
    • Hyperpigmentation
    • Dehydration
    • Hypotension
    • Decreased pubic/axillary hair in women
    • Low basal serum cortisol level (<5.0 µg/dL [138 nmol/L]) with a suboptimal response (<18.5 µg/dL [510.6 nmol/L]) to cosyntropin; low serum DHEA and DHEA-S levels but high plasma renin activity and ACTH level
    • Hyponatremia, high potassium level, azotemia, anemia, hypoglycemia, and leukopenia (with a high % of eosinophils and lymphocytes)
  111. Examples of Primary Female Hypogonadism
    • Turner syndrome
    • Destruction of the ovaries
    • - Radiation or chemotherapy
    • - Autoimmune
  112. Causes of Secondary Female hypogonadism
    • Kallman's syndrome
    • Hypothalamic and pituitary disease
    • Uremia and chronic renal failure
    • Anorexia nervosa
    • Strenuous weight bearing exercise (swimmers not affected)
    • Stress
  113. Lab tests in Turner syndrome:
    • Gonadotropins (LH, FSH) are elevated
    • Karyotype to verify (Some women will have Y chromosome). This points to a high risk of gonadoblastoma. Need referral to surgery to remove all the tissue around where the ovaries would be.
  114. S/s of Turner syndrome
    • HTN
    • Heart murmur, often aortic stenosis
    • Coarctation of the aorta
    • Renal abnormalities
    • Increased risk of:
    • Hashimoto's thyroiditis
    • Osteoporosis
    • DM
    • Aortic dissection
  115. Therapy of Turner Syndrome
    • Begin exogenous estrogen at expected time of puberty and later add periodic progesterone
    • Estrogen to help bone density
    • Progesterone to induce menses and protect the endometrium
    • Eche q 3-5 years (due to high risk of aortic dissection)
    • Excision of gonadal area if Y chromosome is present.
  116. Define Primary Amenorrhea
    • No history of any menses by age 16
    • No secondary sex characteristics by age 14
  117. Define secondary amenorrhea
    • Past history of menses
    • No menses for 3 months
  118. Evaluation of Amenorrhea
    • Pregnancy test
    • Prolactin and TSH
    • Ovarian axis (FSH, LH)
    • - Elevated implies ovarian failure
    • - Decreased or inappropriately normal implies CNS or pituitary dysfunction
    • Assess endogenous estrogens
    • - Check estradiol
    • - Induce withdrawal bleeding
  119. Definition of PCOS (Polycystic Ovarian Syndrome)
    Anovulatory with continuous stimulation of the ovary by LH
  120. Characteristics of PCOS:
    • Infertility
    • Hirsutism
    • Amenorrhea
    • Obesity
    • Virilization
    • Ovary thickened, enlarged, with multiple follicles at different levels of maturation
  121. What are associated problems of PCOS?
    • Increased risk of endometrial hyperplasia and cancer from unopposed estrogens
    • Insulin resistance
    • Increased risk of coronary artery disease
  122. How do you evaluate PCOS?
    • LH (elevated)
    • FSH (often normal)
    • LH/FSH ratio (usually > 3)
    • Testosterone (elevated)
    • Estrogens (elevated)
    • Check PRL and TSH
  123. PCOS treatment?
    Clomiphine citrate

    Metformin (not FDA approved for this), less effective than clomiphene
  124. What is the normal Testicular volume?
    18 +/- 4.8 ml
  125. On testicular exam, the following words would make you suspicious of what pathology?
    1. Small and firm
    2. Small and rubbery
    3. Mush or soft
    • 1. Klinefilter
    • 2. low gonadotropins
    • 3. postpuberal atrophy
  126. Causes of Primary Male Hypogonadism
    • Trauma, torsion
    • Infection (mumps, leprosy)
    • Cryptorchidism
    • Klinefilter's syndrome
    • Radiation or chemo
    • Autoimmune destruction
  127. A buccal scraping from a patient that comes back positive for a Barr body will make you think of what pathology?
  128. Characteristics of a patient with Klinefilter syndrome
    • 47 XXy (Barr body is present)
    • Onset is prepubertal
    • Testes small and firm, often < 2.5 cm (4 ml), smaller than prepubertal size
    • Increased length of lower body segment
    • Arm span not increased (unexpected)
    • Gynecomastia
    • Testosterone low or low-normal
    • Gonadotropins elevated
  129. Describe Kallman Syndrome
    • Can occur in both men and women
    • 46, XY (or XX)
    • Testes small, but larger than in Klinefelter -- 3-4 cm, normal prepubertal size
    • Eunochoid proportions -- lower body segment and arm span
    • Normal mental development
    • Anosmia or hyposmia (olfactory bulb neuron migrationd defect)
    • Basal FSH and LH low or undetectable
    • Low testosterone
    • Do not order karyotype to verify
  130. A patient who works in a smelly job for many years report that he is unable to smell will make you think of what pathology?
    Kallman syndrome
  131. Treatment of Kallman syndrome
    • Androgen replacement does not address infertility
    • Fertility treament
    • -- hCG (LH replacement) to stimulate Leydig cells
    • -- Once testosterone levels are normal, begin rhFSH for spermatogenesis
    • - - alternatively LHRH pulsatile infusion pump
  132. When ordering phosphodiesterase 5 inhibitors for impotence, what should you be cautious about?
    • Nitrates are contraindicated
    • LV outflow obstruction (i.e., aortic stenosis, idiopathic hypertrophic subaortic stenosis)
    • Concomitant use of alpha-blockers
  133. In males with gynecomastia, when is biopsy absolutely necessary?
    unilateral, hard contender, irregular mass
  134. What are the initial lab tests in patients with gynecomastia?
    Testosterone, LH, FSH, β-hCG, TSH, estradiol, prolactin
  135. What are the accepted uses of androgens?
    • Hereditary angioneurotic edema
    • -- Danazol stimulates C1q production
    • Hypogonadism
    • -- titrate dose based on subjective response. Do not measure testosterone
  136. What are the complications of androgens?
    • Hepatotoxicity, including liver cancer
    • Decreases fertility and testicular sizes
    • Cardiomyopathy
    • Thrombosis
    • Gynecomastia
    • Behavioral disturbances
    • In women: hirsutism and virilization
  137. What are the clinical findings in Hypertriglyceridemia?
    • Lactescent serum
    • Eruptive xanthoma
    • Lipemia retinalis
    • - retinal vessels are white
    • Abdominal findings
    • - pain
    • - acute pancreatitis
    • - hepatosplenomegaly
  138. What are common secondary causes of Hypertriglyceridemia?
    • Ethanol abuse
    • Insulin resistance
    • Obesity
    • Hypothyroidism
    • Nephrotic Syndrome
    • Medications
  139. What medications can cause hypertriglyceridemia?
    • Antiretroviral therapy (not atazanavir)
    • Estrogens (oral > patch)
    • Tamoxifen
    • Glucocorticoids
    • Non-selective beta blockers
    • 13-cis-retinoic acid
    • HCTZ (> 50 mg/day)
  140. Secondary causes of LDL elevation:
    • DM
    • Hypothyrodism
    • Nephrotic syndrome
    • CRF
    • Obstructive liver disease
    • Glucocorticoids
    • Anabolic steroids
    • Progestins
  141. What can lower HDL?
    • diet high in trans-fatty acids
    • Beta-blockers (except labetalol)
  142. Discuss Familial Hypercholesterolemia:
    • Uncommon
    • LDL typically > 250 mg/dL
    • First line treatment -- statins
  143. Discuss Familial Combined Hyperlipidemia
    • Common
    • Most common cause of lactescent plasma
    • High LDL and VLDL
    • Increased production of VLDL, which leads to high LDL (VLDL gets converted into LDL)
    • LDL typically 190-230
    • Treat with statin
  144. Discuss Familial Hypertriglyceridemia
    • High TG (from VLDL)
    • Treatment:
    • -- First choice: niacin (inhibits hepatic syntheses of VLDL)
    • -- 2nd choice: fibrates (increase activity of LPL, which removes TG from VLDL)
  145. Discuss Dysbetalipoproteinemia
    • High IDL
    • Familial but usually in conduction with DM, obesity, hypothyroidism, or alcohol abuse
    • Characteristic finding is yellow palmar crease
    • Treatment:
    • -- Nicotinic acid
    • -- Low-fat diet
  146. In hyperlipidemia, what would you order if you see the following clinical clues?

    Tendon Xanthomas
  147. In hyperlipidemia, what would you order if you see the following clinical clues?

    Eruptive xanthomas
  148. In hyperlipidemia, what would you order if you see the following clinical clues?

  149. In hyperlipidemia, what would you order if you see the following clinical clues?

    Tuberous or palmer xanthomas
    LDL + TG
  150. In hyperlipidemia, what would you order if you see the following clinical clues?

    Yellow palmar crease
  151. Major risk factors for Hypercholesterolemia
    • Age
    • -- Men > 45 years
    • -- Women > 55 years

    • Family history if premature CHD in first degree relatives
    • -- male < 55 years
    • -- female < 65 years

    Current cigarette smoking
  152. What are the Coronary Heart Disease (CHD) risk equivalents?

    • Non-CHD atherosclerotic disease
    • -- peripheral arterial disease
    • -- abdominal aortic aneurysm
    • -- symptomatic carotid artery disease

    Multiple risk factors conferring 10-year risk of CHD > 20%
  153. According to the NCEP guidelines, what is the LDL goal and when do you begin drugs for the ff?

    Known or presumed CHD
    • LDL goal is < 100
    • Begin drugs if LDL > 130
  154. According to the NCEP guidelines, what is the LDL goal and when do you begin drugs for the ff?

    2 or more risk factors
    • LDL goal < 130
    • Begin drugs if LDL > 160
  155. According to the NCEP guidelines, what is the LDL goal and when do you begin drugs for the ff?

    < 2 risk factors
    • LDL goal < 160
    • Begin drugs if LDL > 190
  156. Discuss management of patients on statin
    • Check baseline LFTs and repeat in 12 weeks after starting or increasing the dose
    • If ALT > 3X ULN, reduce dose or switch statins
  157. Discuss the action of Fibric Acid Derivatives (Fibrates)
    • Decrease VLDL
    • May raise LDL
    • Increase HDL
    • No effect on chylomicrons
  158. Which fibrate is approved for use with statin?
    Fenofibric acid (Trilipix)
  159. Discuss the action of Ezetimibe
    • Inhibits intestinal absorption of dietary and biliary cholesterol
    • Effect on lipids:
    • -- reduces TC and LDL
    • -- Increases HDL
    • Small risk of myopathy and elevated transaminases, mostly in combination with a statin
  160. What are the major effects of Bile Acid Sequestrants?
    • Examples include Cholestyramine and Colestipol
    • Decrease LDL
    • No effect on HDL
    • May increase production of VLDL (TG)
    • -- avoid if TG elevated
    • -- avoid in dysbetalipoproteinemia because VLDL gets converted into IDL
    • Do not take within 4 hours of other drugs
    • Side effects include N/V, constipation, bloating
  161. If you have a patient with dyslipidemia and yellow palmar crease, what medication will be contraindicated?
    Bile acid sequestrates (cholestyramine, colestipol)
  162. Discuss the effects of Nicotinic acid (Niacin)
    • Inhibits hepatic production of VLDL
    • Lowers TG, LDL
    • Raises HDL
  163. Preferred med for LDL↑, HDL↔↓, TG↔
  164. Preferred medication for LDL↑, HDL ↓, TG↑
    Nicotinic acid

    • Other choices:
    • Fibrates (but may raise LDL)
    • Statin with fibrate
    • Ezetimibe
  165. Preferred med for TG↑ , HDL↓ , LDL↔
    Nicotinic acid or fibrate
  166. Absolute contraindications for statins?
    Active or Chronic liver diease
  167. Absolute contraindication for Ezetimibe
    Active of chronic liver disease
  168. Absolute contraindication for Bile acid resins
    • Dysbetalipoproteinemia
    • TG > 400 mg/dL
  169. Absolute contraindications for Fibrates
    Severe kidney or liver disease
  170. Absolute contraindication for Nitotinic acid
    • Chronic liver disease
    • Severe gout
  171. Discuss the diagnosis of Diabetes
    • Symptoms plus casual glucose ≥ 200 mg/dL
    • or fasting glucose ≥ 126 mg/dL
    • or 2-hour glucose ≥ 200 mg/dL during a 75 g OGTT
  172. What is the range for Impaired fasting glucose, how about impaired glucose tolerance?
    • 100-125 mg/dL
    • 140-199 mg/dL two hours after 75 g OGTT
  173. What is associated with insulin resistance?
    Acanthosis nigricans
  174. Microvascular complications in diabetics -- onset, and when to screen?
    • Usual onset is 10-15 years after developing diabetes.
    • Type 1 diabetics do not need to be screened for microvascular complications for the first five years.
  175. What two drugs are FDA-approved for painful neuropathy?
    • duloxetine
    • pregabalin
  176. How often do you screen for microalbuminuria?
    • screen every 6 months
    • Random urine for albumin and creatinine:
    • Normal: < 30 mg albumin/g Cr
    • Microalbuminuria: 30-300 mg albumin/g Cr
    • Macroalbuminuria: > 300 mg albumin/g Cr
  177. When do you use bicarb in a DKA patient?
    If very acidotic (pH < 7.1) and discontinue when it reaches 7.2
  178. Discuss LADA
    • Latent Autoimmune Diabetes of Adults
    • Type 2 DM but with autoantibodies
    • -- Anti-GAD (Glutamic Acid Decarboxylase)
    • -- Anti-islet cell
    • Antibodies will convert type 2 into type 1
    • May respond to oral treatment initially, but will soon require insulin
  179. Briefly discuss Dawn Phenomenon
    • Glucose levels often rise just before we wake up
    • Minimal increase
    • Due to early morning rise in growth hormone levels
    • Not associated with preceding hypoglycemia
  180. Discuss the Somogyi Effect
    • Early morning rise in glucose caused by nocturnal hypoglycemia
    • Need to decrease the evening insulin
    • Look for evidence of nocturnal hypoglycemia
    • -- sweating during the night
    • -- restless sleeping
    • -- waking up feeling tired and drained
    • -- bad nightmares
  181. What are examples of Sulfonylureas?
    • Glipizide
    • Glyburide
    • Glimepiride
  182. What drug is good for Postprandial hyperglycemia?
    • Meglitinides
    • "Immediate" release of insulin
    • Very short half-life
    • Available agents are -- Repaglinide, Nateglinide
    • Avoid if with significant liver disease
    • Use low dose in mild hepatic dysfunction
    • Safe in renal failure -- no dose adjustment needed
    • Nateglinide is not indicated if patient failed other oral secretagogues
  183. Discuss the action of Biguanides
    • Only metformin is available
    • Reduce insulin resistance primarily at the level of the liver
    • Reduce hepatic glucose production
  184. What are the absolute contraindications of Metformin?
    Creatinine ≥ 1.5 in men and ≥ 1.4 in women
  185. Discuss Thiazolidinediones
    • Improve insulin resistance at the level of the adipocytes and muscles
    • No adjustment needed for renal failure
    • May cause or worsen edema
    • May reduce Hgb levels
    • Examples are: Rosiglitazone, Pioglitazone
    • Risk of hepatic dysfunction
    • -- check ALT before initiation and periodically thereafter
    • -- Hold if ALT ≥ 2.5 x ULN
    • Cardiac risk is suspected with rosiglitazone
    • May cause/worsen heart failure
    • -- do not use in class III or IV CHF
    • -- Risk is greater when used in combination with insulin
    • -- avoid highest dose if also on insulin
  186. Discuss a-Glucosidase Inhibitors
    • Currently available -- Acarbose, Miglitol
    • Work in GI tract wo slow the digestion of complex COOH
    • Little or no systemic drug levels
  187. Discuss Amylin
    • Normally secreted by β-cells along with insulin
    • Suppresses postprandial rise in glucagon, thus decrease hepatic gluconeogenesis
    • Slows gastric emptying
    • Decreases appetite
  188. Discuss Pramlintide
    • Can be used with insulin in type 1 or 2
    • Injectable only -- cannot be mixed with insulin
    • Associated with weight loss
    • Most common side effect is nausea, hypoglycemia
    • Initially reduce insulin dose by 50% if taking it with Pramlintide
  189. Discuss GLP-1
    • Normally secreted bu certain intestinal cells in response to a meal
    • Suppresses postprandial rise in glucagon
    • Stimulates glucose-dependent insulin secretion
    • Stimulates increase in beta cells
    • Slows gastric emptying
    • Decreases appetite
  190. Discuss Exenatide
    • Approved for DM-2, not type 1
    • Approved for use with sulfonylurea, metformin, or TZD
    • Cannot be mixed with insulin
  191. Discuss DPP-IV
    • Oral
    • Inhibits breakdown of GLP-1
  192. What is the treatment for postprandial hypoglycemia?
    • low carbohydrate diet
    • multiple small meals
  193. Diagnosis of Insulinoma
    • 72-hour fast
    • Terminate 72-hour fast if with 2 or more glucose levels < 40 mg/dL and neuroglycopenic signs
    • Detectable levels of insulin and C-peptide
    • No evidence of surreptitious insulin secretagogues
    • Refer for localization of islet cell tumor and surgical excision
    • Screen for sulfonylurea also
  194. What are the neuroglycopenic signs?
    • Confusion
    • Lightheadedness
    • Aberrant behavior
    • Blurred vision
    • Loss of consciousness
    • Seizures
  195. What stimulates intestinal absorption of calcium?
    1,25(OH)2 Vit D
  196. What are s/s of Hypercalcemia?
    • Apathy, drowsiness, depression, obtundation, coma
    • Muscle weakness
    • Bowel hypomotility
    • Shortening of QTc time interval
    • Decreased GFR, impaired concentrating ability, nephrolithiasis, nephrocalcinosis
  197. What are bone manifestations of Primary Hyperparathyroidism?
    • Salt-and-pepper appearance of skull
    • Resorption of distal phalanges
    • Tapering of distal clavicle
    • Bone cysts (osteitis fibrosa cystica)
    • Osteopenia
  198. Diagnosis of Primary Hyperparathyrodism?
    • Measure iPTH
    • Elevated iPTH (or even WNL) with high Ca++
    • Usually low phosphate levels
  199. Treatment of Primary Hyperparathyrodism?
    Surgical exploration and resection if indicated.
  200. What are indications for surgery in Primary Hyperparathyrodism?
    • Serum Ca ≥ 1 mg/dL over ULN
    • Urine calcium > 400 mg/day
    • Symptomatic
    • Low bone density (t score < -2.5)
    • Age < 50 years
    • Cr Cl reduced by ≥ 30%
  201. S/S of Hypercalcemia?
    • Apathy, drowsiness, drowsiness, depression, obtundation, coma
    • Muscle weakness
    • Bowel hypomotility
    • Shortening of QTc time interval
    • Decreased GFR, impaired concentrating ability, nephrolithiasis, nephrocalcinosis
  202. Causes of Hypercalcemia
    • Primary hyperparathyroidism
    • Malignancy related
    • Medications
    • Granulomatous disease
    • Immobilization
    • Milk-alkali syndrome
  203. Diagnosis of Primary Hyperparathyroidism
    • Measure intact PTH (iPTH)
    • Elevated iPTH (or even WNL) with high Ca++
    • Usually low phosphate levels (PTH stimulates renal excretion of phosphate)
  204. Treatment of Primary Hyperparathyroidism
    Surgical exploration and resection if indicated
  205. Treatment of mild Hypercalcemia
    • Mild is Ca < 12 mg/dL with no or mild symptoms
    • Encourage hydration
    • Avoid thiazides, high calcium diet, bed rest
  206. Treatment of Severe Hypercalcemia
    • Severe is Ca++ > 14 mg/dL
    • IV hydration
    • IV calcitonin (if responsive, works in hours)
    • IV bisphosphonate (works in a few days)
    • -- Pamidronate
    • -- Zoledronic acid -- more efficacious, faster infusion, but higher risk of jaw osteonecrosis
  207. S/S of Hypocalcemia
    • Carpal spasm with pressure-- ischemia or upper arm nerves (Trosseau sign)
    • Twitch with tapping of facial nerve (Chvosted sign)
    • Prolongation of QTc interval
    • Circumoral numbness, cramps, fatigue, irritability, anxiety, depression
  208. Causes of Vitamin D disorders
    • Insufficient exposure to sunlight
    • Inadequate vitamin D intake
    • Malabsorption
    • Measure 25(OH) Vit D for (vitamin D stores)
  209. Discuss Hungry Bone Syndrome
    • Seen in patients with prolonged primary hyperparathyroidism
    • Bones become very deficient in calcium
    • Following parathyroid adenoma resection, PTH levels drop and the bones avidly take up calcium
    • May require calcium and Vit D supplements for a limited time
  210. Discuss Correct calcium levels for low albumin
    Corrected calcium = measure calcium + (4-albumin) x 0.8
  211. Phenotype of patient with Pseudohypoparathyroidism
    • It is a genetic disorder that results from impaired PTH receptor
    • Main characteristic is shortened 4th and 5th metacarpals and metatarsals (watch for picture of hand with short 4th and 5th fingers)
    • Round faces
    • Short stature
    • Obesity
    • Image Upload 1
  212. Does secondary hyperparathyroidism cause hypercalcemia?
  213. Explain MEN 1
    • Family must have adenomas of at least 2 of the following organs:
    • - Pituitary
    • - Pancreas -- Gastrinoma, Insulinoma, Glucagon, serotonin, VIP
    • - Parathyroid
  214. Discuss MEN 2
    • Medullary thyroid cancer
    • Pheochromocytoma
    • Two "flavors" of MEN 2 based on other tumors

    2A: Parathyroid adenoma

    2B: Ganglioneuroma phenotype -- Thickened lips, Multiple small bumps of the tip of the tongue
  215. Discuss Medullary Thyroid Cancer
    • Arises from the calcitonin-secreting C cells
    • Occurs in 4 settings:
    • - Sporadic
    • - Component of MEN 2A
    • - Component of MEN 2B
    • - Familial non-MEN medullary thyroid cancer
    • Fatal if not treated early
    • Requires early thyroidectomy at an early age.
    • But must be sure before you send a child for a total thyroidectomy antis possible complications
  216. How do you screen for Medullary Thyroid Cancer?
    • Check for RET proto-oncogene mutations
    • If index cases has a detectable mutation:
    • - Check all primary relatives for the same mutation
    • - If found, refer for cervical exploration and total thyroidectomy (even if very young) after screenig for pheochromocytoma
    • If relative does not have the mutation, then no risl
  217. What do you order to screen for carcinoid?
    24-hour urine 5-HIAA
  218. Hypertension and Hypokalemia make you think of what pathology?
    • Hyperaldosteronism
    • Order saline suppression test with aldosterone and renin while supine
  219. When do you measure 24-urine free cortisol?
    • It is useful when investigating the possibility of excessive glucocorticoid secretion
    • Not helpful in diagnosing adrenal insufficiency because of the wide range of normal values
  220. What is the use of an insulin-induced hypoglycemia test?
    • used as the gold standard to investigate the integrity of the hypothalamic-pituitary-adrenal axis.
    • hypoglycemia stimulates ACTH secretion from the pituitary gland, which in turn stimulates the adrenal glands to secrete cortisol.

    *Given its serious potential adverse effects, the insulin-induced hypoglycemia test should be performed only by experienced endocrinologists and should not be pursued as a routine diagnostic test in this patient.
  221. What are the endocrine effects of hemochromatosis?
    • DM
    • Hypogonadotropic hypogonadism
    • Adrenal insufficiency
  222. What are hallmark findings for myxedema coma?
    Mental status changes and hypothermia
  223. What is the suggested goal for serum TSH levels in patients ofn levothyroxine therapy?
    1.0 to 2.5 µU/mL (1.0 to 2.5 mU/L).
  224. What can suggest Hashimoto thyroditis as the cause of hypothyroidism?
    The presence of anti–thyroid peroxidase antibodies
  225. What would you advise your pregnant and lactating patients who have hypothyroidism?
    Adequate iodine intake is imperative for thyroid hormone production; pregnant and lactating women require 50% or 100%, respectively, more iodine intake than the general population.
  226. What would you use to distinguish hyperthyroidism from hypothyroidism?
    Color-flow Doppler ultrasonography
  227. What diseases involve thyroid gland overactivity?
    • Graves disease
    • toxic multinodular goiter
    • toxic adenoma
  228. What should you obtain in a patient with suppressed TSH level but a normal free T4?
    A T3 level (total or free) should be obtained in patients with a suppressed TSH level but a normal free T4 level because some patients have T3 toxicosis
  229. What lab findings are classically associated with Graves disease?
    TSH receptor antibodies TSI and TBII
  230. What is Grave's disease?
    • an autoimmune process characterized by the production of antibodies against the TSH receptor.
    • On TSH receptor binding, these antibodies stimulate autonomous thyroid gland function and lead to excess serum T4 or T3 levels.
    • can present with either subclinical or overt thyrotoxicosis.
  231. What three main treatments are available for Grave's disease?
    • Antithyroidal drugs
    • radioactive iodine (131I)
    • thyroid surgery
  232. When is thyroid surgery indicated in Grave's disease?
    typically reserved for patients with 1concurrent suspicious nodules, 2extremely large goiters, or 3ophthalmopathy in whom radioactive iodine has aggravated their eye condition.
  233. What two antithyroid drugs are available in the US?
    • Propylthiouracil
    • methimazole
  234. In patients taking PTU, what do you watch out for?
    • elevated aminotransferase levels
    • higher rate of serious adverse effects on the liver than methimazole.
    • Rarely, severe hepatic necrosis has been reported, predominantly with propylthiouracil
  235. Between PTU and methimazole, which drug is preferred first?
    a recent advisory suggested that propylthiouracil should not be used as a first-line antithyroidal medication, with the possible exception of the first trimester of pregnancy, during which methimazole has been associated with possible teratogenicity.
  236. What side effect should you watch out for in patients taking methimazole and PTU?
    Both are know to cause agranulocytosis
  237. What is not recommended in patients with Grave's ophthalmopathy?
    Radioactive iodine treatment has been associated with worsening of Graves ophthalmopathy
  238. A thyroid scan reveals a solitary overactive (“hot”) nodule with suppression of the nonautonomous extranodular tissue. What is the diagnosis?
    toxic adenoma
  239. A thyroid scan reveals patchy uptake of radioactive iodine with increased uptake in autonomous regions and reduced uptake outside those areas. What is the diagnosis?
    toxic multinodular goiter
  240. Hirsutism
    How do you evaluate for it?
    Differential dx?
    How do you exclude other causes?
    • Good history is essential.
    • Evaluate onset, rate of progression, presence of virilization, and presence of other symptoms, such as galactorrhea, bruising, or myopathy.
    • Differential dx includes -- PCOS, androgen producing tumors, Cushing syndrome, and occult 21-hydroxylase deficiency, particularly when the hirsutism involves sudden onset and rapid progression
    • PCOS, the most common cause of hirsutism, normally starts during pubertal development, progresses slowly, and does not cause virilization or cushingoid features.
  241. What is the diagnostic criteria for PCOS?
    according to the current Rotterdam criteria, requires two of the three following findings: ovulatory dysfunction, laboratory or clinical evidence of hyperandrogenism, and ultrasonographic evidence of polycystic ovaries.
  242. Discuss the management of hirsutism and PCOS
    • If fertility is not desired, spironolactone plus an oral contraceptive pill containing a progestin with low androgenicity (desogestrel, norgestimate, gestodene, or drospirenone) is a good first-line combination therapy.
    • Metformin decreases the serum testosterone level and improves ovulation rates in women with PCOS, even in those with normal insulin sensitivity
    • Clomiphene is superior to metformin for producing live births with oral therapy alone in women with PCOS who desire children, but infertility treatments such as clomiphene should be prescribed only by a reproductive endocrinologist
  243. How do you treat an invasive macroprolactinoma?
    • Dopamine agonists (cabergoline and bromocriptine) are preferred as the initial treatment of prolactinomas because of their fery high efficacy
    • Dopamine agonists are effective for patients with small and large prolactinomas, and cabergoline is more efficacious and better tolerated than bromocriptine.
    • Cabergoline causes a normalization of prolactin levels in greater than 90% of patients and also a significant reduction in prolactinoma size in nearly 90%. If the large tumor has caused hypopituitarism, a restoration of normal pituitary function may also occur.
  244. How do you diagnose MEN type 1?
    • MEN1 is characterized by tumors of the parathyroid, pituitary, and pancreatic islet cells (the three “P”s)
    • MEN1 is inherited in an autosomal or sporadic manner
    • The most common familial form of hyperparathyroidism is a component of MEN1.
    • Primary hyperparathyroidism is almost always present in this disorder
    • Pancreatic tumors, present in 30% to 80% of patients with MEN1, are islet cell tumors that most commonly secrete gastrin and cause Zollinger-Ellison syndrome
    • The second most common pancreatic tumor is an insulinoma.
    • Pituitary adenomas affect 15% to 50% of patients with MEN1 and are mostly prolactinomas, although tumors causing acromegaly and Cushing disease also occur.
  245. What is MEN2?
    • MEN2 is characterized by medullary carcinoma of the thyroid gland in combination with pheochromocytoma and parathyroid adenomas (MEN2a) or with a pheochromocytoma, ganglioneuromas, and a marfanoid habitus (MEN2b)
    • MEN2 is inherited as an autosomal dominant trait
  246. What is Autoimmune polyglandular syndrome type 1 (APS1)?
    • An inherited autosomal recessive disorder with a 25% incidence among siblings of patients with the disease.
    • Characterized by the triad of chronic mucocutaneous candidiasis, autoimmune hypoparathyroidism, and adrenal insufficiency.
  247. What is Osteosclerotic myeloma?
    • or POEMS syndrome
    • consists of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein (M spike) on serum protein electrophoresis, and Skin abnormalities
    • This syndrome is associated with several endocrinopathies in the setting of lymphoproliferative disorders and presumed B-cell dysfunction.
    • Hypogonadism appears to be the most common endocrine abnormality.
  248. How do you evaluate secondary amenorrhea?
    What is Asherman syndrome?
    What does menstrual flow on progestin withdrawal indicate?
    • If results of the initial laboratory assessment are normal, the cornerstone of the evaluation for secondary amenorrhea rests on the results of a progestin withdrawal challenge (medroxyprogesterone acetate, 10 mg orally for 10 days).
    • Menstrual flow on progestin withdrawal indicates relatively normal estrogen production and a patent outflow tract, which limits diagnostic evaluation to chronic anovulation.
    • Absence of flow indicates estrogen absence and/or an anatomic defect. In patients with no flow, pelvic anatomy is assessed with ultrasonography and/or MRI. The absence of menses for several months after dilation and curettage in this patient suggests severe endometrial damage or formation of scar tissue (Asherman syndrome).
  249. How do you treat hypercalcemia in pts with sarcoidosis or lymphoma?
    What is the cause of the hypercalcemia in granulomatous diseases?
    • This is due to increased 1,25-dihydroxy vitamin D production in patients with granulomatous diseases (sarcoidosis or lymphoma)
    • 1. Can be treated with prednisone for 2 to 5 days.
    • 2. Calcium absorption can be partially blocked by phosphate-containing drugs that form insoluble calcium phosphate complexes and prevent absorption.
    • 3. Reducing calcium intake to 400 mg/d or less is also beneficial.
  250. What level of hypercalcemia should you treat regardless of symptoms?
    Pts with Ca level 14 mg/dL should be treated regardless of symptoms
  251. A pt with "small, firm testes" likely has what diagnosis?
    Klinefilter syndrome
  252. How do you treat papillary thyroid cancer?
    Papillary thyroid cancer and follicular thyroid cancer are treated with total thyroidectomy followed generally by therapy with iodine-131.
  253. What is the appropriate intervention in euthyroid patient with a nodule?
    • fine-needle aspiration biopsy should be performed to establish diagnosis
    • radionuclide scanning should be reserved for patients with indeterminate cytology or thyrotoxicosis
  254. What is a characteristic feature of medullary thyroid carcinoma?
    • production of calcitonin
    • Serum calcitonin levels can be used to monitor disease status.
  255. What is the treatment for a thyroid nodule if cytologic results show malignant or indeterminate cells?
  256. What is secondary hyperparathyroidism?
    Secondary hyperparathyroidism occurs when decreased circulating serum calcium levels stimulate secondarily increased secretion of PTH. This commonly occurs in vitamin D deficiency and chronic kidney disease. Although hypercalcemia does not occur in secondary hyperparathyroidism, patients with chronic kidney disease who have hypercalcemia can develop dysregulation of parathyroid function, which results in a condition known as tertiary hyperparathyroidism.
  257. What is osteitis fibrosa cystica?
    More advanced forms of hyperparathyroid bone disease, such as osteitis fibrosa cystica, also can rarely occur; radiographic manifestations of osteitis fibrosa cystica include periosteal resorption of the digits, irregular demineralization of the skull, and brown tumors of the long bones.
  258. How do you manage a pheochromocytoma preoperatively?
    initiate therapy with an α-blocker, either a long-acting, noncompetitive antagonist, such as phenoxybenzamine, or a short-acting antagonist, such as prazosin, doxazosin, or terazosin. Recent data indicate that many centers use a short-acting α-blocker instead of phenoxybenzamine because the latter can be associated with more prolonged postoperative hypotension. Preoperative preparation with α-adrenergic blockade reduces the incidence of intraoperative hypertensive crisis and postoperative hypotension. The primary goal is to maintain blood pressure in the range of 140 to 150/90 mm Hg. Preoperative medical therapy should be instituted once the diagnosis is reached and before surgical resection.
  259. How do you differentiate low thyroid uptake from thyroiditis vs. exogenous uptake of thyroid hormone?
    A low radioactive iodine uptake in a patient with symptoms of thyrotoxicosis suggests thyroiditis or exogenous thyroid hormone exposure; the erythrocyte sedimentation rate and thyroglobulin level are low in patients taking exogenous thyroid hormone and elevated in those with thyroiditis.
  260. What is Paget disease, and how is uncomplicated Paget disease treated?
    Paget disease is a focal disorder of bone remodeling that leads to greatly accelerated rates of bone turnover, disruption of the normal architecture of bone, and sometimes gross deformities of bone (such as enlargement of the skull and bowing of the femur or tibia). Most patients with Paget disease are asymptomatic. The diagnosis is often suspected from radiographs obtained for other reasons or from an isolated elevation of the serum alkaline phosphatase level. There is no cure for Paget disease, but bisphosphonates (such as alendronate, risedronate, tiludronate, pamidronate, zoledronate, and etidronate) decrease the accelerated rate of osteoclastic bone resorption.
  261. What are the established guidelines for referral for bariatric surgery?
    BMI ≥40 or ≥35 with medical comorbidities such as sleep apnea, obesity-related cardiomyopathy, severe arthritis, hyperlipidemia, diabetes, or glucose intolerance
  262. How do you diagnose lymphocytic hypophysitis in a pregnant woman?
    In lymphocytic hypophysitis, a pituitary mass that mimics an adenoma is typically seen on an MRI. Diffuse enhancement of a symmetrically enlarged pituitary gland on MRI is also characteristic. This disorder, which usually develops intrapartum, is a destructive process thought to have an autoimmune basis. Adrenocorticotropic hormone (ACTH) deficiency occurs in two thirds of patients with such lesions and is a major cause of death in patients with lymphocytic hypophysitis.
  263. How does pituitary apoplexy usually present?
    Pituitary tumor apoplexy, which is usually due to hemorrhage into a prior tumor, has a dramatic presentation, with sudden onset of severe headache, stiff neck, and (often) a decreased level of consciousness.
  264. How do you evaluate unexplained hypertension and unprovoked hypokalemia?
    The evaluation of unexplained hypertension and unprovoked hypokalemia begins with measurement of the plasma renin activity and aldosterone level. A serum aldosterone to plasma renin activity ratio greater than 20 and a serum aldosterone level greater than 15 ng/dL (414 pmol/L) strongly suggest primary hyperaldosteronism. After hyperaldosteronism is confirmed, a search for the anatomic or pathologic cause should begin. CT of the adrenal glands is the appropriate initial step in identifying the anatomic cause of the disease.
  265. What is the expected outcome when aldosterone is secreted excessively?
    • When aldosterone is secreted excessively, the expected outcome is hypertension, hypokalemia, and metabolic alkalosis. For these reasons, patients with hypertension should be screened for primary hyperaldosteronism, especially when the hypertension is difficult to control or associated with hypokalemia.
    • Screening of patients for primary hyperaldosteronism focuses on the physiologic changes (namely, suppressed renin activity) and thus involves the simultaneous measurements of the plasma aldosterone level and plasma renin activity. A ratio of plasma aldosterone (measured in ng/dL) to plasma renin activity (measured in ng/mL/h) of greater than 20 is highly suggestive of primary hyperaldosteronism, especially when the plasma aldosterone level is greater than 15 ng/dL (414 pmol/L). This ratio is particularly helpful in patients taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs), in whom plasma renin activity is expected to be generally high but plasma aldosterone levels are usually low. In a patient receiving an ACE inhibitor or an ARB, one would expect the plasma aldosterone level to be lower than 10 ng/dL (276 pmol/L) and the plasma renin activity to be greater than 3 ng/mL/h (3 µg/L/h) with an aldosterone-to-renin ratio of less than 5. Thus, in a patient receiving an ACE inhibitor or ARB, an aldosterone-to-renin ratio of 10 or more would be highly suggestive of hyperaldosteronism.
    • The screening tests can be performed on random blood samples, even in patients on antihypertensive medications (except the aldosterone receptor antagonists spironolactone and eplerenone). Confirmation of the biochemical diagnosis involves showing persistent elevation (poor suppressibility) of plasma aldosterone in response to a high salt load. Salt can be given orally (sodium chloride, 2 g three times daily for 3 days) or intravenously (with normal saline, 500 mL/h for 3 hours). During either method of salt loading, plasma aldosterone levels are suppressed to less than 5 ng/dL (138 pmol/L) in normal subjects but remain elevated (often greater than 10 ng/dL [276 pmol/L]) in patients with primary hyperaldosteronism.
  266. How do you treat acromegaly?

    Give examples of somatostatin analogues.
    What are they used for?
    • The goal of treatment in patients with acromegaly is to normalize anterior pituitary function and GH secretion, control tumor growth, and treat systemic complications. Transsphenoidal surgical resection is typically the treatment of choice. Medical treatment is often also required because many of these tumors are too large at presentation to be completely excised by surgery. In patients with such tumors, medical therapy is indicated.
    • Examples of somatostatin analogues are octreotide or lanreotide.
  267. What is the diagnostic requirement for PCOS?
    Diagnosis requires two of the three following features: (1) ovulatory dysfunction, (2) laboratory or clinical evidence of hyperandrogenism, and (3) ultrasonographic evidence of polycystic ovaries.
  268. What is the most appropirate therapy in pts with hirsutism and poycystic ovavy snyndrome who does not wish to become pregnant?
    In patients with hirsutism and polycystic ovary syndrome who do not wish to become pregnant, the most appropriate initial therapy is spironolactone and an oral contraceptive pill.
  269. What treatments options are available for women with PCOS who desire to have children?
    • Metformin decreases the serum testosterone level and improves ovulation rates in women with PCOS, even in those with normal insulin sensitivity. Although metformin is effective and does not appear to be teratogenic, patients should be counseled that the treatment of PCOS with metformin is an off-label indication and that ovulation and pregnancy may occur. Given the favorable effect of metformin on lipid profiles and progression to diabetes in selected populations, chronic metformin therapy offers many advantages and should be considered, either alone or in combination with other agents, a first-line therapy when metabolic abnormalities are significant.
    • Clomiphene is superior to metformin for producing live births with oral therapy alone in women with PCOS who desire children
  270. What is Benign familial hypocalciuric hypercalcemia?
    a rare familial condition caused by inactivating mutations of the calcium-sensing receptor, which has a major function in regulating calcium metabolism through parathyroid tissue and renal calcium. The disorder is autosomal dominant with high penetrance. There is decreased sensitivity of the calcium-sensing receptor to calcium; therefore, higher calcium levels are required to suppress PTH secretion. Heterozygous patients generally have hypercalcemia, hypocalciuria, and mild hypermagnesemia at presentation. Fractional excretion of calcium is less than 1% despite the hypercalcemia, and the PTH level is normal or slightly elevated.
  271. To evaluate if granulomatous disease (sarcoidosis or tuberculosis) is the cause of hypercalcemia on a pt, what lab work would you order?
    increased 1,25-dihydroxy vitamin D production
  272. How do you evaluate suspected hypogonadism in men?
    • Measurement of total testosterone, preferably from two blood samples collected in the early morning, is the initial diagnostic test for suspected hypogonadism. Although normal ranges are somewhat assay-dependent, values consistently less than 200 ng/dL (6.9 nmol/L) are considered low, and values consistently greater than 350 ng/dL (12.1 nmol/L) are considered normal. In patients with values that are between 200 and 350 ng/dL (6.9 and 12.1nmol/L) or that are inconsistent with the clinical situation, the free and/or bioavailable testosterone should be measured.
    • Serum testosterone on two separate mornings before 1000 is ideal. Value less than 200 mg/dl confirms hypogonadism, and > 350 mg/dl rules it out. Values between 200-350 is equivocal.
    • If equivocal, send free testosterone level, FSH, LH, PRL. If high or normal FSH, normal LH and prolactin, give Testosterone supplementation. However, if FSH and LH are low, and Prolactin high, the problem is in the pituitary and order MRI of pituitary and pituitary function testing.
  273. What is cerebral salt wasting syndrome?
    Cerebral salt wasting, a syndrome characterized by hypovolemia and hyponatremia, usually occurs within 10 days of a neurosurgical procedure or disease, particularly subarachnoid hemorrhage.
Card Set
hormones and diseases