Endocrinology Review

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Endocrinology Review

• A Smattering.

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• 55F w/ FASTING blood glucose of 130 at her state
  fair. She has no symptoms of polyuria or
  polydipsia. Her mother and sister have developed
  T2DM in their 50s. On physical Exam, Bp 130/75,
  P 72, BMI 28.
• Which should be done next to establish the dx of
  DM?
• Measure HgbA1c
• Repeat fasting plasma glucose measurement
• Perform 100g glucose tolerance test
• Measure 2-hr postprandial blood glucose level
• Measure fasting plasma insulin level

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Textbook Answer - B. Repeat Fasting Glucose

• ADA criteria for DM are
• Fasting plasma Glucose gt126
• 2hr plasma glucose gt200 after 75g oral load
• Random gluose gt200 plus symptoms of DM.
• Now HgbA1c gt6.5 is accepted

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• A 26F is seen in the ED for episodes of lower
  abdominal/pelvic discomfort. BP is 160/90 during
  this episode, and was normal prior. BMI 26, no
  hirsutism, striae, or central adiposity. CBC,
  Glucose, Electrolytes normal. CT scan of the
  abdomen reveals 1.8cm irregularity in the right
  adrenal gland. She feels better and is released.
• Which of the following is the most appropriate
  follow-up?
• A. MRI of the abdomen
• B. Observation only
• C. Repeat CT scan in 1 to 3 months
• D. Screen for pheochromocytoma, Cushings
  syndrome, and primary aldostertonism.

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D. Screen!!

• Incidentalomas discovered in up to 6.9 of
  abdominal/pelvic imaging studies
• Most hormonally silent, recent study of 2000
  masses revealed 82 were nonfunctional
• Most Endocrinologist recommend Screen!
• Cushings Overnight dexamethasone
• Pheo Fractionated plasma metanephrines
• Hypertensive pts plasma aldo/renin activity

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• Non-functioning Lesions lt4 cm in diameter do not
  require surgical intervention but should be
  re-imaged in 3-6months
• Lesions gt4 cm in diameter OR any size lesions
  that are hormonally active should be referred for
  resection.
• CT vs. MRI? Go with CT. MRI more costly and of
  little extra benefit.

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• 36M is seen in the ED for HA and palpitations.
  He is anxious, tremulous, and diaphoretic. Bp
  198/106 and pulse 110. Hypertensive x2 years and
  suboptimally controlled on a 4 drug regimen. He
  frequently experiences similar episodic HA and
  diaphoresis, during which his BP is alarmingly
  high. He was prescribed propranolol for migraine
  headaches which increased their frequency and
  severity.
• Which of the following tests is the most
  appropriate next step?
• A. Serum Catecholamines
• B. Serum potassium
• C. Insulin-like growth factor 1
• D. Fractionated plasma metanephrines
• E. 24-hour urine collection for cortisol

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D. Fractionated Plasma Metanephrines

• The classic triad of HA, Palpitations, and
  Diaphoresis is suggestive Pheochromocytoma.
• The sensitivity of fractionated plasma
  metanephrines for catecholamine-producing tumors
  is nearly 97, Specificity (false positives) 85.
• Acetaminophen is the only drug that interferes
  with the test and should be withdrawn for 48hrs.
• Can confirm plasma metanephrines test with 24hr
  urine metanephrines 94 specificity.

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• 38F w/ 3cm heterogeneous mass in the right
  adrenal gland is found to have plasma
  fractionated metanephrines 2x the upper limit of
  normal. 24hr urine collection of metanephrines
  contains 2.5x the normal daily excretion.
  Pheochromocytoma is suspected and laparoscopic
  adrenalectomy is planned w/n 14-21 days. Her
  blood pressure is 206/110 and her pulse is 104.
  She is taking no other meds.
• Which of the following is indicated prior to
  surgery?
• Carvediolol therapy
• Blood transfusions
• Fine-needles aspiration of the mass
• Phenoxybenzamine therapy

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D. Phenoxybenzamine (alpha-antagonist)

• Surgical resection is the only cure for a PHEO.
• Perioperative mortality 4, blood pressure
  control should be started w/n 2wks prior to
  nonemergent surgery using alpha-adrenergic
  antagonists. Goal is lt140/90.
• Alpha-antagonists can minimize hypertensive
  crisis during intubation, induction, and tumor
  manipulation, but its half life of 24hrs can
  contribute to post-op hypotension.
• Beta-blockers should never be administered prior
  to alpha blockade as it permits unopposed alpha
  activity causing HTN crisis.
• Fine-needles aspiration may precipitate a
  hypertensive crisis, and the procedure is never
  preformed if PHEO is suspected.

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• 33M seen for a mass in the right side of his
  neck. He has no neck pain, hoarseness, or
  dysphagia. No hx of radiation exposure. No
  family hx of thyroid tumors or disorders. On
  physical Exam he has a 2.5cm right thyroid nodule
  that is moderately mobile and nontender. No
  palpable cervical lymph nodes.
• Which serum test is the most important to order?
• TSH
• Thyroglobulin
• Antithyroid Peroxidase and Antithyroglobulin
  Antibodies
• Total T3
• Calcitonin

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A. TSH

• The first step in the eval of a thyroid nodule is
  measurement of serum TSH.
• If TSH is normal the nodule is most likely
  nonfunctioning or COLD. In this case FNA would
  be indicated to r/o malignancy.
• If TSH is low the nodule is more likely
  hyperfunctioning or HOT. A HOT nodule has low
  likelihood of being malignant so an FNA would not
  be necessary in most patients. But a thyroid
  scan would be indicated to confirm the presence
  of a HOT nodule and see if others are present.
• Measurement of serum thyroglobulin is useful for
  following thyroid cancers in response to
  treatment, but not useful to distinguish benign
  from malignant nodules.

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• 45F seen for a sensation of fullness in her neck
  and occasional difficulty swallowing. She feels
  well otherwise. No hx of head/neck radiation.
  Her mother developed a goiter at age 40.
• On physical exam the thyroid gland is 2x normal
  size and there is a dominant 2-cm nodule in the
  left lobe. No cervical lymph nodes are palpable.
  TSH is 1.8. Thyroid U/S reveals multiple small
  nodules in both lobes and a 2.2cm dominant nodule
  in the left lobe.
• Which of the following is the next best step?
• Thyroid Scan
• FNA of dominant nodule
• Serum thyroglobulin test
• Serum antithyroid peroxidase and
  antithyroglobulin antibodies
• Serial ultrasound measurements

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B. Fine Needle Aspiration

• A dominant nodule in multinodular goiter has the
  same risk of malignancy as a solitary one.
• TSH should always be measured
• Ultrasound is recommended to define the
  characteristics of the dominant nodule and other
  nodules.
• The next step would be FNA, if it is benign then
  serial monitoring to assess size stability would
  be reasonable.

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• 69M admitted to MICU w/ hypotension, urosepsis,
  and CHF. No hx of thyroid dysfunction. Pulse
  64, no proptosis, no goiter. DTR slightly
  diminished. T4 4.7(ug/dl), Free T4 0.8 (ng/dl)
  (boderline low), Total T3 5.21(ng/dl) -- LOW, and
  TSH 6.1. Antithyroid peroxidase and
  antithyroglobulin abs are negative.
• Levothyroxine 1.6ug/kg PO
• Levothyroxine 0.05ug/kg IV
• No thyroid hormone therapy
• Liothyronine (T3) 12.5ug PO BID

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C. No thyroid hormone replacement

• Euthyroid Sick Syndrome ? precipitous drop in
  serum total free T3 levels and a concomitant
  increase in reverse T3 (rT3).
• TSH may be low, normal, or high.
• Can occur in a host of non-thyroidal illness
  (sepsis, major surgery).
• Change in thyroid hormone level during acute
  illness are believed to be adaptive, protecting
  the body from catabolic illness.
• Thyroid hormone replacement therapy in patients
  with euthyroid sick syndrome has not been shown
  to be beneficial.

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• 38F w/ 6kg wgt gain over the last 2 years. She
  has fasting blood glucose of 130 and 136 on 2
  separate visits. She is not taking any other
  medications. On physical exam her BMI is 32 and
  Bp is 160/94. She has scant terminal hairs over
  her chin, mild acne over her face, and violaceous
  striae approximately 1cm wide bilaterally over
  her lateral abdomen. Her face is full, abdomen
  prominent, and her arms an legs seem
  disproportionately thin.
• Which of the following is the best next step?
• Serum cortisol 1600
• 24hr urine collection for cortisol
• Serum cortisol 0800 following dex 8mg the prior
  evening
• Serum ACTH 0800
• MRI of the HEAD.

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B. 24hr Urine Cortisol

• Patients w/ Cushings produce 3-4x the amount of
  urine free cortisol than normal
• The three screening tests for Cushing's syndrome
  are measurement of urine free cortisol, overnight
  dex suppression test, and the late-evening
  salivary cortisol test.
• Initial testing for Cushings syndrome relies on
  demonstartion of excess cortisol production.

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• 24hr urine cortisol is often the first test in
  pts with strong suspicion for Cushings. (CRI
  should be known prior)
• Overnight Dex w/ 1mg (8mg used to differentiate
  b/t ACTH-dependent forms of Cushings) at 2300 is
  adequate to suppress ACTH by the normal central
  axis, but not corticotropin-producing pituitary
  adenomas or cortisol producing adrenal adenomas.
  0800 cortisol will be suppressed in normal
  patients, but not Cushings
• Saliva contains cortisol that is unbound, if
  collected at 2300 during the normal phsyciologic
  nadir of production, it may indicate autonomous
  cortisol production. This screening is not widely
  available, but gaining experience with this assay
  is growing.
• 1600 cortisol levels are not sensitive or
  specific for diagnosis.
• 0800 ACTH is useful if ectopic source of ACTH is
  present
• MRI not performed unless excess hormonal excess
  performed (high incidence of incidentalomas in
  pituitary will confound diagnosis)

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• 38F evaluated for ELEVATED salivary cortisol
  concentration collected at 2300hrs on two
  separate occasions. The patient has poorly
  controlled diabetes mellitus and signs of
  cortisol excess. Serum ACTH is 29 (normal).
• Which is the next best test?
• Dex 8mg suppression test
• MRI of the head
• Somatostatin receptor scintigraphy
• Inferior petrosal sinus sampling

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A. 8mg Dex suppresion test

• Causes of ACTH dependent Cushings can be
  distinguished by the dex 8mg (high dose)
  suppression test and Corticotropin-releasing
  hormone stimulation test (CRH).
• Patient has evidence of excess cortisol
  production based on 2300hrs salivary cortisol
  test. Cortisol is cyclically produced w/ nadir
  of ACTH and cortisol near midnight.
• Her ACTH is in the normal range which may
  represent the source of ACH may be a corticotrope
  adenoma or ectopic production by a tumor.
• If the source of ACTH is a corticotrope then 8mg
  of dex will suppress ACTH and cortisol production
  by at least 68. If the source is ectopic then
  the source is negliable.
• CRH stimulation test increases ACTH by 35-50
  over baseline in corticotrope adenomas. Cortisol
  concentrations rise by 20-50. Nonpituitary
  tumors producing ectopic ACTH do not respond.

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• 40F w/ new HTN and T2DM is noted to have central
  adiposity and wide violaceous striae over her
  flanks. Two 24h urine collections for free
  cortisol contain 4x the normal amount. Serum
  ACTH is in the mid-normal range. Dex 8mg
  suppression test is given and cortisol is only
  supprsed by 30. CRH stimulation causes a rise
  in ACTH by 70 and a rise in cortisol by 60.
  MRI reveals no pituitary abnormalities.
• Which test will differentiate the source of ACTH?
• Inferior petrosal sinus sampling
• Somatostatin receptor scintigraphy
• Selective adrenal venous sampling
• PET

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A. Inferior Petrosal Sampling

• Inferior Petrosal Sampling is the confirmatory
  test for Cushings syndrome in patients with
  ambiguous results in screening tests. This is
  very sensitive and specific, but costly,
  difficult, and somewhat hazardous.
• A pt w/ suspected Cushings dz, confirmed
  biochemically (dex suppression, CRH), and who has
  pituitary adenoma on MRI, may be taken directly
  for resection.
• When CRH and Dex 8mg suppression are equivocal or
  conflicting, petrosal sampling is required.
• If both tests did indicate a pituitary source,
  but no abnormality noted on MRI (up to 40 of
  cases) then inferior petrosal sinus sampling is
  again suggested.

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• 28F seen for serum calcium level of 11.0 obtained
  during routine physical exam. All other labs are
  normal. PTH level was 40pg/ml (normal). Pt is
  healthy, no polyuria, constipation, or fatigue.
  Her mother and grandfather have a history of
  hyperparathyroidism and both underwent
  parathyroidectomy but remained mildly
  hypercalcemic. The patient had a recent renal
  u/s that showed no evidence of stones. Her diet
  is rich in dairy products and no hx of GI
  illness.
• Which of the following tests is likely to confirm
  dx?
• 25-hydroxyvitamin D
• 1,25-dihydroxyvitamin D
• Urine Calcium/creatinine clearance ratio
• Parathyroid hormone related peptide
• Prolactin

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C. Urine Calcium/Creatinine

• In an asymptomatic patient w/ mild hypercalcemia
  and an inappropriately normal PTH (represents a
  parathyroid-dependent cause), the differential
  includes primary hyperparathyroidism vs. benign
  familial hypocalciuric hypercalcemia.
• Familial hypocalciuric hypercalcemia is diagnosed
  by urinary calcium/creatinine clearance ratio
  lt0.01 measured in a fasting morning urine spot
  collection.
• BFH is characterized by lifelong mild
  asymptomatic hypercalcemia. Autosomal Dominant
  mutation of the calcium-sensing receptor. These
  people DO NOT REQUIRE SURGERY, so it is important
  to differentiate.

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• A 51-year-old man is undergoing a routine
  physical examination. He has no significant
  personal or family medical history. He still
  exercises regularly, running 2 to 3 miles at
  least three times a week. He does not smoke,
  drink alcohol, or use recreational drugs.
  Physical examination is normal. Laboratory tests
  are normal other than a calcium level of 11.0
  mg/dL (2.74 mmol/L). A subsequent serum
  parathyroid level is 120 pg/mL (120 ng/L). A
  24-hour urine calcium excretion is 250 mg (6.3
  mmol). The creatinine clearance is normal. A DEXA
  scan shows a T score of 0.99 at the left femoral
  neck, 0.68 at the lumbar spine, and -2.5 at the
  distal third of the forearm.
• Which of the following is the most appropriate
  management for this patient?
• Calcium and vit D supplementation
• Alendronate
• Parathyroidectomy
• Nasal calcitonin
• Ibandronate

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• Primary hyperparathyroidism is the most common
  cause of hypercalcemia in the outpatient setting
• Single parathyroid adenoma is the cause in 85 of
  cases
• Double adenoma or multi-gland hyperplasia in 15
  of cases. Usually associated with MEN type 1 or
  MEN type 2 syndromes
• 2002 National Institutes of Health consensus
  conference guidelines for the management of
  asymptomatic primary hyperparathyroidism
• Indications for surgery
• Serum calcium level gt1 mg/d above upper limit of
  normal
• 24-Hour urine calcium excretion gt 400 mg
• Creatinine clearance reduced by 30
• Bone mineral density T-score lt-2.5 at any site
• Age younger than 50 years
• Recommended follow-up measurements for patients
  not undergoing surgery
• Biannual serum calcium
• Annual serum creatinine
• Annual bone mineral density (lumbar spine,
  proximal femur, distal forearm)

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• 55F is concerned about osteoporosis. Her mother
  had a hip fracture at 65. The patient is healthy
  and exercises 3x/wk for 45 minutes at the gym.
  She eats a balanced diet and attempts to consume
  two servings of mild or yogurt a day. She
  attained menopause at 50. She does not drink or
  smoke. She has a hx of HTN which is treated with
  ramipril. PE reveals BMI of 26, Bp 120/70. All
  labs are normal.
• Which of the following is the most appropriate
  evaluation for the patient?
• DEXA scan at 65
• DEXA now
• Radiographs of the hip and lumbosacral spine
• Serum osteocalcin
• Urine pyridinoline and deoxypyridinoline
  cross-links of bone

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B. DEXA now

• Risk factors age gt65, female, white, Asian, fx
  of osteoporosis, small body size or weight,
  premature or surgical menopause, inadequate
  calcium intake, smoking, excessive etoh
  consumption, excessive physical activity causing
  amenorrhea, corticosteroids, anticonvulsants,
  hormonal, lifestyle, nutrition, medications, and
  medical conditions.
• Indications for measurement of bone mass include
  women gt65 years of age who have at least one risk
  factor for osteoporosis other than menopause,
  post menopausal women who present with fractures,
  women receiving hormonal replacement, and women
  who are on steroids for more than 3 months.
• Since this patient is post-menopausal and has a
  family hx of osteoporosis, the DEXA scan should
  be done now.

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• 34F seen for polyuria and polydipsia. Hx of
  depression, BMI 28, no Fhx of DM. No meds.
  Fasting PBG 100, no glucose in urine. Her urine
  spec gravity is lt1.005. Her measured 24hr urine
  output is 7-8L! Serum Na is 140, and other lytes
  are normal. A water deprivation test raises the
  sodium to 148 and the urine osm remains lt 300 and
  the plasma osm increases to 300. Despite no oral
  intake her UOP remains 275ml/hr. At this time
  blood is collected to measure ADH and 1ug of
  vasopressin is administered subcutaneously. One
  hour later her urine osm increases to 600 and the
  UOP is less than 100ml/hr.
• What is the most likely dx?
• Normal, no pathology
• Nephrogenic DI
• Central DI
• Primary Polydipsia

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C. Central DI

• In the H20 deprivation test, impaired ability to
  concentrate urine is consistent with either
  nephrogenic or central DI.
• In the H20 deprivation test, a large increase in
  Uosm after the administration of desmopressin is
  indicative of central DI, no such increase occurs
  in nephrogenic DI (resistance to ADH).
• Primary Polydipsia patients can usually partially
  concentrate their urine in response to H20
  Deprivation, but can be difficult to distinguish
  from partial-central DIin these cases ADH level
  may be helpful.
• After h20 deprivation, ADH lvls are undetectable
  in complete central DI, very low in partial
  central DI, and variable in primary polydipsia,
  and usually gt5 in nephrogenic DI. ADH levels
  only help confirm the dx, as it was made