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Endocrinology Review

Endocrinology Review. A Smattering. 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 50’s. On physical Exam, Bp 130/75, P 72, BMI 28. Which should be done next to establish the dx of DM?

phyllis-warren
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Endocrinology Review

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  1. Endocrinology Review A Smattering.

  2. 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 50’s. 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

  3. Textbook Answer - B. Repeat Fasting Glucose • ADA criteria for DM are: • Fasting plasma Glucose >126 • 2hr plasma glucose >200 after 75g oral load • Random gluose >200 plus symptoms of DM. *** Now HgbA1c >6.5% is accepted

  4. 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, Cushing’s syndrome, and primary aldostertonism.

  5. 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! • Cushing’s: Overnight dexamethasone • Pheo: Fractionated plasma metanephrines • Hypertensive pts: plasma aldo/renin activity

  6. Non-functioning Lesions <4 cm in diameter do not require surgical intervention but should be re-imaged in 3-6months • Lesions >4 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.

  7. 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

  8. 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.

  9. 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

  10. 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 <140/90. • 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. B. 24hr Urine Cortisol • Patients w/ Cushing’s 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 Cushing’s syndrome relies on demonstartion of excess cortisol production.

  19. 24hr urine cortisol is often the first test in pts with strong suspicion for Cushing’s. (CRI should be known prior) • Overnight Dex w/ 1mg (8mg used to differentiate b/t ACTH-dependent forms of Cushing’s) 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 Cushing’s • 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)

  20. 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

  21. A. 8mg Dex suppresion test • Causes of ACTH dependent Cushing’s 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.

  22. 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

  23. A. Inferior Petrosal Sampling • Inferior Petrosal Sampling is the confirmatory test for Cushing’s 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 Cushing’s 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.

  24. 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

  25. 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 <0.01 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.

  26. 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

  27. 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 >1 mg/d above upper limit of normal • 24-Hour urine calcium excretion > 400 mg • Creatinine clearance reduced by ≥ 30% • Bone mineral density: T-score <−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)

  28. 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

  29. B. DEXA now • Risk factors – age >65, 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 >65 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.

  30. 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 <1.005. 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 < 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

  31. 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 DI…in 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 >5 in nephrogenic DI. ADH levels only help confirm the dx, as it was made

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