Board Pearls in Endocrinology Part 1

1. Board Pearlsin EndocrinologyPart 1 Rey Vivo, MD Assistant Professor of Medicine Texas Tech University Health Sciences Center

2. Discuss frequently tested Endocrine cases in the IM Boards Pituitary Cushing’s, Adrenal Incidentaloma Amenorrhea, Hirsutism, Anorexia vs. Bulimia Parathyroid, Calcium homeostasis, Bone disorders Hemochromatosis, Wilson’s disease Diabetes insipidus Examine practice questions from MKSAP 14 and other sources Objectives

3. Pituitary

4. Pituitary tumors Acromegaly Cushing’s disease

5. PEARLS: S/Sx: galactorrhea, infertility, amenorrhea Prolactin >200 ug/L Check TSH: need to R/O hypothyroid always Drugs: Reglan, H-blockers, estrogens Treatment indicated only if fertility desired or very symptomatic Medical tx: bromocriptine or cabergoline Surgical tx: if drug-resistant or intolerant Prolactinoma

6. A post-menopausal 57F presents to the clinic with galactorrhea. She denies taking any medications. Prolactin level is normal. What is the most appropriate next step in evaluating this patient? A. Cranial MRI B. Measure TSH C. Start cabergoline D. Recheck prolactin in 1 year E. Refer to surgery Board Q

7. A 42F presents with galactorrhea. She has no significant medical history and is not taking any medications. She qualified that her symptom occurs on manipulation of nipples only. Her TSH and prolactin levels are WNL. Pregnancy test is negative. MRI of the brain is unremarkable. Next best step? A. Remeasure prolactin in 6 months B. Start bromocriptine C. Refer for radiation therapy D. Avoid manipulation of nipples Board Q

8. A 38M is evaluated for fatigue, decreased libido, and worsening headaches of 2 years. PE bitemporal hemianopsia. The testes are <10 mL and soft. Labs: testosterone level of 165 ng/dL (low), LH level of 0.5 mU/mL (low) and a prolactin level of 2520 ng/mL (high). Levels of IGF-1, TSH, free thyroxine, and cortisol are normal. MRI of the head shows a 2.7-cm pituitary mass arising from the sella and elevating the optic chiasm. What is the most appropriate management? A. Remeasure prolactin level in 3 months B. Start testosterone therapy C. Start dopamine agonist therapy D. Refer for transsphenoidal surgery E. Refer for radiation therapy MKSAP Q #52

9. PEARLS: S/Sx: bitemporal hemianopsia, macroglossia, acanthosis nigricans (IR), increased sweating, heat intolerance Screen: age- and gender-matched IGF-1 levels (increased) Confirm: OGTT – GH not suppressed to <2 ug/L after 2 hours; then MRI Tx: TSS, then irradiation Acromegaly

10. Acromegaly

11. A 58F has a remote history of a pituitary macroadenoma treated with surgery and radiation. Recently, she noted fatigue and weight gain of 7 kg, particularly in the abdomen, and daily headaches. She is 8 years postmenopausal. Meds: MV, a calcium supplement and acetaminophen for headaches. She also has cold intolerance, constipation and nausea. On PE, BP is 124/80, pulse 90/min. She is pale and has mild periorbital edema, dry skin, and thin, brittle hair. DTRs are mildly delayed. Labs: hematocrit 32%, electrolytes WNL, morning cortisol low normal, estradiol undetectable, FSH normal, LH normal, prolactin 8 ng/mL, TSH 0.2 µU/mL, free T4 0.5 ng/dL, GH undetectable, IGF-1 low. Pituitary MRI shows postoperative changes but no clear evidence for residual tumor. Which of the following is the most likely cause of these findings? A. Primary hypothyroidism and menopause B. Central adrenal insufficiency C. Growth hormone deficiency D. Panhypopituitarism E. Pituitary apoplexy MKSAP Q #6

12. Cushing’s syndrome

13. Cushing’s syndrome

14. PEARLS S/Sx: buffalo hump, purple striae, proximal weakness, hyperglycemia, hypertension, hypokalemia, osteoporosis, hirsutism* Screen: 24 hr. urine free cortisol (>50ug/day), overnight dexamethasone suppression test (plasma cortisol > 5 ug/dL) Dexa 1 mg at 2300, check cortisol at 0800 the next morning Cushing’s

15. A 38F is evaluated for a 13.2-lb weight gain over 2 years. She was recently found to have a fasting blood glucose of 130 mg/dL and 136 mg/dL on two separate visits. She is taking no medications other than a multivitamin and has taken no prescribed medications in the past 5 years. On physical examination, the patient's BMI is 32 and blood pressure 160/94 mm Hg. The patient has scant terminal hairs over her chin, mild acne over her face, and violaceous striae, bilaterally over her lateral abdomen. Her face is full, abdomen prominent, and her arms and legs seem disproportionately thin. Which of the following is the most appropriate next step? A. Serum cortisol, 1600 hrs B. 24-hour urine collection for cortisol C. Serum cortisol, 0800 hrs, following dexamethasone 8 mg the prior evening D. Serum ACTH, 0800 hrs E. MRI of the head MKSAP Q #5

16. 35F with obesity, purple abdominal striae and hyperglycemia is evaluated for possible cortisol excess. She receives a 1 mg of dexamethasone at midnight and plasma cortisol level drawn at 8AM is 15 ug/dL (N <5 ug/dL). What is the next most appropriate test? A. CT of the brain B. CT of the abdomen C. 2-day low dose dexamethasone suppression D. 2-day high dose dexamethasone suppression BoardQ

17. PEARL: Definitive diagnosis: 2-day low-dose dexamethasone suppression test Give dexa 0.5 mg Q6, check plasma cortisol on 2nd day (+) test: failure of plasma cortisol to fall to <5 ug/dL Cushing’s

18. Adrenal Incidentaloma

19. Pheochromocytoma S/Sx: episodic HA, sweating, palpitations, HTN, postural hypotension Dx: urine/plasma metanephrines Localize: CT or MRI; MIBG scan for extra-adrenal lesions Pre-op Tx: Phenoxybenzamine Conn’s syndrome S/Sx: diastolic HTN, hypokalemia, polyuria, polydipsia Dx: plasma renin low, aldosterone high Tx: Spironolactone, surgery Incidentaloma

20. PEARLS: 1st step: hormonal assessment (urine free cortisol, urine/plasma metanephrines, paired plasma renin and aldosterone) CT features of carcinoma: >3 cm. in size Irregular border, heterogenous consistency Attenuation value >10 Housfield units Follow up: Repeat CT 3-6 months Surgical Tx: If functional or >6cm or enlarging on serial CT Adrenal Incidentaloma

21. Abdominal CT scan of an otherwise healthy 51M displays an incidental 3 cm left adrenal mass. He is referred to your outpatient clinic for further evaluation. He reports family history of “abdominal tumor”. BP is 140/100. What is the next step? A. Repeat CT in 6 months B. Refer for surgical excision C. Refer to Endocrinologist D. Check serum catecholamines, renin, aldosterone and urine cortisol E. Start HCTZ and follow up in 1 year Board Q

22. A 56M is evaluated for anorexia and a 5-kg unintentional weight loss. He has vague abdominal discomfort and occasional flank pain. He does not have polyuria, polydipsia or increased pigmentation. On PE, BMI is 27 and BP is 108/72. Aside from mild tenderness to deep palpation over the left upper abdominal quadrant, the examination is unremarkable. CT abdomen shows a 6-cm left adrenal mass. Attenuation value of the mass is 32 Hounsfield units. The margins of the lesion are irregular and the consistency is heterogeneous. Xray of the lungs and kidneys were unremarkable. Plasma fractionated metanephrines are normal. Plasma aldosterone/plasma renin activity (ARR) is 6 (normal <12). Serum cortisol at 0800 hrs after dexamethasone 1 mg the preceding evening is 1.4 µg/dL. Next best step? A. Selective adrenal venous sampling B. Repeat biochemical evaluation and CT in 6 months C. Iodocholesterol imaging of the adrenals D. Referral for surgical resection of mass MKSAP Q #39

23. A 36M is evaluated in the ED for headache and palpitations. He is anxious, tremulous, and diaphoretic. The blood pressure is 198/106 mm Hg, and the pulse rate is 110/min. He has been hypertensive for the past 2 years, but has been suboptimally controlled with a combination of hydrochlorothiazide, diltiazem, and lisinopril. He frequently experiences episodic headache and diaphoresis, during which his blood pressure is alarmingly high. These episodes had been attributed to migraine headaches, but addition of propranolol for prophylaxis worsened their frequency and severity. What 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 MKSAP Q #80

24. A 43M has persistent hypertension. At 29, he was found to have BP of 160/100 and was initially treated with a β-blocker. Since then, his BP has remained high despite weight loss, compliance with therapy, and abstinence from alcohol. His current meds consist of maximal doses of HCTZ, atenolol, lisinopril, and amlodipine. On PE, his BMI is 26 and BP is 156/98. He has no striae, normal facies and no abdominal bruits. The fasting glucose is 98 mg/dL, potassium is 3.3 meq/L, and creatinine is 1.3 mg/dL. What are the most appropriate tests? A. Serum insulin-like growth factor 1 B. 24-hour urine for free cortisol C. Plasma fractionated metanephrines D. Plasma aldosterone/plasma renin activity ratio E. Magnetic resonance angiography of the renal arteries MKSAP Q #91

25. Amenorrhea

26. Amenorrhea

27. 5 Most common “P”s: 1. Pregnancy 2. Prolactinoma 3. Premature menopause 4. PCO syndrome 5. Pituitary failure Excessive stress/exercise Amenorrhea Check FSH Progesterone challenge

28. PEARLS: aka Stein Leventhal syndrome Major associations: insulin resistance, virilization, acanthosis nigricans Excess fat…high estrogen (aromatization of excess androgen)…low FSH and high LH (positive feedback)…LH/FSH ratio >2…bleeding after progesterone because estrogen is present Tx: weight reduction, OCP, clomiphene (increases FSH secretion) PCO syndrome

29. 22F is training for the marathon and is running 50 miles/week. She has also recently started a post-graduate course. She consults for amenorrhea in the last 10 months and is becoming concerned. BMI is 18. Pregnancy test is negative. Prolactin level is normal. LH and FSH are equally low. What is the most appropriate next step in management? A. Psychiatry consult B. MRI of the brain C. No further tests. Advise to cut down on exercise program. D. No further tests. Return in 1 year; if symptoms persist, refer to gynecology. Board Q

30. 38F is evaluated for amenorrhea. She reports cessation of menses since 6 months ago. She denies any excessive stress or exercise. She denies any medications. Pregnancy test in negative. Prolactin and TSH levels are normal. Serum LH and FSH are both elevated and serum estradiol is low. What is the most likely diagnosis? A. Panhypopituitarism B. PCO syndrome C. Hypogonadotropic hypogonadism D. Premature menopause Board Q

31. Amenorrhea • PEARL: FSH level

32. A 26F is evaluated for amenorrhea. Her last menstrual period was 3 months ago, and three home pregnancy tests have been negative. She states that she has no other symptoms and takes no medications. Menarche occurred at age 12 years, and her menstrual cycle has been regular until 3 months ago. Upon further questioning, she recounts weekly headaches and occasional galactorrhea on breast palpation. PE is normal. Deep tendon reflexes are normal. Serum prolactin level is 1665 ng/mL. What is the most likely cause of her hyperprolactinemia? A. Pregnancy B. Cirrhosis C. Primary hypothyroidism D. Prolactin-producing pituitary tumor MKSAP Question 57

33. Hirsutism

34. Hirsutism • PEARLS: • Drugs: phenytoin, anabolic steroids, minoxidil, cyclosporine • 4 tests to consider:

35. 19F presents to the outpatient clinic for hirsutism. In the last year, she has observed noticeable hair growth involving her upper lip and sideburns. She is not on any medications. She has normal periods are regular intervals and has no signs of virilization. BMI is 20. All endocrine work-up is within normal limits. She mentions that her aunt had similar facial hair pattern. What is the next best step? A. Cosmetic measures, i.e. bleaching/removal of hair B. Empiric trial of OCP C. 24 hour urine free cortisol D. CT abdomen to look for any masses Board Q

36. A 68F is evaluated for facial hair, voice deepening, and increased muscle mass over the past 6 months. She has not changed medications recently. She also notes that she is more aggressive and irritable recently. PE reveals a full beard and terminal hairs on the chest and abdomen. The clitoris is 3 cm long, 2 cm across, and firm. Laboratory results include a serum total testosterone of 350 ng/dL (high). What is the best next step? A. Measure serum prolactin, DHEA-sulfate, and 17- hydroxyprogesterone B. Start spironolactone therapy C. Measure serum free and bioavailable testosterone D. Perform 4-day dexamethasone suppression test for cortisol and DHEA-sulfate E. CT scan of abdomen and pelvis MKSAP Q #18

37. 24F is very concerned about excessive facial hair growth. On examination, she looks very thin and she admits having lost 35 lbs in “a short period of time”. She has also experienced absence of menses and severely dry skin. Pulse rate is 48/min. Serum potassium is very low. Which of the following findings is most likely part of this disease? A. Antisocial behavior B. Binge eating C. Hypothermia D. Dental caries Board Q

38. Anorexia vs Bulimia

40. 21F is brought to the office by her mother to the office for facial swelling. She admits to episodes of recurrent vomiting. BMI is normal. She is afebrile. She has dental caries and bilateral parotid gland enlargement. There are excoriations on her knuckles. Blood work reveals hypokalemic alkalosis. What is the most likely diagnosis? A. Anorexia nervosa B. Bulimia C. Parotitis D. Sjogren’s syndrome Board Q

41. Thank you Part 2 27 May 2008