12/22/2011

October 3, 2011

patient presents with the gradual onset of:

Weakness Nausea/Vomiting Sporadic abdominal pain Fevers BP and tanned skin Serum Na+, K+, and glucose ( eosinophilia) 60 minutes after cosyntropin, serum cortisol = 7 g/dL
Diagnosis:
Adrenal Insufficiency (Primary)

12/22/2011

Primary AI Autoimmune adrenalitis

Central AI Exogenous corticosteroids

Infection (TB, mycosis, bacterial, Hypothalamic/Pituitary disease HIV) (adenoma, Rathke cyst, hypothalamic tumors, sarcoid) Metastatic cancer Medications (etomidate, ketoconazole, metyrapone) Adrenal hemorrhage Cranial irradiation Medications with steroid activity (megestrol acetate)

Primary
ACTH Cortisol

AI

Aldosterone

Response to cosyntropin: minimal to none Tx: corticosteroids and mineralocorticoids

Central
ACTH Cortisol

AI

Normal
subnormal

Aldosterone

Response to cosyntropin: Tx: corticosteroids only

12/22/2011

On

Endocrine/Infectious Disease/GI on December 9th, during Friday Conference be available the week beforehand

Will

12/22/2011

October 4, 2011

premenopausal female presents with:

Gradual onset of truncal weight gain, acne, amenorrhea BP, hirsutism, fat in a cervicodorsal distribution, moon facies, plethora, and purple abdominal striae Fasting blood glucose Serum K+ and HCO3DEXA scan: Z-score < -2.0 Diagnosis:
Cushing Syndrome

12/22/2011

3 screening options: 24-h UFC / overnight 1mg DST / 11pm salivary cortisol

+
NL or ACTH-dependent High-dose DST
Will not suppress (or stim) Will suppress (or + stim)

Serum ACTH

ACTH-independent

Adrenal CT or MRI +

Chest/Abd MRI Octreotide scan

Pituitary MRI

IPS sampling Cushings Disease

Ectopic ACTH

Adrenal tumor

12/22/2011

\ 54-year-old man with a 3-year history of multiple myeloma, complicated by hypercalcemia, presented with a 1-month history of severe bilateral jaw pain
What is the diagnosis, and what is the likely cause? Need BOTH for points! E-mail Jen at gilliamj@ecu.edu with the correct answer by 8am, Thursday, October 6th!

October 5, 2011

12/22/2011

healthy patient, age 30-40 years, presents with gradual development of episodic:
Headaches Palpitations Sweating BP

Diagnosis: Pheochromocytoma

Derived from: Adrenal chromaffin cells Secrete: Epi, Norepi, and Dopamine Clinical manifestations (5 Ps):
Pressure (HTN) Pain (HA, CP) Palpitations Perspiration Pallor

Rule of 10 10% are:

Extra-adrenal Children Multiple or B/L Recurrent Malignant Familial Incidentalomas

12/22/2011

Associated Diagnosis:

with:

MEN 2A/2B

Screen with 24h urinary fractionated metanephrines Plasma free metanephrines (higher risk of false positives) Adrenal CT/MRI, MIBG scintigraphy if negative
Treatment:

Resection!

Preoperatively:

-blockers (phenoxybenzamine vs prazosin/ doxazosin/terazosin)

Intraoperatively: Nitroprusside gtt Hypertensive crisis: Nitroprusside, phentolamine, nicardipine

A 47-year-old woman is evaluated for difficult-to-control hypertension. She was previously treated for hypokalemia. On physical examination, temperature is 36.0 C (96.8 F), blood pressure is 178/100 mm Hg, pulse rate is 58/min, respiration rate is 16/min, and BMI is 29. No abdominal bruit is detected. Funduscopic examination shows mild arteriolar narrowing. Laboratory studies: Sodium 143 meq/L (143 mmol/L) Potassium 3.5 meq/L (3.5 mmol/L) (after replacement therapy) Chloride 101 meq/L (101 mmol/L) Bicarbonate 33 meq/L (33 mmol/L) Aldosterone [NL: Supine - 2-5 ng/dL (55-138 pmol/L); Standing - 7-20 ng/dL (194-554 pmol/L)] Baseline 23 ng/dL (635 pmol/L) 3 Days after high salt intake 15 ng/dL (414 pmol/L) Renin activity Baseline <0.1 ng/mL/h (0.1 g/L/h) 3 Days after high salt intake <0.1 ng/mL/h (0.1 g/L/h) Aldosterone: renin activity ratio >50 Which of the following is the most appropriate next step in management? (A) Adrenalectomy (B) Bilateral adrenal vein catheterization (C) CT of the adrenal glands (D) Duplex ultrasonography of the renal arteries

Dx: Primary Hyperaldosteronism

12/22/2011

Suspect Hyperaldosteronism Plasma renin and aldosterone AM collection

renin aldosterone
Non-aldosterone mineralocorticoid excess: Cushings syndrome CAH 11 -hydoxylase deficiency Licorice Liddles syndrome Exogenous mineralocorticoids

renin aldosterone Aldo:renin > 20

Salt suppression + 1 Hyperaldosteronism
Adrenal CT/MRI

renin aldosterone Aldo:renin < 10

2 Hyperaldosteronism Renin-secreting tumor Renovascular disease CHF, cirrhosis, nephrotic Hypovolemia, diuretic use Bartters Syndrome Gitelmans Syndrome

Unilateral lesion

No or B/L lesions

Adenoma or Carcinoma

Localize

Adrenal vein sampling

No localization

Tx: spironolactone, eplerenone

Hyperplasia

12/22/2011

\ 54-year-old man with a 3-year history of multiple myeloma, complicated by hypercalcemia, presented with a 1-month history of severe bilateral jaw pain
What is the diagnosis, and what is the likely cause? Need BOTH for points! E-mail Jen at gilliamj@ecu.edu with the correct answer by 8am, TOMORROW, October 6th!

October 6, 2011

10

12/22/2011

patient presents with the gradual onset of:

Weakness Nausea/Vomiting Sporadic abdominal pain Fevers BP and tanned skin Serum Na+, K+, and glucose ( eosinophilia) 60 minutes after cosyntropin, serum cortisol = 7 g/dL Diagnosis:
Adrenal Insufficiency (Primary)

Primary
ACTH Cortisol

AI

Aldosterone

Response to cosyntropin: minimal to none Tx: corticosteroids and mineralocorticoids

Central
ACTH Cortisol

AI

Normal
subnormal

Aldosterone

Response to cosyntropin: Tx: corticosteroids only

11

12/22/2011

3 screening options: 24-h UFC / overnight 1mg DST / 11pm salivary cortisol

+
NL or ACTH-dependent High-dose DST
Will not suppress (or stim) Will suppress (or + stim)

Serum ACTH

ACTH-independent

Adrenal CT or MRI +

Chest/Abd MRI Octreotide scan

Pituitary MRI

IPS sampling Cushings Disease

Ectopic ACTH

Adrenal tumor

12

12/22/2011

54-year-old man with a 3-year history of multiple myeloma, complicated by hypercalcemia, presented with a 1-month history of severe bilateral jaw pain
What is the diagnosis, and what is the likely cause? Need BOTH for points!
Osteonecrosis of the jaw, secondary to bisphosphonate use!

October 11, 2011

13

12/22/2011

tall, introspective male has:

Long arms and legs Small testes Sparse hair growth and muscle development Gynecomastia Learning disabilities FSH and LH Testosterone Diagnosis:
Klinefelter syndrome 47, XXY

Hypothalamus

Inhibin B

Spermatogenesis Estradiol

14

12/22/2011

Screening: Total serum testosterone, no later than 10am

Random testosterone > 350 ng/dL excludes hypogonadism < 350 requires second measurement, including determination of free testosterone

If

testosterone , then check

FSH Normal LH/FSH/PRL

FSH, LH, prolactin levels LH/FSH, PRL

Testicular Failure: Kilnefelters HIV Cryptorchidism Infectious orchitis Chemotherapy, RT Orchiectomy

Age-related decline

Pituitary disease

Benefits: increased libido, increased bone density, improved cognitive function, increased Hct Preparations: injections, patches, gels (most popular), buccal Monitoring: DRE, PSA, Hgb/Hct beforehand

PSA often DOUBLES, then stabilizes after 3-6 months If PSA by more than 2x (to > 4) or continues to 612 months of tx, STOP testosterone and pursue urologic workup

Most worrisome adverse effect: Growth of occult prostate cancer _______________________________________

15

12/22/2011

This patient was being treated by an endocrinologist for which one of the following conditions? A. Acromegaly B. Cushings Disease C. Graves Disease D. Hashimotos Thyroiditis E. Type 1 DM

E-mail Jen at gilliamj@ecu.edu with the correct answer by 8am, TOMORROW Wednesday, October 12th! You have 24 HOURS!

October 12, 2011

16

12/22/2011

A 26-year-old woman is evaluated for a 4-month history of amenorrhea. Menses began at age 13 years. At age 18 years, the patient was placed on an oral contraceptive pill to control heavy bleeding. She discontinued the oral contraceptive pill 4 months ago because she and her husband want to become pregnant, and she has had no menses since then. There is no family history of infertility or premature menopause. On physical examination, vital signs are normal, and BMI is 24. There is no acne, hirsutism, or galactorrhea. Examination of the thyroid gland and visual field testing yield normal findings. Pelvic examination findings are also normal. An office pregnancy test is negative. Laboratory studies: FSH 2 mU/mL [Normal: follicular or luteal phase, 5-20 mU/mL; midcycle peak, 30-50 mU/mL; postmenopausal, greater than 35 mU/mL] Prolactin 17 ng/mL [Normal: less than 20 ng/mL] TSH 1.1 U/mL [Normal: 0.5-5.0 U/mL] FT4 1.0 ng/dL [Normal: 0.5-5.0 U/mL] Which of the following is the most appropriate next diagnostic test? (A) Measurement of the plasma dehydroepiandrosterone sulfate level (B) Measurement of serum estradiol level (C) MRI of the pituitary gland (D) Progestin withdrawal challenge

Hypothalamus

Inhibin B

Granulosa Cells

Theca Cells

Ovulation

Estradiol Androstenedione

17

12/22/2011

Primary

Causes: anatomic, ovarian failure, chronic anovulation w/ NL or low estrogen levels

spontaneous menses by age 16, or age 14 amenorrhea: No in the absence of 2 sexual characteristics

Secondary

menses after 3 or more mos, in amenorrhea: No someone w/ previous menstruation

Incidence is the same OCPs vs spontaneous amenorrhea

Workup:

Pregnancy test FSH, prolactin, TSH, FT4 Progestin withdrawal challenge Pelvic U/S, MRI, hysterosalpingography

18

12/22/2011

MCC

of secondary amenorrhea MCC of hirsutism Dx: First check total serum testosterone (r/o tumor, Cushing, 21-hydroxylase deficiency) Rotterdam criteria: (need 2 of 3)
Ovulatory dysfunction Lab/clinical evidence of hyperandrogenism U/S evidence of polycystic ovaries

Due

to assoc. w/ metabolic syndrome, check Fasting glucose, lipid levels ________________________________________ Tx: No babies spironolactone + OCP
+ babies metformin, clomiphene

A 21-year-old woman is evaluated for a 7-year history of oligomenorrhea and slowly progressive hirsutism. Menses began at age 14 years and were always irregular. She has gained weight at a rate of approximately 4.5 kg (10 lb) per year. Her facial hair has become progressively thicker since age 18 years, and she now menstruates only three to four times per year. She is sexually active but does not want to become pregnant at this time. Family history is noncontributory, and she takes no medications. On physical examination, vital signs are normal, and BMI is 28. Prominent terminal hairs are noted on the upper lip and chin, with some on the upper cheeks and chest; there is thick hair from the pubis to the umbilicus. Results of a pelvic examination and Pap smear are normal. Laboratory studies: DHEA 4.3 g/mL [Normal: 0.6-3.3 mg/mL] -hCG Negative for pregnancy 17-Hydroxyprogesterone 105 ng/dL [Normal: <400 ng/dL] Prolactin 11 ng/mL [Normal: less than 20 ng/mL] Testosterone, total 84 ng/dL [Normal: Female: 20-75 ng/dL] TSH 1.4 U/mL [Normal: 0.5-5.0 U/mL] A progestin withdrawal challenge with medroxyprogesterone acetate results in a temporary resumption of menses. Which of the following is the most appropriate next step in management? (A) Measurement of free testosterone level (B) Prednisone therapy (C) Spironolactone and oral contraceptive therapy (D) Transvaginal ovarian ultrasonography

19

12/22/2011

This patient was being treated by an endocrinologist for which one of the following conditions? A. Acromegaly B. Cushings Disease C. Graves Disease D. Hashimotos Thyroiditis E. Type 1 DM

ENDOCRINOLOGY
September 19, 2011

20

12/22/2011

DIABETES MELLIITUS DIAGNOSIS

Fasting blood glucose 126 mg/ dL Random blood glucose 200 mg/ dL with symptoms 2-hour blood glucose 200 mg/ dL after a 75-gram glucose load HbA1c 6.5% Confirmed by retesting at least once unless there are clear signs of metabolic decompensation (DKA, hyperosmolar coma)

SCREENING GUIDELINES FOR DM PER AMERICAN DIABETES ASSOCIATION

45 years old (every 3 years) BMI > 25 with any of the following risk factors: Physically inactive First-degree relative with DM High-risk ethnic group History of gestational DM or previous delivery of an infant 4.1 kg HTN ( 140/90 mmHg) Low HDL ( 35 mg/dL) High Triglycerides ( 250 mg/dL) Polycystic ovary syndrome Acanthosis nigricans Impaired fasting glucose History of vascular disease

21

12/22/2011

DIABETES MELLITUS METABOLIC TARGETS:

HbA1c < 7% Pre-prandial glucose 70 130 mg/dL 2-hours postprandial glucose < 180 mg/dL Blood pressure < 130/80 mmHg LDL < 100 mg/dL HDL Men > 40 mg/dL Women > 50 mg/dL Triglycerides < 150 mg/dL

45 year old female was diagnosed with Type 2 DM 4 months ago. At that time, she had a fasting blood glucose of 170 mg/dL and HbA1c of 8.9%. She started an intense exercise and diet regimen. She returns today for follow-up. Her fasting blood glucose is 165 mg/dL and HbA1c of 8.0%. Her weight is 205 lbs and the rest of her physical exam is normal. What do you do next? A. Start glipizide B. Start metformin C. Start insulin D. Start acarbose E. Start insulin and glipizide

22

12/22/2011

50 year old male with Type 2 DM presents for follow-up. The patient was doing well on glargine insulin at bedtime and metformin 2000 mg/d for a year. Today, HbA1c is 8% but fasting blood glucoses are 115-130 mg/dL. What do you do next? A. Increase metformin B. Increase glargine insulin C. Start lispro insulin
Increased postpranial glucose

71 year old male is evaluated in the emergency department for new dyspnea on exertion. He has a 15-year history of Type 2 DM and has had a number of changes in his medications over the past 12 weeks to improve glycemic control. His dosage of metformin has been increased to 1000 mg/d, glyburide to 10 mg/d, and pioglitazone to 45 mg/d. Within the past week, bedtime insulin glargine was initiated. On physical examination, BP 140/90 mmHg, HR 90 /min, and RR 20 /min. JVD, an S3, basilar pulmonary crackles and 3+ pitting edema at the ankles are noted. Besides the initiation of insulin glargine, which of the following most likely contributed to these findings? A. Increased glyburide dosage B. Increased metformin dosage C. Increased pioglitazone dosage D. Medication-associated hypoglycemia

23

12/22/2011

NO MORNING REPORT TOMORROW, 9/20/11

Due to Senior Switch Day

THIS WEEK (9/21-23)

If there are any problems, please call or email us. Daphne: harringtonda@ecu.edu or (252) 714-0658

Jen: gilliamj@ecu.edu or (708) 207-0538

Alexa: simona@ecu.edu or (617) 794-2681 Dr. Kraemer: kraemerm@ecu.edu We will have our cell phones at all times so dont hesitate. The baby chiefs (Reed, Arjun, and Azeem) will be leading Morning Report and helping with Friday Conference.

24

12/22/2011

ENDOCRINOLOGY
September 26, 2011

MANAGEMENT OF TYPE 2 DM
At diagnosis: Lifestyle + Metformin Lifestyle + Metformin + basal insulin Lifestyle + Metformin + intensive insulin

Lifestyle + Metformin + sulfonylurea

Lifestyle + Metformin + pioglitazone
No hypoglycemia Edema/HF Bone loss

Lifestyle + Metformin + pioglitazone + sulfonylurea

Lifestyle + Metformin + GLP-1 agonist

No hypoglycemia Weight loss Nausea/vomiting

Lifestyle + Metformin + basal insulin

STEP 1

STEP 2

STEP 3

25

12/22/2011

Hypothalamus
TRH Dopamine GHRH CRH GnRH

Anterior Pituitary

Posterior Pituitary

Prolactin GH TSH ACTH FSH & LH Oxytocin ADH

HYPERPROLACTINEMIA

Hypothalamus
Dopamine TRH

GnRH

X Anterior Pituitary
Prolactin
TSH : Impotence : Amenorrhea, glactorrhea and hirsutism

FSH & LH

Thyroid Hormone

26

12/22/2011

HYPERPROLACTINEMIA CAUSES
Prolactinoma Pituitary tumor Stalk disease Hypothyroidism Pregnancy Nipple manipulation Drugs: Phenothiazines Amitriptyline Methyldopa Verapamil
Macroadenoma Microadenoma

TREATMENT
Medical Dopamine agonist Bromocriptine Cabergoline
Preferred

Contraindicated in patients with known lung, heart valve, and retroperitoneal fibrotic disease Surgical Transsphenoidal surgery followed by irradiation

27

12/22/2011

INDICATIONS FOR SURGERY

Dopamine agonist resistance Invasive tumor Lack of improvement on visual field testing

35 year old female presents with amenorrhea over the past 4 months. She has been trying to get pregnant without success. She complains of a thin milky discharge from her nipples and over the past several days has noted some blurry vision. On laboratory testing, her prolactin level is 110 g/L. A head MRI is performed and reveals an 11 mm pituitary macroadenoma. What is the next step in management? A. Follow visional fields; if worse in 1 month, refer for surgery B. Reassure the patient and follow-up closely C. Refer for urgent neurosurgery D. Repeat MRI in 4 months E. Do visual field testing and initiate a dopamine agonist
MRI and visual field testing 6 to 12 months

28

12/22/2011

25 year old female who is post partum continues to have galactorrhea after finishing nursing her baby. TSH is normal. Prolactin level is 281 g/L. She takes no medications. What is the most likely cause of her galactorrhea? A. Lactation B. Prolactinoma C. Hypothyroidism What do you do next? MRI brain

ANNOUNCEMENTS
Today Meet & Greet at 12:30 in the Elm Room Tuesday Mentoring Panel at 7:30 am 9:00 am in the MSCR-D (Physician Lounge) There will be breakfast Wednesday Nephrology Review

29

12/22/2011

ENDOCRINOLOGY
September 29, 2011

HYPERTHYROIDISM
Free T4 Graves Disease T3 TSH Radioactive Iodine Uptake

Normal/

diffuse

focal

> 35%,

Multinodular Goiter
Toxic Nodule T3 Thyrotoxicosis TSH Adenoma Thyroiditis TBG Exogenous T3
TBG

Exogenous T4

30

12/22/2011

18 yo female is evaluated for tachycardia, nervousness, decreased exercise tolerance, and weight loss of 6 months duration. She has otherwise been healthy. Her sister has Graves disease. She takes no medication On physical examination, BP 128/78 mmHg, HR 124 /min, RR 16 /min, and BMI 19.5. There is no proptosis. An examination of the neck reveals a smooth thyroid gland that is greater than 1.5 times the normal size. Cardiac examination reveals regular tachycardia with a grade 2/6 early systolic murmur at the base. Her lungs are clear to auscultation. Laboratory studies: HCG negative; TSH < 0.01 U/mL; Free T4 5.5 ng/dL; Free T3 9.1 ng/L Which of the following is the most appropriate treatment regimen at this time? A. Atenolol only B. Methimazole only C. Atenolol and Methimazole D. Radioactive iodine and Methimazole

Thyroid Nodule

31

12/22/2011

35 yo female comes to the office for her annual physical examination. The patient says she feels well. She has no pertinent personal or family medical history and takes no medications. On physical examination, vital signs are normal. Palpation of the thyroid gland suggests the presence of a nodule. All other findings of the general physical examination are normal. Laboratory studies show a TSH of 1.3 U/mL and a free thyroxine (T4) of 1.3 ng/dL. An ultrasound of the thyroid gland reveals a normal-sized gland with a 2 cm hypoechoic right midpole nodule. Which of the following is the most appropriate next step in management? A. Fine-needle aspiration biopsy of the nodule B. Measurement of anti-thyroperoxidase and anti-thyroglobulin antibody titiers C. Neck CT with contrast D. Thyroid scan with technetium E. Trial of levothyroxine therapy
Cancerous microcalcifications, central nodule vascularity, hypoechogenicity, irregular borders, taller than wide (sagittal view)

HYPOTHYROIDISM
Free T4 Primary Hypothyroidism Normal TSH

Hypopituitary hypothyroidism
Subclinical hypothyroidism

32

12/22/2011

ENDOCRINOLOGY
October 13, 2011

FEMALE REPRODUCTIVE AXIS

33

12/22/2011

MENSTRUAL CYCLE

AMENORRHEA WORKUP
Primary amenorrhea: characteristics Causes: anatomic, ovarian failure, chronic anovulation with NML or low estrogen levels Secondary amenorrhea: No menses after 3 or more months in someone with previous menstruation Incidence is the same OCPs vs spontaneous amenorrhea Workup: Pregnancy test FSH, prolactin, TSH, FT4 Progestin withdrawal challenge Pelvic U/S, MRI, hysterosalpingography
No spontaneous menses by age 16, or age 14 in the absence of 2 sexual

34

12/22/2011

A 26-year-old woman is evaluated for a 4-month history of amenorrhea. Menses began at age 13 years. At age 18 years, the patient was placed on an oral contraceptive pill to control heavy bleeding. She discontinued the oral contraceptive pill 4 months ago because she and her husband want to become pregnant, and she has had no menses since then. There is no family history of infertility or premature menopause. On physical examination, vital signs are normal, and BMI is 24. There is no acne, hirsutism, or galactorrhea. Examination of the thyroid gland and visual field testing yield normal findings. Pelvic examination findings are also normal. An office pregnancy test is negative. Laboratory studies: FSH Prolactin TSH FT4 2 mU/mL [Normal: follicular or luteal phase, 5-20 mU/mL; midcycle peak, 30-50 mU/mL; postmenopausal, greater than 35 mU/mL] 17 ng/mL [Normal: less than 20 ng/mL] 1.1 U/mL [Normal: 0.5-5.0 U/mL] 1.0 ng/dL [Normal: 0.5-5.0 U/mL]

Which of the following is the most appropriate next diagnostic test? A. B. C. D. Measurement of the plasma dehydroepiandrosterone sulfate level Measurement of serum estradiol level MRI of the pituitary gland Progestin withdrawal challenge

POLYCYSTIC OVARY SYNDROME

Most common cause of secondary amenorrhea Most common cause of hirsutism Diagnosis: First check total serum testosterone (r/o tumor, Cushing, 21-hydroxylase deficiency) Rotterdam criteria: (need 2 of 3) Ovulatory dysfunction Lab/clinical evidence of hyperandrogenism U/S evidence of polycystic ovaries Due to association with metabolic syndrome, check

Fasting glucose, lipid levels

Tx:

No babies spironolactone + OCP + babies metformin, clomiphene

35

12/22/2011

A 21-year-old woman is evaluated for a 7-year history of oligomenorrhea and slowly progressive hirsutism. Menses began at age 14 years and were always irregular. She has gained weight at a rate of approximately 4.5 kg (10 lb) per year. Her facial hair has become progressively thicker since age 18 years, and she now menstruates only three to four times per year. She is sexually active but does not want to become pregnant at this time. Family history is noncontributory, and she takes no medications. On physical examination, vital signs are normal, and BMI is 28. Prominent terminal hairs are noted on the upper lip and chin, with some on the upper cheeks and chest; there is thick hair from the pubis to the umbilicus. Results of a pelvic examination and Pap smear are normal. Laboratory studies: DHEA -hCG 17-Hydroxyprogesterone Prolactin Testosterone, total TSH 4.3 g/mL [Normal: 0.6-3.3 mg/mL] Negative for pregnancy 105 ng/dL [Normal: <400 ng/dL] 11 ng/mL [Normal: less than 20 ng/mL] 84 ng/dL [Normal: Female: 20-75 ng/dL] 1.4 U/mL [Normal: 0.5-5.0 U/mL]

A progestin withdrawal challenge with medroxyprogesterone acetate results in a temporary resumption of menses. Which of the following is the most appropriate next step in management? A. B. C. D. Measurement of free testosterone level Prednisone therapy Spironolactone and oral contraceptive therapy Transvaginal ovarian ultrasonography

BONUS QUESTION

This patient was being treated by an endocrinologist for which one of the following conditions?
A. B. C. D. E.

Acromegaly Cushings Disease Graves Disease

Hashimotos Thyroiditis
Type 1 DM

36

12/22/2011

GRAND ROUNDS TOMORROW!

Drs. Paul Cook and Mark Mazer How Long to Treat Infections and Why it Matters Antibiotics in Critical Illness

ENDOCRINOLOGY
October 17, 2011

37

12/22/2011

MATCHING
A. B. C. D. E. F. Insulin Sulfonylurea Metformin Acarbose Glitazones Exanatide
1. Use in patients with postpranial hyperglycemia. Inhibits breakdown of carbohydrates and decreases absorption of glucose.

2. Use in patients with normal weight. release of insulin from cells. Side B effect of hypoglycemia. 3. Use in hospitalized patients, Type I DM, Pregnancy. Side effect of weight gain, hypoglycemia. 4. Use in obese patients. hepatic gluconeogenesis, insulin resistance. Side effect of weight loss, lactic acidosis. triglycerides. Avoid in renal insufficiency.

A C

5. GLP1 agonist, hepatic gluconeogenesis, gastric emptying. Side effect F of weight loss (good for obese patients failing metformin). 6. Bind PPAR receptors; glucose transport, insulin resistance. Avoid in CHF patients. triglycerides.

45 yo male with a PMH of obstructive sleep apnea presents to clinic with multiple complaints that include deepening of his voice, increasing ring/shoe size, parasthesias in his hands (specifically the 4 th and 5th digits) bilaterally. On physical exam, he is noted to have frontal bossing, tan-colored, fleshy rash in his armpits, and multiple dental caries. Laboratory studies include an fasting plasma glucose. What is the diagnosis? Acromegaly Screening test: GH is secreted in a pulsatile manner. IGF-1 Confirmation test: 100 g of glucose is administered orally which should suppress GH levels to OGTT < 1ng/mL after 120 minutes. Treatment: Transsphenoidal surgery; somatostatin analogues (Octreotide and Lanreotide); GH analogue (Pegvisomant)

38

12/22/2011

25 yo male with an acute illness is intubated and hospitalized in the ICU. He has been hypotensive and placed on vasopressors. Labs show: TSH, FT4, FT3, reverse T3 What is the diagnosis? Euthyroid sick syndrome What do you do next? Treat the underlying cause. Levels normalize in 4-8 weeks after recovery.

Changes due to cytokines, other mediators of inflammation.

INDICATIONS FOR PARATHYROIDECTOMY

Serum Calcium > 1 mg/dL above the upper limit of NL Creatinine clearance < 60 mL/min Reduction of bone mineral density of the femoral neck, lumbar spine, or distal radius greater than > 2.5 standard deviations below peak bone mass (T score below -2.5) < 50 yo Medical surveillance is not desirable or possible

39

12/22/2011

RADIOACTIVE IODINE UPTAKE

Diffuse uptake Focal uptake
Graves Disease Toxic Nodule Thyroiditis or Factitious thyrotoxicosis

Decreased uptake

Areas of increased and decreased uptake

Multinodular Goiter

THYROID BINDING GLOBULIN (TBG)

Increased TBG Thyroiditis, Estrogens, Pregnancy, Residual cancer ( thyroglobulin) Decreased TBG Factitious thyrotoxicosis

40

12/22/2011

CUSHING SYNDROME WORKUP

3 screening options: 24-h UFC / overnight 1mg DST / 11pm salivary cortisol + NL or ACTH-dependent High-dose DST
Will not suppress (or stim) Will suppress (or + stim)

Serum ACTH

ACTH-independent

Adrenal CT or MRI + +

Chest/Abd MRI Octreotide scan

Pituitary MRI

IPS sampling

+ Ectopic ACTH

+ Cushings Disease Adrenal tumor

Endocrine Morning Report

41

12/22/2011

Regulation of Calcium Metabolism

NL Serum calcium 9-10.5 REMEMBER TO CORRECT FOR ALBUMIN
0.8 x [(NL albumin pts albumin) + Ca++]

Approx 40% of Ca++ bound to plasma proteins

Then 60% includes Cai and Ca complexed w/ phos and citrate

Calcium Homeostasis
Parathyroids PTH

Bone

1,25 (OH)2D3
Kidney

GI tract

Increased osteoclast bone resorption

Increased tubular calcium reabsorption Decreased calcium excretion

Increased intestinal calcium absorption

Serum Ca++

42

12/22/2011

So, measurement of ________ provides best indicator of total body vitamin D stores?
25-hydroxy vitamin D3

Question?
A healthy patient w/ no symptoms and screening lab work shows:
serum Ca+ NL albumin NL or iPTH

Diagnosis?
Primary hyperparathyroidism

43

12/22/2011

Most common cause of hypercalcemia in outpatient setting?

Primary hyperparathyroidism

Most common cause of hypercalcemia in hospitalized patient?

Cancer

A 45 yo M evaluated for a 3 mo. History of fatigue, constipation, and polyuria. He also has a 5 year history of HTN. Current medications are losartan and diltiazem. Physical examination, including VS are WNL Labs: Ca 11.4, Cr 1.1, gluc fasting 88, Phos 2.2, TSH 1.2 Measurement of which of the following levels should be done next?
1. 2. 3. 4. Calcitonin 25-Hydroxy vitamin D Parathyroid Hormone Parathyroid horomone-related protein

44

12/22/2011

A 45 yo M evaluated for a 3 mo. History of fatigue, constipation, and polyuria. He also has a 5 year history of HTN. Current medications are losartan and diltiazem.

Physical examination, including VS are WNL

Labs: Ca 11.4, Cr 1.1, gluc fasting 88, Phos 2.2, TSH 1.2 Measurement of which of the following levels should be done next?
1. 2. 3. 4. Calcitonin 25-Hydroxy vitamin D Parathyroid Hormone Parathyroid horomone-related protein

Indications for Parathyroidectomy in ASYMPTOMATIC Patients

Serum Calcium > 1mg/dL (0.25mmol/L) above the upper limit of NL Creatinine clearance (calculated) < 60mL/min BMD >2.5 SD below peak bone mass (T score < -2.5) Age < 50 Patients for whom medical surveillance is not desirable or possible

45

12/22/2011

A 76 yo F is evaluated in the ER for a 2-month history of fatigue, anorexia, thirst, polydipsia, and polyuria. Squamous cell lung cancer was dx 6 mos ago; the patient declined surgery and chemo. She takes no meds. On physical exam; Temp 37.5C, BP 90/60, HR 118, RR 22/min, BMI 18. patient appears cachectic and remaining PE is NL Labs: BUN 70, Ca++ 13.5, Cr 2.9, PTH undetectable Aggressive volume replacement w/ IV NS is initiated. Which of the following drugs is likely to provide the most sustained benefit in decreasing this patients calcium level? A. B. C. D. Calcitonin Cinacalcet Prednisone Zoledronate

A 76 yo F is evaluated in the ER for a 2-month history of fatigue, anorexia, thirst, polydipsia, and polyuria. Squamous cell lung cancer was dx 6 mos ago; the patient declined surgery and chemo. She takes no meds. On physical exam; Temp 37.5C, BP 90/60, HR 118, RR 22/min, BMI 18. patient appears cachectic and remaining PE is NL Labs: BUN 70, Ca++ 13.5, Cr 2.9, PTH undetectable Aggressive volume replacement w/ IV NS is initiated. Which of the following drugs is likely to provide the most sustained benefit in decreasing this patients calcium level? A. B. C. Calcitonin Cinacalcet Prednisone

D.

Zoledronate

46

12/22/2011

A 19 yo F is evaluated for a 2-month history of increasing fatigue and polyuria. Medical history is remarkable for a prolactinoma treated w/ cabergoline. Her father has h/o kidney stones.
On physical exam: VS are NL, and BMI is 21. All other findings are unremarkable. Labs: Ca++ 12, Cr 0.8, PTH 260, Prolactin 15 Which of the following is the most likely diagnosis? A. Autoimmune polyglandular syndrome type 1 B. Multiple endocrine neoplasia type 1 C. Multiple endocrine neoplasia type 2 D. Osteosclerotic myeloma

A 19 yo F is evaluated for a 2-month history of increasing fatigue and polyuria. Medical history is remarkable for a prolactinoma treated w/ cabergoline. Her father has h/o kidney stones. On physical exam: VS are NL, and BMI is 21. All other findings are unremarkable. Labs: Ca++ 12, Cr 0.8, PTH 260, Prolactin 15 Which of the following is the most likely diagnosis? A. Autoimmune polyglandular syndrome type 1 B. Multiple endocrine neoplasia type 1 C. Multiple endocrine neoplasia type 2

D. Osteosclerotic myeloma

47

12/22/2011

Multiple Endocrine Neoplasia Type 1 & 2

MEN 1 Multigland hyperparathyroidism (MC manifestation) MEN 2 Medullary thyroid cancer (MC manifestation)

Pituitary neoplasms assoc w/ prolactinoma, acromegaly, Cushing disease

Pheochromocytoma

Pancreatic neuroendocrine tumors assoc. w/ gastrinoma, insulinoma, vasoactive intestinal polypeptidesecreting tumor, carcinoid syn

Multigland hyperparathyroidism (least common)

A 66 yo M is seen for his annual physical exam. The patient feels well and has no current symptoms. Takes no medications. On physical exam: VS NL. All other PE findings, including those from a prostate exam are NL. Labs: ALT 30, AST 28, AP 350, T bili 0.9, Ca 9, Phos 4, PSA 1.2, 25Hydroxy vitamin D 42 A radionuclide bone scan reveals increased uptake in skull and left tibia. Radiographs show lytic erosions in the skull and lytic flameshaped lesion in the metaphysis of the left tibia.

Which of the following if the most likely diagnosis?

A. B. C. D. Bony metases Osteomalacia Osteoporosis Paget disease of bone

48

12/22/2011

A 66 yo M is seen for his annual physical exam. The patient feels well and has no current symptoms. Takes no medications.
On physical exam: VS NL. All other PE findings, including those from a prostate exam are NL. Labs: ALT 30, AST 28, AP 350, T bili 0.9, Ca 9, Phos 4, PSA 1.2, 25Hydroxy vitamin D 42 A radionuclide bone scan reveals increased uptake in skull and left tibia. Radiographs show lytic erosions in the skull and lytic flameshaped lesion in the metaphysis of the left tibia. Which of the following if the most likely diagnosis?

A.
B. C. D.

Bony metases
Osteomalacia Osteoporosis Paget disease of bone

Paget disease of bone

Sx: pain, fractures, deformity At least 2/3 asymptomatic Isolated elevated Alkaline Phosphatase level

Bone scans are MOST sensitive although are nonspecific

Four reasons to treat are bone pain, HA, back pain, radiculopathy Bisphosphonates are first line agents

49

12/22/2011

A healthy patient presents w/:

Ca++ on screening labs +FHx of relatives w/ hypercalcemia NL or slightly PTH Urine Ca++ < 200 mg/d What is the cause of the hypercalcemia?

A healthy patient presents w/: Ca++ on screening labs +FHx of relatives w/ hypercalcemia NL or slightly PTH Urine Ca++ < 200 mg/d What is the cause of the hypercalcemia?

Familial hypocalciuric hypercalcemia (FHH)

mimics 1 hyperparathyroidism, Uca is LOW +FHx, AD

50

12/22/2011

Hepatitis B
Transmitted parentally via:
IVDA, sexual contact, infected mom to infant during pregnancy

Can become chronic (>6months) cirrhosis hepatocellular carcinoma Presence of hepatitis B e antigen and hep B virus DNA are markers of ACTIVE viral replication Chronic hepatitis B may present as MGN, PAN or cryoglobulinemia

Serologic Dx of Hep B
Acute Hep B Hepatitis B surface antigen (HBsAg) Antibody to hep B surface antigen (anti-HBs) Antibody to hep B core antigen (antiHBc) Hepatitis B virus DNA (HBV DNA) Hep B e antigen (HBeAg) Antibody to hep B e antigen (anti-HBe) Inactive Carriers Chronic Hep B Prior Exposure Prior Vaccination

51

12/22/2011

Serologic Dx of Hep B
Acute Hep B Hepatitis B surface antigen (HBsAg) Antibody to hep B surface antigen (anti-HBs) Antibody to hep B core antigen (antiHBc) Hepatitis B virus DNA (HBV DNA) Hep B e antigen (HBeAg) Antibody to hep B e antigen (anti-HBe) + Inactive Carriers + Chronic Hep B + Prior Exposure + Prior Vaccination +

+ (IgM)

+ (IgG)

+ (IgG)

+ + +/-

+ +/+/-

+/-

Treatment
Treat w/ interferon alpha, lamivudine, or adefovir if:
HBeAg+, HBV DNA+, ALT >2xNL HBeAg-, HBV DNA+, ALT >2xNL Hbeag+/-, HBV DNA+, +cirrhosis

Observe if:
HBeAg+, HBV DNA+, ALT < 2xNL HBeAg-, HBV DNA-, ALT < 2xNL

52