7/1/2013 ENDOCRINE Elizabeth J. Murphy, MD, DPhil Associate - - PDF document

7/1/2013 1

ENDOCRINE

Elizabeth J. Murphy, MD, DPhil

Associate Professor of Clinical Medicine, UCSF Chief, Division of Endocrinology, SFGH July 8, 2013

Endocrine Resources

• UpEndocrine Society Guidelineshttp://www.endo-

society.org/guidelines/Current-Clinical-Practice-Guidelines.cfm:

• Pituitary Incidentaloma
• Diagnosis and treatment of hyperprolactinemia
• Testosterone Therapy in Adult Men
• Primary Aldosteronism
• Cushing’s Syndrome
• Hirsutism in Premenopausal Women
• Post-menopausal Hormone Therapy
• Vitamin D deficiency
• Adult Growth Hormone Deficiency
• Post-Bariatric Surgery Management
• Androgen Therapy in Women
• Endocrine Treatment of Transsexual Persons

2

Diabetes Resources

• Diabetes Care January Supplement:

http://professional.diabetes.org/CPR_Search.aspx

• American Diabetes Association Clinical Practice Recommendations
• Standards of Medical Care in Diabetes

3

7/1/2013 2

Endocrine Content

• Diabetes (5-8)
• Thyroid (2-4)
• Disorders of calcium metabolism and bone (1-5)
• Adrenal disorders (0-2)
• Testes/Male reproductive health (0-2)
• Other (0-1)
• Anterior pituitary
• Posterior pituitary
• Hypothalamic disorders
• Polyglandular disorders
• (Hypoglycemia not due to insulinoma)
• (Nutritional disorders)
• (Women’s health endocrine issues)
• (Hypertension)
• (Ovarian Disorders/Female Reproductive Health)
• (Lipids 2-4)

4

Case #1

5

64 yom with HTN, CAD, CHF, and hyper-TG with a prior episode of pancreatitis is found to have a random plasma glucose of 205 mg/dl

• n labs obtained for another reason. An A1C

was obtained and was 6.4%. The patient has no symptoms such as polyuria, polydipsia or polyphagia.

Does he meet the criteria for the diagnosis of diabetes?

Diagnosis of Diabetes

Meeting any one criteria makes Dx

1) Fasting plasma glucose (FPG) ≥ 126 mg/dl 2) Plasma glucose ≥ 200 mg/dl 2 h after a 75 g

• ral glucose load (OGTT)

3) Random plasma glucose ≥ 200 mg/dl with symptoms of hyperglycemia 4) A1C ≥ 6.5% In the absence of unequivocal hyperglycemia, results should be confirmed.

6

7/1/2013 3

Diagnosis of Diabetes

Meeting any one criteria makes Dx

1) Fasting plasma glucose (FPG) ≥ 126 mg/dl 2) Plasma glucose ≥ 200 mg/dl 2 h after a 75 g

• ral glucose load (OGTT)

3) Random plasma glucose ≥ 200 mg/dl with symptoms of hyperglycemia 4) A1C ≥ 6.5% In the absence of unequivocal hyperglycemia, results should be confirmed.

7

Pre-diabetes

Categories of Increased Risk For Diabetes

• Impaired Fasting Glucose:

FPG = 100 - 125 mg/dl

• Impaired Glucose Tolerance:

2 hr OGTT = 140 - 199 mg/dl

• Abnormal A1C:

A1C% = 5.7 - 6.4 %

8

Case #1

9

64 yom with HTN, CAD, CHF, and hyperTG with a prior episode of pancreatitis is found to have a random plasma glucose of 205 mg/dl on labs obtained for another reason. The patient has no symptoms such as polyuria, polydipsia or polyphagia. You obtain a fasting BG which is 154 mg/dl confirming the diagnosis of diabetes mellitus for which he has a strong family

• history. You obtain further labs and need to chose treatment.

LABS: A1C = 8.8%, 140 111 28 4.5 28 1.9 TC 350 LDL NC HDL 22 TG 505

MEDS: furosemide 40 mg BID; KCl 20 meq; ASA 81 mg; lisinopril 40 mg; metoprolol 100 mg BID

EXAM: 100 kg BMI 32 145/94 82 lungs: CTA CV: S3 gallop Ext: tr edema, feet with no ulcerations, sensation intact

7/1/2013 4

Case #1

10

Which choice below would be the most appropriate initial therapy for this patient’s DM2? a) metformin b) glyburide c) colesevelam d) pioglitazone e) glipizide f) diet and exercise alone

Certainties in Glucose Lowering Treatment

LOWERING A1C PREVENTS MICROVASCULAR COMPLICATIONS

11

Testing On DM Therapy

• Lots of different practice styles
• Focus on medications – contraindications

and basic prescribing info

• Some delay in test question writing so

newest medications unlikely to be on the test

12

7/1/2013 5

Sulfonylureas Glinides

Sulfonylureas

• Stimulates insulin release
• Lower A1C 1-2%
• Advantages
• Long history of use
• Disadvantages
• Weight gain ( 2 kg)
• Hypoglycemia
• Earlier pancreatic failure?
• Increased CV mortality?

14

Sulfonylureas

• Glyburide
• Micronase, Diabeta, Glynase; Glucovance with metformin
• 1.25, 2.5, and 5 gm tabs QD or BID, max 20 mg a day
• Non-linear dose response, more effect of 1.25 to 2.5 than 10 to 20
• Caution in renal failure and in elderly
• Glipizide
• Glucotrol, Glucotrol XL; Metaglip with metformin
• 2.5, 5 and 10 mg tabs QD, > 15 mg dose BID, max 20 mg BID; Glucotrol

XL, once daily to max of 20 mg, though no significant change in A1C

• ver 10 mg
• Glimepiride
• Amaryl; Avadaryl with rosiglitazone; Duetact with pioglitazone
• 1, 2, 4 mg tabs, max 8 mg daily
• Caution in renal failure, liver failure, elderly

15

• Typically discontinued when patient on basal and prandial insulin

7/1/2013 6

Glinides

• Enhances insulin release
• Lowers A1C 1-1.5%
• Advantages:
• Short acting, take 15 minutes prior to meal and skip

dose if meal is missed

• Disadvantages
• Short acting, TID dosing
• Hypoglycemia
• No head to head comparison with first generation SU
• Expensive
• Metabolized by CYP2C8 and CYP3A4

16

Glinides

• Nateglinide (Starlix)
• 60 and 120 mg tabs
• 30-360 mg before meals
• Repaglinide (Prandin)
• Better A1C lowering
• 0.5, 1 and 2 mg tabs
• 0.5-4 mg before meals

17

Sulfonylureas Glinides

Biguanides

7/1/2013 7

Biguanides (Metformin)

• Improves hepatic insulin sensitivity
• Lowers A1C 1.5-2%
• Advantages:
• Weight loss (0-2 kg)
• Lowers TG, LDLc; Increases HDLc
• No hypoglycemia when used alone
• Inexpensive
• CVD benefit
• Disadvantages
• Majority of patients with GI SE
• Risk of lactic acidosis
• Impaired B12 absorption (5% or more of patients)

19

Metformin

• metformin (Glucophage, Glucophage XR)
• 500, 850, 1000 mg tabs. Start 500 mg daily with

meals, increase q week, max dose 2550 mg (850 mg TID)

• 500, 750 mg XR tabs, max dose 2000 mg q

evening.

• Works especially well in obese/overweight

patients and for fasting hyperglycemia

• First choice agent for DM2

20

Metformin - Contraindications

• Decreased renal function (check Cr q yr)
• Cr < 1.5, men
• Cr < 1.4, women
• “Abnormal CrCl”
• During IV contrast studies
• Age ≥ 80 unless renal fn wnl
• Hypoxemia
• Excessive alcohol consumption
• Impaired liver function
• CHF (now more relaxed contraindication)

21

7/1/2013 8

Sulfonylureas Glinides

Bile Acid Sequestrants

Biguanides

Bile Acid Sequestrants

• Approved for years for cholesterol lowering
• Lower A1C 0.4%
• Advantages:
• Lowers LDLc
• Presumed CVD benefit
• Not absorbed
• Disadvantages:
• GI SE, constipation
• Lots of pills
• Increases TG, theoretical risk of pancreatitis
• Colasevelam HCL (Welchol)
• Contraindicated
• TG > 500 mg/dl or history of TG induced pancreatitis, caution

>300 mg/dl

• Bowel obstruction
• Cholestyramine (Questran)

23

Sulfonylureas Glinides Bile Acid Sequestrants

PPAR-  Agonists PPAR-  Agonists Biguanides

7/1/2013 9

PPAR- Agonists

• Activate PPAR-, improve insulin sensitivity
• Lower A1C 0.5-1.4%
• CVD risk unclear (possibly increased rosi, decreased

pio)

• Advantages:
• Improved lipid profile with decrease in TG, increase in HDL

(pioglitazone only)

• No hypoglycemia when used alone
• Disadvantages:
• Weight gain ( 2 kg)
• Fluid retention
• Two-fold increased risk of CHF
• Increased fracture risk
• Pioglitazone associated with increased incidence of bladder

cancer

25

PPAR- Agonists

• Thiazoladinediones - PPAR- agonists
• rosiglitazone (Avandia; AvandaMet with metformin,

Avandaryl with glimepiride)

• pioglitazone (Actos;ActoplusMet with MF, Duetact

with glimepiride)

• Use –
• Used in combination with metformin or sulfonylurea
• Fluid retention worse when used in combination

with insulin (consider stopping when insulin started)

• Extreme caution in CHF

26

Case #1

27

64 yom with HTN, CAD, CHF, and hyperTG with a prior episode of pancreatitis is found to have a random plasma glucose of 205 mg/dl on labs obtained for another reason. The patient has no symptoms such as polyuria, polydipsia or polyphagia. You obtain a fasting BG which is 154 mg/dl confirming the diagnosis of diabetes mellitus for which he has a strong family

• history. You obtain further labs and need to chose treatment.

LABS: A1C = 8.8%, 140 111 28 4.5 28 1.9 TC 350 LDL NC HDL 22 TG 505

MEDS: furosemide 40 mg BID; KCl 20 meq; ASA 81 mg; lisinopril 40 mg; metoprolol 100 mg BID

EXAM: 100 kg BMI 32 145/94 82 lungs: CTA CV: S3 gallop Ext: tr edema, feet with no ulcerations, sensation intact

7/1/2013 10

Case #1

28

Which choice below would be the most appropriate initial therapy for this patient’s DM2? a) metformin b) glyburide c) colesevelam d) pioglitazone e) glipizide f) diet and exercise alone

Case #2

29

54 yow with DM2 diagnosed 7 years ago presents to you for f/u complaining of increasing hypoglycemia and several URIs. At your last visit you added sitigliptin (Januvia) to her medications for an A1C of 7.6% and persistent SMBG values in the 200s. Which of the following statements is true? The addition of sitigliptin: a) did not contribute to hypoglycemia b) should have been done with renal dosing c) was not related to the increased number of URIs d) typically results in a 1-2 kg weight loss DM MEDS: metformin 1 gm BID glyburide 10 mg daily sitagliptin 100 mg daily LABS: A1C = 7.0%, 140 111 28 4.5 28 1.9 CrCl is 45 ml/min

Sulfonylureas Glinides GLP-1 Analogues DPPIV Inhibitors Bile Acid Sequestrants GLP-1 Analogues DPPIV Inhibitors

PPAR-  Agonists PPAR-  Agonists Biguanides

7/1/2013 11

The Incretin Effect

31

Incretins

• Hormones released by the GI tract that effect

glucose metabolism

• Include:
• GIP – Gastric Inhibitory Peptide OR Glucose-

dependent Insulinotropic Peptide

• GLP-1 – Glucagon-Like Peptide
• GLP-2
• Half-life of < 5 minutes
• Inactivated by DPPIV

32

Incretin Hormones

• GIP
• Secretion triggered by glucose and fat and enhances insulin

secretion from beta-cells in glucose dependent manner

• Accounts for about 50% of incretin activity
• Stimulates LPL activity in adipocytes
• GLP-1
• Enhances insulin secretion from the beta cells in a glucose-

dependent manner

• Inhibits postpranidal glucagon secretion from the alpha cells in a

glucose-dependent manner

• Slows gastric emptying
• Reduces food intake and body weight? Appetite suppression?
• Increases beta-cell mass and function?

33

7/1/2013 12

GLP-1 as a Therapeutic Target

34

Longer Acting GLP-1 Heloderma suspectum Gila Monster

• Prevent

Breakdown via DPPIV Inhibition

GLP-1 Analogue Actions

• Lower A1C 0.5-1.5%
• Used as monotherapy in DM2 or in conjunction

with metformin, SU, TZD

• Advantages:
• Weight loss (2-3 kg); less hypoglycemia
• Disadvantages:
• Injectable
• GI Side Effects (nausea, vomiting)
• AE:
• Pancreatitis, medullary thyroid cancer?

35

Long Acting GLP-1 Analogues

• Exenatide (Byetta/Bydureon)
• BID SC injection before am and evening meal
• Q week SC Injection (LAR)
• Liraglutide (Victoza)
• QD SC injection any time of day
• Albiglutide (Syncria)
• Taspoglutide

36

7/1/2013 13

DPPIV Inhibitors

• Increases GLP-1 and GIP levels
• Lowers A1C 0.5-0.8% (mean diff from baseline)
• Use in conjunction with other oral hypoglycemic agents in

DM2 or as monotherapy

• Advantages:
• Oral, weight neutral
• Disadvantages:
• Not great A1C lowering, expensive
• AE:
• Small, “not clinically relevant” increases in WBC due to an

increases in neutrophils (0.2)

• Increased incidence of URI, nasophyrngitis,

37

DPPIV Inhibitors

• Sitagliptin (Januvia) 25, 50, 100 mg tabs; max 100

mg daily; Janumet with metformin; renal dosing

• Saxagliptin (Onglyza) 2.5, 5 mg tabs; max 5 mg
• nce daily; renal dosing
• Linagliptin (Tradjenta) 5 mg tabs; no renal dosing
• Vidagliptin (Galvus)
• Alogliptin
• Dutogliptin
• Gemigliptin

38

You are asked to see a 72 year old man with a CHF with previously well controlled DM2, but now a HbA1c

• f 9.1%. He is on glyburide and metformin at max

doses. What is the most appropriate change to his regimen?

• a. Add pioglitazone
• b. Add basal insulin (NPH or glargine)
• c. Add acarbose
• d. Add saxagliptin

Case #3

7/1/2013 14

Sulfonylureas Glinides Amylin Analogues GLP-1 Analogues DPPIV Inhibitors

-Glucosidase Inhibitors

GLP-1 Analogues DPPIV Inhibitors

-Glucosidase Inhibitors

• Reversible competitive inhibition of -glucosidase so

difficulty breaking down sucrose, complex carbohydrates

• Lowers A1C 0.5-0.8%; Improves postprandial glucose
• Advantages:
• No hypoglycemia when used alone; weight neutral
• Disadvantages:
• GI SE, flatulance; TID dosing
• acarbose (Precose) - nonabsorbable
• 25 mg QD up to 100 mg TID with meals
• miglitol (Glyset) - absorbable
• 25 mg QD up to 100 mg TID with meals
• Caution with hypoglycemia, sucrose is ineffective

41

A1C and Cost per 100 doses

Glipizide 1-2% 10 mg $2.44 Glyburide 1-2% 5 mg $2.42 Metformin 1.5-2% 1000 mg $2.67 Pioglitazone 0.6-1.5% 15 mg $69 Acarbose 0.5-0.8% 100 mg $59.20 Colasevelam 0.4% 625 mg $122 Sitigliptin 0.5-0.8% 100 mg $420 Exenatide 0.5-1.5% 10 mcg $350 Bromocriptine 0.2%-0.5% 0.8 mg $270

42

7/1/2013 15

Case #4

43

66 yom with DM2 for 5 years started on insulin 2 years ago but still can’t get A1C below 8.5%. Patient reports no symptomatic lows. DM Meds: Metformin 1 gm BID NPH 20 units am, 10 units at bedtime Regular 5 units before each meal BS records: fasting 115-150 pre-lunch 85 -155 pre-dinner 92 - 145 bedtime 170-290

What would be the best first next step for improving A1C? a) Change NPH to glargine 24 units b) Change NPH to glargine 30 units c) Increase morning NPH dose to 25 units d) Increase bedtime NPH dose 15 units e) Increase meal time R insulin dose to 8 units before each meal f) Increase dinner time R insulin to 8 units g) Change R to glulisine insulin

Case #4

44

66 yom with DM2 for 5 years started on insulin 2 years ago but still can’t get A1C below 8.5%. Patient reports no symptomatic lows. DM Meds: Metformin 1 gm BID NPH 20 units am, 10 units at bedtime Regular 5 units before each meal BS records: fasting 115-150 pre-lunch 85 -143 pre-dinner 92 - 145 bedtime 170-290

What would be the best first next step for improving A1C? a) Change NPH to glargine 24 units b) Change NPH to glargine 30 units c) Increase morning NPH dose to 25 units d) Increase bedtime NPH dose 15 units e) Increase meal time R insulin dose to 8 units before each meal f) Increase dinner time R insulin to 8 units g) Change R to glulisine insulin

Polonsky KS et al. N Engl J Med. 1988;318:1231-1239 0600 0600

Time of day

20 40 60 80 100 B L D

Normal Plasma Insulin Profile

B=breakfast; L=lunch; D=dinner 0800 1800 1200 2400

Insulin U/mL

Basal insulin

• Near-constant levels
• Important during night/between meals
• 50% or more of daily needs

Mealtime insulin

• Limits hyperglycemia after meals
• Rise and peak post meal
• 10% to 20% of daily needs at

each meal

7/1/2013 16

Types of Insulin

• Basal Insulin
• NPH, BID dosing, peaks 4-8 hrs
• glargine (lantus), once daily dosing, no peak, can’t mix with
• ther insulins
• detemir (levemir), BID dosing, no peak, can’t mix
• Mealtime Insulin
• Regular (humalin R, novalin R), take 30 m premeal
• Aspart (novolog), take 5-20 m premeal
• Lispro (humalog)
• Glulisine (apidra)
• Combination Insulin
• 70/30 (70%N, 30% R; 70% intermediate, 30% aspart)
• 75/25 (75% intermediate;25% lispro)

46

0600 0800 1800 1200 2400 0600

Time of day

20 40 60 80 100 B L D

Basal-Bolus Insulin Treatment

B=breakfast; L=lunch; D=dinner

Meal time insulin Normal pattern

U/mL

NPH NPH at bedtime

0600 0800 1800 1200 2400 0600

Time of day

20 40 60 80 100 B L D

Basal-Bolus Insulin Treatment

B=breakfast; L=lunch; D=dinner

Glargine Meal time insulin Normal pattern

U/mL

7/1/2013 17

Case #5

49

54 yow was admitted with severe hyperglycemia and newly diagnosed DM2. She was well controlled at time of discharge on glargine 40 units once daily and regular insulin 10 units before every meal. However, at discharge she informs you she refuses to take more than two shots a day. She also tells you breakfast is her biggest meal of the day. Which of the following are reasonable options? (multiple answers ok) a) 70/30 am and bedtime b) NPH with R in prebreakfast and N at bedtime c) glargine with R in am/breakfast and R at dinner d) 70/30 am and pre-dinner

Case #5

50

54 yow was admitted with severe hyperglycemia and newly diagnosed DM2. She was well controlled at time of discharge on glargine 40 units once daily and regular insulin 10 units before every meal. However, at discharge she informs you she refuses to take more than two shots a day. She also tells you breakfast is her biggest meal of the day. Which of the following are reasonable options? (multiple answers ok) a) 70/30 am and bedtime b) NPH with R in prebreakfast and N at bedtime c) glargine with R in am/breakfast and R at dinner d) 70/30 am and pre-dinner

A 64 year old woman with DM presents with worsening glycemic

• control. Fasting glucose values are constantly above 200. She

doesn’t check BS at other times of the day. Medicines include metformin 1 g BID and glipizide 20 mg BID. A1C 9.1%. Of the options listed below, which is the most appropriate therapy for this patient?

• a. Start morning NPH or glargine and discontinue all oral agents
• b. Start morning NPH or glargine, maintain sulfonylurea and

discontinue metformin

• c. Start bedtime NPH or insulin glargine, discontinue metformin

and continue sulfonylurea.

• d. Start bedtime NPH or glargine, maintain oral agents

Case #6

7/1/2013 18

67 yo obese man (BMI 34) man has had DM2 for 8 yrs. Originally treated successfully with diet, over time his HBA1c increased to 8.1%, and improved again to 6.6% with the addition of glyburide 10 mg a day. He continues to exercise and follow dietary recommendations, but his HbA1c is now 7.7%, Cr 1.2 mg/dl. What is the most appropriate intervention now?

• a. Add repaglinide therapy before bkfst and dinner
• b. Increase glyburide to 10 mg bid
• c. D/c glyburide and begin metformin
• d. Add metformin to the glyburide
• e. Switch from glyburide to glipizide

Case #7 Case #8

55 yow with DM2, HTN and obesity complains

• f fatigue, depressive symptoms and weight

gain What should you check?

THYROID

54

7/1/2013 19

GENERAL ENDO PRINCIPLES

• FIRST – establish the biochemical

abnormality

• Always assess hormones in relation to what

they regulate

• Endocrine is basically knowing the role of

various hormones and knowing if you have too much or too little

• Image ONLY after establishing the

biochemical diagnosis

55

Case #8

55 yow with DM2, HTN and obesity complains of fatigue, depressive symptoms and weight gain Exam: 80 kg, BMI 32, dry skin

56

TSH 8.9 H (0.45-4.20) TSH 35 H (0.45-4.20) FT4 0.63 L (0.65-1.78) Hypothyroid - Treat

Which of the following is true about treatment? a) Start L-thyroxine at 125 mcg daily (weight based estimate) b) Data show combination preparations with T4 and T3 provide better symptomatic relief and should be used c) Starting dose of 25-50 mcg daily (just start low) d) Recheck TSH and free T4 two weeks after starting treatment and increase dose if TSH still low

Hypothyroidism

• 2% of adult women
• Most common etiologies: Hashimoto’s

thyroiditis, post surgery/radiation/XRT, drugs (lithium, amiodarone, interferon)

• Treat with L-thyroxine
• Roughly 1.4-1.8 mcg/kg/day
• Start low and go up slowly to avoid exacerbation
• f undiagnosed CAD
• Recheck/adjust dose in 6-8 weeks
• Calcium, iron interfere with absorption

57

7/1/2013 20

Case #8

55 yow with DM2, HTN and obesity complains

• f fatigue, depressive symptoms and weight

gain Exam: 80 kg, BMI 32, dry skin

58

TSH 8.9 H (0.45-4.20) TSH 12 H (0.45-4.20) FT4 1.1 (0.65-1.78) Subclinical Hypothyroidism What now?

Subclinical Hypothyroidism

Deciding When to Treat

• Reasons to treat
• Prevent progression to frank hypothyroidism
• Risk greater if +TPO antibodies
• Improve symptoms
• Improve lipids
• Long term treatment benefit inconclusive
• Reasons not to treat
• Long term treatment benefit inconclusive
• Expense
• Could do harm

59

Subclinical Hypothyroidism

Deciding When to Treat

• Never treat based on a single value.
• Treat most patients with TSH > 10
• Guidelines suggest don’t treat otherwise
• Taylor decision to patient
• Do no harm (dont make someone

hyperthyroid)

60

7/1/2013 21

Case #9a

35 yow complains of fatigue, documented weight gain, cold intolerance and amenorrhea. TSH 1 (0.45-4.20) FT4 0.3 L (0.65-1.78) Would you start treatment with l-thyroxine? a)Yes b)No

61

Case #9b

35 yow complains of fatigue, documented weight gain, cold intolerance and amenorrhea. TSH 1 (0.45-4.20); FT4 0.3 L (0.65-1.78) Treat with 100 mcg daily of l-thyroxine (70 kg x 1.4 mcg/kg/d = 98 mcg) Get a call from ED that your patient came in with nausea, vomiting and hypotension. Why? a) Adrenal insufficiency b) Unrelated appendicitis c) Gave to high a starting dose of l-thyroxine d) Allergic reaction to l-thyroxine

62

Case #9

• Low free T4 with a “normal” or low TSH is a pituitary

tumor until proven otherwise. With a low FT4 it would be “normal” for the TSH to be high.

• Amenorrhea was another hint that the patient had a

pituitary problem. Treatment with l-thyroxine pushed borderline adrenal insufficiency into frank adrenal insufficiency resulting in the ED visit.

• If you suspect pituitary tumor, get endo input ASAP.

63

7/1/2013 22

With respect to primary adrenal insufficiency which one of the following statements is false

• a. AI can occur in both autoimmune polyglandular

syndrome type 1 and type 2

• b. Bilateral adrenal hemorrhage is now a relatively

common cause of adrenal insufficiency

• c. A normal cortisol value excludes the diagnosis
• d. Postural hypotension is often a feature
• e. Eosinophilia is a feature of Addison’s

disease

Case #10 Adrenal Insufficiency

• Primary AI:
• Autoimmune destruction
• Gland infiltration or destruction
• Metastases, lymphoma
• Hemorrhage
• Amyloid, hemochromatosis
• Infections
• Drugs: ketoconazole, etomidate
• Rare: congenital adrenal hyperplasia, adrenal

leukodystrophy

• Secondary AI:
• Iatrogenic: glucocorticoids & anabolic steroids
• Pituitary or hypothalamic tumors
• Symptoms: Weakness, fatigue, anorexia, weight

loss, nausea, vomiting, diarrhea, unexplained abdominal pain, postural lightheadedness

• Labs:
• ↓ Na+, ↑ K+
• eosinophilia
• mild metabolic acidosis
• ↑ Ca++

Adrenal Insufficiency

7/1/2013 23

Adrenal Insufficiency

Diagnosis

1) Establish diagnosis:

• normal random cortisol  18-20 g/dl
• cosyntroin stimulated cortisol  18-20 g

(baseline cortisol/ACTH, cortrosyn 250 g IM/IV, Cortisol 60 min post)

2) Use ACTH to determine primary (high) versus secondary (normal or low) adrenal insufficiency 3) Image as appropriate

67

Case #11

29 yow with ten pound weight loss, tremor, insomnia and just not feeling right for 6 months TSH < 0.01 H (0.45-4.20) TSH < 0.01 H (0.45-4.20) FT4 4.59 H (0.65-1.78) What about a total T4 or T4 index? What about Free T3?

68

Thyroid Lab Testing

• Total T4/Free T4 index
• Inferior tests for assessing thyroid function and used
• nly in special situtations; Free T4 preferred
• Free T3
• Can be preferentially elevated in toxic nodules
• Most useful in a patient with a suppressed TSH and

normal free T4 (subclinical hyperthyroidism)

• anti-thyroglobulin antibodies
• Least useful in diagnosing thyroid autoimmunity
• Used to determine validity of thyroglobulin assay

69

7/1/2013 24

Thyroid Lab Testing

• TSH receptor antibodies
• 80-99% sensitive for Graves’
• Doesn’t differentiate between activating and

blocking antibodies

• TSI (thyroid stimulating immunoglobulin)
• Bioassay (results as a % of control)
• Specific (100%), sensitive (95%) for Graves’
• anti-TPO (thyroid peroxidase) antibodies
• Best indicator of Hashimoto’s Thyroiditis
• Sensitive, but not specific (+ in 10-15% of euthyroid folks)

70

Case #11a

29 yow with ten pound weight loss, tremor, insomnia and just not feeling right for 6 months. Labs: TSH < 0.01 H (0.45-4.20) FT4 4.59 H (0.65-1.78)

What is the most likely etiology of this patient’s hyperthyroidism? a)Graves’ disease b)Toxic nodule c)Thyroiditis d)TSH secreting tumor

71

Hyperthyroidism

Differential Diagnosis

• Graves’ Disease (60-80%)
• Toxic Nodules
• Toxic Multi-Nodular Goiter
• Toxic Adenoma
• Thyroiditis
• Painless/silent thyroiditis – transient thyrotoxicosis
• Postpartum thyroiditis – as above, post partum
• Subacute thyroiditis – fever, tender thyroid, viral
• Other
• Thyrotoxicosis factitia
• Struma Ovarii
• Hydatiform mole, choriocarcinoma
• TSH secreting tumor
• Pituitary resistance to thyroid hormone
• Thyroid cancer

72

7/1/2013 25

Hyperthyroidism

Graves Disease

• Most prevalent autoimmune disorder in US
• Antibodies to the TSH-receptor
• Highest risk of onset age 40-60
• Hyperthyroid Symptoms: fatigue,

palpitations, heat intolerance, weight loss, anxiety

• Graves’ Signs: firm, diffusely enlarged and

non-tender thyroid, bruit, dermopathy (rare),

• phthalmopathy

73

Case #11b

29 yow with ten pound weight loss, tremor, insomnia and just not feeling right for 6 months. Labs: I-123 Radioiodine Scan: TSH < 0.01 H (0.45-4.20) decreased uptake (5%) at 24 FT4 4.59 H (0.65-1.78) hrs (normal 15-30%)

74

Which diagnoses would be consistent with this scenario? More than one result is possible. a)Toxic nodule b)Thyroiditis c)Graves’ disease d)TSH secreting tumor e)Surreptitious l-thyroxine use

I-123 Thyroid Uptake and Scan

Decreased Uptake Diffusely Increased Uptake Irregular Uptake Thyroiditis Graves’ Dz Multinodular goiter (hot and cold) Exogenous hyperthyroidism TSH secreting tumor Solitary Toxic nodule (hot) Struma Ovarii Cancer (cold)

7/1/2013 26

Case #11

• 29 yow with weight loss, tremor, insomnia and just

not feeling right. No recent URI. Exam: HR 115 (regular) wt 65 kg BP 115/72

HEENT: PERRL, EOMI, + scleral injection, +proptosis bilat, periorbital edema Thyroid: smooth, firm, approximately 3x nl size, no nodules palpated, non-tender, + bruit Ext: + tremor Skin: warm, smooth, diaphoretic, no rash

Labs: TSH < 0.01 H Are more lab tests FT4 4.59 H needed? Ultrasound?

76

Case #11

• 29 yow with weight loss, tremor, insomnia and just

not feeling right. No recent URI. Exam: HR 115 (regular) wt 65 kg BP 115/72

HEENT: PERRL, EOMI, + scleral injection, +proptosis bilat, periorbital edema Thyroid: smooth, firm, approximately 3x nl size, no nodules palpated, non-tender, + bruit Ext: + tremor Skin: warm, smooth, diaphoretic, no rash

Labs: TSH < 0.01 H Are more lab tests FT4 4.59 H needed? Ultrasound?

77

Case #11

• 29 yow hyperthyroid with Graves’ disease.

NKDA Meds: none PMH: none Need to treat.

78

7/1/2013 27

Hyperthyroidism

Treatment Options

• Surgery
• Not very common in US
• Radioactive Iodine (I-131) Ablation
• More popular in the US than antithyroid drugs
• Treatment of choice for nodules, toxic multinodular goiter
• Medication
• PTU – oldest, black box warning for liver failure; use in

pregnancy or allergy to methimazole, can get agranulocytosis

• Methimazole – Liver failure, rash, agranulocytosis
• Beta-blockers – Use any, may need more frequent dosing

79

39 yo woman with Graves’ disease presents to the ER with severe dyspnea, nausea, diarrhea and a feeling of impending doom. She had been on methimazole for 7 months, but self d/c 9 mth ago. Exam: T 39.6C, HR 144; BP 106/48 BMI 22 Hyperkinetic, delirious, diaphoretic and dyspnic. Thyroid: large goiter with loud bruit. While awaiting laboratory results, therapy could include each of the following EXCEPT:

a. PTU or methimazole b. Iodide c. Corticosteroids d. Radioactive iodine e. -blockers

Case #12 Take Home Points

• Graves Disease
• Most common cause of hyperthyroidism
• Clinically associated with bruit, eye findings, and

smooth, enlarged non-tender gland

• Check TSH receptor or TSI antibodies if not sure

clinically (TPO can also be +)

• Can treat medically for 18 months with methimazole

which is dosed daily at doses of 20 mg or less and twice daily for higher doses

• Provide patient warning for agranulocytosis
• Beta-blocker for symptoms
• Remember TSH recovery lags behind euthyroid status

81

7/1/2013 28

A 42 year old man presents with weight loss, palpitations and a sore neck. He had a viral illness about 2 weeks ago. No PMH or FH of thyroid disease. On exam: pulse: 104, T: 103F; extreme neck tenderness Labs: TSH < 0.01(0.5-4.7); FT4 1.59 (0.65-1.78) Which results are most consistent with the likely diagnosis?

• a. Low I-123 uptake, high ESR, TPO ab –
• b. TPO Ab +, high ESR, TSI +
• c. Diffusely increased I-123 uptake, TPO ab +, TSI +
• d. Irregular increased I-123 uptake, TPO-, TSI -

Case #13a Case #13b

What is the best treatment for this patient? a)Methimazole and a beta-blocker b)I-131 ablation c)NSAIDs, beta-blocker and time d)PTU and a beta-blocker e)Surgery

83

A 75 year old man is referred for a palpable right thyroid nodule. He has no family history of thyroid cancer or history of radiation exposure. TSH = 3.5 (0.45-4.20) The next step is to

• a. Place patient on L thyroxine suppressive

treatment

• b. Refer him to a thyroid surgeon
• c. Obtain a fine needle aspiration biopsy
• d. Arrange for a radionucleotide uptake scan

Case #14

7/1/2013 29

Thyroid Nodule Evaluation

• Check TSH, if suppressed get I-123 scan

to rule out toxic nodules

• Biopsy with FNA all palpable nodules in

euthyroid or hypothyroid patients

• Standard of care is ultrasound guided FNA

in most instances

• Criteria for FNA of incidentally found

nodules are in flux

• > 1 cm solid, hypoechoic nodule or palpable
• Microcalcifications, increased vascularity,

irregular are worrisome US features

Thyroid Cancer

• Differentiated thyroid cancers (90%):

Papillary, follicular, excellent prognosis.

• Medullary (5%): Tumor of parafollicular cells.

Secretes calcitonin. Associated with RET-gene mutation

• familial medullary thyroid cancer
• MEN 2A
• MEN 2B
• Anaplastic: very poor prognosis.

75 yo man is in the ICU with urosepsis complicated by hypotension, aspiration pneumonia. Patient intubated getting pressors. Thyroid function tests are obtained because patient is obese. LABS: TSH 1.0 (0.45-4.2) FT4 0.75 ng/dl (0.8-2) T3 52 mcg/dl (70-132) Which of the following is the most likely explanation of these test results?

• A. Pituitary tumor
• B. Hashimoto’s thyroiditis
• C. Myxedema
• D. Severe nonthyroidal illness

Case #15

7/1/2013 30

75 yo man is in the ICU. Patient improves considerably over the next

• week. Are the following labs are consistent with your diagnosis?

LABS INITIAL: TSH 1.0 (0.45-4.2) FT4 0.75 ng/dl (0.8-2) T3 52 mcg/dl (70-132)

Case #15

LABS ONE WEEK LATER: TSH 22 (0.45-4.2) FT4 1.2 ng/dl (0.8-2) T3 102 mcg/dl (70-132)

Euthyroid Sick Syndrome

• Also known as non-thyroidal illness
• Severely ill patients
• Most common abnormality is low T3
• Low T4 suggests very poor prognosis
• TSH levels can be anywhere
• Low-normal acutely
• Can be frankly elevated in recovery phase
• Treatment with thyroid hormone has not been

shown to be of benefit

• Try and avoid getting TFTs in hospitalized

patients A 62 yo man with a history of prostate cancer is referred because on routine laboratories, he was noted to have a serum calcium of 10.8 mg/dL (8.7- 10.1). He denies constipation, abdominal discomfort, confusion or a history of renal stones. What laboratory tests would you order next?

• a. PTHrP
• b. PTH
• c. calcium, phosphorus, and PTH
• d. 25 hydroxy vitamin D and PTH
• e. 1,25 di-hydroxy vitamin D and PTH

CASE# 16

7/1/2013 31

Calcium/PTH

91

PTH 95 H (10-65) Ca 8.6 (8.5-10.1) Phos 2.4 (2.4-4.6) PTH 95 H (10-65) Ca 10.5 H (8.5-10.1) Phos 2.4 (2.4-4.6) PTH 2 L (10-65) Ca 12.5 H (8.5-10.1) Phos 5.6 H (2.4-4.6) PTH 2 L (10-65) Ca 12.5 H (8.5-10.1) Phos 2.4 (2.4-4.6) a) Primary hyperparathyroidism b) vitamin D deficiency c) vitamin D intoxication d) malignancy/high PTHrP

Calcium/Phosphorus

• PTH

 Ca,  Phos

• Vitamin D

 Ca,  Phos

• HYPOPARA
• Low calcium, high phosphorus
• Vitamin D deficiency
• Low calcium, low phosphorus

92

Hypercalcemia: Clinical

• “Psychic moans, abdominal groans, stones

and bones”

• Confusion, fatigue etc
• Constipation, abd. pain
• Nephrolithiasis, renal insufficiency
• Osteoporosis, osteitis fibrosa cystica (fractures,

cysts, severe bone resorption)

• 85% pts asymptomatic

7/1/2013 32

Hypercalcemia - Differential

• Primary Hyperparaparathyroidism
• Malignancy (inpatient/acute)
• Via PTHrp secretion
• Osteolytic lesions (breast cancer, liquid tumors)
• Vitamin D intoxication (high phosphorus)
• Granulomatous disease, Lymphomas (increased

1,25 D)

94

Primary Hyperparathyroidism

•  PTH,  Ca,  Phos
• 0.4% women over 60; 2-3Xs the rate in

men

• Single adenoma 80%, rest hyperplasia
• Associated with MEN1, MEN 2A,

isolated familial hyperparathyroidism

Case #17

68 yo Philippino man with DM2, CHF, CAD, CRI, BPH admitted for fatigue, weakness, constipation. ROS: 20 lb weight loss, abd pain, constipation Called by the lab with a panic value of Ca++ 12.9

96

7/1/2013 33

Case #17 - Other labs

3/04

Calcium 12.9 Albumin 4.3

12/03

Calcium 8.0 Albumin 3.9

Acute hypercalcemia in a hospitalized patient so most likely diagnosis is?

97

Acute Hypercalcemia

• Signs/Symptoms
• Altered mental status
• Nausea/vomiting
• Dehydration
• Bradyarrhythmias/BBB/HB/etc.
• Treatment
• If severe metastatic cancer, assess prognosis/need to

treat

• Fluids, fluids, fluids NS, 2-4L/day for 2 days
• Can augment with furosemide but only if giving enough

fluid/concern re fluid overload

• In renal failure might need dialysis
• IV Bisphosphonates
• Treat the underlying problem

98

Case# 17 More labs

Calcium 12.9 Albumin 4.3 Phosphorus 4.7 (2.5-4.5)

99

At this point what would you expect the PTH and Vitamin D to be? a) Low PTH, High Vitamin D b) Low PTH, Low Vitamin D c) High PTH, Low Vitamin D d) High PTH, Normal Vitamin D

7/1/2013 34

Case# 17 More labs

Calcium 12.9 Albumin 4.3 Phosphorus 4.7 (2.5-4.5) Cr 2.7 PTH 9 (10-65) PTHrp <0.7 (<1.3) SPEP, UPEP normal Chest CT – bilat small effusions, 3 tiny R lung nodules PSA 10, nl prostate bx Bone scan negative 25 OH D 13

What else to order?

100

Case #17 More Labs

• 1,25 D 62 (15-60)
• Differential:
• Sarcoid
• Lymphoma
• Tb
• Other granulomatous disease
• Patient went to OR for GIB and found to

have tumor like mass encasing duodenum and hepatic hilum with extensive abdominal carcinomatosis that was AFB staining positive on pathology c/w TB.

101

Case#18

Covering med consult. Called by surgery intern who got a panic value for low calcium at 6.6. They are running to a trauma and don’t know anything about the patient. Please help. What to do first? History? Exam? Which labs would you get?

102

7/1/2013 35

More Labs

• Sleep Scenario
• ICU patient, ARDS, MOF, really sick
• Albumin 2.0
• Calcium 6.7, corrected Calcium 8.3
• Ionized calcium 1.13 (1.12-1.32)
• For every decrease in albumin by 0.5 mg/dl,

increase calcium 0.4 mg/dl

103

No Sleep Scenario

• 7/23/10
• Albumin 3.3
• Calcium 6.6, corrected 7.2
• Ionized calcium 1.00 (1.12-1.32)
• 7/14/10
• Calcium 13.2
• Albumin 4.3
• What now?
• What to check, examine?

104

Case 18 Hypocalcemia

• Patient reports peri-oral tingling, cramping

right hand

• Exam: a big neck wound from recent surgery

with bandage in place; + Chvostek sign, hand with tetany

• You get an ECG which most likely shows?

105

a) Sinus tachycardia b) Sinus bradycardia c) First degree heart block d) QT prolongation

7/1/2013 36

Treatment of Severe Hypocalcemia

• Call endocrine.
• IV calcium gluconate (usually a drip)
• Treat Mg deficiency
• Calcitriol (1,25OH Vitamin D)
• Oral calcium

106

A 46 year old woman presents with chronic fatigue and cramps in her hands and feet. She has a hx of pernicious anemia and hypothyroidism due to Hashimoto’s. On examination, she has a + Chvostek’s sign. Her serum calcium is 7.9 mg/dl (8.7- 10.1) and her serum phosphorus level is 4.1 (2.4-4.6) mg/dl The most likely diagnosis is:

• a. Vitamin D deficiency
• b. Hypoparathyroidism
• c. Renal failure
• d. Hypoalbuminemia

Case# 19

A 56 yr old African American man is referred because a DXA scan demonstrated T score of -2.8 at the spine. He complains of aches in his upper and lower extremities. There was no history of fractures

• r kidney stones. He has lactose intolerance, and is not on any

medications or supplements. LABS: Calcium 8.9 (8.7-10.1), phosphorus 2.4 (2.4-4.6) What would be a reasonable next step?

• a. Give a bisphosphonate, calcium and vitamin D
• b. Check 25 OHD and testosterone level
• c. Check a 1, 25 OHD level
• d. Give Raloxifene, calcium and Vitamin D
• e. Give Calcitonin, calcium and Vitamin D
• f. Check a PTH

Case# 20

7/1/2013 37

Secondary osteoporosis

• Vitamin D deficiency
• Hypogonadism
• Primary hyperparathyroidism
• Tobacco, alcohol use
• Malignancy
• Hyperthyroidism
• Drugs: glucocorticoids, anticonvulsants,

immunosuppressants, tenofovir, lithium, chemotherapy

• Inflammatory disease (RA, IBD)

Male Osteoporosis

• We currently use same definitions as for

women:

• Osteopenia: T-score < -1 and > -2.5
• Osteoporosis: T-score < -2.5
• Search for causes of secondary osteoporosis

in male osteoporosis (2/3rds will have)

• Treatment options same as for women:
• Bisphosphonates
• Calcium 1500 mg/d + 800-1000 IU Vit D/day
• Teriparatide
• Calcitonin esp. for acute vertebral fracture pain

Male Hypogonadism DDx

• Hypothalamic/pituitary Dz: T & nl- LH/FSH
• Idiopathic hypogonadotrophic hypogonadism
• Panhypopituitarism
• LH and FSH deficiency: if associated with anosmia 

Kallmann’s

• Primary Gonadal Failure: T & LH and FSH
• ****Klinefelter’s Syndrome: XXY karyotype
• Testicular damage: mumps orchitis, irradiation, alcoholism,

lead poisoning, chemorx

• Andropause: gradual decrease in testicular function after

age 50

• Anorchia
• Androgen synthesis defects
• Androgen action defects:  T &  LH & nl FSH
• Complete or incomplete androgen insensitivity

7/1/2013 38

Syndromes of Hormone Excess

The fun stuff

• FIRST – establish the biochemical

abnormality

• Always assess hormones in relation to their

appropriate effect

• Image ONLY after establishing the

biochemical diagnosis

112

• a. Repeat the prolactin in 3 months
• b. Refer to neurosurgery
• c. Initiate treatment with bromocriptine or cabergoline
• d. Check a TSH and Free T4 level

A 32 yr old woman presents to her gynecologist with a 6 month history of fatigue, some weight gain and amenorrhea. Exam reveals dry skin, coarse hair and delayed DTR relaxation and galactorrhea. LABS: Prolactin 58 ng/ml (<20); u preg negative Pituitary MRI: enlarged pituitary gland without any obvious adenoma What is the appropriate next step?

CASE #21 Hyperprolactinemia

• Physiologic:
• Pregnancy
• Lactation or even nipple stimulation
• Pathologic:
• Pituitary tumors – mostly microadenomas
• Pituitary stalk lesions
• Hypothyroidism
• Chronic kidney disease
• Hypothalamic lesions
• Pharmacologic:
• Estrogen
• Psychiatric meds (antipsychotic dopamine

antagonists, SSRIs, TCAs)

• H2 blockers (ranitidine, cimetidine)

7/1/2013 39

Hyperprolactinemia

• Diagnosis:
• Elevated prolactin
• Normal TFT’s and negative pregnancy test
• Assess medication use
• MRI of pituitary
• Treatment: medical with dopamine

agonists (bromocriptine/cabergoline) in most cases

A 63 yo woman is referred for evaluation of hypertension. Recently had severe hypertensive episode during ocular surgery, which responded poorly to medications. Also reports worsening HA. PMH only notable for hypertension for many years. LABS: Plasma metanephrines were 3X normal value. What anti-hypertensive do you NOT want to give initially to this patient?

• a. Beta-blocker
• b. Calcium channel blocker
• c. ACE-I
• d. Alpha-blocker

CASE #22 Pheochromocytoma

• Symptoms:
• Headaches
• Diaphoresis
• Palpitations
• Tremor, anxiety, nausea, vomiting, fatigue
• Abdominal or chest pain
• Weight loss
• Episodic throbbing in the chest, trunk and head
• Cold hands and feet

7/1/2013 40

Pheochromocytoma

• First – make BIOCHEMICAL dx:
• 24-hr urinary metanephrine and normetanephrine
• plasma free metanephrine and normetanephrine
• 24 hr urinary catecholamines
• VMA/plasma catechols – NOT USED
• Elevations 1-2X normal common in sick patients
• Second – Image:
• CT or MRI of the adrenal
• Third – OR with appropriate pre-medication

A 35 year old man with one yr h/o hypertension. Despite treatment with blocker, calcium channel blocker and ACE inhibitor, his blood pressure remains elevated. EXAM: 210/110; Fundi – grade III retinopathy. PMH: none FH: no h/o hypertension LABS: Na: 142, K: 3.3, Creatinine: 1.2 What is the next step?

• a. Plasma renin activity and plasma aldosterone concentration
• b. CT scan of the adrenals
• c. 24 hr urine for VMA
• d. 24 hr urine for catecholamines and metanepharines

CASE #23 Primary Aldosteronism

• Accounts for 0.5-10% of HTN cases
• Hypertension
• Hypokalemia
• May be absent
• Exacerbated by diuretics
• Mild alkalosis on laboratory tests

7/1/2013 41

Primary Aldosteronism: Dx

• Many medications interfere with testing
• Screening:
• Must first replete potassium
• Plasma aldosterone (PA)

Plasma Renin Activity (PRA)

• But aldosterone must be high (>15 ng/dL)
• Confirmatory test:
• Salt load: 1 g NaCl tid for 3 days
• 24 hr urine aldosterone>12 mcg/24 hr with

concomitant 24 hr urine Na>200 mmol/d >20-25  suggestive

Primary Aldosteronism

• Imaging with CT
• Unilateral lesion (adrenal vein sampling?)
• Bilateral Hyperplasia, or no lesion seen:
• Adrenal vein sampling to lateralize source of

aldosterone excess

• Management:
• Unilateral lesion  resect
• Bilateral hyperplasia or no lesion  medical rx

with spironolactone or eplerenone A 38 year old man had an abdominal CT scan for evaluation of right abdominal pain. An incidental 4 cm left adrenal mass was discovered. The patient is otherwise healthy. What is the next step?

• a. Referral to a surgeon for laparoscopy adrenalectomy
• b. FNA of lesion to determine pathology
• c. Repeat CT scan in 6 to 12 months to make sure that

the mass has not increased in size.

• d. None of the above

CASE #24a

7/1/2013 42

Adrenal Incidentalomas

• Very common (6% on autopsy;4% on CT)
• Prevalence increases with age
• Hormone secreting?
• Cortisol
• Aldosterone
• Catecholamines
• Androgens
• Other weird stuff
• Malignant or infiltrative?
• Metastatic disease
• Adrenal carcinoma
• Granulomatous disease

Case 24b

A 38 year old man had an abdominal CT scan for evaluation of right abdominal pain. An incidental 4 cm left adrenal mass was discovered. The patient is otherwise healthy with normal exam and no symptoms. What biochemical testing below would be appropriate?

125

a) Plasma catecholamines, aldosterone and renin, and am cortisol b) Plasma catecholamines, aldosterone and renin, and 1 mg dexamethasone suppression test c) Plasma metanepharines and 1 mg dexamethasone suppression test d) Urine metanepharines, 1 mg dexamethasone suppression test, aldosterone and renin e) 1 mg dexamethasone suppression test f) No testing required

Adrenal Incidentalomas

very rough numbers

• >80% non-functioning adenoma
• 5% pheo
• 5% cortisol secreting (subclinical)
• 1% aldosterone secreting (maybe higher

now)

• < 5 % cancer (adrenal carcinoma or

metastatic disease)

• < 5% other

126

7/1/2013 43

Incidentaloma Evaluation

All patients:

Screen for pheochromocytoma Screen for Cushing’s syndrome (1 mg overnight dexamethasone suppression test)

Patients with hypertension:

Screen for primary aldosteronism

Imaging Characteristics

Low density, high washout, likely benign 4 cm more worrisome for malignancy

BENIGN ON IMAGING DOESN’T MEAN NO FURTHER EVALUATION NEEDED

A middle aged woman is referred with thirst, polydipsia and

• polyuria. She was in a car accident 9 months previously and

has limited mobility since then due to a hip fracture. She also reports taking lithium for BAD and recently Examination is normal - BP 120/80 without postural changes. Her 24 hr urine volumes range from 7 to 12 liters. LABS: Na: 145, K: 3.5 glucose: 100, plasma osmolality: 295 mOsm/kg (285-293); Urine: osmolality 50 mOsm/kg (300-900 mOsm/kg), no glucose What is the appropriate next step?

• a. MRI of the pituitary gland
• b. 10 mg DDAVP treatment once or twice a day
• c. Water restriction to 2-3 liters/day
• d. Thiazide diuretic
• e. Evaluate urine osmolality after a dose of IV DDAVP

CASE #25 Diabetes Insipidus (DI)

• Hallmarks
• ↓ ADH concentration or action
• Dilute urine (SG<1.005, osmolality <200)
• Eunatremia if free access to water
• Hypernatremia/hyperosmolar otherwise
• Central DI – deficient secretion of ADH by

posterior pituitary gland

• Nephrogenic DI – resistance to ADH actions
• Primary polydipsia (Psychogenic Polydipsia)

7/1/2013 44

Diagnosing etiology of polyuria

Test Central DI Nephrogenic DI Primary Polydipsia Random plasma osmolality

Nl- Nl- 

Random urine osmolality

  

Urine osmolality during water deprivation No Change No Change



Urine osmolality after IV DDAVP



No Change



Plasma ADH



Normal to 



SOME EXTRA THINGS

131

MEN 1 – the three Ps

• HyperParathyroidism – hyperplasia of

parathyroids

• EnteroPancreatic tumors – gastrinomas,

insulinomas

• Pituitary tumors – prolactinoma, GH,

nonfunctional, ACTH

• Others – carcinoid, adrenal adenomas,

subcutaneous lipomas, facial angiofibromas

• Autosomal dominant, MENIN gene mutation

7/1/2013 45

MEN 2A

• Medullary carcinoma of the thyroid
• Pheochromocytoma
• Hyperparathyroidism
• Mutations in RET proto-oncogene
• Autosomal dominant

MEN 2B

• Medullary carcinoma of the thyroid
• Pheochromocytoma
• Marfanoid habitus
• Mucosal neuromas
• Ganglioneuromatosis of the bowel
• Mutations in RET protooncogene
• Autosomal dominant

APS I APS II

Alternative Name APCED (Autoimmune

Polyendocrinopathy-candidiasis- ectodermal dystrophy syndrome)

Schmidt’s Syndrome Genetics Autosomal Recessive Mutations in AIRE (autoimmune regulator gene) Linked to HLA-DR3 or HLA- DR4 Female-to-male ratio = 3:1 Endocrine manifestations Hypoparathyroidism a – 90% Adrenal Insufficiency a – 60%

Hypogonadism – 45% Hypothyroidism – 12% Type 1 DM

Adrenal Insufficiency – 70% Hypothyroidism b – 70% Type 1 DM b – 50%

Hypogonadism – 5-50% Hyperthyroidism

Non- endocrine Manifestations Mucocutaneous candidiasis

a – 75%

Malabsorption – 25% Alopecia – 20% Pernicious Anemia – 15% Autoimmune hepatitis – 10% Vitiligo – 4% Pernicious Anemia – 15% Vitiligo – 4% Celiac disease – 3% Autoimmune hepatitis a: dx requires 2 of these 3 dz b: dx requires at least 2 of these 3 dz

7/1/2013 46

SOME ANSWERS

1E,2B,3B,4F,5BD,6D,7D,8C,9aA,9bA,10C, 11aA,11bE,12D,13aA,13bC,14C,15D, 16C,17A, 18D,19B, 20B, 21D, 22A, 23A, 24aD, 24bC, 25E

136