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7/1/2013
1
ENDOCRINE
Elizabeth J. Murphy, MD, DPhilAssociate Professor of Clinical Medicine,
UCSFChief, Division of Endocrinology, SFGH
July 8, 2013
Endocrine Resources
UpEndocrine Society Guidelineshttp://www.endo-society.org/guidelines/Current-Clinical-Practice-Guidelines.cfm:
o Pituitary Incidentalomao Diagnosis and treatment of hyperprolactinemiao Testosterone Therapy in Adult Meno Primary Aldosteronismo Cushing’s Syndromeo Hirsutism in Premenopausal Womeno Post-menopausal Hormone Therapyo Vitamin D deficiencyo Adult Growth Hormone Deficiencyo Post-Bariatric Surgery Managemento Androgen Therapy in Womeno Endocrine Treatment of Transsexual Persons
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Diabetes Resources
Diabetes Care January Supplement: http://professional.diabetes.org/CPR_Search.aspx
o American Diabetes Association Clinical Practice Recommendationso Standards of Medical Care in Diabetes
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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)
o Anterior pituitaryo Posterior pituitaryo Hypothalamic disorderso Polyglandular disorderso (Hypoglycemia not due to insulinoma)o (Nutritional disorders)o (Women’s health endocrine issues)o (Hypertension)o (Ovarian Disorders/Female Reproductive Health)
(Lipids 2-4)
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Case #1
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64 yom with HTN, CAD, CHF, and hyper-TGwith a prior episode of pancreatitis is found tohave a random plasma glucose of 205 mg/dlon labs obtained for another reason. An A1Cwas obtained and was 6.4%. The patient hasno symptoms such as polyuria, polydipsia orpolyphagia.
Does he meet the criteria for the diagnosis of diabetes?
Diagnosis of DiabetesMeeting 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 oral 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.
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Diagnosis of DiabetesMeeting 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 oral 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.
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Pre-diabetesCategories 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 %
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Case #1
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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%, 140 111 284.5 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 gallopExt: tr edema, feet with no ulcerations, sensation intact
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Case #1
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Which choice below would be the most appropriate initial therapy for this patient’s DM2?
a) metforminb) glyburidec) colesevelamd) pioglitazonee) glipizidef) diet and exercise alone
Certainties in Glucose Lowering Treatment
LOWERING A1C PREVENTS
MICROVASCULAR COMPLICATIONS
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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
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SulfonylureasGlinides
Sulfonylureas
Stimulates insulin release Lower A1C 1-2% Advantages
o Long history of use
Disadvantageso Weight gain ( 2 kg)o Hypoglycemiao Earlier pancreatic failure?o Increased CV mortality?
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Sulfonylureas Glyburide
o Micronase, Diabeta, Glynase; Glucovance with metformino 1.25, 2.5, and 5 gm tabs QD or BID, max 20 mg a dayo Non-linear dose response, more effect of 1.25 to 2.5 than 10 to 20 o Caution in renal failure and in elderly
Glipizide o Glucotrol, Glucotrol XL; Metaglip with metformino 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 over 10 mg
Glimepirideo Amaryl; Avadaryl with rosiglitazone; Duetact with pioglitazoneo 1, 2, 4 mg tabs, max 8 mg dailyo Caution in renal failure, liver failure, elderly
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Typically discontinued when patient on basal and prandial insulin
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Glinides
Enhances insulin release Lowers A1C 1-1.5% Advantages:
o Short acting, take 15 minutes prior to meal and skip dose if meal is missed
Disadvantageso Short acting, TID dosingo Hypoglycemiao No head to head comparison with first generation SUo Expensiveo Metabolized by CYP2C8 and CYP3A4
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Glinides
Nateglinide (Starlix)o 60 and 120 mg tabso 30-360 mg before meals
Repaglinide (Prandin)o Better A1C loweringo 0.5, 1 and 2 mg tabso 0.5-4 mg before meals
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SulfonylureasGlinides
Biguanides
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Biguanides (Metformin)
Improves hepatic insulin sensitivity Lowers A1C 1.5-2% Advantages:
o Weight loss (0-2 kg)o Lowers TG, LDLc; Increases HDLco No hypoglycemia when used aloneo Inexpensiveo CVD benefit
Disadvantageso Majority of patients with GI SEo Risk of lactic acidosiso Impaired B12 absorption (5% or more of patients)
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Metformin
metformin (Glucophage, Glucophage XR)o 500, 850, 1000 mg tabs. Start 500 mg daily with
meals, increase q week, max dose 2550 mg (850 mg TID)
o 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
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Metformin - Contraindications
Decreased renal function (check Cr q yr)o Cr < 1.5, meno Cr < 1.4, womeno “Abnormal CrCl”
During IV contrast studies Age ≥ 80 unless renal fn wnl Hypoxemia Excessive alcohol consumption Impaired liver function CHF (now more relaxed contraindication)
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SulfonylureasGlinides
Bile Acid Sequestrants
Biguanides
Bile Acid Sequestrants
Approved for years for cholesterol lowering Lower A1C 0.4% Advantages:
o Lowers LDLco Presumed CVD benefito Not absorbed
Disadvantages:o GI SE, constipationo Lots of pillso Increases TG, theoretical risk of pancreatitis
Colasevelam HCL (Welchol)o Contraindicated
• TG > 500 mg/dl or history of TG induced pancreatitis, caution >300 mg/dl
• Bowel obstruction Cholestyramine (Questran)
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SulfonylureasGlinides
Bile Acid Sequestrants
PPAR- Agonists
PPAR- Agonists
Biguanides
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PPAR- Agonists
Activate PPAR-, improve insulin sensitivity Lower A1C 0.5-1.4% CVD risk unclear (possibly increased rosi, decreased
pio) Advantages:
o Improved lipid profile with decrease in TG, increase in HDL (pioglitazone only)
o No hypoglycemia when used alone
Disadvantages:o Weight gain ( 2 kg)o Fluid retentiono Two-fold increased risk of CHFo Increased fracture risko Pioglitazone associated with increased incidence of bladder
cancer25
PPAR- Agonists
Thiazoladinediones - PPAR- agonistso rosiglitazone (Avandia; AvandaMet with metformin,
Avandaryl with glimepiride) o pioglitazone (Actos;ActoplusMet with MF, Duetact
with glimepiride)
Use –o Used in combination with metformin or sulfonylureao Fluid retention worse when used in combination
with insulin (consider stopping when insulin started)o Extreme caution in CHF
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Case #1
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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%, 140 111 284.5 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 gallopExt: tr edema, feet with no ulcerations, sensation intact
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Case #1
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Which choice below would be the most appropriate initial therapy for this patient’s DM2?
a) metforminb) glyburidec) colesevelamd) pioglitazonee) glipizidef) diet and exercise alone
Case #2
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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 hypoglycemiab) should have been done with renal dosingc) was not related to the increased number of URIsd) typically results in a 1-2 kg weight loss
DM MEDS: metformin 1 gm BIDglyburide 10 mg dailysitagliptin 100 mg daily
LABS: A1C = 7.0%, 140 111 284.5 28 1.9
CrCl is 45 ml/min
SulfonylureasGlinidesGLP-1 AnaloguesDPPIV Inhibitors
Bile Acid SequestrantsGLP-1 AnaloguesDPPIV Inhibitors
PPAR- Agonists
PPAR- Agonists
Biguanides
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The Incretin Effect
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Incretins
Hormones released by the GI tract that effect glucose metabolism Include:
o GIP – Gastric Inhibitory Peptide OR Glucose-dependent Insulinotropic Peptide
o GLP-1 – Glucagon-Like Peptideo GLP-2
Half-life of < 5 minutes Inactivated by DPPIV
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Incretin Hormones GIP
o Secretion triggered by glucose and fat and enhances insulin secretion from beta-cells in glucose dependent manner
o Accounts for about 50% of incretin activity
o Stimulates LPL activity in adipocytes
GLP-1
o Enhances insulin secretion from the beta cells in a glucose-dependent manner
o Inhibits postpranidal glucagon secretion from the alpha cells in a glucose-dependent manner
o Slows gastric emptying
o Reduces food intake and body weight? Appetite suppression?
o Increases beta-cell mass and function?
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GLP-1 as a Therapeutic Target
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Longer Acting GLP-1
Heloderma suspectumGila 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:o Weight loss (2-3 kg); less hypoglycemia
Disadvantages:o Injectable
o GI Side Effects (nausea, vomiting)
AE:o Pancreatitis, medullary thyroid cancer?
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Long Acting GLP-1 Analogues
Exenatide (Byetta/Bydureon)o BID SC injection before am and evening mealo Q week SC Injection (LAR)
Liraglutide (Victoza)o QD SC injection any time of day
Albiglutide (Syncria) Taspoglutide
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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:o Oral, weight neutral
• Disadvantages:o Not great A1C lowering, expensive
• AE:o Small, “not clinically relevant” increases in WBC due to an
increases in neutrophils (0.2)
o Increased incidence of URI, nasophyrngitis,
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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
once daily; renal dosing Linagliptin (Tradjenta) 5 mg tabs; no renal dosing Vidagliptin (Galvus) Alogliptin Dutogliptin Gemigliptin
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You are asked to see a 72 year old man with a CHF with previously well controlled DM2, but now a HbA1c of 9.1%. He is on glyburide and metformin at max doses.
What is the most appropriate change to his regimen?
a. Add pioglitazoneb. Add basal insulin (NPH or glargine)c. Add acarbosed. Add saxagliptin
Case #3
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SulfonylureasGlinidesAmylin AnaloguesGLP-1 AnaloguesDPPIV Inhibitors
-Glucosidase InhibitorsGLP-1 AnaloguesDPPIV 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:
o No hypoglycemia when used alone; weight neutral
Disadvantages:o GI SE, flatulance; TID dosing
acarbose (Precose) - nonabsorbableo 25 mg QD up to 100 mg TID with meals
miglitol (Glyset) - absorbableo 25 mg QD up to 100 mg TID with meals
Caution with hypoglycemia, sucrose is ineffective
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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
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Case #4
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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 BIDNPH 20 units am, 10 units at bedtimeRegular 5 units before each meal
BS records:fasting 115-150 pre-lunch 85 -155pre-dinner 92 - 145bedtime 170-290
What would be the best first next step for improving A1C?a) Change NPH to glargine 24 unitsb) Change NPH to glargine 30 unitsc) Increase morning NPH dose to 25 unitsd) Increase bedtime NPH dose 15 unitse) Increase meal time R insulin dose to 8 units before each mealf) Increase dinner time R insulin to 8 unitsg) Change R to glulisine insulin
Case #4
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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 BIDNPH 20 units am, 10 units at bedtimeRegular 5 units before each meal
BS records:fasting 115-150 pre-lunch 85 -143pre-dinner 92 - 145bedtime 170-290
What would be the best first next step for improving A1C?a) Change NPH to glargine 24 unitsb) Change NPH to glargine 30 unitsc) Increase morning NPH dose to 25 unitsd) Increase bedtime NPH dose 15 unitse) Increase meal time R insulin dose to 8 units before each mealf) Increase dinner time R insulin to 8 unitsg) 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
100B L D
Normal Plasma Insulin Profile
B=breakfast; L=lunch; D=dinner
0800 18001200 2400
Insulin U/mL
Basal insulino Near-constant levels
o Important during night/between meals
o 50% or more of daily needs
Mealtime insulino Limits hyperglycemia after meals
o Rise and peak post meal
o 10% to 20% of daily needs at
each meal
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Types of Insulin Basal Insulin
o NPH, BID dosing, peaks 4-8 hrs o glargine (lantus), once daily dosing, no peak, can’t mix with
other insulinso detemir (levemir), BID dosing, no peak, can’t mix
Mealtime Insulino Regular (humalin R, novalin R), take 30 m premealo Aspart (novolog), take 5-20 m premealo Lispro (humalog)o Glulisine (apidra)
Combination Insulino 70/30 (70%N, 30% R; 70% intermediate, 30% aspart)o 75/25 (75% intermediate;25% lispro)
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0600 0800 18001200 2400 0600
Time of day
20
40
60
80
100B L D
Basal-Bolus Insulin Treatment
B=breakfast; L=lunch; D=dinner
Meal time insulin
Normal pattern
U/mL
NPHNPH at bedtime
0600 0800 18001200 2400 0600
Time of day
20
40
60
80
100B L D
Basal-Bolus Insulin Treatment
B=breakfast; L=lunch; D=dinner
Glargine
Meal time insulin
Normal pattern
U/mL
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Case #5
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54 yow was admitted with severe hyperglycemia andnewly diagnosed DM2. She was well controlled attime of discharge on glargine 40 units once daily andregular insulin 10 units before every meal. However,at discharge she informs you she refuses to take morethan two shots a day. She also tells you breakfast isher biggest meal of the day.
Which of the following are reasonable options? (multiple answers ok)a) 70/30 am and bedtimeb) NPH with R in prebreakfast and N at bedtimec) glargine with R in am/breakfast and R at dinnerd) 70/30 am and pre-dinner
Case #5
50
54 yow was admitted with severe hyperglycemia andnewly diagnosed DM2. She was well controlled attime of discharge on glargine 40 units once daily andregular insulin 10 units before every meal. However,at discharge she informs you she refuses to take morethan two shots a day. She also tells you breakfast isher biggest meal of the day.
Which of the following are reasonable options? (multiple answers ok)a) 70/30 am and bedtimeb) NPH with R in prebreakfast and N at bedtimec) glargine with R in am/breakfast and R at dinnerd) 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 agentsb. Start morning NPH or glargine, maintain sulfonylurea and
discontinue metforminc. Start bedtime NPH or insulin glargine, discontinue metformin
and continue sulfonylurea.d. Start bedtime NPH or glargine, maintain oral agents
Case #6
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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 dinnerb. Increase glyburide to 10 mg bidc. D/c glyburide and begin metformind. Add metformin to the glyburidee. Switch from glyburide to glipizide
Case #7
Case #8
55 yow with DM2, HTN and obesity complains of fatigue, depressive symptoms and weight gain
What should you check?
THYROID
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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
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Case #8
55 yow with DM2, HTN and obesity complains of fatigue, depressive symptoms and weight gainExam: 80 kg, BMI 32, dry skin
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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 usedc) 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-thyroxineo Roughly 1.4-1.8 mcg/kg/day
o Start low and go up slowly to avoid exacerbation of undiagnosed CAD
o Recheck/adjust dose in 6-8 weeks
o Calcium, iron interfere with absorption
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Case #8
55 yow with DM2, HTN and obesity complains of fatigue, depressive symptoms and weight gain
Exam: 80 kg, BMI 32, dry skin
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TSH 8.9 H (0.45-4.20)
TSH 12 H (0.45-4.20)FT4 1.1 (0.65-1.78)
Subclinical HypothyroidismWhat now?
Subclinical HypothyroidismDeciding When to Treat
Reasons to treato Prevent progression to frank hypothyroidism
• Risk greater if +TPO antibodies
o Improve symptomso Improve lipidso Long term treatment benefit inconclusive
Reasons not to treato Long term treatment benefit inconclusiveo Expenseo Could do harm
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Subclinical HypothyroidismDeciding 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)
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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)Yesb)No
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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 insufficiencyb) Unrelated appendicitisc) Gave to high a starting dose of l-thyroxined) Allergic reaction to l-thyroxine
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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.
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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:o Autoimmune destructiono Gland infiltration or destruction
• Metastases, lymphoma• Hemorrhage• Amyloid, hemochromatosis• Infections
o Drugs: ketoconazole, etomidateo Rare: congenital adrenal hyperplasia, adrenal
leukodystrophy
Secondary AI:o Iatrogenic: glucocorticoids & anabolic steroidso Pituitary or hypothalamic tumors
Symptoms: Weakness, fatigue, anorexia, weight loss, nausea, vomiting, diarrhea, unexplained abdominal pain, postural lightheadedness Labs:
o ↓ Na+, ↑ K+
o eosinophiliao mild metabolic acidosiso ↑ Ca++
Adrenal Insufficiency
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Adrenal InsufficiencyDiagnosis
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
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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?
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Thyroid Lab Testing
Total T4/Free T4 indexo Inferior tests for assessing thyroid function and used
only in special situtations; Free T4 preferred
Free T3o Can be preferentially elevated in toxic noduleso Most useful in a patient with a suppressed TSH and
normal free T4 (subclinical hyperthyroidism)
anti-thyroglobulin antibodies
o Least useful in diagnosing thyroid autoimmunity
o Used to determine validity of thyroglobulin assay
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Thyroid Lab Testing
TSH receptor antibodies
o 80-99% sensitive for Graves’
o Doesn’t differentiate between activating and blocking antibodies
TSI (thyroid stimulating immunoglobulin)
o Bioassay (results as a % of control)
o 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)
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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’ diseaseb)Toxic nodulec)Thyroiditisd)TSH secreting tumor
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HyperthyroidismDifferential Diagnosis Graves’ Disease (60-80%) Toxic Nodules
o Toxic Multi-Nodular Goiter o Toxic Adenoma
Thyroiditiso Painless/silent thyroiditis – transient thyrotoxicosiso Postpartum thyroiditis – as above, post partumo Subacute thyroiditis – fever, tender thyroid, viral
Othero Thyrotoxicosis factitia
o Struma Ovarii
o Hydatiform mole, choriocarcinoma
o TSH secreting tumor
o Pituitary resistance to thyroid hormone
o Thyroid cancer
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HyperthyroidismGraves 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), ophthalmopathy
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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%)
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Which diagnoses would be consistent with this scenario? More than one result is possible.
a)Toxic noduleb)Thyroiditisc)Graves’ diseased)TSH secreting tumore)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)
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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 115/72HEENT: PERRL, EOMI, + scleral injection, +proptosis bilat, periorbital edema Thyroid: smooth, firm, approximately 3x nl size, no nodules palpated, non-tender, + bruitExt: + tremorSkin: warm, smooth, diaphoretic, no rash
Labs:TSH < 0.01 H Are more lab testsFT4 4.59 H needed? Ultrasound?
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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 115/72HEENT: PERRL, EOMI, + scleral injection, +proptosis bilat, periorbital edema Thyroid: smooth, firm, approximately 3x nl size, no nodules palpated, non-tender, + bruitExt: + tremorSkin: warm, smooth, diaphoretic, no rash
Labs:TSH < 0.01 H Are more lab testsFT4 4.59 H needed? Ultrasound?
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Case #11
29 yow hyperthyroid with Graves’ disease.
NKDAMeds: nonePMH: none
Need to treat.
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HyperthyroidismTreatment Options
Surgeryo Not very common in US
Radioactive Iodine (I-131) Ablationo More popular in the US than antithyroid drugso Treatment of choice for nodules, toxic multinodular goiter
Medicationo PTU – oldest, black box warning for liver failure; use in
pregnancy or allergy to methimazole, can get agranulocytosis
o Methimazole – Liver failure, rash, agranulocytosis
o Beta-blockers – Use any, may need more frequent dosing
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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 methimazoleb. Iodidec. Corticosteroidsd. Radioactive iodinee. -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
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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-blockerb)I-131 ablationc)NSAIDs, beta-blocker and timed)PTU and a beta-blockere)Surgery
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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 surgeonc. Obtain a fine needle aspiration biopsyd. Arrange for a radionucleotide uptake scan
Case #14
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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 fluxo > 1 cm solid, hypoechoic nodule or palpableo 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
o familial medullary thyroid cancero MEN 2Ao 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 tumorB. Hashimoto’s thyroiditisC. MyxedemaD. Severe nonthyroidal illness
Case #15
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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
o Low-normal acutelyo 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. PTHrPb. PTHc. calcium, phosphorus, and PTHd. 25 hydroxy vitamin D and PTHe. 1,25 di-hydroxy vitamin D and PTH
CASE# 16
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Calcium/PTH
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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
HYPOPARAo Low calcium, high phosphorus
Vitamin D deficiencyo Low calcium, low phosphorus
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Hypercalcemia: Clinical
“Psychic moans, abdominal groans, stones and bones”
o Confusion, fatigue etco Constipation, abd. paino Nephrolithiasis, renal insufficiencyo Osteoporosis, osteitis fibrosa cystica (fractures,
cysts, severe bone resorption)
85% pts asymptomatic
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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)
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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
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Case #17 - Other labs
3/04Calcium 12.9Albumin 4.3
12/03Calcium 8.0Albumin 3.9
Acute hypercalcemia in a hospitalized patient so most likely diagnosis is?
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Acute Hypercalcemia
Signs/Symptomso Altered mental statuso Nausea/vomitingo Dehydrationo Bradyarrhythmias/BBB/HB/etc.
Treatmento If severe metastatic cancer, assess prognosis/need to
treato Fluids, fluids, fluids NS, 2-4L/day for 2 dayso Can augment with furosemide but only if giving enough
fluid/concern re fluid overloado In renal failure might need dialysiso IV Bisphosphonateso Treat the underlying problem
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Case# 17 More labs
Calcium 12.9Albumin 4.3Phosphorus 4.7 (2.5-4.5)
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At this point what would you expect the PTH and Vitamin D to be?
a) Low PTH, High Vitamin Db) Low PTH, Low Vitamin Dc) High PTH, Low Vitamin Dd) High PTH, Normal Vitamin D
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Case# 17 More labs
Calcium 12.9Albumin 4.3Phosphorus 4.7 (2.5-4.5)Cr 2.7PTH 9 (10-65)PTHrp <0.7 (<1.3)SPEP, UPEP normalChest CT – bilat small effusions, 3 tiny R lung nodulesPSA 10, nl prostate bxBone scan negative25 OH D 13
What else to order?
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Case #17 More Labs
1,25 D 62 (15-60) Differential:
o Sarcoido Lymphomao Tbo 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.
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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?
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More Labs
Sleep Scenarioo ICU patient, ARDS, MOF, really sicko Albumin 2.0o Calcium 6.7, corrected Calcium 8.3o Ionized calcium 1.13 (1.12-1.32)
For every decrease in albumin by 0.5 mg/dl, increase calcium 0.4 mg/dl
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No Sleep Scenario
7/23/10o Albumin 3.3o Calcium 6.6, corrected 7.2o Ionized calcium 1.00 (1.12-1.32)
7/14/10o Calcium 13.2o Albumin 4.3
What now?What to check, examine?
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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?
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a) Sinus tachycardiab) Sinus bradycardiac) First degree heart blockd) QT prolongation
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Treatment of Severe Hypocalcemia
Call endocrine. IV calcium gluconate (usually a drip) Treat Mg deficiency Calcitriol (1,25OH Vitamin D) Oral calcium
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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 deficiencyb. Hypoparathyroidismc. Renal failured. 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 or 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 Db. Check 25 OHD and testosterone levelc. Check a 1, 25 OHD leveld. Give Raloxifene, calcium and Vitamin De. Give Calcitonin, calcium and Vitamin Df. Check a PTH
Case# 20
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Secondary osteoporosis
Vitamin D deficiency Hypogonadism Primary hyperparathyroidism Tobacco, alcohol useMalignancy Hyperthyroidism Drugs: glucocorticoids, anticonvulsants,
immunosuppressants, tenofovir, lithium, chemotherapy Inflammatory disease (RA, IBD)
Male Osteoporosis
We currently use same definitions as for women:
o Osteopenia: T-score < -1 and > -2.5o Osteoporosis: T-score < -2.5
Search for causes of secondary osteoporosis in male osteoporosis (2/3rds will have) Treatment options same as for women:
o Bisphosphonateso Calcium 1500 mg/d + 800-1000 IU Vit D/dayo Teriparatideo Calcitonin esp. for acute vertebral fracture pain
Male Hypogonadism DDx
Hypothalamic/pituitary Dz: T & nl- LH/FSHo Idiopathic hypogonadotrophic hypogonadismo Panhypopituitarismo LH and FSH deficiency: if associated with anosmia
Kallmann’s
Primary Gonadal Failure: T & LH and FSHo ****Klinefelter’s Syndrome: XXY karyotypeo Testicular damage: mumps orchitis, irradiation, alcoholism,
lead poisoning, chemorxo Andropause: gradual decrease in testicular function after
age 50o Anorchiao Androgen synthesis defects
Androgen action defects: T & LH & nl FSHo Complete or incomplete androgen insensitivity
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Syndromes of Hormone ExcessThe fun stuff
FIRST – establish the biochemical abnormality Always assess hormones in relation to their
appropriate effect Image ONLY after establishing the
biochemical diagnosis
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a. Repeat the prolactin in 3 monthsb. Refer to neurosurgeryc. Initiate treatment with bromocriptine or cabergolined. 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 negativePituitary MRI: enlarged pituitary gland without any obvious adenoma
What is the appropriate next step?
CASE #21
Hyperprolactinemia
Physiologic:o Pregnancy o Lactation or even nipple stimulation
Pathologic:o Pituitary tumors – mostly microadenomaso Pituitary stalk lesionso Hypothyroidismo Chronic kidney diseaseo Hypothalamic lesions
Pharmacologic:o Estrogen o Psychiatric meds (antipsychotic dopamine
antagonists, SSRIs, TCAs)o H2 blockers (ranitidine, cimetidine)
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Hyperprolactinemia
Diagnosis:o Elevated prolactino Normal TFT’s and negative pregnancy testo Assess medication useo 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-blockerb. Calcium channel blockerc. ACE-Id. Alpha-blocker
CASE #22
Pheochromocytoma
Symptoms:o Headaches o Diaphoresiso Palpitationso Tremor, anxiety, nausea, vomiting, fatigueo Abdominal or chest paino Weight losso Episodic throbbing in the chest, trunk and heado Cold hands and feet
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Pheochromocytoma
First – make BIOCHEMICAL dx:o 24-hr urinary metanephrine and normetanephrine
o plasma free metanephrine and normetanephrine
o 24 hr urinary catecholamines
o VMA/plasma catechols – NOT USED
o Elevations 1-2X normal common in sick patients
Second – Image:o 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 hypertensionLABS: Na: 142, K: 3.3, Creatinine: 1.2
What is the next step?
a. Plasma renin activity and plasma aldosterone concentrationb. CT scan of the adrenalsc. 24 hr urine for VMAd. 24 hr urine for catecholamines and metanepharines
CASE #23
Primary Aldosteronism
Accounts for 0.5-10% of HTN cases Hypertension Hypokalemia
o May be absento Exacerbated by diuretics
Mild alkalosis on laboratory tests
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Primary Aldosteronism: Dx
Many medications interfere with testing Screening:
o Must first replete potassiumo Plasma aldosterone (PA)
Plasma Renin Activity (PRA)• But aldosterone must be high (>15 ng/dL)
Confirmatory test:o Salt load: 1 g NaCl tid for 3 dayso 24 hr urine aldosterone>12 mcg/24 hr with
concomitant 24 hr urine Na>200 mmol/d
>20-25 suggestive
Primary Aldosteronism
Imaging with CTo Unilateral lesion (adrenal vein sampling?)o Bilateral Hyperplasia, or no lesion seen:
• Adrenal vein sampling to lateralize source of aldosterone excess
Management:o Unilateral lesion resecto 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 adrenalectomyb. FNA of lesion to determine pathologyc. 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
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Adrenal Incidentalomas
Very common (6% on autopsy;4% on CT) Prevalence increases with age Hormone secreting?
o Cortisolo Aldosteroneo Catecholamineso Androgenso Other weird stuff
Malignant or infiltrative?o Metastatic diseaseo Adrenal carcinomao 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?
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a) Plasma catecholamines, aldosterone and renin, and am cortisolb) Plasma catecholamines, aldosterone and renin, and 1 mg
dexamethasone suppression testc) Plasma metanepharines and 1 mg dexamethasone suppression
testd) Urine metanepharines, 1 mg dexamethasone suppression test,
aldosterone and renine) 1 mg dexamethasone suppression testf) No testing required
Adrenal Incidentalomasvery 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
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Incidentaloma Evaluation
All patients:Screen for pheochromocytomaScreen for Cushing’s syndrome (1 mg overnight
dexamethasone suppression test)
Patients with hypertension:Screen for primary aldosteronism
Imaging CharacteristicsLow density, high washout, likely benign4 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 glandb. 10 mg DDAVP treatment once or twice a dayc. Water restriction to 2-3 liters/dayd. Thiazide diuretice. Evaluate urine osmolality after a dose of IV DDAVP
CASE #25
Diabetes Insipidus (DI)
Hallmarkso ↓ ADH concentration or actiono Dilute urine (SG<1.005, osmolality <200)o Eunatremia if free access to watero Hypernatremia/hyperosmolar otherwise
Central DI – deficient secretion of ADH by posterior pituitary gland Nephrogenic DI – resistance to ADH actions Primary polydipsia (Psychogenic Polydipsia)
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Diagnosing etiology of polyuria
Test Central DI Nephrogenic DIPrimary
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
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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
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MEN 2A
Medullary carcinoma of the thyroid Pheochromocytoma Hyperparathyroidism
Mutations in RET proto-oncogene Autosomal dominant
MEN 2B
Medullary carcinoma of the thyroid PheochromocytomaMarfanoid habitusMucosal neuromas Ganglioneuromatosis of the bowel
Mutations in RET protooncogene Autosomal dominant
APS I APS IIAlternative 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 = 3:1Endocrine 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 dzb: dx requires at least 2 of these 3 dz
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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
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