Download A Quick Tour Through: Endocrinology

A Quick Tour Through:
Endocrinology
Veronica Piziak MD,PhD
Scott & White
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Obesity
New medications and surgical outcomes
Hirsutism – evaluation and management
Disclosures: none
2010
2006
1990
Prevalence* of Self-Reported Obesity Among U.S. Adults 2011
*us years.
30.4
15%–<20%
20%–<25%
34.9
25%–<30%
Obesity = BMI >/=30
30%–<35%
≥35%
17% OBESE
Therapy Old and New
Combination Therapy (Qsymia)
• A combination of phentermine, a sympathomimetic
amine anorectic, and topiramate extended-release,
an antiepileptic drug, indicated as an adjunct to a
reduced-calorie diet and increased physical activity
for chronic weight management in adults initial body
mass index (BMI) of:
• • 30 kg/m2 or greater (obese)
• • 27 kg/m2 or greater (overweight) in the presence
of at least one weight-related comorbidity such as
hypertension, type 2 diabetes mellitus, dyslipidemia
Combination Therapy
• Phentermine and Topiramate extendedrelease
• Phentermine - enhancing the effect of
dopamine
• Topiramate - enhances the activity of GABA in
the brain creates a feeling of fullness
• Patients on the highest dose of lost an average
of 10.6% of their starting body weight.
• Weight loss persists at two years if drug
continued
Phentermine/Topiramate
• Recommended dose: P/T 3.75 mg/23 mg daily for 14
days; then increase to 7.5 mg/46 mg daily
• Discontinue or escalate dose if 3% weight loss is not
achieved after 12 weeks on 7.5 mg/46 mg dose
• Maximum daily dose of 15 mg/92 mg Discontinue
P/T if 5% weight loss is not achieved after 12 weeks
on maximum dose.
• Discontinue 15 mg/92 mg dose gradually to prevent
possible seizure
Phentermine/Topiramate
• Increase in Heart Rate: Monitor heart rate in all
patients, especially
• those with cardiac or cerebrovascular disease
• Suicidal Behavior and Ideation: Monitor for depression
or suicidal
• thoughts. Discontinue if symptoms develop.
• • Acute Myopia and Secondary Angle Closure
Glaucoma:
• Discontinue.
Phentermine/Topiramate
• Fetal Toxicity: Females of reproductive
potential:
• Obtain negative pregnancy test before
treatment and monthly thereafter; use
• effective contraception.
• P/T is available through a limited
• program under a Risk Evaluation and
Mitigation Strategy (REMS)
Phentermine/Topiramate
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Mood and Sleep Disorders: Consider dose reduction or withdrawal
for clinically significant or persistent symptoms.
Cognitive Impairment: May cause disturbances in attention or
memory. Caution patients about operating automobiles or
hazardous machinery when starting treatment.
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Metabolic Acidosis: Measure electrolytes before/during treatment
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Elevated Creatinine: Measure creatinine before/during treatment
• Use of Antidiabetic Medications: Weight loss may cause
• hypoglycemia. Measure serum glucose before/during treatment
Phentermine/Topiramate
Drug Interactions
• • Oral contraceptives: Altered exposure may cause
irregular bleeding but not increased risk of pregnancy.
Advise patients not to discontinue oral contraceptives
if spotting occurs.
• CNS depressants including alcohol: Potentiate CNS
depressant effects. Avoid concomitant use of alcohol.
• Non-potassium sparing diuretics: May potentiate
hypokalemia.
• Measure potassium before/during treatment
Lorcaserin (Belviq)
• A serotonin 2C receptor agonist indicated as an
adjunct to a reduced-calorie diet and increased
physical activity for chronic weight management
in adults
• Initial body mass index (BMI) of:
• • 30 kg/m2 or greater (obese)
• • 27 kg/m2 or greater (overweight) in the
presence of at least one weight-related comorbid
condition
• hypertension, dyslipidemia, type 2 diabetes
Lorcaserin (Belviq)
• Dosage: One tablet of 10 mg twice daily
• Discontinue if 5% weight loss is not
achieved by week 12
• Contraindicated in pregnancy
• Do not use with other weight loss
medications.
• Monitor for hypoglycemia in diabetes
Lorcaserin (Belviq)
• Binds to serotonin receptors in the brain to increase
satiety but much greater affinity for brain receptors
then heart receptors.
• Valvular heart disease: If signs or symptoms develop
consider discontinuation and evaluate the patient for
possible valvulopathy.
• Study participants were monitored closely for heart
valve irregularities, and no difference was seen in the
two groups
Lorcaserin Side Effects
• Most common adverse reactions
• (greater than 5%)
• Non-diabetic: headache, dizziness, fatigue,
nausea, dry mouth, constipation
• Diabetic patients: hypoglycemia, headache,
• back pain, cough, and fatigue
Lorcaserin Side Effects
• Cognitive Impairment: May cause
disturbances in attention or memory.
• Caution with use of hazardous machinery.
• Psychiatric Disorders, including euphoria and
dissociation:
• Monitor for depression or suicidal thoughts.
• Priapism: Patients should seek emergency
treatment if an erection lasts >4 hours
Lorcaserin- Drug Interactions
• Serotonergic drugs use with extreme caution
due to the risk of serotonin syndrome
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin-norepinephrine reuptake inhibitors
(SNRIs)
• Monoamine oxidase inhibitors (MAOIs)
Triptans, Bupropion, Dextromethorphan, St.
• John’s Wort, lithium, tramadol
Lorcaserin
• About half of obese people who took the drug
for a year lost at least 5% of their body weight,
compared to 20% of dieters who took a
placebo
• 1 in 5 Lorcaserin users lost 10% or more of
their body weight, compared to 1 in 14
placebo users.
• People on medication for two years were able
to maintain their weight loss better than those
who switched to placebo after one year.
NEJM 7/2010
Surgery
Comorbid conditions
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Sleep apnea
Hypertension
Type 2 diabetes
Dyslipidemia
Fatty liver
GERD
Metabolic syndrome
Lap Band Long Term
• No malabsorption / Weight loss more user dependent
• At 2 years percentage of excess weight loss was
47.5%
• 12 year follow up from Univ of Penn >50% revisions
• Medical outcomes:
• Hypertension: 25.6% at baseline, 29.5% at follow-up
• Type 2 diabetes: 6.4% at baseline, 14.1% at follow-up
• Treatment for obstructive sleep apnea: 2.6% at
baseline, 7.7% at follow-up
• Himpens J, et al Long term outcomes of laparoscopic adjustable gastric
banding Arch Surg 2011
Which is better?
• Gastric bypass – more complications, malabsorption, vitamin
deficiency
• 2 years 61.6% excess weight lost
• 6 years 76% still maintained a 20% weight loss
• 62 % of patients with diabetes were still in remission
• Development of diabetes: 2% surgery group
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15% control group
• LDL, HDL and triglycerides all significantly improved over
control P<0.001
• Adams et al JAMA 2012;308:1122 (prospective Utah bases
study)
Gastric bypass is better!
• 8 years, 83% of patients with preoperative
T2DM had normal levels of plasma glucose,
• Hypertension - not different
• Sleep apnea – not resolved in most
• Dyslipidemia improved in majority
• .Can J Surgery. 2013 Feb;56(1):47-57.
Gastric sleeve gastrectomy
Sleeve Vs Gastric Bypass
• Same comorbidity resolution at 1 year
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Surgery 11/12
• Sleep apnea 58%
• Diabetes 58%
• Dyslipidemia 63%
• Hypertension 38%
• No resolution of GERD
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Vidal et al Obesity
Zhang et al Surg Endosc 2012,Dec 13
Hirsutism
Approach to Hirsutism
Type of Hair
Vellus hair is short, soft, and lightly pigmented.
Terminal hair is longer, stiff, and pigmented.
Scalp hair is an example of terminal hair.
Distribution
Female terminal hair pattern lacks temporal balding
and terminal facial hair other than on the upper lip
and chin and eyebrows
• Amount of Hair, Duration of the condition
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Approach to the Patient with Androgen Excess
• Hormones of interest: Testosterone (5α-reductase)
Dihydrotestosterone (DHT) (DHEA) – adrenal
• Increased levels lead to hirsutism, which is excessive
androgenic hair growth in a female pattern.
• Virilization result from higher levels of hormone or
prolonged stimulation with modest elevations.
• Developing a male hair pattern, increased
• pectoral musculature, and huskiness of the voice.
• voice change, changes in libido, and clitoromegaly.
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Must exclude tumors.
Approach to Hirsutism
• “In the United States, the
“ideal” woman has, no
terminal hair except for the
scalp, eyebrows, eyelashes,
and pubis.
• This standard puts most,
normal women in the
hirsute category.”
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Etching from the 14th century
Lynn Loriaux
Therapy for Hirsutism
• Determine the degree of patient concern
• Cosmetic procedures
• Hair Growth Attenuation
• Eflornithine (Vaniqa)
• Cream is applied topically twice daily. 70% of women
have a favorable response compared to control
subjects
Treatment
• Treat the underlying Problem
• Antiandrogens
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Spironolactone 100 and 200 mg/day.
Side effects mild diuretic effect,postural hypotension and hyperkalemia.
High incidence of menstrual irregularity
Coadministration of an estrogen/progestin-based birth
control pill. Contraception is necessary
• Finasteride 5 and 7.5 mg/day is an inhibitor of type II 5- reductase. There
are no reported serious complications with this
• medication in the treatment of hirsutism.
• Contraception should be used
Hirsutism
Annoying Facial Hair
Distribution is important
Pathological Hair Distribution
Frequently associated with virilization and
tumors
Case 1
• 18 yo lady comes to your office for amenorrhea and
excess hair growth on her face and thinning of the hair
on her head worsening over about the last two years.
• She was told when she was a child that she might have
a problem with her adrenal glands and she takes
hydrocortisone 10 mg in the AM and 5 mg in the PM
• Family history is positive for early puberty in males
• On exam Blood pressure 120/70 BMI 25
Congenital Adrenal Hyperplasia
ACTH high
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low
Most commonly
partial 21 hydroxylase deficiency
Measure
Androstenedione
And Testosterone
Therapy: increase hydrocortisone
Case 2
• 28 yo lady with progressive hirsutism over three
months,
• Deepening of her voice, “hot spells/headaches”
• Enlarging upper body muscles secondary to
weight training (virilization). Amenorrhea
• 20 pound weight gain over last 4 months
• BP 160/100 p 76
• Severe terminal hair hirsutism
• What lab would you like to order?
What lab would you like?
• Abnormal menses, terminal hair hirsutism
• Measure testosterone less then 200 ng/dl --benign
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greater then/= 200 ng/dl --•
adrenal or ovarian tumor
• Remember the time course ---
Case 2
Our patient Testosterone 400ng/dl
Differentiating the adrenal from the ovary
Exclude adrenal causes
Measure adrenal steroids
DHEA 4x normal
Cortisol (24 hour urine) 10 x normal
ACTH below assay limit
MRI abdomen large left adrenal tumor with
multiple metastases
• Adrenal carcinoma
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