Morning Report

Morning Report
November 23, 2010
Kishan Parikh, MD & Ronald Cohen, MD
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Session ID: A700

MKSAP
A 72-year-old man comes to the office for a follow-up
evaluation. He has had type 2 diabetes mellitus for
13 years. Over the past 5 years, his hemoglobin A1c value has slowly risen to 9.8%, and his fasting blood
glucose levels at home have frequently exceeded 180
mg/dL (10.0 mmol/L). He has been adherent to
recommended lifestyle changes. The patient is
currently on metformin, 1000 mg twice daily, and
extended-release glipizide, 20 mg/d. He has
hypertension treated with candesartan and
hydrochlorothiazide and hyperlipidemia treated with
atorvastatin.
• Results of physical examination are normal.

Which of the following is the best
A. Add exenatide
next step in therapy?
B. Add insulin glargine
C. Add pioglitazone
D. Add sitagliptin
E. Double his dosage of glipizide

Which of the following is the best
A. Add exenatide
next step in therapy?
B. Add insulin glargine
C. Add pioglitazone
D. Add sitagliptin
E. Double his dosage
of glipizide
20% 20% 20% 20% 20%
A. B. C. D. E.

• This patient has poor glycemic control, despite combination therapy with metformin
and extended-release glipizide (a sulfonylurea), and thus requires insulin. The
standard method of initiating insulin therapy is to begin with a single daily injection of
a basal insulin, such as insulin glargine, insulin detemir, or neutral protamine Hagedorn
(NPH) insulin; this approach minimizes the risk of hypoglycemia. Starting doses in the
0.2 to 0.3 U/kg range will be well tolerated in most patients, with future titration based
on the results of home glucose monitoring.
• Dose changes are typically made in increments of 2 to 4 units every few days or weekly
until the fasting glucose level is consistently in the range of 70 to 130 mg/dL (3.9 to 7.2
mmol/L). The addition of insulin glargine or insulin detemir to this patient’s regimen
should result in a substantial reduction in his hemoglobin A1c value.
• Randomized studies of stepped therapy in type 2 diabetes showed that most patients
were able to achieve target hemoglobin A1c goals of 7% using a combination of oral
antihyperglycemic agents and basal insulin therapy. If such a reduction is not achieved
and postprandial hyperglycemia occurs, the addition of a mealtime rapid-acting insulin
analogue or the substitution of a premixed insulin should be recommended.
• Adding the injectable agent exenatide or another oral agent to this patient’s medication
regimen is unlikely to reduce his hemoglobin A1c value sufficiently. When added to a
combination oral regimen, exenatide has been shown to reduce hemoglobin A1c values by only 1% and the oral agents pioglitazone and sitagliptin by 1% or less.
• In most studies of patients with diabetes, increasing the sulfonylurea dosage beyond
the half maximal dosage has resulted in little to no improvement in glycemic control.
Therefore, doubling this patient’s dosage of glipizide is unlikely to be effective.

Chief Complaint
• 18 year old female presents with concern over
no menstrual periods

HPI
• Only 2 menses in lifetime both at age 15, each lasted a week
• Not sexually active
• Doing well in school, no fatigue or headaches
• Noticed pubic hair/breast development at age 14
• No acne problems, no weight gain
• Denies weight self-consciousness
• No hx of strenuous emotional or physical activities
• No galactorrhea

PMHx
• Scoliosis
PSHx
• None
FamHx
• Paternal aunt had thyroid
cancer and thyroidectomy;
also myasthenia gravis
• Paternal GM and GGM had
thyroid dysfunction
• No hx of abnormal menses
Meds
• None
Allergies
• NKA
SocHx
• High school
• Occasional cigarette and EtOH
• No other drugs
• No sexual activity

Differential?

Amenorrhea: Historical Clues
Master-Hunter T, Helman D. Amenorrhea: evaluation and treatment. Am Fam Physician. 2006 Apr 15;73(8):1374-

Amenorrhea: Physical Exam
Findings

Physical Exam
Vitals: Ht 5’5” | Wt 60kg | RR 14 | P 72 | BP 110/62
Gen: NAD
HEENT: symmetrically enlarged thyroid w/o discrete nodules, no neck
webbing
RESP: CTAB
CV: rrr, nl s1 s2 and no murmurs
BREAST: Tanner III development. No nipple discharge.
ABD: soft, nt/nd +BS
LYMPH: no LAD
SKIN: no acne, no hirsutism. no hyperpigmentation.
No axillary or pubic hair (Brazilian bikini wax)
GU: vaginal canal patent, nl cervical and vaginal mucosa. On bimanual exam,
uterus palpated, no adnexal masses

What labs do you want to order?
• Which labs/studies do you order first?
• How do you work up secondary amenorrhea?

Assuming the pregnancy test is
negative, what are the next lab tests
A. Prolactin and TSH
B. FSH/LH
C. Estradiol and
Progesterone
D. FSH/LH, estradiol
and progesterone
E. All of the above
to order?
20% 20% 20% 20% 20%
A. B. C. D. E.

Hypogonadism?
Obstruction?
Hypo/hypergonadotropic d/o?
Pregnancy Test
Thyroid dx or prolactinoma
Master-Hunter T, Helman D. Amenorrhea: evaluation and
treatment. Am Fam Physician. 2006 Apr 15;73(8):1374-82.

142 102 11
4.1
5.6
26
11.9
292
0.7
100
8.8
Urine preg neg
7.7 4.7
0.3
TSH 61.14
T4 4.5 (5.0-11.6)
FT4 0.53 (0.9-1.7)
FTI 4.4 (6-10.5)
PRL 7.5 (

How do you work up
hypothyroidism?

Please make your selection...
A. Thyrotropin
receptor antibodies
B. Anti-TPO and Antithyroglobulin
C. 24 hour radioiodine
uptake and scan
D. Both A and B
E. All of the above
20% 20% 20% 20% 20%
A. B. C. D. E.

• Thyroglobulin ab 40
• TPO 1280

Hashimoto’s Thyroiditis
• Most common cause of
hypothyroidism if iodine replete
• Goitrous vs atrophic (10%, may be
end-stage)
• Ab’s to Tg (20-50% sens) & TPO (90%)
• RAIU variable (vs. painful subacute)
• RR for progression to follicular
lymphoma
– Although absolute risk is small
Pearce E.N., Farwell A.P., Braverman
L.E.N Engl J Med 2003; 348:2646 – 2655
Chistiakov Journal of
Autoimmune Diseases 2005 2:1

Additional Workup
10/19; 10/29 Normal range
Estradiol 52 30-400 pg/mL
Progesterone 0.5 ≤ 27 ng/mL
LH 25; 12.6 ≤ 85 mIU/mL
FSH 73. 0; 32.2 ≤ 19 mIU/mL

Any imaging?

• Pelvic u/s:
– Endometrial stripe 0.39cm
– R ovary 2.6 x 1.6 x 1.9cm, normal appearing
– L ovary 2 x 1.6 x 0.9cm, normal appearing
• Thyroid u/s:
– Heterogenous, enlarged
– Very small L lobule nodules too small for biopsy

Premature Ovarian Failure
• AKA Primary Ovarian Insufficiency
• Mean age of menopause is 50±4yo
– ‘Premature’ if less than 40yo, amenorrhea ≥ 4 mths &
menopausal-range FSH
• Biopsy not helpful
Turner syndrome
Fragile X syndrome
Chemotherapy
Radiation
Cigarette smoke
Follicle Depletion Follicle Dysfunction
FSH, LH
receptor
mutations
Autoimmunity

How to link premature ovarian
failure with Hashimoto’s
thyroiditis?

Premature Ovarian Failure
• 90% of cases are idiopathic, but some can be
associated with syndromes
• Hashimoto’s is present in 14-27% of women
with premature ovarian failure
– Points strongly towards an autoimmune etiology
Nelson. Primary Ovarian Insufficiency. N Engl J Med 2009;360:606-14.

Nelson. Primary Ovarian Insufficiency. N Engl J Med 2009;360:606-14.

Polyglandular Autoimmune Syndrome
• Type 2 (more prevalent): Ab to steroidogenic
enzymes (e.g. 21-OH).
– Adrenal insufficiency (100%)
– gonadal failure (5-50%)
– thyroid dz (70%)
– DM I (50%)

How do you work this up?

Predicting DM 1: GAD65 ab
© 2010 UpToDate, Inc.

Adrenal Ab < 1
GAD65 ab 0
Karytoype normal
Additional Workup
ACTH Cortisol
9.5 8.9
30min post 25.4
1hr post 30.3

• Emotional health
• HRT
• Bone health
• Family planning
Now What?
– Unlike menopause, 5-10% women will still
conceive after the diagnosis is given

Teaching points
• Understand the work up of secondary
amenorrhea
• Learn the interpretation of thyroid function
tests
• Understand the role of autoimmunity in
primary ovarian insufficiency
• Anticipate the clinical implications for primary
ovarian insufficiency for women’s health