Download Diabetes and Endocrinology

Diabetes and
Endocrinology
1
Glucose
 The fasting blood glucose level is used to screen for and
diagnose diabetes and pre-diabetes.
 A fasting plasma glucose (about an 8 hour fast) or an
oral glucose tolerance test (OGTT)
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OGTT
(Oral Glucose Tolerance Test)
 OGTT requires that the patient have a fasting plasma
glucose test, followed by the patient drinking a standard
amount of glucose solution to “challenge” their system,
followed by another plasma glucose test 2 hours later.
3
Gestational diabetes
Gestational diabetes is usually diagnosed using a
glucose challenge test (GCT) as a screen, followed by
OGTT if the screen is abnormal
Routine Dipstick urine test
4
Hemoglobin A1c
A1c (also called hemoglobin A1c or glycohemoglobin)
It is a measure of the average amount of glucose present
in the blood over the last 2 to 3 months
A measure of treatment effectiveness over a period of
time
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Microalbumin and
Microalbumin/Creatinine Ratio
Measures very small amounts of protein in the urine
(microalbuminuria).
This is a symptom of the very early stages of kidney disease.
Microalbumin is usually measured annually
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Fasting Plasma Glucose Test
Plasma Glucose Result (mg/dL)
Diagnosis
99 and below
Normal
100 to 125
Pre-diabetes
(impaired fasting glucose)
126 and above
Diabetes*
*Confirmed by repeating the test on a different day
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Oral Glucose Tolerance Test
2-Hour Plasma Glucose Result (mg/dL)
Diagnosis
139 and below
Normal
140 to 199
Pre-diabetes
(impaired glucose tolerance)
200 and above
Diabetes*
*Confirmed by repeating the test on a different day.
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Gestational Diabetes: Above-Normal
Results for the Oral Glucose Tolerance Test
When
Plasma Glucose Result
(mg/dL)
Fasting
95 or higher
At 1 hour
180 or higher
At 2 hours
155 or higher
At 3 hours
140 or higher
Note: Some laboratories use other numbers for this test.
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Random Plasma Glucose Test
A random blood glucose level of 200 mg/dL
or more,
plus presence of the following
symptoms, can mean that
patient has
diabetes:
increased urination
increased thirst
unexplained weight loss
Other symptoms include fatigue, blurred vision,
increased hunger, and sores that do not heal.
Check blood glucose level on another day using the FPG
or the OGTT to confirm the diagnosis.
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Causes for Glucose Intolerance
Genetic defects of beta- cell function
Genetic defects in insulin action
Diseases of the exocrine pancreas
Pancreatitis
Trauma/pancreatectomy
Neoplasia
Cystic fibrosis
Hemochromatosis
 Others
 Endocrinopathies
 Acromegaly
 Cushing's syndrome
 Glucagonoma
 Pheochromocytoma
 Hyperthyroidism
 Somatostatinoma
 Aldosteronoma
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Causes for Glucose Intolerance
 Drug- or chemical-induced
 Pentamidine
 Nicotinic acid
 Glucocorticoids
 Thyroid hormone
 Diazoxide
 Beta-adrenergic agonists
 Thiazides
 Phenytoin
 Alfa-interferon
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Glycated hemoglobin (GHb or A1C)
Should be measured at least twice a year in known
diabetes to document glycemic control
Goal of keeping GHb levels below 6%
When to test?
4 times each year if you have type 1 or type 2 diabetes and
use insulin; or
2 times each year if you have type 2 diabetes and do not
use insulin.
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Is there a home test for A1c?
Yes. There is an FDA-approved test that
can be used at home.
Unlike some home tests, this one requires
a prescription.
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Microalbuminuria
Type 2 diabetics under the age of 70
Type 1 diabetics over the age of 12 be screened annually
for microalbuminuria.
According to the American Diabetes Association, in Type 1
diabetes, annual testing should begin 5 years after
diagnosis.
Is microalbumin just smaller molecules of albumin?
Microalbumin tests for a small amount of albumin, not
smaller molecules.
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THE BASICS of
Endocrinology
16

Abbreviations: AHA, anterior hypothalamic
area; AR, arcuate nucleus; DMN, dorsomedial
nucleus; MB, mammillary body; ME, median
eminence; MN, medial nucleus; OC, optic
chiasm; PHN, posterior hypothalamic
nucleus; POA, preoptic area; PVN,
paraventricular nucleus; SCN,
suprachiasmatic nucleus; SO, supraoptic
nucleus; VMN, ventromedial nucleus.
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 HYPOTHALAMICPITUITARY-GONADAL- AXIS
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?NEGATIVE
FEEDBACK
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Negative feed back:
 In HYPO states of the gland function the pituitary and
hypothalamic hormones will be elevated
 The target endocrine gland hormone will be decreased
 Example: In Hypothyroid patients
 TSH increased
 T3 and T4 (or free T4) levels decreased
 In Addison’s disease:
 ACTH levels increased
 Serum cortisol levels decreased
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Negative feed back:
 In HYPER states of the gland function the pituitary and
hypothalamic hormones will be decreased
 The target endocrine gland hormone will be increased
 Example: In HYPER thyroid states TSH decreased
 T3 and T4 (or free T4) levels increased
 In Cushing’s disease:
 ACTH levels decreased
 Serum cortisol levels increased
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Adrenal Insufficiency &
Addison's Disease
 often vague and nonspecific.
 Symptoms may include:
 Abdominal pain
 Decreased body hair
 Dehydration (only in Addison’s disease)
 Diarrhea or Constipation
 Dizziness and Fainting
 Fatigue
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Other Findings:
Hyperpigmentation (only in Addison’s disease - dark patches of skin,
especially in the folds of the skin. Sometime black freckles on the
forehead, and face and/or discoloration around areas such as the nipples,
lips, and rectum)
Joint and muscle aches
Low blood pressure
hypoglycemia)
Muscle weakness
Salt craving (only in Addison’s disease)
Vomiting
Weight loss
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Can Present as Crisis!
Caused by a period of increased stress, trauma, surgery, or a severe
infection.
If left untreated it can be fatal.
In acute adrenal failure (addisonian crisis), the signs and symptoms
may include:
Kidney failure
Loss of consciousness
Low blood pressure
Severe pain in the lower back, abdomen or legs
Severe vomiting and diarrhea, leading to dehydration
Shock
Adrenal antibodies are present in Addison’s disease
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Investigating
Thyroid
Function
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The thyroid gland
 The thyroid is a small (25 grams) butterfly-shaped gland located at
the base of the throat.
 It is the largest of the endocrine glands, and consists of two lobes
joined by the isthmus. The thyroid hugs the trachea on either side of
the second and third tracheal ring, opposite the 5th, 6th and 7th
cervical vertebrae. It is composed of many functional units called
follicles, which are separated by connective tissue.
 Thyroid follicles are spherical and vary in size. Each follicle is lined
with epithelial cells which encircle the inner colloid space (colloid
lumen). Cell surfaces facing the lumen are made up of microvilli and
surfaces distal to the lumen lie in close proximity to capillaries.
 The thyroid is stimulated by the pituitary hormone TSH to produce
two hormones, thyroxine (T4) and triiodothyronine (T3) in the
presence of iodide.
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The
pituitary
 The anterior pituitary is crucial for proper thyroid
function through the production and secretion of
thyroid stimulating hormone (TSH).
 TSHsecretion is positively regulated by a
neurohormone known as thyrotropin releasing
hormone (TRH) from the hypothalamus.
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When to test?
• Despite the development of highly sensitive laboratory
tests, clinical assessment and judgement remain
paramount1
• Initial testing for thyroid dysfunction should be based
on clinical suspicion. When more of the common signs
and symptoms of thyroid disease are present, there is
increased prevalence of disease.
Key point
Signs and symptoms provide
the best indication to request
thyroid tests
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When to test?
In 1997, Bandolier revisited a 1978
study2
which
emphasised
the
importance of clinical examination and
history as the most significant factors
when deciding to request thyroid
function tests.
- High suspicion patients = 78% had
thyroid disease
- Intermediate suspicion patients =
2.9% had thyroid disease
- Low suspicion patients = 0.45% had
thyroid disease.
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Signs and symptoms provide the best indication to
request thyroid tests
Hypothyroidism
Hyperthyroidism
High Suspicion
Goitre
Delayed reflexes
Goitre
Thyroid bruit
Lid lag
Proptosis
Intermediate
Suspicion
Fatigue
Weight gain
difficulty losing weight
Cold intolerance
Dry, rough, pale skin
Constipation
Family history
Hoarseness
Fatigue
Weight loss despite increased appetite
Heat intolerance/sweating
Fine tremor
Family history
Increased bowel movements
Fast heart rate/palpitations
Staring gaze
Low Suspicion
Non specific
symptoms
Coarse, dry hair
Hair loss
Muscle cramps/muscle aches
Depression
Irritability
Memory loss
Abnormal menstrual cycles
Decreased libido
Nervousness
Insomnia
Breathlessness
Light or absent menstrual periods
Weight loss
Muscle weakness
Warm moist skin
Hair loss
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Patients who are likely to be at
increased risk of thyroid dysfunction
•
•
•
•
•
•
•
•
•
•
Presence of:
Other autoimmune diseases:
(e.g. type 1 diabetes, celiac disease)
Dyslipidemia:
(high cholesterol and/or high triglyceride)
Medications: e.g. amiodarone, lithium, interferon
Past history of neck surgery or irradiation
Suspicious thyroid symptoms postpartum or a previous
episode of postpartum thyroiditis
Chronic cardiac failure, coronary artery disease, arrhythmias,
pulse >90/min, hypertension
Menstrual disturbance or unexplained infertility
Some genetic conditions (e.g. Down, Turner syndromes)
31
Which test should be used?
• In most situations use TSH as the sole test of thyroid
function.
• It is the most sensitive test of thyroid function and
adding other tests is only of value in specific
circumstances.
• In normal patients, when the TSH is within the reference
range, there is a 99% likelihood that the FT4 will also be
within the reference range.
32
Monitoring patients on
thyroxine
TSH is the most appropriate test when monitoring
patients receiving thyroxine for the treatment of
hypothyroidism.
It should be measured no sooner than 6-8 weeks
after the start of treatment.
In the unusual situation where thyroid function
needs to be assessed before this time, FT4
should be used, as the TSH will not have
plateaued at this stage.
33
Thyroid tests in the
pregnant patient
controversial
TSH
Temporarily suppressed during the first trimester of
pregnancy, due to the thyroid stimulating effect
of hCG.
FT4 levels tend to fall slowly in the second half of
pregnancy.
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The effects of drugs on
thyroid function
Amiodarone
Thyroid function should be checked prior to commencing amiodarone.
Mildly abnormal thyroid function tests often occur in the first six months of
treatment (mild TSH and FT4 elevation).
Patients on long term therapy should be monitored with 6 monthly TSH and
FT4 tests. An early repeat should be arranged if there are abnormalities of
concern (such as falling TSH) or the patient develops symptoms of thyroid
dysfunction.
Lithium
Can lead to hypothyroidism, especially in patients with underlying
autoimmune thyroid disease. An annual check of thyroid function
is recommended.
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Amiodarone
therapy
Amiodarone therapy can induce the
development of hypothyroidism or
hyperthyroidism in 14-18% of patients.
Pre-existing Hashimoto’s thyroiditis and/or
thyroid peroxidase antibodies are a risk
factors for developing hypothyroidism
during treatment.
36
Range of tests available
TSH(thyroid stimulating hormone, thyrotropin)
FT4 (free thyroxine)
FT3 (free triiodothyronine)
Thyroglobulin
Thyroid autoantibodies
Thyroid stimulating antibody
Two Autoimmune diseases of Thyroid:
Hashimoto’s
Graves disease
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CPC cases
CASE 1: NECK MASS
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Patient with Upper-Left Neck Mass
 32 year old female complaining of a non-tender nodule on left side of the neck. Temp
37C
 BP 110/72, HR 85 beats/min. A 3cm non-tender nodule palpated along the left
sternocleidomastoid near the superior aspect of the thyroid cartilage. The thyroid
was symmetrical except for a hard 2.5 cm nodule on the left lobe of the thyroid. The
rest of the exam was noncontributory.
 CBC normal, normal differential, urine normal.
 Which of the following courses of action would be the best?
 1. Do you want to see an X-ray of the neck?
 2.Do you want to see a radioactive iodine scan?
 3. Do you want to tell the patient to come back in a week ?
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1. Do you want to see an X-ray of
the neck?
 You just cost the patient 500 Dollars of unnecessary X-rays!
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2.Do you want to see a
radioactive iodine scan?
 Radioactive thyroid scan
showed a cold nodule .
 You just saved the patient five
days of unnecessary
hospitalization.
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3. Do you want to tell the patient to
come back in a week ?
 You just lost your patient!
 A friend of her's told her she knew of another friend who
had similar symptoms and it turned out to require
surgery, so your patient went to another doctor.
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Radioactive thyroid scan showed a
cold nodule .
 You would now do the following:
 Open biopsy of the thyroid
 Fine needle aspirate of the thyroid
 Surgical ablation of thyroid and parathyroids.
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Open biopsy of the thyroid
 Not the best course of action, if the nodule is a cyst you
just caused the patient $2000
worth of unnecessary surgery.
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Fine needle aspirate of the
thyroid
 You made the right choice!
 Fine needle aspiration is a
relatively non-invasive procedure
and should be tried first, before
doing an open bx of the thyroid.
 The sample is sent to pathology
and cells similar to the following
figure are observed.
Papillary Carcinoma of the thyroid
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 Notice that some of the nuclei
have groves and a ground
glass appearance.
 On further exam of the neck
you find another mass in the
right base of the neck.
 You would now recommend
46
 Sampling the other mass in the neck.
 Radical neck dissection
 Complete ablation of the gland
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Sampling the other mass in the
neck.
 Your approach is correct, the
patient had metastatic
papillary Ca in the lymph-node
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Radical neck dissection
 The surgeon refuses your request before sampling the
node and sending to pathology!
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Complete ablation of the gland
 The surgeon refuses and suggests sampling the other
mass first.
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 You would now refer your patient to the surgical
oncologist for treatment and follow-up you have
completed this case successfully!
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CASE 2
Cantankerous Professor
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 This 50 year old professor of Medicine has recently
become quite cantankerous with his students for the
past year or so.
 He complains of pain in his back, legs, and hands but
has no clinical evidence of inflammatory arthritis, such
as heat and redness are not evident.
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His physical exam revealed the following:
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Middle aged gentleman with erratic behavior, tenderness on index finger Rt and Lft hands
Augmented peristalsis.
His laboratory studies are summarized:
Hemoglobin 14.7 g%
Hematocrit 48%
WBC 7430 nl diff.
Serum calcium 13 mg/dL (Nl 10.5)
PTH elevated to 3 SI units (Nl =1)
Urine Nl.
Alkaline Phosphatase 7 (nl 1-4 B units)
Thyroid scan Nl.
Hand X-ray shows bony resorption of distal phalange of index finger.
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 Hypoparathyroidism
 Hyperparathyroidism
 Renal hyperparathyroidism
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 The diagnosis is unlikely because the other glands were
normal in size. (Hypo)
 This diagnosis cannot be ruled out from the gross but
given the history one would think otherwise (Lymphoma)
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Hyperparathyroidism
 You got the right answer!
 Your patient went to surgery
and the following tumor was
found where one of the
parathyroids should have
been the others were
unremarkable:
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CASE 3
Geography Student with Hypertension
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 C.P. is a 31-year-old student with a four year history of hypertension.
 Upon initial evaluation, her K was 2.9 mEq/L, and the possibility of primary
aldosteronism was considered.
 Random serum renin and aldosterone levels were normal, however, and the issue
was dropped.
 Her hypertension was not controlled during treatment with metoprolol, but she did
respond favorably to treatment with Aldactazide.
 She later discontinued medications, her hypertension persisted and K was 3.0
mEq/L.
59
 Physical examination, except for a BP of 185/102, was
unremarkable.
 She did not have a cushingoid habitus.
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Laboratory data: Laboratory
data:
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Na 146 (135-145 mEq/L) Cr 0.7 (<1.2 mg/dL)
K 3.0 (3.5-5 mEq/L)
C1 107 (95-110 mEq/L)
CO2 27 (22-29 mEq/L)
EKG nonspecific ST changes, strain
Your Diagnosis ?
Most probably a cortical adenoma
Most probably a cortical carcinoma
Most probably a pheochromocytoma
61
Cortical Adenoma
 CT adrenals -- 2 cm
homogeneous mass R adrenal
 The postoperative course was
uncomplicated, and her BP
and serum K on follow-up
were normal.
62
CASE 4
House Wife with Polyuria and Polydipsia
63
 B.B. is a 35-year-old housewife having symptoms of
polyuria, polydipsia, polyphagia and hyperglycemia. She
gives a history of a 70 lb. weight gain over the last 8
years, easy bruisability, and irregular menses.
64
On Examination
 Has generalized obesity, with normal hair distribution, and no
evidence of masculinization.
 BP 150/102 and other vital signs are normal. She has mild facile
plethora, but did not have dorsal or supreclavicular fat pad fullness.
 The skin is normal in thickness and there are no bruises.
 There are no violaceous striae, and she has no peripheral edema
65
 Overnight dexamethasone >> AM
cortisol 18 ug/dl (normal<5ug/dl)
 She was treated with diet and  Urine free cortisol - 201 ug/2 hrs.
insulin and after education was  Other data: Dexamethasone
discharged for further evaluation suppression: low dose - no
in the endocrinology clinic
suppression, high dose - suppression
 ACTH normal: AM > 140 pg/ml; PM
about 1/2 - 2/3 AM value).
66
This reveals a gradient of ACTH levels between the
peripheral sample and the petrosal sinus sample which
strongly suggests that the ACTH over-production is of
pituitary origin.
 Inferior petrosal sinus
sampling:
 peripheral ACTH 133 pg/ml
 L inf. petr. ACTH 128 pg/ml
 R inf. petr, ACTH 3033 pg/ml
67
 Transsphenoidal surgery was
performed, and a small mass was
discovered in the right lobe of the
pituitary. Postoperatively, she required
brief treatment with DDAVP for
transient Diabetes insipidus.
 Urine cortisol became normal. Over the
year after surgery, she lost 80 lbs, and
her requirement for insulin decreased
from 80 units NPH daily to 0.




Your Diagnosis ?
Diabetes secondary to pancreatitis
Diabetes secondary to insulinoma
Diabetes secontary to pituitary
adenoma
68
 Diabetes secondary to pituitary adenoma.
 This patient had an adenoma of the pituitary with over
production of ACTH.
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CASE 5
Twenty Year-old Woman with Amenorrhea and Lactorrhea
70
 L.B. is a 20-year-old college student with amenorrhea. She had normal
menarche and thelarche, but when she went to college at the age of 18 her
menses became irregular and ultimately stopped completely when she was
19.
 She was otherwise healthy, and participated actively in intramural athletics
including basketball.
 She had a history of classic migraine headaches, but had noted no persistent
visual disturbance.
 She had a fracture of her right ankle one year earlier when stepping off a
curb.
71
 On examination, she had a normal body habitus, and vital signs
were normal.
 Breasts were Tanner stage III, and a small amount of milky fluid
could be expressed bilaterally during the exam.
 Skin and deep tendon reflexes were normal. Visual fields were
tested formally and were normal.
72
Lab Data:
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Routine hematology and chemistry tests - normal
Endocrine studies included:
Total T4 4.6-12 ug/dl
Free T4 1.4 ng/dl
TSH 1.0 uU/ml
LH 5.4 mU/ml
FSH 4.0 mU/ml
Estradiol within normal limits
Prolactin 129 ng/ml (reference range 0-17 ng/ml)
X-ray see
73
CT scan of sella pituitary
asymmetry R>L distortion and
erosion of floor
74
Pituitary Prolactinoma
 She has transsphenoidal surgery. Her
recovery was uneventful except for
mild transient diabetes insipidus
which occurred on the day following
surgery and required treatment with a
single dose of subcutaneous DDAVP.
 On follow up evaluation, menses had
returned, galactorrhea had ceased,
and her serum prolactin has fallen to
11 ng/ml.
 The biopsy material showed the
followinng
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CASE 6
White Male With Red Face
76
 A 43 year old white male comes to you with the chief complaint of flushing of
the face, watery diarrhea .
 The physical exam reveals a medium built white male with redness of the
face, increased intestinal sounds, and malar telangiectasias.
 Thoracic exam reveals wheezing and the cardiac exam reveals tricuspid
regurgitation.
 His laboratory tests only reveal increased glucose in serum and glucose
intolerance.
 Stool reveals 5+ guaic. (Fecal Occult Blood)
77
Which Test?
 ACTH
 Gastrin
 Urinary 5-hydroxyindoleactic
acid
 urinary 5-hydroxyindoleactic
acid. The most informative
test in this case would be 5HIAA.
78
Before Urine Test




the patient must not eat
which of the following?
Meat
Broccoli
Bananas
 Bananas. Also, pineapple,
kiwi, eggplant, plums,
tomatoes avocados walnuts
and other nuts can increase
HIAA levels and must
therefore not be ingested
before measuring
79
 Our patient had 45mg of 5-HIAA in 24 hour urine as well
increased serum serotonin after a diet free of the items
mentioned in this page. Now, what is your recommendation:
 Bronchoscopy
 GI series and endoscopy
 Cystoscopy
80
GI series and endoscopy
 The patient had an ulcerated
submucosal mass in the
duodenum measuring about
3cm.
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