Yellow Man Syndrome

“Síndrome do homem amarelo”

UCSD MORNING REPORT

PRESENTED BY BRIAN KWAN
 Uma História Muito Peculiar

 Chief Complaint: “People are telling me that I am

yellow, and my urine is dark.”
 History of Present Illness:
84 yo male with past medical history of emphysema
and hypothyroidism presents with painless jaundice
as well as darker urine for one week. He was seen in
clinic the day of admission and was told that his skin
was yellow, which he did not personally notice. He
thought that he was coming to the hospital for his
shortness of breath, which was unchanged from
baseline.
 A História Continua…

 This patient was a very poor historian. He noticed

that he has had darker urine for several days prior to
presentation. He also noted pale stools for several
days prior to presentation accompanied by diarrhea.
He thought that they were strange appearing because
they floated around the toilet bowl like wispy clouds.
He does not keep track of how many times he goes a
day but just that they are large and loose and
bothersome. Denies any abdominal pain, fevers or
chills. Has not been nauseous and has not vomited.
Questions? Têm perguntas?
 The plot thickens…

 He denies ever having this problem before, claiming

he is very healthy and does not take any medications.
 He denies any black stools or bright red blood per
rectum. He has not lost any weight as far as he
knows. He denies any night sweats.
 He has had a problem with itching all over his body
for a couple of weeks associated with a rash on his
trunk. He lives at a Veteran’s home in which the
doctor prescribed an unknown substance which the
nurses smeared all over his body, which caused his
skin to burn.
Past Medical History (Otra História Médica)

 Chronic Obstructive Pulmonary Disease

 Hypothyroidism
 Cataract Surgery (11/2009, 2/2007)
 Allergies (Alergias)

 No known drug allergies

 Medications (Medicamentações)

 Prednislone eye drops

 Social History (História Social)

 Tobacco: Smoked for 56 years; quit 13 years ago.

 Alcohol: Drinks rarely now. Drank moderately as a
youth in the Marines.
 Illicits: Denies any recreational drug use. Denies any
history of intravenous drugs.
 Social History (História Social)

 Other: Denies having any tattoos or blood

transfusions. Of note, he frequently goes to Mexico
to help improverished families. He drinks bottled
water usually, but when he eats with the families, he
partakes in their food.
 Back in 1950s, he did report living in northern Africa
for a few years briefly and also reported spending
some time in Okinawa and Japan.
 Family History (Antecedentes Familiares)

 Father: Died from bleeding out of intestines

 Mother: Died right before turning 100 years old of
old age
 Paternal Grandmother: Died of unknown cancer
Physical Exam (Examinação Física)
 Physical Exam (Examinação Física)

 Vital Signs:
Temp = 98.6 F
Blood Pressure = 129/78
Heart Rate = 98
Respiratory = 19
Oxygen Saturation = 97% on Room Air
Height = 65 inches
Weight = 145 lbs
Body Mass Index = 24
 Physical Exam (Examinação Física)

 General: Friendly old chap. Alert and oriented to

name, place and date. Not in any acute respiratory
distress. Appropriate and conversant.
 Physical Exam (Examinação Física)

 Skin: Jaundiced. Multiple erythematous pruritic

papules on anterior chest wall with excoriation
marks, multiple skin tags and moles throughout
trunk. Some ecchymoses on the arms. No
teleangiectasias.
Physical Exam (Examinação Física)
 Physical Exam (Examinação Física)

 Head, Ears, Nose, Throat: Pupils equal and reactive

to light and accomodation, icteric sclera, conjunctiva
pink, oropharynx clear, moist mucous membranes
 Neck: Supple, no cervical lymphadenopathy, no
axillary, epitrochlear, or inguinal lymphadenopathy
 Cardiovascular: Flat jugular venous pulsations, rate
regular. Normal S1 with physiological splitting of the
S2. No murmurs, rubs or gallops.
 Lung: Diminished breath sounds and bibasilar
wheezes at the bases
 Physical Exam (Examinação Física)

 Abdomen: Healthy bowel sounds, soft and

compressible, nontender to palpation, nondistended
but obese. No hepatosplenomegaly. Negative
Murphy’s, negative Rovsing’s. Liver span about 11
cm by percussion. Gallbladder not palpable. No
ascites
 Extremities: Trace lower extremity edema bilaterally,
no asterixis.
 Neuro: 5/5 strength in all extremities; cranial nerves
II-XII grossly intact, sensation grossly intact to light
touch in all extremities
Thoughts? Differential?
 Labs (Laboratórios)

 Complete Blood Count:

White blood cells: 15.2 [76% segs, few bands, 10%
lymphs]
Hemoglobin = 16.8/Hematocrit = 49.6 [MCV = 93.8]
Platelets = “Platelets adequate but clumping”
 Chemistry Panel:
Sodium = 138 [135-145], Potassium = 4.3 [3.5-5], Cl =
103 [95-106], HCO3 = 25 [24-31], BUN = 18 [8-23],
Creatinine = 0.69 [0.4-1.2]. Glucose = 100. Calcium
= 9 [8.5-10.4], Phosphate = 2.8 [2.5-4.5]
 Labs (Laboratórios)

 Liver Function Tests:

Aspartate Aminotransferase (AST): 1532 [10-30]
Alanine Aminotransferase (ALT): 2982 [11-45]
Alkaline Phosphatase: 187 [30-130]
Total Bilirubin = 28.6 [0.4-1.2]
Direct Bilirubin = 21.5 [0-0.2]
Albumin = 3.6 [3.4-4.8]
Lipase = 42 [22-70]
Amylase = 51 [28-85]
 Labs (Laboratórios)

 Coagulation Tests:
Prothrombin Time (PT) = 13.1 [9.6-13]
International Normalized Ratio (INR) = 1.2
Partial Thromboplastin Time (PTT) = 36.3 [24.2-36]
 Urinalysis: Cloudy, orange, pH = 6 [4.5-8.5], 3+
bilirubin, 2-5 WBCs, trace LE, negative nitrites,
negative blood/ketones/protein
 Other labs:
Acetaminophen Level < 10
Ethanol < 10
Chest X-Ray
 Abdominal Ultrasound

1. Gallbladder sludge with gallbladder wall thickening,

nonspecific, representing nonfasting state versus
cholecystitis.
2. Prominent pancreatic duct.
3. A 6.3 cm left midpole renal cyst.
4. A 1.7 cm right superior pole renal cyst.
5. A 1.4 cm right hepatic lobe cyst.
CT Abdomen and Pelvis
CT Abdomen and Pelvis
 CT Abdomen and Pelvis

 1. Mild dilatation of the pancreatic duct however no

evidence of pancreatic mass.
 2. Multiple renal cysts are seen bilaterally. The
dominant cyst is located in the upper pole of the left
kidney measuring 6.7 cm and showing an enhancing
central septation consistent with a Bosnian IIF cyst.
Recommend follow-up CT in six months for interval
monitoring.
Other labs? Outros Laboratórios?
 Labs (Laboratórios)

 Hepatitis Serologies:
Anti-HAV Antibodies: Positive
Hepatitis B Surface Antibody: Positive
Hepatitis B Surface Ag: Negative
Hepatitis B Core Antibody: Negative
Hepatitis C Antibody: Negative
Asleep? Adormecido?
 Labs (Laboratórios)

 Iron Studies:
Fe = 135 [36-160], TIBC = 133 [228-428]
Transferrin = 95 [200-400], Iron Saturatation = 102%.
Ferritin = 7814 [30-400]
 Autoimmune tests:
ANA within normal limits, antismooth muscle
antibodies within normal limits, P-ANCA and C-
ANCA not detectable
 Labs (Laboratórios)

 Other interesting labs:

Anti-HAV IgM = Positive
HFE genetic mutation = Heterozygous for C282Y
mutation
 Summary

 The patient had a conjugated hyperbilirubinemia

with a story concerning for obstructive jaundice.
However, after imaging, there was no evidence for an
obstructive jaundice. We did receive the positive
IgM Hep A, and his liver function tests began to
trend down at the time of discharge.
 However, we did investigate other causes of acute
hepatitis, and found that the patient had a very high
ferritin, high iron saturation, and was heterozygous
for the HFE gene, concerning for his being a carrier
for hemochromatosis.
 Iron Absorption

DMT1 moves iron into cell

until apoferritin saturated

Ferroportin moves iron out of

cell, but controlled by hepcidin

If iron does not leave cell

within 72 hrs, cell sloughed
and iron lost

FERROPORTIN
 Hepcidin

 Hepcidin 20-25 AA member of the defensin family

of antimicrobial peptides mainly expressed by
liver, inhibits iron export from enterocytes
(decreasing absorption) and macrophages
 Uptake from the gut is controlled by Hepcidin
which regulates the activity of Ferroportin
 Hepcidin binds to Ferroportin causing it to be
internalized and degraded
 Role of Hepcidin(IL-6)
Ganz T. Blood 2003;102:783-8

Iron deficiency and

hypoxia inhibit hepcidin
synthesis, and iron
excess and inflammatory
cytokines stimulate its
production.
 Hereditary Hemochromatosis

 HFe gene on chr 6; homozygosity for mutation

(CY) at position 282(85% of cases), 63(<5%),
or compound heterozygosity for 282/63
 HFe gene product fails to augment hepcidin
synthesis despite iron overload
 Rare causes of hemochromatosis include HAMP
gene mutations producing a dysfunctional
hepcidin, and mutations in genes for
ferroportin, hemojuvelin, and the transferrin
receptor
 Hereditary Hemochromatosis

 Prevalence is about 1 case in every 300 people. Most

are of Northern European origin.
 10% estimated carrier prevalence in Western
countries
 Adult onset disease
 Hemochromatosis:Symptoms
Prevalence(%)

Symptom Women Men

Fatigue 65 42
Pigmentation 58 45
Arthritis 45 35
Cirrhosis 14 26
Cardiac 14 15
Diabetes 7 16

Moirand et al, Ann Intern Med 1997;127:105

Thank you! Obrigado!