Grand Rounds
Livingston HealthCare
Unexplained Weight Loss:
A Case of Apathetic Hyperthyroidism
Julie Silverman, MD
March 21, 2012
Disclosures
I have no disclosures.
Outline
Case presentation
 Unintended Weight Loss in the Elderly
 Review of thyroid physiology
 Apathetic Hyperthyroidism

Chief Complaint

80 y.o. man presenting to the ED s/p fall
complaining of R leg pain
Chief Complaint

80 y.o. man presenting to the ED s/p fall
complaining of R leg pain

80 y.o. man complaining of 60lb weight
loss
History of Present Illness





40-60 lb weight loss over prev 4-5 months
CVA 3 months ago
 spent 5 wks in inpatient rehab followed by 2
mos at subacute rehab
 PEG placed on d/c from hospital d/t
swallowing difficulties; removed when left
inpatient rehab
 residual deficits: aphasia, confusion, R-sided
weakness
Decreased PO intake
? odynophagia or dysphagia
? Δ appetite
Pertinent Negatives
 No fevers, chills or night sweats
 No Δ in bowel habits (diarrhea, constipation, Δ
stool color)
 No nausea/vomiting
 No abdominal pain
 No chest pain, palpitations, SOB
 No Δ in physical activity level
 No Δ in sleep habits
Past Medical and Surgical Hx







CVA (2 months ago)
PEG placement and removal
CAD
DM Type 2
HTN
Paroxysmal a-fib (remote past)
Prostate CA 1993 s/p resection, chemo and
radiation therapy
 Appendectomy
 Polio (age 12) L arm weakness
Remainder of History
Meds:
Social:
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











Metformin 1000mg BID
Metoprolol 25mg BID
Simvastatin 20mg QHS
MVI
Warfarin
ASA
Glimepiride
Glyburide
Plavix
Amiodarone
Casodex
Lives with wife
Metropolitan YMCA VP, retired
1-2 drinks/wk prior to stroke
No tobacco use
No illicit drug use
Family Hx:
 3 siblings with DM
 Mother ? heart problem
Differential Dx
Differential Dx
Malignancies
Visceral
GI
Lymphomas
Differential Dx
Malignancies
Visceral
GI
Lymphomas
Non-malignant GI disorders
Advanced liver disease
Celiac disease
Chronic pancreatitis
Crohn’s
Gastroparesis
Malabsorption NOS
Peptic ulcer disease
Swallowing dysfunction
Differential Dx
Malignancies
Visceral
GI
Lymphomas
Non-malignant GI disorders
Advanced liver disease
Celiac disease
Chronic pancreatitis
Crohn’s
Gastroparesis
Malabsorption NOS
Peptic ulcer disease
Swallowing dysfunction
Endocrinopathies
Adrenal insufficiency
Diabetes mellitus
Hypercalemia
Hyperthryoidism
Panhypopituitarism
Pheochromocytoma
Differential Dx
Malignancies
Visceral
GI
Lymphomas
Non-malignant GI disorders
Advanced liver disease
Celiac disease
Chronic pancreatitis
Crohn’s
Gastroparesis
Malabsorption NOS
Peptic ulcer disease
Swallowing dysfunction
Endocrinopathies
Adrenal insufficiency
Diabetes mellitus
Hypercalemia
Hyperthryoidism
Panhypopituitarism
Pheochromocytoma
Other Illnesses
Advanced COPD
Advanced CHF
Advanced renal disease
Smoldering infections
HIV
SBE
Tuberculosis
Vasculitis
Differential Dx
Malignancies
Visceral
GI
Lymphomas
Non-malignant GI disorders
Advanced liver disease
Celiac disease
Chronic pancreatitis
Crohn’s
Gastroparesis
Malabsorption NOS
Peptic ulcer disease
Swallowing dysfunction
Endocrinopathies
Adrenal insufficiency
Diabetes mellitus
Hypercalemia
Hyperthryoidism
Panhypopituitarism
Pheochromocytoma
Other Illnesses
Advanced COPD
Advanced CHF
Advanced renal disease
Smoldering infections
HIV
SBE
Tuberculosis
Vasculitis
Medications/Drugs
Alcohol
Amphetamines
Cocaine
Digoxin
Levodopa
Metformin
NSAIDs
Opiates
SSRIs
Differential Dx
Malignancies
Visceral
GI
Lymphomas
Non-malignant GI disorders
Advanced liver disease
Celiac disease
Chronic pancreatitis
Crohn’s
Gastroparesis
Malabsorption NOS
Peptic ulcer disease
Swallowing dysfunction
Endocrinopathies
Adrenal insufficiency
Diabetes mellitus
Hypercalemia
Hyperthryoidism
Panhypopituitarism
Pheochromocytoma
Other Illnesses
Advanced COPD
Advanced CHF
Advanced renal disease
Smoldering infections
HIV
SBE
Tuberculosis
Vasculitis
Medications/Drugs
Alcohol
Amphetamines
Cocaine
Digoxin
Levodopa
Metformin
NSAIDs
Opiates
SSRIs
Psychiatric
Bipolar disorder
Dementia
Depression
Dysmorphic syndromes
Paranoid delusional states
Personality disorders
Differential Dx
Malignancies
Visceral
GI
Lymphomas
Non-malignant GI disorders
Advanced liver disease
Celiac disease
Chronic pancreatitis
Crohn’s
Gastroparesis
Malabsorption NOS
Peptic ulcer disease
Swallowing dysfunction
Endocrinopathies
Adrenal insufficiency
Diabetes mellitus
Hypercalemia
Hyperthryoidism
Panhypopituitarism
Pheochromocytoma
Other Illnesses
Advanced COPD
Advanced CHF
Advanced renal disease
Smoldering infections
HIV
SBE
Tuberculosis
Vasculitis
Psychiatric
Bipolar disorder
Dementia
Depression
Dysmorphic syndromes
Paranoid delusional states
Personality disorders
Medications/Drugs
Alcohol
Amphetamines
Cocaine
Digoxin
Levodopa
Metformin
NSAIDs
Opiates
SSRIs
Psychosocial/Functional
Inability to shop/prepare food
Loss of teeth, poor denture fit
Marked increase physical
activity
Poverty
Social isolation
Mayo Clinic Proceedings
76(9), September 2001, pp 923-929
Unintentional Weight Loss in the
Elderly

Weight loss is associated with increased mortality or morbidity or
both

15-20% prevalence, though estimates vary widely; no gender
difference

Similar causes as non-elderly but additional factors

Person with dementia or late-life psychotic d/o may be paranoid and
suspicious that food being poisoned
 Person with dementia and habitual wandering may expend significant
energy in pacing

Physiologic changes in elderly  early satiety and anorexia




Decline in taste and smell
Reduced efficiency of chewing
Slowed gastric emptying
Alternations in neuroendocrine axis
CMAJ • MAR. 15, 2005; 172 (6)
Unintentional Weight Loss in the
Elderly
CMAJ • MAR. 15, 2005; 172 (6)
Physical Exam
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape

LAD: No lymphadenopathy
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape

LAD: No lymphadenopathy

CV: Tachycardic, irregular rhythm, S1, S2, no murmurs/rubs/gallops
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape

LAD: No lymphadenopathy

CV: Tachycardic, irregular rhythm, S1, S2, no murmurs/rubs/gallops
Resp: CTAB, no wheezing, rales, ronchi

Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape

LAD: No lymphadenopathy


CV: Tachycardic, irregular rhythm, S1, S2, no murmurs/rubs/gallops
Resp: CTAB, no wheezing, rales, ronchi

GI: +BS, S/NT/ND, no hepatomegaly
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape

LAD: No lymphadenopathy


CV: Tachycardic, irregular rhythm, S1, S2, no murmurs/rubs/gallops
Resp: CTAB, no wheezing, rales, ronchi

GI: +BS, S/NT/ND, no hepatomegaly

Ext: R foot bandaged to knee, no edema L leg
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape

LAD: No lymphadenopathy


CV: Tachycardic, irregular rhythm, S1, S2, no murmurs/rubs/gallops
Resp: CTAB, no wheezing, rales, ronchi

GI: +BS, S/NT/ND, no hepatomegaly

Ext: R foot bandaged to knee, no edema L leg

Neuro: CN II-XII grossly intact, AAOx1 (to self), strength 5/5 left leg & 3/5 B
arms, aphasia, B resting tremor (did not improve with intention), DTR 2+
Physical Exam

Temp 36.2, HR 117, RR 20, BP 121/63

Gen: well-appearing, NAD, B resting tremor

HEENT: PERRLA, EOMI, arcus senilis, brown spots on sclerae, anicteric,
pink conjunctivae, nl dentition, oropharynx MMM, thyroid nl size/shape

LAD: No lymphadenopathy


CV: Tachycardic, irregular rhythm, S1, S2, no murmurs/rubs/gallops
Resp: CTAB, no wheezing, rales, ronchi

GI: +BS, S/NT/ND, no hepatomegaly

Ext: R foot bandaged to knee, no edema L leg

Neuro: CN II-XII grossly intact, AAOx1 (to self), strength 5/5 left leg & 3/5 B
arms, aphasia, B resting tremor (did not improve with intention), DTR 2+

Skin: no evidence of sacral skin breakdown
Labs & Tests
Labs & Tests
5.9
8.3
192
142 107 22
4.2
27 1.1
152
MCV 83
MCH 27.2
MCHC 32.8
RDW 13.0
EKG: Normal sinus rhythm with freq PACs
10.2
1.5
3.2
Labs & Tests
5.9
8.3
192
142 107 22
4.2
MCV 83
MCH 27.2
MCHC 32.8
RDW 13.0
27 1.1
152
Iron 18 (40-160)
Ferritin 374 (20-300)
TIBC 173 (230-430)
EKG: Normal sinus rhythm with freq PACs
10.2
1.5
3.2
VitB12 743 (240-900)
Folate 15.1 (4.0-19.9)
FOBT neg
UA
neg for blood
Labs & Tests
5.9
8.3
192
142 107 22
4.2
MCV 83
MCH 27.2
MCHC 32.8
RDW 13.0
27 1.1
152
Iron 18 (40-160)
Ferritin 374 (20-300)
TIBC 173 (230-430)
EKG: Normal sinus rhythm with freq PACs
Chol
HDL
LDL
TGs
78 (120-199)
43 (40-80)
25 (60-129)
52 (30-149)
HbA1C 6.6
10.2
1.5
3.2
VitB12 743 (240-900)
Folate 15.1 (4.0-19.9)
FOBT neg
UA
neg for blood
Labs & Tests
5.9
8.3
192
142 107 22
4.2
MCV 83
MCH 27.2
MCHC 32.8
RDW 13.0
27 1.1
152
Iron 18 (40-160)
Ferritin 374 (20-300)
TIBC 173 (230-430)
10.2
1.5
3.2
VitB12 743 (240-900)
Folate 15.1 (4.0-19.9)
FOBT neg
UA
neg for blood
EKG: Normal sinus rhythm with freq PACs
Chol
HDL
LDL
TGs
78 (120-199)
43 (40-80)
25 (60-129)
52 (30-149)
HbA1C 6.6
TSH 0.01 (0.3-3.8)
T3 132 (80-195)
T4 18.1 (5.0-11.6)
FT4 34 (6-10.5)
Labs & Tests
5.9
8.3
192
142 107 22
4.2
MCV 83
MCH 27.2
MCHC 32.8
RDW 13.0
27 1.1
152
Iron 18 (40-160)
Ferritin 374 (20-300)
TIBC 173 (230-430)
10.2
1.5
3.2
VitB12 743 (240-900)
Folate 15.1 (4.0-19.9)
FOBT neg
UA
neg for blood
EKG: Normal sinus rhythm with freq PACs
Chol
HDL
LDL
TGs
78 (120-199)
43 (40-80)
25 (60-129)
52 (30-149)
HbA1C 6.6
TSH 0.01 (0.3-3.8)
T3 132 (80-195)
T4 18.1 (5.0-11.6)
FT4 34 (6-10.5)
Thyroid Basics
 The thyroid gland synthesizes, stores, & secretes the thyroid
hormones (T4 and T3)
Approximately 99.98% of T4 and 99.7% of T3 are bound to
proteins (thyroxine-binding globulin, transthyretin and albumin)
Thyroid Basics
 The thyroid gland synthesizes, stores, & secretes the thyroid
hormones (T4 and T3)
 Approximately 99.98% of T4 and 99.7% of T3 are bound to
proteins (thyroxine-binding globulin, transthyretin and albumin)
Thyroid Basics
TRH = Thyroid Releasing Hormone
TSH = Thyroid Stimulating Hormone = Thyrotropin
T4 = Thyroxine
T3 = Triiodothyronine
Thyroid Basics
TSH normal = no dysfunction
TRH = Thyroid Releasing Hormone
TSH = Thyroid Stimulating Hormone = Thyrotropin
T4 = Thyroxine
T3 = Triiodothyronine
Thyroid Basics
TSH normal = no dysfunction
↓ TSH = hyperthyroidism
TRH = Thyroid Releasing Hormone
TSH = Thyroid Stimulating Hormone = Thyrotropin
T4 = Thyroxine
T3 = Triiodothyronine
Thyroid Basics
TSH normal = no dysfunction
↓ TSH = hyperthyroidism
↑ TSH = hypothyroidism
TRH = Thyroid Releasing Hormone
TSH = Thyroid Stimulating Hormone = Thyrotropin
T4 = Thyroxine
T3 = Triiodothyronine
Thyroid Basics
TSH normal = no dysfunction
↓ TSH = hyperthyroidism
↑ TSH = hypothyroidism
To confirm diagnosis, check
free T4 and free T3 levels
TRH = Thyroid Releasing Hormone
TSH = Thyroid Stimulating Hormone = Thyrotropin
T4 = Thyroxine
T3 = Triiodothyronine
Thyrotoxicosis/Hyperthyroidism


Hypermetabolic clinical syndrome resulting from serum elevations in thyroid
hormone levels
Hyperthyroidism = a type of thyrotoxicosis in which accelerated thyroid
hormone biosynthesis and secretion by the thyroid gland produce
thyrotoxicosis
Endocrinol Metab Clin North Am. 2007 Sep;36(3):617-56, v. Review.
Manifestations of Thyrotoxicosis
Hyperthyroidism in the Elderly
(a.k.a. Apathetic Hyperthyroidism)
Ann Intern Med May 1, 1970 72:679-685
Hyperthyroidism in the Elderly
Comparison between young and old patients with symptoms and signs of hyperthyroidism
Differences in the Signs and Symptoms of Hyperthyroidism in Older and Younger Patients
Journal of the American Geriatrics Society - Volume 44, Issue 1 (January 1996)
Hyperthyroidism in the Elderly
Comparison between old patients with hyperthyroidism and old controls
`
`
“The following seem to be the salient clinical
characteristics of apathetic thyrotoxicosis:

An elderly patient with a fairly typical placid apathetic facies, quite
different from the usual hyperkinetic thyrotoxic patient
 A smaller goiter
 The presence of depression, lethargy, or apathy
 Absence of ocular manifestations usually associated with
hyperthyroidism
 Substantial muscular weakness and wasting
 Excessive weight loss; and
 Cardiovascular dysfunction with atrial fibrillation.
The patient may present with the complete syndrome of apathetic
thyrotoxicosis or may present any of a spectrum of findings, the most
important of which is the central nervous system ‘nonactivation.’”
Ann Intern Med May 1, 1970 72:679-685
Back to My Patient…
TSH 0.01 (0.3-3.8)
T3 132 (80-195)
T4 18.1 (5.0-11.6)
FT4 34 (6-10.5)
Back to My Patient…
TSH 0.01 (0.3-3.8)
T3 132 (80-195)
T4 18.1 (5.0-11.6)
FT4 34 (6-10.5)
5.9
8.3
192
Iron 18 (40-160)
Ferritin 374 (20-300)
TIBC 173 (230-430)
Back to My Patient…
TSH 0.01 (0.3-3.8)
T3 132 (80-195)
T4 18.1 (5.0-11.6)
FT4 34 (6-10.5)
Chol
HDL
LDL
TGs
78 (120-199)
43 (40-80)
25 (60-129)
52 (30-149)
5.9
HbA1C 6.6
8.3
192
Iron 18 (40-160)
Ferritin 374 (20-300)
TIBC 173 (230-430)
Manifestations of Thyrotoxicosis
Take Home Points
Differential for unintentional weight loss is
wide
 Apathetic hyperthyroidism differs in
presentation from typical hyperthyroidism
and can be easily missed
 Should consider hyperthyroidism in older
patients with weight loss, apathy, cardiac
dysfunction

Thank you
To everyone for making me feel so welcome!
And a special thanks to Doug, Mary and Terri!
Questions
Hospital Course & Discharge








Soft cast  hard cast for weight-bearing; acute rehab
Speech and swallow eval: no aspiration but
recommended formal OPM
Discontinued simvastatin
Re-started ASA (did not re-start coumadin)
Started on lisinopril
Continued B-blocker and metformin
Transfused 2 units pRBCs
Follow-up appts with endocrine, neuro, ortho
Endocrine Follow up
TSH
T3
T4
FT4
Ur. I
0.01  0.6  3.6 (0.3-3.8)
132  39  NM (80-195)
18.1  9.1  8.1 (5.0-11.6)
34  10.8  8.7 (6-10.5)
17453  7982 (42-350)
Chol
HDL
LDL
TGs
78  181(120-199)
43  66 (40-80)
25  100 (60-129)
52  73 (30-149)
Thyroglobulin Ab neg
Thyroid peroxidase Ab titer 20
Thyroid u/s with doppler imaging: nl size thyroid gland with diffusely
homogenous echotexture; no thyroid nodules detected and no evidence
of increased vascularity, but rather appear hypovascular.
Presumed diagnosis: silent thyroiditis
Non-Thyroidal Illness Syndrome



Formerly “Euthyroid Sick Syndrome”
Low serum total T3: the most commonly identified abnormality
(70% of patients in the hospital)
Low serum total T3 and T4: most common in critically ill patients in
the MICU. Low total T4 is predictive of a bad outcome
Thyroid Basics
TSH stimulates lysosomal enzymes to release
T3 & T4 (T4>T3 20:1) from thyroglobulin.
T4→T3 & T3R in cells by deiodinase
T3 = 4x as potent as T4
FTI = better reflection of thyroid function than
total T4 due to TBG
• i.e. if TBG   binds to T4   free
T4; to compensate total T4 must  to
keep free T4 normal
Silent Thyroiditis
N Engl J Med 2003;348:2646-55.
Silent Thyroiditis




Inflammatory destruction of the thyroid 
release of preformed thyroid hormones 
transient thyrotoxicosis
Serum T4 concentrations proportionally higher
than T3 concentrations (reflects ratio of stored
hormone in the thyroid gland)
Signs/symptoms not usually severe
TPO antibodies present; normal ESR
Amiodarone
Class III antiarrhythmic agent (blocks K channels, prolonging
repolarization) used for tx refractory VT or VF, particularly in setting of
acute MI
Long half-life (22-55 days)
37% by weight = organic iodine, ≈10%
released daily
Maintenance dose of 200 to 600 mg/d
results in a daily intake of
organic iodide of 75 to 225 mg
Normal dietary iodine requirement = 0.2
to 0.8 mg/d
Effects on Thyroid Physiology
↓ peripheral deiodination of
T4 to T3 by inhibiting type I
iodothyronine 5'deiodinase → ↑ serum T4 &
T3R and ↓ serum T3
Inhibits entry of T3 & T4 into
peripheral tissue
Inhibits T4-T3 deiodination in
the pituitary (crucial step in
the feedback regulation) →
↑ TSH
Serum T4 ↑ an average of
40% above pretreatment
levels s/p 1-4 mos tx
Amiodarone-Induced Thyrotoxicosis
Incidence = 1% to 23%
Prevails in areas with low iodine intake (hypothyroidism prevalent in areas with high iodine intake)
Type I: underlying autoimmunity exacerbated by iodine load liberated by metabolism of
amiodarone
Type II: destructive thyroiditis that releases pre-stored thyroid hormone