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Unexplained Weight Loss: A Case of Apathetic Hyperthyroidism
Julie Silverman, MD
March 21, 2012
Grand RoundsLivingston HealthCare
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
Metformin 1000mg BID Metoprolol 25mg BID Simvastatin 20mg QHS MVI Warfarin ASA Glimepiride Glyburide Plavix Amiodarone Casodex
Meds:
Family Hx: 3 siblings with DM Mother ? heart problem
Social: Lives with wife Metropolitan YMCA VP, retired 1-2 drinks/wk prior to stroke No tobacco use No illicit drug use
Differential Dx
Differential DxMalignanciesVisceral GI Lymphomas
Differential Dx
Non-malignant GI disordersAdvanced liver diseaseCeliac diseaseChronic pancreatitisCrohn’sGastroparesisMalabsorption NOSPeptic ulcer diseaseSwallowing dysfunction
MalignanciesVisceral GI Lymphomas
Differential Dx
Non-malignant GI disordersAdvanced liver diseaseCeliac diseaseChronic pancreatitisCrohn’sGastroparesisMalabsorption NOSPeptic ulcer diseaseSwallowing dysfunction
MalignanciesVisceral GI Lymphomas
EndocrinopathiesAdrenal insufficiencyDiabetes mellitusHypercalemiaHyperthryoidismPanhypopituitarismPheochromocytoma
Differential Dx
Non-malignant GI disordersAdvanced liver diseaseCeliac diseaseChronic pancreatitisCrohn’sGastroparesisMalabsorption NOSPeptic ulcer diseaseSwallowing dysfunction
MalignanciesVisceral GI Lymphomas
EndocrinopathiesAdrenal insufficiencyDiabetes mellitus HypercalemiaHyperthryoidismPanhypopituitarismPheochromocytoma
Other IllnessesAdvanced COPDAdvanced CHFAdvanced renal diseaseSmoldering infections HIV SBE TuberculosisVasculitis
Differential Dx
Non-malignant GI disordersAdvanced liver diseaseCeliac diseaseChronic pancreatitisCrohn’sGastroparesisMalabsorption NOSPeptic ulcer diseaseSwallowing dysfunction
MalignanciesVisceral GI Lymphomas
EndocrinopathiesAdrenal insufficiencyDiabetes mellitus HypercalemiaHyperthryoidismPanhypopituitarismPheochromocytoma
Other IllnessesAdvanced COPDAdvanced CHFAdvanced renal diseaseSmoldering infections HIV SBE TuberculosisVasculitis
Medications/DrugsAlcoholAmphetaminesCocaineDigoxinLevodopaMetforminNSAIDsOpiatesSSRIs
Differential Dx
Non-malignant GI disordersAdvanced liver diseaseCeliac diseaseChronic pancreatitisCrohn’sGastroparesisMalabsorption NOSPeptic ulcer diseaseSwallowing dysfunction
PsychiatricBipolar disorderDementiaDepressionDysmorphic syndromesParanoid delusional statesPersonality disorders
MalignanciesVisceral GI Lymphomas
EndocrinopathiesAdrenal insufficiencyDiabetes mellitus HypercalemiaHyperthryoidismPanhypopituitarismPheochromocytoma
Other IllnessesAdvanced COPDAdvanced CHFAdvanced renal diseaseSmoldering infections HIV SBE TuberculosisVasculitis
Medications/DrugsAlcoholAmphetaminesCocaineDigoxinLevodopaMetforminNSAIDsOpiatesSSRIs
Differential Dx
Non-malignant GI disordersAdvanced liver diseaseCeliac diseaseChronic pancreatitisCrohn’sGastroparesisMalabsorption NOSPeptic ulcer diseaseSwallowing dysfunction
PsychiatricBipolar disorderDementiaDepressionDysmorphic syndromesParanoid delusional statesPersonality disorders
MalignanciesVisceral GI Lymphomas
EndocrinopathiesAdrenal insufficiencyDiabetes mellitus HypercalemiaHyperthryoidismPanhypopituitarismPheochromocytoma
Other IllnessesAdvanced COPDAdvanced CHFAdvanced renal diseaseSmoldering infections HIV SBE TuberculosisVasculitis
Medications/DrugsAlcoholAmphetaminesCocaineDigoxinLevodopaMetforminNSAIDsOpiatesSSRIs
Psychosocial/FunctionalInability to shop/prepare foodLoss of teeth, poor denture fitMarked increase physical activityPovertySocial isolation
Mayo Clinic Proceedings76(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
5.95.98.3
1924.2 27 1.1
152142 107 22
10.2
1.5
3.2
MCV 83 MCH 27.2MCHC 32.8RDW 13.0
EKG: Normal sinus rhythm with freq PACs
Labs & Tests
5.95.98.3
1924.2 27 1.1
152142 107 22
10.2
1.5
3.2
MCV 83 MCH 27.2MCHC 32.8RDW 13.0
EKG: Normal sinus rhythm with freq PACs
Iron 18 (40-160)Ferritin 374 (20-300)TIBC 173 (230-430)
VitB12 743 (240-900)Folate 15.1 (4.0-19.9)FOBT negUA neg for blood
Labs & Tests
5.95.98.3
1924.2 27 1.1
152142 107 22
10.2
1.5
3.2
MCV 83 MCH 27.2MCHC 32.8RDW 13.0
EKG: Normal sinus rhythm with freq PACs
Iron 18 (40-160)Ferritin 374 (20-300)TIBC 173 (230-430)
VitB12 743 (240-900)Folate 15.1 (4.0-19.9)FOBT negUA neg for blood
Chol 78 (120-199)HDL 43 (40-80)LDL 25 (60-129)TGs 52 (30-149)
HbA1C 6.6
Labs & Tests
5.95.98.3
1924.2 27 1.1
152142 107 22
10.2
1.5
3.2
MCV 83 MCH 27.2MCHC 32.8RDW 13.0
EKG: Normal sinus rhythm with freq PACs
Iron 18 (40-160)Ferritin 374 (20-300)TIBC 173 (230-430)
VitB12 743 (240-900)Folate 15.1 (4.0-19.9)FOBT negUA neg for blood
Chol 78 (120-199)HDL 43 (40-80)LDL 25 (60-129)TGs 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
5.95.98.3
1924.2 27 1.1
152142 107 22
10.2
1.5
3.2
MCV 83 MCH 27.2MCHC 32.8RDW 13.0
EKG: Normal sinus rhythm with freq PACs
Iron 18 (40-160)Ferritin 374 (20-300)TIBC 173 (230-430)
VitB12 743 (240-900)Folate 15.1 (4.0-19.9)FOBT negUA neg for blood
Chol 78 (120-199)HDL 43 (40-80)LDL 25 (60-129)TGs 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 = ThyroxineT3 = Triiodothyronine
Thyroid Basics
TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = ThyroxineT3 = Triiodothyronine
TSH normal = no dysfunction
Thyroid Basics
TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = ThyroxineT3 = Triiodothyronine
TSH normal = no dysfunction
↓ TSH = hyperthyroidism
Thyroid Basics
TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = ThyroxineT3 = Triiodothyronine
TSH normal = no dysfunction
↓ TSH = hyperthyroidism
↑ TSH = hypothyroidism
Thyroid Basics
TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = ThyroxineT3 = Triiodothyronine
TSH normal = no dysfunction
↓ TSH = hyperthyroidism
↑ TSH = hypothyroidism
To confirm diagnosis, check free T4 and free T3 levels
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
Differences in the Signs and Symptoms of Hyperthyroidism in Older and Younger PatientsJournal of the American Geriatrics Society - Volume 44, Issue 1 (January 1996)
Comparison between young and old patients with symptoms and signs of hyperthyroidism
Hyperthyroidism in the ElderlyComparison 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)
5.98.3
192Iron 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)
5.98.3
192Iron 18 (40-160)Ferritin 374 (20-300)TIBC 173 (230-430)
Chol 78 (120-199)HDL 43 (40-80)LDL 25 (60-129)TGs 52 (30-149)
HbA1C 6.6
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 youTo 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 0.01 0.6 3.6 (0.3-3.8)
T3 132 39 NM (80-195)
T4 18.1 9.1 8.1 (5.0-11.6)
FT4 34 10.8 8.7 (6-10.5)
Ur. I 17453 7982 (42-350)
Thyroglobulin Ab neg
Thyroid peroxidase Ab titer 20
Chol 78 181(120-199)HDL 43 66 (40-80)LDL 25 100 (60-129)TGs 52 73 (30-149)
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 oforganic 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 ThyrotoxicosisIncidence = 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