unexplained weight loss: a case of apathetic hyperthyroidism

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