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Unexplained Weight Loss: A Case of Apathetic Hyperthyroidism Julie Silverman, MD March 21, 2012 Grand Rounds Livingston HealthCare.

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Presentation on theme: "Unexplained Weight Loss: A Case of Apathetic Hyperthyroidism Julie Silverman, MD March 21, 2012 Grand Rounds Livingston HealthCare."— Presentation transcript:

1 Unexplained Weight Loss: A Case of Apathetic Hyperthyroidism Julie Silverman, MD March 21, 2012 Grand Rounds Livingston HealthCare

2 Disclosures I have no disclosures.

3 Outline Case presentation Unintended Weight Loss in the Elderly Review of thyroid physiology Apathetic Hyperthyroidism

4 Chief Complaint 80 y.o. man presenting to the ED s/p fall complaining of R leg pain

5 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

6 History of Present Illness 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

7 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

8 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

9 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

10 Differential Dx

11 Malignancies Visceral GI Lymphomas

12 Differential Dx Non-malignant GI disorders Advanced liver disease Celiac disease Chronic pancreatitis Crohn’s Gastroparesis Malabsorption NOS Peptic ulcer disease Swallowing dysfunction Malignancies Visceral GI Lymphomas

13 Differential Dx Non-malignant GI disorders Advanced liver disease Celiac disease Chronic pancreatitis Crohn’s Gastroparesis Malabsorption NOS Peptic ulcer disease Swallowing dysfunction Malignancies Visceral GI Lymphomas Endocrinopathies Adrenal insufficiency Diabetes mellitus Hypercalemia Hyperthryoidism Panhypopituitarism Pheochromocytoma

14 Differential Dx Non-malignant GI disorders Advanced liver disease Celiac disease Chronic pancreatitis Crohn’s Gastroparesis Malabsorption NOS Peptic ulcer disease Swallowing dysfunction Malignancies Visceral GI Lymphomas Endocrinopathies Adrenal insufficiency Diabetes mellitus Hypercalemia Hyperthryoidism Panhypopituitarism Pheochromocytoma Other Illnesses Advanced COPD Advanced CHF Advanced renal disease Smoldering infections HIV SBE Tuberculosis Vasculitis

15 Differential Dx Non-malignant GI disorders Advanced liver disease Celiac disease Chronic pancreatitis Crohn’s Gastroparesis Malabsorption NOS Peptic ulcer disease Swallowing dysfunction Malignancies Visceral GI Lymphomas 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

16 Differential Dx Non-malignant GI disorders Advanced liver disease Celiac disease Chronic pancreatitis Crohn’s Gastroparesis Malabsorption NOS Peptic ulcer disease Swallowing dysfunction Psychiatric Bipolar disorder Dementia Depression Dysmorphic syndromes Paranoid delusional states Personality disorders Malignancies Visceral GI Lymphomas 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

17 Differential Dx Non-malignant GI disorders Advanced liver disease Celiac disease Chronic pancreatitis Crohn’s Gastroparesis Malabsorption NOS Peptic ulcer disease Swallowing dysfunction Psychiatric Bipolar disorder Dementia Depression Dysmorphic syndromes Paranoid delusional states Personality disorders Malignancies Visceral GI Lymphomas 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 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

18 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)

19 Unintentional Weight Loss in the Elderly CMAJ MAR. 15, 2005; 172 (6)

20 Physical Exam

21 Temp 36.2, HR 117, RR 20, BP 121/63

22 Physical Exam Temp 36.2, HR 117, RR 20, BP 121/63 Gen: well-appearing, NAD, B resting tremor

23 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

24 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

25 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

26 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

27 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

28 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

29 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+

30 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

31 Labs & Tests

32 MCV 83 MCH 27.2 MCHC 32.8 RDW 13.0 EKG: Normal sinus rhythm with freq PACs

33 Labs & Tests MCV 83 MCH 27.2 MCHC 32.8 RDW 13.0 EKG: Normal sinus rhythm with freq PACs Iron 18 (40-160) Ferritin 374 (20-300) TIBC 173 ( ) VitB ( ) Folate 15.1 ( ) FOBT neg UA neg for blood

34 Labs & Tests MCV 83 MCH 27.2 MCHC 32.8 RDW 13.0 EKG: Normal sinus rhythm with freq PACs Iron 18 (40-160) Ferritin 374 (20-300) TIBC 173 ( ) VitB ( ) Folate 15.1 ( ) FOBT neg UA neg for blood Chol 78 ( ) HDL 43 (40-80) LDL 25 (60-129) TGs 52 (30-149) HbA1C 6.6

35 Labs & Tests MCV 83 MCH 27.2 MCHC 32.8 RDW 13.0 EKG: Normal sinus rhythm with freq PACs Iron 18 (40-160) Ferritin 374 (20-300) TIBC 173 ( ) VitB ( ) Folate 15.1 ( ) FOBT neg UA neg for blood Chol 78 ( ) HDL 43 (40-80) LDL 25 (60-129) TGs 52 (30-149) HbA1C 6.6TSH 0.01 ( ) T3 132 (80-195) T ( ) FT4 34 (6-10.5)

36 Labs & Tests MCV 83 MCH 27.2 MCHC 32.8 RDW 13.0 EKG: Normal sinus rhythm with freq PACs Iron 18 (40-160) Ferritin 374 (20-300) TIBC 173 ( ) VitB ( ) Folate 15.1 ( ) FOBT neg UA neg for blood Chol 78 ( ) HDL 43 (40-80) LDL 25 (60-129) TGs 52 (30-149) HbA1C 6.6TSH 0.01 ( ) T3 132 (80-195) T ( ) FT4 34 (6-10.5)

37 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)

38 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)

39 Thyroid Basics TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = Thyroxine T3 = Triiodothyronine

40 Thyroid Basics TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = Thyroxine T3 = Triiodothyronine TSH normal = no dysfunction

41 Thyroid Basics TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = Thyroxine T3 = Triiodothyronine TSH normal = no dysfunction ↓ TSH = hyperthyroidism

42 Thyroid Basics TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = Thyroxine T3 = Triiodothyronine TSH normal = no dysfunction ↓ TSH = hyperthyroidism ↑ TSH = hypothyroidism

43 Thyroid Basics TRH = Thyroid Releasing Hormone TSH = Thyroid Stimulating Hormone = Thyrotropin T4 = Thyroxine T3 = Triiodothyronine TSH normal = no dysfunction ↓ TSH = hyperthyroidism ↑ TSH = hypothyroidism To confirm diagnosis, check free T4 and free T3 levels

44 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 Sep;36(3):617-56, v. Review.

45 Manifestations of Thyrotoxicosis

46 Hyperthyroidism in the Elderly (a.k.a. Apathetic Hyperthyroidism) Ann Intern Med May 1, :

47 Hyperthyroidism in the Elderly 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) Comparison between young and old patients with symptoms and signs of hyperthyroidism

48 Hyperthyroidism in the Elderly Comparison between old patients with hyperthyroidism and old controls ` `

49 “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, :

50 Back to My Patient… TSH 0.01 ( ) T3 132 (80-195) T ( ) FT4 34 (6-10.5)

51 Back to My Patient… TSH 0.01 ( ) T3 132 (80-195) T ( ) FT4 34 (6-10.5) Iron 18 (40-160) Ferritin 374 (20-300) TIBC 173 ( )

52 Back to My Patient… TSH 0.01 ( ) T3 132 (80-195) T ( ) FT4 34 (6-10.5) Iron 18 (40-160) Ferritin 374 (20-300) TIBC 173 ( ) Chol 78 ( ) HDL 43 (40-80) LDL 25 (60-129) TGs 52 (30-149) HbA1C 6.6

53 Manifestations of Thyrotoxicosis

54 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

55 Thank you To everyone for making me feel so welcome! And a special thanks to Doug, Mary and Terri!

56 Questions

57

58 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

59 Endocrine Follow up TSH 0.01  0.6  3.6 ( ) T3 132  39  NM (80-195) T  9.1  8.1 ( ) FT4 34  10.8  8.7 (6-10.5) Ur. I  7982 (42-350) Thyroglobulin Ab neg Thyroid peroxidase Ab titer 20 Chol 78  181( ) 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

60 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

61 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

62 Silent Thyroiditis N Engl J Med 2003;348:

63 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

64 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

65 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

66 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


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