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Endocrine Rounds Endocrine Rounds Mood Disorders Mood Disorders and the Thyroid and the Thyroid Wednesday, March 16, 2005 Wednesday, March 16, 2005 Dr. Merrill Edmonds Dr. Merrill Edmonds

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Page 1: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Endocrine RoundsEndocrine Rounds

Mood Disorders and Mood Disorders and the Thyroidthe Thyroid

Wednesday, March 16, 2005Wednesday, March 16, 2005

Dr. Merrill EdmondsDr. Merrill Edmonds

Page 2: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 3: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 4: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Iodothyronine seleno-Iodothyronine seleno-cysteine deiodinasescysteine deiodinases

Page 5: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 6: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

TT33 production production

Page 7: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 8: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 9: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 10: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 11: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Hypothyroid & DepressionHypothyroid & Depression

Page 12: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Thyroid & DepressionThyroid & DepressionAbnormalities in Thyroid AxisAbnormalities in Thyroid Axis• Standard Tests variableStandard Tests variable

• Some studies suggest increase in free T4 and Some studies suggest increase in free T4 and decrease in free T3 and others suggest the oppositedecrease in free T3 and others suggest the opposite

• Sick Euthyroid pictureSick Euthyroid picture• Increased incidence of thyroid antibodies? (TBII)Increased incidence of thyroid antibodies? (TBII)

• TRH stimulationTRH stimulation• Blunted response in 25-30%Blunted response in 25-30%• Exaggerated response in 10%Exaggerated response in 10%

• TRH levels in CSF increasedTRH levels in CSF increased• No correlation with circulating TSHNo correlation with circulating TSH

• Transthyretin levels in CSF are lowTransthyretin levels in CSF are low

Page 13: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Thyroid & DepressionThyroid & DepressionAnimal studiesAnimal studies

• antidepressants increase deiodinases in rat brainantidepressants increase deiodinases in rat brain• increase T3 levels in brainincrease T3 levels in brain

Mood stabilizing agentsMood stabilizing agents• Lithium, carbamazepine, valproic acidLithium, carbamazepine, valproic acid

• lower thyroid levelslower thyroid levels

Page 14: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 15: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Thyroid hormone in depressionThyroid hormone in depression

Augmentation agents?Augmentation agents?• First used in 1958First used in 1958• Numerous studies of variable methodologic rigorNumerous studies of variable methodologic rigor• Meta-analysis (1996) Meta-analysis (1996)

Triiodothyronine augmentation in the treatment of refractory depression. Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Aronson R, Offman HJ, Joffe RT, Naylor CD.A meta-analysis. Aronson R, Offman HJ, Joffe RT, Naylor CD.

– – 8 studies with 292 patients – 2 fold 8 studies with 292 patients – 2 fold improvement in response rate = 23% improvement in response rate = 23% absolute improvementabsolute improvement

Page 16: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Thyroid hormone in depressionThyroid hormone in depression

Augmentation agents?Augmentation agents?• TT33 better than T better than T44??

Joffe RT and Singer 1990 Psychiatry ResearchJoffe RT and Singer 1990 Psychiatry Research

53% response rate with T53% response rate with T33 vs 19% with T vs 19% with T44

• TT44 in larger doses as effective as T in larger doses as effective as T33??Bauer et al 1998, NeuropsychopharmacologyBauer et al 1998, NeuropsychopharmacologyRudas et al 1999, Biol PsychiatryRudas et al 1999, Biol Psychiatry

Page 17: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Thyroid hormone in depressionThyroid hormone in depression

• Accelerate Tricyclic Response?Accelerate Tricyclic Response?• Meta-analysis (2001) Meta-analysis (2001) (treated before 1975)(treated before 1975)

Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response?Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response?A Review and Meta-Analysis of the LiteratureA Review and Meta-Analysis of the LiteratureAltshuler, Bauer, Frye,et al. Altshuler, Bauer, Frye,et al. Am J Psychiatry 2001; 158:1617–1622Am J Psychiatry 2001; 158:1617–1622

– – 6 studies with 125 patients – 20-25 ug T36 studies with 125 patients – 20-25 ug T3

Page 18: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Thyroid hormone in depressionThyroid hormone in depression

• Supraphysiologic Doses?Supraphysiologic Doses?• ThyroxineThyroxine

(mean 368 ug/day for 1 year [250-500]) (mean 368 ug/day for 1 year [250-500])Effects of supraphysiological thyroxine administration in healthy Effects of supraphysiological thyroxine administration in healthy controls and patients with depressive disorderscontrols and patients with depressive disorders

Michael Bauer, al. Journal of Affective Disorders 68 (2002) 285–Michael Bauer, al. Journal of Affective Disorders 68 (2002) 285–294294

– – fewer side-effects in depressed patientsfewer side-effects in depressed patients– improved subjective response– improved subjective response

Page 19: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Thyroid hormone in depressionThyroid hormone in depression

Page 20: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Hypothyroid & DepressionHypothyroid & DepressionAdding T3 to T4 in depressed patientsAdding T3 to T4 in depressed patients• Does a Combination Regimen of Thyroxine (T4) and Does a Combination Regimen of Thyroxine (T4) and

Triiodothyronine Improve Depressive Symptoms Better Triiodothyronine Improve Depressive Symptoms Better Than T4 Alone in Patients with Hypothyroidism? Results Than T4 Alone in Patients with Hypothyroidism? Results of a Double-Blind, Randomized, Controlled Trialof a Double-Blind, Randomized, Controlled Trial

• A. M. SAWKA, H. C. GERSTEIN, M. J. MARRIOTT, G. M. A. M. SAWKA, H. C. GERSTEIN, M. J. MARRIOTT, G. M. MACQUEEN, AND R. T. JOFFE (MACQUEEN, AND R. T. JOFFE (JCEM 88: 4551–4555, 2003)JCEM 88: 4551–4555, 2003)

• Substituting T3 (12.5 ug, twice daily) for 50% of the Substituting T3 (12.5 ug, twice daily) for 50% of the T4 replacement dose did not improve self-assessed T4 replacement dose did not improve self-assessed mood or well-being over 15 wk to a greater extent mood or well-being over 15 wk to a greater extent than continuing the pre-study dose of T4 and than continuing the pre-study dose of T4 and adding a placebo.adding a placebo.

Page 21: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Hypothyroid & DepressionHypothyroid & Depression

SummarySummary• Thyroid hormone probably useful to augment a Thyroid hormone probably useful to augment a

poor response to standard treatmentpoor response to standard treatment• Best dose and length of treatment?Best dose and length of treatment?

• Whether TWhether T33 or T or T44 is best still up in the air is best still up in the air

• No evidence for substituting TNo evidence for substituting T33 for T for T44 in in

hypothyroid patients with depressive symptomshypothyroid patients with depressive symptoms

Page 22: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 23: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds

Wilson’s SyndromeWilson’s SyndromeAdding T3 to T4 in hypothyroid patientsAdding T3 to T4 in hypothyroid patients

Combined Thyroxine/Liothyronine Treatment Does Not Combined Thyroxine/Liothyronine Treatment Does Not Improve Well-Being, Quality of Life, or Cognitive Function Improve Well-Being, Quality of Life, or Cognitive Function Compared to Thyroxine Alone: A Randomized Controlled Compared to Thyroxine Alone: A Randomized Controlled Trial in Patients with Primary HypothyroidismTrial in Patients with Primary Hypothyroidism

• JOHN P. WALSH, LAUREN SHIELS, EE MUN LIM, CHOTOO I. JOHN P. WALSH, LAUREN SHIELS, EE MUN LIM, CHOTOO I. BHAGAT, LYNLEY C. WARD, BRONWYN G. A. STUCKEY, BHAGAT, LYNLEY C. WARD, BRONWYN G. A. STUCKEY, SATVINDER S. DHALIWAL, GERARD T. CHEW, MINOTI C. SATVINDER S. DHALIWAL, GERARD T. CHEW, MINOTI C. BHAGAT, AND ANDREA J. CUSSONSBHAGAT, AND ANDREA J. CUSSONS ( (JCEM 88: 4553–4550, 2003)JCEM 88: 4553–4550, 2003)

Combined T4/T3 treatment does not improve well-Combined T4/T3 treatment does not improve well-being, cognitive function, or quality of life compared being, cognitive function, or quality of life compared with T4 alone.with T4 alone.

Page 24: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds
Page 25: Endocrine Rounds Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds