Table 2 |.

Studies showing altered QOL during treatment of overt hypothyroidism^a

Overt hypothyroidism					Ref.
Condition	QOL measure	Type of study	Effect on QOL	Number of patients
Untreated versus treated with levothyroxine: initiation of levothyroxine	ThyPRO, SF-36	Open label (all untreated to treated)	Improved, based on both ThyPRO and SF-36	78 (15% overt hypothyroidism)	Winther et al. (2016)107
Untreated versus treated with levothyroxine: initiation of levothyroxine	Clinical and symptom scores RAND-36	Open label (all untreated to treated), low dose versus full dose initiation	Improved based on RAND-36 in both low and full dose arms	50 (median TSH 48–61 mIU per litre)	Roos et al. (2005)108
Untreated versus treated with levothyroxine: withdrawal of levothyroxine	SF-36	Withdrawal compared with rTSH	Decreased QOL with withdrawal	228	Schroeder et al. (2006)109
Untreated versus treated with levothyroxine: withdrawal of levothyroxine	Questionnaire designed by investigators	Withdrawal compared with rTSH	Decreased QOL with withdrawal	291	Lee et al. (2010)110
Untreated versus treated with levothyroxine: withdrawal of levothyroxine	FACT-F	Withdrawal compared with rTSH	Decreased QOL with withdrawal	74	Taieb et al. (2009)111
Untreated versus treated with levothyroxine: withdrawal of levothyroxine	FACT-F	Withdrawal compared with rTSH	Decreased QOL with withdrawal and duration of withdrawal	78	Chow et al. (2006)112
Levothyroxine treated versus control populations (matched controls)	GHQ	Cross-sectional euthyroid patients versus matched controls	Decreased QOL in patients	1,922	Saravanan et al. (2002)46
Levothyroxine treated versus control populations (reference values)	Symptom checklist-90 RAND-36	Cross-sectional euthyroid patients versus reference values	Decreased QOL in patients	2,509 (141 patients; 2,368 reference individuals)	Wekking et al. (2005)47
Levothyroxine treated versus healthy controls	ThySRQ, ThyDQoL HDS, BDI, SF-36, WBQ-12, SCL-90-R	Cross-sectional euthyroid patients versus healthy controls	Decreased QOL in patients using ThySRQ symptom number and tiredness, BDI, WBQ-12	36	Quinque et al. (2013)113
Patients receiving levothyroxine to target different TSH goals	GHQ-28, SF-36, TSQ	Randomized, blinded, three-period crossover study	No significant effect	56	Walsh et al. (2006)115
Patients receiving levothyroxine to target different TSH goals	SF-36, mood profile of states	Randomized, double-blind trial	No significant effect	138	Samuels et al. (2018)116
Patients receiving levothyroxine with different TSH values within the normal range	ThySRQ, ThyDQoL HDS, BDI,SF-36, WBQ-12, SCL-90-R	Cross-sectional	QOL (based on ThySRQ) worse with upper normal TSH values	102	Quinque et al. (2013)113
Patients receiving levothyroxine, some with iatrogenic hypothyroidism	SF-36	Cross-sectional	Decreased QOL with undertreatment (both subclinical and overt hypothyroidism)	2,057 (21.5% subclinical, 4.4% overt)	dos Santos Vigario et al. (2013)117
Patients receiving levothyroxine, some with iatrogenic hypothyroidism	RAND-36	Cross-sectional	No significant effect	9,491 (10.3% TSH 4–10 mU per litre, 0.7% TSH >10 mU per litre)	Klaver et al. (2013)118
Patients taking levothyroxine switched from tablet to liquid levothyroxine	ThyTSQ	Open label	Improved QOL with liquid levothyroxine	418	Guglielmi et al. (2018)119
Patients taking levothyroxine switched to levothyroxine versus levothyroxine and liothyronine	SF-36, BDI, SCL-90-R	Randomized blinded, two-period crossover study	Improved with levothyroxine and liothyronine	59	Nygaard et al. (2009)123
Patients taking levothyroxine switched to levothyroxine versus levothyroxine and liothyronine	Visual analogue scale	Randomized, non-blinded, two-period crossover study	Improved with levothyroxine and liothyronine	33	Bunevicius et al. (1999)124
Patients taking levothyroxine switched to levothyroxine versus levothyroxine and liothyronine	GHQ-12, TSQ, HADS	Randomized, double-blind trial	GHQ-12 caseness (but not GHQ Likert) and HADS improved with levothyroxine and liothyronine at 3 months but not at 12 months	697	Saravanan et al. (2005)126
Patients taking levothyroxine switched to levothyroxine versus levothyroxine and liothyronine	GHQ-28	Randomized trial	Reduced anxiety and/or insomnia scores with levothyroxine and liothyronine	71	Valizadeh et al. (2009)125
Patients taking levothyroxine switched to levothyroxine and liothyronine	ThyPRO-39	Open label trial	Improved ThyPRO composite score with levothyroxine and liothyronine	23	Michaelsson et al. (2018)146
Patients taking levothyroxine, levothyroxine and liothyronine, liothyronine, or DTE	Scale from 0–100	Online survey	Improved QOL associated with levothyroxine and liothyronineor DTE	969	Mitchell et al. (2021)8
Patients taking levothyroxine, levothyroxine and liothyronine, liothyronine, or DTE	Scale from 0–10	Online survey	Improved QOL associated with DTE	12,146	Peterson et al. (2018)57
Patients taking levothyroxine switched to levothyroxine versus DTE	GHQ-12, TSQ-36, BDI	Randomized, double-blind crossover trial	No statistically significant effect	70	Hoang et al. (2013)132
Patients taking levothyroxine switched to levothyroxine monotherapy vs levothyroxine and liothyronine combination vs DTE	TSQ-36, GHQ-12, WMS-IV, BDI	Randomized double-blind crossover trial	No statistically significant effect	75	Shakir et al. (2021)122

BDI, Beck’s Depression Inventory; DTE, desiccated thyroid extract; FACT-F, Functional Assessment of Chronic illness Therapy-Fatigue; GHQ, General Health Questionnaire; HADS, Hospital Anxiety and Depression questionnaire; SCL, Symptom Check List; ThyDQoL, Underactive Thyroid-Dependent Quality of Life Questionnaire; TSQ, Thyroid Symptom Questionnaire; WBQ, Well-Being Questionnaire; WMS, Wechsler Memory Scale.

^aNine randomized controlled trials of combination therapy did not show a benefit of levothyroxine and liothyronine to QOL. One trial did not report QOL parameters¹⁴⁷.