Thyroxin Treatment in Sub Clinical Hypothyroidism, on the Apnea Hypopnea Index Score, Lipids and Highly Sensitive CRP
Thyroxin Treatment in Sub Clinical Hypothyroidism, on the Apnea Hypopnea Index Score, Lipids and Highly Sensitive CRP
Obstructive sleep apnea (OSA) and hypothyroidism are both commonly found in clinical
 practice, and share a number of symptoms and clinical features. It has been shown that
 hypothyroid subjects are at high risk of developing sleep disorder breathing and OSA, and
 adequate thyroxine treatment may reduce the sleep disordered breathing.. However, the
 time-course and effect of treating subclinical hypothyroidism in OSA patients on the
 respiratory events during sleep is not known.

 Subclinical hypothyroidism is associated with an increased risk of coronary heart disease
 (CHD). Dyslipidemia is a known complications of subclinical hypothyroidism and the effect of
 thyroxine treatment on lipid profile is controversial . Some reports suggested higher serum
 high-sensitivity C-reactive protein (hs-CRP), than healthy subjects; however, the effect of
 levothyroxine is controversial.

 This project will help us to know if the treatment of subclinical hypothyroidism will improve
 the symptoms and reduce the progression of OSA, which may improve patients' quality of life
 by reducing the complication of OSA (hypertension, , depression, Cardiovascular diseases,
 etc.) or may even reduce mortality.It will help us to know the effect of subclinical
 hypothyroidism treatment on of lipid profiles and hs-CRP.
Research Problem:

 Obstructive sleep apnea (OSA) and hypothyroidism are both commonly found in clinical
 practice, and share a number of symptoms and clinical features. It has been shown that
 hypothyroid subjects are at high risk of developing sleep disorder breathing and OSA, and
 adequate thyroxine treatment may reduce the sleep disordered breathing.. However, the
 time-course and effect of treating subclinical hypothyroidism in OSA patients on the
 respiratory events during sleep is not known.

 Subclinical hypothyroidism is associated with an increased risk of coronary heart disease
 (CHD). Dyslipidemia is a known complications of subclinical hypothyroidism (2)and the effect
 of thyroxine treatment on lipid profile is controversial . Some reports suggested higher
 serum high-sensitivity C-reactive protein (hs-CRP), than healthy subjects ; however, the
 effect of levothyroxine is controversial .

 Research Significance:

 This project will help us to know if the treatment of subclinical hypothyroidism will improve
 the symptoms and reduce the progression of OSA, which may improve patients' quality of life
 by reducing the complication of OSA (hypertension, , depression, Cardiovascular diseases,
 etc.) or may even reduce mortality.

 It will help us to know the effect of subclinical hypothyroidism treatment on of lipid
 profiles and hs-CRP.

 Research Objectives:

 Primary objective:

 • Effect of the treatment of subclinical hypothyroidism on the apnea hypopnea index (AHI)
 score.

 Secondary objectives:

 -  Effect of the treatment of subclinical hypothyroidism on the lipid profile in patient
 with dyslipidemia.

 -  Effect of the treatment of subclinical hypothyroidism on hs-CRP

 Research Methodology:

 Patients with subclinical hypothyroidism will undergo first Polysomnography (PSG) (night 0)
 and laboratory investigations including lipid profiles and hc-CRP and then they will be
 enrolled and randomly assigned to receive either levothyroxine replacement therapy or
 identical placebo tablets in a blinded manner. The starting dose will be 25 mcg/day and the
 dose will be adjusted every 6 weeks to target TSH level between (0.25 -2.5 IU/mL). We will
 keep all patients on replacement dose for duration of 24 weeks. PSG will be performed twice
 only for OSA patient, after 12 weeks (night 1) and after 24 weeks (night 2). Lipid profile
 and hs-CRP will be done at the end of 24th weeks.
Inclusion Criteria:

 -  Patients >18 years old

 -  With Subclinical hypothyroidism defined as serum TSH concentration above 5.0 IU/mL
 when serum FT4 level is within the reference range

 -  With OSA defined as mild OSA: AHI 5 to 15/h; moderate OSA:AHI 15 to 30/h; and severe
 OSA: AHI greater than 30/h (30) will be enrolled.

 -  With confirmed sustained subclinical hypothyroidism, thus excluding patients with a
 temporary condition such as that in recovery from a non-thyroidal illness, measurement
 of TSH and FT4 will be conducted within four weeks before randomization.

 Exclusion Criteria:

 -  Current treatment with Levothyroxine and lipid lowering medications or within two
 months before randomization.

 -  Conditions known to cause dyslipidemia e.g. uncontrolled diabetes mellitus (HbA1c >9),
 alcoholism and some medication use e.g. Estrogens. Glucocorticoids, Retinoids or
 Interferons.

 -  Conditions indicating levothyroxine treatment (34); including TSH levels more than 10
 mU/l, clear symptoms or signs associated with thyroid failure and not related to OSA .
 e.g. goiter.

 -  State of pregnancy, Breast feeding or allergy to levothyroxine.