The aim of this study is to develop a metabolome signature of thyroid hormone status. The metabolome signature could be useful in diagnosis and treatment of thyroid dysfunction diseases, especially in cases where TSH cannot be reliably used.

Primary Hypothyroidism is a frequent endocrine disorder, where the thyroid gland does not produce sufficient amounts of thyroid hormones. The substitution therapy is guided by measurement of the pituitary gland hormone thyrotropin (TSH). Patients with central hypothyroidism in whom pituitary insufficiency leads to hypothyroidism, TSH cannot be used to guide therapy. So far there are no reliable methods for therapy control in patients with central hypothyroidism.

The measurement of small endogenous metabolites might give investigators a metabolomics profile. This could help to discriminate between euthyroid, hypothyroid and hyperthyroid state and therefore could be used for diagnosis and therapy control of thyroid dysfunction diseases.

Inclusion Criteria:

All participants:

• Age 18 to 80 years
• BMI 19 to 35 kg/m2
• Informed consent as documented by signature

A) Patients with primary hyperthyroidism TSH < 0.2 mIU/l and free thyroxine (fT4) > 25 pM or fT3 > 8 pM

B) Patients with primary hypothyroidism, currently not sufficiently substituted TSH > 8 milli-International unit (mIU)/l or fT4 < 10 pM

C) Patients with diagnosis of primary hypothyroidism, sufficiently substituted Documented diagnosis of primary hypothyroidism Substitution with L-Thyroxin TSH in target range between 0.5 and 2.5 mIU/l

D) Patients with secondary hypothyroidism Pituitary disease with documented secondary hypothyroidism

Exclusion Criteria:

• Diabetes mellitus (HbA1c >6.5%)
• Severe concomitant diseases: chronic heart failure, liver cirrhosis, kidney failure, active cancer
• Abuse of alcohol or illicit drugs
• Women who are pregnant or breast feeding
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
• Previous enrolment into the current study

Healthy volunteers will be recruited by means of advertisements (online or in the newspaper).

Patients will be recruited from the endocrinology outpatient clinics of the Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel and patients referred from practicing endocrinologists.