ThyrOp: A Study of Individual Subclinical Hypothyroidism After Hemithyroidectomy for Benign Nontoxic Goiter

The hypothesis of the study is that among patients that do not develop overt hypothyroidism after hemithyroidectomy, weight gain is a clinical manifestation of a postoperatively lowered set point of thyroid function - even if the thyroid function is lowered within the laboratory reference range. The investigators refer to this hypothesized condition as individual subclinical hypothyroidism.

Thyroid hormones are major regulators of mitochondrial function and subclinical hypothyroidism affects mitochondrial activity. The aim of the study is to examine if a lowered set point of thyroid function after hemithyroidectomy can be measured in the mitochondrial function, the body weight and the basal oxygen consumption.

The operation of hemithyroidectomy (total thyroid lobectomy and isthmusectomy with preservation of the contralateral lobe) is indicated for patients with a unilateral thyroid mass that is causing compressive symptoms, cosmetic concern or to exclude thyroid carcinoma.

The incidence and risk factors for development of hypothyroidism after hemithyroidectomy remain unclear. The reported rates of postoperative hypothyroidism vary from 5.0% to 41.9 % because of variable follow-up and definition of hypothyroidism (Wormald et al). There are no nationally nor universally accepted guidelines for the monitoring of thyroid function after hemithyroidectomy.

Subclinical hypothyroidism is associated with an increased risk of coronary heart events and coronary heart mortality (Rodondi et al) and a high level of thyrotropin (within the laboratory reference range) has been related to an increased risk of fatal coronary heart disease (Asvold et al) Variation in thyroid function is seen between individuals also within the normal range. The individual variation in serum levels of thyroid hormones and thyrotropin between measurements in the same individual is relatively small compared with variations between individuals (Andersen et al). This implicates that around half of the laboratory reference range for thyrotropin is abnormal for a given individual. The fact that a thyrotropin value of an individual can be within the reference range but still represent an abnormal thyroid function in that given person has consequences for the monitoring of thyroid function after hemithyroidectomy. It implies that the postoperative thyroid function should be monitored by having the preoperative thyroid function in mind and that postoperative hypothyroidism should be understood in a broader term. After hemithyroidectomy a change in the individual unique set point that results in a lowered thyroid function can represent a condition that the investigators refer to as individual subclinical hypothyroidism.

Weight gain following hemithyroidectomy for benign nodular goiter among patients that do not develop overt hypothyroidism is a frequent clinical observation. Body weight is influenced by many factors, there among thyroid function. Even small differences in thyroid function with s-thyrotropin variations within the normal laboratory range for patients on T4 substitution therapy are associated with differences in resting energy expenditure. A prolonged decrease in REE could lead to increased body weight (al-Adsani et al).

Overweight and obesity are major threats to public health. The importance of lifestyle for weight gain is not to be doubted but other factors such as slight differences in thyroid function might be of importance in the risk of gaining weight as well (Knudsen et al).

The mitochondria provide cellular energy by converting oxygen and nutrients into ATP by aerobe respiration and mitochondrial energy production is regulated by thyroid hormones (Weitzel et al). Subclinical hypothyroidism has previously been shown to affect mitochondrial function in mononuclear blood cells (Kvetny et al).

The investigators hypothesize that after hemithyroidectomy some patients develop lowered thyroid function which results in a postoperative higher value of serum thyrotropin as a consequence of less negative feed-back on the pituitary gland. Weather the postoperative lowered thyroid function results in overt hypothyroidism (serum thyrotropin above the upper reference limit, lowered serum levels of free T3 and T4), subclinical (serum thyrotropin above the upper reference limit, free T3 and T4 within the reference range) or individual subclinical hypothyroidism (serum thyrotropin rises within the reference range, free T3 and T4 within the reference range) depends on the preoperative set point of thyroid function of the given patient but either condition represents a condition that is abnormal. The investigators hypothesize that a postoperative lowered thyroid function will affect mitochondrial function and result in weight gain.

Eligibility Criteria:
Inclusion Criteria:

* Is going to undergo hemithyroidectomy for nontoxic goiter at the department of otorhinolaryngology at Slagelse Hospital, Denmark.
* BMI 20-40
* No past thyroid diseases
* No medication with influence on the pituitary-thyroid axis
* No hormone replacement therapy
* No childbirth or pregnancy within the last year
* Not currently breastfeeding

Exclusion Criteria:

* Malignant goiter, diagnosed by histological examination of the resected tissue
* Pregnancy