Tsh

The Thyroid Stimulating Hormone is a glycoprotein hormone produced in the basophilic cells of the anterior pituitary gland that stimulates the thyroid gland. TSH consists of two subunits, the alpha-subunit with 92 amino acids and the beta-subunit with 112 amino acids. This alpha subunit is identical to that of chorionic gondaotropin, LH and FSH. The beta subunit is specific for TSH. The production and release of TSH is stimulated by the releasing hormone TRH, which is produced in the hypothalamus. TSH production is subject to a circadian and ultradiane rhythm (Samuels JD et al. 1990).

TSH enters the thyroid gland hematogenically. There it causes an accelerated division of the thyroid cells, increased iodine uptake and increased production of the thyroid hormones thyroxine (T4) and triiodothyronine (T3). Furthermore, it promotes the conversion of T4 into the more effective T3 in the periphery (Böhm BO 2018).

Under physiological conditions, euthyroidism is obtained by feedback between the thyroid and pituitary glands. For example, fT3 and fT4 inhibit the production and secretion of hypothalamic TRH and pituitary TSH through negative feedback. Under physiological conditions, this feedback mechanism causes a constant or demand-adapted euthyrotic metabolic state.

In primary hyperthyroidism, TSH is suppressed (via feedback with fT3/fT4, in primary hypothyroidism it is increased. The regulation of TSH secretion is already very sensitive and specific in borderline hypo- or hyperthyroidism.

The causes can be many and varied, which is why the thyroid hormones FT3 and FT4 must always be examined if the TSH value is abnormal. All values taken together allow a diagnosis in most cases.

Different diseases can cause a low TSH value. In most cases a low TSH value indicates hyperthyroidism (blocking feedback from increased FT3 and FT4.

A significantly increased TSH blood level is a clear indication of hypothyroidism.

Elevated TSH levels can occur in Hashimoto's thyroiditis (in addition, 90 % of affected patients have serum thyrooperoxidase (TPO) antibodies).

In case of overproduction of TSH (e.g. by a TSH-producing adenoma), the thyroid gland is constantly stimulated to accelerate growth, increased iodine uptake and increased thyroid hormone production. This results in pituitary hyperthyroidism or secondary hyperthyroidism. These secondary thyroid dysfunctions are rare.

Disturbances in TRH production and secretion can also lead to a TSH deficiency or excess and thus to the very rare tertiary hypo- or hyperthyroidism.

In autoimmune thyroid dysfunctions, e.g. in hyperthyroid Graves' disease, TSH receptor antibodies (TSH-R-Ak =TRAK) of the IgG type block the TSH receptors of the thyroid gland. TRAK unregulated stimulate the growth, iodine uptake and hormone production of the thyroid gland. The antibodies of the mostly hypothyroid Hashimoto's thyroiditis lead to destruction of the thyroid tissue, to a reduction in size and thus to a loss of thyroid function.

In adults, the normal serum TSH level is approximately between 0.40 and 4.5 mU/l. This reference range may vary depending on the age and sex of the patient and the investigating laboratory. In children and adolescents up to 18 years of age, the TSH value may be higher. In adults > 80J the upper limit is 7.5 mU/l (Barbesino G 2018). Pregnancy 1st third: 0,4-2,5 mU/l. Pregnancy 2nd third: 0.4-3.0 mU/l. pregnancy 3rd third: 0.4-3.5 mU/l (Böhm BO 2018).

Drugs and endogenous influences can influence the TSH value (Classen M et al. 2004)

The TSH secretion is reduced by (Böhm BO 2018):

• Amiodarone
• Dopamine and dopamine agonists (L-dopa, bromocriptine, lisuride, apomorphine)
• Diphenylhydantoin
• Serotonin antagonists
• Somatostatin and somatostatin analogues
• Opiates
• Morphine and morphine derivatives
• Glucocorticosteroids
• Heparin
• L-Thyroxine
• interferon alpha

TSH secretion is increased by:

• dopamine antagonists (metoclopramide, chlorpromazine, sulpiride, haloperidol)
• Naloxone
• Thyrostatic agents (thiamazole, carbimazole, propylthiouracil)
• Sodium perchlorate
• Clomiphene (men)
• Lithium
• Carbamazepine
• Theophylline
• iodide in high doses

Endogenous influences of TSH secretion:

• Endogenous depression (TSH lowering)
• Terminal renal failure (TSH lowering)
• Decompensated cirrhosis of the liver (TSH lowering)
• Severe cumulative diseases (TSH lowering)
• Malnutrition (TSH lowering)
• Disturbance of the adrenal cortex function

1. Barbesino G (2018) Thyroid Function Changes in the Elderly and Their Relationship to Cardiovascular Health: A Mini-Review. Gerontology20: 1-8.
2. Classen M et al (2004) In: Classen M et al (eds.) Endocrine Diseases. Urban § Fischer Publishing House Munich, Jena p.323
3. Böhm BO (2018) Thyroid hormones. In: Neumeister B et al. (Eds) Clinical guide to laboratory diagnostics. Elsevier GmbH S. 294-295
4. Hennessey VY (2015) Diagnosis and Management of Subclinical Hypothyroidism in Elderly Adults: A Review of the Literature. Journal of the American Geriatrics Society 63: 1663-1673.
5. Samuels JD et al (1990) Pathophysiology of pulsatile and copulsatile release of thyroid-stimulating hormones, luteinizing hormones, follicle-stimulating hormones, and alpha-subunit. The Journal of clinical endocrinology and metabolism 71: 425-432
6. Yılmaz U et al.(2014) The effect of antiepileptic drugs on thyroid function in children. Seizure 23:29-35.