by Jeffrey Dach MD
The TSH Test is perhaps the most important single test mainstream endocrinology relies on for evaluating thyroid function. Surprisingly, TSH, which stands for Thyroid Stimulating Hormone, is not made by the thyroid gland and is not a thyroid hormone. Rather, TSH is made by the pituitary gland, a small nubbin of tissue at the end of a slender stalk attached to the base of the brainstem resting in a bony indentation at the skull base called the sella turcica. Understanding TSH requires an understanding of the HPA, the hypothalamic-pituitary-axis.
TSH, also called Thyrotropin, is a pituitary glycoprotein consisting of α and β subunits. The α subunit is 92 amino acids in length, and the TSH β (hTSH β) subunit contains 118 amino acids, What is the action of the TSH ? TSH stimulates the thyroid gland to produce more thyroid hormone (thyroxine), like the thermostat in your house which automatically turns on the furnace to make more heat whenever the room temperature falls.
Regulation of TSH-the HPA
TSH production by the pituitary is itself regulated by two things. The first is the level of thyroid hormones in the blood stream which inhibits TSH production by the pituitary, as a negative feedback loop. Secondly. TSH production is stimulated by the action of TRH (Thyrotropin Releasing Horomone), a hormone produced by the hypothalamus in the brainstem. TRH production is itself regulated by thyroid hormone levels in the blood stream, similar to the thermostat analogy above. Increasing thyroid hormone levels inhibits TRH production, and decreasing thyroid hormone levels allows for more TRH production by the hypothalamus. Thus thyroid hormone production by the thyroid gland is part of a feed back loop called the HPA, the hyothalamic pituitary axis.
Various drugs such as Glucocorticoids (steroids) and opiates may inhibit the HPA axis and decrease TSH production by causing hypothalamic dysfunction or suppression. “Many drugs may cause hypothalamic dysfunction, including opiates, alcohol, anti-psychotics, and even inhaled or topical corticosteroids. There are many others.”(2)
The TSH in Disease States.
Starvation and Chronic Illness
Starvation and moderate to severe illness are associated with a decrease in serum TSH, thought to be due to suppression of the hypothalamus resulting in decreased TRH release. In very severe illness, the serum TSH will decrease and T3 and T4 thyroid hormone levels will be low. This is called a paradoxically low TSH caused by hypothalamic suppression or dysfunction.(5)
Various neuropsychiatric disorders and/or psychoactive drug therapies may be associated with hypothalmic suppression and reduced TSH levels. These include eating disorders, anorexia nervosa, bulemia and depressive illness. (7)
Hypothalamic Dysfunction – hypothalamic-pituitary-thyroid axis suppression in non-thyroidal illnesses
As mentioned above, various drugs may inhibit the HPA and cause hypothalamic dysfunction resulting in a suppressed TSH. In acutely ill patients, excessive production of glucocorticoids may cause Hypothalamic dysfunction and a paradocically low TSH . (3)
Activation of pro-inflammatory cytokines IL-2β, TNFα and IL-6 inhibit TRH-TSH synthesis/secretion causing a paradoxically low TSH. (4)
Clinical Causes of Reduced TSH
1) A true hyperthyroid state with increased thyroid production by the thyroid gland will inhibit TSH resulting in a low TSH test result. Graves Disease and Toxic Nodular Goiter are the most commonly seen forms of hyperthyroidism.
2) Excessive use of thyroid pills with excess thyroid hormone intake will suppress the TSH to subnormal levels.
3) Severe illness may suppress the TSH.
4) Patients receiving high dose glucocorticoids (prednisone) will have suppressed TSH.
5) Psychiatric patients with acute or agitated psychosis or depression may have suppressed TSH values.
6) Autonomous thyroid nodule which has a mutation in the TSH receptor will produce thyroid hormone uncontrollably and cause suppression of TSH along with a hyperthyroid state.
Causes of Elevated TSH
1) True Hypothyroidism with decreased production of thyroid hormone by the thyroid gland due to thyroid disease. Autoimmune Hashimotos thyroiditis is the most common.
2) Pituitary adenoma with uncontrolled production of TSH by a tumor.
3) Transient elevation of TSH may occurs during the recovery phase after a severe illness. (5,6)
4) Iodine or Lithium administration may cause elevated TSH values due to impairment of thyroid hormone release(8,9,10)
Jeffrey Dach MD
7450 Griffin Road, Suite 180/190
Davie, Fl 33314
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References and Links
2) home.comcast.net/~staticnrg/Cushings/HPA_Drugs.pdf (full pdf file)
Drugs and HPA axis. by Ambrogio AG, Pecori Giraldi F, Cavagnini F. Istituto Auxologico Italiano, Ospedale San Luca, IRCCS, University of Milan, Milan, Italy. This paper outlines the interferences of the most widely used drugs with hypothalamo-pituitary-adrenal function and the related laboratory parameters, with the purpose of providing practical help to clinicians during testing for hypo- or hypercortisolemic states.
3) Delitala, G., Tomasi, P.& Virdis, R. (1987). Prolactin, growth hormone and thyrotropin-thyroid hormone secretion during stress states in man. Baillieres Clin Endocrinol Metab , 1 , 391-414.
Cytokine. 1993 Nov;5(6):531-8.
Cytokines and hypothalamic-pituitary function.
Jones TH, Kennedy RL.
Longitudinal study of thyroid function in acutely ill elderly patients using a sensitive TSH assay-defer testing until recovery.
Bhakri HL, Fisher R, Khadri A, MacMahon DG.
6) http://www.ncbi.nlm.nih.gov/pubmed/11800517 Fliers, E., Alkemade, A.& Wiersinga, W.M. (2001). The hypothalamic-pituitary-thyroid axis in critical illness. Best Pract Res Clin Endocrinol Metab , 15 , 453-464.
8) http://press.endocrine.org/doi/abs/10.1210/jcem-36-2-338 Emerson, C.H., Dysno, W.L.& Utiger, R.D. (1973). Serum thyrotropin and thyroxine concentrations in patients receiving lithium carbonate. J Clin Endocrinol Metab , 36 , 338-346.
Endocrinology. 1983 Nov;113(5):1608-15.
Evidence that organic iodine attenuates the adenosine 3′,5′-monophosphate response to thyrotropin stimulation in thyroid tissue by an action at or near the adenylate cyclase catalytic unit. Filetti S, Rapoport B.
Biol Trace Elem Res. 2013 Aug;154(2):244-54. doi: 10.1007/s12011-013-9708-6. Epub 2013 Jun 16.
Iodine-induced thyroid blockade: role of selenium and iodine in the thyroid and pituitary glands. Basalaeva NL.
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