The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions. (5th April 2021)

• Record Type: Journal Article
• Authors: Feldt-Rasmussen, Ulla; Effraimidis, Grigoris; Klose, Marianne
• Is Part Of: Molecular and cellular endocrinology. Volume 525(2021)
• Publication Date: 2021-04-05
• Subjects: Central hypothyroidism -- Neuroendocrinology -- Hypothalamus-pituitary-thyroid axis -- Hormone interactions -- Clinical management; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2021.111173
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: The hypothalamus-pituitary-thyroid axis is one of several hormone regulatory systems from the hypothalamus to the pituitary and ultimately to the peripheral target organs. The hypothalamus and the pituitary gland are in close anatomical proximity at the base of the brain and extended through the pituitary stalk to the sella turcica. The pituitary stalk allows passage of stimulatory and inhibitory hormones and other signal molecules. The target organs are placed in the periphery and function through stimulation/inhibition by the circulating pituitary hormones. The several hypothalamus-pituitary-target organ axis systems interact in very sophisticated and complicated ways and for many of them the interactive and integrated mechanisms are still not quite clear. The diagnosis of central hypothyroidism is complicated by itself but challenged further by concomitant affection of other hypothalamus-pituitary-hormone axes, the dysfunction of which influences the diagnosis of central hypothyroidism. Treatment of both the central hypothyroidism and the other hypothalamus-pituitary axes also influence the function of the others by complex mechanisms involving both central and peripheral mechanisms. Clinicians managing patients with neuroendocrine disorders should become aware of the strong integrative influence from each hypothalamus-pituitary-hormone axis on the physiology and pathophysiology of central hypothyroidism. As an aid in this direction the present review summarizes and highlights the importance of the hypothalamus-pituitary-thyroid axis, pitfalls in diagnosing central hypothyroidism, diagnosing/testing central hypothyroidism in relation to panhypopituitarism, pointing at interactions of the thyroid function with other pituitary hormones, as well as local hypothalamic neurotransmitters and gut-brain hormones. Furthermore, the treatment effect of each axis on the regulation of the others is described. Finally, these complicating aspects require stringent diagnostic testing, particularly in clinical settings with lower or at least altered à priori likelihood of hypopituitarism than in former obvious clinical patient presentations. Highlights: The diagnosis of central hypothyroidism is mostly based on finding of a low/low normal free T4 estimate combined with an inappropriately low/normal serum TSH concentration. In complicated cases such as suspicion of non-thyroidal illness or interfering factors, access to more elaborate laboratory measurements i.e. total T4, T3, a T4 or T3 uptake test and rT3 should be available to ensure a correct diagnosis. Other hypothalamus-pituitary-hormone axes are also often affected in central hypothyroidism, depending on the underlying diagnosis. The diagnosis of central hypothyroidism is affected by dysfunction from and interaction with the other axes. Hypothalamus-pituitary-thyroid function is highly dependent on a variety of local hypothalamic neurotransmitters and gut-brain hormones. Treatment of the central hypothyroidism and the other hypothalamus-pituitary axes influence each other by complex mechanisms. Managing neuroendocrine disorders requires knowledge of the interactions between the hypothalamus-pituitary-hormones axes.