- Clinical science
Endocrinology is the field of medicine concerned with endocrine tissue (e.g., the pituitary gland, thyroid gland, adrenals, testicles, and ovaries), metabolic diseases, and to an extent, nutritional medicine. Endocrine tissue is responsible for producing and secreting hormones, which influence the function of certain cells and organs. Hormone secretion is controlled by highly regulated pathways that involve cell signaling and positive or negative feedback. Disruption to these pathways can lead to an imbalance of hormones, resulting in various pathological conditions involving hyperactive or hypoactive glands (e.g., hyperthyroidism or hypothyroidism, respectively). One complex pathway is known as the hypothalamic-pituitary axis, which is the main focus in this article. An understanding of these hormone pathways is important for determining the next best step of management, particularly when interpreting changes in hormone levels and the results of suppression or stimulation tests.
- Definition: Hormones are endogenous messengers that are produced in glands or single cells; . They are responsible for signal transduction; and influence the function and metabolic rate of other organs and cells. Complex regulatory circuits normally control their secretion.
- Hormones can be categorized based on their signaling pathways:
- Based on their chemical nature:
- Steroid hormones: derived from cholesterol (e.g., testosterone, progesterone, estrogen, glucocorticoids, mineralocorticoids)
- Amine hormones: derived from a single amino acid such as phenylalanine, tyrosine, or tryptophan (e.g., catecholamines, thyroid hormones (T3 and T4))
- Peptide/protein hormones: derived from a few or many amino acids (e.g., oxytocin, vasopressin, prolactin, glucagon, insulin)
- Based on their biochemical properties:
Hydrophilic hormones (e.g., catecholamines) are stored in secretory granules and are released when needed. Lipophilic hormones (e.g., adrenocortical steroid hormones) pass into the bloodstream once synthesized. They are not stored by cells.
Degradation of hormones
- Steroid hormones and thyroid hormones: inactivation and conjugation in the liver and excretion in bile
- Catecholamines: enzymatic degradation and excretion in urine (e.g., )
- Peptide/protein hormones: proteolytic degradation mainly in the liver and kidneys
Feedback control mechanisms
- Receptors in the hypothalamus measure plasma osmolality (measuring system).
- If the osmolality exceeds a set point, the neural pituitary gland excretes ADH (controlled variable).
- ADH increases renal reabsorption of water (process unit).
- Receptors in the hypothalamus detect falling osmolality and reduce ADH secretion, which decreases the amount of water reabsorption in the kidneys.
Diagnosis of endocrine diseases
The following methods may be used:
- Direct measurement of hormone blood levels (e.g., measuring prolactin blood level upon clinical suspicion of )
- Stimulation of glands to detect underactivity (e.g., for Addison's disease = chronic adrenal insufficiency)
- Inhibition of glands to detect hyperactivity (e.g., for Cushing's syndrome = hypercortisolism)
- Imaging of glands to determine:
- Specific laboratory studies (e.g., determination of thyrotropin receptor antibodies, or HbA1c for diabetes mellitus)
- Ventral part of the diencephalon (forebrain) composed of several nuclei
- Regulates hormonal pathways and autonomic functions (e.g., control of body temperature and food intake)
- Hormones of the hypothalamus mostly affect hormonal secretion of the anterior pituitary gland.
- There are two types of hormones: releasing hormones (increase hormonal secretion from the pituitary gland) and inhibiting hormones (decrease hormonal secretion from the pituitary gland)
- For more information on the anatomy of the hypothalamus, see the article for .
- Located in a midline depression of the sphenoid bone (sella turcica) in the middle cranial fossa
- Connects to the hypothalamus through the pituitary stalk (infundibulum)
- Divided into two parts:
Overview of hypothalamic-pituitary axis
Hypothalamic-(anterior) pituitary axis
- The anterior pituitary produces two different types of hormones:
|Hypothalamus||Pituitary gland||Main effect|
|Somatostatin (growth hormone–inhibiting hormone)|| |
|Hypothalamic-pituitary-prolactin axis||: stimulates secretion of ( , )prolactin in the pituitary gland|| |
|Dopamine, also called : inhibits secretion of prolactin in the pituitary gland|
Hormones of the hypothalamus-(posterior) pituitary axis
- The posterior pituitary gland (= neurohypophysis) stores and secretes two peptide hormones from the hypothalamus
- Antidiuretic hormone (ADH, vasopressin): regulation of free water balance (and blood pressure)
- Oxytocin: induces uterine contractions and the release of milk
Important diseases associated with the hypothalamus and pituitary gland
- The thyroid gland secretes two thyroid hormones: T3 (triiodothyronine) and T4 (thyroxine, tetraiodothyronine).
More T4 is produced than T3 but T4 is less potent.
- Peripheral 5'-deiodinase in the blood converts T4 into the biologically active T3.
- T4 is therefore considered a hormonal precursor (prohormone).
- Half of the T4 is processed into biologically inactive T3 (reverse T3).
- The half-life of T3 is about one day (∼ 20 hours), whereas the half-life of T4 is about one week (∼ 190 hours). This longer half life makes T4 suitable for use as a depot form that can be used replacement therapy.
- Furthermore, the C cells of the thyroid gland produce calcitonin, which regulates calcium balance.
Physiological effects of thyroid hormones
- ↑ Basal metabolic rate (↑ oxygen consumption, and ↑ body temperature)
- Stimulation of carbohydrate metabolism
- Anabolism of proteins (in high doses: catabolism of proteins)
- Induces either lipolysis or liponeogenesis depending on metabolic status
- Permissive effect on catecholamines (particularly via β receptors)
- In children: stimulation of bone growth
- CNS effects
- Reproductive effects
Feedback control mechanisms
- Hypothalamus: TRH (thyrotropin-releasing hormone, thyroliberin) → stimulates secretion of TSH (thyroid-stimulating hormone, thyrotropin) in the pituitary gland → stimulates release of T3 (triiodothyronine) and T4 (thyroxine, tetraiodothyronine) in the thyroid gland
Important diseases associated with the thyroid gland
- ♀: Ovaries
- ♂: Testicles
Feedback control mechanisms
- Hypothalamus: GnRH → stimulates release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone) in the pituitary gland → the effects of LH and FSH on the gonads are different in men and women
Important diseases associated with the gonads
Drugs that act on the hypothalamic-pituitary-gonadal axis
- Leptin: A hormone predominantly produced in adipose tissue that is a key mediator of long-term regulation of food intake and body weight and inhibits hunger.
Neuropeptide Y (NPY): A neurotransmitter primarily stored in the hypothalamus that has several functions in the central and peripheral nervous systems, including:
- Appetite stimulation
- Regulation of anxiety-related behavior
- Neuronal excitability
- Ghrelin: A hormone secreted by the stomach that stimulates appetite. Levels increase during fasting states and decrease after intake of food.
Regulation of satiety: occurs in the ventromedial nucleus of the hypothalamus
- Cholecystokinin (short-term effect via inhibition of gastric emptying and food intake)
- Leptin (long-term)
- Stimulated by:
- Polyphagia: excessive hunger (e.g., due to hyperthyroidism, hypoglycemia)
Ghrelin makes you a gluttonous gremlin. Leptin makes you thin!