Deficiency of all anterior pituitary hormones is more common than individual hormone deficiency. Deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), together referred to as the gonadotropins, leads to different symptoms in men and women. Women experience oligo- or amenorrhea (infrequent/light or absent menstrual periods respectively) and infertility. Men lose facial, scrotal and trunk hair, as well as suffering decreased muscle mass and anemia. Both sexes may experience a decrease in libido and loss of sexual function, and have an increased risk of osteoporosis (bone fragility). Lack of LH/FSH in children is associated with delayed puberty. Growth hormone (GH) deficiency leads to a decrease in muscle mass, central obesity (increase in body fat around the waist) and impaired attention and memory.
Anterior pituitary
Hypopituitarism
Hypopituitarism | Anterior pituitary
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hypothalamic amenorrhea will result in the increased secretion of thyroid stimulating hormone (tsh)
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An increase in the serum TSH level following TRH administration means that the cause of the hypothyroidism is in the hypothalamus (tertiary hypothyroidism), i.e. the hypothalamus is not producing TRH. Therefore, when TRH is given exogenously, TSH levels increase.If the increase in serum TSH level following TRH administration is absent or very slight, then the cause of the hypothyroidism is in the anterior pituitary gland, i.e. the pituitary is not secreting TSH. Therefore, even when TRH is given exogenously, TSH levels do not rise as the pituitary is diseased.
TRH stimulation test | Process and interpretation
Stimulation tests with GnRH are possible, but their use is not encouraged. For TSH, basal measurements are usually sufficient, as well as measurements of thyroxine to ensure that the pituitary is not simply suppressing TSH production in response to hyperthyroidism (an overactive thyroid gland). A stimulation test with thyrotropin-releasing hormone (TRH) is not regarded as useful. Prolactin can be measured by basal level, and is required for the interpretation of LH and FSH results in addition to the confirmation of hypopituitarism or diagnosis of a prolactin-secreting tumor.
Hypopituitarism | Basal tests
The thyroid gland is an auxiliary organ to the hypothalamus-pituitary system. Thyrotropin-releasing hormone (TRH) produced by the hypothalamus signals to the pituitary to release thyroid-stimulating hormone (TSH), which then stimulates the thyroid to secrete T and T thyroid hormones. Secondary hypothyroidism occurs when TSH secretion from the pituitary is impaired, whereas tertiary hypothyroidism is the deficiency or inhibition of TRH. Thyroid hormones are responsible for metabolic activity. Insufficient production of the thyroid hormones result in suppressed metabolic activity and weight gain. Hypothalamic disease may therefore have implications for obesity.
Hypothalamic disease | Tertiary hypothyroidism
If the TSH level is normal or low and serum free T levels are low, this is suggestive of central hypothyroidism (not enough TSH or TRH secretion by the pituitary gland or hypothalamus). There may be other features of hypopituitarism, such as menstrual cycle abnormalities and adrenal insufficiency. There might also be symptoms of a pituitary mass such as headaches and vision changes. Central hypothyroidism should be investigated further to determine the underlying cause.
Hypothyroidism | Central
In response to the releasing hormone rate, the anterior pituitary produces its hormones (TSH, ACTH, LH, FSH, GH) which in turn stimulate effector hormone glands in the body, while prolactin (PRL) acts directly on the breast gland. Once the effector glands produce sufficient hormones (thyroxine, cortisol, estradiol or testosterone and IGF-1), both the hypothalamus and the pituitary cells sense their abundance and reduce their secretion of stimulating hormones. The hormones of the posterior pituitary are produced in the hypothalamus and are carried by nerve endings to the posterior lobe; their feedback system is therefore located in the hypothalamus, but damage to the nerve endings would still lead to a deficiency in hormone release.
Hypopituitarism | Pathophysiology
Deficiency of all anterior pituitary hormones is more common than individual hormone deficiency. Deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), together referred to as the gonadotropins, leads to different symptoms in men and women. Women experience oligo- or amenorrhea (infrequent/light or absent menstrual periods respectively) and infertility. Men lose facial, scrotal and trunk hair, as well as suffering decreased muscle mass and anemia. Both sexes may experience a decrease in libido and loss of sexual function, and have an increased risk of osteoporosis (bone fragility). Lack of LH/FSH in children is associated with delayed puberty. Growth hormone (GH) deficiency leads to a decrease in muscle mass, central obesity (increase in body fat around the waist) and impaired attention and memory.
Hypopituitarism | Anterior pituitary
If the hypopituitarism is caused by the blood loss associated with childbirth, the disorder is referred to as Sheehan syndrome.
Anterior pituitary | Decreased activity
Children experience growth retardation and short stature.
Hypopituitarism | Anterior pituitary
The hypothalamus and pituitary gland are tightly integrated. Damage to the hypothalamus will impact the responsiveness and normal functioning of the pituitary. Hypothalamic disease may cause insufficient or inhibited signalling to the pituitary leading to deficiencies of one or more of the following hormones: thyroid-stimulating hormone, adrenocorticotropic hormone, beta-endorphin, luteinizing hormone, follicle-stimulating hormone, and melanocyte–stimulating hormones. Treatment for hypopituitarism involves hormone replacement therapy.
Hypothalamic disease | Hypopituitarism
Production of TSH and TRH is decreased by thyroxine by a negative feedback process. Not enough TRH, which is uncommon, can lead to not enough TSH and thereby to not enough thyroid hormone production.
Hypothyroidism | Pathophysiology
While GnRH receptors in the hypothalamus do not contain receptors for leptin, a positive correlation has been shown to exist between leptin receptor mRNA and the kisspeptin-expressing cells which are known to stimulate GnRH release.
Functional hypothalamic amenorrhea | Neuroendocrine
Deiodination is controlled by numerous hormones and nerval signals including TSH, vasopressin and catecholamines. Both peripheral thyroid hormones (iodothyronines) inhibit thyrotropin secretion from the pituitary (negative feedback). Consequently, equilibrium concentrations for all hormones are attained.
Hypothalamic–pituitary–thyroid axis | Physiology
Specifically, this underlies why the hypothalamus is necessarily sensitive to internal and external stimuli in its regulation of menstruation. Complete synchrony or the HPO axis is required for ovulation and reproduction in order to ensure pulsatile release of GnRH. Without this pulsatile release, the reduced levels of gonadotropins LH and FSH are insufficient to maintain full folliculogenesis and ovulatory ovarian function, resulting in profound hypoestrogenism. Additionally, external stress factors activate the HPA axis; increased corticotropin-releasing hormone (CRH) secretion results in increased secretion of ACTH from the pituitary gland, and thus increased secretion of cortisol from the adrenal glands. CRH, a regulator of the HPA and HPO axis, can be stimulated for release by the central nervous system in states of physical or mental stress that accompany the lifestyle factors contributing to amenorrhea.
Functional hypothalamic amenorrhea | Hormonal
The homeostatic maintenance of the anterior pituitary is crucial to our physiological well being. Increased plasma levels of TSH induce hyperthermia through a mechanism involving increased metabolism and cutaneous vasodilation. Increased levels of LH also result in hypothermia but through a decreased metabolism action. ACTH increase metabolism and induce cutaneous vasoconstriction, increased plasma levels also result in hyperthermia and prolactin decreases with decreasing temperature values. follicle-stimulating hormone (FSH) also may cause hypothermia if increased beyond homeostatic levels through an increased metabolic mechanism only. Gonadotropes, primarily luteinising hormone (LH) secreted from the anterior pituitary stimulates the ovulation cycle in female mammals, whilst in the males, LH stimulates the synthesis of androgen which drives the ongoing will to mate together with a constant production of sperm.
Anterior pituitary | Effects of the anterior pituitary
As a result, ACTH is released from the pituitary along with other pro-opiomelanocortin-related peptides such as beta-endorphin and b-lipotropic hormone. It is possible that increased levels of ghrelin in amenorrheic populations sensitizes the adrenal cortex to ACTH and is thereby associated with both hypothalamic CRH release and the frequency of cortisol bursts. Glucocorticosteroids are generally associated with inhibition of GnRH, adding strength to the stress-induced hypothesis of amenorrhea in some patients. By stimulating beta-endorphin, a hypothalamic and pituitary endogenous peptide, CRH can indirectly alter LH function by acting upstream on GnRH. A combination of this factor, along with the direct inhibition of GnRH caused by elevated CRH, may suggest a relationship between the incidence of stress- and exercise-related FHA and opioidergic activity.
Functional hypothalamic amenorrhea | Hormonal
Overexpression of deiodinase can thus lead to consumptive hypothyroidism. The thyroid gland is the only source of thyroid hormone in the body; the process requires iodine and the amino acid tyrosine. Iodine in the bloodstream is taken up by the gland and incorporated into thyroglobulin molecules. The process is controlled by the thyroid-stimulating hormone (TSH, thyrotropin), which is secreted by the pituitary. Not enough iodine, or not enough TSH, can result in decreased production of thyroid hormones. The hypothalamic–pituitary–thyroid axis plays a key role in maintaining thyroid hormone levels within normal limits. Production of TSH by the anterior pituitary gland is stimulated in turn by thyrotropin-releasing hormone (TRH), released from the hypothalamus.
Hypothyroidism | Pathophysiology
Thyrotropin releasing hormone (TRH) neurons in the hypothalamus integrate global signals about the body's energy state. They may be stimulated by signals such as leptin, alpha-MSH, and catecholamines; and inhibited by glucocorticoids, neuropeptide Y, and agouti-related peptide. In critical illness, inflammation increases tanycyte D2 in the paraventricular nucleus (PVN) of the hypothalamus, leading to local tissue hyperthyroidism. There may also be decreased central D3. This causes negative feedback on the HPT axis, and therefore reduced TRH gene expression in the PVN. This is exemplified by the common NTIS phenotype of low TSH even in the face of peripheral hypothyroidism.
Euthyroid sick syndrome | Hypothalamic-pituitary-thyroid axis downregulation
Hypopituitarism is characterized by a decreased secretion of hormones released by the anterior pituitary. For example, hypo-secretion of GH prior to puberty can be a cause of dwarfism. In addition, secondary adrenal insufficiency can be caused by hypo-secretion of ACTH which, in turn, does not signal the adrenal cortex to produce a sufficient amount of cortisol. This is a life-threatening condition. Hypopituitarism could be caused by the destruction or removal of the anterior pituitary tissue through traumatic brain injury, tumor, tuberculosis, or syphilis, among other causes. This disorder used to be referred to as Simmonds' disease but now according to the Diseases Database it is called Sheehan syndrome.
Anterior pituitary | Decreased activity
These potential conditions include hyperprolactinemia, POI, and polycystic ovary syndrome.
Hypoestrogenism | Functional hypothalamic amenorrhea
Each transcription factor acts in particular groups of cells. Therefore, various genetic mutations are associated with specific hormone deficiencies. For instance, "POU1F1" (also known as Pit-1) mutations cause specific deficiencies in growth hormone, prolactin and TSH. In addition to the pituitary, some of the transcription factors are also required for the development of other organs; some of these mutations are therefore also associated with specific birth defects. Most of the hormones in the anterior pituitary are each part of an "axis" that is regulated by the hypothalamus. The hypothalamus secretes a number of releasing hormones, often according to a circadian rhythm, into blood vessels that supply the anterior pituitary; most of these are stimulatory (thyrotropin-releasing hormone, corticotropin-releasing hormone, gonadotropin-releasing hormone and growth hormone-releasing hormone), apart from dopamine, which suppresses prolactin production.
Hypopituitarism | Pathophysiology
Because many of the symptoms overlap with those of organic hypothalamic, pituitary, or gonadal disease and therefore must be ruled out, FHA is a diagnosis of exclusion; "functional" is used to indicate a behavioral cause, in which no anatomical or organic disease is identified, and is reversible with correction of the underlying cause. Diagnostic workup includes a detailed history and physical, laboratory studies, such as a pregnancy test, and serum levels of FSH and LH, prolactin, and thyroid-stimulating hormone (TSH), and imaging. Additional tests may be indicated in order to distinguish FHA from organic hypothalamic or pituitary disorders. Patients present with a broad range of symptoms related to severe hypoestrogenism (including cardiovascular and skeletal irregularities) as well as hypercortisolemia, low serum insulin levels, low serum insulin-like growth factor 1 (IGF-1), and low total triiodothyronine (T3).
Functional hypothalamic amenorrhea | Introduction
Occasionally, the pituitary hormone may be normal but the effector gland hormone decreased; in this case, the pituitary is not responding appropriately to effector hormone changes, and the combination of findings is still suggestive of hypopituitarism.
Hypopituitarism | Diagnosis
Lower strength estimates, abnormal bone microarchitectures, and deficient volumetric bone density has been found in young adult amenorrheic athletes.
Functional hypothalamic amenorrhea | Diagnosis
Main article "Hypothalamic-pituitary-adrenal axis"
Anterior pituitary | Effects of the anterior pituitary
Relative energy expenditure (REE) is also closely linked to T, as is evidenced by a correlation between macronutrient intake, REE, and thyroid hormone levels. It has been found that AN patients who regain weight can restore T and REE independent of changes in FFM. Other hormonal changes in FHA include increased levels of nighttime serum growth hormone (GH), decreased levels of 24 hour prolactin, low serum insulin and IGF-1, and increased insulin sensitivity. GH has been found to be higher systemically in AN and exercise-induced FHA, with women who have the lowest FFM and body mass index BMI displaying the highest levels of circulating GH The result is peripheral resistance to GH, and this underlies the reduction in hepatic IGF-1 synthesis observed in many of these patients.
Functional hypothalamic amenorrhea | Hormonal
Thus, reproductive function can be altered through psychological or physiological stress through the HPA axis due to the modulatory effects that this pathway has on the HPO axis: its activation, which can occur in states of low energy availability (LEA) as an adaptive response to physical, nutritional, or extreme emotional stress, causes the release of CRH; In turn, this leads to the inhibition of GnRH pulsatility directly at the level of the hypothalamus and therefore precludes multilevel inhibition of the HPO axis. The hypothalamic-pituitary-thyroid axis is also altered in FHA; TSH levels are low-to-normal and there is an increase in reverse triiodothyronine and low level of triiodothyronine.
Functional hypothalamic amenorrhea | Hormonal
The risk of FHA due to weight-related factors increases across a series of four behaviors: 1) aesthetic dieting; 2) dieting due to obsessive ideals about diet and/or weight; 3) suppression of appetite, whether by drugs or self; 4) eating disorder, generally anorexia nervosa. Patients affected by eating disorders have overactive hypothalamic-pituitary systems, causing increased cortisol release and elevated β-endorphin concentrations. Hyperactivation of the hypothalamic-pituitary system appears to be manifested through increased secretion of CRH and beta-endorphin by the central nervous system, both of which can alter GnRH pulsatility. LH secretion may return to prepubertal levels, which is likely due to decreased GnRH secretion.
Functional hypothalamic amenorrhea | Weight-related
Together, these cellular signals stimulate a group of cells from the oral cavity to form Rathke's pouch, which becomes independent of the nasal cavity and develops into the anterior pituitary; this process includes the suppression of production of a protein called Sonic hedgehog by the cells of Rathke's pouch. The cells then differentiate further into the various hormone-producing cells of the pituitary. This requires particular transcription factors that induce the expression of particular genes. Some of these transcription factors have been found to be deficient in some forms of rare combined pituitary hormone deficiencies (CPHD) in childhood. These are "HESX1", "PROP1", "POU1F1", "LHX3", "LHX4", "TBX19", "SOX2" and "SOX3".
Hypopituitarism | Pathophysiology
A GnRH stimulation or challenge test should be used to identify FHA as the cause hypogonadotropic hypogonadism in women presenting with symptoms, as hypothalamic dysfunction due to delayed-onset puberty or other pituitary disease will not respond to exogenous GnRH. Hypothalamic disorders are differentiated when GnRH administration results in abnormal increases of gonadotropins. Combined pituitary and hypothalamic impairment is differentiated when there is a decreased or absent response to GnRH secretion; as a result, it impossible to determine if the observed low levels of FSH/LH are due to hypothalamic or pituitary dysfunction, and pulsatile GnRH administration with cyclomate is required to diagnose this distinction (pulsatile LH-RH challenge).
Functional hypothalamic amenorrhea | Diagnosis
Three hormones (usually synthetic analogues) are injected as a bolus into the patient's vein to stimulate the anterior pituitary gland: The gland's response is assessed by measuring the rise in cortisol and growth hormone (GH) in response to the hypoglycaemia caused by insulin, rises in prolactin and thyroid-stimulating hormone (TSH) caused by TRH and rises in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) caused by GnRH. Blood glucose levels are also monitored to ensure appropriate levels of hypoglycemia are achieved.
Combined rapid anterior pituitary evaluation panel | Process
In the case of prolactin and leptin, there is evidence of active uptake at the choroid plexus from the blood into the cerebrospinal fluid (CSF). Some pituitary hormones have a negative feedback influence upon hypothalamic secretion; for example, growth hormone feeds back on the hypothalamus, but how it enters the brain is not clear. There is also evidence for central actions of prolactin. Findings have suggested that thyroid hormone (T4) is taken up by the hypothalamic glial cells in the infundibular nucleus/ median eminence, and that it is here converted into T3 by the type 2 deiodinase (D2). Subsequent to this, T3 is transported into the thyrotropin-releasing hormone (TRH)-producing neurons in the paraventricular nucleus.
Hypothalamus | Blood-borne stimuli
FHA results from a functional reduction or disruption in GnRH release due to chronic negative energy balance, metabolism, body composition, and stress; such risk factors become relevant in cases of emotional stress, excessive exercise, and nutrient starvation. Metabolic cues, including an increase in body weight, are influential in the initiation of pulsatile GnRH release from the hypothalamus during puberty; this event allows for the pituitary to begin producing and releasing pulses of LH. Full folliculogenesis cannot occur if the initial GnRH drive is disrupted, and this can be caused by reduced leptin from loss of body fat due to nutritional deprivation, excessive exercise in which the calories burned are more than those consumed, and states of hypercortisolism due to stress-inducing attitudinal or environmental pressures.
Functional hypothalamic amenorrhea | Hormonal
However, the rest of the tissues will instead selectively display the defective gene, resulting in haploinsufficiency of the GNAS1 product in most tissues, and giving the phenotype of pseudohypoparathyroidism type 1a. As a result, there is also a normal response of urinary cAMP to PTH, and normal serum PTH.
Pseudopseudohypoparathyroidism | Pathophysiology
FHA may present with weight loss, bradycardia, mottled, cool extremities, and/or yellowing of the skin.
Functional hypothalamic amenorrhea | History and physical exam
Prostaglandins are now known to inhibit adrenocorticotropic hormone (ACTH) and also to stimulate TSH, GH and LH release. GABA, through action with the hypothalamus, has been shown experimentally to influence the level of GH secretion. Clinical evidence supports the experimental findings of the excitatory and inhibitory effects GABA has on GH secretion, dependent on GABA’s site of action within the hypothalamic-pituitary unit.
Anterior pituitary | Role in the endocrine system
In turn, the hypothalamus controls the release of hormones from the anterior pituitary by secreting a class of hypothalamic neurohormones called releasing and release-inhibiting hormones—which are released to the hypothalamo-hypophyseal portal system and act on the anterior pituitary.
Tropic hormone | Hypothalamus
The hypothalamus contains neurons that react strongly to steroids and glucocorticoids – (the steroid hormones of the adrenal gland, released in response to ACTH). It also contains specialized glucose-sensitive neurons (in the arcuate nucleus and ventromedial hypothalamus), which are important for appetite. The preoptic area contains thermosensitive neurons; these are important for TRH secretion.
Hypothalamus | Steroids
The hypothalamic–pituitary–thyroid axis (HPT axis for short, a.k.a. thyroid homeostasis or thyrotropic feedback control) is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress. As its name suggests, it depends upon the hypothalamus, the pituitary gland, and the thyroid gland. The hypothalamus senses low circulating levels of thyroid hormone (Triiodothyronine (T3) and Thyroxine (T4)) and responds by releasing thyrotropin-releasing hormone (TRH). The TRH stimulates the anterior pituitary to produce thyroid-stimulating hormone (TSH). The TSH, in turn, stimulates the thyroid to produce thyroid hormone until levels in the blood return to normal. Thyroid hormone exerts negative feedback control over the hypothalamus as well as anterior pituitary, thus controlling the release of both TRH from hypothalamus and TSH from anterior pituitary gland.
Hypothalamic–pituitary–thyroid axis | Introduction
Granulomas in the pituitary gland, which produces numerous hormones, is rare but leads to any of the symptoms of hypopituitarism: amenorrhoea (cessation of the menstrual cycle), diabetes insipidus (dehydration due to inability to concentrate the urine), hypothyroidism (decreased activity of the thyroid) or hypocortisolism (deficiency of cortisol).
Neurosarcoidosis | Endocrine
Hypothalamus secretes a hormone called thyrotropin releasing hormone (TRH) which in turn release thyroid stimulating hormone (TSH). TSH signals thyroid to secrete thyroid hormones thyroxine (T4) and triiodothyronine (T3). T4 gets converted to active T3 in peripheral tissues with the help of deiodinase enzymes. T3 negatively feedback on the pituitary and decreases TSH secretion.
Thyroid hormone resistance | Regulation of thyroid hormone secretion
-- Method for Heating the Preoptic Anterior Hypothalamus
Preoptic anterior hypothalamus | References
Thyrotropes (also called thyrotrophs) are endocrine cells in the anterior pituitary which produce thyroid stimulating hormone (TSH) in response to thyrotropin releasing hormone (TRH). Thyrotropes consist around 5% of the anterior pituitary lobe cells. Thyrotropes appear basophilic in histological preparations.
Thyrotropic cell | Introduction
Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus by GnRH-expressing neurons. The anterior portion of the pituitary gland produces luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the gonads produce estrogen and testosterone.
Hypothalamic–pituitary–gonadal axis | Introduction
Unless the pituitary damage is being caused by a tumor that overproduces a particular hormone, it is the lack of pituitary hormones that leads to the symptoms described above, and an excess of a particular hormone would indicate the presence of a tumor. The exception to this rule is prolactin: if a tumor compresses the pituitary stalk, a decreased blood supply means that the lactotrope cells, which produce prolactin, are not receiving dopamine and therefore produce excess prolactin. Hence, mild elevations in prolactin are attributed to stalk compression. Very high prolactin levels, though, point more strongly towards a prolactinoma (prolactin-secreting tumor).
Hypopituitarism | Pathophysiology
Hormone secretion from the anterior pituitary gland is regulated by hormones secreted by the hypothalamus. Neuroendocrine cells in the hypothalamus project axons to the median eminence, at the base of the brain. At this site, these cells can release substances into small blood vessels that travel directly to the anterior pituitary gland (the hypothalamo-hypophyseal portal vessels). Aside from hypothalamic control of the anterior pituitary, other systems in the body have been shown to regulate the anterior pituitary’s function. GABA can either stimulate or inhibit the secretion of luteinizing hormone (LH) and growth hormone (GH) and can stimulate the secretion of thyroid-stimulating hormone (TSH).
Anterior pituitary | Role in the endocrine system
This is due to the possible confusion with white blood cells, where one may also find basophils and acidophils.
Anterior pituitary | Structure
These hypophysiotropic hormones stimulate or inhibit the release of hormones from the anterior pituitary. Further, anatomical evidence exists for bidirectional communication between the median eminence and the arcuate and ventromedial nucleus of the hypothalamus.
Median eminence | Physiology
All of these modulators cause energy to be moved away from growth and reproduction in order to maintain vital cellular processes, thereby suppressing the aforementioned processes. The effect of nutrition/metabolic status on reproduction is mediated through GnRH secretion. GABA neurons, KNDy neurons, and leptin are specifically responsible for alterations in GnRH secretion. GABA and KNDy neurons synapse with GnRH neurons at sites where leptin receptors are absent to favor LH release. Decreased leptin results in decreased LH release and is observed in periods of long term caloric restriction and fasting. These effects appear to be dose-dependent, where cases of more severe energy restriction (due to inadequate caloric intake or excess exercise) result in greater alterations of LH pulsatility.
Functional hypothalamic amenorrhea | Risk factors
The symptoms depend on what part of the pituitary is affected. Lymphocytic adenohypophysitis (LAH) occurs when the anterior pituitary cells are affected by autoimmune inflammation resulting in either no symptoms, adrenal insufficiency (if the ACTH producing cells are affected), hypothyroidism (if the TSH producing cells are damaged), or hypogonadism (if the LH and/or FSH producing cells are involved). In some cases, the presence of inflammation within the pituitary gland leads to interruption of dopamine flow from the hypothalamus into the pituitary causing high levels of the hormone prolactin and, often as a consequence, milk production from the breasts (in older girls and women).
Autoimmune hypophysitis | Signs and symptoms
Hypopituitarism commonly develops after radiation therapy for sellar and parasellar neoplasms, extrasellar brain tumours, head and neck tumours, and following whole body irradiation for systemic malignancies. Radiation-induced hypopituitarism mainly affects growth hormone and gonadal hormones. In contrast, adrenocorticotrophic hormone (ACTH) and thyroid stimulating hormone (TSH) deficiencies are the least common among people with radiation-induced hypopituitarism. Changes in prolactin-secretion is usually mild, and vasopressin deficiency appears to be very rare as a consequence of radiation.
Radiation therapy | Effects on pituitary system
The genes implicated included the following: FGFR1, which is involved in the specification, fate, migration, and survival of GnRH-secreting neurons, PROKR2 and KAL1, which enable the migration of GnRH-secreting neurons, and GNRHR, which encodes the pituitary receptor activated by GnRH1. Mutations in PROKR2 or FGFR1 may cause mechanistic dysfunction of GnRH pathways by either decreasing the number of GnRH-secreting cells that are able to migrate to the hypothalamus in development, inhibiting maturation of these cells during maturity, or disrupting GnRH secretion in adulthood. FHA patients harboring these mutations have been shown to be able to resume regular menses, further reinforcing that while genetic defects may predispose one to the condition, environmental factors play a pivotal role in disease manifestation.
Functional hypothalamic amenorrhea | Genetic Predisposition
Hypopituitarism is the decreased ("hypo") secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism ("pan" meaning "all") is used. The signs and symptoms of hypopituitarism vary, depending on which hormones are undersecreted and on the underlying cause of the abnormality. The diagnosis of hypopituitarism is made by blood tests, but often specific scans and other investigations are needed to find the underlying cause, such as tumors of the pituitary, and the ideal treatment.
Hypopituitarism | Introduction
According to the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists, menstrual status should be considered a “vital sign” for all routine clinical visits because of the known effects of hypoestrogenism on bone and tissue health.
Functional hypothalamic amenorrhea | Presentation
The diagnosis of hypopituitarism is made on blood tests. Two types of blood tests are used to confirm the presence of a hormone deficiency: basal levels, where blood samples are taken–usually in the morning–without any form of stimulation, and dynamic tests, where blood tests are taken after the injection of a stimulating substance. Measurement of ACTH and growth hormone usually requires dynamic testing, whereas the other hormones (LH/FSH, prolactin, TSH) can typically be tested with basal levels. There is no adequate direct test for ADH levels, but ADH deficiency can be confirmed indirectly; oxytocin levels are not routinely measured. Generally, the finding of a combination of a low pituitary hormone together with a low hormone from the effector gland is indicative of hypopituitarism.
Hypopituitarism | Diagnosis
Dysfunction of the hypothalamus results in loss of regulation over behavior and function of the pituitary gland (master gland). Hypopituitarism is present in 75% to 80% of patients with ONH. The anterior pituitary gland contributes to growth, metabolism, and sexual development. The most common pituitary endocrinopathies are growth hormone (GH) deficiency (70%), hypothyroidism (43%), adrenal insufficiency (27%), and diabetes insipidus (5%). Absence of GH may often be indicated by short stature, although this is not always the case. Other indicators of GH deficiency may include hypoglycemic events (including seizures), prolonged jaundice, micropenis in boys, and delayed dentition. Testing for GH may involve blood tests (IGF-1 and IGFBP-3), growth hormone stimulation test, or bone age x-ray of the hand or wrist (or body for children younger than 2 years).
Optic nerve hypoplasia | Hypothalamic dysfunction
In this population, where success in sport is highly emphasized, decreasing training intensity is typically not an option. Parents and legal guardians should be made aware of the long-term risk factors for osteoporosis and infertility which underlie this condition when deciding on a treatment plan. A multi-disciplinary team approach in management that includes a medical doctor, dietitian, and a psychiatrist or psychologist to provide psychological support is recommended. If menstruation does not resume spontaneously following lifestyle changes, the patient should be monitored for thyroid function, HPO axis function, and concentrations of ACTH, cortisol, and prolactin every 4–5 months.
Functional hypothalamic amenorrhea | Management
Hypothalamic disease therefore affects the functioning of the pituitary and the target organs controlled by the pituitary, including the adrenal glands, ovaries and testes, and the thyroid gland. Numerous dysfunctions manifest as a result of hypothalamic disease. Damage to the hypothalamus may cause disruptions in body temperature regulation, growth, weight, sodium and water balance, milk production, emotions, and sleep cycles. Hypopituitarism, neurogenic diabetes insipidus, tertiary hypothyroidism, and developmental disorders are examples of precipitating conditions caused by hypothalamic disease.
Hypothalamic disease | Introduction
Tropic hormones from the anterior pituitary include:
Tropic hormone | Anterior pituitary
There is no direct way of increasing thyroid hormone secretion by the thyroid gland.
Hypothyroidism | Hormone replacement
Functional hypothalamic amenorrhea (FHA) is a form of amenorrhea and chronic anovulation and is one of the most common types of secondary amenorrhea. It is classified as hypogonadotropic hypogonadism. It was previously known as "juvenile hypothalamosis syndrome," prior to the discovery that sexually mature females are equally affected. FHA has multiple risk factors, with links to stress-related, weight-related, and exercise-related factors. FHA is caused by stress-induced suppression of the hypothalamic-pituitary-ovarian (HPO) axis, which results in inhibition of gonadotropin-releasing hormone (GnRH) secretion, and gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Severe and potentially prolonged hypoestrogenism is perhaps the most dangerous hormonal pathology associated with the disease, because consequences of this disturbance can influence bone health, cardiovascular health, mental health, and metabolic functioning in both the short and long-term.
Functional hypothalamic amenorrhea | Introduction
Standard procedures cover the determination of serum levels of the following hormones: For special conditions the following assays and procedures may be required:
Hypothalamic–pituitary–thyroid axis | Diagnostics
Loss of function of LH receptors can cause male pseudohermaphroditism. In females mutations would have analogous effects. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis.
Hypothalamic–pituitary–gonadal axis | Gene mutations
Inhibition of dopamine allows for an increase in prolactin secretion and concentration (hyperprolactinemia), which leads to inhibition of LH, and in turn leads to anovulation. Inhibition of the HPO axis also results in inhibition of the hypothalamic-pituitary-thyroid (HPT) axis and a decrease in thyroid hormones, in an attempt to minimize energy depletion. This allows the body to focus on survival, rather than reproduction. High concentrations of dopamine and low concentrations of prolactin (and serotonin) can also cause FHA. Females with these levels characteristically have higher levels of aggression, higher levels of testosterone, and lower levels of estrogen.
Functional hypothalamic amenorrhea | Stress-related
Thyroid hormone receptors have been found in these neurons, indicating that they are indeed sensitive to T3 stimuli. In addition, these neurons expressed MCT8, a thyroid hormone transporter, supporting the theory that T3 is transported into them. T3 could then bind to the thyroid hormone receptor in these neurons and affect the production of thyrotropin-releasing hormone, thereby regulating thyroid hormone production.
Hypothalamus | Blood-borne stimuli
Most hormones controlled by the secretions of the pituitary can be replaced by tablets or injections. Hypopituitarism is a rare disease, but may be significantly underdiagnosed in people with previous traumatic brain injury. The first description of the condition was made in 1914 by the German physician Dr Morris Simmonds.
Hypopituitarism | Introduction
The pituitary was known to the ancients, such as Galen, and various theories were proposed about its role in the body, but major clues as to the actual function of the gland were not advanced until the late 19th century, when acromegaly due to pituitary tumors was described. The first known report of hypopituitarism was made by the German physician and pathologist Dr Morris Simmonds. He described the condition on autopsy in a 46-year-old woman who had suffered severe puerperal fever eleven years earlier, and subsequently suffered amenorrhea, weakness, signs of rapid aging and anemia. The pituitary gland was very small and there were few remnants of both the anterior and the posterior pituitary.
Hypopituitarism | History
The cause of hyperpituitarism in most cases is due to pituitary adenomas. They usually come from the anterior lobe, are functional and secrete the hormone, GH and prolactin.
Hyperpituitarism | Cause
Hyponatremia, an unusually low level of sodium in the blood that may cause confusion and seizures, is found in 40% of cases. This may be caused by low cortisol levels or by inappropriate release of antidiuretic hormone (ADH) from the posterior pituitary. Several other hormonal deficiencies may develop in the subacute phase. 50% have a deficiency in thyroid-stimulating hormone (TSH), leading to hyposecretion of thyroid hormone by the thyroid gland and characteristic symptoms such as fatigue, weight gain, and cold intolerance. 75% develop a deficiency to gonadotropins (LH and FSH), which control the reproductive hormone glands. This leads to a disrupted menstrual cycle, infertility, and decreased libido.
Pituitary apoplexy | Endocrine dysfunction
Long-term follow up by specialists in endocrinology is generally needed for people with known hypopituitarism. Apart from ensuring the right treatment is being used and at the right doses, this also provides an opportunity to deal with new symptoms and to address complications of treatment. Difficult situations arise in deficiencies of the hypothalamus-pituitary-gonadal axis in people (both men and women) who experience infertility; infertility in hypopituitarism may be treated with subcutaneous infusions of FSH, human chorionic gonadotropin–which mimics the action of LH–and occasionally GnRH.
Hypopituitarism | Hormone replacement
Conversely, acromegaly and gigantism are conditions of GH and IGF-1 excess usually due to a pituitary tumor, and are characterized by overgrowth and tall stature.
Hypothalamic–pituitary–somatotropic axis | Introduction
Studies indicate that the loss of endogenous estrogens through hypothalamic suppression may worsen an already-existing hyperglycemia, further antagonizing estrogen-mediated NO release and compounding the risk for vascular dysfunction in patients with both FHA and diabetes mellitus.
Functional hypothalamic amenorrhea | Cardiovascular
It is easy to see from these interplays why anorexics with decreased leptin and athletes who consume less calories than they expend are likely to present with FHA as a mechanism to preserve energy for processes critical to survival.
Functional hypothalamic amenorrhea | Risk factors
Excessive or intense psychosocial, emotional, or mental stress can lead to hypothalamic dysfunction. In adolescents, this is called "adolescence crisis" and can occur during, or post, puberty. This crisis can cause young adults to develop behavioral or eating disorders (mentioned below), and, if severe and prolonged enough, can result in the menstrual irregularities seen in FHA. When the body is stressed, the sympathetic adrenal-medullary (SAM) axis, followed by the hypothalamic-pituitary-adrenal (HPA) axis. These events suppress the HPO axis because the corticotropin-releasing hormone (CRH) released by the HPA axis inhibit the secretion of GnRH by the hypothalamus. CRH also stimulates secretion of beta(β)-endorphins, which suppresses release of GnRH and dopamine.
Functional hypothalamic amenorrhea | Stress-related
Sheehan's syndrome is caused by damage to the pituitary, thereby causing a decrease in one or more of the hormones it normally secretes. The anterior pituitary is supplied by a low pressure portal venous system. A 1995 study found that 56.2% of patients with diagnosed Sheehan’s syndrome experienced a loss of all pituitary hormones (with the remaining 43.8% having selective pituitary insufficiency). Since the growth hormone-secreting cells are located at the periphery of the pituitary (and are therefore most likely to be affected by ischemia), all of the patients experienced growth hormone deficiency.
Sheehan's syndrome | Pathophysiology
These mutations also lead to varying degrees of hypopituitarism.
Development of the endocrine system | Parathyroid glands
It is possible that heterozygosity at these loci are not sufficient to cause IHH, but decrease the threshold for HPO inhibition due to environmental factors such as weight loss, stress, and excessive exercise. Functionally speaking, carrying these mutations could confer a selective advantage in a famine conditions, and it is not uncommon for the alleles to be inherited from an asymptomatic parents in both heterozygous and homozygous recessive manifestations of IHH.
Functional hypothalamic amenorrhea | Genetic Predisposition
The anterior pituitary is also known as the adenohypophysis, meaning "glandular undergrowth", from the Greek "adeno-" ("gland"), "hypo" ("under"), and "physis" ("growth").
Anterior pituitary | Etymology
The pituitary gland is located at the base of the brain, and intimately connected with the hypothalamus. It consists of two lobes: the posterior pituitary, which consists of nervous tissue branching out of the hypothalamus, and the anterior pituitary, which consists of hormone-producing epithelium. The posterior pituitary secretes antidiuretic hormone, which regulates osmolarity of the blood, and oxytocin, which causes contractions of the uterus in childbirth and participates in breastfeeding. The pituitary develops in the third week of embryogenesis from interactions between the diencephalon part of the brain and the nasal cavity. The brain cells secrete FGF-8, Wnt5a and BMP-4, and the oral cavity BMP-2.
Hypopituitarism | Pathophysiology
In addition, physicians should also inquire about eating and reproductive disorders within the family. In patients presenting with structural abnormalities that may preclude regular menses, it is still necessary to take emotional history and lifestyle into account before establishing a diagnosis. These patients may still demonstrate patterns of excessive exercise or restrictive eating, proving the important role of behavioral etiology in FHA diagnosis. A full physical exam, external gynecological and bimanual exam can be performed to assess for organic causes of amenorrhea. Symptoms of hypoestrogenism, whose severity will positively correlate with the duration of hypoestrogenism, will be present in FHA patients; these can can include lack of cervical mucus, pale areola and nipples, thinned, reddened vaginal and vestibular epithelium, and uterine hyperplasia, though FHA is not typically associated with hot flashes.
Functional hypothalamic amenorrhea | History and physical exam
Successful treatment varies depending on the diagnosis of amenorrhea. In patients with functional hypothalamic amenorrhea due to physical or psychological stress, non-pharmacological options include weight gain, resolution of emotional issues, or decreased intensity of exercise. Patients experiencing amenorrhea due to hypothyroidism may be started with thyroid replacement therapy. Dopamine agonists such as bromocriptine are used in patients with pituitary adenomas. Amenorrhea associated with gonadal dysgenesis or a hypoestrogenic state may be treated with oral contraceptives, patches, or vaginal rings. Amenorrhea associated with structural anomalies can be addressed with surgical treatment such as gonadectomy.
Menstrual disorder | Amenorrhea
TRH-stimulation testing however continues to be useful for the differential diagnosis of secondary (pituitary disorder) and tertiary (hypothalamic disorder) hypothyroidism. Patients with these conditions appear to have physiologically inactive TSH in their circulation that is recognized by TSH assays to a degree such that they may yield misleading, "euthyroid" TSH results.Use and Interpretation: • Helpful in diagnosis in patients with confusing TFTs. In primary hyperthyroidism TSH are low and TRH administration induces little or no change in TSH levels • In hypothyroidism due to end organ failure, administration of TRH produces a prompt increase in TSH • In hypothyroidism due to pituitary disease (secondary hypothyroidism)administration of TRH does not produce an increase in TSH
TRH stimulation test | Differential diagnosis use
Functional hypothalamic amenorrhea (FHA) is diagnosed based on findings of amenorrhea lasting three months or more, low serum hormone of gonadotropins and estradiol. Since common causes of FHA include exercising too much, eating too little, or being under too much stress, diagnosis of FHA includes accessing for any changes in exercise, weight, and stress. In addition, evaluation of amenorrhea includes a history and physical examination, biochemical testing, imaging, and measuring estrogen level. Examination of menstrual problems and clinical tests to measure hormones such as serum prolactin, thyroid-stimulating hormone, and follicle-stimulating hormone (FSH) can help rule out other potential causes of amenorrhea.
Hypoestrogenism | Functional hypothalamic amenorrhea
In adult women, FHA can lead to atrophic changes, such as lack of cervical mucus, thinning of vaginal epithelium, and uterine muscle atrophy (hypoplasia), which can lead to painful intercourse (dyspareunia).
Functional hypothalamic amenorrhea | Reproductive
The use of the term hypogonadotropic relates to the fact that the hypogonadism found in HH is caused by a disruption in the production of the gonadotropin hormones normally released by the anterior pituitary gland known as luteinising hormone (LH) and follicle stimulating hormone (FSH). Failure in GnRH activity can otherwise be due to the absence of the GnRH releasing neurons inside the hypothalamus. HH can occur as an isolated condition with just the LH and FSH production being affected or it can occur in combined pituitary deficiency conditions. In the first 10 weeks of normal embryonic development, the GnRH releasing neurons migrate from their original source in the nasal region and end up inside the hypothalamus.
Kallmann syndrome | Pathophysiology
Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T), and then triiodothyronine (T) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid. In 1916, Bennett M. Allen and Philip E. Smith found that the pituitary contained a thyrotropic substance.
Thyroid-stimulating hormone | Introduction
The complex mechanisms of FHA are unclear, though it is known that many neuromodulatory signals are involved in the regulation of pulsatile GnRH secretion. Some notable substances include kisspeptin, neuropeptide Y (NPY), ghrelin, peptide YY (PYY), leptin, adiponectin, CRH, β-endorphin, and allopregnanolone. Kisspeptin and its G-protein coupled receptor, GPR54, activate the HPO axis to directly stimulate GnRH secretion from the hypothalamus. NPY regulates energy balance and affects feeding behavior and appetite. If estradiol (E2) levels are sufficient, NPY induces GnRH secretion. Amenorrheic women have been found to have lower serum NPY than controls. Thus, in these hypoestrogenic subjects, decreased concentrations of this peptide may contribute to the observed disruption of GnRH release.
Functional hypothalamic amenorrhea | Neuroendocrine
A pituitary disease is a disorder primarily affecting the pituitary gland. The main disorders involving the pituitary gland are: Overproduction or underproduction of a pituitary hormone will affect the respective end-organ. For example, insufficient production (hyposecretion) of thyroid stimulating hormone (TSH) in the pituitary gland will cause hypothyroidism, while overproduction (hypersecretion) of TSH will cause hyperthyroidism. Thyroidisms caused by the pituitary gland are less common though, accounting for less than 10% of all hypothyroidism cases and much less than 1% of hyperthyroidism cases.
Pituitary disease | Introduction
Measuring the level of thyroid-stimulating hormone (TSH), produced by the pituitary gland (which in turn is also regulated by the hypothalamus's TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T and/or T in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness (euthyroid sick syndrome) and so checking the T and T is still clinically useful.
Hyperthyroidism | Diagnosis
After traumatic brain injury, as much as a quarter have persistent pituitary hormone deficiencies. Many of these people may have subtle or non-specific symptoms that are not linked to pituitary problems but attributed to their previous condition. It is therefore possible that many cases of hypopituitarism remain undiagnosed, and that the annual incidence would rise to 31 per 100,000 annually if people from these risk groups were to be tested.
Hypopituitarism | Epidemiology
The presumed pathogenesis is that primary hypothyroidism causes enlargement and hyperstimulation of the pituitary gland which in turn cause ovarian hyperstimulation, ovarian cysts and precocious puberty.
Van Wyk and Grumbach syndrome | Mechanism
GH may also modulate reproduction at the level of the pituitary and ovaries by altering LH/FSH secretion as well as estradiol and progesterone production. Some studies suggest that GH is needed for the maturation and survival of dominant follicles and corpora lutea. Increased insulin sensitivity is likely common in many FHA patients because a state of chronic low EA incentivizes high GH secretion to maintain euglycemia; thus, euglycemia can be maintained in FHA patients despite low levels of IGF-1.
Functional hypothalamic amenorrhea | Hormonal
Thyrotropin-releasing hormone (TRH), is a hypophysiotropic hormone, produced by neurons in the hypothalamus, that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary. TRH has been used clinically for the treatment of spinocerebellar degeneration and disturbance of consciousness in humans. Its pharmaceutical form is called protirelin (INN) ().
Thyrotropin-releasing hormone | Introduction
Thyroid homeostasis results from a multi-loop feedback system that is found in virtually all higher vertebrates. Proper function of thyrotropic feedback control is indispensable for growth, differentiation, reproduction and intelligence. Very few animals (e.g. axolotls and sloths) have impaired thyroid homeostasis that exhibits a very low set-point that is assumed to underlie the metabolic and ontogenetic anomalies of these animals. The pituitary gland secretes thyrotropin (TSH; Thyroid Stimulating Hormone) that stimulates the thyroid to secrete thyroxine (T4) and, to a lesser degree, triiodothyronine (T3). The major portion of T3, however, is produced in peripheral organs, e.g. liver, adipose tissue, glia and skeletal muscle by deiodination from circulating T4.
Hypothalamic–pituitary–thyroid axis | Physiology
Other specific cases may warrant other useful measures: for example, IGF-1 may be indicated in FHA patients with AN, as resistance to GH can expose a connection between bone metabolism and malnutrition; this population may also present with low DHEA-S, which may work to actively lower IGF-1 levels.
Functional hypothalamic amenorrhea | Laboratory testing
The anterior pituitary contains five types of endocrine cell, and they are defined by the hormones they secrete: somatotropes (GH); Lactotropes (PRL); gonadotropes (LH and FSH); corticotropes (ACTH) and thyrotropes (TSH). It also contains non-endocrine folliculostellate cells which are thought to stimulate and support the endocrine cell populations. Hormones secreted by the anterior pituitary are trophic hormones (Greek: trophe, “nourishment”). "Trophic hormones" directly affect growth either as hyperplasia or hypertrophy on the tissue it is stimulating. "Tropic hormones" are named for their ability to act directly on target tissues or other endocrine glands to release hormones, causing numerous cascading physiological responses.
Anterior pituitary | Function
If interested, a good explanation of this process and the consequences of abnormal levels of TSH can be found under this link. Reduced levels of thyroid hormones have many physical and cognitive implications for a fetus once fully developed. Because of ethical reasons, most research has been carried out on rats and other mammals. However, in the hypothyroid rat brain, numerous malformations were found: reduced myelin of neurons in the CNS, deficiency of neurons in the cerebral cortex, the visual cortex and auditory cortex, hippocampus and cerebellum, which relate to general learning and motor skill acquisition.
Prenatal memory | Hypothyroidism
Amenorrhea, defined as the cessation of a woman’s menstrual cycle for more than three months, is the second disorder in the Triad. Weight fluctuations from dietary restrictions and/or excessive exercise affect the hypothalamus’s output of gonadotropic hormones. Gonadotropic hormones “stimulate growth of the gonads and the secretion of sex hormones.” (e.g. gonadotropin-releasing hormone, lutenizing hormone and follicle stimulating hormone.) These gonadotropic hormones play a role in stimulating estrogen release from the ovaries. Without estrogen release, the menstrual cycle is disrupted. Exercising intensely and not eating enough calories can lead to decreases in estrogen, the hormone that helps to regulate the menstrual cycle.
Relative energy deficiency in sport | Amenorrhea
Mice lacking a functional "Igsf1" gene similarly exhibit hypothyroidism of central origin. The "IGSF1" gene is particularly active in the pituitary gland. The pituitary synthesizes and secretes thyroid-stimulating hormone (TSH). TSH, in turn, stimulates production of the thyroid hormones, thyroxine and triiodothyronine, by the thyroid gland. TSH secretion is controlled by thyrotropin-releasing hormone (TRH), which is released by neurons in the hypothalamus of the brain. In "Igsf1" deficient mice, the receptor for TRH is downregulated in the pituitary. This decrease could explain, at least in part, the central hypothyroidism observed in both humans and mice with IGSF1 deficiency. How the loss of IGSF1 causes a decrease in TRH receptors is presently unknown.
IGSF1 | Animal Model
The pituitary gland is divided into two sections: the anterior pituitary and the posterior pituitary. The hypothalamus controls the anterior pituitary's hormone secretion by sending trophic hormones down the hypothalamohypophysial portal system. For example, thyrotropin-releasing hormone stimulates the secretion of thyroid-stimulating hormone by the anterior pituitary. The posterior pituitary is innervated by the hypothalamus; the hormones oxytocin and vasopressin are synthesized by neuroendocrine cells in the hypothalamus and stored at the nerves' ends in the posterior pituitary. They are secreted directly into systemic circulation by the hypothalamic neurons.
Neuroendocrinology | Pituitary gland
An anti-NTIS phenotype is observed in some circumstances, wherein TSH, T3, and T4 are generally elevated rather than suppressed. This can occur during pregnancy, obesity, cold adaptation, stay in high altitudes, endurance exercise, acute psychosis, and post-traumatic stress disorder. According to newer theories, elevated concentrations of TSH and thyroid hormones in type 2 allostasis result from an up-regulated set point of the feedback loop, which ensues from increased TRH expression in the basolateral amygdala and the paraventricular nucleus of the hypothalamus in response to stress. High-T3 syndrome in thyroid carcinoma may result from autonomous thyroid hormone secretion or overexpression of type 2 deiodinase in cancer cells rather than from type 2 allostasis.
Euthyroid sick syndrome | Alternative phenotype (type 2 thyroid allostasis)