This is a form of dysautonomia but differentiated from familial dysautonomia by a lack of familial dysautonomic symptoms such as loss of sense of pain and smell. While L-threo-DOPS has been described as being "very effective for restoring noradrenergic tone and correcting postural hypotension, response to treatment is variable and the long-term and functional outcome is unknown."

Researchers have put together retrospective data collections in order to better under the progression of this orphan disease. Most studies show a perinatal period marked by inadequacy of the ANS to control blood pressure, blood sugar, and body temperature. The experiences of orthostatic hypotension, exercise intolerance, and "traumatic morbidity related to falls and syncope" have been documented later in lives of people with this condition. To provide a basis for improving the understanding of the epidemiology, genotype/phenotype correlation, outcome of these diseases, their impact on the quality of life of patients, and for evaluating diagnostic and therapeutic strategies, a patient registry was established by the non-commercial International Working Group on Neurotransmitter Related Disorders (iNTD).

Untreated individuals with DβH deficiency should avoid hot environments, strenuous exercise, standing still, and dehydration.

Glucocorticoid remediable aldosteronism (GRA), also describable as "aldosterone synthase hyperactivity", is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.

It is a cause of primary hyperaldosteronism.

The number of events that can lead to the development of PSH symptoms is many. The exact pathways or causes for the development of the syndrome are not known. Traumatic brain injury, hypoxia, stroke, anti-NMDA receptor encephalitis (although further associations are being explored), injury of the spinal cord, and many other forms of brain injury can cause onset of PSH. Even more obscure diseases such as intracranial tuberculoma have been seen to cause onset of paroxysmal sympathetic hyperactivity. It is observed that these injuries lead to the development of PSH or are seen in conjunction with PSH, but the pathophysiology behind these diseases and the syndrome is not well understood.

This condition is very rare; approximately 600 cases have been reported worldwide. In most parts of the world, only 1% to 2% of all infants with high phenylalanine levels have this disorder. In Taiwan, about 30% of newborns with elevated levels of phenylalanine have a deficiency of THB.

Adipsia, also known as hypodipsia, is a symptom of inappropriately decreased or absent feelings of thirst. It involves an increased osmolality or concentration of solute in the urine, which stimulates secretion of antidiuretic hormone (ADH) from the hypothalamus to the kidneys. This causes the person to retain water and ultimately become unable to feel thirst. Due to its rarity, the disorder has not been the subject of many research studies.

Adipsia may be seen in conditions such as diabetes insipidus and may result in hypernatremia. It can occur as the result of abnormalities in the hypothalamus, pituitary and corpus callosum, as well as following pituitary/hypothalamic surgery.

It is possible for hypothalamic dysfunction, which may result in adipsia, to be present without physical lesions in the hypothalamus, although there are only four reported cases of this. There are also some cases of patients experiencing adipsia due to a psychiatric disease. In these rare psychogenic cases, the patients have normal levels of urine osmolality as well as typical ADH activity.

In GRA, the hypersecretion of aldosterone and the accompanying hypertension are remedied when ACTH secretion is suppressed by administering glucocorticoids.

Dexamethasone, spironolactone and eplerenone have been used in treatment.

The diagnosis of sepiapterin reductase deficiency in a patient at the age of 14 years was delayed by an earlier diagnosis of an initially unclassified form of methylmalonic aciduria at the age of 2. At that time the hypotonia and delayed development were not considered to be suggestive of a neurotransmitter defect. The clinically relevant diagnosis was only made following the onset of dystonia with diurnal variation, when the patient was a teenager. Variability in occurrence and severity of other symptoms of the condition, such as hypotonia, ataxia, tremors, spasticity, bulbar involvement, oculogyric crises, and cognitive impairment, is comparable with autosomal dominant GTPCH and tyrosine hydroxylase deficiency, which are both classified as forms of DOPA-responsive dystonia.

Patients who develop PSH after traumatic injury have longer hospitalization and longer durations in intensive care in cases where ICU treatment is necessary. Patients often are more vulnerable to infections and spend longer times on ventilators, which can lead to an increased risk of various lung diseases. PSH does not affect mortality rate, but it increases the amount of time it takes a patient to recover from injury, compared to patients with similar injuries who do not develop PSH episodes. It often takes patients who develop PSH longer to reach similar levels of the brain activity seen in patients who do not develop PSH, although PSH patients do eventually reach these same levels.

Dopamine, a neurotransmitter, has been linked with feeding behaviors. In an experiment, scientists measured how much food and water mice consumed when they were born without dopamine in their systems. They found that without dopamine, the mice would starve and be dehydrated to the point of death. The scientists then injected the mice without dopamine with its precursor, L-DOPA, and the mice started eating again. But, even though the mice were born without dopamine in their systems, they still had the capacity to control their feeding and drinking behaviors, suggesting that dopamine does not play a role in developing those neural circuits. Instead, dopamine is more closely related to the drive for hunger and thirst. Although the lack of dopamine resulted in adipsia in these rats, low levels of dopamine do not necessarily cause adipsia.

Other findings in support of the role of dopamine in thirst regulation involved the nigrostriatal pathway. After completely degenerating the pathway, the animal becomes adipsic, aphagic, and loses its interest in exploring. Although dopamine plays a role in adipsia, there is no research involving exclusively the relationship between adipsia and dopamine, as changes in dopamine simultaneously mediate changes in eating and curiosity, in addition to thirst.

Human findings provide insufficient data for developing treatments due to differences in the patients physiological and metabolic disorders thus, a suitable alternative animal model is essential in obtaining a better understanding of the SR deficiency. In this particular case, researchers used silkworms to identify and characterize mutations relating to SPR activity from an initial purified state created in the larvae of the silkworm. The researchers used genetic and biochemical approaches to demonstrate oral administration of BH and dopamine which increased the survival rates of the silkworm larvae. The results indicate that BH deficiency in silkworms leads to death in response to the lack of dopamine. This shows that silkworms can be useful insect models in additional SR deficiency research and study.

RLS symptoms may gradually worsen with age, though more slowly for those with the idiopathic form of RLS than for patients who also have associated medical condition. Nevertheless, current therapies can control the disorder, minimizing symptoms and increasing periods of restful sleep. In addition, some patients have remissions, periods in which symptoms decrease or disappear for days, weeks, or months, although symptoms usually eventually reappear. Being diagnosed with RLS does not indicate or foreshadow another neurological disease.

There are several known causes of adrenergic storms; in the United States, cocaine overdose is the leading cause. Any stimulant drug has the capacity to cause this syndrome if taken in sufficient doses, but even non-psychotropic drugs can very rarely provoke a reaction.

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the enzyme monoamine oxidase. This enzyme is responsible for breaking down many compounds; basically, anything with a primary amine moiety is likely to be oxidized by monoamine oxidase. An important substrate of the enzyme MAO is tyramine. MAOIs inhibit the enzyme either reversibly, in which MAO is inhibited only until the drug is cleared from the system, or irreversibly, in which the substrate binds permanently to the enzyme, rendering it inactive and effectively destroying it. Irreversible MAOIs are potentially more dangerous, because the body takes about two weeks to regenerate MAO enzymes to functional levels. Two subtypes of MAO exist: MAO-A and MAO-B; this is relevant to adrenergic storms, as there are significant differences between the two types, such as their differential expression throughout the body, and range of substrates. While both MAO-A and MAO-B metabolize tyramine, only MAO-A is present in the gastrointestinal tract and singularly metabolizes the majority of consumed tyramine. (The small portion normally passing into circulation is mostly degraded in the liver where both MAO types act.) Consequently, MAOIs that irreversibly inhibit MAO-A will permit high levels of circulating tyramine able to cause tyramine-induced hypertensive crisis. Aged cheese, beer, red wine, some mushrooms, and fermented products such as pickles are foods containing high levels of tyramine that passed into circulation can such a hypertensive crisis.

Adrenergic storms are not provoked often from MAOI-tyramine interactions; hypertensive crisis alone does not diagnose adrenergic storm, although there will always be hypertension in an adrenergic storm, along with tachycardia and rapid, shallow breathing. However, if a patient on MAOIs uses recreational quantities of any drug with stimulant effects on the CNS, it can provoke an adrenergic crisis (along with the inevitable hypertensive crisis). Deaths have occurred from individuals attempting to combine MAOIs with various entheogens to attain a stronger psychedelic experience, both from adrenergic storms and serotonin syndrome. Combining drugs like MDMA, 2C-B, mescaline, 2C-T-7, etc. with even small quantities of MAOIs - small quantities of both drugs - is still extremely risky. Nevertheless, some users claim to use certain combinations successfully.

Subarachnoid hemorrhage is an extremely serious condition in which a neural membrane is breached and the brain itself is compromised. The onset is sudden, described as "the worst headache of one's life," and many grave symptoms follow. Adrenergic storm is often present among these symptoms, and is responsible for some of the dangers, both long-term and short, of subarachnoid hemhorrhage adrenergic storm, through a complex cascade of processes starting with the movement of subarachnoid blood into the brain. Apparently, as the intracranial pressure increases, the brain is squeezed and catecholamines are forced out of their vesicles into the synapses and extracellular space. An alternative explanation that has been proposed is that this increased in intracranial pressure transduces through the brain parenchyma through to the blood vessels producing a loss in effective cerebral perfusion. This triggers the sympathetic nervous system to secrete more norepinepherine and epinepherine increasing blood pressure and heart rate to dangerous levels to maintain cerebral perfusion.

Rarely, a pheochromocytoma (tumor of the medullar tissue of the adrenal glands, which are located anterior to the kidney), may result in an adrenergic storm. This type of tumor is not common to begin with, and furthermore, the subtype that can cause massive adrenaline release is rarer still. Patients with pheochromocytoma can unexpectedly fly into a rage or sink into trembling fear, possibly dangerous to themselves and others as their judgment is impaired, their senses and pain threshold are heightened, and the level of the adrenalin in their bloodstream is more than most people ever experience; pheochromocytoma can, very rarely, kill by internal adrenaline overdose. But overall, adrenergic storm is an uncommon but certainly not rare phenomenon associated with the also uncommon condition of pheochromocytoma.

Porphyria

Certain medications may cause or worsen RLS, or cause it secondarily, including:

- Certain antiemetics (antidopaminergic ones)

- Certain antihistamines (especially the sedating, first generation H1 antihistamines often in over-the-counter cold medications)

- many antidepressants (both older TCAs and newer SSRIs)

- antipsychotics and certain anticonvulsants.

- a rebound effect of sedative-hypnotic drugs such as a benzodiazepine withdrawal syndrome from discontinuing benzodiazepine tranquillizers or sleeping pills.

- alcohol withdrawal can also cause restless legs syndrome and other movement disorders such as akathisia and parkinsonism usually associated with antipsychotics

- opioid withdrawal is associated with causing and worsening RLS.

Both primary and secondary RLS can be worsened by surgery of any kind; however, back surgery or injury can be associated with causing RLS.

The cause vs. effect of certain conditions and behaviors observed in some patients (ex. excess weight, lack of exercise, depression or other mental illnesses) is not well established. Loss of sleep due to RLS could cause the conditions, or medication used to treat a condition could cause RLS.

For women with phenylketonuria, it is important for the health of their children to maintain low Phe levels before and during pregnancy. Though the developing fetus may only be a carrier of the PKU gene, the intrauterine environment can have very high levels of phenylalanine, which can cross the placenta. The child may develop congenital heart disease, growth retardation, microcephaly and intellectual disability as a result. PKU-affected women themselves are not at risk of additional complications during pregnancy.

In most countries, women with PKU who wish to have children are advised to lower their blood Phe levels (typically to between 2 and 6 mg/dL) before they become pregnant, and carefully control their levels throughout the pregnancy. This is achieved by performing regular blood tests and adhering very strictly to a diet, in general monitored on a day-to-day basis by a specialist metabolic dietitian. In many cases, as the fetus' liver begins to develop and produce PAH normally, the mother's blood Phe levels will drop, requiring an increased intake to remain within the safe range of 2–6 mg/dL. The mother's daily Phe intake may double or even triple by the end of the pregnancy, as a result. When maternal blood Phe levels fall below 2 mg/dL, anecdotal reports indicate that the mothers may suffer adverse effects, including headaches, nausea, hair loss, and general malaise. When low phenylalanine levels are maintained for the duration of pregnancy, there are no elevated levels of risk of birth defects compared with a baby born to a non-PKU mother.

Hypoglycemia due to endogenous insulin can be congenital or acquired, apparent in the newborn period, or many years later. The hypoglycemia can be severe and life-threatening or a minor, occasional nuisance. By far the most common type of severe but transient hyperinsulinemic hypoglycemia occurs accidentally in persons with type 1 diabetes who take insulin.

- Hypoglycemia due to endogenous insulin

- Congenital hyperinsulinism

- Transient neonatal hyperinsulinism (mechanism not known)

- Focal hyperinsulinism (K channel disorders)

- Paternal SUR1 mutation with clonal loss of heterozygosity of 11p15

- Paternal Kir6.2 mutation with clonal loss of heterozygosity of 11p15

- Diffuse hyperinsulinism

- K channel disorders

- SUR1 mutations

- Kir6.2 mutations

- Glucokinase gain-of-function mutations

- Hyperammonemic hyperinsulinism (glutamate dehydrogenase gain-of-function mutations)

- Short chain acyl coenzyme A dehydrogenase deficiency

- Carbohydrate-deficient glycoprotein syndrome (Jaeken's Disease)

- Beckwith-Wiedemann syndrome(suspected due to hyperinsulinism but pathophysiology uncertain: 11p15 mutation or IGF2 excess)

- Acquired forms of hyperinsulinism

- Insulinomas (insulin-secreting tumors)

- Islet cell adenoma or adenomatosis

- Islet cell carcinoma

- Adult nesidioblastosis

- Autoimmune insulin syndrome

- Noninsulinoma pancreatogenous hypoglycemia

- Reactive hypoglycemia (also see idiopathic postprandial syndrome)

- Gastric dumping syndrome

- Drug induced hyperinsulinism

- Sulfonylurea

- Aspirin

- Pentamidine

- Quinine

- Disopyramide

- Bordetella pertussis vaccine or infection

- D-chiro-inositol and myo-inositol

- Hypoglycemia due to exogenous (injected) insulin

- Insulin self-injected for treatment of diabetes (i.e., diabetic hypoglycemia)

- Insulin self-injected surreptitiously (e.g., Munchausen syndrome)

- Insulin self-injected in a suicide attempt or successful suicide

- Various forms of diagnostic challenge or "tolerance tests"

- Insulin tolerance test for pituitary or adrenergic response assessment

- Protein challenge

- Leucine challenge

- Tolbutamide challenge

- Insulin potentiation therapy

- Insulin-induced coma for depression treatment

An adrenergic storm is a sudden and dramatic increase in serum levels of the catecholamines adrenalin and noradrenalin (also known as epinephrine and norepinephrine respectively), with a less significant increase in dopamine transmission. It is a life-threatening condition because of extreme tachycardia and hypertension, and is especially dire for those with prior heart problems. If treatment is prompt, prognosis is good; typically large amounts of diazepam or other benzodiazepines are administered alongside beta blockers. Beta blockers are contraindicated in some patients, so other anti-hypertensive medication such as clonidine may be used. It is usually caused by overdose of stimulants, especially cocaine or methamphetamine, or eating foods high in tyramine while taking monoamine oxidase inhibitors. A subarachnoid hemorrhage can also cause an adrenergic storm. A catecholamine storm is part of the normal course of Rabies infection, and is responsible for the severe feelings of agitation, terror, and dysautonomia present in the pre-coma stage of the disease.

Paroxysmal hypertension is episodic and volatile high blood pressure, which may be due to stress of any sort, or from a pheochromocytoma, a type of tumor involving the adrenal medulla. Patients with paroxysmal hypertension who test negative for pheochromocytoma are said to be suffering from a clinical entity called "pseudopheochromocytoma." This disorder is due to episodic dopamine discharge and has been observed predominantly in hypertensive women, that had episodes that shared similar characteristics of pheochromocytoma but testing proved negative and had ruled out the tumor. In patients with pseudopheochromocytoma dopamine was found to be significantly increased post-paroxysm. The paroxysm is said to be similar to the hypertensive episodes described by Page. These episodes commonly occur after diencephalic stimulation. Therefore, pseudopheochromocytoma, shares many characteristics of "Page's syndrome."

Pseudopheochromocytoma, colloquially known as page's syndrome, is caused predominantly by episodic dopamine discharge, stressors including pain or anxiety, or possibly repressed emotions caused by prior emotional trauma and commonly, a repressive way of coping emotionally. Therefore, treatment of pseudopheochromocytoma is aimed at psychological support and intervention with antidepressants, but also treatment with alpha and then beta blockers in resistant cases.

Persons with the genotype for PKU are unaffected in utero, because maternal circulation prevents buildup of [phe]. After birth, PKU in newborns is treated by a special diet with highly restricted phenylalanine content. Persons with genetic predisposition to PKU have normal mental development on this diet. Previously, it was thought safe to withdraw from the diet in the late teens or early twenties, after the central nervous system was fully developed; recent studies suggest some degree of relapse, and a continued phenylalanine-restricted diet is now recommended.

PKU or hyperphenylalaninemia may also occur in persons without the PKU genotype. If the mother has the PKU genotype but has been treated so as to be asymptomatic, high levels of [phe] in the maternal blood circulation may affect the non-PKU fetus during gestation. Mothers successfully treated for PKU are advised to return to the [phe]-restricted diet during pregnancy.

A small subset of patients with hyperphenylalaninemia shows an appropriate reduction in plasma phenylalanine levels with dietary restriction of this amino acid; however, these patients still develop progressive neurologic symptoms and seizures and usually die within the first 2 years of life ("malignant" hyperphenylalaninemia). These infants exhibit normal phenylalanine hydroxylase (PAH) enzymatic activity but have a deficiency in dihydropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydrobiopterin (THB or BH), a cofactor of PAH.

Less frequently, DHPR activity is normal but a defect in the biosynthesis of THB exists. In either case, dietary therapy corrects the hyperphenylalaninemia. However, THB is also a cofactor for two other hydroxylation reactions required in the syntheses of neurotransmitters in the brain: the hydroxylation of tryptophan to 5-hydroxytryptophan and of tyrosine to L-dopa. It has been suggested that the resulting deficit in the CNS neurotransmitter activity is, at least in part, responsible for the neurologic manifestations and eventual death of these patients.

Hawkinsinuria, also called 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency, is an autosomal dominant metabolic disorder affecting the metabolism of tyrosine. Normally, the breakdown of the amino acid tyrosine involves the conversion of 4-hydroxyphenylpyruvate to homogentisate by 4-Hydroxyphenylpyruvate dioxygenase. Complete deficiency of this enzyme would lead to tyrosinemia III. In rare cases, however, the enzyme is still able to produce the reactive intermediate 1,2-epoxyphenyl acetic acid, but is unable to convert this intermediate to homogentisate. The intermediate then spontaneously reacts with glutathione to form 2-L-cystein-S-yl-1,4-dihydroxy-cyclohex-5-en-1-yl acetic acid (hawkinsin).

Patients present with metabolic acidosis during the first year of life, which should be treated by a phenylalanine- and tyrosine-restricted diet. The tolerance toward these amino acids normalizes as the patients get older. Then only a chlorine-like smell of the urine indicates the presence of the condition, patients have a normal life and do not require treatment or a special diet.

The production of hawkinsin is the result of a gain-of-function mutation, inheritance of hawkinsinuria is therefore autosomal dominant (presence of a single mutated copy of the gene causes the condition). Most other inborn errors of metabolism are caused by loss-of-function mutations, and hence have recessive inheritance (condition occurs only if both copies are mutated).

The disorder may be associated with Addison's disease, atherosclerosis (build-up of fatty deposits in the arteries), diabetes, pheochromocytoma, porphyria, and certain neurological disorders, including multiple system atrophy and other forms of dysautonomia. It is also associated with Ehlers–Danlos syndrome and anorexia nervosa. It is also present in many patients with Parkinson's disease resulting from sympathetic denervation of the heart or as a side-effect of dopaminomimetic therapy. This rarely leads to fainting unless the person has developed true autonomic failure or has an unrelated heart problem.

Another disease, dopamine beta hydroxylase deficiency, also thought to be underdiagnosed, causes loss of sympathetic noradrenergic function and is characterized by a low or extremely low levels of norepinephrine, but an excess of dopamine.

Quadriplegics and paraplegics also might experience these symptoms due to multiple systems' inability to maintain a normal blood pressure and blood flow to the upper part of the body.

Few women of childbearing age have high blood pressure, up to 11% develop hypertension of pregnancy. While generally benign, it may herald three complications of pregnancy: pre-eclampsia, HELLP syndrome and eclampsia. Follow-up and control with medication is therefore often necessary.

This condition is very rare, only affecting one in two million people. It is more common in females than in males. There are several hundred cases in the United States, 25 known cases in the United Kingdom, and less than that in Australia and New Zealand.

Treatment of THB deficiencies consists of THB supplementation (2–20 mg/kg per day) or diet to control blood phenylalanine concentration and replacement therapy with neurotransmitters precursors (L-DOPA and 5-HTP) and supplements of folinic acid in DHPR deficiency.

Tetrahydrobiopterin is available as a tablet for oral administration in the form of "tetrahydrobiopterin dihydrochloride" (BH4*2HCL). BH4*2HCL is FDA approved under the trade name Kuvan. The typical cost of treating a patient with Kuvan is $100,000 per year. BioMarin holds the patent for Kuvan until at least 2024, but Par Pharmaceutical has a right to produce a generic version by 2020. BH4*2HCL is indicated at least in tetrahydrobiopterin deficiency caused by GTPCH deficiency or PTPS deficiency.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. The various types of familial hyperaldosteronism have different genetic causes. Familial hyperaldosteronism type I is caused by the abnormal joining together (fusion) of two similar genes called CYP11B1 and CYP11B2, which are located close together on chromosome 8. These genes provide instructions for making two enzymes that are found in the adrenal glands.

The CYP11B1 gene provides instructions for making an enzyme called 11-beta-hydroxylase. This enzyme helps produce hormones called cortisol and corticosterone. The CYP11B2 gene provides instructions for making another enzyme called aldosterone synthase, which helps produce aldosterone. When CYP11B1 and CYP11B2 are abnormally fused together, too much aldosterone synthase is produced. This overproduction causes the adrenal glands to make excess aldosterone, which leads to the signs and symptoms of familial hyperaldosteronism type I.

Familial hyperaldosteronism type III is caused by mutations in the KCNJ5 gene. The KCNJ5 gene provides instructions for making a protein that functions as a potassium channel, which means that it transports positively charged atoms (ions) of potassium into and out of cells. In the adrenal glands, the flow of ions through potassium channels produced from the KCNJ5 gene is thought to help regulate the production of aldosterone. Mutations in the KCNJ5 gene likely result in the production of potassium channels that are less selective, allowing other ions (predominantly sodium) to pass as well. The abnormal ion flow results in the activation of biochemical processes (pathways) that lead to increased aldosterone production, causing the hypertension associated with familial hyperaldosteronism type III.

The genetic cause of familial hyperaldosteronism type II is unknown.