Hypothyroidism is the disease state in humans and in animals caused by insufficient production of thyroid hormone by the thyroid gland. Cretinism is a form of hypothyroidism found in infants.

About three percent of the general population is hypothyroid.[1] Factors such as iodine deficiency or exposure to Iodine-131 (I-131) can increase that risk. There are a number of causes for hypothyroidism. Historically, and still in many developing countries, iodine deficiency is the most common cause of hypothyroidism worldwide. In iodine-replete individuals, hypothyroidism is mostly caused by Hashimoto’s thyroiditis, or by a lack of the thyroid gland or a deficiency of hormones from either the hypothalamus or the pituitary.

Hypothyroidism can result from postpartum thyroiditis, a condition that affects about 5% of all women within a year after giving birth. The first phase is typically hyperthyroidism. Then, the thyroid either returns to normal or a woman develops hypothyroidism. Of those women who experience hypothyroidism associated with postpartum thyroiditis, one in five will develop permanent hypothyroidism requiring life-long treatment.

Hypothyroidism can also result from sporadic inheritance, sometimes autosomal recessive.

Hypothyroidism is also a relatively common hormone disease in domestic dogs, with some specific breeds having a definite predisposition.[2]

Temporary hypothyroidism can be due to the Wolff-Chaikoff effect. A very high intake of iodine can be used to temporarily treat hyperthyroidism, especially in an emergency situation. Although iodine is substrate for thyroid hormones, high levels prompt the thyroid gland to take in less of the iodine that is eaten, reducing hormone production.

Hypothyroidism is often classified by the organ of origin:[3][4]

Hypothyroidism can be caused by lithium-based mood stabilizers, usually used to treat bipolar disorder (previously known as manic depression).

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Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus (opening). Instead of opening at the tip of the glans of the penis, a hypospadic urethra opens anywhere along a line (the urethral groove) running from the tip along the underside (ventral aspect) of the shaft to the junction of the penis and scrotum or perineum. A distal hypospadias may be suspected even in an uncircumcised boy from an abnormally formed foreskin and downward tilt of the glans.

The urethral meatus opens on the glans penis in about 50-75% of cases; these are categorized as first degree hypospadias. Second degree (when the urethra opens on the shaft), and third degree (when the urethra opens on the perineum) occur in up to 20 and 30% of cases respectively. The more severe degrees are more likely to be associated with chordee, in which the phallus is incompletely separated from the perineum or is still tethered downwards by connective tissue, or with undescended testes (cryptorchidism).

Hypospadias are among the most common birth defects of the male genitalia (second to cryptorchidism), but widely varying incidences have been reported from different countries, from as low as 1 in 4000 to as high as 1 in 125 boys.

There has been some evidence that the incidence of hypospadias around the world has been increasing in recent decades. In the United States, two surveillance studies reported that the incidence had increased from about 1 in 500 total births (1 in 250 boys) in the 1970s to 1 in 250 total births (1 in 125 boys) in the 1990s. Although a slight worldwide increase in hypospadias was reported in the 1980s, studies in different countries and regions have yielded conflicting results and some registries have reported decreases.

Most occurences of hypospadias are sporadic, without inheritance or family recurrence; however, it can result from genetics (a pericentric inversion of chromosome 16). For most cases, no cause can be identified though a number of hypotheses related to inadequate androgen effect, or environmental agents interfering with androgen effect, have been offered. Among the suspected environmental agents have been various chemicals, sometimes termed endocrine disruptors, that interact with steroid receptors. Putative endocrine disruptors include phthalates, DDT, and polychlorinated biphenyls. [1] The associations are as yet uncorroborated by additional surveys or other methods. There are also indications that phthalates contained in hairspray can increase the risk by more than double if the mother is exposed to high concentrations of hairspray during pregnancy (such as workers in hair-dressing salons).[2][3]

Prenatal testosterone, converted in the genital skin to dihydrotestosterone, causes migration of skin fibroblasts to fully enclose the urethral groove in fetal males, normally resulting in an enclosed penile urethra by the second trimester of pregnancy. Failure of adequate prenatal androgen effect is therefore thought to be involved in many cases, making hypospadias a very mild form of intersex (under-virilization of a genetic male). Since postnatal androgen deficiency can only be demonstrated in a minority of cases, it has been proposed that transient deficiency of testosterone can occur during critical periods of fetal genital development, due to elevation of anti-müllerian hormone or more subtle degrees of pituitary-gonadal dysfunction. More recently, abnormalities of transcription factors have been proposed.

In animals, several teratogenic drugs or chemicals can cause hypospadias by interfering with androgen action in the embryo. Speculation that environmental agents– endocrine disruptors– might be interfering with human hormone systems has not been proven. The agents that have caused hypospadias in a small number of boys have been maternal use of synthetic progestins and finasteride in the first two trimesters of pregnancy. In 2008, it was suggested that maternal use of diethylstilbestrol, a synthetic estrogen, resulted in a 20-fold increase in prevalence of hypospadias[4] although a followup study showed the risk, though present, to be much lesser. [5]

In a minority of cases a postnatal deficiency of, or reduced sensitivity to, androgens (testosterone and dihydrotestosterone) can be demonstrated. These are often associated with a chordee, and in severe cases a residual perineal urogenital opening and small phallus. This combination of birth defects is referred to as pseudovaginal perineoscrotal hypospadias and is part of the spectrum of ambiguous genitalia. Treatment with testosterone postnatally does not close the urethra.

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Hypoplastic left heart syndrome (also known as HLHS), is a rare congenital heart defect in which the left side of the heart is severely underdeveloped.

While many authorities believe the cause of HLHS is unknown,[1] [2][3] recent research indicates that HLHS may be due to genetic factors. [4][5]

There is evidence associating it with Gap junction protein, alpha 1.[6]

In babies with HLHS, the aorta and left ventricle are very small, and the aortic and mitral valves are either too small to allow sufficient blood flow or are atretic (closed) altogether. As blood returns from the lungs to the left atrium, it must pass through an atrial septal defect to the right side of the heart.

In a healthy human, the left side of the heart receives oxygen-rich blood from the lungs and pumps it out to the rest of the body; with these structures underdeveloped, they cannot circulate blood to other organs, and the right ventricle must pump blood to both the lungs, as it would normally, and to the rest of the body, a situation which cannot be sustained for long.

In cases of HLHS, the right side of the heart often must pump blood to the body through a patent ductus arteriosus. As the ductus arteriosus usually closes within eleven days after birth, blood flow is severely restricted and eventually cut off, leading to dangerously low circulation and eventually to shock.

Without treatment, HLHS is fatal, but with intervention, an infant may survive. A pediatric cardiothoracic surgeon may perform a series of operations or a full heart transplant. In the meantime, the ductus may be kept open to allow bloodflow using medication containing prostaglandin. Because these operations are complex and need to be individualized for each patient, a cardiologist must assess all medical and surgical options on a case-by-case basis. After assessment the child’s parents are given a percentage chance of survival and the choice of surgery or to take the child home to pass away.

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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.[1][2] If there is decreased secretion of most pituitary hormones, the term panhypopituitarism (pan meaning “all”) is used.[3]

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. 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.[1] The first description of the condition was made in 1914 by the German physician Dr Morris Simmonds.[4]

The hormones of the pituitary have different actions in the body, and the symptoms of hypopituitarism therefore depend on which hormone is deficient. The symptoms may be subtle and are often initially attributed to other causes.[1][5] In most of the cases, three or more hormones are deficient.[6] The most common problem is insufficiency of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) leading to sex hormone abnormalities. Growth hormone deficiency is more common in people with an underlying tumor than those with other causes.[1][6]

Sometimes, there are additional symptoms that arise from the underlying cause; for instance, if the hypopituitarism is due to a growth hormone-producing tumor, there may be symptoms of acromegaly (enlargement of the hands and feet, coarse facial features), and if the tumor extends to the optic nerve or optic chiasm, there may be visual field defects. Headaches may also accompany pituitary tumors,[1] as well as pituitary apoplexy (stroke of the pituitary gland) and lymphocytic hypophysitis (autoimmune inflammation of the pituitary).[7]

Pituitary failure results in many changes in the skin, hair and nails as a result of the absence of pituitary hormone action on these sites.[8]:501

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.[1][5]

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. Children experience growth retardation and short stature.[1][5]

Adrenocorticotropic hormone (ACTH) deficiency leads to adrenal insufficiency, a lack of production of glucocorticoids such as cortisol by the adrenal gland. If the problem is chronic, symptoms consist of fatigue, weight loss, failure to thrive (in children), delayed puberty (in adolescents), hypoglycemia (low blood sugar levels), anemia and hyponatremia (low sodium levels). If the onset is abrupt, collapse, shock and vomiting may occur.[1][5] ACTH deficiency is highly similar to Addison’s disease, which is cortisol deficiency as the result of direct damage to the adrenal glands; the latter form, however, often leads to hyperpigmentation of the skin, which does not occur in ACTH deficiency.[9]

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Hypoglycaemia or hypoglycemia is the medical term for a pathologic state produced by a lower than normal level of blood glucose. The term hypoglycemia literally means “under-sweet blood” (Gr. hypo-, glykys, haima). The term also refers to a putative condition that is scientifically disputed and which is perhaps more properly considered as a part of “alternative” medicine.[neutrality disputed] This is covered at the end of this article.

Hypoglycemia can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose as fuel to the brain, resulting in impairment of function (neuroglycopenia). Derangements of function can range from vaguely “feeling bad” to coma, anymous seizures, and (rarely) permanent brain damage or death. Hypoglycemia can arise from many causes and can occur at any age. It also sometimes occurs at random.

The most common forms of moderate and severe hypoglycemia occur as a complication of treatment of diabetes mellitus treated with insulin or less frequently with certain oral medications. Hypoglycemia is usually treated by the ingestion or administration of dextrose, or foods quickly digestible to glucose.

Endocrinologists (specialists in hormones, including those which regulate glucose metabolism) typically consider the following criteria (referred to as Whipple’s triad) as proving that individual’s symptoms can be attributed to hypoglycemia:

However, not everyone has accepted these suggested diagnostic criteria, and even the level of glucose low enough to define hypoglycemia has been a source of controversy in several contexts. For many purposes, plasma glucose levels below 70 mg/dl or 3.9 mmol/L are considered hypoglycemic; these issues are detailed below.

No single glucose value alone serves to define the medical condition termed hypoglycemia for all people and purposes. Throughout the 24 hour cycles of eating, digestion, and fasting, blood plasma glucose levels are generally maintained within a range of 70-150 mg/dL (3.9-7.8 mmol/L) for healthy humans.[1] Although 60 or 70 mg/dL (3.3 or 3.9 mmol/L) is commonly cited as the lower limit of normal glucose, different values (typically below 40, 50, 60, or 70 mg/dL) have been defined as low for different populations, clinical purposes, or circumstances.

The precise level of glucose considered low enough to define hypoglycemia is dependent on (1) the measurement method, (2) the age of the person, (3) presence or absence of effects, and (4) the purpose of the definition. While there is no disagreement as to the normal range of blood sugar, debate continues as to what degree of hypoglycemia warrants medical evaluation or treatment, or can cause harm.[2][3][4]

This article expresses glucose in milligrams per deciliter (mg/dL or mg/100 mL) as is customary in the United States, while millimoles per litre (mmol/L or mM) are the units used in most of the rest of the world. Glucose concentrations expressed as mg/dL can be converted to mmol/L by dividing by 18.0 g/dmol (the molar mass of glucose). For example, a glucose concentration of 90 mg/dL is 5.0 mmol/L or 5.0 mM.

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In medicine (endocrinology), hypoaldosteronism refers to decreased levels of the hormone aldosterone.

There are several causes for this condition, including primary adrenal insufficiency, congenital adrenal hyperplasia, and medications (certain diuretics, NSAIDs, and ACE inhibitors).

This condition may result in hyperkalemia, when it is sometimes termed ‘type 4 renal tubular acidosis’ even though it doesn’t actually cause acidosis. It can also cause urinary sodium wasting, leading to volume depletion and hypotension.

Na+ is lost in the urine. K+ is retained, and the plasma K+ rises. When adrenal insufficiency develops rapidly, the amount of Na+ lost from the ECF exceeds the amount excreted in the urine, indicating that Na+ also must be entering cells. When the posterior pituitary is intact, salt loss exceeds water loss, and the plasma Na+ falls. However, the plasma volume also is reduced, resulting in hypotension, circulatory insufficiency, and, eventually, fatal shock. These changes can be prevented to a degree by increasing the dietary NaCl intake. Rats survive indefinitely on extra salt alone, but in dogs and most humans, the amount of supplementary salt needed is so large that it is almost impossible to prevent eventual collapse and death unless mineralocorticoid treatment is also instituted

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Hypervalinemia (occasionally called valinemia) is a rare autosomal recessive metabolic disorder in which urinary and serum levels of the branched-chain amino acid valine are elevated, without related elevation of the branched-chain amino acids leucine and isoleucine. It is caused by a deficiency of the enzyme valine transaminase.

Presenting in infancy, symptoms include lack of appetite, vomiting, dehydration, hypotonia and failure to thrive.

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Hypertryptophanemia, also called familial hypertryptophanemia,[1] is a rare autosomal recessive[2] metabolic disorder that results in a massive buildup of the amino acid tryptophan in the blood, with associated symptoms and tryptophanuria (-uria denotes “in the urine”).[3][4]

Elevated levels of tryptophan are also seen in Hartnup disease,[5] a disorder of amino acid transport.[6] However, the increase of tryptophan in that disorder is negligible when compared to that of hypertryptophanemia.[1][5]

A number of abnormalities and symptoms have been observed with hypertryptophanemia.

Musculoskeletal effects include: joint contractures of the elbows and interphalangeal joints of the fingers and thumbs (specifically the distal phalanges), pes planus (fallen arches), an ulnar drift affecting the fingers of both hands (an unusual, yet correctible feature where the fingers slant toward the ulnar side of the forearm), joint pain and laxity, and adduction of the thumbs (where the thumb appears drawn into the palm, related to contracture of the adductor pollicis).[1][2]

Behavioral, developmental and other anomalies often include: hypersexuality, perceptual hypersensitivity, emotional lability (mood swings),[3] hyperaggressive behavior;[2] hypertelorism (widely-set eyes), optical strabismus (misalignment) and myopia.[2][1]

Metabolically, hypertryptophanemia results in tryptophanuria and exhibits significantly elevated serum levels of tryptophan, exceeding 650% of maximum (normal range: 25-73 micromole/l) in some instances.[2][3]

A product of the bacterial biosynthesis of tryptophan is indole.[7][8] The excess of tryptophan in hypertryptophanemia also results in substantial excretion of indoleic acids. These findings suggest a possible congenital defect in the metabolic pathway where tryptophan is converted to kynurenine.[3]

At present, no specific enzyme deficiency nor genetic mutation has been implicated as the cause of hypertryptophanemia.[1][2] Several known factors regarding tryptophan metabolism and kynurenines, however, may explain the presence of behavioral abnormalities seen with the disorder.

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Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the blood pressure is chronically elevated. In current usage, the word “hypertension”[1] without a qualifier normally refers to systemic, arterial hypertension.[2]

Hypertension can be classified either essential (primary) or secondary. Essential hypertension indicates that no specific medical cause can be found to explain a patient’s condition. Secondary hypertension indicates that the high blood pressure is a result of (i.e., secondary to) another condition, such as kidney disease or tumours (pheochromocytoma and paraganglioma).

Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysm, and is a leading cause of chronic renal failure. Even moderate elevation of arterial blood pressure leads to shortened life expectancy. At severely high pressures, defined as mean arterial pressures 50% or more above average, a person can expect to live no more than a few years unless appropriately treated.[3]

In individuals older than 50 years, hypertension is considered to be present when a person’s systolic blood pressure is consistently 140 mm Hg or greater or when the diastolic blood pressure is consistently 90 mm Hg or greater. Beginning at a systolic pressure of 115 and diastolic pressure of 75 (commonly written as 115/75 mm Hg), cardiovascular disease (CVD) risk doubles for each increment of 20/10 mmHg.[4] Prehypertension is defined as blood pressure from 121/81 mm Hg to 139/89 mm Hg. Prehypertension is not a disease category; rather, it is a designation chosen to identify individuals at high risk of developing hypertension.[4] The Mayo Clinic specifies that blood pressure is normal if it is 120/80 or below.[5] Patients with blood pressures over 130/80 mm Hg along with Type 1 or Type 2 diabetes, or kidney disease require further treatment.[4]

Resistant hypertension is defined as the failure to reduce BP to the appropriate level after taking a three-drug regimen.[4] The American Heart Association released guidelines for treating resistant hypertension.[6]

By definition, essential hypertension has no identifiable cause. However, several risk factors have been identified, including obesity,[7] salt sensitivity, renin homeostasis, insulin resistance, genetics, and age.

The risk of hypertension is 5 times higher in the obese as compared to those of normal weight and up to two-thirds of cases can be attributed to excess weight. More than 85% of cases occur in those with a Body mass index greater than 25.[7]

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Hypeprolinemia, also referred to as prolinemia or prolinuria, is a condition which occurs when the amino acid proline is not broken down properly by the enzymes proline oxidase or pyrroline-5-carboxylate dehydrogense, causing a build up of proline in the body.

It is difficult to determine the prevalence of hyperprolinemia type I, as many people with the condition are asymptomatic.[1] People with hyperprolinemia type I have proline levels in their blood between 3 and 10 times the normal level. Some individuals with type I exhibit seizures, mental retardation or other neurological problems.[1]

Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This rare form of the disorder may appear benign at times,[2] but often involves seizures, convulsions, and mental retardation.[1]

Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood, such as lactic acidemia, are likely to have elevated proline levels, because lactic acid inhibits the breakdown of proline.[1]

Mutations in the ALDH4A1 and PRODH genes cause hyperprolinemia.[1]

Hyperprolinemia type I is caused by a mutation in the PRODH gene, which codes for the enzyme proline oxidase. This enzyme begins the process of degrading proline by starting the reaction that converts it to pyrroline-5-carboxylate.

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