People with Laron syndrome have strikingly low rates of cancer and diabetes, although they appear to be at increased risk of accidental death due to their stature.

The incidence of idiopathic GHD in infants is about 1 in every 3800 live births, and rates in older children are rising as more children survive childhood cancers which are treated with radiotherapy, although exact rates are hard to obtain.

The incidence of genuine adult-onset GHD, normally due to pituitary tumours, is estimated at 10 per million.

Most XY children are so undervirilized that they are raised as girls. The testes are uniformly nonfunctional and undescended; they are removed when the diagnosis is made due to the risk of cancer development in these tissues.

Growth hormone deficiency in childhood commonly has no identifiable cause (idiopathic), and adult-onset GHD is commonly due to pituitary tumours and their treatment or to cranial irradiation. A more complete list of causes includes:

- mutations of specific genes (e.g., GHRHR, GH1)

- congenital diseases such as Prader-Willi syndrome, Turner syndrome, or short stature homeobox gene (SHOX) deficiency

- congenital malformations involving the pituitary (e.g., septo-optic dysplasia, posterior pituitary ectopia)

- chronic renal insufficiency

- intracranial tumors in or near the sella turcica, especially craniopharyngioma

- damage to the pituitary from radiation therapy to the head (e.g. for leukemia or brain tumors), from surgery, from trauma, or from intracranial disease (e.g. hydrocephalus)

- autoimmune inflammation (hypophysitis)

- ischemic or hemorrhagic infarction from low blood pressure (Sheehan syndrome) or hemorrhage pituitary apoplexy

There are a variety of rare diseases which resemble GH deficiency, including the childhood growth failure, facial appearance, delayed bone age, and low IGF levels. However, GH testing elicits normal or high levels of GH in the blood, demonstrating that the problem is not due to a deficiency of GH but rather to a reduced sensitivity to its action. Insensitivity to GH is traditionally termed Laron dwarfism, but over the last 15 years many different types of GH resistance have been identified, primarily involving mutations of the GH binding protein or receptors.

This condition is associated with genetic imprinting. It is thought to be inherited in an autosomal dominant pattern, and seems to be associated with a Gs alpha subunit deficiency.

Molecular genetic investigations have shown that this disorder is mainly associated with mutations in the gene for the GH receptor. These can result in defective hormone binding to the ectodomain or reduced efficiency of dimerization of the receptor after hormone occupancy. There are exceptionally low levels of insulin-like growth factor (IGF-1) and its principal carrier protein, insulin-like growth factor binding protein 3.

A related condition involving postreceptor insensitivity to growth hormone has been associated with STAT5B.

The mechanism of this condition is due to Gs signaling decrease in hormones having to do with signal transduction which is when a signal from outside cell causes change within the cell (in function). Renal tubular cells don't expresses paternal only maternal alleles(variant form of a gene).

PDP occurs more frequently in men than in women (ratio around 7:1). Moreover, men suffer from more severe symptoms (see table 1). African American people are affected to a higher extent.

Table 1. Distribution of different forms of PDP among 201 reported affected men and women (167 men and 34 women).

An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism.

A variety of conditions of abnormal steroidogenesis exist due to genetic mutations in the steroidogenic enzymes involved in the process, of which include:

- 18,20-Desmolase (P450scc) deficiency: blocks production of all steroid hormones from cholesterol

- 3β-Hydroxysteroid dehydrogenase type 2 deficiency: impairs progestogen and androgen metabolism; prevents the synthesis of estrogens, glucocorticoids, and mineralocorticoids; causes androgen deficiency in males and androgen excess in females

- Combined 17α-hydroxylase/17,20-lyase deficiency: impairs progestogen metabolism; prevents androgen, estrogen, and glucocorticoid synthesis; causes mineralocorticoid excess

- Isolated 17,20-lyase deficiency: prevents androgen and estrogen synthesis

- 21-Hydroxylase deficiency: prevents glucocorticoid and mineralocorticoid synthesis; causes androgen excess in females

- 11β-Hydroxylase type 1 deficiency: impairs glucocorticoid and mineralocorticoid metabolism; causes glucocorticoid deficiency and mineralocorticoid excess as well as androgen excess in females

- 11β-Hydroxylase type 2 deficiency: impairs corticosteroid metabolism; results in excessive mineralocorticoid activity

- 18-Hydroxylase deficiency: impairs mineralocorticoid metabolism; results in mineralocorticoid deficiency

- 18-Hydroxylase overactivity: impairs mineralocorticoid metabolism; results in mineralocorticoid excess

- 17β-Hydroxysteroid dehydrogenase deficiency: impairs androgen and estrogen metabolism; results in androgen deficiency in males and androgen excess and estrogen deficiency in females

- 5α-Reductase type 2 deficiency: prevents the conversion of testosterone to dihydrotestosterone; causes androgen deficiency in males

- Aromatase deficiency: prevents estrogen synthesis; causes androgen excess in females

- Aromatase excess: causes excessive conversion of androgens to estrogens; results in estrogen excess in both sexes and androgen deficiency in males

In addition, several conditions of abnormal steroidogenesis due to genetic mutations in "receptors", as opposed to enzymes, also exist, including:

- Gonadotropin-releasing hormone (GnRH) insensitivity: prevents synthesis of sex steroids by the gonads in both sexes

- Follicle-stimulating (FSH) hormone insensitivity: prevents synthesis of sex steroids by the gonads in females; merely causes problems with fertility in males

- Luteinizing hormone (LH) insensitivity: prevents synthesis of sex steroids by the gonads in males; merely causes problems with fertility in females

- Luteinizing hormone (LH) oversensitivity: causes androgen excess in males, resulting in precocious puberty; females are asymptomatic

No activating mutations of the GnRH receptor in humans have been described in the medical literature, and only one of the FSH receptor has been described, which presented as asymptomatic.

Lipoid CAH is quite rare in European and North American populations. Most cases occur in Japan and Korea (where the incidence is 1 in 300,000 births) and Palestinian Arabs. Despite autosomal inheritance, there has been an unexplained preponderance of genetic females in reported cases.

In 25-38% of the cases, patients have a familial history of PDP. It is suggested that the incomplete form and complete form are inherited in different ways: either autosomal dominant inheritance (involving a dominant allele) or autosomal recessive inheritance (involving a recessive allele).

The autosomal dominant model of inheritance with penetrance and variable expression is confirmed in about half of the families, associated with the incomplete form. Of several families, an autosomal recessive model of inheritance is known, associated with the complete form with much more severe symptoms involving joint, bone and skin features. While the male-female ratio in PDP is skewed, this cannot be fully explained by X-linked inheritance.

Two genes have been associated with this condition: hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) and solute carrier organic anion transporter family, member 2A1/prostaglandin transporter (SLCO2A1). The underlying pathophysiology appears to be an abnormality of prostglandin E2 but the details have yet to be elucidated.

Adrenocorticotropic hormone deficiency (ACTH deficiency) is a result of a decreased or absent production of adrenocorticotropic hormone (ACTH) by the pituitary gland.

It can be associated with "TBX19".

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are two different substances that have been identified as influencing growth plate formation and bone growth and, therefore, gigantism. The specific mechanisms of these are still not completely understood.

More broadly, GH and IGF have both been identified to be involved most stages of growth: embryonic, prenatal, and postnatal. Moreover, the receptor gene for IGF has been shown to be particularly influential throughout various stages of development, especially prenatally. This is the same for GH receptor genes which have been known to drive overall growth throughout various pathways.

Growth hormone is a precursor (upstream) of IGF-I, but each have their own independent roles in hormonal pathways. Although, both seem to ultimately come together to have a joint effect on growth.

Finding a specific genetic cause for gigantism has proven to be difficult. Gigantism is the primary example of growth hormone hyper-secretion disorders, a group of illnesses that are not yet deeply understood.

Some common mutations (errors in DNA) have been associated with gigantism. Pediatric gigantism patients have shown to have duplications of genes on a specific chromosome, Xq26. Typically, these patients also experienced an onset of typical gigantism symptoms before reaching the age of 5. This indicates a possible linkage between gene duplications and the gigantism.

Additionally, DNA mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are common in gigantism patients. They have been found to be present in about 29 percent of patients with gigantism. AIP is labeled as a tumor suppressor gene and a pituitary adenoma disposition gene.

Mutations in AIP sequencing can have deleterious effects by inducing the development of pituitary adenomas which in turn can cause gigantism.

Two specific mutations in the AIP gene have been identified as possible causes of pituitary adenomas. These mutations also have the ability to cause adenoma growth to occur early in life. This is typical in gigantism.

Additionally, a large variety of other known genetic disorders have been found to influence the development of gigantism such as multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, X-linked acrogigantism (X-LAG).

Although various gene mutations have been associated with gigantism, over 50 percent of cases cannot be linked to genetic causes, showing the complex nature of the disorder.

Allen Avinoam Kowarski et al. described the first two cases of the Kowarski syndrome in 1978. The group speculated that their patients' growth impairment was caused by a mutation in the growth hormone gene, which altered the structure of their secreted growth hormone, reducing its biological activity while retaining its ability to bind the antibodies used in the RIA-GH. Their RIA-GH measured growth hormone of reduced bioactivity. The children retained the ability to respond to treatment with active growth hormone.

The speculation of Kowarski et al. was confirmed by Valenta et al in 1985, Takahshi et al in 1996 and 1997 and Besson et al in 2005. Valenta et al studied a case of Kowarski syndrome where they confirmed a structural abnormality of the growth hormone molecule. 60 to 90% of circulating growth hormone of the patient was in the form of tetramers and dimers (normal, 14% to 39% in plasma) and the patients' growth hormone polymers were abnormally resistant to conversion into monomers by urea.

Takahashi et al. reported a case of a boy with short stature who was heterozygous for a mutation in the GH1 gene. In this child, growth hormone not only could not activate the GH receptor (GHR) but also inhibited the action of wild type GH because of its greater affinity for GHR and GH-binding protein (GHBP) that is derived from the extracellular domain of the GHR. Thus, a dominant-negative effect was observed.

Takahashi et al. demonstrated in a girl with short stature, a biologically inactive growth hormone resulting from a heterozygous mutation in the GH1 gene. At age 3 years, the girl's height was 3.6 standard deviations below the mean for age and sex. Bone age was delayed by 1.5 years. She had a prominent forehead and a hypoplastic nasal bridge with normal body proportions. She showed lack of growth hormone action despite high immunoassayable GH levels in serum and marked catch-up growth to exogenous GH administration. Results of other studies were compatible with the production of a bioinactive GH, which prevented dimerization of the growth hormone receptor, a crucial step in GH signal transduction.

Besson et al described in 1955 a Serbian patient with Kowarski syndrome who was homozygous for a mutation in the GH1 gene that disrupted the first disulfide bridge in growth hormone. The parents were each heterozygous for the mutation and were of normal stature.

Neonatal thyroid screening programs from all over the world have revealed that congenital hypothyroidism (CH) occurs with an incidence of 1:3000 to 1:4000. The differences in CH-incidence are more likely due to iodine deficiency thyroid disorders or to the type of screening method than to ethnic affiliation. CH is caused by an absent or defective thyroid gland classified into agenesis (22-42%), ectopy (35-42%) and gland in place defects (24-36%). It is also found to be of increased association with female sex and gestational age >40 weeks.

Several studies have shown that hypopituitarism is associated with an increased risk of cardiovascular disease and some also an increased risk of death of about 50% to 150% the normal population. It has been difficult to establish which hormone deficiency is responsible for this risk, as almost all patients studied had growth hormone deficiency. The studies also do not answer the question as to whether the hypopituitarism itself causes the increased mortality, or whether some of the risk is to be attributed to the treatments, some of which (such as sex hormone supplementation) have a recognized adverse effect on cardiovascular risk.

The largest study to date followed over a thousand people for eight years; it showed an 87% increased risk of death compared to the normal population. Predictors of higher risk were: female sex, absence of treatment for sex hormone deficiency, younger age at the time of diagnosis, and a diagnosis of craniopharyngioma. Apart from cardiovascular disease, this study also showed an increased risk of death from lung disease.

Quality of life may be significantly reduced, even in those people on optimum medical therapy. Many report both physical and psychological problems. It is likely that the commonly used replacement therapies do not completely mimic the natural hormone levels in the body. Health costs remain about double those of the normal population.

Hypopituitarism is usually permanent. It requires lifelong treatment with one or more medicines.

Gonadotropin-releasing hormone (GnRH) insensitivity is a rare autosomal recessive genetic and endocrine syndrome which is characterized by inactivating mutations of the gonadotropin-releasing hormone receptor (GnRHR) and thus an insensitivity of the receptor to gonadotropin-releasing hormone (GnRH), resulting in a partial or complete loss of the ability of the gonads to synthesize the sex hormones. The condition manifests itself as isolated hypogonadotropic hypogonadism (IHH), presenting with symptoms such as delayed, reduced, or absent puberty, low or complete lack of libido, and infertility, and is the predominant cause of IHH when it does not present alongside anosmia.

Most children born with congenital hypothyroidism and correctly treated with thyroxine grow and develop normally in all respects. Even most of those with athyreosis and undetectable T levels at birth develop with normal intelligence, although as a population academic performance tends to be below that of siblings and mild learning problems occur in some.

Congenital hypothyroidism is the most common preventable cause of intellectual disability. Few treatments in the practice of medicine provide as large a benefit for as small an effort.

The developmental quotient (DQ, as per Gesell Developmental Schedules) of children with hypothyroidism at age 24 months that have received treatment within the first 3 weeks of birth is summarised below:

Kowarski syndrome describes cases of growth failure (height and bone age two standard deviations below the mean for age), despite the presence of normal or slightly high blood growth hormone by radioimmunoassay (RIA-GH) and low serum IGF1 (formerly called somatomedin), and who exhibit a significant increase in growth rate following recombinant GH therapy.

The exact genetic mutation that causes congenital circumscribed, localized, and nevoid hypertrichosis is unknown.

Acquired hypertrichosis lanuginosa is commonly present with cancer. This condition is also linked to metabolic disorders, such as anorexia, hormone imbalances, such as hyperthyroidism, or as a side effect of certain drugs.

Acquired generalized hypertrichosis may be caused by cancer. The resulting hair growth is known as malignant down. The mechanism behind cancer induced hypertrichosis is unknown. Oral and topical minoxidil treatments are also known to cause acquired generalized hypertrichosis.

IHH is divided into two syndromes: IHH with olfactory alterations or anosmia, Kallmann syndrome and IHH with normal smell (normosmic IHH).

Kallmann syndrome is responsible for approximately 50% of all cases of the condition. It is associated with mutations in "KAL1", "FGFR1/FGF8", "FGF17", "IL17RD", "PROKR2", "NELF", "CHD7"(which positively regulates GnRH secretion), HS6ST1, "FLRT3", "SPRY4", DUSP6, "SEMA3A", and "WDR11 (gene)", genes which are related to defects in neuronal migration.

Gene defects associated with IHH and normal smell include "PROKR2, FGFR1, FGF8, CHD7, DUSP6," and "WDR11", as in KS, but in addition

also mutations in "KISS1R", "TACR3", GNRH1/GNRHR, LEP/LEPR, HESX1, FSHB, and LHB.

GnRH insensitivity is the second most common cause of IHH, responsible for up to 20% of cases.

A minority of less than 5-10% is due to inactivating mutations in genes which positively regulate GnRH secretion such as ,"CHD7", "KISS1R", and "TACR3".

The causes of about 25% of all IHH cases are still unknown.

Isolated hypogonadotropic hypogonadism (IHH), also called idiopathic or congenital hypogonadotropic hypogonadism (CHH), as well as isolated or congenital gonadotropin-releasing hormone deficiency (IGD) constitutes a small subset of cases of hypogonadotropic hypogonadism (HH).

IHH is due to deficiency in or insensitivity to gonadotropin-releasing hormone (GnRH), where the function and anatomy of the anterior pituitary is otherwise normal, and secondary causes of HH are not present.

There is only one study that has measured the prevalence (total number of cases in a population) and incidence (annual number of new cases) of hypopituitarism. This study was conducted in Northern Spain and used hospital records in a well-defined population. The study showed that 45.5 people out of 100,000 had been diagnosed with hypopituitarism, with 4.2 new cases per year. 61% were due to tumors of the pituitary gland, 9% due to other types of lesions, and 19% due to other causes; in 11% no cause could be identified.

Recent studies have shown that people with a previous traumatic brain injury, spontaneous subarachnoid hemorrhage (a type of stroke) or radiation therapy involving the head have a higher risk of hypopituitarism. 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.

Although the exact pathology of Dubowitz syndrome is not known yet, it is heritable and classified as an autosomal recessive disease. Furthermore, there is an occasional parental consanguinity. Several cases point to Dubowitz syndrome occurring in monozygotic twins, siblings, and cousins. There is considerable phenotypic variability between cases, especially in regards to intelligence. Although substantial evidence points to the genetic basis of this disorder, the phenotypic similarity is found in fetal alcohol syndrome. Further studies need to be done to determine whether this environmental agent effects the expression of the genotype. Breakdown of chromosomes is known to occur.