Macroorchidism on:
[Wikipedia]
[Google]
[Amazon]
Macroorchidism is a
disorder
Disorder may refer to randomness, non-order, or no intelligible pattern.
Disorder may also refer to:
Healthcare
* Disorder (medicine), a functional abnormality or disturbance
* Mental disorder or psychological disorder, a psychological pattern ...
found in males, specifically in children, where a subject has abnormally large testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...
. The condition is commonly inherited in connection with fragile X syndrome (FXS), which is also the second most common genetic cause of intellectual disability
Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...
. The condition is also a rare sign of the McCune-Albright syndrome. The opposite of macroorchidism is called microorchidism, which is the condition of abnormally small testes.
Macroorchidism is related to IGFS1 deficiency
A deficiency is generally a lack of something. It may also refer to:
*A deficient number, in mathematics, a number ''n'' for which ''σ''(''n'') < 2''n''
* secretion of follicle stimulating hormone (FSH). There are other causes for macroorchidism such as hypothyroidism, local tumors, and aromatase deficiency. Macroorchidism can be diagnosed by measuring the testicular volume using a prader orchidometer. There is no cure for macroorchidism, however,
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
s are currently being tested and used to control the disorder to promote quality living.
Signs and symptoms
The most distinguishing physical symptom of macroorchidism in patients is the increased testicular size. To determine enlargement of the testes (i.e. macroorchidism), the testes must be greater than the 95thpercentile
In statistics, a ''k''-th percentile (percentile score or centile) is a score ''below which'' a given percentage ''k'' of scores in its frequency distribution falls (exclusive definition) or a score ''at or below which'' a given percentage fal ...
of the confidence interval in males after puberty. The 95th percentile means that the child's testicular size exceeds 95% of children similar in age. This rules out males with early puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a bo ...
. Another symptom of macroorchidism is if there is an increase in testicular volume that is at least twice the normal testicular volume for the age.
Macroorchidism is mostly found in prepubescent
Preadolescence is a stage of human development following middle childhood and preceding adolescence.New Oxford American Dictionary. 2nd Edition. 2005. Oxford University Press. It commonly ends with the beginning of puberty. Preadolescence is ...
boys with fragile X syndrome. However, true macroorchidism does not start until the testicular size is greater than 4 cm, which can only occur later in the prepubertal period. Because macroorchidism is associated with fragile X syndrome patients, the signs in patients with FXS is similar in patients with macroorchidism. These signs include protruding ear
Prominent ear, otapostasis or bat ear is an abnormally protruding human ear. It may be unilateral or bilateral. The concha is large with poorly developed antihelix and scapha. It is the result of malformation of cartilage during primitive ear deve ...
s, long face, bulging jaw and forehead, macrocephaly
Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to ...
, mid-facial hypoplasia, and a high arched palate
The palate () is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity.
A similar structure is found in crocodilians, but in most other tetrapods, the oral and nasal cavities are not truly separ ...
.
Even though FXS affects both males and females, the prevalence
In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
in males is approximately 1 in 4000 males.
Cause
The cause of macroorchidism is still unclear. However, there are studies that show a connection between macroorchidism and other disorders related tohormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...
s that reveal their possible role with the abnormal enlargement of the testes. An excessive increase in the interstitial volume
In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...
and the connective tissue of the testes
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...
can lead to macroorchidism.
There are other causes of macroorchidism such as long-standing primary hypothyroidism, adrenal tissue remains in congenital adrenal hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cort ...
(CAH), follicle stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
(FSH) secreting pituitary macroadenomas, local tumors, lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...
s, and aromatase deficiency.
Pathophysiology or mechanism
Macroorchidism result from an increased secretion of thefollicle stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, an ...
. The follicle stimulating hormone is secreted without being affected by an increase in the secretion of the luteinizing hormone
Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) ...
(LH) or a luteinizing hormone response to Gonadotropin-releasing hormone
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and release ...
(GnRH).
Macroorchidism is related to a genetic defect in the Immunoglobulin Superfamily 1 (IGSF1) gene. However, not all patients with a failing IGSF1 gene present with macroorchidism. In gonadotropes, there is activin A
Activin and inhibin are two closely related protein complexes that have almost directly opposite biological effects. Identified in 1986, activin enhances FSH biosynthesis and secretion, and participates in the regulation of the menstrual c ...
. Gonadotropes are endocrine cell
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neur ...
s in the anterior pituitary that control and regulate reproduction. These cells release the FSH and LH hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...
s and play an important role in puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a bo ...
. Activin A is a dimeric glycoprotein that is a member of the transforming growth factor-β (TGF-β) family. Activin A is responsible for hormonal homeostasis, gonadal functions, muscle growth, immunity
Immunity may refer to:
Medicine
* Immunity (medical), resistance of an organism to infection or disease
* ''Immunity'' (journal), a scientific journal published by Cell Press
Biology
* Immune system
Engineering
* Radiofrequence immunity desc ...
, inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
, and bone remodeling
Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called ''bone resorption'') and new bone tissue is formed (a process called ''ossification'' or ''new bone formation''). ...
. Activin A binds to activin receptors (ActRs) in the gonadotropes and stimulates the Smad2
Mothers against decapentaplegic homolog 2 also known as SMAD family member 2 or SMAD2 is a protein that in humans is encoded by the ''SMAD2'' gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the ''Dros ...
or Smad3
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene.
SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by t ...
pathway to increase follicle-stimulating hormone beta subunit (FSHB). The follicle stimulating hormone (FSH) then stimulates the follicle-stimulating hormone receptor (FSHR) of the sertoli cell
Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-stimu ...
s, therefore producing inhibin B which brings into play a negative feedback over the pituitary FSHB expression. The IGSF1 gene inhibits the activin A pathway which decreases the rate of FSHB expression. IGSF1 gene deficiency leads to over-secretion of pituitary FSH causing an early and rapid increase in the testicular sertoli cell mass (i.e. macroorchidism) in children and adults with FSH-secreting pituitary adenoma
Pituitary adenomas are tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas.
Definition from the National Library of Medicine
Diagnosis
Macroorchidism is usually found inprepubertal
Preadolescence is a stage of human development following middle childhood and preceding adolescence.New Oxford American Dictionary. 2nd Edition. 2005. Oxford University Press. It commonly ends with the beginning of puberty. Preadolescence is c ...
boys with long-standing primary hypothyroidism, boys with Van Wyk Grumbach Syndrome (VWGS), and boys with fragile X syndrome (FXS).
When macroorchidism is considered, the testicular volume is measured using a prader orchidometer. The prader orchidometer is used to quickly and accurately measure the testicular volume to evaluate male growth and development. The prader orchidometer is the most widely used orchidometer since 1966 and is calculated using the formula: Length*Width*Height*0.71. The correct final value from the calculation is compared with an age percentile
In statistics, a ''k''-th percentile (percentile score or centile) is a score ''below which'' a given percentage ''k'' of scores in its frequency distribution falls (exclusive definition) or a score ''at or below which'' a given percentage fal ...
table that shows how much the child exceeds the percentage of children their age for testicular volume.
The testicular volume changes throughout a males life and is as follows:
* Childhood: 1 - 3 ml
* Early Adolescence (puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a bo ...
begins, 10 to 13 years): 4 - 6 ml
* Middle Adolescence (puberty changes continue, 14 to 17 years): 8 - 10 ml
* Late Adolescence/young adulthood (18 to 21 years and beyond): 12 - 15 ml
* Adulthood: 20 - 25 ml
People with macroorchidism have testicular volume larger than 4 ml before puberty.
Treatment or management
Treatment of macroorchidism depends onpathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
.
Surgical
Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
removal of the tumor is the most important and advised option for treating macroorchidism caused by non-functioning pituitary macroadenoma. A non-functioning pituitary adenoma is a kind of benign tumor
A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize (spread throughout the body). Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have re ...
that does not secrete 440px
Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
active hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...
s, and is from the pituitary gland
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The ...
.
Macroorchidism caused from congenital adrenal hyperplasia (CAH) is treated using glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...
. Using glucocorticoid at the beginning of macroorchidism can help reduce the abnormal testicular size. Glucocorticoid treatment is a dosage treatment in which glucocorticoids such as hydrocortisone
Hydrocortisone is the name for the hormone cortisol when supplied as a medication. Uses include conditions such as adrenocortical insufficiency, adrenogenital syndrome, high blood calcium, thyroiditis, rheumatoid arthritis, dermatitis, asthm ...
, prednisolone
Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthr ...
, and dexamethasone
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena ...
are taken at various amounts and times of the day. Glucocorticoid treatment can help restore male fertility
Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Fertili ...
prohibited by macroorchidism. However, overusing glucocorticoid for long periods of time can lead to low semen quality
Semen quality is a measure of male fertility, a measure of the ability of sperm in semen to accomplish fertilization. Semen quality involves both sperm quantity and quality
Cryptorchidism, hypospadias, testicular cancer and poor semen quali ...
.
Metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
is considered a long-term treatment of macroorchidism due to its relationship with FXS. Metformin lowers the excessive production of the protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s that cause abnormal testicular growth in people with FXS.
Prognosis
Macroorchidism becomes more clear afterpuberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a bo ...
. Testicular size starts to increase normally from 8 to 9 years of age in boys. However, in patients with macroorchidism, around this time is when the testicle
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...
s become abnormally and noticeably enlarged. Also, because macroorchidism is usually associated with intellectual disability
Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...
, the brainpower
Gerrit-Jan Mulder, known professionally as Brainpower (born 5 February 1975), is a Dutch rapper who writes, records and performs in both English as well as his native Dutch. He was born in Belgium and grew up in the Netherlands. He started mak ...
typically declines with age.
The life expectancy
Life expectancy is a statistical measure of the average time an organism is expected to live, based on the year of its birth, current age, and other demographic factors like sex. The most commonly used measure is life expectancy at birth ...
of patients with macroorchidism is normal. There is no cure for macroorchidism; however, there are medications tested in clinical trails identified to bring positive results.
Epidemiology
Macroorchidism only affects males. Theprevalence
In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
of macroorchidism is approximately 1 in 4000 males. Macroorchidism is present in more than 80 - 90% of postpubertal males with fragile X syndrome.
Research section
A research study was done in 2014 to learn if there is a relationship between macroorchidism andintellectual disability
Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...
associated with decreased levels of Fragile X Mental Retardation 1 gene protein (FMRP), but in the pre-mutation or carrier state. FMRP is made from FMR1 gene, and is mainly in the brain and testis
A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testostero ...
. They used the analysis of covariance (ANCOVA) to compare the IQs of the macroorchidism patients with and without pre-mutation carriers. The results showed that there is a relationship between macroorchidism and intellectual disability in FMR1 pre-mutation carrier males. Further studies need to be done to determine if the correlation is due to higher or lower levels of FMR1 mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
and FMRP respectively.
Another study done in 2018 researched the role of Immunoglobulin Superfamily 1 (IGSF1) serves in hypothyroidism and macroorchidism as a regulator of pituitary hormone
In vertebrate anatomy, the pituitary gland, or hypophysis, is an endocrine gland, about the size of a chickpea and weighing, on average, in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain. The hypop ...
secretion. A defect in the IGSF1 gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
is one of the causes of macroorchidism. The results showed that IGSF1 is important for pituitary hormone regulation, and that there are two important mechanisms of macroorchidism related to IGSF1 deficiency.
References
Further reading
Definition from the National Library of Medicine
External links
{{Medical resources , ICD10 = , ICD9 = , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = , DiseasesDB = 27460 , Testicle disorders Men's health