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Gigantism

Pituitary Gigantism

Gigantism is characterized by abnormal growth in children due to excessive production of insulinlike growth factor I (IGF-I). Basically there is excess production of growth hormone which contributes to the accelerated linear growth.


Presentation

Children with gigantism are taller than other age matched children. In many instances, certain parts are proportionately bigger than other parts. Affected children can also have long hands and feet, with signs of thickening of fingers and toes along with a prominent forehead and jaw. Children with gigantism may also have coarse facial features which include a larger than normal head, flat nose, and large lips and tongue.

Symptoms of gigantism largely depend on the size of the tumor on the pituitary gland. When the tumor gradually increases in size, it may exert pressure on the neighboring nerves in the brain. This may further cause the children to suffer from headaches or loss of vision. In addition, children would also experience weakness, fertility problems, delay in onset of puberty and excessive sweating. In severe cases, deafness can also set in [7].

Tall Stature
  • This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.[ncbi.nlm.nih.gov]
  • Most common causes of tall stature/growth acceleration Normal variant genetic tall stature Endocrine abnormalities Precocious puberty Hyperthyroidism Gigantism Exogenous obesity Syndromes Sotos Beckwith-Wiedemann Marfan Homocystinuria Weaver Fragile X[doi.org]
  • Convert to ICD-10-CM : 253.0 converts approximately to: 2015/16 ICD-10-CM E22.0 Acromegaly and pituitary gigantism Approximate Synonyms Acromegaly Constitutional tall stature Growth hormone overproduction Hypersomatotropic gigantism Overproduction of[icd9data.com]
  • 2018 2019 Billable/Specific Code Applicable To Constitutional gigantism E34.4 ) constitutional tall stature ( ICD-10-CM Diagnosis Code E34.4 Constitutional tall stature 2016 2017 2018 2019 Billable/Specific Code Applicable To Constitutional gigantism[icd10data.com]
Accelerated Growth
  • A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects.[ncbi.nlm.nih.gov]
  • growth for the first 4 or 5 years and normal growth after that.[web.archive.org]
  • growth continues for the first 4 or 5 years, the rate being normal thereafter.[medical-dictionary.thefreedictionary.com]
  • The consequence is an accelerated growth rate and increased height as well as a number of additional soft tissue changes.[yourhormones.info]
  • Postoperatively his GH was 37.2 μg/liter, IGF-I was 2023 μg/liter, and accelerated growth continued.[doi.org]
Prisoner of War
  • At the outbreak of the First World War he was interned as a “prisoner of war” by the Germans in 1914. He prompt fell ill and was hospitalized until his release in 1916.[ncbi.nlm.nih.gov]
Pediatric Disorder
  • Conclusions We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone.[doi.org]
Prognathism
  • It appears in childhood and many morphological signs lead us to suspect it: enlarged hands and feet, thick skin, a prominent chin (called prognathism), and an abnormal tendency to sweat ... The organs are also increased in size.[health.ccm.net]
  • What you'll see in someone with acromegaly is they get what's called frontal bossing [an enlarged forehead], prognathism--their jaw juts out--they get spreading of the teeth, they get enlarged hands and feet.[scientificamerican.com]
  • Overgrowth of the jawbone (mandible) can cause the jaw to protrude (prognathism). Cartilage in the voice box (larynx) may thicken, making the voice deep and husky. The ribs may thicken, creating a barrel chest. Joint pain is common.[merckmanuals.com]
Foot Ulcer
  • Systemic sepsis from an infected foot ulcer necessitated treatment by an above-knee amputation. Postoperatively, the stump increased in size by 19 kg. A trial of rapamycin to reverse the growth of the stump has shown promise.[ncbi.nlm.nih.gov]
Skin Ulcer
  • A 24 year old woman with systemic lupus erythematosus (SLE) developed widespread necrotic skin ulceration and gigantism of both breasts during an exacerbation of SLE in the last trimester of her second pregnancy.[ncbi.nlm.nih.gov]
Macrocephaly
  • Abstract We report on a neonate presenting with polyhydramnios; macrosomia; macrocephaly; visceromegaly including bilateral nephromegaly, hepatomegaly, cardiomegaly; thymus hyperplasia; cryptorchidism; generalized muscle hypotonia; and a distinctive facial[ncbi.nlm.nih.gov]
  • His growth-hormone excess manifested as tall stature, coarse facial features, and macrocephaly. More than 95% of acromegaly cases are caused by a pituitary adenoma that secretes excess amounts of GH.[emedicine.medscape.com]
  • All growth parameters are affected, although not necessarily symmetrically because mild to moderate obesity is common and macrocephaly has been noted to precede linear and weight acceleration in at least one case ( 34 ).[doi.org]
Advanced Bone Age
  • Her precocious manifestations were public hair, acne vulgaris, hirsutism, and advanced bone age. Endocrinological examination revealed markedly increased serum growth hormone (GH) and prolactin (PRL), which responded paradoxically to a TRH test.[ncbi.nlm.nih.gov]
Short Hands
  • Voice is hoarse and affected individuals have a plump, stocky body with pectus excavatum, thoracic scoliosis, hepatosplenomegaly, umbilical and/or inguinal hernias, broad short hands and feet, and in some cases preauricular dimples, abnormal ears, postaxial[ncbi.nlm.nih.gov]
Grieving
  • The Wadlow family was especially mortified and grieved by the following phrase in the Humberd paper: “His expression is surly and indifferent, and he is definitely inattentive, apathetic and disinterested, unfriendly and antagonistic.[ncbi.nlm.nih.gov]
Frontal Bossing
  • Other symptoms include: Delayed puberty Double vision or difficulty with side (peripheral) vision Very prominent forehead ( frontal bossing ) and a prominent jaw Gaps between the teeth Headache Increased sweating Irregular periods (menstruation) Joint[nlm.nih.gov]
  • Other symptoms include: Delayed puberty Double vision or difficulty with side (peripheral) vision Very prominent forehead (frontal bossing) and a prominent jaw Gaps between the teeth Headache Increased sweating Irregular periods (menstruation) Joint pain[medlineplus.gov]
  • Other symptoms may include delayed puberty ; double vision or difficulty with side (peripheral) vision; prominent forehead ( frontal bossing ) and a prominent jaw; headache; increased sweating ( hyperhidrosis ); irregular periods; large hands and feet[rarediseases.info.nih.gov]
  • What you'll see in someone with acromegaly is they get what's called frontal bossing [an enlarged forehead], prognathism--their jaw juts out--they get spreading of the teeth, they get enlarged hands and feet.[scientificamerican.com]
Leontiasis
  • An impressive feature was his asymmetrical left facial hypertrophy, which was initially diagnosed as “leontiasis ossea” [ 36, 48, 50 ].[ncbi.nlm.nih.gov]
Excruciating Headache
  • Months before his death he first suddenly lost the vision in his left eye and suffered from excruciating headaches. Later he became blind in his right eye.[ncbi.nlm.nih.gov]
Frontal Headache
  • The medical history revealed that he had frontal headaches since the age of 28. There was progressive loss of the bitemporal visual fields from the age of 31 till age of 41 after which there was stabilization but no improvement.[ncbi.nlm.nih.gov]
Cerebral Calcification
  • ., cutaneous hypomelanotic macules, poliosis, cyst-like lesions of the right upper limb and cerebral calcifications.[ncbi.nlm.nih.gov]
Primary Amenorrhea
  • The patient presented with delayed puberty and primary amenorrhea along with a sudden appearance of clinical signs of hypersomatotropinism, which were the reasons for seeking medical help at the age of 16.[ncbi.nlm.nih.gov]

Workup

Measuring the blood levels of growth hormone and insulinlike growth factors forms the preliminary basis of diagnostic procedure. Another method of measuring the insulinlike growth factor is to determine the levels about 1 hour after administration of a glucose load. Under normal circumstances, the hormone levels decrease after a glucose load. In children with gigantism, the values remain normal even after consuming glucose. This indicates that the body produces excessive growth hormones, which causes the levels to remain normal [8]. Imaging studies such as CT scan and MRI are indicated to detect the location as well as size of the tumor in the pituitary gland. 

Enlarged Sella
  • A sellar radiograph showed an enlarged sella turcica with a diameter of 28 mm (1¼ in). A hand radiograph showed that the epiphysial plates had not yet fully closed. Furthermore there was marked osteoporosis [ 59, 60 ].[ncbi.nlm.nih.gov]
Enlarged Sella
  • A sellar radiograph showed an enlarged sella turcica with a diameter of 28 mm (1¼ in). A hand radiograph showed that the epiphysial plates had not yet fully closed. Furthermore there was marked osteoporosis [ 59, 60 ].[ncbi.nlm.nih.gov]
Testosterone Increased
  • We can speculate that growth acceleration in our patients was shorter than expected due to only transient pubertal testosterone increase in subject 2 and intermittent testosterone administration in subject 3.[doi.org]
Testosterone Decreased
  • Subject 2 went into spontaneous puberty as was evident by 120 ng/dl testosterone at age 11 yr 5 months, but by 12 yr 7 months, his testosterone decreased to subnormal levels.[doi.org]
Lymphocytic Infiltrate
  • Histological examination showed a mixed GH- and prolactin-secreting adenoma with lymphocytic infiltration of B and T cells.[ncbi.nlm.nih.gov]

Treatment

Treatment of gigantism is aimed at slowing down the progression of production of growth hormones as well as effective management of symptoms. The following methods are employed in order to fulfill the objectives:

  • Surgery is the first line of treatment if tumors in the pituitary gland are the major factor for gigantism. 
  • Medicines are employed when surgery cannot be performed. In such cases, medications are administered for management of the symptoms. Medicines such as lanreotide or octreotide are given monthly intravenously to reduce the excessive production of growth hormones. Another new drug known as pegvisomant has been developed to lower the production of growth hormones. The drug has to be injected daily and is used when other options or medications fail to yield positive results [9].
  • Gamma knife radiosurgery: This type of method is given when surgery is not an option. In such cases, high beam radiation is given to the tumor cells in order to destroy it. This method takes several years for bringing the levels of growth hormone back to normal and is also associated with several side effects; hence it is used very rarely [10].

Prognosis

Research has shown that, about 80% of cases can be successfully treated with surgery to remove the tumor. In situations, when surgery cannot be successfully accomplished then medications are employed for effective management of symptoms. In either of the cases, individuals can live a long and healthy life [6].

Etiology

Development of a tumor in the pituitary gland is the major cause of gigantism. Excessive release of growth hormone due to a benign tumor in the pituitary gland favors abnormal growth development in children [2].

In addition to excess production of growth hormones, gigantisms can also occur as a result of other conditions, which include neurofibromatosis, Carney complex, multiple endocrine neoplasia type I, tuberous sclerosis and McCune-Albright syndrome. It has been estimated that, about 20% patients suffering from gigantisms also suffer from McCune-Albright syndrome [1].

Epidemiology

Gigantism is a rare phenomenon, and only about 100 cases are reported till date. The condition of acromegaly is more common than gigantism, with a reported incidence of 3 – 4 cases per million each year; having a prevalence rate of 40 – 70 cases per million population. Gigantism can strike at any age before the epiphyseal fusion takes place. Agromegaly occurs in the third decade of life; with mean age of diagnosis being 40 years and 54 years in females and males respectively [4]. No sex predilection is known. 

Sex distribution
Age distribution

Pathophysiology

The excess production of insulinlike growth factor can be divided into the following factors:

  • Production and release of excessive growth hormone from the pituitary gland
  • Increase in the secretion of growth hormone releasing hormone 
  • Excess production of insulinlike growth hormone-binding protein, which in turn is responsible for prolonging the half-life of insulinlike growth hormone
  • The malfunctioning of the pituitary gland due to development of benign tumor is the major cause, and this promotes excessive production of growth hormones. This gland is located at base of the brain and is important for production of hormones that control the various functions of the body [5].

Prevention

Gigantism cannot be prevented. However, with early initiation of treatment, the onset of complications can certainly be kept at bay.

Summary

Gigantism occurs during childhood, much before the epiphyseal growth plates have closed. Early diagnosis along with prompt initiation of treatment is important for arresting the accelerated growth pattern. However, many parents fail to recognize that their child is suffering from gigantism as they consider the sudden growth as normal childhood growth spurts. Individuals with gigantism measure between 2.13 m to 2.74 m [1].

Patient Information

  • Definition: Gigantism is a condition wherein there is excessive production of growth hormones that causes abnormal growth in affected children. Prompt diagnosis and early initiation of treatment is required to arrest complications to set in.
  • Cause: Excessive production of growth hormones due to development of tumor in the pituitary gland is the major cause for gigantism. Other less common causes include various conditions such as neurofibromatosis, Carney complex, multiple endocrine neoplasia type I and McCune-Albright syndrome.
  • Symptoms: Symptoms of gigantism include larger than normal height compared to other children of same age. Affected children also suffer from delayed onset of puberty, difficulty in vision, sleep problems, weakness, excessive sweating, prominent jaws, headache, irregular menstruation, larger than normal hands and feet which have thickened fingers and toes.
  • Diagnosis: Determining the blood levels of growth hormone helps in arriving at a definitive diagnosis. The levels of the hormone can also be checked an hour later after administration of glucose load. MRI and CT scan would be required for locating the site and determining the shape of the tumor.
  • Treatment: Surgery forms the first line of treatment. If surgery isn’t an option then, medications are given to control the excessive production of growth hormones. A new drug that has been introduced to control the growth hormone release is pegvisomant. Gamma knife radiosurgery is the last resort and employed only when surgery and medications have not been successful in bringing about the desired results.

References

Article

  1. Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American children. J Pediatr 1985; 107:317.
  2. Nainggolan L. Gene Discovery in Giants Could Shed Light on Human Growth. Medscape Medical News.
  3. Sotos JF. Overgrowth.Hormonal Causes.ClinPediatr (Phila) 1996; 35:579.
  4. Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, et al. A consensus on criteria for cure of acromegaly. J ClinEndocrinolMetab. Jul 2010;95(7):3141-8.
  5. Khandelwal D, Khadgawat R, Mukund A, Suri A. Acromegaly with no pituitary adenoma and no evidence of ectopic source. Indian J EndocrinolMetab. Sep 2011;15Suppl 3:S250-2.
  6. Thomsett MJ. Referrals for tall stature in children: a 25-year personal experience. J Paediatr Child Health 2009; 45:58.
  7. Abe T, Tara LA, Lüdecke DK. Growth hormone-secreting pituitary adenomas in childhood and adolescence: features and results of transnasal surgery. Neurosurgery. Jul 1999;45(1):1-10
  8. Sippell WG, Partsch CJ, Wiedemann HR. Growth, bone maturation and pubertal development in children with the EMG-syndrome. Clin Genet 1989; 35:20.
  9. Rix M, Laurberg P, Hoejberg AS, Brock-Jacobsen B. Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl. Eur J Endocrinol. Aug 2005;153(2):195-201
  10. Jagannathan J, Yen CP, Pouratian N, Laws ER, Sheehan JP. Stereotactic radiosurgery for pituitary adenomas: a comprehensive review of indications, techniques and long-term results using the Gamma Knife. J Neurooncol. May 2009;92(3):345-56.

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Last updated: 2019-07-11 22:40