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You are watching: Post-puberty hypersecretion of growth hormone from the anterior pituitary gland

StatPearls . Treasure Island (FL): StatPearls Publishing; 2021 Jan-.


Continuing education Activity

Acromegaly and also gigantism are disorders the the abnormal excess cheap of growth hormone. Gigantism occurs when development hormone hypersecretion occurs prior to the fusion of the long bone epiphysis and is defined by tall stature. Acromegaly occurs as soon as GH hypersecretion wake up after the fusion of the epiphysis leading to huge extremities and also characteristic facies. This task explains the evaluation and management the gigantism and acromegaly and emphasizes the function of the interprofessional team in improving the care for patients v this condition.

Identify the pathophysiology the gigantism and also acromegaly.
Describe the IGF-1 levels in the initial testimonial of gigantism and also acromegaly.
Summarize the usage of surgical, medical, and also radiation treatment in the monitoring of gigantism and also acromegaly.
Describe the prestige of collaboration and also communication among the interprofessional team to enhance the delivery of care for patients impacted by gigantism and also acromegaly.
Access complimentary multiple selection questions on this topic.


Acromegaly and gigantism space disorders of growth hormone hypersecretion. The most common cause is a development hormone (GH) secreting adenoma in the pituitary gland. Gigantism occurs when expansion hormone hypersecretion occurs before the fusion of the long bone epiphysis and also is characterized by high stature. Acromegaly occurs as soon as GH hypersecretion wake up after the fusion of the epiphysis top to big extremities and also characteristic facies. An elevated insulin-like growth factor-1 (IGF-1) level develops the diagnosis. The first line of therapy is surgical excision of the tumor; however, this hardly ever results in a cure, and further medical treatment through somatostatin analogs or radiation is necessary.<1>


In around 95% that the instances of acromegaly and gigantism are second to a GH secreting adenoma in the pituitary gland. Expansion hormone-releasing hormone (GHRH) secretion from a hypothalamic adenoma or ectopic GHRH cheap from lung or kidneys neuroendocrine tumors can additionally cause acromegaly. Rarely, ectopic expansion hormone secretion second to ab and hemopoietic malignancies can cause acromegaly. Genetic syndromes that have actually been linked with GH hypersecretion are multiple endocrine neoplasia-1 (MEN-1), neurofibromatosis, Carney complex, and McCune-Albright syndrome. Familial idiopathic pituitary adenomas (FIPA) which are as result of aryl hydrocarbon protein-interacting (AIP) mutations can be associated with familial acromegaly. Around 25% of cases with familial acromegaly present as adolescents with gigantism.<2>


The prevalence of acromegaly is 78 situations per million population, and also the incidence is 10 new cases every year every million population.<3> over there is no sex preponderance v equal incidence in males and females. The average period of presentation is 44 years with younger patients tending to have much more aggressive disease. Around 33% of instances of acromegaly have co-existent hyperprolactinemia.<4>


GH is a 191 amino acid long protein through two de defiders bonds. The is secreted through the somatotroph cells in the anterior pituitary. It circulates because that the most part as a 22kD protein and the remaining as a 20kD protein. It is secreted in a pulsatile manner, 4 to 11 pulses in a day. As result of this pulsatile nature of secretion measurement of arbitrarily GH levels space not useful. Expansion hormone-releasing hormone (GHRH) stimulates the release of GH indigenous the pituitary. GHRH comprise neurons are largely seen in the arcuate nucleus and also ventromedial nucleus. Somatostatin, i beg your pardon is also secreted from the hypothalamus, exerts one inhibitory action on the secretion of GH. GHRH and also somatostatin also regulate every other"s cheap in a paracrine manner. GH stimulates the synthesis of IGF-1 native the liver. IGF-1 is a 70 amino acid protein the is comparable to insulin. Besides, post-receptor signaling mechanisms including tyrosine kinase and also insulin receptor substrate-1 (IRS-1) room also comparable for IGF-1 and insulin. IGF-1  circulates bound come IGF-1 binding proteins. IGF-1 exerts a negative feedback system through GHRH and also somatostatin.

Several various other hormones can additionally modulate the cheap of GH. The thyroid hormone facilitates the expression that the growth hormone gene. Hypothyroidism has been well-known to be connected with low GH and also IGF-1 which are reversible with thyroid hormone instead of therapy. Gonadal hormones can likewise upregulate the secretion of GH as evident during the start of puberty. Hypoglycemia decreases the secretion of somatostatin indigenous the hypothalamus and increases the release of GH. Mutations in the somatotrophs room a prerequisite for the abnormal solution to GHRH. Suggest mutations in Arg 201 and Gly227 have actually been reported which are the website for adenosene diphosphate (ADP) ribosylation and the binding domain of guanine tree phosphate (GTP) respectively an outcome in adenyl cyclase activation comparable to GHRH. The tumorigenesis which leads to a monoclonal cell development is multifactorial, and also the existence of a mutation alone is not enough.<5>


Densely Granulated GH cell Adenomas

These constitute about 30% the GH secreting pituitary adenomas and also are characterized by cells that are comparable to somatotrophs and also contain numerous big secretory granules. These space slow-growing tumors which current in middle age.

Sparsely Granulated GH cabinet Adenomas

These constitute about 30% the GH secreting pituitary adenomas and are characterized by pleomorphic cells with few secretory granules. These are rapidly farming tumors that current with severe disease at a young age.

Mixed GH Cell and Prolactin cell Adenoma

These are around 20% the GH secreting pituitary adenomas i beg your pardon are identified by densely granulated somatotrophs and also sparsely granulated lactotrophs. Lock secrete GH and prolactin.

Acidophilic Stem cell Adenomas

These room rare tumors and also are characterized by huge mitochondria. Clinically these are aggressive tumors that invade the surrounding structures. They additionally secrete GH and also prolactin.

Mammosomatotroph cabinet Adenoma

These comprise about 10% that GH secreting pituitary adenomas and also are characterized by cells the secrete both GH and also prolactin. They frequently occur in children and also present v gigantism and also hyperprolactinemia.

Plurihormonal cabinet Adenomas

As the name suggests, this tumors may secrete multiple hormone GH, prolactin, follicle-stimulating hormone (FSH), Thyrotropin stimulating hormone (TSH), or Adrenocorticotrophic hormone (ACTH); the an additional hormonal assets may it is in silent.<6><7>

History and Physical

Acromegaly is a really insidious condition where changes occur over numerous years. Consequently, studies have actually reported that the diagnosis is regularly delayed for around nine years on average. Patients may seek treatment for dental problems, cardiac or rheumatological issues before being described endocrinology.

GH secreting pituitary adenomas are often large (> 1 cm) and also can have actually compressive symptom in the form of visual field deficits, ophthalmoplegia, and headaches which are out that proportion to the size of the tumor. Co-existent hyperprolactinemia can an outcome in galactorrhea and symptoms that hypogonadism (irregular durations in females and also decreased libido in males).

Acromegaly Characteristics

Increased size of extremities: Enlargement that the hands and feet is detailed secondary come both bony expansion and soft organization swelling. Patients regularly appreciate an increase in ring and shoe size. The extremities have a "dough" choose consistency due to the soft organization swelling. There is a to decrease in the shoes size and also ring size with the therapy of acromegaly as result of the resolution that soft organization swelling; the bony changes, however, space permanent.

Hyperhidrosis and also skin tag are current in around 98% of situations of acromegaly; these features are a sensitive authorize for the detection of acromegaly. Skin sign are as result of the epithelial cell hyperproliferation induced by GH.

Acromegalic facies: influential supraorbital ridge, vast nose, acne, big lips, overbite, prognathism, tongue enlargement, and coarsening of face features type the characteristic acromegalic facies. These changes, however, are really subtle and often go i could not recognize it by family members. A comparison of present and also old photographs may present gradual changes and is critical part of the evaluate of acromegaly.

Musculoskeletal: generalised weakness and lethargy are usual symptoms. Elongation of the jaw deserve to lead to teeth malocclusion, temporomandibular share pain, and also a characteristic interdental separation. Carpal tunnel syndrome is watched in around 60% of patients and is second to swelling of the typical nerve quite than extrinsic compression. Early-onset osteoarthritis because of incongruent articular surfaces in the hips, knees, and spine may be seen. Kyphoscoliosis has also been report in association with acromegaly.

Deep voice and obstructive sleep apnea have the right to occur an additional to soft organization swelling of the upper airway and large tongue.<8><9><10>


Gigantism is very rare and should be suspected when the patient"s height is 3 typical deviations over normal mean height or 2 conventional deviations over the readjusted mean parental height. Due to the fact that gigantism is connected with miscellaneous syndromes choose neurofibromatosis, Carney facility and McCune Albright syndrome, testimonial for neurofibromas with cafe au lait spots, optic gliomas, and skin lentigines need to be done.<11>


Biochemical diagnosis: measurement of IGF-1 level is the early test because that the diagnosis of acromegaly together it is a stable molecule with a half-life that 15 hours. It must be measure up in instances where over there is clinical uncertainty of acromegaly and also pituitary masses – normal IGF-1 level rules out acromegaly. False-positive IGF-1 levels can be viewed in pregnancy and also adolescence, and also false-negative levels may be seen through estrogen therapy. Furthermore, hepatic failure, renal failure, hypothyroidism, malnutrition, sepsis, and poorly regulated diabetes mellitus can additionally influence IGF-1 levels. All instances with elevated IGF-1 levels need to have actually an oral glucose tolerance test (OGTT) with GH measure up to confirm the diagnosis that acromegaly or gigantism. A GH level of 1 mcg/lt or less 2 hrs after a 75 gms of oral glucose yongin test rules the end acromegaly. Plasma glucose requirements to be measured before and after the management of glucose come make sure hyperglycemia has actually been achieved.

Imaging: Pituitary Magnetic resonance imaging (MRI) is the preferred imaging modality for the diagnosis the acromegaly. The size, degree of the tumor, optic chiasmal compression, and cavernous sinus invasion can all be assessed ~ above the MRI scan. Visual field testing is come be done in all cases where the tumor is in contact with the optic chiasm ~ above the MRI scan.

Other tests: Prolactin levels must be assessed especially in the presence of galactorrhea or symptoms of hypogonadism. Anterior pituitary hormonal assessment requirements to be done based on the clinical picture. Rarely, in the presence of common pituitary and biochemically evidenced acromegaly GHRH levels and also imaging of the chest and abdomen have to be excellent to evaluate for ectopic GH or GHRH secretion.<1>

There space three main modalities obtainable for the therapy of acromegaly each through its benefits and disadvantages: surgery, medical therapy, and radiation. The decision to usage these modalities is make on a case-by-case basis.


Surgical excision of the tumor is the wanted initial treatment unless the patient is understood unfit for surgery. Surgical treatment is likewise the wanted modality in situation of recurrence as lengthy as the tumor continues to be accessible. The transsphenoidal method involves accessing the tumor by acquiring to the sphenoid sinus either with a nasal or sublabial approach and removing the sellar floor. Also tumors with suprasellar extension can be removed with this approach. Endoscopic transsphenoidal resection has far better tumor clearance, reduced morbidity, and also complications as contrasted to the microscope approach. Post-surgical complications include diabetes insipidus and anterior pituitary deficiencies.<12><13>

IGF-1 and also GH levels need to be measure up 12 weeks after ~ surgery. The goal is a normalization the IGF-1 and also an undetectable GH level.

Medical Treatment

Various medical therapies are accessible for the monitoring of acromegaly. Lock are used in the therapy of persistent an illness after surgery.

Radiation Therapy

Radiation is regularly used as an adjunct because that the treatment of persistent condition after surgery; hardly ever it may be used as a first-line treatment in patient unfit for surgery. Two commonly used radiation therapy modalities are exterior irradiation and also stereotactic single high dose irradiation.

External irradiation: Using direct accelerators radiation is concentrated on the pituitary fossa. CT or MRI are supplied for dosimetry to minimization radiation exposure to the bordering tissues. The full radiation sheep (around 4500 cGy) is split into fractions (generally 25 fountain of 180 cGy) and also given end 6 weeks; this fractionation helps minimize injury to bordering tissues. Around 60% the patients attain normalization of IGF-1 with radiation in 10 years. Hypopituitarism is a well-known side effect of radiation and can happen years ~ cessation the radiation, therefore yearly clinical and laboratory assessment because that hypopituitarism must be done. With external irradiation, there is a resolution of even radiologically invisible disease.

Differential Diagnosis

Acromegaloidism: This is a problem where the patients have acromegaloid facial functions or high stature, however, activities assessment of GH and also IGF-1 are normal. Imaging the pituitary in these cases is unremarkable.<22>

Soto"s syndrome: This is a congenital overgrowth syndrome identified by high stature, acromegaloid facies, pundit disabilities, macrocephaly, and progressed bone age.  various other clinical features encompass neonatal hypotonia, congenital heart defects, strabismus, scoliosis, and a prejudice to cancer. Soto syndrome is because of haploinsufficiency of NSD1 gene ~ above chromosome 5. Laboratory assessment the IGF-1 and also GH levels are normal. Hereditary studies are necessary to distinguish it native acromegaly.<23>


The prognosis counts on the stage at i beg your pardon the diagnosis is made as well as the solution of hormone levels to therapy - operation or non-surgical.

Hypertension is watched in about 40% that patients with acromegaly and is typically mild. Anti-hypertensive treatment is comparable to non-acromegalic patients. Good control of blood pressure is very important irrespective of the modality offered for acromegalic treatment.

Obstructive Sleep Apnea (OSA)

The prevalence of sleep apnea is 70% in patients through acromegaly. Prognathism, enlarged tongue, and also soft tissue build-up in the upper airways every predispose to having actually OSA. Clinical assessment (Epworth score) and if needed polysomnography need to be done at baseline and also repeated every year. Operation correction that prognathism may help, and referral to the maxillofacial surgeon must be considered.


Around 75% of patients with acromegaly are impacted with arthropathy. Both tiny and big joints room affected. Bony expansion and also soft tissue swelling deserve to lead to nerve entrapment. Beforehand diagnosis and aggressive therapy of acromegaly are necessary to stop arthropathy as these changes are irreversible.

Colon Polyps

Colon length is increased in acromegaly, and also so room the mucosal folds. There is an increased prevalence that colonic polyps with acromegaly; however, the threat of colon cancer might or might not be increased. Patient should obtain a colonoscopy in ~ baseline and every 5 years.<25>

Hypopituitarism can happen as a result of surgical procedure or radiation. Yearly assessment the pituitary hormones is recommended and then replace hormones as needed.<26>

Deterrence and Patient Education

Patients need to be educated on the importance of beforehand diagnosis and also adhering to the treatment. They should undergo continual endocrinology evaluation and check the blood pressure and blood street regularly.

Acromegaly and also gigantism are as result of oversecretion of development hormone. The most common reason is a GH secreting pituitary adenoma. Rarely, ectopic GH cheap or excess secretion of GHRH may be the cause.
Gigantism is characterized by tall stature and should be doubt in children three traditional deviations over the mean. Acromegaly is identified by large hands and feet, coarse facial features, broad nose, acne, hyperhidrosis, underbite, and also teeth separation.

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Enhancing healthcare Team Outcomes

The monitoring of acromegaly and also gigantism need to be done with an interprofessional team that has an endocrinologist, neurosurgeon, internist, cardiologist, rheumatologist, pulmonologist, and also oncologist. Untreated acromegaly has actually increased mortality as contrasted to the basic population. The major contributors to mortality are cardiovascular disease (60%), respiratory condition (25%), and malignancies (15%). Mortality rates are comparable to the general population in patients with controlled GH secretion. Besides the level that GH, the visibility of cardiac condition is vital prognostic indicator. The visibility of cardiac disease at diagnosis has a 100% mortality price at 15 years. The mortality rate of patients through acromegaly and also diabetes at 20 years is 80%.<27><28>