Growth Hormone

Random growth hormone (GH) levels in a healthy person range as follows ^[1] :

• Men - < 5 ng/mL (mcg/L [SI units])

• Women - < 10 ng/mL (mcg/L [SI units])

• Newborns - 5-23 ng/mL (mcg/L [SI units])

• 1 week - 2-27 ng/mL (mcg/L [SI units])

• 1-12 mos - 2-10 ng/mL (mcg/L [SI units])

• 1 year (female) - 0-10 g/mL (mcg/L [SI units])

• 1 year (male) - 0-6 ng/mL (mcg/L [SI units])

GH suppression test value (using 100 g glucose) in a healthy person is as follows ^[1] :

• < 2 ng/mL

GH stimulation test values (normal) ^[1] :

• GH - > 10 mg/mL (mcg/L [SI units])
• Insulin-like growth factor 1 (IGF-1) - > 80 ng/mL

Obesity impairs GH release, so the GH levels required to diagnose deficiency should be lower in persons with obesity.

A study by Lee et al indicated that in patients with GH deficiency undergoing a GH stimulation test using dopamine, insulin, or arginine, a negative association exists between the individual’s body mass index standard deviation score (BMI SDS) and the peak serum GH level derived through the test. Thus, according to the investigators, BMI factors should be taken into account in the interpretation of GH stimulation testing results. ^[2]

SI Units = Conventional Units X 1 (mcg/L = ng/mL X 1)

High growth hormone levels

High growth hormone (GH) levels associated with high IGF-1 concentrations and normal GH and IGF-1 receptors, seen in the following conditions, cause gigantism in children and acromegaly in adults:

• Pituitary gland tumor (mostly, benign adenoma)

• Multiple endocrine neoplasia type I (MEN-I)

• Ectopic production - Some tumors located in the lungs, adrenal glands, pancreas, or elsewhere can secrete either GH or GH-releasing hormone (GHRH); the latter can stimulate the production of GH by the pituitary gland

• McCune-Albright syndrome - An early postzygotic genetic disease resulting from activating mutations in the alpha subunit of the G protein (s subtype); it can cause constitutional activation of the post-GHRH receptor pathway and increase GH production from the pituitary gland

High GH concentrations not associated with high IGF-1 levels are seen in the following conditions:

• Uncontrolled diabetes mellitus

• Kidney disease

• Starvation

• Inherited resistance to GH (Laron syndrome)

High GH levels associated with high IGF-1 concentrations are seen in the following condition:

• Dwarfism due to IGF-1 resistance because of inactivating mutations in the IGF-1 receptor

Low growth hormone levels

Low levels of GH associated with low IGF-1 levels cause dwarfism in children and vague, nonspecific symptoms (fatigue, decreased muscle mass, osteoporosis), along with increased risk of cardiovascular disease in adults.

Genetic causes

Genetic causes of low GH levels include the following ^[3] :

• Combined pituitary hormone deficiencies -  HESX1, LHX3, LHX4, SOX3, GLI2, PROP1, PITX2,  and  PIT1 gene mutations
• Isolated GH deficiency -  GH1, GHRH, and  GHRHR gene mutations
• Holoprosencephaly
• Schizencephaly
• Septo-optic dysplasia
• Pallister-Hall syndrome
• Rieger syndrome
• Prader-Willi syndrome

Tumors

Tumor-related causes of low GH levels include the following ^[3] :

• Benign - Craniopharyngioma, arachnoid cyst, pituitary adenoma, Rathke cleft cyst
• Malignant - Dysgerminoma, meningioma, glioma, metastatic Hodgkin disease

Trauma

Traumatic causes of low GH levels include the following ^[3] :

• Surgical trauma
• Skull fracture
• Birth injury

Inflammatory causes

Inflammatory causes of low GH levels include the following ^[3] :

• Histiocytosis
• Sarcoidosis
• Tuberculosis
• Meningitis
• Hemochromatosis
• Autoimmune hypophysitis

Other

Additional causes of low GH levels include the following:

• Pituitary apoplexy ^[3]
• Irradiation ^[3]
• Cardiac failure ^[4]

The patient should not exercise or eat anything for 10 hours before the test (unless specifically instructed to do so for some of the dynamic tests); water is permitted. The patient may be asked to sit quietly for 30 minutes right before the test. ^[5]

Certain medicines can affect growth hormone (GH) test results, such as corticosteroids and estrogen (including birth control pills). The patient may be asked to stop taking these medicines before the test. ^[6]

Contraindications for stimulation tests ^[1] :

• Epilepsy
• Cerebrovascular disease
• Myocardial infarction
• Low basal plasma cortisol levels

Drugs that can increase GH levels include the following ^[1] :

• Amphetamines
• Dopamine
• Estrogens
• Histamine
• Nicotinic acid
• Arginine
• Glucagon
• Insulin
• L-DOPA
• Methyldopa
• Propranolol, clonidine (children) ^{[7, 8]}
• Ghrelin ^[9]

Drugs that can decrease GH levels include the following ^[1] :

• Corticosteroids

• Phenothiazines

To prepare the specimen, usually 5 mL of blood serum is collected by venipuncture and drawn in a red top container. ^[5]

Related tests are as follows ^{[5, 6]} :

• GH suppression test

• GH stimulation test

• IGF-1 test

• GHRH test

• Cortisol test

• Corticotropin test

• Thyroid-stimulating hormone (TSH) test

• Prolactin test

• Luteinizing hormone (LH)/follicle-stimulating hormone (FSH) test

Simplified sampling schemes, especially a day profile, are enough to estimate GH secretion in patients with active acromegaly and under medical treatment. On the other hand, 24-hour secretion is sufficiently reflected through prolonged and frequent sampling schemes, performed at at least 2-hour intervals, in healthy controls and following successful surgery in patients. ^[10]

Description  ^{[5, 6, 11]}

Note the image below.

Growth hormone (GH), or somatotropin, is produced and released by specialized cells (somatotrophs) in the anterior part of the pituitary gland. GH is needed for growth and has important effects on protein, lipids, and carbohydrate metabolism. GH's functions are accomplished directly as a result of GH binding to its receptor on target cells or indirectly primarily through IGF-1, a hormone secreted from the liver and other tissues in response to GH. The majority of the growth-promoting effects of GH are through IGF-1 acting on its target cells.

GH release in the pituitary is primarily determined by the balance of two antagonistic regulatory hormones secreted from the neurosecretory nuclei of the hypothalamus. These are GHRH, or somatocrinin, which is stimulatory, and GH-inhibiting hormone (GHIH), or somatostatin, which is inhibitory. These two hypothalamic hormones, in turn, are modulated by many factors, including stress, exercise, nutrition, sleep, IGF-1, and GH itself (negative feedback loop).

Integration of all the factors that affect GH synthesis and secretion leads to a pulsatile pattern of release. The largest and most predictable GH peak occurs about an hour after the onset of deep sleep.

Indications/applications  ^{[5, 6, 12]}

The following conditions suggest the possible need for GH testing:

• Signs or symptoms of GH excess - Acromegaly in adults (eg, soft tissue swelling and enlargement of extremities, coarsening of facial features, prognathism, macroglossia) and gigantism in children

• Signs or symptoms of GH deficiency - Short stature in children (the child is significantly shorter than others of the same age) and changes in muscle mass, cholesterol levels, and bone strength in adults

• History of a pituitary gland problem (eg, trauma, surgery, radiation)

• Adult with signs or symptoms suggestive of a deficiency in other pituitary hormones (eg, thyroid, adrenal, gonads)

• Follow-up for other abnormal hormone test results

• Children who have had radiation treatment of the central nervous system or whole body irradiation (eg, treatment for malignancy, prior to stem cell transplantation)

Monitor treatment in patients on GH replacement therapy. Assess the success of therapy for acromegaly or gigantism.

Considerations/precautions

GH levels in blood change during the day and are affected by exercise, sleep, emotional stress, and diet. ^{[5, 6]}

To avoid interpretation dilemmas from the variations in GH secretion, screening for IGF-1 or somatomedin C are mandated and can provide superior accuracy regarding the mean plasma concentration of GH. ^[1]

GH is released in pulses. A higher level may be normal if the blood was drawn during a pulse. A lower level may be normal if the blood was drawn around the end of a pulse. Because of this, random GH levels are generally not very useful; too much overlap occurs between abnormal GH results and normal daily variations. It is more useful to perform a GH stimulation test (if one suspects deficiency) and a GH suppression test (if one suspects excess) and to correlate GH levels with IGF-1 levels, as IGF-1 levels integrate GH excesses and deficiencies and are stable throughout the day. ^{[5, 6]}

For the GH stimulation test, a sample of blood is drawn after 10-12 hours of fasting. Then, under close medical supervision, a person is given an intravenous solution of insulin or arginine (or other stimulus). Blood samples are then drawn at timed intervals, and GH levels are tested in each sample to see if the pituitary gland was stimulated to produce the expected levels of GH. If GH levels are not adequately stimulated during a GH stimulation test (usually on at least two tests) and the person has symptoms of GH deficiency and a low IGF-1 level, then a GH deficiency is likely. ^{[5, 6]}

For the GH suppression test, a sample of blood is drawn after 10-12 hours of fasting. A person is then given a standard glucose solution to drink. Blood samples are drawn at timed intervals, and GH levels are tested. If a person's GH levels are not adequately suppressed during a GH suppression test and the person has symptoms of gigantism or acromegaly and a high IGF-1 level, then it is likely that the patient is producing too much GH. If a mass shows up on a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pituitary, then a pituitary tumor (usually benign) is likely present. ^{[5, 6]}

If the person has hypothyroidism, then GH testing for GH deficiency should not be performed until the individual's thyroid function has been evaluated and treated, as thyroid deficiency can cause symptoms similar to GH deficiency. ^{[5, 6]}

GH abnormalities can usually be treated once the causes are identified, but to have a good outcome, they should be identified as soon as possible, because some changes are not reversible. ^[11]

In younger children, IGF binding protein 3 (IGFBP-3) is a superior screening test for GH deficiency than is IGF-1 because it can determine low-normal levels of IGFBP-3 in this age group in contrast to truly low levels. ^{[13, 14]}