The pituitary gland works hard to keep you healthy, doing everything from ensuring proper bone and muscle growth to helping nursing mothers produce milk for their babies. Its functionality is even more remarkable when you consider the gland is the size of a pea.
“The pituitary is commonly referred to as the ‘master’ gland because it does so many important jobs in the body,” says Karen Frankwich, MD, a board-certified endocrinologist at Mission Hospital. “Not only does the pituitary make its own hormones, but it also triggers hormone production in other glands. The pituitary is aided in its job by the hypothalamus. This part of the brain is situated above the pituitary, and sends messages to the gland on when to release or stimulate production of necessary hormones.”
These hormones include:
Growth hormone, for healthy bone and muscle mass
Thyroid-stimulating hormone, which signals the thyroid to produce its hormones that govern metabolism and the body’s nervous system, among others
Follicle-stimulating and luteinizing hormones for healthy reproductive systems (including ovarian egg development in women and sperm formation in men, as well as estrogen and testosterone production)
Prolactin, for breast milk production in nursing mothers
Adrenocorticotropin (ACTH), which prompts the adrenal glands to produce the stress hormone cortisol. The proper amount of cortisol helps the body adapt to stressful situations by affecting the immune and nervous systems, blood sugar levels, blood pressure and metabolism.
Antidiuretic (ADH), which helps the kidneys control urine levels
Oxytocin, which can stimulate labor in pregnant women
The work of the pituitary gland can be affected by non-cancerous tumors called adenomas. “These tumors can affect hormone production, so you have too little or too much of a certain hormone,” Dr. Frankwich says. “Larger tumors that are more than 1 centimeter, called macroadenomas, can also put pressure on the area surrounding the gland, which can lead to vision problems and headaches. Because symptoms can vary depending on the hormone that is affected by a tumor, or sometimes there are no symptoms, adenomas can be difficult to pinpoint. General symptoms can include nausea, weight loss or gain, sluggishness or weakness, and changes in menstruation for women and sex drive for men.”
If there’s a suspected tumor, a doctor will usually run tests on a patient’s blood and urine, and possibly order a brain-imaging scan. An endocrinologist can help guide a patient on the best course of treatment, which could consist of surgery, medication, radiation therapy or careful monitoring of the tumor if it hasn’t caused major disruption.
“The pituitary gland is integral to a healthy, well-functioning body in so many ways,” Dr. Frankwich says. “It may not be a major organ you think about much, but it’s important to know how it works, and how it touches on so many aspects of your health.”
Aim—To contribute to the debate about whether growth hormone (GH) and insulin-like growth factor 1 (IGF-1) act independently on the growth process.
Methods—To describe growth in human and animal models of isolated IGF-1 deficiency (IGHD), such as in Laron syndrome (LS; primary IGF-1 deficiency and GH resistance) and IGF-1 gene or GH receptor gene knockout (KO) mice.
Results—Since the description of LS in 1966, 51 patients were followed, many since infancy. Newborns with LS are shorter (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine growth. Newborn mice with IGF-1 gene KO are 30% smaller. The postnatal growth rate of patients with LS is very slow, the distance from the lowest normal centile increasing progressively. If untreated, the final height is 100–136 cm for female and 109–138 cm for male patients. They have acromicia, organomicria including the brain, heart, gonads, genitalia, and retardation of skeletal maturation. The availability of biosynthetic IGF-1 since 1988 has enabled it to be administered to children with LS. It accelerated linear growth rates to 8–9 cm in the first year of treatment, compared with 10–12 cm/year during GH treatment of IGHD. The growth rate in following years was 5–6.5 cm/year.
Conclusion—IGF-1 is an important growth hormone, mediating the protein anabolic and linear growth promoting effect of pituitary GH. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH.
Keywords: insulin-like growth factor I, growth hormones, Laron syndrome, growth
In recent years, new technologies have enabled many advances in the so called growth hormone (GH) axis (fig 1▶). Thus, it has been found that GH secretion from the anterior pituitary is regulated not only by GH releasing hormone (GHRH) and somatostatin (GH secretion inhibiting hormone),1 but also by other hypothalamic peptides called GH secretagogues,2 which seem to act in synergism with GHRH3 by inhibiting somatostatin.4 One of these has been cloned and named Ghrelin.5 The interplay between GHRH and somatostatin induces a pulsatile GH secretion,6 which is highest during puberty. GH induces the generation of insulin-like growth factor 1 (IGF-1, also called somatomedin 1) in the liver and regulates the paracrine production of IGF-1 in many other tissues.7
IGF-1 and IGF-2 were identified in 1957 by Salmon and Daughaday8 and designated “sulphation factor” by their ability to stimulate 35-sulphate incorporation into rat cartilage. Froesch et al described the non-suppressible insulin-like activity (NSILA) of two soluble serum components (NSILA I and II).9 In 1972, the labels sulphation factor and NSILA were replaced by the term “somatomedin”, denoting a substance under control and mediating the effects of GH.10 In 1976, Rinderknecht and Humbel11 isolated two active substances from human serum, which owing to their structural resemblance to proinsulin were renamed “insulin-like growth factor 1 and 2” (IGF-1 and 2). IGF-1 is the mediator of the anabolic and mitogenic activity of GH.12
The IGFs are members of a family of insulin related peptides that include relaxin and several peptides isolated from lower invertebrates.13 IGF-1 is a small peptide consisting of 70 amino acids with a molecular weight of 7649 Da.14 Similar to insulin, IGF-1 has an A and B chain connected by disulphide bonds. The C peptide region has 12 amino acids. The structural similarity to insulin explains the ability of IGF-1 to bind (with low affinity) to the insulin receptor.
THE IGF-1 GENE
The IGF-1 gene is on the long arm of chromosome 12q23–23.15,16 The human IGF-1 gene consists of six exons, including two leader exons, and has two promoters.17
In the plasma, 99% of IGFs are complexed to a family of binding proteins, which modulate the availability of free IGF-1 to the tissues. There are six binding proteins.18 In humans, almost 80% of circulating IGF-1 is carried by IGFBP-3, a ternary complex consisting of one molecule of IGF-1, one molecule of IGFBP-3, and one molecule of an 88 kDa protein named acid labile subunit.19 IGFBP-1 is regulated by insulin and IGF-120; IGFBP-3 is regulated mainly by GH but also to some degree by IGF-1.21
The human IGF-1 receptor (type 1 receptor) is the product of a single copy gene spanning over 100 kb of genomic DNA at the end of the long arm of chromosome 15q25–26.22 The gene contains 21 exons (fig 2▶) and its organisation resembles that of the structurally related insulin receptor (fig 3▶).23 The type 1 IGF receptor gene is expressed by almost all tissues and cell types during embryogenesis.24 In the liver, the organ with the highest IGF-1 ligand expression, IGF-1 receptor mRNA is almost undetectable, possibly because of the “downregulation” of the receptor by the local production of IGF-1. The type 1 IGF receptor is a heterotetramer composed of two extracellular spanning α subunits and transmembrane β subunits. The α subunits have binding sites for IGF-1 and are linked by disulphide bonds (fig 3▶). The β subunit has a short extracellular domain, a transmembrane domain, and an intracellular domain. The intracellular part contains a tyrosine kinase domain, which constitutes the signal transduction mechanism. Similar to the insulin receptor, the IGF-1 receptor undergoes ligand induced autophosphorylation.25 The activated IGF-1 receptor is capable of phosphorylating other tyrosine containing substrates, such as insulin receptor substrate 1 (IRS-1), and continues a cascade of enzyme activations via phosphatidylinositol-3 kinase (PI3-kinase), Grb2 (growth factor receptor bound protein 2), Syp (a phophotyrosine phosphatase), Nck (an oncogenic protein), and Shc (src homology domain protein), which associated to Grb2, activates Raf, leading to a cascade of protein kinases including Raf, mitogen activated protein (MAP) kinase, 5 G kinase, and others.26
IGF-1 is secreted by many tissues and the secretory site seems to determine its actions. Most IGF-1 is secreted by the liver and is transported to other tissues, acting as an endocrine hormone.27 IGF-1 is also secreted by other tissues,28 including cartilagenous cells, and acts locally as a paracrine hormone (fig 4▶).29 It is also assumed that IGF-1 can act in an autocrine manner as an oncogene.30 The role of IGF-1 in the metabolism of many tissues including growth has been reviewed recently.31,32
The discussion on the role of IGF-1 in body growth will be based on growth in states of IGF-1 deficiency and the effects of exogenous IGF-1 administration. Experiments in nature (gene deletion or gene mutations) or experimental models in animals, such as gene knockouts, help us in this endeavour. In 1966 and 1968,33,34 we described a new type of dwarfism indistinguishable from genetic isolated GH deficiency (IGHD), but characterised by high serum GH values. Subsequent studies revealed that these patients cannot generate IGF-1.35
This syndrome of GH resistance (insensitivity) was named by Elders et al as Laron dwarfism,36 a name subsequently changed to Laron syndrome (LS).37 Molecular studies revealed that the causes of GH resistance are deletions38 or mutations39 in the GH receptor gene, resulting in the failure to generate IGF-1 and a reduction in the synthesis of several other substances, including IGFBP-3. This unique model in humans has enabled the study of the differential effects of GH and IGF-1.
Growth and development in congenital (primary) IGF-1 deficiency (LS)
Our group has studied and followed 52 patients (many since birth) throughout childhood, puberty, and into adulthood. We found that newborns with LS are slightly shorter at birth (42–47 cm) than healthy babies (49–52 cm), suggesting that IGF-1 has some influence on intrauterine linear growth.40 This fact is enforced by the findings that already at birth, and throughout childhood, skeletal maturation is retarded, as is organ growth.41 These growth abnormalities include a small brain (as expressed by head circumference),41 a small heart (cardiomicria),42 and acromicria (small chin, resulting from underdevelopment of the facial bones, small hands, and small feet).33,34 IGF-1 deficiency also causes underdevelopment and weakness of the muscular system,43 and impairs and weakens hair44 and nail growth. These findings are identical to those described in IGHD.45 IGF-1 deficiency throughout childhood causes dwarfism (final height if untreated, 100–135 cm in female and 110–142 cm in male patients),40,41 with an abnormally high upper to lower body ratio.41 One patient reported from the UK was found to have a deletion of exons 4 and 5 of the IGF-1 gene and he too was found to have severe growth retardation.46
Impaired growth and skeletal development in the absence of IGF-1 were confirmed in mice using knockout (KO) of the IGF-1 gene or GH receptor gene.47–49
Knockout of the IGF-1 gene or the IGF-1 receptor gene reduces the size of mice by 40–45%.49 Lack of the IGF-1 receptor is lethal at birth in mice owing to respiratory failure caused by impaired development of the diaphragm and intercostal muscles.49 In another model, the mice remained alive and their postnatal growth was reduced.50
In conclusion, findings in humans and in animals show that IGF-1 deficiencies causes pronounced growth retardation in the presence of increased GH values.
The following is a summary of the results of the growth stimulating effects of the administration of exogenous IGF-1 to children and experimental data.
The first demonstration that exogenous IGF-1 stimulates growth was the administration of purified hormone to hypophysectomised rats.51,52 After the biosynthesis of IGF-1 identical to the native hormone,53 trials of its use in humans were begun; first in adults54 and then in children.55,56 Our group was the first to introduce long term administration of biosynthetic IGF-1 to children with primary IGF-1 deficiency—primary GH insensitivity or LS.57 The finding that daily IGF-1 administration raises serum alkaline phosphatose, which is an indicator of osteoblastic activity, and serum procollagen,57,58 in addition to IGFBP-3,21 led to long term treatment. Treatment of patients with LS was also initiated in other parts of the world.59–62 The difference between us and the other groups was that we used a once daily dose, whereas the others administered IGF-1 twice daily.60 Table 1▶ compares the linear growth response of children with LS treated by four different groups. It can be seen that before treatment the mean growth velocity was 3–4.7 cm/year and that this increased after IGF-1 treatment to 8.2–9.1 cm/year, followed by a lower velocity of 5.5–6.4 cm/year in the next two years. (In GH treatment the highest growth velocity registered is also in the first year of treatment.) Figure 5▶ illustrates the growth response to IGF-1 in eight children during the first years of treatment.65 Ranke and colleagues60 reported that two of their patients had reached the third centile (Tanner), as did the patient of Krzisnik and Battelino66; however, most patients did not reach a normal final height. The reasons may be late initiation of treatment, irregular IGF-1 administration, underdosage, etc. Ranke et al conclude that long term treatment of patients with LS promoted growth and, if treatment is started at an early age, there is a considerable potential for achieving height normalisation.60 Because no patient in our group was treated since early infancy to final height we cannot confirm this opinion.
Growth velocity before and during insulin-like growth factor 1 (IGF-1) treatment. Note that in infancy, when the non-growth hormone/IGF-1 dependent growth velocity is relatively high (but low for age), the change induced by IGF-1 administration is less than in older children.
Linear growth response of children with Laron syndrome treated by means of insulin-like growth factor 1 (IGF-1)
*The younger children had a growth velocity of 5.5 and 6.5 cm/year.
BA, bone age; b.i.d., twice daily; CA, chronological age; i.d., once daily; Ht SDS, height standard deviation score.
When the growth response to GH treatment in infants with IGHD was compared with that of IGF-1 in infants with LS we found that the infants with IGHD responded faster and better than those with LS.67 However, the small number of patients and the differences in growth retardation between the two groups makes it difficult to reach a conclusion.
Both hormones stimulated linear growth, but GH seemed more effective than IGF-1. One cause may be the greater growth deficit of the infants with LS than those with IGHD, an insufficient dose of IGF-1, or that there is a need for some GH to provide an adequate stem cell population of prechondrocytes to enable full expression of the growth promoting action of IGF-1, as postulated by Green and colleagues68 and Ohlson et al.69 All the above findings based on a few clinical studies with small groups of patients and a few experimental studies remain at present controversial. The crucial question is whether there are any, and if so, whether there are sufficient IGF-1 receptors in the “progenitor cartilage zone” of the epiphyseal cartilage (fig 4▶) to respond to endocrine and exogenous IGF-1. Using the mandibular condyle of 2 day old ICR mice, Maor et al showed that these condyles, which resemble the epiphyseal plates of the long bones, contain IGF-1 and high affinity IGF-1 receptors also in the chondroprogenitor cell layers, which enables them to respond to IGF-1 in vitro.70
Sims et al,71 using mice with GH receptor KO showed that IGF-1 administration stimulates the growth (width) of the tibial growth plate and that IGF-1 has a GH independent effect on the growth plate. These findings are similar to those found when treating hypophysectomised rats with IGF-1.51,52
In conclusion, IGF-1 is an important growth hormone, mediating the anabolic and linear growth promoting effect of pituitary GH protein. It has a GH independent growth stimulating effect, which with respect to cartilage cells is possibly optimised by the synergistic action with GH.
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Dexamethasone suppression test measures whether adrenocorticotrophic hormone (ACTH) secretion by the pituitary can be suppressed.
How the Test is Performed
During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn so that the cortisol level in your blood can be measured.
There are two different types of dexamethasone suppression tests: low dose and high dose. Each type can either be done in an overnight (common) or standard (3-day) method (rare). There are different processes that may be used for either test. Examples of these are described below.
Low-dose overnight — You will get 1 milligram (mg) of dexamethasone at 11 p.m., and a health care provider will draw your blood the next morning at 8 a.m. for a cortisol measurement.
High-dose overnight — The provider will measure your cortisol on the morning of the test. Then you will receive 8 mg of dexamethasone at 11 p.m. Your blood is drawn the next morning at 8 a.m. for a cortisol measurement.
Standard low-dose — Urine is collected over 3 days (stored in 24-hour collection containers) to measure cortisol. On day 2, you will get a low dose (0.5 mg) of dexamethasone by mouth every 6 hours for 48 hours.
Standard high-dose — Urine is collected over 3 days (stored in 24-hour collection containers) for measurement of cortisol. On day 2, you will receive a high dose (2 mg) of dexamethasone by mouth every 6 hours for 48 hours.
Read and follow the instructions carefully. The most common cause of an abnormal test result is when instructions are not followed.
How to Prepare for the Test
The provider may tell you to stop taking certain medicines that can affect the test, including:
Medicines that contain corticosteroids, such as hydrocortisone, prednisone
Oral birth control (contraceptives)
Water pills (diuretics)
How the Test will Feel
When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging. Afterward, there may be some throbbing or slight bruising. This soon goes away.
Why the Test is Performed
This test is done when the provider suspects that your body is producing too much cortisol. It is done to help diagnose Cushing syndrome and identify the cause.
The low-dose test can help tell whether your body is producing too much ACTH. The high-dose test can help determine whether the problem is in the pituitary gland (Cushing disease) or from a different site in the body (ectopic).
Dexamethasone is a man-made (synthetic) steroid that binds to the same receptor as cortisol. Dexamethasone reduces ACTH release in normal people. Therefore, taking dexamethasone should reduce ACTH level and lead to a decreased cortisol level.
If your pituitary gland produces too much ACTH, you will have an abnormal response to the low-dose test. But you can have a normal response to the high-dose test.
Cortisol level should decrease after you receive dexamethasone.
Overnight — 8 a.m. plasma cortisol lower than 1.8 micrograms per deciliter (mcg/dL) or 50 nanomoles per liter (nmol/L)
Standard — Urinary free cortisol on day 3 lower than 10 micrograms per day (mcg/day) or 280 nmol/L
Overnight — greater than 50% reduction in plasma cortisol
Standard — greater than 90% reduction in urinary free cortisol
Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or may test different specimens. Talk to your doctor about the meaning of your specific test results.
What Abnormal Results Mean
An abnormal response to the low-dose test may mean that you have abnormal release of cortisol (Cushing syndrome). This could be due to:
The high-dose test can help tell a pituitary cause (Cushing disease) from other causes. An ACTH blood test may also help identify the cause of high cortisol.
Abnormal results vary based on the condition causing the problem.
Cushing syndrome caused by an adrenal tumor:
Low-dose test — no decrease in blood cortisol
ACTH level — low
In most cases, the high-dose test is not needed
Ectopic Cushing syndrome:
Low-dose test — no decrease in blood cortisol
ACTH level — high
High-dose test — no decrease in blood cortisol
Cushing syndrome caused by a pituitary tumor (Cushing disease)
Low-dose test — no decrease in blood cortisol
High-dose test — expected decrease in blood cortisol
False test results can occur due to many reasons, including different medicines, obesity, depression, and stress. False results are more common in women than men.
Most often, the dexamethasone level in the blood is measured in the morning along with the cortisol level. For the test result to be considered accurate, the dexamethasone level should be higher than 200 nanograms per deciliter (ng/dL) or 4.5 nanomoles per liter (nmol/L). Dexamethasone levels that are lower can cause a false-positive test result.
There is little risk involved with having your blood taken. Veins and arteries vary in size from one patient to another, and from one side of the body to the other. Taking blood from some people may be more difficult than from others.
Other risks associated with having blood drawn are slight, but may include:
Fainting or feeling lightheaded
Multiple punctures to locate veins
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)
DST; ACTH suppression test; Cortisol suppression test
Chernecky CC, Berger BJ. Dexamethasone suppression test – diagnostic. In: Chernecky CC, Berger BJ, eds. Laboratory Tests and Diagnostic Procedures. 6th ed. St Louis, MO: Elsevier Saunders; 2013:437-438.
Guber HA, Oprea M, Russell YX. Evaluation of endocrine function. In: McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 24th ed. St Louis, MO: Elsevier; 2022:chap 25.
Newell-Price JDC, Auchus RJ. The adrenal cortex. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, eds. Williams Textbook of Endocrinology. 14th ed. Philadelphia, PA: Elsevier; 2020:chap 15.
Review Date 5/13/2021
Updated by: Brent Wisse, MD, Board Certified in Metabolism/Endocrinology, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.
The endocrine system is a complex network of glands and organs. It uses hormones to control and coordinate your body’s metabolism, energy level, reproduction, growth and development, and response to injury, stress, and mood. The following are integral parts of the endocrine system:
Hypothalamus. The hypothalamus is located at the base of the brain, near the optic chiasm where the optic nerves behind each eye cross and meet. The hypothalamus secretes hormones that stimulate or suppress the release of hormones in the pituitary gland, in addition to controlling water balance, sleep, temperature, appetite, and blood pressure.
Pineal body. The pineal body is located below the corpus callosum, in the middle of the brain. It produces the hormone melatonin, which helps the body know when it’s time to sleep.
Pituitary . The pituitary gland is located below the brain. Usually no larger than a pea, the gland controls many functions of the other endocrine glands.
Thyroid and parathyroid. The thyroid gland and parathyroid glands are located in front of the neck, below the larynx (voice box). The thyroid plays an important role in the body’s metabolism. The parathyroid glands play an important role in the regulation of the body’s calcium balance.
Thymus. The thymus is located in the upper part of the chest and produces white blood cells that fight infections and destroy abnormal cells.
Adrenal gland . An adrenal gland is located on top of each kidney. Like many glands, the adrenal glands work hand-in-hand with the hypothalamus and pituitary gland. The adrenal glands make and release corticosteroid hormones and epinephrine that maintain blood pressure and regulate metabolism.
Pancreas . The pancreas is located across the back of the abdomen, behind the stomach. The pancreas plays a role in digestion, as well as hormone production. Hormones produced by the pancreas include insulin and glucagon, which regulate levels of blood sugar.
Ovary. A woman’s ovaries are located on both sides of the uterus, below the opening of the fallopian tubes (tubes that extend from the uterus to the ovaries). In addition to containing the egg cells necessary for reproduction, the ovaries also produce estrogen and progesterone.
Testis. A man’s testes are located in a pouch that hangs suspended outside the male body. The testes produce testosterone and sperm.
Headaches are a common complaint in patients with pituitary tumors. Although many patients presumably have headaches which are unrelated to their pituitary tumor, there are several important direct and indirect mechanisms by which pituitary tumors may elicit or exacerbate headaches. Pituitary tumors may directly provoke headaches by eroding laterally into the cavernous sinus, which contains the first and second divisions of the trigeminal nerve, by involvement of the dural lining of the sella or diaphragma sella (which are innervated by the trigeminal nerve), or via sinusitis, particularly after transsphenoidal surgery. Headache pain in these situations is typically characterized by steady, bifrontal or unilateral frontal aching (ipsilateral to tumor). In some instances, pain is localized in the midface (either because of involvement of the second division of the trigeminal or secondary to sinusitis).
In contrast to the insidious, subacute development of headaches in most patients with pituitary tumors, patients with pituitary apoplexy may experience acute, severe headaches, perhaps associated with signs and symptoms of meningeal irritation (stiff neck, photophobia), CSF pleocytosis or occulomotor paresis. Routine CT scans of the head occasionally skip the sella, hence the presence of blood or a mass within the sella may not be detected and patients can be misdiagnosed with meningitis or aneurysm. Because pituitary apoplexy represents a neurosurgical emergency, MRI should be used in patients with symptoms suggestive of this disorder. A subacute form of pituitary apoplexy has also been reported. Patients with subacute pituitary apoplexy experience severe and/or frequent headaches over weeks to months and have heme products within the sella on MRI scans.
In most instances, headaches are not attributable to direct effects of the pituitary tumor and indirect causes must be considered. Generally, indirect effects of pituitary tumors are caused by reduced secretion of pituitary hormones and are manifested by promotion of “vascular” headaches (e.g., migraine). The major exception to this rule relates to the potential for acromegalic patients to develop headaches secondary to cervical osteoarthritis. Vascular headaches may be exacerbated in association with disruption of normal menstrual cyclicity and impaired gonadal steroid secretion (e.g., from hyperprolactinemia or gonadotropin deficiency). Hyperprolactinemia, hypothyroidism and hyperthyroidism may also have direct effects, independent of gonadal hormones. Headaches are common in acromegaly, and in the majority of cases the etiology is not well understood.
Finally, drug management of pituitary tumors may inadvertently impact headaches. Octreotide results in extremely rapid headache improvement with patients with acromegaly. The rapid time course suggests it is not due to lowering of GH levels. Octreotide also has a dramatic beneficial effect on migraine and may be producing relief of headache by vascular mechanisms. Occasionally severe headaches surface in acromegalic patients after reduction or discontinuation of octreotide, as a “withdrawal” phenomenon.|
Bromocriptine or other dopamine agonists occasionally trigger severe headaches. When this occurs, it is important to recognize that bromocriptine has been reported as a cause of pituitary apoplexy, and it may be necessary to perform an MRI or CT to rule out infarction or hemorrhage within the pituitary. Once it is established that the patient is not infarcting the pituitary, it is generally safe to treat the headaches symptomatically (not with an ASA containing drug) and consider alternative therapies for the prolactinoma if the problem remains severe.
Pituitary tumor patients with vascular headaches are generally quite responsive to standard prophylactic migraine drugs (e.g., tricyclic antidepressants, verapamil and beta-blockers). It is best to begin therapy with very low-dose medication (e.g., 10 mg of amitriptyline at bedtime) and resist the impulse to escalate the dose rapidly to higher levels. Often patients have an excellent response to 10-30 mg of a tricyclic antidepressant, although it may take up to six or more weeks to reach the ultimate benefit. The choice of tricyclic antidepressant should be based upon the desired side effects (e.g., either more sedation or less sedation) The newer, serotonin-selective antidepressants are generally less effective for headaches than tricyclics, although some patients do respond nicely to these agents. In some cases it may be necessary to use combination therapy (e.g., verapamil plus a tricyclic).
Acute adrenal crisis is a life-threatening state caused by insufficient levels of cortisol, which is a hormone produced and released by the adrenal gland.
Alternative Names: Adrenal crisis; Addisonian crisis; Acute adrenal insufficiency
Causes, incidence, and risk factors:
The two adrenal glands are located on top of the kidneys. They consist of the outer portion, called the cortex, and the inner portion, called the medulla. The cortex produces three types of hormones, all of which are called corticosteroids.
Cortisol is a glucocortoid, a corticosteroid that maintains glucose (blood sugar) regulation, suppresses the immune response, and is released as part of the body’s response to stress. Cortisol production is regulated by a small gland just below the brain called the pituitary gland. Cortisol is essential for life. Acute adrenal crisis is a medical emergency caused by a lack of cortisol. Patients may experience lightheadedness or dizziness, weakness, sweating, abdominal pain, nausea and vomiting, or even loss of consciousness.
Adrenal crisis occurs if the adrenal gland is deteriorating (Addison’s disease, primary adrenal insufficiency), if there is pituitary gland injury (secondary adrenal insufficiency), or if adrenal insufficiency is not adequately treated. Risk factors for adrenal crisis include physical stress such as infection, dehydration, trauma, or surgery, adrenal gland or pituitary gland injury, and ending treatment with steroids such as prednisone or hydrocortisone too early.
Slow, sluggish movement
Low blood pressure
Confusion or coma
Darkening of the skin
Rapid heart rate
Unintentional weight loss
Rapid respiratory rate (see tachypnea)
Unusual and excessive sweating on face and/or palms
Skin rash or lesions may be present
Loss of appetite
Signs and tests:
An ACTH (cortrosyn) stimulation test shows low cortisol.
The baseline cortisol level is low.
Fasting blood sugar may be low.
Serum potassium is elevated ( usually primary adrenal insufficiency).
Serum sodium is decreased (usually primary adrenal insufficiency).
In adrenal crisis, an intravenous or intramuscular injection of hydrocortisone (an injectable corticosteroid) must be given immediately. Supportive treatment of low blood pressure with intravenous fluids is usually necessary. Hospitalization is required for adequate treatment and monitoring. If infection is the cause of the crisis, antibiotic therapy may be needed.
Death may occur due to overwhelming shock if early treatment is not provided.
Calling your health care provider:
Call your health care provider if you have Addison’s disease and are unable to retain usual medications because of vomiting.Go to the emergency room or call the local emergency number (such as 911) if symptoms of acute adrenal crisis develop.
People who have Addison’s disease should be taught to recognize signs of potential stress that may cause an acute adrenal crisis. Most people with Addison’s disease are taught to give themselves an emergency injection of hydrocortisone or increase their dose of oral prednisone in times of stress.
It is important for the individual with Addison’s disease to always carry a medical identification card that states the type of medication and the proper dose needed in case of an emergency.
Never omit medication. If unable to retain medication due to vomiting, notify the health care provider.
Health Alert: Adrenal Crisis Causes Death in Some People Who Were Treated With hGH
Recently, doctors conducting the follow-up study of individuals treated with hGH looked at causes of death among recipients and found some disturbing news. Many more people have died from a treatable condition called adrenal crisis than from CJD. THIS RISK DOES NOT AFFECT EVERY RECIPIENT. IT CAN AFFECT THOSE WHO LACK OTHER HORMONES IN ADDITION TO GROWTH HORMONE. Please read on to find out if this risk applies to you. Death from adrenal crisis can be prevented.
Adrenal crisis is a serious condition that can cause death in people who lack the pituitary hormone ACTH. ACTH is responsible for regulating the adrenal gland. Often, people are unaware that they lack this hormone and therefore do not know about their risk of adrenal crisis.
Most people who were treated with hGH did not make enough of their own growth hormone. Some of them lacked growth hormone because they had birth defects, tumors or other diseases that cause the pituitary gland to malfunction or shut down. People with those problems frequently lack other key hormones made by the pituitary gland, such as ACTH, which directs the adrenal gland to make cortisol, a hormone necessary for life. Having too little cortisol can be fatal if not properly treated.
TREATMENT WITH HGH DOES NOT CAUSE ADRENAL CRISIS, but because a number of people lacking growth hormone also lack ACTH, adrenal crisis has occurred in some people who were treated with hGH. In earlier updates we have talked about how adrenal crisis can be prevented, but people continue to die from adrenal crisis, which is brought on by lack of cortisol. These deaths can be prevented. Please talk to your doctor about whether you are at risk for adrenal crisis.
Why should people treated with hGH know about adrenal crisis? Among the people who received hGH, those who had birth defects, tumors, and other diseases affecting the brain lacked hGH and often, other hormones made by the pituitary gland. A shortage of the hormones that regulate the adrenal glands can cause many health problems. It can also lead to death from adrenal crisis. This tragedy can be prevented.
What are adrenal hormones? The pituitary gland makes many hormones, including growth hormone and ACTH, a hormone which signals the adrenal glands to make cortisol, a hormone needed for life. If the adrenal gland doesn’t make enough cortisol, replacement medications must be taken. The most common medicines used for cortisol replacement are:
What is adrenal crisis? Adrenal hormones are needed for life. The system that pumps blood through the body cannot work during times of physical stress, such as illness or injury, if there is a severe lack of cortisol (or its replacement). People who lack cortisol must take their cortisol replacement medication on a regular basis, and when they are sick or injured, they must take extra cortisol replacement to prevent adrenal crisis. When there is not enough cortisol, adrenal crisis can occur and may rapidly lead to death.
What are the symptoms of lack of adrenal hormones? If you don’t have enough cortisol or its replacement, you may have some of these problems:
feeling tired all the time
feeling sick to your stomach
When someone with adrenal gland problems has weakness, nausea, or vomiting, that person needs immediate emergency treatment to prevent adrenal crisis and possible death.
• Why are adrenal hormones so important? Cortisol (or its replacement) helps the body respond to stress from infection, injury, or surgery. The normal adrenal gland responds to serious illness by making up to 10 times more cortisol than it usually makes. It automatically makes as much as the body needs. If you are taking a cortisol replacement drug because your body cannot make these hormones, you must increase the cortisol replacement drugs during times of illness, injury, or surgery. Some people make enough cortisol for times when they feel well, but not enough to meet greater needs when they are ill or injured. Those people might not need cortisol replacement every day but may need to take cortisol replacement medication when their body is under stress. Adrenal crisis is extremely serious and can cause death if not treated promptly. Discuss this problem with your doctor to help decide whether you need more medication or other treatment to protect your health.
• How is adrenal crisis treated? People with adrenal crisis need immediate treatment. ANY DELAY CAN CAUSE DEATH.When people with adrenal crisis are vomiting or unconscious and cannot take medicine, the hormones can be given as an injection. Getting an injection of adrenal hormones can save your life if you are in adrenal crisis. If you lack the ability to make cortisol naturally, you should carry a medical ID card and wear a Medic-Alert bracelet to tell emergency workers that you lack adrenal hormones and need treatment. This precaution can save your life if you are sick or injured.
• How can I prevent adrenal crisis?
• If you are always tired, feel weak, and have lost weight, ask your doctor if you might have a shortage of adrenal hormones.
• If you take hydrocortisone, prednisone, or dexamethasone, learn how to increase the dose when you become ill.
• If you are very ill, especially if you are vomiting and cannot take pills, seek emergency medical care immediately. Make sure you have a hydrocortisone injection with you at all times, and make sure that you and those around you (in case you’re not conscious) know how and when to administer the injection.
• Carry a medical ID card and wear a bracelet telling emergency workers that you have adrenal insufficiency and need cortisol. This way, they can treat you right away if you are injured.
Remember: SOME PEOPLE WHO LACKED GROWTH HORMONE MAY ALSO LACK CORTISOL, A HORMONE NECESSARY FOR LIFE. LACK OF CORTISOL CAN CAUSE ADRENAL CRISIS, A PREVENTABLE CONDITION THAT CAN CAUSE DEATH IF TREATED IMPROPERLY .
Deaths from adrenal crisis can be prevented if patients and their families recognize the condition and are careful to treat it right away.
Adrenal crisis is a medical emergency. Know the symptoms and how to adjust your medication when you are ill. TAKING THESE PRECAUTIONS CAN SAVE YOUR LIFE.
DebMV suggested that you should have a Medic Alert bracelet from medicalert.org
Toll free number in the USA is: by phone 7 days a week, 24 hours a day: 888-633-4298
209-668-3333 from outside the U.S.
An abrupt, life-threatening state caused by insufficient cortisol, a hormone produced and released by the adrenal gland.
Causes, incidence, and risk factors:
The two adrenal glands are located on top of the kidneys. They consist of the outer portion, called the cortex, and the inner portion, called the medulla. The cortex produces three types of hormones, which are called corticosteroids. The androgens and estrogens affect sexual development and reproduction. The glucocorticoids maintain glucose regulation, suppress the immune response, and provide for the response to stress (cortisol). The mineralocorticoids regulate sodium and potassium balance. These hormones are essential for life.
Acute adrenal crisis is an emergency caused by decreased cortisol. The crisis may occur in a person with Addison’s disease, or as the first sign of adrenal insufficiency. More uncommonly, it may be caused by a pituitary gland disorder. It may also be caused by sudden withdrawal of corticosteroids, removal or injury of the adrenal glands, or destruction of the pituitary gland. Risk factors are stress, trauma, surgery, or infection in a person with Addison’s disease, or injury or trauma to the adrenal glands or the pituitary gland. The incidence is 4 out of 100,000 people.
People who have Addison’s disease should be taught to recognize signs of potential stress that may precipitate an acute adrenal crisis (cause it to occur suddenly and unexpectedly). Most people with Addison’s disease are taught to give themselves an emergency injection of hydrocortisone in times of stress. It is important for the individual with Addison’s disease to always carry a medical identification card that states the type of medication and the proper dose needed in case of an emergency. Never omit medication. If unable to retain medication due to vomiting, notify the health care provider.
slow, sluggish, lethargic movement
low blood pressure
confusion or coma
darkening of the skin
rapid heart rate
unintentional weight loss
rapid respiratory rate
unusual and excessive sweating on face and/or palms
skin rash or lesion may be present
Signs and tests:
An ACTH (cortrosyn) stimulation test shows low cortisol.
The cortisol level is low.
The fasting blood sugar may be low.
The serum potassium is elevated.
The serum sodium is decreased.
This disease may also alter the results of the following tests:
In adrenal crisis, an intravenous or intramuscular injection of hydrocortisone (an injectable corticosteroid) must be given immediately. Supportive treatment of low blood pressure is usually necessary. Hospitalization is required for adequate treatment and monitoring. Low blood pressure may be treated with intravenous fluids. If infection is the cause of the crisis, antibiotic therapy is indicated.
Death may occur due to overwhelming shock if early treatment is not provided.
As with most mornings, this one began with nausea. I’m used to it, so didn’t think much about it. I made it to the bathroom and was feeling really awful. Decided to just go to the toilet because I had that impending feeling.
Next thing I knew I was waking up, but it wasn’t like a normal awakening. I remember being in a tunnel and then thinking, “Well, this isn’t where I normally sleep.” Then I realized of course it wasn’t where I normally slept! Normally I sleep in a bed, not wedged between a wall and the toilet. (Not that I was that coherent).
I was completely disoriented as to time, place, etc. I had one big yell in me and yelled “HELP”. My four year old brought me the phone and my son got me a towel. I called 911 (thank God I had a 911 sticker on the phone because I really couldn’t remember the number). I kept telling the dispatcher I was in adrenal crisis. Of course, that meant nothing to him. I had my son get my shot but somewhere I knew that I wasn’t together enough to give myself the shot. So I puked a few more times and told my son to take my daughter upstairs so she wasn’t scared when the ambulance came.
I decided to rest on the floor of the bathroom. I had, at first, tried to go to the couch but I was much, much too weak. So my son directed the medics into the bathroom. They eventually carried me to the couch. I kept telling them about my shot, but couldn’t remember where I had my letter from Dr. Cook. They thought I was an overdose or a psych case (they told me later). They had all my pills lined up and were asking when I took this or that one last. I finally told them to look at the friggin date on the bottle and see that they were all 3/4 full. (I was agitated, too)
They put the heart monitor on me and inserted an IV and took me to the hospital. I puked one more time in the ambulance and when we arrived (though my tummy was empty). My brother and sister-in-law where there (hospital) when I arrived and my mom had arrived at my house to take care of the kids as we were leaving. Then she met us up there.
Before we arrived at the hospital, my husband had faxed a copy of Dr. Cook’s letter on how to treat me over (Brian was at work when this happened). So they came in and inserted another fluid bag. Then about ten minutes later (after my brother told the doctor, “I fully expect that my sister will have her shot withing the next ten minutes” – patient advocates are a good thing because I could’ve cared less at that point) I had my 100 mg shot of solu-medrol. I was lucky because my doctor in the ER knew about adrenal crisis.
Then I had another bag and repeated tests of my bp and heartrate. It wasn’t pretty – every time my bp was low, generally around 80/50, sometimes lower and my heart rate was 120+. They decided to admit me, but I fought and fought. Once I got a shot of Zofran (anti-nausea, best in the world) and my cortisone and some fluid, I was feeling decent. I look and feel like I’ve been through a war, but I’m alive.
As to why this happened, we’re not entirely sure at this point. I have one urine test that they’re culturing or something. I might also have shingles, but again – that’ll show up in due time (a day or two, if I have it). Or, as Dr. Cook said when I talked to him, sometimes we just don’t know. I was doing so well on my meds, back up to 27.5 and feeling good. Now I’m on 40 for the next day, and 30 for a week. Frustrating.
Adrenal crisis is awful. It’s terrifying. And what makes me want to cry as I write this (who am I kidding, I am crying) is that I couldn’t have cared less if I lived or died. I was not in my right mind, I felt so horrid. All the surgeries combined, today was the worst day I’ve ever had. And it was a huge wake-up call. I need to have a better medic-alert bracelet because they had no idea what “Stress dose steroids” were. I need to have a list of what to do in crisis on my fridge, in my purse and with every family member. Same with the letter from my endo on how to treat me. Because when I’m in crisis, I don’t know any better. I need to have things that speak for me. Thank God for family that knows, and for good doctors.
Anyway, I didn’t post this to scare anyone but Adrenal Crisis is not something to take lightly. When I felt myself hurting the night before (back pain, possibly shingles though I doubt it) I should’ve just taken an extra 5 mgs. Would’ve been a heck of a lot easier than what happened today.
A few funny parts of the day: My daughter had to dress herself and my mom was in a hurry to get her to daycare and come see me. So my daughter spent the day at daycare in tights, too small shorts and a turtleneck (none of which came close to matching). Oh, and black patent leather shoes.
Also, the medics asked what I weighed. Out of habit, I said 222 (my highest Cushing’s weight). They ALL did a double take and said no way. One guessed 140 – bless his heart. I never did get myself weighed so I don’t even know.
Oh, and if any of you called at about 8 am and spoke with a medic, call me back. lol I had a blocked call at 8am, and I vaguely remember the medic talking to someone but I wasn’t with it enough to ask who called. lol
Something I don’t say enough: I love and value you all.
The following is from the June 2002 issue of Addison News. Joan Hoffman, editor/publisher, kindly sent this issue to me and I wanted to share this with you.
This is a flow chart to show the pathway of events in a crisis. It is very important to intervene as early as possible. Use your injectable and head for the hospital! The rate at which these events take varies with individuals and circumstances. The chart is a variation of one found in a nursing encyclopedia.
Cortisol is a hormone which produced by the adrenal gland (cortex) to control blood sugar. The production of cortisol is triggered by the pituitary hormone ACTH. Cortisol is a glucocorticoid which stimulates an increase in blood glucose. Cortisol will also stimulate the release of amino acids from muscle tissue and fatty acids from adipose tissue. The amino acids are then converted in the liver to glucose (for use by the brain). The fatty acids can be used by skeletal muscles for energy (rather than glucose) thereby freeing up glucose for selective utilization by the brain. Cortisol levels are often measured to evaluate the function of the pituitary or adrenal glands. Some of the cortisol is metabolized by the liver to produce 17 hydroxycorticosteroids, which is then excreted in the urine.
The primary stress hormone. Cortisol is the major natural GLUCOCORTICOID (GC) in humans.
Synthetic cortisol, also known as hydrocortisone, is used as a drug mainly to fight allergies and inflammation.
The amount of cortisol present in the serum undergoes diurnal variation, with the highest levels present in the early morning, and lower levels in the evening, several hours after the onset of sleep. Information about the light/dark cycle is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus. Changed patterns of the serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression, psychological stress, and such physiological stressors as hypoglycemia, illness, fever, trauma, surgery, fear, pain, physical exertion or extremes of temperature. There is also significant individual variation, although a given person tends to have consistent rhythms.
Cortisol also inhibits the secretion of corticotropin releasing hormone (CRH), resulting in feedback inhibition of ACTH secretion. Some researchers believe that this normal feedback system may break down when animals are exposed to chronic stress.
In normal release, cortisol has widespread actions which help restore homeostasis after stress. It acts as a physiological antagonist to insulin by promoting gluconeogenesis, breakdown of lipids, and proteins, and mobilization of extrahepatic amino acids and ketone bodies. This leads to increased blood glucose concentrations, resulting in increased glycogen formation in the liver (Freeman, 2002). It also increases blood pressure. In addition, immune and inflammatory cells have their responses to stress attenuated by cortisol, and the hormone thus lowers the activity of the immune system. Bone formation is also lowered by cortisol.
These normal endogenous functions are the basis for the physiological consequences of chronic stress – prolonged cortisol secretion causes muscle wastage, hyperglycemia, and suppresses immune / inflammatory responses. The same consequences arise from long-term use of glucocorticoid drugs.
Also, long-term exposure to cortisol results in damage to cells in the hippocampus. This damage results in impaired learning. However, short-term exposure of cortisol helps to create memories; this is the proposed mechanism for storage of flash bulb memories.
As an oral or injectable drug, cortisol is also known as hydrocortisone. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients who need steroid treatment but cannot take oral medication, and peri-operatively in patients on long-term steroid treatment to prevent an Addisonian crisis.
It is given by topical application for its anti-inflammatory effect in allergic rashes, eczema and certain other inflammatory conditions. It may also be injected into inflamed joints resulting from diseases such as gout.
Compared to prednisolone, hydrocortisone is about 1/4th the strength. Dexamethasone is about 40 times stronger than hydrocortisone. For side effects, see corticosteroid and prednisolone.
A certain amount of cortisol is necessary for life. Without cortisol even a small amount of stress will kill you. Addison’s disease is a disease which causes low cortisol levels, and which is treated by cortisol replacement therapy.
helps maintain blood pressure and cardiovascular function;
helps slow the immune system’s inflammatory response;
helps balance the effects of insulin in breaking down sugar for energy; and
helps regulate the metabolism of proteins, carbohydrates, and fats.