eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hyperaldosteronism

Author: George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
Coauthor(s): Antony Lafferty, MB ChB, FRACP, Senior Lecturer of Pediatric Endocrinology, Monash University Department of Pediatrics, National Institutes of Health, Bethesda, MD, and Princess Margaret Hospital for Children, Perth, Western Australia
Contributor Information and Disclosures

Updated: Mar 4, 2009

Introduction

Background

Aldosterone is a steroid hormone produced exclusively in the zona glomerulosa of the adrenal cortex. It is the major circulating mineralocorticoid in humans. The principal regulators of its synthesis and secretion are the renin-angiotensin system and potassium ion concentrations. Minor regulators include adrenocorticotropic hormone (ACTH) from the pituitary, atrial natriuretic peptide from the heart, and local adrenal secretion of dopamine. Numerous aldosterone precursors, including deoxycorticosterone and 18-hydroxycorticosterone, have mineralocorticoid activity and may produce or exacerbate features typical of mineralocorticoid hypertension when present in excessive amounts in various pathologic states.

The principal site of action of aldosterone is the distal nephron, although several other sites of aldosterone-sensitive sodium regulation are noted, including the sweat glands and GI tract. Hyperaldosteronism is characterized by excessive secretion of aldosterone, which causes increases in sodium reabsorption and loss of potassium and hydrogen ions. It may be either primary (autonomous) or secondary. It represents part of a larger entity of hypermineralocorticoidism that may be caused by aldosterone, its mineralocorticoid precursors, or from defects that modulate aldosterone effects on its target tissues.

Pathophysiology

Aldosterone Secretion and Its Regulation

Aldosterone participates in the homeostasis of circulating blood volume and serum potassium concentration that, in turn, feed back to regulate aldosterone secretion by the zona glomerulosa of the adrenal cortex. Aldosterone secretion is stimulated by actual or apparent depletion in blood volume detected by stretch receptors and by an increase in serum potassium ion concentrations; it is suppressed by hypervolemia and hypokalemia. The mechanisms regulating aldosterone secretion are complex, involving the zona glomerulosa of the adrenal glands, the juxtaglomerular apparatus in the kidneys, the cardiovascular system, the autonomic nervous system, the lungs, and the liver (see Media file 1).

Steroid biosynthetic pathway.

Steroid biosynthetic pathway.

[ CLOSE WINDOW ]
Steroid biosynthetic pathway.

Steroid biosynthetic pathway.


The major factors stimulating aldosterone production and release by the zona glomerulosa are angiotensin II and the serum potassium concentration.

ACTH stimulates aldosterone secretion in an acute and transient fashion but does not appear to play a significant role in the long-term regulation of mineralocorticoid secretion. The major inhibitors of the zona glomerulosa include circulating atrial natriuretic peptide (ANP) and, locally, dopamine. Although ANP levels are clearly increased in hyperaldosteronism, neither ANP nor dopamine has been implicated as a primary cause of clinically disordered aldosterone secretion. Metoclopramide has been shown to increase aldosterone secretion, suggesting that dopamine may tonically inhibit aldosterone release. The physiologic roles of adrenomedullin and vasoactive intestinal peptide (VIP) on aldosterone secretion remain to be clarified, although both of these neuropeptides are produced in rat zona glomerulosa.

The juxtaglomerular apparatus is the principal site of regulation of angiotensin II production (see Media file 1). The synthesis of prorennin, its conversion to renin, and its systemic secretion are stimulated by blood volume contraction detected by stretch receptors, beta-adrenergic stimulation of the sympathetic nervous system, and prostaglandins I2 and E2. These processes are inhibited by volume expansion and ANP. Renin converts angiotensinogen, a proenzyme synthesized in the liver, into the decapeptide angiotensin I, which is then converted in the lungs into an octapeptide, angiotensin II, by angiotensin-converting enzyme. Angiotensin II is both a stimulator of aldosterone secretion and a potent vasopressor. Angiotensin II is metabolized to angiotensin III, a heptapeptide that is also a stimulator of aldosterone secretion.

The synthesis and secretion of prostaglandins I2 and E2 and the normal function of the stretch receptors are dependent upon intracellular ionized calcium concentration. Renal prostaglandin secretion is stimulated by catecholamines and angiotensin II. The complex regulation of aldosterone synthesis and secretion provides several points at which disturbance in the regulation of aldosterone secretion may occur.

Aldosterone biosynthesis

Aldosterone is synthesized from cholesterol in a series of 6 biosynthetic steps (see Media file 2).

Physiologic regulation of the renin-angiotensin-a...

Physiologic regulation of the renin-angiotensin-aldosterone axis.

[ CLOSE WINDOW ]
Physiologic regulation of the renin-angiotensin-a...

Physiologic regulation of the renin-angiotensin-aldosterone axis.


Only the last 2 steps are specific to aldosterone synthesis, the first 4 are common to the cortisol synthesis by the zona fasciculata. Consequently, a defect in one of the specific aldosterone synthetic enzymes does not lead to hypercortisolism and secondary ACTH-mediated adrenal hyperplasia. The enzyme aldosterone synthase is encoded by the gene CYP11B2 and has 11beta-hydroxylase, 18-hydroxylase, and 18-hydroxydehydrogenase activity. This gene is located on human chromosome arm 8q24.3-tel, close to the gene CYP11B1 that encodes 11beta-hydroxylase, the enzyme that catalyzes the final step of cortisol synthesis. Mutations in these genes can result in a number of disorders of aldosterone synthesis that are discussed below (see Differentials).

Aldosterone receptors

Aldosterone action on target tissues (eg, distal renal tubule, sweat glands, salivary glands, large intestinal epithelium) is mediated via a specific mineralocorticoid receptor. Mineralocorticoid receptors exhibit equal affinity for mineralocorticoids and cortisol, yet the aldosterone receptors in the distal tubule and elsewhere are protected from the activation by cortisol by 11beta-hydroxysteroid dehydrogenase type 2, which locally converts cortisol to inactive cortisone.

Primary Aldosteronism

Primary aldosteronism or primary hyperaldosteronism refers to a renin-independent increase in the secretion of aldosterone. Approximately 99% of cases of primary aldosteronism are due to either an aldosterone-producing adenoma (APA), which accounts for approximately 40% of cases, or idiopathic hyperaldosteronism (IHA), which accounts for approximately 60% of cases (almost all of which are bilateral). Adrenocortical carcinomas that are purely aldosterone secreting are exceedingly rare and are usually large at the time of diagnosis. Unilateral adrenocortical hyperplasia is a rare occurrence.

Primary hyperaldosteronism is principally a disease of adulthood, with its peak incidence in the fourth to sixth decades of life. APAs are usually benign encapsulated adenomas that are less than 2 cm in diameter. Most cases are solitary, although in as many as one third of cases, evidence exists of nodularity in the same adrenal, suggesting that it has arisen in a previously hyperplastic gland.

Patients with IHA have bilateral thickening and variable nodularity of their adrenal cortex. A wide spectrum of severity exists for this disorder, which may go undetected for a long period with no hypokalemia and only mild hypertension. A proposal is that IHA arises as a result of an undetected adrenal cortical–stimulating factor. Possibly, this disorder may arise as a result of an activating mutation in an adrenal cortex–specific gene, although neither hypothesis has been proven.

Inherited forms of primary hyperaldosteronism account for only 1% of cases of primary aldosteronism but are more likely to occur during childhood years. These include familial hyperaldosteronism types I and II.

Familial hyperaldosteronism type I (glucocorticoid-remediable aldosteronism)

Familial hyperaldosteronism type I (FH-I) represents about 1% of cases of primary hyperaldosteronism. It may be detected in asymptomatic individuals when screening the offspring of affected individuals, or patients may present in infancy with hypertension, weakness, and failure to thrive due to hypokalemia. It is inherited in an autosomal dominant manner and has a low frequency of new mutations. The first clinical description of glucocorticoid-remediable aldosteronism (GRA) was in 1966, with the genetic mechanism discovered in 1992. It arises as a result of unequal crossing over of CYP11B1 (11beta-hydroxylase gene) and CYP11B2 (aldosterone synthase gene) during meiosis, producing a fusion product that couples the ACTH-sensitive promoter of CYP11B1 to the CYP11B2 gene.

The result is ACTH-dependent aldosterone production and production of 17-hydroxylated analogs of 18-hydroxycortisol under ACTH regulation from ectopic enzyme expression in the zona fasciculata. Bilateral hyperplasia of the zona fasciculata occurs and high levels of novel 18-hydroxysteroids appear in the urine. Adenoma formation is rare, but patients do have a significant increase in incidence of cerebrovascular aneurysms, for which they require screening.

Familial hyperaldosteronism type II

Familial hyperaldosteronism type II (FH-II) is a familial nonglucocorticoid-suppressible inherited form of hyperaldosteronism that was recognized as a distinct entity by Gordon et al, although cases had previously been described in the 1980s. Similar to FH-I, it is also inherited in an autosomal dominant manner. The mechanism and gene locus have not yet been identified, although CYP11B2, the renin and angiotensin II receptor genes, have been excluded. Current analysis suggests that this is not a single disorder. Unlike FH-I, some kindreds with FH-II exhibit a high rate of adenoma formation.

Secondary Hyperaldosteronism

This represents a diverse group of disorders characterized by physiologic activation of the renin-angiotensin-aldosterone (R-A-A) axis as a homeostatic mechanism designed to maintain serum electrolyte concentrations or fluid volume. In the presence of normal renal function, it may lead to hypokalemia. Secondary hyperaldosteronism can be divided into 2 categories depending on whether associated hypertension is present. The former category includes renovascular hypertension, which results from renal ischemia and hypoperfusion leading to activation of the R-A-A axis. The most common causes of renal artery stenosis in children are fibromuscular hyperplasia and neurofibromatosis. Hypokalemia may occur in as many as 20% of patients.

Plasma renin activity (PRA) levels are often in the reference range, but elevated levels of PRA may be detected after provocation with a single dose of captopril 1 mg/kg. Renal ischemia is also thought to underlie the secondary hyperaldosteronism observed in malignant hypertension. Hyperreninemia and secondary aldosteronism have also been reported in patients with pheochromocytoma, apparently as a result of functional renal artery stenosis. Renin-producing tumors are very rare, and very high levels of PRA (up to 50 ng/mL/h) are noted, frequently with an increased prorennin-to-renin ratio. The tumors are generally of renal origin and include Wilms tumors and renal cell carcinomas. Hyperkalemia due to chronic renal failure also causes secondary hyperaldosteronism. Low sodium-to-potassium ratios can be measured in saliva and stool. Cyclosporin-induced hypertension in solid organ transplant patients may also involve a component of hyperaldosteronism.

Secondary hyperaldosteronism in the absence of hypertension occurs as a result of homeostatic attempts to maintain sodium or circulatory volume or to reduce potassium. Clinical situations where this may occur include the presence of diarrhea, excessive sweating, low cardiac output states, and hypoalbuminemia due to liver or renal disease or nephrotic syndrome. As outlined below, this also occurs developmentally in newborn infants.

Increased mineralocorticoid dependency in the young

The mineralocorticoid dependency of sodium reabsorption is increased during infancy and childhood, with its peak in the neonatal period before decreasing progressively with advancing age. This arises because the reabsorption of sodium and water by the proximal tubule is least efficient in early life, resulting in an increased sodium and water load at the level of the distal renal tubule.

Because sodium and water resorption from the distal tubule is mediated by the R-A-A axis, the PRA of a newborn infant is approximately 10-fold to 20-fold higher than that of an adult. This results in relative increases in aldosterone production rates (>300 mcg/m2/d in a newborn infant compared with 50 mcg/m2/d in an adult) and plasma aldosterone concentrations (80 pg/dL versus 16 pg/dL, respectively) in the neonate. This increased mineralocorticoid dependency in early life explains why young infants exhibit profound clinical symptoms of hypoaldosteronism that gradually improve with advancing age.

Frequency

International

Primary hyperaldosteronism is a rare condition in children. The youngest child reported with an aldosterone-secreting adenoma was aged 3 years. Earlier use of hypokalemia as a diagnostic requirement, as advocated by some authorities, may have led to underrecognition of the contribution of primary aldosteronism to hypertension. A study that used saline infusion as a screening test for primary aldosteronism reported a frequency of 2.2% of primary aldosteronism among 1036 unselected adults with hypertension.1 A smaller study that used the aldosterone-to-PRA ratio in plasma suggested that primary aldosteronism might account for an even greater proportion of cases of hypertension.2

Most hyperaldosteronism observed in the general population is sporadic, with most cases due to bilateral adrenal hyperplasia. APAs are likely to be diagnosed earlier than IHA because they are more likely than IHA to produce early symptomatic hypertension and hypokalemia. APAs account for 40% of cases of primary hyperaldosteronism. Possibly, the distinction between adenoma and hyperplasia is not as clear as was once thought because, in one third of cases, associated hyperplasia or nodules of the adjacent zona glomerulosa is present, implying that the adenoma may have arisen in previously hyperplastic tissue.

Inherited forms of primary hyperaldosteronism (ie, FH-1 [GRA] and FH-II and a very rare form FH-III) account for approximately 1% of cases of primary aldosteronism, although they are more likely than other causes of primary hyperaldosteronism to occur during childhood and adolescent years.

Studies of secondary hyperaldosteronism have found that approximately 15% of adults who attend hypertension clinics have elevated PRA. Reliable figures for children are not readily available.

Mortality/Morbidity

Primary hyperaldosteronism can result in a significant increase in morbidity and mortality as a result of hypertensive vascular (hypertrophy then sclerosis of intimal smooth muscle), renal (sclerosis), and cardiac (hypertrophy then dilatation) complications. Through early recognition and treatment of hypertension, these complications can be avoided in children.

Patients with GRA must undergo assessment of their cerebral circulation because this disorder is associated with a significant risk of cerebral vascular aneurysms. Provided that hypertension is well treated, morbidity and mortality are not increased significantly.

Hypokalemia is more frequently observed in patients with adenomas, although it should not be considered a diagnostic feature of primary hyperaldosteronism, as was once thought. Patients with adenomas are more likely to develop this complication, as are patients who have milder disease but receive treatment with diuretics for their hypertension, before the hyperaldosteronism is diagnosed. Hypokalemic patients may experience neuromuscular symptoms such as weakness or paralysis, constipation, and polyuria and polydipsia because of an associated renal concentrating defect. Hypokalemia also impairs insulin secretion and can promote the development of diabetes mellitus.

Although cardiac fibrosis has been reported in adults with primary aldosteronism, no such reports exist in children, possibly because of their shorter duration of disease at the time of diagnosis. Cardiac fibrosis has also been reported in rats treated with excess mineralocorticoids, especially if hyperglycemia is also present. This effect can be ameliorated with amiloride. The role of aldosterone in diabetic heart disease has been questioned, and trials of mineralocorticoid antagonists in this condition have been initiated.

Race

The literature on adults demonstrates that blacks are at significantly greater risk of hypertension-related morbidity and mortality than whites. They are also more likely to develop low-renin hypertension, although no studies indicate that the prevalence of primary hyperaldosteronism is significantly higher in blacks.

Sex

Data on adults suggest that hyperaldosteronism has a female preponderance. Equivalent information is not available for children, where primary hyperaldosteronism due to inherited syndromes is likely to represent a greater proportion of cases.

Age

Because the 2 causes that account for about 99% of cases of primary hyperaldosteronism have a peak age of onset in adulthood, the less common causes account for a larger percentage of children with hyperaldosteronism. For this reason, children with apparent hyperaldosteronism should be evaluated for evidence of congenital defects of the R-A-A axis and inherited forms of hypermineralocorticoidism.

Clinical

History

Primary hyperaldosteronism may be asymptomatic, particularly in its early stages. When present, symptoms are related to hypertension (if severe), hypokalemia, or both.

  • The spectrum of hypertension-related symptoms includes the following:
    • Headaches
    • Facial flushing
    • If severe, weakness, visual impairment, impaired consciousness, and seizures (hypertensive encephalopathy)
  • Hypokalemia can be precipitated by non–potassium-sparing diuretics or sodium loading. Symptoms of hypokalemia include the following:
    • Constipation
    • Polyuria and polydipsia (because of impaired renal concentrating ability)
    • Weakness
    • If low enough, paralysis and disturbances of cardiac rhythm3
  • Hyperglycemia or frank diabetes mellitus is possible because insulin secretion is a potassium-dependent process that may be impaired by hypokalemia.
  • If secondary hyperaldosteronism is suspected as the cause of hypertension, history should include questions about flushing, diaphoresis, anxiety attacks, and headaches (pheochromocytoma) and about hematuria and abdominal fullness (Wilms tumor or other renal tumor), in addition to the above symptoms.
  • For patients in whom secondary hyperaldosteronism is suggested, questions should be specifically directed at potential causes (eg, the presence and duration of swelling, the child's exercise tolerance).
  • Information should be sought about a family history of essential hypertension and familial syndromes that include the following:
    • Neurofibromatosis (associated with renal artery stenosis and pheochromocytoma)
    • Multiple endocrine neoplasia (MEN) type 2
      • MEN 2A - Parathyroid adenoma, medullary thyroid carcinoma (MTC), pheochromocytoma
      • MEN 2B - Mucosal neuromas of eyelids, lips, and tongue with long thin face, pheochromocytoma, and MTC
    • von Hippel-Lindau syndrome - Cerebellar hemangioblastoma; renal and pancreatic cysts and carcinoma; hemangiomas of the retina, liver, and adrenal glands; pheochromocytomas

Physical

Any child or adolescent with significant hypertension deserves thorough investigation into the cause.

  • Hypermineralocorticoidism should be considered in any patient with associated hypokalemia, although it should not be excluded in its absence.
  • Patients with significant hypertension should have their blood pressure repeated several times, preferably with an automated device after a supine rest.
  • Examination of the hypertensive patient should include the following:
    • General - Dysmorphic features (eg, MEN 2B), evidence of neurofibromatosis type 1 (ie, café-au-lait lesions, axillary freckling, short stature, and evidence of disease in parents), features of Cushing syndrome (ie, obesity, short stature, striae, and hirsutism)
    • Neck - Thyroid mass (MTC associated with MEN 2)
    • Cardiovascular - Assessment of left ventricular muscle mass as well as exclusion of murmurs and pulse differential (eg, coarctation of the aorta), abdominal bruits (renal artery stenosis), and peripheral edema (secondary hyperaldosteronism)
    • Abdomen - Masses (Wilms tumor), hepatomegaly (cardiac failure or liver disease), splenomegaly, ascites
    • Neurologic - Examination of the eyes and visual acuity (severe hypertension may interfere with vision); examination of the eye grounds (important to look for retinal angiomas [von Hippel-Lindau syndrome]); hypertensive retinopathy, which is of prognostic significance, including arterial narrowing, hemorrhages, cotton-wool spots, papilledema; Lisch nodules of the iris (neurofibromatosis type 1)
    • Strength assessment - Evaluation of weakness, focal neurologic signs or impaired conscious state in a patient with severe hypertension, which requires urgent treatment and CNS imaging to exclude infarct or hemorrhage
    • Skin - In patients who have secondary hyperaldosteronism, evidence of NF-1

Causes

The following is a summary of etiologies of hyperaldosteronism and conditions that mimic hyperaldosteronism:

  • Primary hyperaldosteronism
    • Aldosterone-producing adenoma (APA) - High aldosterone, low plasma renin activity (PRA)
    • Idiopathic hyperaldosteronism (IHA) - Responds to posture (bilateral adrenal hyperplasia)
    • Primary adrenal hyperplasia - Responds to posture (unilateral disease)
    • Glucocorticoid remediable aldosteronism (GRA) - Sustained suppression of aldosterone (<4 ng/dL) with dexamethasone
    • Familial hyperaldosteronism type II (FH-II) - Familial (probably autosomal dominant)
  • Secondary hyperaldosteronism
    • Edema disorders (eg, cardiac failure, nephrotic syndrome) - High aldosterone, nonsuppressed plasma renin activity (>2 ng/mL)
    • Renovascular hypertension
    • Renin-producing tumors
    • Pregnancy4
  • Conditions that mimic aldosterone excess
    • Congenital adrenal hyperplasia (11beta-hydroxylase deficiency, 17alpha-hydroxlyase deficiency) - Low aldosterone, low PRA, elevated steroid intermediates
    • Primary glucocorticoid resistance - High glucocorticoid secretion unsuppressed by dexamethasone
    • Deoxycorticosterone-secreting tumors - Elevated deoxycorticosterone levels
    • Syndrome of apparent mineralocorticoid excess
    • Liddle syndrome
    • Licorice ingestion
    • Carbenoxolone

The following is a discussion of causes of hypokalemia:

  • Hypokalemia may be precipitated by a diet that is rich in sodium or the concomitant administration of drugs that produce kaliuresis (including diuretics and carbenoxolone).
  • Taking carbenoxolone or eating large quantities of licorice may result in hypokalemia because of blockade of the target tissue enzyme that protects the aldosterone receptor from the relatively higher levels of circulating cortisol (apparent mineralocorticoid excess).

More on Hyperaldosteronism

Overview: Hyperaldosteronism
Differential Diagnoses & Workup: Hyperaldosteronism
Treatment & Medication: Hyperaldosteronism
Follow-up: Hyperaldosteronism
Multimedia: Hyperaldosteronism
References
[ CLOSE WINDOW ]

References

  1. Holland OB, Brown H, Kuhnert L, Fairchild C, Risk M, Gomez-Sanchez CE. Further evaluation of saline infusion for the diagnosis of primary aldosteronism. Hypertension. Sep-Oct 1984;6(5):717-23. [Medline].

  2. Ignatowska-Switalska H, Chodakowska J, Januszewicz W, Feltynowski T, Adamczyk M, Lewandowski J. Evaluation of plasma aldosterone to plasma renin activity ratio in patients with primary aldosteronism. J Hum Hypertens. Jun 1997;11(6):373-8. [Medline].

  3. Kasifoglu T, Akalin A, Cansu DU, Korkmaz C. Hypokalemic paralysis due to primary hyperaldosteronism simulating gitelman's syndrome. Saudi J Kidney Dis Transpl. Mar-Apr 2009;20(2):285-7. [Medline].

  4. Escher G. Hyperaldosteronism in pregnancy. Ther Adv Cardiovasc Dis. Jan 26 2009;[Medline].

  5. Gordon RD. Primary aldosteronism. J Endocrinol Invest. Jul-Aug 1995;18(7):495-511. [Medline].

  6. Gordon RD, Stowasser M, Klemm SA, Tunny TJ. Primary aldosteronism--some genetic, morphological, and biochemical aspects of subtypes. Steroids. Jan 1995;60(1):35-41. [Medline].

  7. Spence JD. Diagnosis of primary aldosteronism: for medical management, not just surgery. J Hypertens. Jan 2009;27(1):204-5; author reply 205. [Medline].

  8. Abdelhamid S, Muller-Lobeck H, Pahl S, et al. Prevalence of adrenal and extra-adrenal Conn syndrome in hypertensive patients. Arch Intern Med. Jun 10 1996;156(11):1190-5. [Medline].

  9. Batlle DC, Hizon M, Cohen E, Gutterman C, Gupta R. The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. N Engl J Med. Mar 10 1988;318(10):594-9. [Medline].

  10. Beckers A, Abs R, Willems PJ, et al. Aldosterone-secreting adrenal adenoma as part of multiple endocrine neoplasia type 1 (MEN1): loss of heterozygosity for polymorphic chromosome 11 deoxyribonucleic acid markers, including the MEN1 locus. J Clin Endocrinol Metab. Aug 1992;75(2):564-70. [Medline].

  11. Biglieri EG. Primary aldosteronism. Curr Ther Endocrinol Metab. 1997;6:170-2. [Medline].

  12. Biglieri EG, Slaton PE Jr, Silen WS, Galante M, Forsham PH. Postoperative studies of adrenal function in primary aldosteronism. J Clin Endocrinol Metab. May 1966;26(5):553-8. [Medline].

  13. Blumenfeld JD, Sealey JE, Schlussel Y, et al. Diagnosis and treatment of primary hyperaldosteronism. Ann Intern Med. Dec 1 1994;121(11):877-85. [Medline]. [Full Text].

  14. Boscaro M, Betterle C, Volpato M, et al. Hormonal responses during various phases of autoimmune adrenal failure: no evidence for 21-hydroxylase enzyme activity inhibition in vivo. J Clin Endocrinol Metab. Aug 1996;81(8):2801-4. [Medline].

  15. Bravo EL, Tarazi RC, Dustan HP, et al. The changing clinical spectrum of primary aldosteronism. Am J Med. Apr 1983;74(4):641-51. [Medline].

  16. Brown JJ, Davies DL, Lever AF. Variations in plasma renin concentration in several physiological and pathological states. Can Med Assoc J. 1964;90:201.

  17. Campbell SE, Diaz-Arias AA, Weber KT. Fibrosis of the human heart and systemic organs in adrenal adenoma. Blood Press. Oct 1992;1(3):149-56. [Medline].

  18. Campbell SE, Janicki JS, Matsubara BB, Weber KT. Myocardial fibrosis in the rat with mineralocorticoid excess. Prevention of scarring by amiloride. Am J Hypertens. Jun 1993;6(6 Pt 1):487-95. [Medline].

  19. Cantin M, Genest J. The heart and the atrial natriuretic factor. Endocr Rev. Spring 1985;6(2):107-27. [Medline].

  20. Carey RM. Acute dopaminergic inhibition of aldosterone secretion is independent of angiotensin II and adrenocorticotropin. J Clin Endocrinol Metab. Feb 1982;54(2):463-9. [Medline].

  21. Chrousos GP, Detera-Wadleigh SD, Karl M. Syndromes of glucocorticoid resistance. Ann Intern Med. Dec 1 1993;119(11):1113-24. [Medline]. [Full Text].

  22. Conn JW. Primary aldosteronism, a new clinical syndrome. J Lab Clin Med. 1955;45:3-17.

  23. Conn JW, Knopf RF, Nesbit RM. Clinical characteristics of primary aldosteronism from an analysis of 145 cases. Am J Surg. 1964;107:159-72.

  24. Corry BC, Tuck ML. Secondary aldosteronism. Endocrinol Metab Clin North Am. 1955;24:511-29.

  25. Corvol P, Pinet F, Plouin PF, Bruneval P, Menard J. Renin-secreting tumors. Endocrinol Metab Clin North Am. Jun 1994;23(2):255-70. [Medline].

  26. Curnow KM, Tusie-Luna MT, Pascoe L, et al. The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex. Mol Endocrinol. Oct 1991;5(10):1513-22. [Medline].

  27. Davis JO, Freeman RH. Mechanisms regulating renin release. Physiol Rev. Jan 1976;56(1):1-56. [Medline].

  28. Doppman JL, Gill JR Jr. Hyperaldosteronism: sampling the adrenal veins. Radiology. Feb 1996;198(2):309-12. [Medline].

  29. Fernandez-Cruz A Jr, Noth RH, Lassman MN, Hollis JB, Mulrow PJ. Low plasma renin activity in normotensive patients with diabetes mellitus: relationship to neuropathy. Hypertension. Jan-Feb 1981;3(1):87-92. [Medline].

  30. Findling JW, Raff H, Hansson JH, Lifton RP. Liddle's syndrome: prospective genetic screening and suppressed aldosterone secretion in an extended kindred. J Clin Endocrinol Metab. Apr 1997;82(4):1071-4. [Medline]. [Full Text].

  31. Fiselier T, Derkx F, Monnens L, Van Munster P, Peer P, Schalekamp M. The basal levels of active and inactive plasma renin concentration in infancy and childhood. Clin Sci (Lond). Oct 1984;67(4):383-7. [Medline].

  32. Forest M. Adrenal steroid excess. In: Brook CGD, ed. Clinical Paediatric Endocrinology. 3rd ed. Cambridge, Mass: Blackwell Science; 1995:520-524.

  33. Funder JW. Apparent mineralocorticoid excess. Endocrinol Metab Clin North Am. Sep 1995;24(3):613-21. [Medline].

  34. Gaillard RC, Riondel AM, Favrod-Coune CA, Vallotton MB, Muller AF. Aldosterone escape to chronic ACTH administration in man. Acta Endocrinol (Copenh). May 1983;103(1):116-24. [Medline].

  35. Gates LJ, MacConnachie AA, Lifton RP, Haites NE, Benjamin N. Variation of phenotype in patients with glucocorticoid remediable aldosteronism. J Med Genet. Jan 1996;33(1):25-28. [Medline].

  36. Gaunt R. Action of adrenal steroids on electrolyte and water metabolism. In: Christy NP, ed. The Human Adrenal Cortex. New York, NY: Harper and Row; 1971:373.

  37. Geley S, Kapelari K, Johrer K, et al. CYP11B1 mutations causing congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. J Clin Endocrinol Metab. Aug 1996;81(8):2896-901. [Medline].

  38. Geller DH, Auchus RJ, Mendonca BB, Miller WL. The genetic and functional basis of isolated 17,20-lyase deficiency. Nat Genet. Oct 1997;17(2):201-5. [Medline].

  39. Geller DS, Zhang J, Wisgerhof MV, Shackleton C, Kashgarian M, Lifton RP. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. Aug 2008;93(8):3117-23. [Medline].

  40. Gordon RD, Bachmann AW, Klemm SA, et al. An association of primary aldosteronism and adrenaline-secreting phaeochromocytoma. Clin Exp Pharmacol Physiol. Mar 1994;21(3):219-22. [Medline].

  41. Gordon RD, Kuchel O, Liddle GW, Island DP. Role of the sympathetic nervous system in regulating renin and aldosterone production in man. J Clin Invest. Apr 1967;46(4):599-605. [Medline]. [Full Text].

  42. Gordon RD, Stowasser M, Tunny TJ, Klemm SA, Rutherford JC. High incidence of primary aldosteronism in 199 patients referred with hypertension. Clin Exp Pharmacol Physiol. Apr 1994;21(4):315-8. [Medline].

  43. Greco RG, Carroll JE, Morris DJ, Grekin RJ, Melby JC. Familial hyperaldosteronism, not suppressed by dexamethasone. J Clin Endocrinol Metab. Nov 1982;55(5):1013-6. [Medline].

  44. Haab F, Duclos JM, Guyenne T, Plouin PF, Corvol P. Renin secreting tumors: diagnosis, conservative surgical approach and long-term results. J Urol. Jun 1995;153(6):1781-4. [Medline].

  45. Hambling C, Jung RT, Gunn A, Browning MC, Bartlett WA. Re-evaluation of the captopril test for the diagnosis of primary hyperaldosteronism. Clin Endocrinol (Oxf). May 1992;36(5):499-503. [Medline].

  46. Hansson JH, Nelson-Williams C, Suzuki H, et al. Hypertension caused by a truncated epithelial sodium channel gamma subunit: genetic heterogeneity of Liddle syndrome. Nat Genet. Sep 1995;11(1):76-82. [Medline].

  47. Higuchi K, Nawata H, Kato K, Ibayashi H, Matsuo H. Alpha-human atrial natriuretic polypeptide inhibits steroidogenesis in cultured human adrenal cells. J Clin Endocrinol Metab. May 1986;62(5):941-4. [Medline].

  48. Hiramatsu K, Yamada T, Yukimura Y, et al. A screening test to identify aldosterone-producing adenoma by measuring plasma renin activity. Results in hypertensive patients. Arch Intern Med. Nov 1981;141(12):1589-93. [Medline].

  49. Holcombe JH, Keenan BS, Nichols BL, Kirkland RT, Clayton GW. Neonatal salt loss in the hypertensive form of congenital adrenal hyperplasia. Pediatrics. Apr 1980;65(4):777-81. [Medline].

  50. Inoue H, Nakajo M, Miyazono N, Nishida H, Ueno K, Hokotate H. Transcatheter arterial ablation of aldosteronomas with high-concentration ethanol: preliminary and long-term results. AJR Am J Roentgenol. May 1997;168(5):1241-5. [Medline].

  51. Iwaoka T, Umeda T, Naomi S, et al. The usefulness of the captopril test as a simultaneous screening for primary aldosteronism and renovascular hypertension. Am J Hypertens. Nov 1993;6(11 Pt 1):899-906. [Medline].

  52. Jacobs DR, van der Poll J, Gabrilove JL. 17-a-hydroxyprogesterone-a salt-losing steroid: relation to congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1961;21:909.

  53. Jamieson A, Slutsker L, Inglis GC, Fraser R, White PC, Connell JM. Glucocorticoid-suppressible hyperaldosteronism: effects of crossover site and parental origin of chimaeric gene on phenotypic expression. Clin Sci (Lond). May 1995;88(5):563-70. [Medline].

  54. Janetschek G, Lhotta K, Gasser R, Finkenstedt G, Jaschke W, Bartsch G. Adrenal-sparing laparoscopic surgery for aldosterone-producing adenoma. J Endourol. Apr 1997;11(2):145-8. [Medline].

  55. Jonsson JR, Klemm SA, Tunny TJ, Stowasser M, Gordon RD. A new genetic test for familial hyperaldosteronism type I aids in the detection of curable hypertension. Biochem Biophys Res Commun. Feb 15 1995;207(2):565-71. [Medline].

  56. Kaplan NM. Endocrine hypertension. In: Wilson JD, Foster DW, eds. Williams Textbook of Endocrinology. 8th ed. Philadelphia, Pa: WB Saunders and Co; 1992:707-731.

  57. Kem DC, Weinberger MH, Mayes DM, Nugent CA. Saline suppression of plasma aldosterone in hypertension. Arch Intern Med. Sep 1971;128(3):380-6. [Medline].

  58. Lack E, Travis W, Oertel J. Adrenal cortical nodules, hyperplasia and hyperfunction. In: Pathology of the Adrenal Glands. New York, NY: Churchill-Livingstone; 1990.

  59. Lafferty AR, Torpy DJ, Stowasser M, et al. A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22). J Med Genet. Nov 2000;37(11):831-5. [Medline]. [Full Text].

  60. Lee PD, Patterson BD, Hintz RL, Rosenfeld RG. Biochemical diagnosis and management of corticosterone methyl oxidase type II deficiency. J Clin Endocrinol Metab. Jan 1986;62(1):225-9. [Medline].

  61. Lenz T, Thiede HM, Nussberger J, Atlas SA, Distler A, Schulte KL. Hyperreninemia and secondary hyperaldosteronism in a patient with pheochromocytoma and von Hippel-Lindau disease. Nephron. 1992;62(3):345-50. [Medline].

  62. Lewin A, Blaufox MD, Castle H, Entwisle G, Langford H. Apparent prevalence of curable hypertension in the Hypertension Detection and Follow-up Program. Arch Intern Med. Mar 1985;145(3):424-7. [Medline].

  63. Lifton RP, Dluhy RG, Powers M, et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature. Jan 16 1992;355(6357):262-5. [Medline].

  64. Litchfield WR, Anderson BF, Weiss RJ, Lifton RP, Dluhy RG. Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension. Jan 1998;31(1 Pt 2):445-50. [Medline].

  65. Litchfield WR, Coolidge C, Silva P, et al. Impaired potassium-stimulated aldosterone production: a possible explanation for normokalemic glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. May 1997;82(5):1507-10. [Medline]. [Full Text].

  66. Litchfield WR, Dluhy RG. Primary aldosteronism. Endocrinol Metab Clin North Am. Sep 1995;24(3):593-612. [Medline].

  67. Litchfield WR, New MI, Coolidge C, Lifton RP, Dluhy RG. Evaluation of the dexamethasone suppression test for the diagnosis of glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. Nov 1997;82(11):3570-3. [Medline]. [Full Text].

  68. London N, Swales J, Hollinrake K, Bell P, Heagerty A. Familial Conn's syndrome. Postgrad Med J. Dec 1992;68(806):976-7. [Medline].

  69. Luo X, Ikeda Y, Parker KL. A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell. May 20 1994;77(4):481-90. [Medline].

  70. McKenna TJ, Island DP, Nicholson WE, Liddle GW. Dopamine inhibits angiotensin-stimulated aldosterone biosynthesis in bovine adrenal cells. J Clin Invest. Jul 1979;64(1):287-91. [Medline].

  71. McKenna TJ, Island DP, Nicholson WE, Liddle GW. Dopamine inhibits angiotensin-stimulated aldosterone biosynthesis in bovine adrenal cells. J Clin Invest. Jul 1979;64(1):287-91. [Medline].

  72. McKenna TJ, Island DP, Nicholson WE, Liddle GW. The effects of potassium on early and late steps in aldosterone biosynthesis in cells of the zona glomerulosa. Endocrinology. Oct 1978;103(4):1411-6. [Medline].

  73. McKenna TJ, Sequeira SJ, Heffernan A, Chambers J, Cunningham S. Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism. J Clin Endocrinol Metab. Nov 1991;73(5):952-7. [Medline].

  74. Nguyen HLT, Luong KVQ. Coexistence of primary aldosteronism and pheochromocytoma in a Vietnamese patient. Endocrinologist. 1996;6490-3.

  75. O'Kelly R, Magee F, McKenna TJ. Routine heparin therapy inhibits adrenal aldosterone production. J Clin Endocrinol Metab. Jan 1983;56(1):108-12. [Medline].

  76. Oates JA, Whorton AR, Gerkens JF, Branch RA, Hollifield JW, Frolich JC. The participation of prostaglandins in the control of renin release. Fed Proc. Jan 1979;38(1):72-4. [Medline].

  77. Orth DN, Kovacs WJ. The adrenal cortex. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR, eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: WB Saunders and Co; 1998:595-598.

  78. Pascoe L, Jeunemaitre X, Lebrethon MC, et al. Glucocorticoid-suppressible hyperaldosteronism and adrenal tumors occurring in a single French pedigree. J Clin Invest. Nov 1995;96(5):2236-46. [Medline]. [Full Text].

  79. Ramayya MS, Zhou J, Kino T, Segars JH, Bondy CA, Chrousos GP. Steroidogenic factor 1 messenger ribonucleic acid expression in steroidogenic and nonsteroidogenic human tissues: Northern blot and in situ hybridization studies. J Clin Endocrinol Metab. Jun 1997;82(6):1799-806. [Medline]. [Full Text].

  80. Rasmussen H, Waisman D. The messenger function of calcium in endocrine systems. In: Litwack G, ed. Biochemical Action of Hormones. Vol 8. New York, NY: Academic Press; 1970:1.

  81. Rodriguez-Soriano J, Vallo A, Castillo G, Oliveros R. Renal handling of water and sodium in infancy and childhood: a study using clearance methods during hypotonic saline diuresis. Kidney Int. Dec 1981;20(6):700-4. [Medline].

  82. Russell DW, White PC. Four is not more than two. Am J Hum Genet. Nov 1995;57(5):1002-5. [Medline].

  83. Rutherford JC, Stowasser M, Tunny TJ, Klemm SA, Gordon RD. Laparoscopic adrenalectomy. World J Surg. Sep 1996;20(7):758-60; discussion 761. [Medline].

  84. Rösler A, Levine LS, Schneider B, Novogroder M, New MI. The interrelationship of sodium balance, plasma renin activity and ACTH in congenital adrenal hyperplasia. J Clin Endocrinol Metab. Sep 1977;45(3):500-12. [Medline].

  85. Sato A, Funder JW. High glucose stimulates aldosterone-induced hypertrophy via type I mineralocorticoid receptors in neonatal rat cardiomyocytes. Endocrinology. Oct 1996;137(10):4145-53. [Medline]. [Full Text].

  86. Sheppard K, Funder JW. Type I receptors in parotid, colon, and pituitary are aldosterone selective in vivo. Am J Physiol. Oct 1987;253(4 Pt 1):E467-71. [Medline].

  87. Shimkets RA, Warnock DG, Bositis CM, et al. Liddle's syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. Nov 4 1994;79(3):407-14. [Medline].

  88. Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CH, Edwards CR. Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet. Oct 10 1987;2(8563):821-4. [Medline].

  89. Stockigt JR, Topliss DJ, Hewett MJ. High-renin hypertension in necrotizing vasculitis. N Engl J Med. May 24 1979;300(21):1218. [Medline].

  90. Stowasser M, Gordon RD, Klemm SA, Tunny TJ. Renin-aldosterone response to dexamethasone in glucocorticoid-suppressible hyperaldosteronism is altered by coexistent renal artery stenosis. J Clin Endocrinol Metab. Sep 1993;77(3):800-4. [Medline].

  91. Stowasser M, Gordon RD, Tunny TJ, Klemm SA, Finn WL, Krek AL. Familial hyperaldosteronism type II: five families with a new variety of primary aldosteronism. Clin Exp Pharmacol Physiol. May 1992;19(5):319-22. [Medline].

  92. Streeten DH, Tomycz N, Anderson GH. Reliability of screening methods for the diagnosis of primary aldosteronism. Am J Med. Sep 1979;67(3):403-13. [Medline].

  93. Sun Y, Ratajska A, Zhou G, Weber KT. Angiotensin-converting enzyme and myocardial fibrosis in the rat receiving angiotensin II or aldosterone. J Lab Clin Med. Oct 1993;122(4):395-403. [Medline].

  94. Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Can Med Assoc J. Nov 26 1966;95(22):1109-19. [Medline].

  95. Suzuki Y, Nagashima T, Nomura Y, Onigata K, Nagashima K, Morikawa A. A new compound heterozygous mutation (W17X, 436 + 5G --> T) in the cytochrome P450c17 gene causes 17 alpha-hydroxylase/17,20-lyase deficiency. J Clin Endocrinol Metab. Jan 1998;83(1):199-202. [Medline]. [Full Text].

  96. Taylor W, Carroll D, Bethwaite P. Adrenal carcinoma presenting as Conn's syndrome. Aust N Z J Med. Apr 1997;27(2):201-2. [Medline].

  97. Taymans SE, Pack S, Pak E, Torpy DJ, Zhuang Z, Stratakis CA. Human CYP11B2 (aldosterone synthase) maps to chromosome 8q24.3. J Clin Endocrinol Metab. Mar 1998;83(3):1033-6. [Medline]. [Full Text].

  98. Torpy DJ, Gordon RD, Lin JP, et al. Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. J Clin Endocrinol Metab. Sep 1998;83(9):3214-8. [Medline]. [Full Text].

  99. Torpy DJ, Stratakis CA, Chrousos GP. Hyper- and hypoaldosteronism. Vitam Horm. 1999;57:177-216. [Medline].

  100. Torpy DJ, Stratakis CA, Gordon RD. Linkage analysis of familial hyperaldosteronism type II--absence of linkage to the gene encoding the angiotensin II receptor type 1. J Clin Endocrinol Metab. Mar 1998;83(3):1046. [Medline].

  101. Ulick S, Blumenfeld JD, Atlas SA, Wang JZ, Vaughan ED Jr. The unique steroidogenesis of the aldosteronoma in the differential diagnosis of primary aldosteronism. J Clin Endocrinol Metab. Apr 1993;76(4):873-8. [Medline].

  102. Weisnagel SJ, Gagner M, Breton G. Laparoscopic adrenalectomy. Endocrinologist. 1996;6:169-78.

  103. White PC, Curnow KM, Pascoe L. Disorders of steroid 11 beta-hydroxylase isozymes. Endocr Rev. Aug 1994;15(4):421-38. [Medline]. [Full Text].

  104. White PC, New MI, Dupont B. Congenital adrenal hyperplasia (2). N Engl J Med. Jun 18 1987;316(25):1580-6. [Medline].

  105. White PC, New MI, Dupont B. Congenital adrenal hyperplasia. (1). N Engl J Med. Jun 11 1987;316(24):1519-24. [Medline].

  106. Williams FA Jr, Schambelan M, Biglieri EG, Carey RM. Acquired primary hypoaldosteronism due to an isolated zona glomerulosa defect. N Engl J Med. Dec 29 1983;309(26):1623-7. [Medline].

  107. Young WF Jr. Primary hyperaldosteronism: update on diagnosis and treatment. Endocrinologist. 1997;7:213-21.

  108. Young WF Jr, Hogan MJ. Renin-independent hypermineralocorticoidism. Trends Endocrinol Metab. 1994;5:97-106.

  109. Young WF Jr, Klee GG. Primary aldosteronism. Diagnostic evaluation. Endocrinol Metab Clin North Am. Jun 1988;17(2):367-95. [Medline].

  110. Zachmann M, Tassinari D, Prader A. Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients. J Clin Endocrinol Metab. Feb 1983;56(2):222-9. [Medline].

  111. Zadik Z, Kahana L, Kaufman H, Benderli A, Hochberg Z. Salt loss in hypertensive form of congenital adrenal hyperplasia (11-beta-hydroxylase deficiency). J Clin Endocrinol Metab. Feb 1984;58(2):384-7. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

hyperaldosteronism, aldosteronism, primary aldosteronism, primary hyperaldosteronism, familial hyperaldosteronism type I, FH-I, glucocorticoid remediable aldosteronism, GRA, familial hyperaldosteronism type II, FH-II, secondary hyperaldosteronism, idiopathic hyperaldosteronism, IHA, hyperkalemia, hypertension, hypoalbuminemia, cardiac output states, nephrotic syndrome, bilateral adrenal hyperplasia, adenoma, diabetes mellitus, cardiac fibrosis, headaches, facial flushing, constipation, polyuria, polydipsia, Wilms tumor, anxiety attacks, neurofibromatosis, multiple endocrine neoplasia type 2, MEN, MEN 2A, MEN 2B, von Hippel-Lindau syndrome, Wilms tumor, hepatomegaly, splenomegaly, ascites

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

Antony Lafferty, MB ChB, FRACP, Senior Lecturer of Pediatric Endocrinology, Monash University Department of Pediatrics, National Institutes of Health, Bethesda, MD, and Princess Margaret Hospital for Children, Perth, Western Australia
Antony Lafferty, MB ChB, FRACP is a member of the following medical societies: Endocrine Society
Disclosure: Nothing to disclose.

Medical Editor

Thomas A Wilson, MD, Professor of Clinical Pediatrics, Department of Pediatrics; Director of Pediatric Endocrinology, Division of Pediatric Endocrinology, Department of Pediatrics, State University of New York at Stony Brook
Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Lynne Lipton Levitsky, MD, Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor, Department of Pediatrics, Harvard University Medical School
Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds PI, also occasional consultant

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfizer, Inc. Honoraria Consulting

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.