WordNet

capable of being remedied or redressed ; "remediable problems"; "a remediable setback"; "not a crime but only a remediable blunder"
a steroid hormone that is produced by the adrenal cortex of animals; affects functioning of gonads and has anti-inflammatory activity
a condition caused by overproduction of aldosterone (同)hyperaldosteronism

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/09 20:45:43」(JST)

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Glucocorticoid remediable aldosteronism (GRA), also describable as aldosterone synthase hyperactivity, is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient.

It is a cause of primary hyperaldosteronism.^[1]

Normal Physiology

Steroidogenesis, showing aldosterone synthase at right.

Aldosterone synthase is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone. It is localized to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and other steroids. Aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex. Aldosterone synthase normally is not ACTH sensitive, and only activated by angiotensin II.

Aldosterone causes the tubules of the kidneys to retain sodium and water. This increases the volume of fluid in the body, and drives up blood pressure.

Steroid hormones are synthesized from cholesterol within the adrenal cortex. Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone).

Aldosterone synthesis is stimulated by several factors:

by increase in the plasma concentration of angiotensin III.

by increased plasma angiotensin II, ACTH, or potassium levels.

The ACTH stimulation test is sometimes used to stimulate the production of aldosterone along with cortisol to determine if primary or secondary adrenal insufficiency is present.

by plasma acidosis.

by the stretch receptors located in the atria of the heart.

by adrenoglomerulotropin, a lipid factor, obtained from pineal extracts. It selectively stimulates secretion of aldosterone.

The secretion of aldosterone has a diurnal rhythm.

Control of aldosterone release from the adrenal cortex:

The role of the renin-angiotensin system:

Angiotensin is involved in regulating aldosterone and is the core regulator. Angiotensin II acts synergistically with potassium.

The role of sympathetic nerves:

Aldosterone production is also affected to one extent or another by nervous control which integrates the inverse of carotid artery pressure, pain, posture, and probably emotion (anxiety, fear, and hostility)(including surgical stress).

The role of baroreceptors:

Pressure in the carotid artery decreases aldosterone

The role of the juxtaglomerular apparatus
The plasma concentration of potassium:

The amount of aldosterone secreted is a direct function of the serum potassium as probably determined by sensors in the carotid artery.

The plasma concentration of sodium:

Aldosterone is a function of the inverse of the sodium intake as sensed via osmotic pressure.

Miscellaneous regulation:

ACTH, a pituitary peptide, also has some stimulating effect on aldosterone probably by stimulating deoxycorticosterone formation which is a precursor of aldosterone.

Aldosterone is increased by blood loss, pregnancy, and possibly by other circumstances such as physical exertion, endotoxin shock, and burns.

Aldosterone feedback:

Feedback by aldosterone concentration itself is of a non-morphological character (that is, other than changes in cell number or structure) and is relatively poor, so that electrolyte feedback predominates in the short term.

Pathophysiology

The genes encoding aldosterone synthase and 11-hydroxylase are 95% identical and are close together on chromosome 8. In individuals with GRA, there is unequal crossing over so that the 5' regulatory region of the 11-hydroxylase gene is fused to the coding region of the aldosterone synthase.

The product of this hybrid gene is aldosterone synthase that is ACTH-sensitive^[2] in the zona fasciculata of the adrenal gland.^[3]

Although in normal subjects, ACTH accelerates the first step of aldosterone synthesis, ACTH normally has no effect on the activity of aldosterone synthase. However, in subjects with glucocorticoid-remediable aldosteronism, ACTH increases the activity of existing aldosterone synthase, resulting in an abnormally high rate of aldosterone synthesis and hyperaldosteronism.

Symptoms

Patients with GRA may be asymptomatic, but the following symptoms can be present:

Fatigue
Headache
High blood pressure
Hypokalemia
Intermittent or temporary paralysis
Muscle spasms
Muscle weakness
Numbness
Polyuria
Polydipsia
Tingling
Hypernatraemia
Metabolic alkalosis

Treatment

In GRA, the hypersecretion of aldosterone and the accompanying hypertension are remedied when ACTH secretion is suppressed by administering glucocorticoids.

Dexamethasone, spironolactone and eplerenone have been used in treatment.^[4]

References

^ Vonend O, Altenhenne C, Büchner NJ et al. (April 2007). "A German family with glucocorticoid-remediable aldosteronism". Nephrol. Dial. Transplant. 22 (4): 1123–30. doi:10.1093/ndt/gfl706. PMID 17277347.
^ Ganong Physiology
^ McMahon GT, Dluhy RG (2004). "Glucocorticoid-remediable aldosteronism". Cardiol Rev 12 (1): 44–8. doi:10.1097/01.crd.0000096417.42861.ce. PMID 14667264.
^ McMahon GT, Dluhy RG (October 2004). "Glucocorticoid-remediable aldosteronism". Arq Bras Endocrinol Metabol 48 (5): 682–6. doi:10.1590/S0004-27302004000500014. PMID 15761539.

UpToDate Contents

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1. 家族性アルドステロン症 familial hyperaldosteronism
2. 低カリウム血症を合併した高血圧症へのアプローチ approach to the patient with hypertension and hypokalemia
3. 原発性アルドステロン症の病態生理および臨床的特徴 pathophysiology and clinical features of primary aldosteronism
4. 低レニン性原発性（本態性）高血圧 low renin primary essential hypertension
5. 原発性アルドステロン症の治療 treatment of primary aldosteronism

English Journal

Chimeric CYP11B2/CYP11B1 causing 11β-hydroxylase deficiency in Chinese patients with congenital adrenal hyperplasia.

Xu L1, Xia W1, Wu X1, Wang X1, Zhao L1, Nie M2.
Steroids.Steroids.2015 Jun 9;101:51-55. doi: 10.1016/j.steroids.2015.06.002. [Epub ahead of print]
CYP11B1 and CYP11B2 are highly homologous genes that can form chimera following unequal crossing-over during meiosis. A chimeric CYP11B1/CYP11B2 gene causes glucocorticoid-remediable aldosteronism (GRA), while the rare CYP11B2/CYP11B1 chimeric gene leads to 11β-hydroxylase deficiency (11-OHD). The
PMID 26066897

Intracranial aneurysm in a patient with glucocorticoid-remediable aldosteronism.

Al Romhain B1, Young AM, Battacharya JJ, Suttner N.
British journal of neurosurgery.Br J Neurosurg.2015 May 29:1-3. [Epub ahead of print]
Glucocorticoid-remediable aldosteronism (GRA) is an autosomal dominant disorder in which the increase in aldosterone secretion produced by Adrenocorticotropic hormone (ACTH) is no longer transient. Here we present a case of a 32-year-old man with GRA who was found to have an intracranial aneurysm fo
PMID 26021674

Genetics of primary aldosteronism.

Funder JW1.
Frontiers of hormone research.Front Horm Res.2014;43:70-8. doi: 10.1159/000360870. Epub 2014 Jun 10.
Primary aldosteronism (PA) accounts for ∼10% of hypertension, which is commonly caused by an aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Germline mutations producing PA are considered rare and termed familial hyperaldosteronism (FH) [1, 2, 3]. Since early 2011, a series o
PMID 24943299

Japanese Journal

グルココルチコイド奏効性アルドステロン症の病態と治療

沖隆
ホルモンと臨牀 54(1), 57-60, 2006-01-01
NAID 10017259400

グルココルチコイド反応性アルドステロン症

佐藤清二,上牧務
ホルモンと臨牀 49(10), 63-69, 2001-10-01
NAID 50000973467

Related Pictures

★リンクテーブル★

リンク元	「原発性アルドステロン症」「糖質コルチコイド反応性アルドステロン症」「グルココルチコイド反応性アルドステロン症」
関連記事	「aldosteronism」「glucocorticoid」「remediable」

「原発性アルドステロン症」

Glucocorticoid remediable aldosteronism
Classification and external resources
Specialty	Endocrinology
ICD-9	255.11
OMIM	103900

　　[★]

英: primary aldosteronism, PA
同: コン症候群 Conn syndrome Conn's syndrome、コン-ルイス症候群 Conn-Louis syndrome; アルドステロン産生腺腫 aldosterone producing adenoma APA
関: 特発性アルドステロン症　←　原発性アルドステロン症の下位概念。原発性アルドステロン症の約10%を占める; アルドステロン症

概念

広義：鉱質コルチコイド(アルドステロン)の過剰分泌により、低カリウム血症を伴った低レニン性高血圧を呈する疾患。
狭義：アルドステロン産生腺腫(APA)によりアルドステロンが過剰分泌している疾患

疫学

30-50歳に多く、女性に多い。(YN.D-59)

病因

副腎皮質球状層に発生したアルドステロン産生腺腫　←　ほとんど
両側副腎皮質球状層の過形成　←　特発性アルドステロン症

病因に基づく分類

SURO.277

局在	名称			原発性アルドステロン症に占める割合	ACTH依存性
片側性	アルドステロン産生腺腫	aldosterone producing adenoma	APA	約7割	○
	片側副腎皮質球状層過形成	unilateral adrenal hyperplasia	UAH
	アルドステロン産生副腎皮質癌	aldosterone producing carcinoma	APC	0.5-1.0%
両側性	両側副腎皮質球状層過形成/特発性高アルドステロン症	idiopathic hyperaldosteronism	IHA	約3割
	原発性副腎過形成	primary adrenal hyperplasia	PAH
	糖質コルチコイド反応性アルドステロン症	glucocorticoid-remediable aldosteronism	GRA
腎外性	異所性アルドステロン産生腫瘍	ectopic aldosteronism

病理

2cm以下の小さなものが多い、らしい。　⇔　クッシング症候群の原因となる副腎腺腫は2-4cmのものがおおい、らしい。

病態

参考2

浮腫は生じない：aldosterone escapeによる。
高血圧
低カリウム血症：アルドステロンの影響で皮質集合管で排泄される。正常な場合もある。詳しくは資料2
代謝性アシドーシス　←　　低カリウム血症による
高ナトリウム血症：中等度。volume expansionの持続により浸透圧調節中枢のセットポイントが数meq/Lだけ上昇する。けっかとして血中ナトリウム濃度が143-147mEq/Lに維持される。
低マグネシウム血症：アルドステロン過剰による。ヘンレのループ上行脚でマグネシウムの再吸収が行われるが、aldosterone escapeが持続している場合、マグネシウムの再吸収が抑制される。

症状

頭痛　　←　　高血圧による。
多尿　　←　　低カリウム血症による
筋力低下、脱力、四肢麻痺　　←　　低カリウム血症による
耐糖能異常　　←　　低カリウム血症による

検査

スクリーニング：血漿アルドステロン濃度 PAC、血漿レニン活性(PRA)の測定
確定検査：カプトプリル試験、立位フロセミド負荷試験、生理食塩水試験

診断

血清アルドステロン濃度の高値、血漿レニン活性の低値、コルチゾール分泌正常

治療

治療目標

血漿中のアルドステロン濃度を正常化、あるいは鉱質コルチコイド受容体を阻害すること。

治療法の原則

参考1

片側の病変は手術療法で治療可能である。
特発性高アルドステロン症は鉱質コルチコイド受容体拮抗薬で治療する。
糖質コルチコイド反応性アルドステロン症は生理的な量の糖質コルチコイドの投与で治療する。

疾患別治療法

アルドステロン産生腺腫 APA ：外科的摘除。アルドステロン受容体阻害薬は手術ができない場合、患者が拒否する場合に選択。
特発性アルドステロン症(IHA)：スピロノラクトン(アルドステロン受容体競合阻害薬)、トリロスタン(副腎皮質酵素阻害薬)。高血圧が持続する場合には利尿薬やACE阻害薬も追加できる。両側副腎の病変部のみを切除したり、一側の腎を切除する手術方法があるが、薬物療法に比べて最適な治療とは言えない。
グルココルチコイド奏効性アルドステロン症：デキサメタゾン