WordNet

enlargement of bones of hands and feet and face; often accompanied by headache and muscle pain and emotional disturbances; caused by overproduction of growth hormone by the anterior pituitary gland (due to a tumor) (同)acromegalia
marked or affected by enlargement or hypertrophy of the extremities or the face; "a protruding acromegalic jaw"

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/06 21:35:50」(JST)

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Acromegaly (/ˌækrɵˈmɛɡəli/; from Ancient Greek άκρος akros "extreme" or "extremities" and μεγάλος megalos "large") is an extremely rare syndrome that results when the anterior pituitary gland produces excess growth hormone (GH) after epiphyseal plate closure at puberty. If GH is produced in excess prior to epiphyseal plate closure, the result is gigantism (or giantism). A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called pituitary adenoma, derived from a distinct type of cell (somatotrophs).

Acromegaly most commonly affects adults in middle age,^[1] and can result in severe disfigurement and fatal complications if unchecked. Because of its pathogenesis and slow progression, it is hard to diagnose in the early stages and is frequently missed for years until changes in external features, especially of the face, become noticeable.

1 Signs and symptoms
- 1.1 Complications
2 Causes
- 2.1 Pituitary adenoma
- 2.2 Other tumors
3 Diagnosis
- 3.1 Pseudoacromegaly
4 Treatment
- 4.1 Medications
  - 4.1.1 Somatostatin analogues
  - 4.1.2 Dopamine agonists
  - 4.1.3 Growth hormone receptor antagonists
- 4.2 Surgery
- 4.3 Radiation therapy
- 4.4 Choices
5 Prognosis
6 Notable cases
7 References
8 External links

Signs and symptoms

Features that result from high level of GH or expanding tumor include:

Soft tissue swelling visibly resulting in enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin
Soft tissue swelling of internal organs, notably the heart with attendant weakening of its muscularity, and the kidneys, also the vocal cords resulting in a characteristic thick, deep voice and slowing of speech
Generalized expansion of the skull at the fontanelle
Pronounced brow protrusion, often with ocular distension (frontal bossing)
Pronounced lower jaw protrusion (prognathism) with attendant macroglossia (enlargement of the tongue) and teeth spacing
Hypertrichosis, hyperpigmentation and hyperhidrosis may occur in these patients.^[2]^:499
Acrochordon (skin tags)
Carpal tunnel syndrome

Compared with the hand of a typical person (left), the hand of a patient with acromegaly (right) is enlarged, with fingers that are widened, thickened and stubby, and with thicker soft tissue
Mandibular overgrowth leads to prognathism, maxillary widening, teeth spacing and malocclusion.
Brow ridge and forehead protrusion remaining after tumor removal and tissue swelling eliminated
Lower jaw showing the classic spacing of teeth due to acromegaly

Complications

Severe headache
Arthritis and carpal tunnel syndrome
Enlarged heart
Hypertension
Diabetes mellitus (excess of GH leads to insulin resistance)
Heart failure
Kidney failure
Colorectal cancer ^[3]
Compression of the optic chiasm leading to loss of vision in the outer visual fields (typically bitemporal hemianopia)
Increased palmar sweating and sebum production over the face (seborrhea) are clinical indicators of active growth hormone (GH) producing pituitary tumors. These symptoms can also be used to monitor the activity of the tumor after surgery although biochemical monitoring is confirmatory.

Causes

Pituitary adenoma

In over 90 percent of acromegaly patients, the overproduction of growth hormones is caused by a benign tumor of the pituitary gland, called an adenoma. These tumors produce excess growth hormones and, as they expand, compress surrounding brain tissues, such as the optic nerves. This expansion causes the headaches and visual disturbances that often accompany acromegaly. In addition, compression of the surrounding normal pituitary tissue can alter production of other hormones, leading to changes in menstruation and breast discharge in women and impotence in men because of reduced testosterone production.

There is a marked variation in rates of GH production and the aggressiveness of the tumor. Some adenomas grow slowly and symptoms of growth hormone excess are often not noticed for many years. Other adenomas grow rapidly and invade surrounding brain areas or the sinuses, which are located near the pituitary. In general, younger patients tend to have more aggressive tumors.

Most pituitary tumors arise spontaneously and are not genetically inherited. Many pituitary tumors arise from a genetic alteration in a single pituitary cell which leads to increased cell division and tumor formation. This genetic change, or mutation, is not present at birth, but is acquired during life. The mutation occurs in a gene that regulates the transmission of chemical signals within pituitary cells; it permanently switches on the signal that tells the cell to divide and secrete growth hormones. The events within the cell that cause disordered pituitary cell growth and growth hormone oversecretion currently are the subject of intensive research.

Other tumors

In a few patients, acromegaly is caused not by pituitary tumors but by tumors of the pancreas, lungs, and adrenal glands. These tumors also lead to an excess of GH, either because they produce GH themselves or, more frequently, because they produce GHRH (growth hormone releasing hormone), the hormone that stimulates the pituitary to make GH. In these patients, the excess GHRH can be measured in the blood and establishes that the cause of the acromegaly is not due to a pituitary defect. When these non-pituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve.

In patients with GHRH-producing, non-pituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Therefore, it is important that physicians carefully analyze all "pituitary tumors" removed from patients with acromegaly in order not to overlook the possibility that a tumor elsewhere in the hypoglycoma is causing the disorder.

Diagnosis

Frequent blood sampling with serum GH measurement shows that in normal subjects (left panel) GH can fluctuate between undetectable levels (most of the time) and peaks of up to 30 μg/l (90 mIU/l), owing to the episodic nature of GH secretion, while in patients with acromegaly (an example is given on right panel), GH hypersecretion is continuous and GH never returns to undetectable levels.

If acromegaly is suspected, medical imaging and medical laboratory investigations are generally used together to confirm or rule out the presence of this condition.

IGF1 provides the most sensitive lab test for the diagnosis of acromegaly, and a GH suppression test following an oral glucose load, which is a very specific lab test, will confirm the diagnosis following a positive screening test for IGF1. A single value of the growth hormone (GH) is not useful in view of its pulsatality (levels in the blood vary greatly even in healthy individuals).

Magnetic resonance image of a pituitary macroadenoma that caused acromegaly with compression of the optic chiasm.

GH levels taken 2 hours after a 75 or 100 gram glucose tolerance test are helpful in the diagnosis: GH levels are suppressed below 1 μg/L in normal people, and levels higher than this cutoff are confirmatory of acromegaly.

Other pituitary hormones have to be assessed to address the secretory effects of the tumor as well as the mass effect of the tumor on the normal pituitary gland. They include TSH (thyroid stimulating hormone), gonadotropic hormones (FSH, LH), ACTH (adrenocorticotropic hormone), prolactin.

An MRI of the brain focusing on the sella turcica after gadolinium administration allows for clear delineation of the pituitary and the hypothalamus and the location of the tumor.

Pseudoacromegaly

Pseudoacromegaly is a condition with the usual acromegaloid features but without an increase in growth hormone and IGF-1. It is frequently associated with insulin resistance.^[4] Cases have been reported due to minoxidil at an unusually high dose.^[5] It can also be caused by a selective post-receptor defect of insulin signalling, leading to the impairment of metabolic but preservation of mitogenic signalling.^[6]

Treatment

The goals of treatment are to reduce GH production to normal levels, to relieve the pressure that the growing pituitary tumor exerts on the surrounding brain areas, to preserve normal pituitary function, and to reverse or ameliorate the symptoms of acromegaly. Currently, treatment options include surgical removal of the tumor, drug therapy, and radiation therapy of the pituitary.

Medications

Somatostatin analogues

Site of action of the different therapeutic tools in acromegaly. Surgery, radiotherapy, somatostatin analogues and dopamine agonists act at the level of the pituitary adenoma, while GH receptor antagonists act in periphery by blocking the growth hormone receptor and thus impairing the effects of GH on the different tissues.

The primary current medical treatment of acromegaly is to use somatostatin analogues – octreotide (Sandostatin) or lanreotide (Somatuline). These somatostatin analogues are synthetic forms of a brain hormone, somatostatin, which stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most patients with acromegaly respond to this medication. In many patients, GH levels fall within one hour and headaches improve within minutes after the injection. Octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat patients with acromegaly caused by non-pituitary tumors.

Somatostatin analogues are also sometimes used to shrink large tumors before surgery.

Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one third of patients. In addition, approximately 25 percent of patients develop gallstones, which are usually asymptomatic. In some cases, octreotide treatment can cause diabetes due to the fact that somatostatin and its analogues can inhibit the release of insulin. On the other hand, scientists have found that in some acromegaly patients who already have diabetes, octreotide can reduce the need for insulin and improve blood sugar control.^{[citation needed]}

Dopamine agonists

For those who are unresponsive to somatostatin analogues, or for whom they are otherwise contraindicated, it is possible to treat using one of the dopamine agonists, bromocriptine or cabergoline. As tablets rather than injections, they cost considerably less. These drugs can also be used as an adjunct to somatostatin analogue therapy. They are most effective in those whose pituitary tumours cosecrete prolactin. Side effects of these dopamine agonists include gastrointestinal upset, nausea, vomiting, light-headedness when standing, and nasal congestion. These side effects can be reduced or eliminated if medication is started at a very low dose at bedtime, taken with food, and gradually increased to the full therapeutic dose. However, bromocriptine lowers GH and IGF-1 levels and reduces tumor size in fewer than half of patients with acromegaly. Some patients report improvement in their symptoms although their GH and IGF-1 levels still are elevated.

Growth hormone receptor antagonists

The latest development in the medical treatment of acromegaly is the use of growth hormone receptor antagonists. The only available member of this family is pegvisomant (Somavert). By blocking the action of the endogenous growth hormone molecules, this compound is able to control disease activity of acromegaly in virtually all patients. Pegvisomant has to be administered subcutaneously by daily injections. Combinations of long-acting somatostatin analogues and weekly injections of pegvisomant seem to be equally effective as daily injections of pegvisomant.

Surgery

Surgery is a rapid and effective treatment, of which there are two alternative methods. The first method, a procedure known as endonasal transphenoidal surgery, involves the surgeon reaching the pituitary through an incision in the nasal cavity wall. The wall is reached by passing through the nostrils with microsurgical instruments. The second method is transsphenoidal surgery during which an incision is made into the gum beneath the upper lip. Further incisions are made to cut through the septum to reach the nasal cavity, where the pituitary is located. Endonasal transphenoidal surgery is a less invasive procedure with a shorter recovery time than the older method of Transphenoidal surgery, and the likelihood of removing the entire tumor is greater with reduced side-effects. Consequently, endonasal transphenoidal surgery is often used as a first option, with transphenoidal and other treatments, such as medicinal therapy or stereotactic radiosurgery, used to reduce the remaining adverse effects of the remaining tumor.

These procedures normally relieve the pressure on the surrounding brain regions and lead to a lowering of GH levels. Surgery is most successful in patients with blood GH levels below 40 ng/ml before the operation and with pituitary tumors no larger than 10 mm in diameter. Success depends on the skill and experience of the surgeon. The success rate also depends on what level of GH is defined as a cure. The best measure of surgical success is normalization of GH and IGF-1 levels. Ideally, GH should be less than 2 ng/ml after an oral glucose load. A review of GH levels in 1,360 patients worldwide immediately after surgery revealed that 60 percent had random GH levels below 5 ng/ml. Complications of surgery may include cerebrospinal fluid leaks, meningitis, or damage to the surrounding normal pituitary tissue, requiring lifelong pituitary hormone replacement.

Even when surgery is successful and hormone levels return to normal, patients must be carefully monitored for years for possible recurrence. More commonly, hormone levels may improve, but not return completely to normal. These patients may then require additional treatment, usually with medications.

Radiation therapy

Radiation therapy has been used both as a primary treatment and combined with surgery or drugs. It is usually reserved for patients who have tumor remaining after surgery. These patients often also receive medication to lower GH levels. Radiation therapy is given in divided doses over four to six weeks. This treatment lowers GH levels by about 50 percent over 2 to 5 years. Patients monitored for more than 5 years show significant further improvement. Radiation therapy causes a gradual loss of production of other pituitary hormones with time. Loss of vision and brain injury, which have been reported, are very rare complications of radiation treatments.

Choices

No single treatment is effective for all patients. Treatment should be individualized depending on patient characteristics, such as age and tumor size. If the tumor has not yet invaded surrounding brain tissues, removal of the pituitary adenoma by an experienced neurosurgeon is usually the first choice. After surgery, a patient must be monitored for a long time for increasing GH levels. If surgery does not normalize hormone levels or a relapse occurs, a doctor will usually begin additional drug therapy. The current first choice is generally octreotide or lanreotide. However, bromocriptine or cabergoline are much cheaper and easier to administer. With both types of medication, long-term therapy is necessary because their withdrawal can lead to rising GH levels and tumor re-expansion. Radiation therapy is generally used for patients whose tumors are not completely removed by surgery; for patients who are not good candidates for surgery because of other health problems; and for patients who do not respond adequately to surgery and medication.

Prognosis

Upon successful treatment, symptoms and complications generally improve substantially or disappear, including headaches, visual disturbances, excess sweating and diabetes.^[7] Soft tissue swellings generally decrease and acromegaly-associated facial features gradually return towards normal although this may take some time.^[7] Life expectancy after the successful treatment of early acromegaly is equal to that of the normal population.^[7]

Notable cases

Famous acromegalics include:

Rondo Hatton, an American soldier, journalist and occasional actor with a minor career playing thuggish bit and extra parts in Hollywood B-movies.
Richard Kiel, actor; "Jaws" from two James Bond movies and Mr. Larson in Happy Gilmore.^[8] He grew up to 7 ft 1½ in, but was slightly under 7 ft in his later years due to age and injury.
Pío Pico, the last Mexican Governor of California (1801–1894), manifested acromegaly without gigantism between at least 1847 and 1858. Some time after 1858 signs of the growth hormone-producing tumor disappeared along with all the secondary effects the tumor had caused in him. He looked normal in his 90's.^[9] His remarkable recovery is likely an example of spontaneous selective pituitary tumor apoplexy.^[10]
Adam Rainer, born in 1899, an Austrian man is so far the only person in recorded history to have been both a dwarf and a giant. His rapid change from dwarf to giant is believed to have been caused by acromegaly.^[11] He died on 4 March 1950.
Anthony Robbins, motivational speaker.^[12]
André the Giant (born André Rousimoff), French professional wrestler and actor^[13]^[14] 2.13 m (7') tall after back surgery; his original wrestling stats listed him at 2.23 m (7'4"). He died at the age of 46 and weighed 520 pounds (240 kg). (He chose not to be treated and died from cardiac complications of acromegaly.)
Big Show (born Paul Wight), American professional wrestler and actor, currently working for the WWE. Had his pituitary tumor removed in 1991.^[15]
The Great Khali (born Dalip Singh Rana), Indian professional wrestler, best known for his tenure with WWE. Had his pituitary tumor removed in 2012, aged 39.^[16]
Maurice Tillet (1903-1954), Russian-born French professional wrestler, better known by his ring name, The French Angel.^[17]
Carel Struycken, Dutch actor, 2.13m (7'0"), best known for playing Lurch in The Addams Family film trilogy.^[18]

References

^ "Acromegaly and Gigantism". Merck.com. Archived from the original on 5 November 2010. Retrieved 2010-10-26.
^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
^ Renehan AG, O'Connell J, O'Halloran D et al. (2003). "Acromegaly and colorectal cancer: a comprehensive review of epidemiology, biological mechanisms, and clinical implications". Horm. Metab. Res. 35 (11-12): 712–25. doi:10.1055/s-2004-814150. PMID 14710350.
^ Yaqub A, Yaqub N (2008). "Insulin-mediated pseudoacromegaly: a case report and review of the literature". W V Med J 104 (5): 12–5. PMID 18846753.
^ Nguyen KH, Marks JG (June 2003). "Pseudoacromegaly induced by the long-term use of minoxidil". J. Am. Acad. Dermatol. 48 (6): 962–5. doi:10.1067/mjd.2003.325. PMID 12789195.
^ "Insulin-mediated "pseudoacromegaly".". Retrieved 2013-05-12.
^ ^a ^b ^c Acromegaly - Patient information from Centre for Diabetes and Endocrinology at The Royal Berkshire NHS Foundation Trust. January 2011
^ "Richard "Jaws" Kiel, Famed Bond Movie Villain, Raises Awareness Oflife-Threatening Hormone Disorder". Prnewswire.com. Retrieved 2010-07-26.
^ Login IS, Login J (July 2008). "Governor Pio Pico, the monster of California...no more: lessons in neuroendocrinology". Pituitary 13 (1): 80–6. doi:10.1007/s11102-008-0127-1. PMC 2807602. PMID 18597174. Open Access; http://www.springerlink.com/content/u7645787h2435373/fulltext.pdf
^ Nawar RN, AbdelMannan D, Selman WR, Arafah BM (2008). "Pituitary tumor apoplexy: a review". J Intensive Care Med 23 (2): 75–90. doi:10.1177/0885066607312992. PMID 18372348.
^ http://thechirurgeonsapprentice.com/2015/01/20/worlds-littlest-giant-the-curious-case-of-adam-rainer/
^ Plaskin, Glenn (2013-08-13). "Playboy Interview: Tony Robbins". Playboy. Retrieved 5 March 2015.
^ "Andre the Giant: Bio". WWE.com. Archived from the original on 2008-01-10. Retrieved 2007-10-16.
^ "André the Giant official website". Archived from the original on 4 July 2007. Retrieved 2007-07-08.
^ "Big Show at home in current role", by Tim Baines, Ottawa Sun
^ "WWE Star Great Khali's Growth-Inducing Tumor Removed", by Alon Harish, ABC News
^ " The French Angel was more man than monster", by Greg Oliver, Producer, SLAM! Wrestling
^ Dennis McLellan for the Los Angeles Times. December 27, 1992 Shedding Light on a Rare Disease : Woman Hopes O.C. Group Will Increase Awareness of Life-Threatening Effects of Excessive-Growth Illness

External links

Acromegaly at DMOZ
New guidelines for the treatment of acromegaly, a serious growth hormone disorder - News-Medical.net
Endocrine and Metabolic Diseases Information Service
AcromegalyAnswersWebinar.com A webinar series
Acromegaly and Gigantism (a very comprehensive article)
Acromegaly and Gigantism (Image of a patient with macroglossia - enlargement of the tongue)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 先端巨大症の診断 diagnosis of acromegaly
2. 先端巨大症の治療 treatment of acromegaly
3. 先端巨大症の原因および臨床症状 causes and clinical manifestations of acromegaly
4. 先端巨大症に関連するリウマチ性疾患および骨疾患 rheumatic and bone disorders associated with acromegaly
5. 高リン血症の原因および治療の概要 overview of the causes and treatment of hyperphosphatemia

English Journal

Aortic root ectasia in patients with acromegaly: an emerging complication*.

Colao A, Grasso LF.SourceDepartment of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Napoli, Italy.
Clinical endocrinology.Clin Endocrinol (Oxf).2011 Oct;75(4):420-1. doi: 10.1111/j.1365-2265.2011.04131.x.
PMID 21623859

Aortic root ectasia in patients with acromegaly: experience at a single center.

Casini AF, Neto LV, Fontes R, Franca RF, Xavier SS, Gadelha MR.SourceEndocrinology Unit, Hospital Universitario Clementino Fraga Filho/Universidade Federal do Rio de Janeiro Endocrinology Unit, Hospital da Lagoa Diagnosticos da America, Medicina Diagnostica, Rio de Janeiro Cardio Diagnostico, Espirito Santo Cardiology Unit, Hospital Universitario Clementino Fraga Filho/Universidade Federal do Rio de Janeiro Endocrinology Unit, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Rio de Janeiro, Brazil.
Clinical endocrinology.Clin Endocrinol (Oxf).2011 Oct;75(4):495-500. doi: 10.1111/j.1365-2265.2011.04067.x.
Background? Acromegaly is associated with increased cardiovascular mortality, and increased aortic root diameter has been recently described in the literature as a possible feature of acromegalic cardiomyopathy. Objective? To assess the aortic root diameter and the prevalence of aortic ectasia i
PMID 21521335

Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis.

Roelfsema F, Biermasz NR, Pereira AM.SourceDepartment of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands, f.roelfsema@lumc.nl.
Pituitary.Pituitary.2011 Sep 15. [Epub ahead of print]
To study the currently available data of recurrence rates of functioning and nonfunctioning pituitary adenomas following surgical cure and to analyze associated predisposing factors, which are not well established. A systematic literature search was conducted using Medline, Embase, Web of Science an
PMID 21918830

Japanese Journal

成長ホルモン分泌異常症 : 先端巨大症と成人成長ホルモン分泌不全症 (特集厚生労働省難治性疾患研究から得られた日本の難病の現状 : 内分泌系4領域の研究成果) -- (間脳下垂体機能障害)

肥塚直美
最新医学 67(9), 1959-1965, 2012-09-00
NAID 40019430959

心臓再同期療法とオクトレオチド療法の併用により劇的な左室逆リモデリングが認められた先端巨大症合併心不全の1例

渡辺清孝,土肥薫,中嶋寛,佐藤雄一,杉浦英美喜,杉本匡史,中森史朗,藤井英太郎,山田典一,中村真潮,伊藤正明
日本心臓病学会誌 =Journal of cardiology. Japanese edition 7(2), 118-124, 2012-06-15
NAID 10030656460

症例報告心臓再同期療法とオクトレオチド療法の併用により劇的な左室逆リモデリングが認められた先端巨大症合併心不全の1例

渡辺清孝,土肥薫,中嶋寛他
日本心臓病学会誌 : Journal of cardiology. Japanese edition 7(2), 118-124, 2012-06-00
NAID 40019362130

Related Pictures

★リンクテーブル★

リンク元	「100Cases 27」「先端巨大症」「100Cases 16」「アクロメガリー」「acromegalic」

「100Cases 27」

Acromegaly
	Facial aspect of a person with acromegaly. The cheekbones are pronounced, the forehead bulges, the jaw is enlarged and facial lines prominent.
Classification and external resources
Specialty	Endocrinology
ICD-10	E22.0inusl
ICD-9-CM	253.0
OMIM	102200
DiseasesDB	114
MedlinePlus	000321
eMedicine	med/27 derm/593
Patient UK	Acromegaly
MeSH	D000172

　　[★]

☆case27　関節痛

■症例

37歳　女性

主訴：関節痛

現病歴：数ヶ月、膝の痛みがだんだん強くなっていると感じていた。痛みは手や足の小関節に多く、朝歩くときに最もこわばる。痛みはジクロフェナクを飲むと和らぐ。そのほかの症状として疲労感を感じ、最近、体重が３ヶ月で４ｋｇ減っている。

喫煙歴：なし。

飲酒歴：機会飲酒

既往歴：なし

家族歴：既婚、子供は２人

服薬歴：ジクロフェナク

職業歴：legal sevretary

身体所見 examination

　顔貌　青白、臨床的な貧血を認める。近位指節間関節・中手指節関節　腫脹・effusionを伴う疼痛。中足趾節関節　圧痛。それ以外は正常。

検査　 investigation

　血液検査

　　Hb低下

　　ESR 上昇

　　尿素軽度上昇

　　クレアチニン軽度上昇

　　正常：白血球、MCV、血小板、ナトリウム、カリウム、グルコース、アルブミン

　尿検査

　　蛋白(-)、尿糖(-)、潜血(-)、

■問題

　本症例では診断とその根拠を考えるのは簡単なので、鑑別疾患をあげてその疾患に特徴的な症候を列挙しましょう。

■関節痛 DIF.283

　V Vascular

　　血友病 hemophilia　血友病性関節症(急性：疼痛、腫脹、熱感(SOR.241)

慢性：可動域の低下、変形、関節周囲筋萎縮(SOR.241))。家族歴

　　壊血病 scurvy　。生活環境。食事歴

　　無菌性骨壊死 aseptic bone necrosis (Osgood-Schlatter diseaseとか)

　I Inflammatory

　　感染性関節炎(細菌性関節炎(化膿性関節炎・淋菌性関節炎・結核性関節炎・嫌気性菌関節炎 )、真菌性関節炎、スピロヘータ関節炎(梅毒性関節炎・ライム関節炎)、マイコプラズマ関節炎、ウイルス性関節炎)

　N Neoplastic disorders

　　骨原性肉腫 osteogenic sarcoma

　　巨細胞腫 giant cell tumors

　D Degenerative disorders

　　degenerative joint disease

　　変形性関節症 osteoarthritis

　I Intoxication

　　痛風 gout (uric acid)

　　偽痛風 pseudogout (calcium pyrophosphate)

　　ループス症候群 lupus syndrome of hydralazine (Apresoline) and procainamide

　　gout syndrome of diuretics

　C Congenital and acquired malformations bring to mind the joint deformities of tabes dorsalis and syringomyelia and congenital dislocation of the hip. Alkaptonuria is also considered here.

　A Autoimmune indicates

　　関節リウマチ RA

　　血清病 serum sickness

　　全身性エリテマトーデス lupus erythematosus

　　リウマチ熱 rheumatic fever

　　ライター症候群 Reiter syndrome

　　潰瘍性大腸炎 ulcerative colitis

　　クローン病=限局性回腸炎 regional ileitis

　　乾癬性関節炎 psoriatic arthritis

　　リウマチ性多発筋痛症 polymyalgia rheumatica

　T Trauma

　E Endcrine

　　先端肥大症 acromegaly

　　閉経 menopause

　　糖尿病 diabetes mellitus

■関節炎の分類

・炎症部位の数

　単関節炎：痛風、偽痛風、離断性骨軟骨炎、血行性の化膿性関節炎のほとんど

　多関節炎：リウマチ性疾患、ウイルス性疾患、白血病での関節症状、易感染性宿主における血行性の化膿性関節炎

■関節リウマチ

　診断基準

　関節症状

　　朝のこわばり、疼痛、腫脹、関節の動揺、関節可動域制限、変形(手指、足趾、膝関節)。(SOR.211)

　　手指の近位指節間関節(PIP 関節)、中手指節関節(MP 関節)。遠位指節間関節(DIP 関節)に初発することは稀。(SOR.211)

　　左右対称性に生じることが多い。手関節、足趾、膝関節に初発する。(SOR.211)

　関節外症状

　　全身症状：発熱

　　皮膚症状：リウマトイド結節(肘の伸側、後頭部、手指)

　　眼症状：上胸膜炎(10日の経過で治癒)、強膜炎(予後不良)。稀に角膜穿孔

　　血液障害：(高頻度)貧血、白血球減少(Felty病。DMARDs投与中の場合は薬剤性の骨髄抑制を考慮)

　　アミロイドーシス：ネフローゼや下痢を来した症例で疑う。アミロイド蛋白はAA

　　腎障害：稀。アミロイドーシスの続発症か薬剤性を考慮。

　　呼吸器症状：間質性肺炎の合併多い。下肺野に好発。通常無症状。メトトレキセートなどの使用により薬剤性の急性間質性肺炎を生じることがある。

　　心・血管障害：リンパ管炎による難治性の浮腫。

　　神経症状：環軸関節亜脱臼により項部痛や脊髄症上が出現しうる。

　　骨粗鬆症

　　腱鞘滑膜炎：手指、手関節、足関節

■両側性多関節炎の鑑別疾患

　OA：遠位指節間関節を冒すのが特徴的で、近位指節間関節、中手指節関節を冒しうる。

　RA：

　SLE：軽度、症状の程度が変動する非びらん性の関節炎

　gout：単関節炎からはじまる。

　血清陰性関節炎：強直性脊椎炎、感染、ライター病：中～大関節に非対称性の関節炎。仙腸関節と遠位指節間関節にも関節炎

　急性ウイルス性関節炎：風疹。

■KEY POINTS

・RAでは遠位指節間関節は冒されない傾向がある。

・RAの全身症状は関節症状に先行することがある。

・RAの活動性と貧血及びESRは相関している。

・NSAIDsは腎機能に悪影響を与えることがある。

■initial plan

　Dx 1. 単純X線写真

　　　　・亜脱臼、関節周囲の骨萎縮(傍関節性骨骨粗鬆症,juxta-articular osteoporosis)、関節裂隙の狭小化、関節辺縁のびらん(bony erosion)

　　　　　・初期のRAで第5趾に骨びらんが一般的に見られる。

　　　　・血液検査

　　　　　・RF、抗DNA 抗体

　Tx 1. 鎮痛薬

　　　　・NSAIDs：鎮痛とこわばりの軽減

　　 2. DMARDs(メトトレキセート、レフルノミド、金製剤、ペニシラミン)

　　　　・NSAIDsで症状が治まらない場合に考慮

　　 3. 抗TNF 抗体

　　　　・重症のRAで効果がある場合がある。

■参考文献

SOR　標準整形外科学第10版医学書院

DIF　Differential Diagnosis in Primary Care Fourth Edition版 Lippincott Williams & Wilkins

「先端巨大症」

　　[★]

英: acromegaly
同: 先端肥大症末端肥大症、マリー症候群 Marie syndrome
関: 成長ホルモン、難病

[show details]

先端巨大症 : 約 170,000 件
先端肥大症 : 約 4,990 件
末端巨大症 : 約 2,190 件
末端肥大症 : 約 46,200 件
マリー症候群 : 53 件

概念

下垂体前葉より成長ホルモンが長期間、過剰に分泌されるために骨、結合組織、内臓の過剰発育をきたす疾患。
特定疾患治療研究事業の対象となる難病

病因

GH産生下垂体腺腫

診断基準

(参考1)

1．主要項目

(1)主症候(注1)

①手足の容積の増大

②先端巨大症様顔貌(眉弓部の膨隆、鼻・口唇の肥大、下顎の突出など)

③巨大舌

(2)検査所見

①成長ホルモン(GH)分泌の過剰：血中GH値がブドウ糖75g経口投与で正常域まで抑制されない。(注2)

②血中IGF-1(ソマトメジンC)の高値(年齢・性別基準値の2SD以上)。(注3)

③CTまたはMRIで下垂体腺腫の所見を認める。(注4)

2．参考事項

副症候および検査所見

(1)発汗過多

(2)頭痛

(3)視野障害

(4)女性における月経異常

(5)睡眠時無呼吸症候群

(6)耐糖能異常

(7)高血圧

(8)咬合不全

(9)頭蓋骨および手足の単純X線の異常(注5)

3．診断基準

確実例：1(1)①から③の1項目以上を満たし、かつ1(2)①から③すべての項目を満たすもの。

可能性を考慮：ブドウ糖負荷でGHが正常域に抑制されたり、臨床症候が軽微な場合でも、IGF-1が高値で、1(2)③を満たすもの。

(注1)発病初期例や非典型例では症候が顕著でない場合がある。

(注2)正常域とは血中GH底値1ng/ml(リコンビナントGHを標準品とするGH測定法)未満である。糖尿病、肝疾患、腎疾患、青年では血中GH値が正常域まで抑制されないことがある。また、本症では血中GH値がTRHやLH-RH刺激で増加(奇異性上昇)することや、ブロモクリプチンなどのドパミン作動薬で血中GH値が増加しないことがある。さらに、腎機能が正常の場合に採取した尿中GH濃度が正常値に比べ高値である。

(注3)健常者の年齢・性別基準値を参照する。栄養障害、肝疾患、腎疾患、甲状腺機能低下症、コントロール不良の糖尿病などが合併すると血中IGF-Iが高値を示さないことがある。IGF-Ⅰの基準値としては別添の資料を参考のこと。

(注4)明らかな下垂体腺腫所見を認めない時や、ごく稀にGHRH産生腫瘍の場合がある。

(注5)頭蓋骨単純X線でトルコ鞍の拡大および破壊、副鼻腔の拡大と突出、外後頭隆起の突出、下顎角の開大と下顎の突出など、手X線で手指末節骨の花キャベツ様肥大変形、足X線で足底部軟部組織厚heelpadの増大＝22mm以上を認める。

負荷試験のまとめ

検査	先端巨大症	正常	備考
グルコース負荷試験	高値を維持	低下
TRH負荷試験	上昇	不変	奇異性上昇
LHRH負荷試験	上昇	不変	奇異性上昇
ドパミン作動薬(ブロモクリプチン)	低下	上昇
日内変動	なし	あり	調節を失う

病態

参考2

甲状繊維状：甲状腺は肥大するが、甲状腺ホルモンの量は正常である事が多い。一方で、下垂体腫瘍により中枢性の甲状腺機能低下症をきたす患者が少数存在する。
心血管系：高血圧(43%の症例に存在)、心肥大(高血圧、およびGHの直接的効果)、心筋症(　→　拡張障害　＋　不整脈　)、心不全(3-10%の症例)、弁膜症(心エコー上、30%の症例でAR, 5%の症例でMRが見いだされた)
睡眠時無呼吸
代謝：インスリン抵抗性を伴う高インスリン血症による糖尿病は10-20%の症例で見られ、耐糖能異常は50%の患者で見られる。
結腸の腫瘍：結腸粘膜上皮細胞の増殖におけるIGF-Iの関与、PPAR(peroxisome proliferator-activated receptor)遺伝子の発現低下が腫瘍発生のメカニズム？

腺腫の頻度は2.5倍
結腸癌の頻度は4倍

検査

負荷試験の結果の見方

QB-D253

	成長ホルモン GH		プロラクチン PRL
	先端巨大症	正常	PRL産生腫瘍	正常
グルコース負荷試験	→	↓	ー	ー
L-ドーパ負荷試験	↓/→⁽¹⁾	↑	↓	↓
TRH	↑
LH-RH

(1) QB.D-254 参考1　→　増加しない

QB.D-254

ブドウ糖負荷試験：GH→　(正常：↓)　　←　コントロール不能？
TRH、LH-RH：GH↑　(正常：→？)
インスリン、低血糖、L-dopa負荷：GH→　(正常：↑)　　←　十分にGHが分泌されているから、これ以上反応できない？

治療

方針：手術療法(腺腫摘出術)が第1選択となり、手術が不可能な例や拒否例、残存腺腫により高GHである例などで薬物療法を行う

手術療法：

経蝶形骨洞下垂体腺腫摘除術(ハーディ手術)：トルコ鞍内に限局している例
経前頭骨下垂体腺腫摘除術：トルコ鞍上に進展している例

薬物療法

放射線療法

定位的放射線照射：従来の外部照射に比べ良好な治療成績が得られているが、放射線障害による下垂体機能低下が問題となっている。

治療効果の判定

足底部軟部組織厚heelpadは治療によって減少し、治療効果の判定に用いられる。(QB.D-253)
IGF-1は治療効果の判定に有用、らしい。

参考

1. 先端巨大症 - 難病情報センター

http://www.nanbyou.or.jp/entry/287

2. [charged] Causes and clinical manifestations of acromegaly - uptodate [1]

「100Cases 16」

　　[★]

☆case16　膝の痛み

■glossary

indigestion 消化障害、消化不良

■症例

80歳　男性

主訴：左膝の痛みと腫脹

現病歴：左膝の痛みを2日前から認めた。膝は発熱・腫脹しており、動かすと疼痛を生じる。時々胸焼けと消化不良が見られる。6ヶ月前のhealth checkで、高血圧(172/102mmHg)と血中クレアチニンが高い(正常高値)こと以外は正常といわれた。その4週間数回血圧を測定したが、高値が継続したため、2.5mg bendrofluamethizide(UK)/ベンドロフルメチアジド bendroflumethiazide(US)で治療を開始した。最近の血圧は138/84 mmHgであった。

喫煙歴：なし。

飲酒歴：一週間に平均4unit。

既往歴：股関節に中程度(mild)の変形性関節症

家族歴：特記なし

服薬歴：アセトアミノフェン(股関節の疼痛に対して)

身体所見 examination

　血圧 142/86mmHg。体温37.5℃。脈拍88/分。grade 2 hypertensive retinopathy(高血圧症性網膜症)。心血管系、呼吸器系に検査場異常なし。手にDIPにヘバーデン結節なし。

　左膝が発熱し腫脹している。関節内に液、patellar tap陽性。90℃以上膝関節を屈曲させると痛みを生じる。右の膝関節は正常に見える。

検査　 investigation

　生化学：白血球増多、ESR 上昇、尿素高値、グルコース高値

　単純X線：関節間隙やや狭小。それ以外に異常は認めない。

■problem list

　#1 左膝の痛み

　#2 胸焼け

　#3 消化不良

　#4 高血圧

　#5 クレアチニン正常高値

　#6 股関節の変形性リウマチ

　#7 高血圧性網膜症

■考え方

　・関節痛の鑑別診断を考える。

　・VINDICATEで考えてみてもよいでしょう。

　・関節痛の頻度としては　外傷＞慢性疾患(OAなど)＞膠原病＞脊椎疾患＞悪性腫瘍

■関節痛の鑑別疾患

DIF 282

V Vascular 血友病 hemophilia, 壊血病 scurvy, 無菌性骨壊死 aseptic bone necrosis (Osgood-Schlatter diseaseとか)

I Inflammatory 淋疾 gonorrhea, ライム病 lyme disease, 黄色ブドウ球菌 Staphylococcus, 連鎖球菌 Streptococcus, 結核 tuberculosis, 梅毒 syphilis, 風疹 rubella, 単純ヘルペス herpes simplex, HIV human immunodeficiency virus, サイトメガロウイルス cytomegalovirus

N Neoplastic disorders 骨原性肉腫 osteogenic sarcoma, 巨細胞腫 giant cell tumors

D Degenerative disorders degenerative joint disease or 変形性関節症 osteoarthritis

I Intoxication 痛風 gout (uric acid), 偽痛風 pseudogout (calcium pyrophosphate), ループス症候群 lupus syndrome of hydralazine (Apresoline) and procainamide, gout syndrome of diuretics

C Congenital and acquired malformations bring to mind the joint deformities of tabes dorsalis and syringomyelia and congenital dislocation of the hip. Alkaptonuria is also considered here.