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Cushing's syndrome

Cushing's syndrome or hypercortisolism is an endocrine disorder caused by excessive levels of the endogenous corticosteroid hormone cortisol. It may also be induced iatrogenically by treatment with exogenous corticosteroids for other medical conditions. It was discovered by American physician, surgeon and endocrinologist Harvey Cushing (1869-1939) and reported by him in 1932. more...

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Signs and symptoms

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), "moon face", excess sweating, telangiectasia (dilation of capillaries), atrophy of the skin (which gets thin and bruises easily) and other mucous membranes, purple or red striae on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth). A common sign is the growth of fat pads along the collar bone and on the back of the neck (known as a buffalo hump). The excess cortisol may also affect other endocrine systems and cause, for example, reduced libido, impotence, amenorrhoea and infertility. Patients frequently suffer various psychological disturbances, ranging from euphoria to frank psychosis. Depression and anxiety, including panic attacks, are common.

Other signs include persistent hypertension (due to the aldosterone-like effects) and insulin resistance, leading to hyperglycemia (high blood sugars); many develop frank diabetes. Untreated Cushing's syndrome can lead to heart disease and increased mortality.

Diagnosis

When Cushing's is suspected, a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH levels) and 24-hour urinary measurement for cortisol have equal detection rates (Raff & Findling 2003). A novel approach is sampling cortisol in saliva over 24 hours, which may be equally sensitive. Other pituitary hormones may need to be determined, and performing physical examination directed for any visual field defect may be necessary if a pituitary lesion is suspected (which may compress the optic chiasm causing typical bitemporal hemianopia).

When these tests are positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed. These should be performed when other tests are positive, to decrease likelihood of incidentalomas (incidental discovery of harmless lesions in both organs). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Very rarely, determining the cortisol levels in various veins in the body by venous catheterisation working towards the pituitary (petrosal sinus sampling) is necessary.

Pathophysiology

Cortisol is secreted by the adrenal glands under regulation by the pituitary gland and hypothalamus. Strictly, Cushing's syndrome refers to excess cortisol of any etiology. Cushing's disease refers only to hypercortisolism secondary to excess production of adrenocorticotropin (ACTH) from a pituitary gland adenoma.

Therapy

If an adrenal adenoma is identified it may be removed by surgery. Pituitary ACTH producing adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients will require steroid replacement postoperatively at least in the interim as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed replacement with hydrocortisone or prednisolone is imperative.

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Spontaneous rupture of Achilles tendon: missed presentation of Cushing's syndrome - Clinical Review: Lesson of the Week - Statistical Data Included
From British Medical Journal, 8/28/99 by Abdusalam Mousa

Non-iatrogenic Cushing's syndrome is an uncommon endocrine disease with an estimated annual incidence of 0.7-2.4 cases per million.[1] If untreated, Cushing's syndrome is associated with appreciable morbidity and premature death.[2 3] The presenting clinical features may be non-specific, and the disease often remains undiagnosed for a considerable time. Spontaneous rupture of the Achilles tendon is unusual, but is well described in patients receiving long term steroid treatment.[4-7] The incidence of spontaneous rupture of tendons in non-iatrogenic Cushing's syndrome is unknown. We report two patients with non-iatrogenic Cushing's syndrome who presented with spontaneous rupture of the Achilles tendon, one to an outpatient orthopaedic clinic and the other to an accident and emergency department. The diagnosis of Cushing's syndrome was made one month later in the first case and seven months later in the second.

Case reports

Case 1--A 49 year old man with a history of hypertension woke up with pain in his left heel. There was no preceding history of trauma or excessive physical exertion. He attended an outpatient orthopaedic clinic a few weeks later, at which time a spontaneous rupture of the left Achilles tendon was diagnosed and was treated conservatively. Non-insulin dependent diabetes was diagnosed three months later, and four months after that the patient presented with cellulitis and poorly controlled diabetes. Typical cushingoid features were noticed at examination (figure), and an inspection of old photographs showed that the man had had these for at least five years. Subsequent investigations confirmed Cushing's syndrome as a result of a pituitary microadenoma (table). The patient underwent transsphenoidal pituitary adenomectomy and remained euadrenal for 18 months. His Cushing's disease relapsed and he subsequently had a second transsphenoidal operation and pituitary irradiation.

[Figure ILLUSTRATION OMITTED]

Results of endocrinological investigations in two patients with spontaneous rupture of Achilles tendon

NA=not applicable.

Case 2--A hypertensive 47 year old woman presented to an accident and emergency department. She had suddenly developed pain in her heel, but had no previous history of trauma or rigorous physical exertion. Spontaneous rupture of the Achilles tendon was diagnosed and treated conservatively. A few weeks later the woman attended a general practitioner in a different town because she needed a prescription for analgesics. Her physical appearance indicated that she might have Cushing's syndrome. Further endocrine assessment showed clinical features typical of Cushing's syndrome, which had been present for at least four years. Investigations confirmed Cushing's syndrome as a result of an adrenal adenoma. This was excised successfully by laparoscopic surgery.

Discussion

Rupture of the Achilles tendon usually occurs in young to early middle aged adults during vigorous physical activity.[8] Tendon rupture at various sites can occur as a complication of long term local or systemic use of glucocorticoid drugs.[4-7] Glucocorticoid drugs inhibit fibroblast proliferation and maturation,[7] which is the likely explanation for the predisposition of patients with Cushing's syndrome to spontaneous rupture of the Achilles tendon. Other systemic disorders associated with spontaneous tendon rupture include rheumatoid arthritis,[9] systemic lupus erythematosus,[19] chronic renal failure requiring haemodialysis,[11] primary and secondary hyperparathyroidism,[12 13] type II hyperlipoproteinaemia,[14] and gout.[15]

The two cases described above had unequivocal clinical signs of Cushing's syndrome when they presented with spontaneous rupture of an Achilles tendon. In both patients, the diagnosis of Cushing's syndrome was missed. Cushing's syndrome and other systemic conditions should be considered in patients who present with spontaneous rupture of an Achilles tendon.

Contributors: AM compiled the data, drafted the manuscript, and coordinated discussions and subsequent drafts. SJ participated in data collection and discussions, and contributed to the writing of the manuscript. AT provided the clinical data for case 2, participated in discussions, and contributed to the writing. PP initiated this case report, participated in discussions, and contributed to the writing; he acts as guarantor.

[1] Von Werder K, Muller OA. Cushing's syndrome. In: Grossman A, ed. Clinical endocrinology. Oxford: Blackwell Science, 1998:415-31.

[2] Ross EJ, Linch DC. Cushing's syndrome--killing disease: discriminatory value of signs and symptoms aiding early diagnosis. Lancet 1982;ii:646-9.

[3] Plotz CM, Knowlton Al, Ragan C. The natural history of Cushing's syndrome. Am J Med 1952;13:597-614.

[4] Haines JF. Bilateral rupture of the Achilles tendon in patients on steroid therapy. Ann Rheum Dis 1983;42:652-4.

[5] Price AE, Evanski PM, Waugh TR. Bilateral simultaneous Achilles tendon ruptures, A case report and review of the literature. Clin Orthop 1986;213:249-50.

[6] Smaill GB. Bilateral rupture of Achilles tendon. BMJ 1961;1:1657-8.

[7] Baruah DR. Bilateral spontaneous rupture of the Achilles tendons in patient on long-term systemic steroid therapy. Br J Sports Meal 1984;18:128-9.

[8] Hanlon DP. Bilateral Achilles tendon rupture: an unusual occurrence. J Emerg Med 1992;10:559-60.

[9] Rask MA. Achilles tendon rupture owing to rheumatoid diseases. JAMA 1978;239:435-6.

[10] Rascher JJ, Marcolin L, James E Bilateral sequential rupture of the patellar tendon in systemic lupus erythematosus. A case report. J Bone Joint Surg 1974;56:821-2.

[11] Morein G, Goldschmidt Z, Pauker M, Seelenfreund M, Rosenfeld JB, Fried A. Spontaneous tendon ruptures in patients treated by chronic hemodialysis` Clin Orthop 1977;124:209-13.

[12] Preston ET. Avulsion of both quadriceps tendons in hyperparathyroidism. JAMA 1972;221:406-7.

[13] Cirincione RJ, Baker BE. Tendon ruptures with secondary hyperparathyroidism. A case report J Bone Joint Surg 1975;57:852-3.

[14] Haacke H, Parwaresch MR. Spontaneous rupture of Achilles tendon--a sign of hyperlipoproteinaemia (HLP) type II. Klin Wochenschr 1979;57:397-400.

[15] Mahoney PG, James PD, Howell CJ, Swannell AJ. Spontaneous rupture of the Achilles tendon in a patient with gout. Ann Rheum D/s 1981;40:416-8. (Accepted 21 January 1999)

Think of Cushing's syndrome in patients with spontaneous rupture of the Achilles tendon

Endocrine Unit, Freeman Hospital, Newcastle upon Tyne NE7 7DN

Abdusalam Mousa specialist registrar

Steve Jones senior registrar

Petros Perros consultant physician

Endocrine Unit, Royal Infirmary, Edinburgh EH3 9YW

Anthony Toft consultant physician

Correspondence to: Dr Mousa ammousa@

BMJ 1999;319:560-13

COPYRIGHT 1999 British Medical Association
COPYRIGHT 2000 Gale Group

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