Diseases of the Adrenal

Diseases of the Adrenal

1.1 Cushing’s Syndrome

Am J Fam Phys 2000;62:5; J Clin Endocrinol Metab 2003;88:5593; N Engl J Med 1995;332:791

Cause: A condition resulting from long-term exposure to excessive glucocorticoids. Most common cause is therapeutic administration of exogenous glucocorticoids. Cushing’s disease is caused by excessive secretion of ACTH by a pituitary tumor, usually an adenoma (Mayo Clin Proc 1986;61:49). Pituitary tumors in Cushing’s disease are usually microadenomas (≥ 10 mm in diameter). Cushing’s disease is responsible for 2/3 of cases of Cushing’s syndrome (N Engl J Med 1995;332:791). Most cases not inherited may be seen with primary pigmented micronodular adrenal disease and multiple endocrine neoplasia (MEN) type I and may be due to pituitary, ectopic (oat cell, ovary, pancreas, carcinoid), or adrenal tumors (http://endocrine.niddk.nih.gov/pubs/cushings/ cushings.htm).

Pathophys: Glucocorticoids cause connective tissue dissolution; have anti-vitamin D effect; cause proteolysis of muscle, lymphocyte/ monocyte inhibition (N Engl J Med 1975;292:236), increased acid/pepsin secretion, increased gluconeogenesis, decreased glucose uptake. Aldosterone and androgens are also elevated when ACTH is the mechanism.

Sx: Muscle weakness, decreased libido, obesity/weight gain; growth retardation in children; easy bruising, bilateral hemianopsia with
central visual field defects, cranial nerve III palsy occurs in up to 25% of pts with pituitary macroadenoma (J Clin Neurophthalmol 1985;5:185).

Si: Impotence, menstrual disorder, acne, muscle weakness, ecchymoses, moon face, buffalo hump, abdominal striae, truncal fat, osteoporosis and fractures, increased number and severity of infections, peptic ulcers, DM, nonketotic insulin resistance, psychoses, virilization, HT (47% in children, more common in pts < 40 years), edema

Crs: Excellent prognosis unless cancer or ectopic ACTH (usually cancer) (N Engl J Med 1971;285:243)

Cmplc: Opportunistic or bacterial infection due to interference with cytokine production


  • Chem: Serum cortisol, nl level 10-25 mgm% (= 280-700 nM/L) in a.m., dropping to 7 mgm% in p.m.; after 1 mg dexamethasone at 11 p.m., 8 a.m. cortisol is < 5 in nl; if > 10, r/o Cushing’s (100% sens, 90% specif [Ann Intern Med 1990;112:738]); false pos with phenytoin (Dilantin) (Aud Dig 1983;30:18). If indeterminate, 0.5 mg dexamethasone q6h for 48 hr and measure cortisol or get 24-hr urinary free cortisol (6% false neg, fewer false pos [Aud Dig 1983;30:18]) and/or 24-hr urine cortisol for 100 mgm or more/24 hr.

  • If tests just listed abnormal, high-dose test to differentiate cause (baseline 8 a.m. cortisol, 8 mg dexamethasone at 11 p.m., then 8 a.m. cortisol). Pituitary Cushing’s pts, unlike adrenal tumors or ectopic ACTH production types, suppress value to < 50% of baseline value (92% sens, 100% specif [Ann Intern Med 1986;104:180], 68% sens in children (N Engl J Med 1994;330:1295 for various test sens and specif).

  • Combined corticotropin-releasing hormone (CRH) stimulus test with dexamethasone suppression test: 0.5 mg dexamethasone q6h for 2 d (8 doses), 2 hr after last dexamethasone taken, 1 mg/kg CRH administered IV—plasma cortisol obtained
    15 min after CRH injection. Plasma cortisol > 1.4 mg/L (40 nmol/L) is pos for Cushing’s syndrome (J Endocrinol Metab 1998;83:349)—nearly 100% sens and specif for Cushing’s syndrome (Endocrinol Metab Clin North Am 1997;26:62)

  • Petrosal sinus sampling is best way to distinguish pituitary from ectopic causes of Cushing’s—samples of blood drawn from petrosal sinuses (veins that drain pituitary)—CRH may be given to improve diagnostic accuracy. Levels of ACTH in the petrosal sinuses are measured and compared with ACTH levels in a forearm vein. Higher levels of ACTH in the sinuses than the forearm vein indicate a pituitary adenoma. Similar levels of ACTH in petrosal sinuses and forearm suggest ectopic ACTH.

Xray: (Ann Intern Med 1988;109:547)

  • CT: Due to small adenomas, 60% false-neg rate

  • MRI with gadolinium enhancement: There is a 71% sens (52% sens in children), 87% specif, but 10% of nl adult population will have a lesion (Ann Intern Med 1994;120:817).

Rx: 1st: surgical transsphenoidal microadenomectomy, 90% successful (N Engl J Med 1984;310:889) vs 76% (Ann Intern Med 1988;109: 487); bilateral adrenalectomy. 2nd: irradiation of pituitary, 83% successful in pts for whom surgery failed (N Engl J Med 1997; 336:172). 3rd: amino-glutethimide, mitotane, metyrapone, trilostane (Med Lett 1985;27:87); bromocriptine; ketoconazole for antisteroid synthesis effect (N Engl J Med 1987;317:812). For pituitary adenoma, radiation to pituitary given over a 6-wk period results in improvement in 40-50% adults and up to 85% children. Stereotactic radiosurgery (gamma knife) can be given in a single high-dose treatment. Ectopic ACTH synthesis: Treatment is elimination of all cancerous ACTH-secreting tissue. Because disease may be widespread, cortisol-inhibiting drugs are an important part of treatment. If other treatments fail, bilateral adrenalectomy may replace drug therapy. For adrenal tumors, treatment is surgical removal.

1.2 Conn’s Syndrome

N Engl J Med 1994;331:250; Horm Res 2009;71(suppl 1):8.

Cause: Bilateral adrenal hyperplasia or unilateral adrenal adenomasecreting aldosterone. Secondary hyperaldosteronism may be the result of cardiac failure with edema, liver cirrhosis with ascites, nephritic syndrome with edema. Other causes include renin-secreting tumor and exogenous mineralocorticoid. Two major subtypes of primary hyperaldosteronism: (1) unilateral aldosterone-producing adenoma or Conn’s syndrome (50-60% cases) and (2) idiopathic hyperaldosteronism (IHA) or bilateral adrenal hyperplasia (40-50% cases) (The Endocrine Society-Disease Specific Society. 2008 Sept, 26 pages. NGC: 006766/ www.guideline.gov/content.aspx?id+13322

Epidem: Approximately 1% of all hypertensive pts (Ann Intern Med 1970;72:9). Primary hyperaldosteronism twice as common in women as in men, peak incidence in third to sixth decades of life

Pathophys: Increased aldosterone production causes Na+ retention and K+ loss, leading to hypervolemia of 2-3 L; HT; H+ loss, causing metabolic alkalosis. Is there an anterior pituitary “aldosterone simulating factor”? (N Engl J Med 1984;311:120)

Sx: Fatigue, weakness, tetany

Si: HT; Trousseau’s si, due to alkalosis; little edema, unlike secondary causes of increased aldosterone; proximal myopathy

Cmplc: R/o Liddle’s syndrome, an aldosterone-like effect caused by autosomal dominantly inherited renal tubular defect (N Engl J Med 1994;330:178). Bartter syndrome and licorice ingestion (N Engl J Med 1991;325:1223), both of which cause a normotensive hyperaldosteronism by peripheral angiotensin resistance and/or prostaglandin induction (Ann Intern Med 1977;281:369; N Engl J Med 1973;289: 1022); rx with NSAIDs, especially indomethacin (Ann Intern Med 1977; 87:281). Secondary causes of
hyperaldosteronism. Rare unilateral adenoma or cancer of adrenal (Ann Intern Med 1984;101:316)

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Aug 21, 2020 | Posted by in UROLOGY | Comments Off on Diseases of the Adrenal

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