Adrenal Incidentaloma-Conn’s S

Adrenal Incidentaloma-Conn’s Syndrome

 

The adrenal glands are bilateral retroperitoneal organs located on the superior medial aspect of the upper pole of each kidney.  The right adrenal gland lies close to the great vessels with the vein draining directly into the inferior vena cava.  The left adrenal vein drains into the left renal vein. Adrenal glands are paired endocrine organs comprised of both cortex and medulla with the normal adult gland weighing 4 grams.   The cortex is composed an outer zona gromerulosa, a middle zona fasciculata and an inner layer, the zona reticularis. The center of the gland is the adrenal medulla. 

 

The adrenal cortex synthesizes three different types of steroids:

 

1) gluccocorticoids (principally cortisol).  Cortisol is the key endogenous hormone for carbohydrate effects and has receptors in almost all tissues of the body.  Cortisol secretion is maintained by a feedback mechanism involving the adrenal gland, anterior pituitary and hypothalalmus.

 

2) mineralocorticoids, most importantly aldosterone is controlled by the hormone angiotensin II which in turn is controlled by rennin.  Renin secretion from the kidney is increased in low blood pressure or decreased sodium concentration.

 

3) sex steroids (estrogens and androgens).

The adrenal gland sits superior and medial to the upper pole of each kidney.  

Chromaffin cells compose the adrenal medulla, which synthesize and secrete catecholamines, mainly norepinephrine.  Factors that increase sympathetic activity include pain, emotional stress, hypoglycemia, hypotension and cold and ultimately result in catecholamine.  Any  excess of adrenal hormones can result in clinical syndromes with significant physiological effects on the patient.

 

The adrenal gland (or suprarenal gland) consists of a cortex and medulla.
The cortex is the external portion of the organ while the internal portion is the medulla.
Image from www.Ctisus.org

 

The term adrenal incidentaloma refers to an adrenal mass detected during abdominal imaging done for other reasons.  Adrenal masses are common; they have been noted in 5-15% of patients in autopsy series.  Adrenal masses increase in frequency with advancing age, with a peak incidence in the sixth and seventh decades.  Nonfunctioning cortical adenomas are the most common lesions, accounting for up to 90% of lesions in some series.

 

The first step in the assessment of adrenal masses is to determine if the lesion is a functioning versus a non-functioning tumor. A functioning tumor is one that secretes hormones and/or neurotransmittors which have biochemical and clinical effects. Simple screening tests include plasma levels of cortisol, renin and serum potassium.  Urine screening for free cortisol, metanephrines and vanillymandellic acid and urinary aldosterone.

 

In 1955 Jerome Conn described a 34 year old female with hypertension, generalized weakness and polyuria.  Her electrolyte analysis revealed hypokalemia, surgical exploration revealed a cortical adrenal adenoma.

 

Laboratory abnormalities include an elevated aldosterone level, hypokalemia and suppressed renin activity.  This was the first description of primary aldosteronism ( Conn’s syndrome).  It is important to distinguish the etiology of excess aldosterone as the management may differ significantly, surgical treatment versus medical treatment.

 

Primary aldosteronism is twice as common in women as in males.  The incidence of Conn’s is thought to be 1%.  The cause of primary aldosteronism is aldosterone producing adenomas in 60-70% of cases followed by idiopathic bilateral adrenal hyperplasia in 30%.  Adrenal carcinoma is a rare cause of hyperaldosteronism ( 1%). 

           

Secondary hyperaldosteronism is a physiologic response of the renin angiotensin system to renal artery stenosis, cirrhosis, congestive heart failure and normal pregnancy.  These conditions result in elevated plasma levels of renin and the adrenals function normally in secreting aldosterone.

Signs and symptoms in patients with hyperaldosteronism include diastolic hypertension caused by aldosterone mediated retention of sodium.  Hypokalemia occurs in 90% of patients. Potassium depletion results in weakness, fatigue, polyuria and polydipsia.  The biochemical diagnosis of primary aldosteronism requires demonstration of an elevated aldosterone level with suppressed plasma renin activity.  An aldosterone to renin ratio of greater than 20 strongly supports the diagnosis of primary aldosteronism.

 

Other adrenal syndromes include Cushing’s syndrome, pheochromocytomas and congenital adrenal hyperplasia.Cushing’s syndrome is caused by excess cortisol.  Clinical features include moon facies, truncal obesity, abdominal striae, hisutism and acne.  The adrenals in Cushing’s syndrome exhibit bilateral adrenal hyperplasia.

Pheochromocytomas are tumors primarily of the adrenal medulla that often produce catecholamines in great excess.  These patients present with hypertension, tachycardia, pallor, and hyperglycemia.  There is a potential for wide swings in blood pressure and nonoperative therapy is usually unsatisfactory.  Pheochromocytomas are found in the multiple endocrine neoplasia (MEN) syndromes.  These familial disorders are inherited in an autosomal dominant fashion and have a predisposition to develop tumors of multiple endocrine glands.  The MEN type II a and II b syndromes develop medullary thyroid carcinoma and pheochromocytomas of the adrenal gland. These adrenal tumors are more likely to be multicentric, bilateral and usually occur in the 2^nd to 3^rd decade of life. 

 

 

Cross Sectional Anatomy

 

The adrenal gland location depends on the side of the body. A normal size for either the left or the right adrenal is 3 cm X 6 mm and are a retroperitoneal organ.  Gerota's fascia connects the gland to the upper pole of the kidney.

 

The right adrenal location posterior to the IVC and the right lobe of the liver places it anterior to the upper pole of the right kidney.  The triangular base of the right adrenal has a downward placement with the anterior and medial portion in contact with the right kidney. 

 

Medial to the right diaphragmatic crus the triangular adrenal has the
right kidney posterior and lateral on the transverse plane.
Image from www.Ctisus.org

 

The left adrenal gland measures slightly larger than its mate and has a semilunar shape.  The medial convex border hugs the medial portion of the left renal.  A left adrenal may extend as inferior as the renal pelvis and as superior as the spleen.

 

 
The vertical ridge seen on the anteriomedial portion of the left adrenal
is in contact with both the diaphragmatic crus and the tail of the pancreas.
Image from www.Ctisus.org

 

Sonographic Imaging

 

Imaging of the adrenal glands, as with any retroperitoneal structure, requires a fasting period of 6-8 hours.  Even with fasting, the left adrenal may be difficult to image due to obstruction by bowel gas.  To move the stomach air, have the patient drink fluids or oral contrast.  This may provide an acoustic window for imaging the adrenal gland.

 

It is helpful to  image the adrenal glands in several patient positions and imaging planes.  A change to a LLD position may move the bowel air onto a different plane allowing for either anterior or coronal scanning.   Erect and semi-erect positions move the peritoneal organs inferior resulting in a clear window for imaging.  Large organs such as the liver or spleen provide windows for posterior coronal approaches.

 

The adrenal gland appears as a less echogenic structure than the surrounding retroperitoneal fat. The normal gland has a medulla which images as a linear echogenic structure.  Loss of this central echogenicity indicates either an infiltrative problem or adrenal hyperplasia.

 

Imaging Modalities

 

Although ultrasound is not the first choice of diagnostic study in the workup of the adrenal mass in adults, a mass may be diagnosed sonographically during routine abdominal examinations.  The right adrenal is easier to identify by ultrasound when it is enlarged than the left, which is often obscured by the gas in the colon or stomach.  Coronal views have been used to identify normal adrenal glands by ultrasound.  Masses seen can be accurately assessed as discrete or diffuse, solid or cystic, mixed or homogeneous.

 

 Simple adrenal cysts are anechoic, smooth-walled masses with enhanced posterior wall sound transmission, whereas cystic neoplasms often demonstrate both solid and cystic components.  Hyperfunctioning adrenal adenomas tend to be small, in the 2 to 2.5 cm range and are therefore best seen by CT.  Adenomas are usually small homogeneous lesions and do not enhance with intravenous contrast.  Most adenomas are low attenuation lesions ( less than 10 Houndsfield units) on nonenhanced CT scans. 

 

Carcinomas have much higher attenuation (18 Houndsfield units) on CT imaging. Magnetic Resonance imaging ( MRI) characteristics include signal intensity equal to liver on T2 weighted images and high lipid content. In asymptomatic adrenal tumors, size appears to be the best criterion for the diagnosis of adrenal carcinoma; some investigators have suggested that lesions greater than 3 cm should be surgically removed. Sonography, CT and scintography are not effective by image alone in the definition of a benign from a malignant adrenal lesion

 

Adrenal masses may be benign or malignant.  Benign lesions include adrenal cysts, myelolipomas, adenomas, and areas of hemorrhage. Malignant lesions include adrenocortical carcinomas, pheochromocytromas and adrenal metastases most commonly from lung, breast or renal carcinoma. Lung cancer is the most common extradrenal primary with adrenal metastases.  Bilateral functional adrenal masses are unusual and may be caused by hereditary pheochromocytomas, micronodular disease and cortical or medullary hyperplasia.  Bilateral nonfunctional adrenal masses may be caused by metastases, infection (tuberculosis, fungus, meningococcus [Waterhouse-Friedrich syndrome]), hemorrhage, lymphomatous infiltrates and replacement by amyloidosis.

 

Surgical Management

 

The presence of a hormonally active adrenal tumor is an indication for adrenalectomy.  Concurrent with their biochemical picture, all adrenal lesions should be evaluated for their malignant potential.  Size is an important variable to consider in assessing the malignant potential of any adrenal mass.  A size threshold for removal of adrenal lesions 4 to 5 cm is reasonable.  Patients with adrenal metastasis should be considered for FNA cytology only if the result will affect subsequent therapy.  Ultrasound or CT guided biopsy may be useful.

           

In most centers laparoscopic adrenalectomy has replaced open adrenalectomy for benign functioning tumors.  Laparoscopic adrenalectomy has been associated with decreased pain, shorter hospitalization, less blood loss and faster recovery when compared with the open procedure.  The treatment for primary aldosteronism due to a adrenal adenoma is surgical resection, whereas treatment of adrenal hyperplasia is medical, because fewer than 20-30% of patients are cured by adrenalectomy.

           

Ultrasonography is useful in monitoring small nonfunctioning adrenal tumors.  Prospective studies assessing the utility of colour flow Doppler have concluded that Doppler is not useful in differentiating benign from malignant lesions.  Therefore increase in size on serial examinations or a size of greater than 6 cm warrant surgical resection.  Endoscopic ultrasound is useful in imaging the adrenal glands and a useful adjunct for fine needle biopsy.

 

 

Glossary

 

adenoma

-benign tumor of glandular origin

 

adipose

-fatty tissue

 

aldosterone

-hormone produced by the adrenal cortex that helps regulate salt and water balance of the body

 

amyloidosis

-abnormal deposit of a waxy substance (amyloid) in tissues or organs

 

Conn, Jerome

-Faculty of Ann Arbor, Michigan medical school who served as an endocrinologist.  He studied metabolic disorders, human nutrition, and normal metabolism. 

 

Conn’s syndrome

-primary aldosteronism due to a adrenal adenoma secreting aldosterone

 

Cushing’s syndrome

-clinical features of excess cortisol most commonly due to a pituitary adenoma, adrenal tumors or endogenous steroid use.

 

endocrine

-glands that secrete hormones directly into the blood stream

 

endogenous

-metabolic synthsis from the gland that changes with metabolism

 

FNA

-fine needle aspiration

 

GFR

-glomerular filtration rate

 

hemorrhage

-bleeding

 

hirsutism

-excessive hair growth in abnormal locations due to endocrine abnormalities

 

hypertension

-blood pressure above the normal range

 

hypoglycemia

-low blood sugar

 

hypokalemia

-low blood potassium levels

 

hypotension

-low blood pressure

 

inferior vena cava (IVC)

-large retroperitoneal vein draining the abdominal visceral organs and enters the right heart

 

incidentaloma

-an incidental lesion found on imaging

 

lipid

-fat

 

perinephric

-around the kidney

 

pheochromocytoma

-chromaffin cell tumor linked to sustained high blood pressure

 

polydipsia

-abnormal thirst

 

polyuria

-excessive urination

 

proteinuria

-protein in the urine

 

renogram

-nuclear medicine procedure using a radioactive labeled material to check the renal excretion

 

retroperitoneal

-behind the abdominal peritoneum

 

SMA

-superior mesenteric artery

 

References/Further Reading

 

1.                   Herrera MF et al.   Incidentally discovered adrenal tumors: an institutional perspective.  Surgery  110:1014, 1991.

2.                   Bravo EL.  Primary aldosteronism: issues in diagnosis and management.  Endocrin Metab Clin North Amer  23:271:1994.

3.                   Abecassis M. Mcloughlin MJ, Langer B, et al.  Serendiptious adrenal masses: Prevalence, significance and management.  AM J Surg 149:783, 1985.

4.                   Stewart P.  Mineralocorticoid hypertension.  Lancet 353:1341-1347, 1999.

5.                   Dietrich CF, Wehrmann T, Hoffman C eta l.  Detection of the adrenal glands by endoscopic or transabdominal ultrasound.  Endoscopy 1997; 29 (9): 859-64.

6.                   Ghiatas AA, Chopra S, Schnitker JB.  Is sonographic flow imaging useful in the differential diagnosis of adrenal masses?  Br J Radiol  1996:69:1005-8.

7.                   Chang KJ, Erickson RA, Nyugen p.  Endoscopic ultrasound and EUS-guided fine needle aspiration of the left adrenal gland.  Gastrointest Endosc 1996;4495):568-72.

8.                   Online Grays Anatomy http://www.bartleby.com/107/