Adrenal Glands Anatomy Adrenal Gland Anatomy was first

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Adrenal Glands

Adrenal Glands

Anatomy

Anatomy

Adrenal Gland Anatomy was first described in 1563. Is located above (or attached to)

Adrenal Gland Anatomy was first described in 1563. Is located above (or attached to) the upper pole of the kidney. Is pyramidal in structure and weighs ~ 4 g. Consists of the adrenal cortex and adrenal medulla Activities are regulation of fluid volume and stress response

Adrenal Gland • Blood supply Arterial - receives 7 cc/gram minute - 3 arterial

Adrenal Gland • Blood supply Arterial - receives 7 cc/gram minute - 3 arterial sources of flow: 1. Inferior phrenic artery 2. Aorta 3. Renal artery Venous – single main vein most important surgical structure - right → post IVC - left → renal vein

Adrenal Gland �Cortex - mesoderm �Medulla - neuroectoderm �Renal agenesis, found in normal anatomic

Adrenal Gland �Cortex - mesoderm �Medulla - neuroectoderm �Renal agenesis, found in normal anatomic position �Size- 5 x 3 x 1 x 5 cm �Retroperitoneal structure, contained in its own subcompartment w/in Gerota’s fascia

Comparison between Rt. & Lt. Suprarenals Right Suprarenal Left Suprarenal Triangular (pyramidal) Crescentic (semilunar)

Comparison between Rt. & Lt. Suprarenals Right Suprarenal Left Suprarenal Triangular (pyramidal) Crescentic (semilunar) Does NOT reach the hilum of the right kidney Reaches the hilum of the left kidney The hilum is directed upwards The hilum is directed downwards Its vein is short and drains to the IVC Its vein is long and drains to the left renal vein. 7

Physiology

Physiology

Adrenal Cortex: Steroid Hormone Production

Adrenal Cortex: Steroid Hormone Production

The General Adaptation Syndrome

The General Adaptation Syndrome

The General Adaptation Syndrome

The General Adaptation Syndrome

Cortisol Effects: Body Responses to Stress to living

Cortisol Effects: Body Responses to Stress to living

Aldosterone �Exclusively synthesized in Z. Glomerulosa �Essential for life. �Promotes sodium retention and Potassium

Aldosterone �Exclusively synthesized in Z. Glomerulosa �Essential for life. �Promotes sodium retention and Potassium elimination by the kidney. �Expands ECF volume

Regulation of Aldosterone Secretion

Regulation of Aldosterone Secretion

Control of Cortisol Secretion: Feedback Loops �External stimuli �Hypothalamic �Anterior Pituitary �Adrenal cortex �Tissues

Control of Cortisol Secretion: Feedback Loops �External stimuli �Hypothalamic �Anterior Pituitary �Adrenal cortex �Tissues

Cortisol and Chronic Stress �Prolonged exposure to high cortisol levels can lead to break

Cortisol and Chronic Stress �Prolonged exposure to high cortisol levels can lead to break down of muscle, excessive epinephrine release, hyperglycemia, weakening of bone, destruction of the immune system, inhibition of reproductive function, and other complications.

Disorders of Adrenal glands: �A- Abnormal anatomy: ( diffuse or localized swelling) �B- Abnormal

Disorders of Adrenal glands: �A- Abnormal anatomy: ( diffuse or localized swelling) �B- Abnormal physiology: ( hyper or hypo secretion of hormones)

Cortical Adenoma �Solitary nodule �Usually encapsulated by rim of connective tissue �Usually small: <50

Cortical Adenoma �Solitary nodule �Usually encapsulated by rim of connective tissue �Usually small: <50 gm, < 5 cm diameter (on the average, much smaller than cortical carcinomas) �Yellow color (majority, because of lipid-laden cells) �Black color (minority, due to excess lipofuscin pigment) �Cured by surgical excision �Endocrine function is unpredictable; 3 syndromes are �no hyperfunction (“silent”) �hypercortisolism �hyperaldosteronism

CT Adenoma Characteristics �Sharp margins �Smooth, homogenous, lipid rich �Most <10 Hu on noncontrast

CT Adenoma Characteristics �Sharp margins �Smooth, homogenous, lipid rich �Most <10 Hu on noncontrast images �Washout >50% @ 15 min

Primary Hyperaldosteronism (Conn's syndrome) 1. 2. 3. 4. Solitary adrenal adenomas (80 -90%) Bilateral

Primary Hyperaldosteronism (Conn's syndrome) 1. 2. 3. 4. Solitary adrenal adenomas (80 -90%) Bilateral adrenal hyperplasia (10 -20%) Adrenal Carcinoma (rare) Unilateral Adrenal Hyperplasia (very rare)

Epidemiology of Conn's syndrome � Represents under 1% of hypertension causes � Peak age

Epidemiology of Conn's syndrome � Represents under 1% of hypertension causes � Peak age 30 -50 years � Most patients are women

Clinical features of Conn's syndrome �Often asymptomatic �Frontal headache �Muscle weakness to flaccid paralysis

Clinical features of Conn's syndrome �Often asymptomatic �Frontal headache �Muscle weakness to flaccid paralysis decreased muscle strength (because of low potassium level) �Polyuria and Polydipsia �Hypertension

Investigation of Conn's syndrome A. 1. 2. 3. Serum Electrolytes Serum Potassium decreased Serum

Investigation of Conn's syndrome A. 1. 2. 3. Serum Electrolytes Serum Potassium decreased Serum Sodium increased (Mild) Metabolic Alkalosis B. Increased serum level of aldosterone C. Greatly decreased serum level of renin D. Sodium loading test

Localization �Ultrasound. �CT Scan. �MRI �Angiographic Blood Sampling.

Localization �Ultrasound. �CT Scan. �MRI �Angiographic Blood Sampling.

Treatment of Conn's syndrome A. Adrenal Adenoma Surgical excision (unilateral adrenalectomy) B. Adrenal Hyperplasia

Treatment of Conn's syndrome A. Adrenal Adenoma Surgical excision (unilateral adrenalectomy) B. Adrenal Hyperplasia Spironolactone (Aldactone)

Cushing's syndrome Endogenous : ACTH dependent 85% �Cushing's disease (pituitary) �Ectopic ACTH syndrome (small

Cushing's syndrome Endogenous : ACTH dependent 85% �Cushing's disease (pituitary) �Ectopic ACTH syndrome (small cell lung carcinoma) �Ectopic CRH syndrome (bronchial carcinoid tumours) ACTH independent 15% �Common: Adrenal adenoma, adrenal carcinoma �Less common: Micronodular hyperplasia, macronodular hyperplasia

Exogenous �Glucocorticoid treatment Pseudo-Cushing's syndrome �Major depressive disorder �Alcoholism �Obesity

Exogenous �Glucocorticoid treatment Pseudo-Cushing's syndrome �Major depressive disorder �Alcoholism �Obesity

Clinical features of Cushing's syndrome � 90% - Central (truncal) obesity. Fat deposits may

Clinical features of Cushing's syndrome � 90% - Central (truncal) obesity. Fat deposits may appear in the cheeks (moon facies), in the dorsocervical area (buffalo hump), and the supraclavicular area � 85% - Hypertension � 65% - Presence of multiple purple striae with a diameter >1 cm on the abdomen or proximal extremities � 60% - Muscle wasting and weakness affect the proximal muscles of leg and shoulder girdle � 40% - Easy bruising of the skin � 40% - Osteoporosis

�Hyperpigmentation (palmar creases and pressure points) in a patient with Cushing's syndrome strongly suggests

�Hyperpigmentation (palmar creases and pressure points) in a patient with Cushing's syndrome strongly suggests an ACTH cause (Cushing's disease) �Patients may have mild hirsutism and acne, but severe hirsutism and especially virilisation strongly suggest an adrenal carcinoma. �Depression, lethargy, and insomnia often occur at the same time as other symptoms. In children the dominant clinical features are cessation of linear growth and weight gain; the clinical course is more aggressive than in adults.

Investigation of Cushing's syndrome Screening tests �Urinary free cortisol The measurement of 24 hour

Investigation of Cushing's syndrome Screening tests �Urinary free cortisol The measurement of 24 hour excretion of cortisol in urine integrates the variations in plasma free cortisol concentrations seen during the entire day; three consecutive 24 hour urine specimens. � There is a false negative rate of 5. 6%, with false positives of 1% in normal people and 5% in obese individuals.

�Dexamethasone suppression tests In normal subjects, administration of a supraphysiological dose of glucocorticoid results

�Dexamethasone suppression tests In normal subjects, administration of a supraphysiological dose of glucocorticoid results in suppression of ACTH and hence of cortisol secretion (cortisol <50 nmol/l). This is the basis of dexamethasone suppression tests, of which there are several types.

�The 48 hour low dose test, which is the most sensitive and specific screening

�The 48 hour low dose test, which is the most sensitive and specific screening test, entails the administration of 0. 5 mg dexamethasone at intervals of exactly 6 hours from 9 am on day one for eight doses, and measurement of serum concentrations of cortisol at 9 am on day three, exactly 6 hours after the last dose of dexamethasone. A negative result is indicated when the serum concentration of cortisol at 9 am on day three is suppressed to < 50 nmol/l. Over 98% of patients with Cushing's syndrome fail to "suppress" serum cortisol on the low dose test.

Confirmatory tests �Insulin tolerance test In normal subjects and those with pseudo. Cushing's, insulin

Confirmatory tests �Insulin tolerance test In normal subjects and those with pseudo. Cushing's, insulin induced hypoglycaemia results in a rise of ACTH and cortisol concentrations. This response to hypoglycaemia is lost in most cases of Cushing's syndrome (90%). .

Treatment of Cushing's syndrome �Transsphenoidal surgery �Pituitary radio-therapy � Bilateral or unilateral adrenalectomy �

Treatment of Cushing's syndrome �Transsphenoidal surgery �Pituitary radio-therapy � Bilateral or unilateral adrenalectomy � Medical therapy

Medical therapy �Metyrapone and ketoconazole are commonly used. Metyrapone blocks the 11 -ß hydroxylase

Medical therapy �Metyrapone and ketoconazole are commonly used. Metyrapone blocks the 11 -ß hydroxylase enzyme involved in the final step in cortisol synthesis, whereas ketoconazole acts at several levels and inhibits cortisol synthesis by a direct action on the P 450 cytochrome enzyme. The adrenolytic agent, mitotane, has a cytotoxic effect on both normal and malignant adrenocorticol tissue. Its use is mainly in the management of adrenal carcinoma and rarely in Cushing's disease.

Pheochromocytoma Rule’s of 10 • • Bilateral Familial (non-sporadic) Pediatric Malignant Normotensive Extra-adrenal Multiple

Pheochromocytoma Rule’s of 10 • • Bilateral Familial (non-sporadic) Pediatric Malignant Normotensive Extra-adrenal Multiple *Childhood presentation breaks the rules- 25% bilateral, multiple, extra-adrenal

Pheochromocytoma � symptoms → release of epi/norepi � hypertension present 90% cases � orthostatic

Pheochromocytoma � symptoms → release of epi/norepi � hypertension present 90% cases � orthostatic hypotension (low plasma vol) � 30% of pheo’s found at autopsy and cause death due to cardiovascular disease

Pheo �Triad: headache, tachycardia, diaphoresis �Other symptoms: Pallor, flushing, palpitations, abd/chest pain, weakness, N/V,

Pheo �Triad: headache, tachycardia, diaphoresis �Other symptoms: Pallor, flushing, palpitations, abd/chest pain, weakness, N/V, psychosis �Small tumors more likely symptomatic

Pheo- The Diagnosis �Plasma free metanephrines : most sensitive test seen 99% of patients

Pheo- The Diagnosis �Plasma free metanephrines : most sensitive test seen 99% of patients � 24 h urinary catecholamines (2 x normal is diagnostic) �VMA �Clonidine suppression test (0. 3 mg oral, test 3 hrs later) >50% reduction catecholamines NO pheo

Pre-op Management �Early alpha blockad �Goal to control hypertension- phenoxybenzamine �Do NOT use b-blocker

Pre-op Management �Early alpha blockad �Goal to control hypertension- phenoxybenzamine �Do NOT use b-blocker before alpha �IV hydration �Prevent cardiac arrhythmias

Adrenal tissue: ADRENAL medullary cortical Extra-adrenal neuroendocrine cells may persist anywhere along normal path

Adrenal tissue: ADRENAL medullary cortical Extra-adrenal neuroendocrine cells may persist anywhere along normal path of neural crest migration Embryologic “rests” of aberrant cortical tissue may be found: a) near kidney b) in pelvis, along path of migration from urogenital ridge c) weird places, such as vagina and coccyx Fig. 37 -10, Sabiston Textbook of Surgery, 17 th ed, Elsevier 2004

Non-neoplastic lesions of adrenal cortex �Heterotopia �Cortical nodules �Congenital and acquired hyperplasia �Autoimmune adrenalitis

Non-neoplastic lesions of adrenal cortex �Heterotopia �Cortical nodules �Congenital and acquired hyperplasia �Autoimmune adrenalitis �Hemorrhage (Waterhouse-Friderichsen syndrome) �Tuberculosis

Heterotopic (Ectopic) Adrenal Cortical Tissue �Most common site: retroperitoneum adjacent normal adrenal gland �Other

Heterotopic (Ectopic) Adrenal Cortical Tissue �Most common site: retroperitoneum adjacent normal adrenal gland �Other sites: celiac plexus, kidney, along spermatic and ovarian veins, testis, epididymis, hernial and hydrocele sacs, mesoappendix, liver, lung, and brain �If ACTH is persistently elevated: hyperplasia or neoplasia may develop in ectopic adrenal cortical tissue

Cortical “Nodules” Multiple small nodules, scattered within cortex • Fairly common, usually not associated

Cortical “Nodules” Multiple small nodules, scattered within cortex • Fairly common, usually not associated with cortical hyperfunction • Increasing incidence with age, hypertension & diabetes • May be MISTAKEN for true neoplasm on imaging

Congenital Adrenal Hyperplasia �Autosomal recessive inheritance �Biochemical defect affecting any of steps in synthesizing

Congenital Adrenal Hyperplasia �Autosomal recessive inheritance �Biochemical defect affecting any of steps in synthesizing aldosterone, glucocorticoids, sex steroids from cholesterol � 90% of CAH cases exhibit absent 21 -hydroxylase excess androgens; deficiency of aldosterone and cortisol �Causes adrenogenital syndromes �pure virilization (1/3 cases) �virilization & “salt-losing”: electrolyte disorders due to aldosterone deficiency: hyponatremia, hyperkalemia, hypotension, even shock �Late-onset adrenal virilization: partial deficiency 21 -hyd. �May remain undetected until adulthood, especially in males �Pathology: diffuse cortical hyperplasia �Treatment: replace cortisol, early surgical correction of virilized external sex organs for genetic females

Consequences of congenital 21 hydroxylase deficiency: increased testosterone, variable deficiency of cortisol and aldosterone

Consequences of congenital 21 hydroxylase deficiency: increased testosterone, variable deficiency of cortisol and aldosterone

Acquired Cortical Hyperplasia �“always” bilateral (with rare exceptions); �may be diffuse or nodular grossly

Acquired Cortical Hyperplasia �“always” bilateral (with rare exceptions); �may be diffuse or nodular grossly �Hyperplasia defined by adrenal gland weight > 6 grams (after peri-adrenal fat has been dissected) �Acquired hyperplasia is usually secondary (due to pituitary adenoma producing ACTH, ectopic ACTH from small cell lung carcinoma), but may be primary (idiopathic)

Acute adrenal (addisonian) crisis �Clinical features – fever, dehydration, nausea, vomiting, hypotension, that evolves

Acute adrenal (addisonian) crisis �Clinical features – fever, dehydration, nausea, vomiting, hypotension, that evolves rapidly to circulatory shock.

Treatment of acute adrenal (addisonian) crisis �Hydrocortison IV 100 mg as a bolus �Intravenous

Treatment of acute adrenal (addisonian) crisis �Hydrocortison IV 100 mg as a bolus �Intravenous saline and glucose �Hydrocortison 10 -15 mg/kg as a continuous infusion for 24 hours Decrease one third of the hydrocortison daily dose every day until a maintenance dosage is reached within 5 days

Adrenal Hemorrhage Clinical settings: (1) newborns: birth trauma with severe hypoxia (2) DIC, usually

Adrenal Hemorrhage Clinical settings: (1) newborns: birth trauma with severe hypoxia (2) DIC, usually post-surgical (3) complicating a bacteremic infection: Waterhouse-Friderichsen syndrome • septic shock, classically due to Neisseria meningitidis (other bacteria occasionally) • DIC with widespread purpura

Neoplasms arising from cortex and metastases �Adenoma �Carcinoma �Myelolipoma �Metastatic carcinoma

Neoplasms arising from cortex and metastases �Adenoma �Carcinoma �Myelolipoma �Metastatic carcinoma

Adrenal Cortical Carcinoma �Mean age 50 years �Larger: typically > 100 gm; mean weight

Adrenal Cortical Carcinoma �Mean age 50 years �Larger: typically > 100 gm; mean weight 900 grams (BIG!) �About 50% show endocrine hyperfunction, most often virilization due to androgen secretion �Gross clues for malignancy (some apparent by imaging) �Large size, hemorrhage, necrosis, invasion of adrenal vein �Microscopic: wide range of differentiation, but usually show increased mitotic rate �Absolute criteria for malignancy: invasion & metastasis � 5 year survival: 20 -30%; most tumor-related deaths occur within first two years after diagnosis

Myelolipoma �Benign neoplasm seen in adrenal and extra-adrenal sites (e. g. , spleen) �Most

Myelolipoma �Benign neoplasm seen in adrenal and extra-adrenal sites (e. g. , spleen) �Most are solitary and unilateral; some are bilateral and multifocal �Composed of mature fat & myeloid cells �Gross: mixed red (myeloid) and yellow (fat)

Metastatic Carcinoma � 10 -30% incidence of adrenal metastases in patients with metastatic carcinomas

Metastatic Carcinoma � 10 -30% incidence of adrenal metastases in patients with metastatic carcinomas (autopsy-based studies) �Clinical diagnosis suspected with high resolution imaging methods; can confirm pathologic diagnosis with CT-guided fine needle aspiration for cytology if clinically important �Large metastases may be confused with primary adrenal neoplasm (especially if there is no history of carcinoma) �Bilateral metastases may produce adrenal cortical insufficiency (Addison’s disease) �Two most common primary carcinomas that metastasize to adrenal : lung, breast

4. The adrenal “Incidentaloma” �Definition: “an adrenal mass, generally more than 1 cm. diameter,

4. The adrenal “Incidentaloma” �Definition: “an adrenal mass, generally more than 1 cm. diameter, that is discovered accidentally during a radiologic examination performed for indications other than an evaluation for adrenal disease. ” * �Excluded: symptomatic adrenal-dependent syndrome that is “missed” because of an inadequate history or physical exam. �Widespread use of abdominal ultrasound, CT, and MRI examinations has increased the number of “incidentalomas”.

Nature of Incidentally Found Adrenal Masses �Review of 2, 005 incidentally-discovered adrenal masses: �

Nature of Incidentally Found Adrenal Masses �Review of 2, 005 incidentally-discovered adrenal masses: � Nonfunctioning adenoma � Functioning: Cushing’s � Pheo � Aldosteronoma � Malignancy: Metastasis � ACC 82% 5% 5% 1% 3% 4% � Young WF, et al. Endocrinol Clin N Am. 2000

Incidental Adrenal Mass Management �Hormonally active → surgical removal �> 5 cm → removal

Incidental Adrenal Mass Management �Hormonally active → surgical removal �> 5 cm → removal (with a scalpel) �< 3 cm observe �Surveillance Recommendations: Old: CT at 6 months then Annual endocrine eval for 4 years New: If mass stable on scans @ 3 m and 1 yr then no further workup

Young, WF; New England Journal of Medicine, 356: 601 -610, 2007, fig. 1

Young, WF; New England Journal of Medicine, 356: 601 -610, 2007, fig. 1

Neuroblastoma � 2 nd most common solid organ malignancy in children (most common is

Neuroblastoma � 2 nd most common solid organ malignancy in children (most common is brain tumor) NB: Overall, acute leukemia is most common malignancy in children � 650 cases annually; 15% of pediatric cancer-related deaths � Median age at diagnosis = 22 months; 85% < 4 years old. � 5 -year survival now 55 -60%; infants have better prognosis than older children � Sites of origin (all derived from primitive neural crest cells): � 40% adrenal medulla � 25% paravertebral region in abdomen � 15% posterior mediastinum � 20% midline along sympathetic chain (brain to pelvis)