Disease of adrenal gland

Disease of adrenal gland

Hypercortisolism-cushing syndrome Hyperaldosteronism-primary (conn syndrome)-secondary Adrenal insufficiency -primary (addison disease)-secondary Congenital adrenal hyperplasia (21OH

deficiency)

Disease of adrenal gland

Clinical presentation Fat redistribution: "Moon face," truncal obesity, "buffalo

hump," thin extremities, increased abdominal fat• Skin: striae, easy bruising, decreased wound healing, and thinning of skin• Osteoporosis• Hypertension: from increased sodium reabsorption in the kidney andincreased vascular reactivity• Menstrual disorders in women• Erectile dysfunction in men• Cognitive disturbance: from decreased concentration to psychosis• Polyuria: from hyperglycemia and increased free water clearance

Hypercortisolism-Cushing syndrome

Cushingsyndrome

 A 42-year-old obese male who does not smoke, presents with diastolic hypertension. Physical exam shows a full, plethoric appearing face, increased facial hair, truncal obesity, and purple stria around the abdomen with scattered echymosis over the entire body. Labs show an HgB of 18 (12-16), a WBC of 18,000 (4,500-11,000) . The leukocyte differential shows and absolute neutrophillic leukocytosis and absolute lymphopenia and eosinopenia. CXR is normal.

Cushings Syndrome

Iatrogenic Cushings patients taking steroids is the most common cause of Cushings Syndrome.

low ACTH  

Pituitary Cushings

Pituitary Adenoma most common pathogenic cause (70%), the majority of adenomas are benign.

high ACTH

Cortisol responds to dexamethasone supression test 

Ectopic Cushings

Small cell carcinoma of the lung.

ectopic ACTH secretion extremely high ACTH

Cortisol does not respond to dexamethasone

supression test

Adrenal Cushings

Adrenal adenoma   low ACTH  

Bilateral hyperplasia   low ACTH  

Adrenal Carcinoma   low ACTH  

Iatrogenic, exogenous (oral prednisone for years)

Cushing syndrome-Cushing disease-adrenal neoplasia-lung cancer

Cushing syndrome-causes

1. 24hour urine cortisol test (#1)2. Overnight dexamethasone test(high dose) 3. MRI 4. Measure ACTH levelLow - adrenal neoplasiaHigh – Lung cancer (CT chest)-hyperpigmentation

Diagnosis

1. Establish the Presence of Hypercortisolism The best initial test for the presence of hypercortisolism is

the 24-hour urine cortisol. If this is not in the choices, then answer is the 1 mg overnight dexamethasone suppression test.

The 1 mg overnight dexamethasone suppression test should normally suppress the morning cortisol level. If this suppression occurs, hypercortisolism can be excluded.

There are false positive tests(Depression, Alcoholism, Obesity) on the 1 mg overnight dexamethasone suppression test.

The 24-hour urine cortisol is a more specific test of hypercortisolism. If the 24-hour urine cortisol is elevated, the presence of hypercortisolism is confirmed.

Diagnosis

2. Establish the Cause of Hypercortisolism

ACTH testing is the best initial test to determine the cause (source) or location of hypercortisolism.

If the ACTH level is elevated, the source could be from:- Pituitary (suppresses with high dose dexamethasone)- Ectopic production: lung cancer, carcinoid (dexamethasone does not suppress) Once the ACTH level is elevated and does not suppress with

high dose dexamethasone, scan the brain with an MRI. If the MRI does not show a clear pituitary lesion, sample the inferior petrosal sinus for ACTH, possibly after stimulating the patient with corticotrophin releasing hormone (CRH).

An elevated ACTH from the venous drainage of the pituitary confirms the pituitary as the source. The petrosal venous sinus must be sampled because some pituitary lesions are too small to be detected on MRI.

Diagnosis

If the ACTH is elevated, and you cannot find a defect in the pituitary either by MRI or by sampling the petrosal sinus, scan the chest looking for an ectopic source of ACTH production. You must always confirm the source of hypercortisolism with biochemical tests before you perform imaging studies.

At least 10% of the population has an abnormality of the pituitary on MRI.If you start with a scan, you may remove the pituitary when the source is in the adrenals.

Diagnosis

Effects of hypercortisolism include:• Hyperglycemia• Hyperlipidemia• Hypokalemia(excrete K+)• Metabolic alkalosis(excrete H+)• Leukocytosis from demargination of white blood cells. At least half of white cells in the blood are on the vessel wall waiting for an acute stress to come into circulation. They are like parked police cars waiting to be called.

Other Laboratory Testing in Hypercortisolism

Surgically remove the source of the hypercortisolism.

Transsphenoidal surgery is done for pituitary sources whereas

laparoscopic removal is done for adrenal sources.

For non resectable tumors: ketoconazole (inhibits P450): aminoglutethimide (inhibits P450) metyrapone (blocks adrenal enzyme synthesis) mitotane (adenolytic)

Treatment

70% of cases are caused by unilateral adrenal adenoma (Conn's Syndrome)

The remaining 30% are caused from bilateral adrenal hyperplasia of zona glomerulosa

Epidemiology twice as common in women then men usually between the ages of 30-50

Primary Hyperaldosteronism

A 27-year-old male present with headaches, muscle weakness, and high blood pressure. Labs showed a Na of 151 and K of 3.1. CT of the abdomen showed an adrenal mass.

Presentation of primary hyperaldosteronism

Hyperaldosteronism

Primary hyperaldosteronism is the autonomous overproduction of aldosterone despite a high pressure with a low renin activity.

Eighty percent are from solitary adenoma. Most of the rest is from bilateral

hyperplasia. It is rarely malignant.

Primary hyperaldosteronism (renin-independent)-Etiology

Hypertension Hypokalemia(muscle

weakness,polyuria,polydipsia) Metabolic alkalosis Pedal edema is uncommon because of

sodium release into the urine Low renin

Primary hyperaldosteronism (renin-independent)

Caused by the kidneys being fooled into thinking that there is low intravascular volume ◦ results in overactivation of the renin-angiotensin

system◦ associated with a high plasma renin levels

Most commonly caused by by renal artery stenosis ◦ other causes include

chronic renal failure CHF cirrhosis nephrotic syndrome

Secondary hyperaldosteronism

Secondary hyperaldosteronism

Presentation

•Symptoms • hypertension (secondary to increased plasma

volume secondary to increased sodium reabsorption)

• headache• polyuria (secondary to hypokalemic

nephropathy)• muscle weakness (secondary to hypokalemia)

•Physical exam • tetany (hypokalemia)• parestesias• peripheral edema in severe cases

Evaluation

•Labs • hypokalemia• hypernatremia• high plasma renin (neg. regulation by high

aldsterone) • low plasma renin in primary

hyperaldosteronism• elevated 24-hour urine aldosterone• metabolic alkalosis (dumping H+ for Na+)

•Obtain imaging to look for adrenal or pituitary mass

2ºHyperaldosteronism

Treated pt with diuretics, metabolic alkalosis,significant hypokalemia,overdiuresis causing secondary hyperaldosteronism. So what u need to do, decrease the diuretics.

Young patient metabolic alkalosis, hypokalemia diuresis(for weight loss) or Bulimia induce vomit decrease intravascular volume increase renin increase aldosterone

Edema High renin hypotension

Secondary hyperaldosteronism (renin-dependent )

All forms of secondary hypertension are more likely in those whose onset:• Is under age 30 or above age 60• Is not controlled by 2 antihypertensive medications• Has a characteristic finding on the history, physical, or labs In the case of primary hyperaldosteronism, there is

high blood pressure in association with a low potassium level.

The low potassium level is either found on routine lab testing or because of symptoms of muscular weakness or diabetes insipidus from the hypokalemia.

Diagnosis

Plasma aldosterone concentration(PAC) and plasma renin activity(PRA).

Positive screen is PAC/PRA ratio>20:1 and PAC>15.

To confirm hyperladosteronism,an NaCl challenge require. PAC should be suppress in normal people.

If PAC still elevated this confirm the diagnosis.

Diagnosis

How far should you go in the evaluation of an unexpected, asymptomatic adrenal lesion found on CT?• Metanephrines of blood or urine to exclude pheochromocytoma• Renin and aldosterone levels to exclude hyperaldosteronism• 1 mg overnight dexamethasone suppression test

Evaluation of Adrenal "lncidentaloma"

Adrenal Pituitary EctopicACTH level Low high highPetrosal sinus Not done High ACTH Low ACTHHigh dose dexamethasone

No suppresion suppression No suppresion

Confirmatory Laboratory Findings in Adrenal Disorders

Unilateral adenoma is resected by laparoscopy

Bilateral hyperplasia is treated with spironolactone

treatment

Congenital adrenal hyperplasia

95% cases Adrenal androgen excess,decrease cortisol

and aldosterone. Females: ambiguous genitalia Males : normal ,later hypotension Diagnosis: elevated progesterone Treatment: hydrocortisone, fludrocortisone

21-OH deficiency

Primary vs secondary Etiology:

-autoimmune-tuberculosis Symptoms:

-hypotension-hyperpigmentation

Disease of the adrenal glands :adrenal insufficiency

A 15-year-old male presents to his pediatrician with complaints of fatigue, weight loss, and recurrent nausea and vomitting. A basic metabolic panel reveals hyponatremia and hyperkalemia.

Addison disease clinical presentation

Addison disease is caused by autoimmune destruction of the gland in more than 80% of cases. Less common causes are:

- Infection (tuberculosis)- Adrenoleukodystrophy- Metastatic cancer to the adrenal gland Acute adrenal crisis is caused by hemorrhage(waterhouse-

friedreichschen syndrome), surgery, hypotension, or trauma that rapidly destroys the gland.

The sudden removal of chronic high-dose prednisone (steroid) use can precipitate acute adrenal crisis.

It is less common to have an acute adrenal crisis from loss of the pituitary because aldosterone is not under the control of ACTH.

1ºAddison disease- Etiology

Weakness, fatigue, altered mental status, nausea, vomiting, anorexia, hypotension, hyponatremia, and hyperkalemia

Acute and chronic presentation of addison disease

Hyperpigmentation from chronic adrenal insufficiency develops over a longer period of time.

Acute adrenal crisis: presents with profound -hypotension,

-fever, -confusion, - coma.

Addison disease presentation

Patients have the opposite of the tests previously described in hypercortisolism. Hypoadrenalism leads to:• Hypoglycemia• Hyperkalemia• Metabolic acidosis• Hyponatremia• High BUN EOSINOPHILIA If hypoadrenalism is from pituitary failure, the ACTH

level is low. A high ACTH level means the etiology of adrenal insufficiency is a primary adrenal failure.

Diagnostic Tests

Cosyntropln Stimulation Test The most specific test of adrenal function is

the cosyntropin test. Cosyntropin is synthetic ACTH. You measure the cortisol level before and after the administration of cosyntropin. In a patient whose health is otherwise normal, there should be a rise in cortisol level after giving cosyntropin.

Diagnosis

1. Replace steroids with hydrocortisone. 2. Fludrocortisone is a steroid hormone

that is particularly high in mineralocorticoid or aldosterone-like effect. Fludrocortisone is most useful if the patient still has evidence of postural instability. Mineralocorticoid supplements should be used in primary adrenal insufficiency when the patient is on oral steroids such as cortisone.

NaCl replacement

Treatment

A patient is brought to the emergency department after a motor vehicle accident in which he sustains severe abdominal trauma. On the second hospital day, thepatient becomes markedly hypotensive without evidence of bleeding. There is fever, a high eosinophil count, hyperkalemia, hyponatremia, and hypoglycemia.What is the most appropriate next step in management?a. CT scan of the adrenalsb. Draw cortisol level and administer hydrocortisonec. Cosyntropin stimulation testingd. ACTH levele. Dexamethasone suppression testing

Answer: B. In a patient with suspected acute adrenal insufficiency, it is critical to administer hydrocortisone. This is more important than diagnosing the etiology.Hydrocortisone possesses sufficient mineralocorticoid activity to be life-saving. In addition, hydrocortisone will increase the blood pressure because there is a permissive effect of glucocorticoids on the vascular reactivity effect of catecholamines. BP will come up fast with steroids because norepinephrine will be more effective on constricting blood vessels.

Definition/Etiology Pheochromocytoma is a nonmalignant

lesion of the adrenal medulla autonomously overproducing catecholamines despite a high blood pressure.

Pheochromocytoma

o Hypertension that is episodic in natureo Headacheo Sweatingo Palpitations and tremor Orthostatic hypertension Death = cardiac arrhythmia/stroke

Pheochromocytoma

The best initial test is the level of free metanephrines in plasma.

This is confirmed with a 24-hour urine collection for metanephrines. This is more sensitive than the urine vanillylmandelic acid level. Direct measurements of epinephrine and norepinephrine are useful as well.

Imaging of the adrenal glands with CT or MRI is done only after biochemical testing.

MIBG scanning: This is a nuclear isotope scan that detects the location of pheochromocytoma that originates outside the adrenal gland.

Pheochromocytoma

Phenoxybenzamine is an alpha blocker that is the best initial therapy of pheochromocytoma

Calcium channel blocker and beta blockers are used afterwards.

Pheochromocytoma is removed surgically or by laparoscopy

Treatment

A 56-year-old male with a history of difficult-to-control hypertension presents to his physician with progressive fatigue and new onset muscle cramps. He has had no recent changes to his medication regimen, which includes hydrochlorothiazide, lisinopril and amlodipine. His physical exam is notable for a blood pressure of 170/100 but is otherwise within normal limits. A routine basic metabolic panel demonstrates the following lab values: Sodium: 147 mEq/L Potassium: 2.6 mEq/L Chloride: 102 mEq/L HCO3: 26 mEq/L BUN: 13 g/dL Creatinie: 0.7 mg/dl Glucose: 98 What is the mechanism causing the patient's elevated blood pressure?

1. Adrenal hemorrhage2. Cortisol excess3. Stress4. Medication toxicity5. Excess sodium retention

Answer : 5 DISCUSSION: This patient has primary

hyperaldosteronism likely secondary to Conn's syndrome (aldosterone-producing adrenal adenoma).

Primary hyperaldosteronism results from excess production of aldosterone. Aldosterone causes increased sodium retention and potassium excretion. The sodium retention leads to hypernatremia and increased plasma volume, as well as difficult-to-control hypertension. Potassium excretion leads to hypokalemia, which causes muscle cramps and weakness. The most common causes of primary hyperaldosteronism are an aldosterone-producing adrenal adenoma (Conn's syndrome) and bilateral adrenal hyperplasia.

Incorrect Answers: Answer 1: Adrenal hemorrhage would cause adrenal failure

with hypoaldosteronism (hyperkalemia, and hyponatremia), without volume retention.

Answer 2: Cushing's Syndrome (excess cortisol production) causes hypertension that is typically accompanied by characteristic metabolic disturbances (weight gain, central fat deposition) without the electrolyte disturbances seen in this patient.

Answer 3: While stressful situations can lead to elevated sympathetic activity which can raise blood pressure, this would not cause the electrolyte abnormalities seen in this patient, nor would they be likely to cause prolonged drug-resistant hypertension.

Answer 4: The patient is on anti-hypertensive medication that would not be expected to cause his elevated blood pressure. Of the patient's medications, only hydrochlorothiazide is known to cause hypokalemia, however it would not be responsible for the patient's hypernatremia.

A 44-year-old female presents to her primary care physician with complaints of headache, fatigue, muscle weakness, and frequent urination. These issues have developed and worsened over the past month. She has no significant prior medical or surgical history other than cholecystitis managed with cholecystectomy 5 years ago. Her vital signs at today's visit are as follows: T 37.1 C, HR 77, BP 158/98, RR 12, and SpO2 99%. Physical examination is significant for tetany, mild abdominal distension, reduced bowel sounds, and hypertensive retinal changes on fundoscopic exam. The physician orders a laboratory and imaging work-up based on his suspected diagnosis. An abdominal CT scan shows an 8 cm unilateral left adrenal mass suggestive of an adrenal adenoma. Which of the following sets of laboratory findings would be most likely in this patient?

1. Metabolic acidosis, hypernatremia, hyperkalemia 2. Metabolic acidosis, hyponatremia, hyperkalemia 3. Metabolic acidosis, hypernatremia, hypokalemia 4. Metabolic alkalosis, hypernatremia, hyperkalemia 5. Metabolic alkalosis, hypernatremia, hypokalemia

Answer : 5 DISCUSSION: This patient's presentation of hypertension, muscle

weakness and tetany (symptoms of hypokalemia), and a unilateral adrenal mass on imaging is suggestive of a diagnosis of primary hyperaldosteronism (Conn's syndrome). Primary hyperaldosteronism is characterized by laboratory findings of increased 24-hour urine aldosterone, decreased plasma renin, metabolic alkalosis, hypernatremia, and hypokalemia.

70% of primary hyperaldosteronism is caused by a unilateral adrenal adenoma (Conn's syndrome), and the remaining 30% is due to bilateral adrenal hyperplasia of the zona glomerulosa. The condition most commonly presents in females ages 30-50. Primary hyperaldosteronism is one of the most common causes of secondary hypertension; it is due to increased plasma volume as a result of increased sodium reabsorption. Presentation includes hypertension, headaches, tetany and muscle weakness (signs of hypokalemia). Management of this condition includes beta blockers and/or diuretics for hypertension, adrenalectomy for Conn's syndrome, or spironolactone for bilateral adrenal hyperplasia.

A 37-year-old female presents to general medical clinic with headache, fatigue, and weakness. She also reports that she has been having to get up at night to urinate. She has no significant past medical history. She denies taking any medications. Her vital signs are stable with the exception of blood pressure of 165/100. Physical examination is unremarkable. She is concerned because she never remembers having high blood pressure. A workup of the patient's hypertension is initiated, and it is found that she has an elevated plasma ratio of aldosterone to renin. Which of the following would also be likely in this patient? Topic Review Topic

1. Metabolic acidosis 2. Hyperkalemia 3. Hyperglycemia 4. Metabolic alkalosis 5. High renin levels

Answer ▼ 4 DISCUSSION: This patient has primary hyperaldosteronism,

which causes increased urinary hydrogen ion secretion and subsequent metabolic alkalosis.

In primary hyperaldosteronism, there is excessive production of aldosterone by the adrenal glands independent of proper regulation from the renin-angiotensin-aldosterone system. Excessive production of mineralocorticoids leads to increased activity of the Na+/K+ channels in the collecting tubules and sodium retention (causing hypertension) as well as potassium loss (causing hypokalemia). Furthermore, increased aldosterone also results in increased hydrogen ion secretion leading to metabolic alkalosis. Causes of primary hyperaldosterone include adrenal adenomas (Conn's syndrome), adrenal hyperplasia, and adrenal carcinomas. Symptoms include hypertension, headache, weakness, polydipsia, and polyuria. Diagnosis may be made through the plasma aldosterone to renin ratio or 24 hour urine aldosterone. CT or MRI of the adrenals may reveal an adenoma which should be removed if found.

A 46-year-old female with a history of type I diabetes mellitus presents with complaints of chronic fatigue, muscle weakness, and headaches. These symptoms have been present for the past year. Her vital signs today are as follows: T 36.9 C, HR 82 bpm, BP 88/52 mmHg, RR 14 rpm, O2 sat98% on room air. Physical exam does not demonstrate any specific abnormalities. After inquiry, the patient reports that her blood pressure has always "run low." Initial work-up reveals an 8AM cortisol level of 3.6 ug/dL. Which of the following is the best next step in management of this patient?

1. Low dose dexamethasone suppression test 2. High dose dexamethasone suppression test 3. Urgent 5mg hydrocortisone injection 4. Cosyntropin stimulation test 5. Pituitary MRI

Answer ▼ 4 DISCUSSION: This patient's presentation of fatigue, weakness, and

headaches in the setting of low blood pressures and a decreased 8 AM cortisol level is suggestive of adrenal insufficiency. A cosyntropin stimulation test is the next diagnostic step in differentiating primary from secondary adrenal insufficiency and determining the etiology of this patient's low cortisol level.

A cosyntropin stimulation test involves measuring baseline serum cortisol levels prior to the injection of cosyntropin (synthetic ACTH). Serum cortisol is then measured again one hour after the injection. A sufficient increase in serum cortisol after administration of cosyntropin rules out primary adrenal insufficiency and necessitates further work-up for other etiologies. An insufficient or absent rise in serum cortisol in response to the injection (typically, a serum cortisol level less than 18 ug/dL) is suggestive of primary adrenal insufficiency (Addison's disease). Primary adrenal insufficiency is often associated with a constellation of other autoimmune diseases such as autoimmune thyroid disease or type I diabetes mellitus

type II autoimmune polyglandular syndrome, which is the coexistence of autoimmune adrenal insufficiency, autoimmune thyroid disease, and/or type I diabetes mellitus. The authors report that the disease typically manifests in middle age and is more common in females. Primary adrenal insufficiency is a necessary requirement for the diagnosis of this syndrome; the existence of this pathology is confirmed by a cosyntropin stimulation test demonstrating absent or insufficient rise in the serum cortisol level.

secondary adrenal insufficiency. Etiologies include pituitary dysfunction, hypothalamic dysfunction, or prolonged, supraphysiologic administration of exogenous steroids. Identification of patients with apparently minimal or subtle hypothalamic-pituitary-axis (HPA) dysfunction is significant in order to prevent life-threatening adrenal crisis in the event of future stressful situations. The insulin tolerance test and cosyntropin stimulation test are two common tools used in the diagnosis of adrenal insufficiency; the authors discuss specific limitations and benefits of these tests in extensive detail.

Incorrect Answers:

Answers 1 & 2: A dexamethasone suppression test is appropriate for work-up of elevated cortisol levels, not depressed levels as seen in this vignette.

Answer 3: Work-up to identify the cause of this patient's adrenal insufficiency should be pursued prior to initiating adrenal replacement therapy. This patient's presentation is not consistent with an acute adrenal crisis.

Answer 5: Secondary adrenal insufficiency should be confirmed prior to pursuit of this expensive diagnostic test.

A 42-year-old female presents to your clinic with complaints of progressive weight loss, dizziness, nausea, and vomiting over the last several months. She returned from a 3-month-long international business trip 6 months ago where she reports being ill with fever, cough, and night-sweats. She reports undergoing treatment abroad with rifampin, isoniazid, pyrazinamide, and ethambutol for a period of time. Vital signs at today's visit are as follows: T 98.7, HR 92, BP 86/44, RR 20, O2 Sat 97% RA. Physical exam is significant for generalized hyperpigmentation of the skin. A CT of the abdomen demonstrates bilateral cystic adrenal hyperplasia. Which of the following sets of laboratory values would be most consistent with this patient's suspected diagnosis?

1. Na: 137 mEq/L, K: 4.2 mEq/L, Cl: 104 mEq/L, HCO3: 25 mEq/L; Glucose: 92 mg/dL 2. Na: 150 mEq/L, K: 2.9 mEq/L, Cl: 98 mEq/L, HCO3: 19 mEq/L; Glucose: 66 mg/dL 3. Na: 137 mEq/L, K: 5.6 mEq/L, Cl: 101 mEq/L, HCO3: 22 mEq/L; Glucose: 65 mg/dL 4. Na: 122 mEq/L, K: 4.1 mEq/L, Cl: 97 mEq/L, HCO3: 24 mEq/L; Glucose: 76 mg/dL 5. Na: 125 mEq/L, K: 5.5 mEq/L, Cl: 98 mEq/L, HCO3: 19 mEq/L; Glucose: 66 mg/dL

Answer ▼ 5 DISCUSSION: This patient has adrenal insufficiency

(Addison disease) secondary to tuberculosis infection. Primary adrenal insufficiency is characterized by elevated plasma ACTH and decreased aldosterone, which leads to hyponatremia, hyperkalemia, hypoglycemia, metabolic acidosis, and eosinophilia.

Clinical manifestations of adrenal insufficiency can include skin hyperpigmentation, nausea/vomiting, fatigue, weight loss, orthostatic hypotension, fatigue, and myalgias/arthralgias. A cosyntropin stimulation test may confirm the diagnosis of adrenal insufficiency, regardless of the particular etiology. Successful treatment of TB often results in a reduction in the size of the adrenal glands back to baseline; however, anti-tuberculosis regimens do not tend to restore function to the adrenal glands.

A 53-year-old nurse presents to the emergency department after experiencing a syncopal episode at work. She reports a 6-month history of worsening fatigue, 20-pound weight loss, and dizziness when standing up from a sitting position. Her PMH is significant for hypothyroidism, for which she takes levothyroxine. Her blood pressure while supine is 105/60, which falls to 75/50 when standing. On exam, she appears fatigued, and you note hyperpigmentation of the gums as shown in Figure A. Labs are notable for sodium of 128 mmol/L, and potassium of 5.6 mEq/L. Which of the following is the most likely pathology underlying this presentation? Topic Review Topic

FIGURES: A

1. Autoimmune adrenalitis 2. Infectious adrenalitis 3. Hemorrhagic infarction of the adrenal glands 4. Metastatic disease involving the adrenal glands 5. Medication-induced suppression of the adrenal glands

1 DISCUSSION: This clinical presentation is consistent with

Addison’s disease with associated hyponatremia and hyperkalemia; the most common cause of Addison’s disease in the United States is autoimmune adrenalitis.

The symptoms and signs of Addison’s disease, or primary adrenal insufficiency, are attributable to loss of adrenal function, including mineralocorticoid production. Common features of primary adrenal insufficiency include chronic malaise, fatigue, anorexia, and weight loss. Hyperpigmentation results from cortisol deficiency and over-production of pro-opiomelanocortin (a prohormone cleaved to form ACTH and melanocyte stimulating hormone); this is a helpful feature to differentiate from secondary adrenal insufficiency, where hyperpigmentation does not occur. Hyponatremia and hyperkalemia results from mineralocorticoid deficiency.

A 53-year-old woman presents to the emergency room in Boston, MA after a syncopal episode at her workplace. She has a history of type 1 diabetes and premature ovarian failure. Over the past 6 months, she has noticed increasing fatigue and unintentional weight loss. On exam, she has a generalized bronzing of her skin. Labs reveal that she is hyponatremic and hyperkalemic. Her vitals are otherwise within normal limits. Subsequent workup with an ACTH-stimulation test and ACTH measurement suggests the diagnosis of primary adrenal insufficiency. What is the most likely cause of primary adrenal insufficiency in this woman? Topic Review Topic

1. Infectious disease 2. Autoimmune disease 3. Adrenal hemorrhage 4. Metastatic cancer 5. Medication effec

2 DISCUSSION: This clinical presentation is suggestive of primary

adrenal insufficiency (Addison's disease), which is most often caused by autoimmune disease in developed countries.

Primary adrenal insufficiency is associated with a number of nonspecific symptoms including chronic malaise, weakness, and weight loss. Physical exam findings include postural hypotension and hyperpigmentation due to increased production of pro-opiomelanocortin (POMC), a prohormone that is cleaved into ACTH and melanocyte stimulating hormone. Cardinal lab abnormalities are hyponatremia and hyperkalemia due to mineralocorticoid deficiency. Following ACTH stimulation testing, there is an inappropriately low cortisol response; if measured, endogenous ACTH levels will be high. There are many potential causes of primary adrenal insufficiency, but the most common in developed countries is autoimmune adrenalitis. Treatment involves both glucocorticoid and mineralocorticoid replacement.

A patient with chronic obstructive pulmonary disease is admitted to the hospital with cholecystitis. He undergoes cholecystectomy uneventfully and is transferred to the floor. Suddenly, he becomes weak and severely hypotensive. If the patient's symptoms are due to adrenal insufficiency from chronic steroid use, one would expect which of the following: Topic Review Topic

1. Elevated renin 2. Elevated cortisol 3. Decreased ACTH 4. Elevated ACTH 5. Elevate aldosterone

3 DISCUSSION: Secondary adrenal insufficiency can be

caused by chronic glucocorticoid use. which suppresses corticotropin-releasing hormone (CRH) and therefore, ACTH.

Secondary adrenal insufficiency is found in patients who are on long-term steroid therapy. When these patients develop an illness, undergo trauma, or have a surgical procedure, they are unable to produce adequate cortisol due to suppression of the CRH - ACTH axis by the exogenous steroids. Aldosterone secretion is not as affected because ACTH doesn't have a significant effect on its secretion. In patients with chronic steroid use, ACTH and cortisol will be low but aldosterone will be relatively normal.

Incorrect Answers: Answer 1: Renin levels are mediated by the juxtaglomerular

apparatus (JGA) primarily, not by the pituitary. Answer 2: This patient has adrenal insufficiency so cortisol

levels would be expected to be low. Answers 4: ACTH levels would be low, not high with

secondary adrenal insufficiency. Answers 5: Aldosterone levels are mediated by angiotensin

which in turn is mediated by renin levels and potassium. Since renin levels are regulated by the JGA, not the pituitary, one would expect aldosterone to be relatively normal in this patient. If any change would be expected, aldosterone levels could be low due to adrenal atrophy with secondary adrenal insufficiency.

A 39-year-old man presents to the emergency room with fever and cough. He has no prior smoking history. He is originally from Russia and since immigrating 5 years ago, he has contracted HIV. On the second day of admission, he develops severe hypotension, abdominal pain and acute renal failure. A CT of the abdomen and pelvis reveals extensive calcification of the adrenal glands bilaterally. What is the most likely diagnosis?

1. Primary adrenal insufficiency secondary to autoimmunity

2. Primary adrenal insufficiency secondary to metastatic lung cancer

3. Primary adrenal insufficiency secondary to M. tuberculosis

4. Secondary adrenal insufficiency 5. Tertiary adrenal insufficnecy

3 DISCUSSION: Tuberculosis can cause adrenocortical

insufficiency via adrenal bacterial invasion, which should be suspected in patients who present with clinical features of adrenal insufficiency and have bilateral calcification of the adrenal glands on CT scan.

The most common cause of Addison's disease (primary adrenal insufficiency) worldwide is tuberculosis, while autoimmune disease is the most common cause in the Western world. However, the most common cause of adrenal insufficiency overall is rapid discontinuation of chronic corticosteroids. Patients with extrapulmonary tuberculosis like this one are unable to contain the bacteria in the primary or secondary stage and experience dissemination throughout the body. Extrapulmonary tuberculosis is more often found in patients with HIV. Sites of extrapulmonary tuberculosis include the lymph nodes, pleura, genitourinary tract, spine (Pott's disease), intestine, meninges, eye, and adrenal glands.

A 47-year-old male has been feeling fatigued and has gained 20 pounds during the last two months. On exam, you note central obesity with proximal muscle atrophy and weakness. Vital signs are as follows: T 98.4 F, BP 155/90 mmHg, HR 85 bpm, RR 14 rpm. BMP is as follows: Na 140 K 3.9 Cl 102 CO2 23 BUN 19 Cr 0.9 Glu 115. 24-hour urinary free cortisol level is 165 nmol/day (upper range of normal 110-138 nmol/day) and morning serum ACTH is 83 pg/mL (normal is 9 - 52 pg/mL). Two days later, he receives 2 mg dexamethasone orally every 6 hours for 48 hours. The following morning at 9 am, his serum cortisol level is 300 nmol/L (normal is 50-200 nmol/L). At 48 hours it is 250 nmol/L. Which of the following should be the next step? Topic Review Topic

1. Bilateral inferior petrosal sampling 2. Initiate treatment with metyrapone 3. Initiate treatment with ketoconazole 4. CT of the thorax and abdomen 5. Brain MRI

Answer ▼ 4 DISCUSSION: This patient likely has an ectopic

ACTH production from a tumor in the abdomen or thorax. High resolution CT will localize the tumor in the majority of cases.

This patient's symptoms of fatigue, central obesity, and proximal muscle wasting with an elevated 24-hour urinary cortisol level are indicative of hypercortisolism. His elevated ACTH suggests that this is an ACTH-dependent process. The failure of the low-dose (2mg) dexamethasone to suppress his cortisol level indicates this is an ectopic source of ACTH.

Incorrect Answers: Answer 1: Bilateral inferior petrosal sampling is considered

the gold standard for identifying a pituitary ACTH-producing tumor. However, it is generally preceded by a brain MRI.

Answer 2: While metyrapone is the first-line adrenolytic due to its rapid onset of action, it should not be initiated until the diagnosis is confirmed. Identification and removal of the ACTH secreting tumor is also of primary importance.

Answer 3: Ketoconazole is a second-line adrenolytic agent. Pharmacologic treatment should not be initiated until the diagnosis is confirmed. Identification and removal of the ACTH secreting tumor is also of primary importance.

Answer 5: Brain MRI would be the test of choice if a pituitary adenoma was suspected. However, due to this patient's failure to suppress cortisol levels in response to dexamethasone, the likely lesion is ectopic.

A 69-year-old with granulomatosis with polyangiitis (formerly Wegener's) diagnosed about 8 months ago. He was treated with rituximab and prednisone for induction remission and required prednisone since his diagnosis. His vital signs are: T 37C, HR 80, BP 150/90, RR 14, and O2 99% on room air. His physical examination is notable for the findings in Figures A and B. What would be the most likely electrolyte abnormality found in this patient?

1. Hypokalemia and hyponatremia 2. Hyperkalemia and hypernatremia 3. Hypokalemia and hypernatremia 4. Hyperkalemia and hyponatremia 5. Hypercalcemia and hypernatremia

answer : 3 DISCUSSION: This patient has Cushing's syndrome from

long-term steroid treatment. Exogenous steroids may have partial mineralocorticoid action, leading to hyperactivation of the Na+/K+ ATPase in the renal collecting tubules, causing K+ wasting and Na+ reabsorption.

Cushing's syndrome results from excessive levels of glucocorticoids due to any cause. Remember to be able to differentiate it from Cushing's disease, which is a form of Cushing's syndrome caused by a pituitary adenoma that secretes ACTH. The most common cause of Cushing's syndrome is long-term steroid use. Other causes include adrenal adenomas, carcinomas, and ectopic ACTH production from small cell carcinomas of the lung. Classic physical exam findings appearance marked by central obesity, hirsutism, moon facies, a buffalo hump, purple striae on the abdomen, lanugo hair, acne, and easy bruising. They may also be hypertensive. Common electrolyte abnormalities are hypokalemia and hypernatremia.

clinical manifestations and diagnostic evaluation. The best screening test for Cushing's syndrome is a 24-hour urine collection with analysis for urinary free cortisol excretion. Low-dose and high-dose dexamethasone suppression tests, corticotropin assays, a corticotropin-releasing hormone stimulation test, and inferior petrosal sinus catheterization may be required for a definitive diagnosis.

Tempark et al. discuss exogenous Cushing's syndrome due to corticosteroid application. Prolonged use of topical corticosteroids causes systemic adverse effects including Cushing's syndrome and hypothalamic-pituitary-adrenal (HPA) axis suppression, which is less common than that of the oral or parenteral route. At least 43 cases with iatrogenic Cushing syndrome from very potent topical steroid usage (Clobetasol) in children and adult have been published over the last 35 years particularly in developing countries. For the adult group, the most common indication for steroid use was treatment of Psoriasis.