Prof. Tariq Waseem

ADRENAL DISORDERS - 3

Prof. Tariq Waseem

Prof. Tariq Waseem

CASE SCENARIO:1 A 22 years old male presents with c/o severe

headache off & on, palpitations and sweating while carrying out his daily activities.

He also complains of having a sense of impending doom and generalized weakness of his body along with trembling of his hands

His co-workers also noticed marked blushing of his face during such episodes.

He was diagnosed HTN one year ago and is using four antihpertensive drugs but his BP is rarely on target.

Prof. Tariq Waseem

ADRENAL MEDULLA

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EXAMINATION On physical examination: BP= 210/140 Pulse…92/min regular Temp…98.6 F Other positive findings include: Pallor…+ve Tremors…present Systemic examination was

unremarkable

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LAB INVESTIGATION SHOWED:

CBC.showing Hb..15g/dl TLC…18000 Serum Na+…139meq/l Random blood glucose..200 mg/dl Normal T3, T4, TSH Normal ECG and echo

Prof. Tariq Waseem

PHEOCHROMOCYTOMA Rare but fatal catecholamines

producing tumor Incidence: 2-8/million people/year Account for 5% of adrenal

incidentaloma Rule of 10s:

10% extra-adrenal, 10% bilateral, 10% familial, 10% malignant

Aside from catecholamines, it can also secrete dopamine, ACTH, PTH, calcitonin, VIP

Prof. Tariq Waseem

PHEOCHROMOCYTOMA 0.01-0.1% of HTN population

Found in 0.5% of those screened M = F 3rd to 5th decades of life Rare, investigate only if clinically

suspicion: Signs or Symptoms Severe HTN, HTN crisis Refractory HTN (> 3 drugs) HTN present @ age < 20 or > 50 ? Adrenal lesion found on imaging (ex.

Incidentaloma)

Prof. Tariq Waseem

PHEO: SIGNS & SYMPTOMS The five P’s:

Pressure (HTN) 90% Pain (Headache) 80% Perspiration 71% Palpitation 64% Pallor 42% Paroxysms

The Classical Triad: Pain (Headache), Perspiration, Palpitations Lack of all 3 virtually excluded diagnosis of pheo

in a series of > 21,0000 patients

Prof. Tariq Waseem

BIOCHEMICAL TESTING Plasma Fractionated free metanephrine

levels Urinary fractionated metanephrines and

metabolites Serum chromogranin A Clonidine suppression test Urinary VMA levels Additional tests include…

erythrocytosis,leukocytosis,hyperglycemia,hypercalcemia,sometimes raised ESR

Prof. Tariq Waseem

FACTORS AFFECTING TEST RESULTS:

Physical or emotional stress Sleep apnea Drugs….MAO inhibitors, TCA’s, beta

blockers, amphetamine, levodopa, methyldopa, labetalol,buspirone, phenoxybenzamine

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IMAGING

Silent 8 cm pheo

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IMAGING

CT/ MRI abdomen Nuclear imaging….123 meta-

iodobenzyl-Guanidine PET scanning…18FDG-PET Somatostatin receptor imaging…111in-

labeled octreotide

Prof. Tariq Waseem

TREATMENT:

SURGERY…treatment of choice for all pheochromocytomas ( laproscopic adrenalectomy, open laprotomy)

Careful pre-operative management to control blood pressure, correct fluid volume and prevent intra-operative hypertensive crises

MEDICATION therapy….for preop management, acute hypertensive crises and as a primary therapy for metastatic pheochromocytoma.

Prof. Tariq Waseem

INTERVENTIONS-PRE-OP Adrenergic blocking agents

Minipress to BP Beta blocking agents

Inderal to Heart Rate, BP & force of contraction

Diet High in vitamin, Mineral, Calorie, No

Caffeine Sedatives

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PREOP PREPERATION REGIMENS Combined + blockade

Phenoxybenzamine Selective 1-blocker (ex. Prazosin) Propanolol

Metyrosine Calcium Channel Blocker (CCB)

Nicardipine

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DURING SURGERYGIVE REGITINE AND NIPRIDE TO PREVENT HYPERTENSIVE CRISIS

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POSTOP Most cases can stop all BP meds postop

Postop hypotension: IV crystalloid HTN free: 5 years 74% 10 years 45%

24h urine collection 2 wk postop Surveillance:

24h urine collections q1y for at least 10y Lifelong f/up

Prof. Tariq Waseem

COMPLICATIONS. All the complications of severe

hypertension Catecholamine induced cardiomyopathy Severe heart failure and cardiovascular

collapse Sudden death due to cardiac

arrhythmias ARDS Hypertensive crises with sudden

blindness and CVA’s…not uncommon

Prof. Tariq Waseem

PHEO: UNRESECTABLE, MALIGNANT -blockade

Selective 1-blockers (Prazosin, Terazosin, Doxazosin) 1st line as less side-effects

Phenoxybenzamine: more complete -blockade -blocker CCB, ACE-I, etc. Nuclear Medicine Rx:

Hi dose 131I-MIBG or 111indium-octreotide depending on MIBG scan or octreoscan pick-up

Sensitize tumor with Carboplatin + 5-FU

Prof. Tariq Waseem

PHEO & PREGNANCY Diagnosis with 24h urine collections

and MRI No stimulation tests, no MIBG if

pregnant 1st & 2nd trimester (< 24 weeks):

Phenoxybenzamine + blocker prep Resect tumor ASAP laprascopically

3rd trimester: Phenoxybenzamine + blocker prep When fetus large enough: cesarian section

followed by tumor resection

A 16 yr old girl was brought to medical OPD with C/O increased facial hair and acne. Her mother is concerned about delayed menarche and not having a smart feminine figure. On her last visit to physician she was told to watch her BP which was recorded 140/95 mmHg.

On examination, pt. is having male type hair pattern along with ambiguous genitalia.

CASE SCENARIO:

Congenital adrenal hyperplasia (CAH) is a group of inherited autosomal-recessive disorders in which a genetic defect results in the deficiency of an enzyme essential for synthesis of cortisol and, at times, aldosterone.

CONGENITAL ADRENAL HYPERPLASIA:

Reduced cortisol secretion and resulting absence of feedback pituitary inhibition increases ACTH to maintain adequate cortisol causing adrenal hyperplasia.

There are several forms of CAH, the most common of which is 21-hydroxylase (21-OH) deficiency, occurring in over 90% of all cases.

CONGENITAL ADRENAL HYPERPLASIA:

Cholesterol

Pregnenolone

17-Hydroxy-pregnenalone

17-Hydroxy-progesterone

11-Deoxycortisol

Cortisol

desmolase

17-a-hydroxylase

11-b-hydroxylase

21-hydroxylase

3-b-OH-dehydrogenase

Androgens

Ambiguous, no androgens, salt-wasting

Ambiguous, low androgens, hypertension

Virilized, high androgens, lethal

Virilized, high androgens, salt-wasting

Virilized, high androgens, hypertension

HGSS: Carey: Figure 5.2 Genitalia, androgen level, medical symptomKey:

CLASSICAL 21-HYDROXYLASE DEFICIENCYPATHOPHYSIOLOGY

Glucocorticoid

Cholesterol(mitochondrial)

Pregnenolone

17OH-Pregnenolo

ne

17OH-Progesterone

Cortisol

Progesterone

11-deoxycorticosteron

e

Aldosterone

Mineralocorticoid

P-45021

Dehydroepiandrosterone

Androstenedione

(Testosterone)

Oestradiol DHT

Androgen

ACTH_

++

11-deoxycortisol

If severe, CAH presents at birth with sexual ambiguity or adrenal failure ( collapse, hypotension, hypoglycemia) sometimes with a salt losing state( hypotension, hyponatremia).

In females, clitoral hypertrophy, urogenital abnormalities, and albioscrotal fusion are common but syndrome may be unrecognized. Milder cases present in adult life only with primary amenorrhea.

In males. Precocious puberty with hirsutism is a later presentation,

CLINICAL FEATURES:

A profile of adrenocortical hormones is measured before and 1hr after ACTH administration.

Basal ACTH levels…are raised

17-hydroxyprogesterone levels…are increased

Urinary 17-ketosteroids are increased

Androstenedione levels…are raised

INVESTIGATIONS:

MANAGEMENT :

Glucocorticoid replacement / Androgen Suppression

Adults: usually dexamethasone, larger dose at bed-time to suppress ACTH

Beware of over-replacement and monitor :17--progesterone (testosterone, cortisol, ACTH etc)growth, bone age, BP, U&E, skin; osteoporosis scans

in adults

Correction of salt-wasting

9-a-fludrocortisone 100-400mcg/day (long-acting)

Sodium chloride supplements until able to select saltier foods

Monitor BP, U&E, oedema (renin)

MANAGEMENT :

Corrective surgery to genitalia

Genetic counselling & psychological support

MANAGEMENT :

A 34 yr old male presents in ER with C/O body aches, episodic muscle weakness, numbness and tingling of the limbs for last 5 days. Symptoms worsened over 2 days leading to severe muscle spasms.

He also has polyuria and polydipsia especially at night. He has frequent episodic headache and Palpitation.

He was diagnosed HTN last year and is on Beta Blockers with poor control.

CASE SCENARIO:3

B.P 160/100 Pulse…86/ min, regular Respiratory rate..18/min No peripheral edema. Systemic examination was

unremarkable

PHYSICAL

CBC , LFT’S, RFT’S…Normal Serum potassium..2.1meq/L, serum

sodium..156meq/l Urinary postassium..> 32mmol/day

What’s the diagnosis ?

INVESTIGATIONS

Primary Hyperaldosteronism

Conn’s Syndrome

HYPERALDOSTERONISM

Excessive secretion of aldosterone causes Increased Sodium reabsorbtion, Increased loss of potassium Increased loss hydrogen ions

Hypokalemia and Hypertension.

Peak incidence between 30-60yrs of age.

HYPERALDOSTERONISM

May be primary ( autonomous) as in primary adrenal hyperplasia, adrenal adenoma, carcinoma

Secondary hyperaldosteronism…associated with renovascular hypertension, cirrhosis, rennin producing tumours, pregnancy.

Testing for primary hyperaldosteronism should be done for all hypertensive patients with hypokalemia.

HYPERALDOSTERONISM:

Frequent urination Increased thirst Weakness and fatigue Headache Muscle cramps Tingling in fingers Transient paralysis Palpitations Hypertension

SYMPTOMS

Hypokalemia ( Without Diuretic therapy) Urinary potassium loss..>30mmol/day Plasma aldosterone:rennin ratio (ARR)…

increased Elevated plasma aldosterone level (PA…that

are not suppressed with 0.9% saline ( 2L over 4hrs) or fludrocortisone administration.

INVESTIGATIONS:

Suppressed plasma rennin activity 18-hydroxycorticosterone level..>100ng/dl seen in

adrenal neoplasms. Adrenal vein sampling..to differentiate unilateral or

bilateral aldosteronism Posture stimulation test Imaging…CT abdomen

INVESTIGATIONS:

Control of blood pressure.

Conn’s syndrome(adenoma ), unilateral aldosterone secreting adrenal tumours…treated by laproscopic adrenalectomy though long term therapy with spironolactone ( aldosterone antagonist) or eplerenone is an option.

TREATMENT:

Bilateral adrenal hyperplasia..best treated with spironolactone or eplerenone.

Secondary hyperaldosternism…ACE’s and ARB’s, spironolactone.

MANAGEMENT :

Prof. Tariq Waseem

THANK YOUQuestions?