Chronic Adrenocortical Insufficiency Flashcards
What is the definition, classification and etiology of chronic adrenocortical insufficiency?
Definition: this is a progressive disease in which there is a hypo production of the hormones in the cortex of the adrenal glands.
Classification
1. Primary- Adrenal gland itself is dysfunctional
2. Secondary- Lack of CRH secretion from hypothalamus- Lack of ACTH production in the pituitary gland.
Etiology
Primary etiology
Autoimmune
Type 1 polyglandular syndrome; autosomal recessive, appears in the 1st decade of life
-Hypoparathyroidism, Hypothyroidism, Gonadal failure, DM, adrenal failure
Type 2; autosomal dominant, appears in 2nd and 3rd stages of life
- Thyroid disease, TB
Iatrogenic
Secondary etiology
Decreased metabolism
Trauma
Symptoms, diagnostic criteria and stages
Symptoms
Weakness, malaise, weight loss, anorexia, depression, decreased memory and mental activity, decreased cold tolerance, hypotension, hypoglycemia, hallucinations.
Objective signs; hyperpigmentation in bone prominence, skin folds, scars, extensor surfaces, over the forehead, blush discoloration of mucosa of lips, mouth, rectum and vagina.
Diagnostic criteria
- Inappropriately low cortisol secretion
- determine if it’s primary or secondary
-detect the cause
Stages of severity: mild, moderate and severe
Methods of diagnosis and laboratory findings
Laboratory findings
Basal morning serum cortisol concentration
At 8am: <3-5micrograms
Morning salivary cortisol: lower than 1.8ng/ml. Normal is 5.8
Urine free cortisol level is decreased
Basal plasma ACTH, renin is elevated and low aldosterone in primary type associated with hyponatremia and hyperkalemia .
In secondary, it’s the opposite.
Standard dose ACTH stimuli test
The ability of adrenals to respond to 250mg IV or IM of ACTH at 0,30,60 mins after stimuli
If it responds, there’s a secondary disease
If it doesn’t respond, it indicates a primary disease.
On CT , there is enlargement of adrenals bilaterally, calcification and atrophy.
On ECG, loss of P waves, peaked T waves and widened QRS as a result of hyperkalemia.
Treatment
I. Etiologic appropriate treatment of complicating infections(tuberculosis)
II. Pathology 1.
Cortisol 20-25mg/daily
Prednisone 5-7.5mg/daily
Hydrocortisone 30-40 mg orally daily
2/3 of the dose can be given in the morning and 1/3 in the afternoon. Night doses should be avoided, as they may produce insomnia
3. Mineralcorticoids DOCSA 5mg daily
Fludrocortisone 0.1-0.2 mg orally once a day
4. Incurrent illness(e.g infections) should be regarded as potential risk and the patient
should double his dose until he or she is well
5. If nause or vomiting preclude oral therapy, parental therapy should be started
PHEOCHROMOCYTOMA: definition, classification, etiology clinical signs, laboratory findings and diagnostic criteria
Pheochromocytomas (‘dusky colored tumor’) are chromaffin-derived tumors (mostly benign)that develop in the adrenal gland. They are non-functional
ETIOLOGY
Etiology is unknown but Pheochromocytoma is likely to occur in some certain syndromes like MEN 2A(Multiple Endocrine Neoplasia)-Sipple syndrome,MEN 2B,neurofibromatosis(Von Recklinghausen disease) and VHL( Von Hipple Lindau syndrome),tuberous sclerosis (Bourneville disease, epiloia) and Sturge-Weber syndrome.
Classification.
1)Paroxysmal form (45%)
2)Permanent form (50%)
-with crisis
-without crisis
3)Latent or silent form-non symptomatic.
Clinical signs-hypertension (due to the secretion of more than one catecholamines),weight loss,pallor,fever,tremor,hypertensive retinopathy,hypertrophy of left ventricle,neurofibromas,pulmonary edema.
Lab findings-hyperglycemia,hypercalcemia,erythrocytosis
2.Diagnostic criteria-A raised plasma free metanephrine level ≥4 times above the upper reference limit of normal indicates almost 100 % probability of the tumor.
TREATMENT OF PHEOCHROMOCYTOMA
• Surgical resection of the tumor.
Alpha and beta blockers preoperatively to control blood pressure and prevent intraoperative hypertensive crisis.
• Alpha blockers blockade with phenoxybenzamine 7-10 days preoperatively to allow for expansion of blood volume
• Volume expansion of blood with isotonic solution.
• Labetalol (Trandate, Normodyne) is a noncardioselective beta-adrenergic blocker
and selective alpha-adrenergic blocker that has been shown to be effective in controlling hypertension associated with pheochromocytoma. It has also been associated with paradoxic episodes of hypertension thought to be secondary to incomplete alpha blockade.
During crisis a combination of α- and β- adrenergic blocking agents (phentolamine
(tropaphen) 2 - 4 mg every 5 - 10 min till stopping of the crisis, phenoxybenzamine 10 – 20 mg 3 – 4 times daily, propranolol 30 – 60 mg/day) and infusion of sodium nitroprusside.
Conn’s syndrome
Primary hyperaldosteronism is a group of disorders, in which excessive production of aldosterone by the zona glomerulosa of the adrenal cortex.
Etiology-mostly from secondary hyperaldosteronism due to excessive renin, such as renal artery stenosis.
Classification:
- solitary aldosterone-producing adenoma (APA),
- bilateral hyperplasia of the zona glomerulosa (also known as idiopathic
hyperaldosteronism [IHA]),
- primary adrenal hyperplasia (PAH),
- adrenal carcinoma, and
- glucocorticoid-remediable aldosteronism.
Clinical signs-Hypertension (most common), manifestations of hypokalemia: weakness, muscle cramping, paresthesias, headaches, palpitations, polyuria, and polydipsia,hyperglycemia due to
insulinopenia.
Diagnostic criteria
Plasma aldosterone concentration/Plasma renin activity ratio.
PAC>15ng/dL
Ratio of PAC/PRC>20.
Tests should be performed in the morning.
Certain drugs like spirinolactone,ace inhibitors like captopril,angiotensin II receptor blockers like losartan
Treatment-After the APA is localized, unilateral adrenalectomy is performed
-For IHA, the agent of choice is spironolactone.
-In patients intolerant of spironolactone, amiloride ,calcium channel blockers,like amlodipine and angiotensin-converting enzyme (ACE) inhibitors like captopril.
Management of a patient with PAH.
-A patient with glucocorticoid-remediable aldosteronism have to be managed with low doses of dexamethasone (0.75 mg/day) or any of the agents used for therapy of IHA (see above) may be effective.
Cushing’s syndrome
This is the excessive production of cortisol in the cortex of the adrenal glands
Can be endogenous or exogenous type based on etiology
Endogenous-
a) ACTH dependent: Increased pituitary ACTH secretion.
b)Non ACTH dependent: Caused by cortisol secretion by benign or malignant adrenal tumors .
Micronodular or macronodular dysplasia of the adrenal gland
Exogenous-most common type,use of glucocorticoids.
Clinical signs-
-Weight gain especially in the face, torso, back and supraclavicular region.
-Purple stretch marks on the skin, easy bruising, skin thinning.
-Hirsutism and irregular menses in women.
-Muscle weakness
-Psychological problems like depression,cognitive dysfunction.
-Patients with an ACTH-producing pituitary tumor (Cushing disease) may develop headaches, polyuria and nocturia, visual problems, or galactorrhea.
-hyposomatotropism, hypothyroidism, hyperprolactinemia or hypoprolactinemia, and hypogonadism may develop.
Hypoglycemia,hypokalemia,hyponatriema,metabolic acidosis.
-moon-face
Diagnosis and treatment of Cushing’s disease
Diagnosis
– hour low dose dexamethasone test: In this procedure, eight 0.5-mg doses of dexamethasone at 6-h intervals are given orally; 24-h urine samples for 17-hydroxycorticosteroids (17- OHCS) excretion are collected before and during dexamethasone administration. In normal subjects, 17-OHCS values are below 3 mg per 24 h on the second dexamethasone day. Patients with Cushing’s syndrome fail to suppress.
-High-dose dexamethasone suppression test. After the oral administration of a single dose of 4.0 mg of dexamethasone between 10 p.m. and midnight, the measured 8 a.m. cortisole the following morning is less than 2 mkg/dl in normal individuals. Patients with pituitary-dependent Cushing’s syndrome demonstrate a plasma cortisol suppression of more than 50 % compared with the baseline values. Those with adrenal tumors or nonpituitary ACTH-secreting tumors do not respond.
5.RADIOLOGIC DIAGNOSIS Includes X-ray examination for a pituitary tumor, and computed tomography which is the most popular procedure for visualizing the adrenals in patients with Cushing’s syndrome.
Treatment -Depends on the etiology, and can be surgical or medical. Unresectable adrenal tumors are treated with ketoconazole or metyrapone.
Pituitary irradiation.
