adrenal disorder: hypercortisolism

Question 1

adrenal gland

Answer 1

-On cephalad portion of each kidney
-Cortex & Medulla
-Bioactive amines and peptides (eg, histamine, serotonin, chromogranins, neuropeptide hormones

Question 2

hyperfunctioning adrenal disorders

Answer 2

-Frequently have overlapping features
-Hypersecretion of cortisol (Cushing’s syndrome)
-Hypersecretion of androgens (virilism)
-Hyperaldosteronism
-Compensatory – as in congenital adrenal hyperplasia
-Acquired hyperplasia – adenomas, or adenocarcinomas
-Variety of genetic abnormalities of steroidogenesis

Question 3

hypofunctioning adrenal disorders

Answer 3

-Adrenal insufficiency
-Deficiency syndromes affect output of all adrenocortical hormones
-Primary (malfunction of the adrenal gland itself, as in Addison’s disease)
-Secondary (due to lack of adrenal stimulation by the pituitary or hypothalamus)

Question 4

adrenal cortex

Answer 4

-3 major classes of steroids
-All important in modulating various parameters and responses

-1. Glucocorticoids
-Cortisol
-Intermediary metabolism and immune responses
-Hepatic gluconeogenesis

-2. Mineralocorticoids
-Aldosterone
-Blood pressure, vascular volume, and electrolytes
-Electrolyte transport across epithelial surfaces, particularly renal conservation of Na in exchange for K

-3. Dehydroepiandrosterone (DHEA)
-Secondary sexual characteristics (in females)
-Adrenal axis →→ important role in stress response by rapidly increasing cortisol levels
-Major precursor of the urinary 17-ketosteroids

Question 5

cushing syndrome

Answer 5

-Caused by excessive quantities of glucocorticoids
-Endogenous
-Exogenous
-S & S are similar:
-Relatively nonspecific
-Multiple physiologic systems affected

Question 6

exogenous etiology: cushing syndrome

Answer 6

-Iatrogenic
-MC cause of Cushing’s syndrome
Administration of excessive glucocorticoids

Question 7

endogenous etiologies: cushing syndrome

Answer 7

-Excessive secretion of cortisol may be caused by:

-Primary hypercortisolism(ACTH-independentCushing syndrome)
-Increased ACTH production by a pituitary tumor -> Cushing’s disease; 65-70% of diagnosed endogenous cases

-Ectopic ACTH production by a nonpituitary tumor
-Neoplasms of - lung, pancreas, kidney, thyroid, thymus
-Small cell lung carcinoma, pancreatic & Adrenal CA

-By excessive cortisol production by an adrenal adenoma or carcinoma

Question 8

other cushing syndrome etiologies

Answer 8

-Bilateral micronodular dysplasia
-Bilateral ACTH-independent macronodular hyperplasia
-Ectopic production of corticotropin-releasing hormone (CRH)

Question 9

age

Answer 9

-Cushing’s disease occurs primarily in women between 25 and 45 years of age
-Age at which ectopic ACTH syndrome develops parallels development of lung cancer -> increasing rapidly after 50 years of age
-Uncommon in children

Question 10

symptoms

Answer 10

-Weakness is common - Associated with proximal myopathy
-Low back pain- vertebral collapse or fracture 2ry to osteoporosis
-Depressed mood
-Emotional lability
-Frank psychosis
-Polyuria & polydipsia
-Weight gain
-Irregular periods
-Stretch marks
-Easy bruising
-Symptoms of hyperandrogenism

Question 11

signs

Answer 11

-Acne
-Oily skin
-Glucose intolerance
-Mild hirsutism in women
-Oligomenorrhea or amenorrhea
-ED in men
-Decreased libido
-Ankle edema
-Hyperpigmentation (a result of excess ACTH)
-Proximal muscle wasting and weakness
-Osteopenia
-moon face
-straie
-axillary pigmentation

Question 12

associated disorders

Answer 12

-Diabetes mellitus
-Pseudo-Cushing’s syndrome- Chronic alcoholism and depression
-Acute illness- Elevated plasma and urine cortisol levels
-Chronic inflammatory disease – use of steroids
-MEN type 1

Question 13

diff dx

Answer 13

-Pseudo-Cushing’s syndrome- alcohol and depression; resolves with abstinence

-Obesity

-Polycystic Ovarian Syndrome (PCOS)
-Amenorrhea or oligomenorrhea
-Obesity
-Hirsutism
-Polycystic ovaries

-depression
-physical stress
-malnutrition
-eating disorder
-uncontrolled diabetes
-OSA
-alcoholism

Question 14

work up

Answer 14

-Screening tests- To establish the presence of pathological hypercortisolism
-Once confirmed, further testing to determine cause
-Clinical features of Cushing’s syndrome are often easily recognizable

Question 15

suspicion chart

Answer 15

Theovernightdexamethasonesuppression testis an easy screening test for hypercortisolism and is particularly sensitive for mild ACTH-independent hypercortisolism from an adrenal nodule.Dexamethasone1 mg is given orally at 11PMand serum collected for cortisol determination at 8AMthe next morning; a cortisol level less than 1.8 mcg/dL (50 nmol/L, high-performance liquid chromatography [HPLC] assay) excludes Cushing syndrome with some certainty. However, 8% of established patients with pituitary Cushing disease have dexamethasone-suppressed cortisol levels less than 2 mcg/dL (55 nmol/L). Several antiseizure drugs(eg,phenytoin,phenobarbital,primidone) andrifampinaccelerate the metabolism ofdexamethasone, causing a lack of cortisol suppression bydexamethasone. Estrogens—during pregnancy or as oral contraceptives or HRT—may also cause lack ofdexamethasonesuppressibility.

bilateral inferior petrosal sinus sampling (BIPSS) is considered gold standard in this regard. Stimulation using corticotrophin-releasing hormone (CRH) improves the sensitivity of BIPSS,

Question 16

another suspicion chart

Answer 16

Question 17

tests

Answer 17

-Late night serum cortisol

-ACTH level
-Low level indicates adrenal adenoma or carcinoma
-High levels indicate pituitary or ectopic source

-Inferior petrosal sinus sampling- Gold standard for differentiating ectopic and pituitary ACTH production

-The high dose dexamethasone suppression tests -> Shows little fall in cortisol in the setting of ectopic ACTH production
-CT abdomen
-MRI - pituitary

Question 18

question

Answer 18

1. Do three 24 urinary-free cortisol collecting tests. If positive, this test only tells you cushing’s is present (but not the cause of cushing).
2. Do a low dose dexamethasonesuppression test. If no suppression that means you have cushing syndrome (adrenal cause) and no further testing is needed. If suppression occurs continue to step 3.
3. Do a high dose dexamethasone suppressiontest. If suppression occurs you have cushing disease (pituitary cause), if suppression doesn’t occur your cause is ectopic.
4. Do an inferior petrosal sinus sampling to confirm whether or not cushing is ectopic or pituitary.

Question 19

treatment goals

Answer 19

-To cure the syndrome by reduction of cortisol secretion to normal
-To eradicate any tumor threatening the health of the patient
-To prevent permanent dependency on medications if possible
-To avoid permanent hormone deficiency if possible
-To correct other concomitant hormonal derangements

Question 20

treatment

Answer 20

-Pts must receive tx for cortisol-dependent comorbidities, including osteoporosis, psychiatric disorders, diabetes mellitus, hypertension, hypokalemia, muscle weakness, and infections.
-Bone densitometry - recommended for all patients and treat osteoporosis

-Adjunctive medications
-Metyrapone – inhibits cortisol synthesis
-Adrenal enzyme inhibitors- Ketoconazole or Adrenal steroidogenesis blocker

-cushing disease:
-surgical therapy
-trans sphenoidal resection

-pituitary radiation

-adrenalectomy- mitotane- antineoplastic (adrenal carcinoma)

Question 21

prognosis

Answer 21

-Cushing’s disease is often curable
-Follow up - essential for late relapses/effects of cortisol

-Mortality due to
-Cardiovascular
-Thromboembolic
-Hypertensive complications
-Increased susceptibility to bacterial infections

-Hypertension and glucose intolerance -Improve but may not be cured

-Vertebral compression fractures
-Aseptic necrosis of proximal long bones- Cause permanent deformity

Question 22

clinical pearls

Answer 22

-Diagnosis and differential of Cushing’s syndrome
-Often quite difficult and confusing
-If there is reasonable doubt - refer to an endocrinologist

-Striae of Cushing’s syndrome
-Differ from those found in endogenous obesity
-Wide, deep, and dark purple in Cushing’s

-Absence of a pituitary adenoma by CT or MRI
-Does not rule out Cushing’s disease
-Up to 50% of surgically proven pituitary adenomas are not radiographically visualized

-Alcoholic patients
-Clinical and biochemical features identical to those of Cushing’s syndrome
-Testing while abstinent is required

-Electrolyte abnormalities
-A more rapid onset, wasting, and a greater degree of illness may point to an ectopic source of ACTH production
–e.g. small cell carcinoma of the lung