14. Glucocorticoid deficiency and overproduction, Addison's and Chusing's Flashcards
What are the physiological causes of glucocorticoid excess?
- Stress,
- pregnancy,
- prolonged and intensive physical activity
What are some pathological causes of glucocorticoid excess?
- Iatrogenic Cushing’s syndrome,
- Cushing’s syndrome
What are some complications of Cushing’s syndrome?
- Cardiovascular (MI, HT, hypokalemia),
- Neuropsychiatric (depression, anxiety),
- Metabolic (diabetes, hepatic steatosis, obesity),
- Reproductive (infertility)
- Skin (skin thinning, poor wound healing)
- Thromboembolic
- Muskuloskeletal (osteoporosis, myopathy)
What is the prevalence of Cushing’s disease? At what age does it usually occur? M/F ratio?
The prevalence is 39/million. It can occur at any age, but it is most frequent between 25-45 years. The female/male ratio is 3-4/1.
What is the prevalence of ACTH-dependent forms of endogenous Cushing’s syndrome in adulthood?
70%
What is the most common form of ACTH dependant Cushing syndrome?
Pituitary adenoma (aka Cushing’s disease)
What is the prevalence of adrenal tumours in endogenous Cushing’s syndrome?
23%
What are the most common concomitant disorders in patients with Cushing’s?
- High blood pressure
- Hyperglycemia
- Osteoporosis
What are the main signs to differenciate between Cushing’s syndrome and simple obesity?
- Skin thinning, easy bruising
- Myopathy
What are the laboratory tests used for the diagnosis of cortisol excess in Cushing’s syndrome?
- Urinary free cortisol,
- midnight serum cortisol,
- midnight salivary cortisol,
- low dose dexamethasone suppression test.
What is the interpretation in the short (overnight) dexamethasone test?
Normal if < 1,8 microg/dl (<50 nmol/l).
What are the different forms of dexamethasone suppression test?
- Once (midnight, short, overnight)
- Repeated (two days, standard, long test / liddle test)
What are the different doses of dexamethasone used in the short dexamethasone suppression test?
Low-dose: 1 mg,
High-dose: 8 mg,
What are the laboratory tests used for the differential diagnosis of ACTH-dependent hypercortisolism?
- Basal ACTH,
- high-dose dexamethasone suppression test,
- CRH test.
What does a high dose decamethasone suppression test tell us?
It tells us wether the problem is from the pituitary (Cushing’s disease) or a different site in the body (ectopic)
What is the difference in the progression of Cushing’s disease and ectopic ACTH syndrome?
- Cushing’s disease has a slow progression
- Ectopic ACTH syndrome has a rapid progression, with myopathy and hyperpigmentation
How is the serum ACTH in Cushing’s disease and in ectopic ACTH syndrome?
- Cushing’s : normal / elevated
- Ectopic : high / very high
Which of the 2 types of Cushing’s syndrome can be suppressed in dexmethasone testing?
Cushing’s disease can be suppressed (aka invisible) in high dose testing
What is inferior petrosal sinus sampling?
Sampling the ACTH levels directly from veins that drain the pituitary to then compare with peripheral blood levels
What is the treatment for ACTH-producing pituitary adenoma in Cushing’s syndrome?
- Surgical intervention with transsphenoidal adenomectomy
- Drugs : inhibition of ACTH secretion or steroid biosynthesis inhibitors
- Pituitary radiation
- Bilateral adrenalectomia
What is the medical treatment for inhibiting ACTH secretion?
- Carbergoline : D2 agonist
- Pasireotide : somatostatin analog
What are some steroid synthesis inhibitors used in the treatment of ACTH producing pituitary adenomas?
- Etomidate
- Metyrapone
- Osilodrostat
What is the potential complication of pituitary irradiation?
Panhypopituitarism.
What are some of the known ectopic tumors that can produce ACTH?
- Bronchial tumors,
- Pheochromocytoma,
- Gastrinoma,
- Other neuroendocrine tumours
Which imaging techniques can be used for differentiating ACTH-producing tumors?
- MRI
- CT
- PET-CT
- Somatostatin receptor scintigraphy
(all this is less good than inferior petrosal sinus sampling)
What are the treatment options for ectopic Cushing’s syndrome?
- Surgical removal,
- steroid-biosynthesis inhibitors,
- chemotherapy,
- inhibition of ACTH secretion (somatostatin-analog),
- isotope therapy
What are the clinical manifestations of cortisol-producing adrenal tumors?
- Cushing’s syndrome,
- abdominal pain,
- mineralocorticoid excess (DOC): hypertension, hypokalaemia, alkalosis,
- androgen excess: severe hirsutism, virilism,
- estrogens : gynecomastia, uterine bleeding
What are the treatment options for cortisol-producing adrenal tumors?
- Surgical removal,
- laparoscopic adrenalectomy
What is the peri-and postoperative management for patients undergoing surgical removal of cortisol-producing adrenal tumors?
Patients are at risk of adrenal insufficiency and should receive iv. hydrocortisone continued by per os replacement.
What is the drug treatment for adrenocortical cancer?
o’p’DDT : a steroid-biosynthesis inhibitor that has a cytolytic effect on adrenocortical cells. It is usually administered lifelong in combination with hydrocortisone and other drugs (EDP-M).
What is the glucocorticoid receptor antagonist used in the drug treatment of cortisol excess?
Mifepristone
What is glucocorticoid insufficiency?
A state of inadequate cortisol production, either due to
1. Primary failure of the adrenal cortex
2. Lack of stimulation of adrenal cortex by ACTH
What is primary adrenal insufficiency?
The lack of gluco-and mineralocorticoids due to adrenal destruction.
What is the etiology of primary adrenal insufficiency?
- autoimmune (70%),
- tuberculosis (20%),
- other (10%) - mycotic infections, amyloidosis, lymphoma, adrenal hemorrhage, ACTH-resistance.
What are the most common signs and symptoms of chronic adrenal insufficiency?
- Fatigue,
- anorexia,
- gastrointestinal symptoms
- salt craving,
- orthostatic hypotension,
- musculoskeletal pain.
What are the most common laboratory features of chronic adrenal insufficiency?
- electrolytes : Hyponatremia, hyperkalemia, alkalosis,
- hormones : low serum cortisol (unresponsive to iv. ACTH), elevated ACTH, low serum aldosterone, and increased plasma renin activity.
What is the laboratory diagnosis for adrenal insufficiency?
Basal serum cortisol levels below 5 microg/dl (140 nmol/l) confirm the diagnosis, while levels above 20 microg/dl (550 nmol/l) exclude it.
What is the recommended glucocorticoid replacement therapy for chronic adrenal insufficiency?
- Glucorticoid replacement
- Mineralocorticoid replacement
What is the recommended daily dose of hydrocortisone for glucocorticoid replacement therapy?
15-30 mg/day, in 2-3 doses.
What is the recommended daily dose of fludrocortisone for mineralocorticoid replacement therapy?
50-150 ug/day, in 1-2 doses.
What is the recommended treatment for Addisonian crisis?
100 mg hydrocortisone bolus, followed by slow infusion of hydrocortisone at 100-200 mg/day for the first day, along with physiological saline infusion
What is autoimmune polyendocrine syndrome?
rare, inherited disease in which the immune system attacks its own tissues (glands)
Hormonal features of cortisol-producing adrenal tumors
Suppressed ACTH, non-suppressible serum cortisol.
