Adrenal Gland Disorders Flashcards
Hypothalamus - Pituitary - Adrenal Axis
- Hypothalamus: Secretes CRH
- Pituitary: Secretes ACTH
- Adrenal glands: Secrete Cortisol
- Cortisol feeds back to suppress at the level of the hypothalamus and pituitary
Physiologic effects of Cortisol
- Supports increased energy substrate
availability during stress (anti-insulin effect)
» Increase hepatic gluconeogenesis
» Permissive for lipolysis leading to increased free fatty acids (FFA)
» Increase skeletal muscle breakdown to
provide amino acids (alanine) for gluconeogenesis
» Decrease glucose uptake into muscle and
fat - Regulates Immune and Inflammatory responses
» Immunosuppressive actions: causes apoptosis
of T lymphocytes, suppresses IL-2 production,
suppresses proliferation of lymphocytes.
» Induces lipocortins which mediate local antiinflammatory responses and inhibits phospholipase, thereby inhibiting production of
aracidonate metabolites (prostaglandins,
leukotrienes, lipoxins).
» Directly inhibits prostaglandin synthesis
» Inhibits inflammatory cytokines
Cortisol actions on various organs
- Bone: Inhibition of collagen synthesis • Skin: inhibits fibroblast proliferation • CNS: Modulates affect (depression or euphoria) • CV: Increases cardiac contractility, increases vascular reactivity to vasoconstrictors (catecholamines and angiotensin-II • Kidney: Decreased calcium reabsorption, increases GFR
Cushing Syndrome
- Excess ACTH (pituitary)
- Characterized by loss of diurnal variability in serum cortisol; levels late in the day are no long suppressed
• “Cushingoid” habitus: centripital obesity,
moon facies, supraclavicular fat pads,
bruising, purple striae
• Immunosuppression: infections
• Bone dimineralization
• Affective disorder: mania or depression
• Glucose intolerance
• Mineralocorticoid effects: hypertension,
hypokalemia
• Androgen effects: hirsutism, acne, balding
DDX of Cushing Syndrome
- Cushing: Pituitary adenoma, releasing excess ACTH
- can have normal serum ACTH, so ACTH measurements are not diagnostic - Adrenal neoplasm: excess cortisol
- low ACTH - Ectopic ACTH production
- have highest levels of ACTH
- most commonly from small cell lung cancer
- Measurement of ACTH can help differentiate, but is not diagnostic
High-Dose Dexamethasone Suppression Test
- Dexamethasone: a potent synthetic glucocorticoid (like cortisol)
- a differentiating test
- The normal response is to suppress
cortisol levels.
• In patients with Cushing syndrome, the
cortisol does not suppress.
- complete suppression indicates cortisol-secreting adrenal tumor)
- partial suppression indicates ACTH-secreting pituitary tumor
- No suppression indicates ectopic ACTH syndrome
CRH Stimulation Test in Cushings
- administer CRH (normally secreted by hypothalamus to raise levels of ACTH)
1. ACTH-secreting adenoma of pituitary: further raises ACTH secretion
2. Adrenal neoplasm: Cortisol is suppressing ACTH, so there will be no rise in ACTH secretion
3. Ectopic ACTH Syndrome: No change in ACTH secretion or cortisol release
Nelson Syndrome
- Growth of a pituitary adenoma in a patient with Cushing disease previously treated by bilateral adrenalectomy
- so patient still has an ACTH-secreting pituitary adenoma
Presentation:
- sella expansion; may impinge on optic chiasm
Clinical Presentation of Acute
Adrenal Insufficiency
• Shock unresponsive to volume expansion and pressors; cortisol is necessary for vascular tone • Weakness, apathy, confusion • Nausea, vomiting, anorexia • Fever, abdominal pain
Laboratory:
» Hyponatremia, hyperkalemia, acidosis, azotemia,
hypoglycemia, lymphocytosis, eosinophilia
Addison’s Disease
- Chronic primary adrenal insufficiency due to adrenal atrophy or destruction by disease (commonly autoimmune, TB or metastasis)
- Characterized by Adrenal Atrophy and Absence of hormone production, involving all 3 cortical divisions (spares medulla)
Deficiency of aldosterone and cortisol results in:
- hypotension
- hyperkalemia
- acidosis
- skin hyper pigmentation (due to MSH, by-product of upregulated ACTH production)
Cosyntropin (or Cortrosyn) Stimulation Test
- Cosyntropin: Synthetic ACTH fragment
Method: Administer cosyntropin, measure basal, 30 min and 60 min serum cortisol
• Normal response: » Maximum cortisol >20 g/dl
• The cosyntropin stimulation test assesses
adrenal reserve, but does not test
pituitary-hypothalamic function directly.
Patients with partial or recent-onset
secondary adrenal insufficiency may have
an inappropriately “normal” response.
- There will be no rise in cortisol production for primary adrenal insufficiency or chronic secondary adrenal insufficiency (due to involution of the adrenal glands)
Distinguish Secondary adrenal insufficiency from Addison’s
- the adrenal glands will be able to make mineralocorticoid (aldosterone)
- no skin hyperpigmentation
- no hyperkalemia: aldosterone aids excretion of potassium
Side effect of long-standing treatments of exogenous glucocorticoids
- suppresses ACTH at level of pituitary
- causes zona faciculata and reticularis to atrophy
- Following prolonged exposure to high levels of glucocorticoids, both the central axis
(hypothalamus-pituitary) and the adrenal glands must recover from suppression - Hence: Patients on long-term glucocorticoids must be tapered off slowly to permit recovery of the adrenal axis while
protecting the patient from acute adrenal insufficiency.
Renin-Angiotensin-Aldosterone Axis
- JGA of kidney detects low blood pressure, triggering renin secretion
- Renin breaks down angiotensinogen into angiotensin I
- ACE (from lungs) converts Angiontensin I into Angiotensin II
- Angiotensin II acts on adrenal glands to secrete Aldosterone
- Angiotensin stimulates the epithelial cells in the distal tubule and collecting ducts of the kidneys to increase re-absorption of sodium and water, and secretion of potassium into the urine
Stimulation & Suppression of RAA in Primary Hyperaldosteronism
Furosemide:
- normal: stimulates renin activity
- Primary: Renin is not stimulated b/c it is being suppressed by high levels of aldosterone
Saline:
- Normal: should suppress aldosterone
- Primary: Aldosterone is not suppressed
