Endocrinology three

ACTH Release

• ACTH release is accompanied by melanocyte-stimulating hormone (MSH).
• Increased ACTH leads to increased MSH, causing increased pigmentation.
• Increased pigmentation is a classic diagnostic sign of Cushing's.

Diagnosing Spontaneous Cushing’s

• Measure urinary free cortisol.
• Repeat cortisol levels to check for loss of circadian rhythm which indicates a lack of control and an excess of cortisol.
• Dexamethasone suppression test (0.5mg Dex qds): endogenous serum cortisol should be suppressed in 48 hours via negative feedback.
• Failure of suppression suggests ACTH-independent pathology, such as ectopic ACTH or direct adrenal tumor secretion
• Low/undetectable plasma ACTH indicates non-ACTH-dependent disease.
• CRF test: exaggerated ACTH response to exogenous CRF suggests pituitary-dependent Cushing’s.
• Use chest X-rays, bronchoscopy, or CT scans to locate tumors.
• Selective venous sampling localizes ACTH-producing tumors in serious cases.

Managing Spontaneous Cushing’s

• Surgical removal of the pituitary (transsphenoidal route).
• Metyrapone inhibits cortisol release in cases unsuitable for surgery.
• Pituitary irradiation is used as salvage for impossible or failed surgeries.
• Iatrogenic Cushing's (chronic overdose) responds to steroid reduction or cessation if possible.
• Reduce immunosuppressive steroid doses using steroid-sparing strategies like azathioprine in immune-diseases.

Dental Implications of Cushing’s

• Patients with Cushing's are at higher risk for periodontal disease and tooth loss due to hypercortisolism.
• Cortisol inhibits white blood cells from migrating to fight bacteria between gums and teeth.
• Cortisol inhibits new bone formation, contributing to osteoporosis of the jawbone.

Addison’s Disease

• Also known as hypoadrenalism.
• Addison’s syndrome is more common than Addison’s disease.
• Endogenous steroid production can be suppressed by exogenous therapeutics.
• Exogenous therapeutics are not long-term solutions; abrupt cessation can cause issues, and side effects include thin bones, skin, and gastric reflux.

Addisonian Crisis

• Occurs when cortisol levels are inadequate, leading to a hypotensive crash.

Consequences of Addisonian Crisis

• Vomiting
• Abdominal pain
• Low sodium (Na+), high potassium (K+)
• Low blood sugar
• Hypovolemic shock: impaired vascular shunting due to lack of cortisol's potentiation of adrenaline.

Clinical Features of Addison’s Disease

• Insidious development of lethargy, anorexia, and weight loss.
• Hypotension, often postural.
• Hyperpigmentation of buccal mucosa, skin creases, and scars.
• Can present as an Addisonian crisis which can involve vomiting, abdominal pain, low sodium/high potassium, low blood sugar, and hypovolemic shock.

Diagnosing Addison’s Disease

• Serum chemistry: low sodium, high potassium, elevated urea, hypoglycemia.
• Adrenal auto-antibodies present.
• Chest/abdominal X-rays may show TB evidence (e.g., calcified nodes and adrenals).
• Short Synacthen test (synthetic ACTH): blood taken for baseline plasma.

Managing Addison’s Disease

• Lifelong supplementation required.
• Hydrocortisone (20mg in the morning, 10mg at night) to mimic circadian rhythm.
• Fludrocortisone (synthetic mineralocorticoid, 0.05-0.4mg once daily).

Secondary Hypoadrenalism

• Caused by hypothalamic-pituitary axis disease or long-term steroid therapy.

Addisonian Patients in Stressful Situations

• Insufficient cortisol production to accompany adrenaline for vascular shunting.

Recommendations for Addison’s Patients Before Surgery

• Monitor blood pressure.
• Establish IV access.
• Take an extra steroid tablet the night before or an hour after the procedure.

Recommendations for Steroid-Dependent Addison’s Patients Before/After Major Dental Surgery (e.g., Extraction)

• Administer 100mg hydrocortisone IM just before anesthesia.
• Double the normal oral medication dose for 24 hours post-surgery, then return to normal dose.

Recommendations for Steroid-Dependent Addison’s Patients Before/After Dental Surgery (e.g., Root Canal)

• Double normal dose (up to 20mg hydrocortisone) one hour prior to surgery.
• Double the normal oral medication dose for 24 hours post-surgery, then return to normal dose.

Recommendations for Steroid-Dependent Addison’s Patients Before/After Minor Dental Procedure (e.g., Filling)

• Take an extra oral dose 60 minutes before the procedure.
• Take an extra dose if hypoadrenal symptoms occur, then return to normal dose.

Mineralocorticoids

• Steroid hormones.
• Promote renal sodium reabsorption and potassium excretion in the distal convoluted tubule (DCT) via Na/K exchange pumps.

Aldosterone

• Example of a mineralocorticoid.
• Secretion is largely independent of ACTH.
• Primarily driven by the renal Renin-Angiotensin system.
• Increased by low plasma sodium or low blood pressure.
• High potassium directly stimulates aldosterone secretion.

Conn’s Syndrome

• Also known as hyperaldosteronism.

Consequences of Primary Adrenal Adenoma in Conn’s Syndrome

• Excess fluid retention.
• Hypokalemia (low potassium, high sodium).
• Secondary hypertension.

Secondary Hyperaldosteronism in Conn’s Syndrome

• Caused by excess stimulation through the renin-angiotensin axis.

Endocrine Causes of Hypertension in Conn’s Syndrome

• Excess renin production due to renal artery stenosis or a renin-secreting tumor.
• Excess aldosterone production from an adrenal adenoma or hyperplasia.
• Excess production of other steroids (e.g., Cushing’s where cortisol acts as a weak mineralocorticoid).
• Excess catecholamines due to Pheochromocytoma (adrenal medulla tumor).
• Oral contraceptive pills (mechanism unclear).

Diagnosing Conn’s Syndrome

• Serum potassium is low.
• Serum sodium is high in primary hyperaldosteronism and low in secondary.
• Alkalosis.
• Serum aldosterone levels are high in primary hyperaldosteronism due to suppressed renin levels, and increased in secondary due to increased plasma renin.
• CT/MRI scans show adrenal/renal masses.

Managing Conn’s Syndrome

• Surgical resection of an adenoma.
• Hypertension from hyperplasia can be managed with spironolactone (aldosterone antagonist).

Congenital Adrenal Hyperplasia

• Congenital defect in steroid synthesis.
• Typically caused by a defect in the steroid-21 hydroxylase enzyme.

Mechanism of Action for Congenital Adrenal Hyperplasia

• 17-hydroxyprogesterone accumulates and is processed to androgens in the zona fasciculata of the adrenal cortex.
• Cortisol, and sometimes aldosterone, levels are low, and ACTH is high.

Common Presentation of Congenital Adrenal Hyperplasia

• Infertile and hirsute young hypotensive females with salt-losing kidneys.
• In young boys, can cause precocious puberty.

Growth Hormone

• Hyperglycemic hormone.
• Secreted by the adenohypophysis (anterior pituitary).
• Its effects are mediated via Insulin-like Growth Factor (IGF-1), synthesized in the liver.