Adrenal Gland Disorders

• Adrenal gland disorders affect the suprarenal glands.
• Suprarenal glands are divided into the cortex and medulla, each with distinct functions including regulating the sympathetic nervous system.
• Suprarenal glands act as anti-stress glands, responding to every kind of stress uniformly.
• Hypoadrenia, or adrenal fatigue, happens when stress exceeds the body's compensatory capacity.

Hormones Secreted by the Adrenal Cortex

• The adrenal cortex secrete corticosteroids.
• These hormones include glucocorticoids (cortisol, cortisone), mineralocorticoids (aldosterone), and androgens (steroid hormones).

Aldosterone (Mineralocorticoid)

• Aldosterone is produced by the outer layer (zona glomerulosa) of the adrenal cortex and affects blood pressure.
• Aldosterone influences the distal convoluted tubule and collecting duct of the kidney.
• Aldosterone leads to increased sodium reabsorption and increased potassium and hydrogen ion excretion.
• This hormone's action results in hypernatremia, hypokalemia, and metabolic alkalosis.
• Angiotensin II and extracellular potassium regulate aldosterone production.

Renin-Angiotensin-Aldosterone System (RAAS)

• RAAS is impacted by reduced renal blood flow and sodium levels.
• The juxtaglomerular apparatus of the kidneys responds to this reduction.
• Renin is released, leading to the conversion of angiotensinogen to angiotensin I.
• Angiotensin I converts to angiotensin II in the lungs.
• Angiotensin II, a powerful vasoconstrictor, stimulates the adrenal cortex to produce aldosterone.
• Aldosterone is the main regulator of sodium retention.

Cortisol (Glucocorticoid)

• Cortisol is produced by the middle layer (zona fasciculata) of the adrenal cortex.
• The zona fasciculata secretes cortisol at a basal level.
• Bursts of cortisol are released in response to adrenocorticotropic hormone (ACTH) from the anterior pituitary.
• Cortisol suppresses the immune system, helps in glycogen and lipid metabolism, and enhances the activity of glucagon and catecholamines.
• This hormone also suppresses inflammatory reactions.

Regulation of Cortisol Secretion

• Stress and diurnal rhythm stimulate the hypothalamus.
• The hypothalamus releases corticotropin-releasing hormone (CRH), which acts on the anterior pituitary.
• CRH stimulates the anterior pituitary to release ACTH, which stimulates the adrenal cortex.
• In turn, the adrenal cortex releases cortisol.
• Increased blood glucose, blood amino acids, and blood fatty acids can increase cortisol levels.
• Cortisol then acts on target organs.

Androgens (Steroid Hormones)

• Sex hormones (DHEA) are produced in the inner layer (zona reticularis) of the adrenal cortex.
• Androgens have minimal direct effect on the development of male characteristics.
• They convert to testosterone and DHT, or to estrogens in gonads, acting as a metabolic intermediate.
• The sympathetic nervous system regulates androgen production.

Hormones of the Adrenal Medulla

• Adrenal medulla hormones are not essential for life, but supports coping with physical and emotional stress.
• Catecholamines are secreted.
• Epinephrine (adrenaline) makes up 80% found within the blood.
• It increases heart rate and force of heart contractions, facilitates blood flow to muscles and the brain, relaxes smooth muscles, helping with the conversion of glycogen to glucose in the liver.
• Norepinephrine (noradrenaline) has little impact on smooth muscle, metabolic processes, and cardiac output, but is strongly vasoconstrictive, increasing blood pressure.

Adrenal Dysfunction

• Adrenal dysfunction includes decreased function (adrenal insufficiency, low cortisol/aldosterone, Addison's disease) and increased function.
• Increased function includes: hyperaldosteronism (high aldosterone), Cushing syndrome (high Cortisol), and Pheochromocytoma (high catecholamine).

Mineralocorticoid Excess

• Primary hyperaldosteronism is caused by adrenal gland problems.
• Conn syndrome features increased aldosterone secretion from adrenal glands.
• Primary hyperaldosteronism results from the excess production of aldosterone from the adrenal gland (zona glomerulosa).
• Peak incidence typically occurs in the third to sixth decades of life.
• Both primary and secondary hyperaldosteronism present more frequently in women.

Pathophysiology of Mineralocorticoid Excess

• Mineralocorticoid excess results primarily from two subtypes: unilateral aldosterone-producing adenoma (Conn syndrome) in one-third of cases, and bilateral idiopathic adrenal hyperplasia in two-thirds of cases.
• Rarely, adrenocortical carcinomas, ectopic aldosterone-secreting tumors, ovarian tumors, and familial hyperaldosteronism can secrete aldosterone.

Secondary Hyperaldosteronism

• Secondary hyperaldosteronism involves problems outside the adrenal glands.
• It's due to overactivity of the renin-angiotensin-aldosterone system (RAAS), increasing renin-angiotensin and aldosterone secretion.
• Causes include CHF, liver cirrhosis and ascites, nephrotic syndrome as a juxtaglomerular cell tumor, and renal artery stenosis.
• Reduced blood supply across the juxtaglomerular apparatus stimulates renin production.
• Secondary hyperaldosteronism is usually treated with medical therapy.

Clinical Manifestations of Aldosteronism

• Patients with aldosteronism can be asymptomatic.
• Hypertension is a key sign.
• Blood pressure can range from normotensive to severe hypertension, even refractory hypertension.
• Resistant hypertension is the most common symptom.
• Hypertension, if untreated, can lead to coronary artery disease, congestive heart failure, stroke, and intracerebral hemorrhage.
• Hypertensive patients, particularly those with drug-resistant hypertension, should be tested for hyperaldosteronism.
• Severe hypokalemia can result in fatigue, muscle weakness, cramping, paralysis, headaches, and palpitations.
• Polydipsia and polyuria can also occur from hypokalemia-induced nephrogenic diabetes insipidus because of antidiuretic hormone resistance in the renal tubule.
• Hyperglycemia or frank diabetes mellitus may present due to impaired potassium dependent insulin secretion.
• Metabolic alkalosis will lower ionized calcium levels, potentially causing tetany.

Conn's Syndrome Indicators

• Hypertension that isn't responding to standard blood pressure medications.
• Indicates reduced blood potassium, headaches, blurred vision, tiredness, muscle weakness and polyuria.

Investigations: Laboratory Studies

• Hypernatremia will be present.
• Hypokalemia may be seen with primary aldosteronism: normokalemic hypertension is the most common presentation, so the lack of hypokalemia does not exclude diagnosis.
• PAC:PRA ratio measures plasma aldosterone concentration to plasma renin activity.
• A ratio of ≥ 25 is indicative of primary hyperaldosteronism.
• The aldosterone-to-renin ratio is abnormally increased in primary hyperaldosteronism.
• The aldosterone-to-renin is decreased or normal, but with high renin in secondary hyperaldosteronism.
• Metabolic alkalosis can be found.

Pre-Screening Test Considerations

• Thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin antagonists, and beta-blockers need to be stopped for 4-6 weeks before testing as they will interfere.
• Additional medications that can affect results include ACE inhibitors and mineralocorticoid receptor antagonists like spironolactone.

Imaging and Genetic Studies

• CT scanning and MRI are used to detect adenomas and confirm primary aldosteronism diagnosis.
• Genetic testing is advised in patients under 20 with a family history of familial hyperaldosteronism.

Conn's Syndrome Treatment

• Surgical removal via unilateral adrenalectomy is the best treatment for patients with unilateral Primary hyperaldosteronism (PA).
• Laparoscopic approach almost always performed.
• Treat bilateral hyperplasia with potassium-sparing diuretics such as spironolactone (aldosterone antagonist).
• Prior to surgery, give patients 8-10 weeks of medical therapy to decrease blood pressure and correct associated metabolic syndromes, decreasing surgical risk.
• Prescribe a sodium-restricted diet (
• Follow-up is recommended in both surgically and medically treated PA patients.
• The estrogen associated adverse effects of spironolactone limits use in men, including impotence and gynecomastia.
• Eplerenone, amiloride, and triametrine, selective anti-aldosterone agents (receptor antagonists), which do not have anti-androgen adverse effects.
• 50-70% of patients experience complete normalization of BP post-adrenalectomy of adenoma, without further antihypertensive therapy.
• Remaining patients need antihypertensive treatment but with reduced doses and/or number of medications.
• Treating the underlying disease for resolution of symptoms.

True/False question and answer

• Test case detection by measuring the aldosterone-renin ratio to differentiate between primary and secondary hyperaldosteronism. (True,)