endocrinology *2

Acute Hypoglycaemia

• Occurs when sugar flow is insufficient for the level of insulin present.
• Should be regulated by hypoglycaemic hormones, but these are overwhelmed by the relative insulin levels.

Causes of Acute Hypoglycaemia

• Frequent complication of insulin therapy.
• Occasional problem with sulphonylurea drugs.
• Fulminant liver and renal failure impairs hepatic and renal cortical gluconeogenesis.
• Excess alcohol inhibits hepatic gluconeogenesis and enhances insulin secretion to carbohydrate stimuli.
• Insulinomas produce excessive insulin.
• Addison’s disease (low cortisone production) impairs gluconeogenesis.
• Patient self-management issues, such as reduced food intake due to vomiting or skipped meals without adjusting insulin levels, leading to insulin overdose.

Signs and Symptoms of Acute Hypoglycaemia

• Hunger, sweating, pallor, and tachycardia (heart rate exceeding 100) due to increased sympathetic tone.
• Personality changes, such as aggression.
• Peripheral tingling and altered sensations.
• Fits, hemiparesis (paralysis), and potential coma.

Diagnosis of Acute Hypoglycaemia

• Fingerprick blood glucose measurement and lab serum glucose analysis.

Treatment of Acute Hypoglycaemia (Conscious Patient)

• Rapid ingestion of sugar.

Treatment of Acute Hypoglycaemia (Unconscious Patient)

• IV glucose (50ml of 50% dextrose).
• Glucagon 1mg IM to rapidly release glucose from liver glycogen, but effect is single and of short duration.

General Rule

• Always administer dextrose or glucagon if acute hypoglycaemia is suspected.
• Never give insulin, as it could be fatal.

Diabetic Ketoacidosis (DKA)

• Two typical scenarios leading to DKA are previously undiagnosed diabetes and missed insulin doses (or relative under-dosing).
• Do not stop insulin when a patient is ill and off food, as DKA could occur.
• Increased metabolism to fight illness requires more insulin.
• Reducing insulin doses can be fatal by causing relative hypoinsulinemia.

Pathophysiology of DKA

• Insulin deficiency leads to uncontrolled catabolism (tissue breakdown).
• Hepatic gluconeogenesis is unrestrained.
• High blood sugar levels produce glycosuria, osmotic diuresis, and dehydration.
• Peripheral lipolysis and proteolysis produce energy, but also circulating free fatty acids.
• Free fatty acids go to the liver and degrade to acidic ketones (acetone/acetoacetate and beta-OH-butyrate).
• Stress hormones (catecholamines, glucagon, and cortisol) accelerate the process.
• Tissues that cannot get sugar from blood start to break themselves down (autolysis).

Clinical Features of DKA

• Profound dehydration due to renal water and electrolyte losses.
• Low blood pressure.
• Air hunger (Kussmaul’s respiration) to compensate for metabolic acidosis.
• An adult can lose approximately 6L of water, 500mmol of Na, and 400mmol of K.

Test Results in DKA

• High blood glucose levels (>20).
• Plasma shows high ketone levels (+++).
• Urine dipstick shows glycosuria (+++) and ketonuria (+++).
• Serum urea and creatinine are elevated (dehydration), while K and Na are low.

Treatment Aims for DKA

• Restore fluid and electrolyte losses.
• Administer insulin to reduce blood sugar levels and allow cells to use glucose.
• Supply extra K, as serum levels decrease with cell glucose return (K and glucose are co-transported).
• Restore acid-base balance.

Hyperosmolar Non-Ketotic State (HONK)

• Severe hyperglycaemia develops without significant ketosis, typical in uncontrolled type 2 diabetes.
• Treatment is the same as for DKA, but there is no acidosis.
• 1/2 normal saline is recommended for fluid replacement if serum Na is very high.

Diabetic Control in Pregnant Women

• Poor diabetic control increases the risk of congenital defects in the offspring.
• Pregnant women tend to be more hypoglycaemic.
• Pregnancy can impair glucose tolerance due to the mother feeding a growing child.
• Gestational diabetes can occur and typically terminates with the pregnancy.

Adrenal Glands

• Two functional parts:
  • Medulla: catecholamine production (Endocrine Sympathetic system).
  • Cortex: steroid hormone production (essential for life).
• Three parts of the adrenal cortex:
  • Zona glomerulosa: aldosterone.
  • Zona fasciculata: glucocorticoids.
  • Zona reticularis: sex hormones.

Glucocorticoids

• Three functions:
  • Increased protein catabolism.
  • Increased glycogenolysis (glycogen to glucose).
  • Increased gluconeogenesis (glucose production).
• Example: Cortisol.
• Mechanism of action:
  • Sensitise arterioles to noradrenaline action, vital for blood pressure maintenance of circulatory volume.
• Effect on water excretion:
  • Inhibits ACTH secretion by negative feedback.
  • Initiates diuresis, thus has a permissive effect on water excretion.
• Serum cortisol levels:
  • Lowest at midnight.
  • Peaks upon waking.

Cushing’s Syndrome

• Persistent and inappropriately elevated plasma cortisol levels.
• Mostly from exogenously supplied steroids.

Cushing’s Disease

• Glucocorticoid excess secondary to inappropriate ACTH secretion only.
• May be due to an ACTH-producing tumour or pituitary tumour.

Aetiologies of Spontaneous Cushing’s

• ACTH-dependent:
  • Pituitary adenoma (Cushing's disease): 60%.
  • Ectopic ACTH-producing tumours: 15% (e.g., oat cell lung cancer).
• ACTH-independent:
  • Adrenal adenoma: 9%.
  • Adrenal carcinoma: 7%.

Clinical Features of Spontaneous Cushing’s

• Obesity with fat centrally distributed (trunk/abdomen/buffalo hump on neck).
• Red, plethoric complexion and thin skin, which bruises easily (protein catabolic effect).
• Moon face.
• Purple striae on the abdomen, breasts, and thighs.
• Pigmentation around wounds and scars (melanin) if ACTH-dependent.

ACTH Release

• Accompanied by MSH (melanocyte-stimulating hormone).
• Increased ACTH leads to increased MSH and increased pigmentation.

Investigations for Spontaneous Cushing’s

• Read urinary free cortisol.
• Repeat cortisol levels to assess for loss of circadian rhythm.
• Dexamethasone suppression test (0.5mg Dex qds) looking for endogenous serum cortisol suppression by negative feedback, unless ACTH-independent pathology.
• Plasma ACTH is low/undetectable in non-ACTH-dependent disease.
• CRF test: exaggerated ACTH response to exogenous CRF implies pituitary-dependent Cushing’s.
• Chest X-ray, bronchoscopy, CT scan to find tumours.
• Selective venous sampling to localise an ACTH-producing tumour in serious cases.

Management of Spontaneous Cushing’s

• Surgical removal of the pituitary (trans-sphenoidal route).
• Metyrapone inhibits cortisol release in cases not amenable to surgery.
• Pituitary irradiation as salvage for impossible or failed surgery.
• Iatrogenic Cushing’s (chronic overdose from clinical features) responds to reduction/ cessation of the steroid and use steroid-sparing strategies (e.g., azathioprine in immuno-diseases).