Module 10 - Endocrine System

Endocrine System

A network of glands and organs that release hormones into the bloodstream

Hormones travel to target tissues and bind receptors to produce their effects

Key functions

• Metabolism and energy

• Reproduction

• Growth and development

• Response to stress

Goal

• Maintain homeostasis - too much or too little hormone has profound effects (e.g. diabetes)

Hormone Receptor Upregulation and Downregulation

Upregulation

• ↑ in the number of receptors on target tissues

• Usually occurs when hormone levels are low (body needs more hormone binding)

• Example: low thyroid hormone → more thyroid receptors expressed

Downregulation

• ↓ in the number of receptors; occurs when hormone levels are high

• Example: long-term drug (hormone) administration → body recognizes abundance → downregulates → cells become less responsive

Negative Feedback in the Endocrine System

Most hormone action is regulated through negative feedback — rising hormone levels inhibit further hormone production

Hormonal stimulus (HPT axis example)

• TRH (hypothalamus) → stimulates TSH (pituitary) → stimulates T3/T4 release (thyroid); rising T3/T4 inhibits TRH and TSH

Humoral stimulus

• Insulin and glucagon secretion driven by blood glucose concentration

Neuronal stimulus

• Hormones regulated by nerve impulses (e.g. epinephrine release, oxytocin from pituitary)

Hormone Pharmacotherapy

Replacement therapy

• When the body cannot secrete sufficient endogenous hormone

• Goal: supply the same amount the body would normally produce

• Example: insulin for type 1 diabetes

Exaggerate response

• Take advantage of a hormone's normal action at higher-than-physiological doses

• Example: corticosteroids for inflammation

Block activity

• Hormone antagonists that block the endogenous hormone

• Example: propylthiouracil to reduce an overactive thyroid

Pancreatic Hormones and Euglycemia

Cell types in the pancreatic islets

• Beta cells (60%) - secrete insulin

• Alpha cells (30%) - secrete glucagon

• Delta cells (10%) - secrete somatostatin

Actions

• After eating → insulin released → promotes glucose uptake into liver, muscle, adipose

• Fasting → glucagon released → promotes glucose release from liver

• Other counter-regulatory hormones: epinephrine, cortisol, growth hormone

Type 1 vs Type 2 Diabetes Mellitus

Type 1 (5-10% of DM)

• Autoimmune destruction of beta cells → no insulin produced

• Usually onset <25 years; peak age 13-14

• Rapid symptom onset; often thin

• DKA common; microvascular complications absent at diagnosis

• Treatment: insulin replacement only

Type 2 (~90% of DM)

• Insulin resistance + impaired insulin secretion

• Usually adults; increasingly seen in adolescents (parallels obesity)

• Gradual onset; often overweight/obese

• Microvascular complications may be present at diagnosis

• Treatment: lifestyle, oral agents, injectables, insulin

Gestational Diabetes (GDM)

A condition that develops during pregnancy primarily due to insulin resistance

Screening

• All pregnant people screened between weeks 24-28

Treatment

• First line: diet and exercise

• If glycemic targets not met within 2 weeks → pharmacotherapy

• Second line: insulin

• Alternative: metformin or glyburide

Diagnosis of Diabetes Mellitus

Any one of the following confirms diagnosis:

• Fasting plasma glucose (FPG) ≥ 7.0 mmol/L (≥ 8 hours no calories)

• A1C ≥ 6.5% (adults; validated assay; not for suspected T1DM)

• 2-hour plasma glucose in a 75g OGTT ≥ 11.1 mmol/L

• Random plasma glucose ≥ 11.1 mmol/L (any time, regardless of last meal)

Diabetic Ketoacidosis (DKA)

Insulin deficiency → body metabolizes lipids → ketone bodies produced

Characterized by:

• Hyperglycemia (usually >14 mmol/L)

• Ketonemia

• Metabolic acidosis (venous pH <7.3, bicarbonate <15 mmol/L, anion gap >12)

Signs

• Fruity breath (ketones), nausea, vomiting, altered consciousness

Treatment

• IV fluid replacement, potassium replacement if low, insulin

Hypoglycemia

Requires:

• Low BG (<3.9 mmol/L)

• Autonomic or neuroglycopenic symptoms

• Symptoms resolve with carbohydrate intake

Common causes

• Missed/insufficient meals, excess physical activity

• Too much antihyperglycemic medication, alcohol

Levels

• Level 1: BG 3.0-3.9, autonomic symptoms only

• Level 2: BG <3.0, neuroglycopenic symptoms, no major mental status change

• Level 3: any BG, severely altered mental/physical status - requires assistance

Bolus (Prandial) Insulin

Controls blood sugar rise after meals

Rapid-acting insulin analogues (clear)

• Onset 4-20 min, peak ~1-1.5h, duration 3-5h

• Administer with or just before meals (0-15 min)

• Examples: insulin aspart (NovoRapid), insulin lispro (Humalog), insulin glulisine (Apidra), faster aspart (Fiasp)

Short-acting insulins (clear)

• Onset ~30 min, peak 2-3h, duration ~6.5h

  • Administer 30-45 min before meals

• Example: insulin regular (Humulin-R, Novolin ge Toronto)

Basal Insulin

Controls blood sugar between meals and during fasting

Intermediate-acting (cloudy)

• NPH insulin: onset 1-3h, peak 5-8h, duration up to 18h

• Administered once or twice daily

Long-acting insulin analogues (LAIA, clear)

• No significant peak; duration 16-42h depending on product (detemir, glargine, degludec)

• Glargine U-300 (Toujeo): >30h; degludec (Tresiba): ~42h

• Icodec (Awiqli): once weekly (>168h)

• Typically administered once daily at bedtime

Sick Day Management

Hold SADMANS meds.

S - Sulfonylureas, other secretagogues

A - ACE-inhibitors

D - Diuretics, direct renin inhibitors

M - Metformin

A - ARBs

N - NSAIDs

S - SGLT2 inhibitors

Thyroid Gland

Thyroid hormones

• Follicular cells produce T3 (tri-iodothyronine) and T4 (thyroxine); iodine is essential for their production

• T4 is the major hormone secreted; converted to T3 at target tissues (T3 is 3-5x more active)

• Most TH is protein-bound; only the free (unbound) fraction is active

Negative feedback (HPT axis)

• Low T3/T4 → hypothalamus releases TRH → pituitary releases TSH → thyroid produces T3/T4

• Rising T3/T4 inhibits TRH and TSH (negative feedback)

Functions of thyroid hormone

• Controls basal metabolic rate, growth, and development; affects cardiovascular, respiratory, GI, and neuromuscular systems

Hypothyroidism

Low serum T3/T4 from a defect anywhere on the HPT axis

Types

• Cretinism (congenital) - neonate appears normal at birth but cannot produce TH; profound developmental deficits if untreated; neonates screened at birth

• Hashimoto's thyroiditis - autoimmune destruction of thyroid; most common cause

• Myxedema coma - severe, life-threatening hypothyroidism; fluid accumulates in tissues (rare)

Levothyroxine

Standard first-line treatment for hypothyroidism.

Administer on empty stomach, 30 min before meals or 1 hour after.

Hyperthyroidism

Excessive synthesis and secretion of thyroid hormone

Common Causes

• Toxic diffuse goiter (Graves disease) - autoimmune; antibodies mimic TSH receptor; most common; younger females

• Toxic multi-nodular goiter (Plummers disease) - second most common; older females (>50); often triggered by iodine deficiency

• Acute phase of thyroiditis

• Toxic adenoma

Radioactive Iodine (I-131)

Taken up by thyroid; radiation destroys cells → reduces T3/T4 production.

Best for mild hyperthyroid, normal/slightly enlarged gland, no exophthalmos.

Thioamides

Antithyroid drugs.

Methimazole (faster onset, preferred in most cases) and propylthiouracil (PTU)

Inhibit thyroid peroxidase → block T3/T4 synthesis

PTU also blocks peripheral T4 → T3 conversion

Adrenal Gland

Adrenal Medulla (10%)

• Secretes epinephrine (75-85%) and norepinephrine

Adrenal cortex (90%) - three zones

• Mineralocorticoids (aldosterone) - regulate plasma volume; promote Na reabsorption and K excretion; controlled by RAAS; regulates blood pressure

• Glucocorticoids (cortisol/hydrocortisone) - mediate stress response; regulate metabolism, inflammation, and immune system; secretion regulated by HPA axis

• Gonadocorticoids (sex hormones) - mainly androgens; significant source of estrogen in postmenopausal women