CHI335 - Endocrine System PDF

CHI335 Diagnosis I Endocrine System Aims & Objectives Aim Familiarise you with the common disorders associated with the endocrine system Provide the opportunity to appreciate common endocrine disorders and recognise them in clinical practice, with a view to managing patient a...

CHI335 Diagnosis I Endocrine System Aims & Objectives Aim Familiarise you with the common disorders associated with the endocrine system Provide the opportunity to appreciate common endocrine disorders and recognise them in clinical practice, with a view to managing patient appropriately Objectives Briefly review the anatomy & physiology of the endocrine system Cover common disorders and their presentations Mention the role of laboratory investigations and patient management Introduction Nervous and endocrine systems are the two regulatory systems of the body Nervous system Acts very rapidly through nerves and nerve impulses, or action potentials Endocrine system Slower acting, but is very important in terms of health and disease for its longer acting effects Chemical messengers called hormones Nervous and Endocrine Systems Endocrine Glands Often referred to as ductless glands Substances secreted by endocrine glands directly enter the circulatory system or act directly on specific cells Each endocrine gland secretes one or more hormones Chemical messengers that are typically steroids, proteins, amino acids, or lipids Major Endocrine Glands Endocrine Regulation Hypothalamic-Pituitary Axis Hypothalamus-pituitary axis & Regulation Hypothalamic releasing hormones Hypophysial hormones Anterior Pituitary Posterior Pituitary Posterior Pituitary Classification of endocrine disease 1. Hormone excess Primary (gland over-production, therefore -ve feedback occurs) Secondary (excess of a stimulating hormone from pituitary) 2. Hormone deficiency Primary (gland failure, therefore +ve feedback occurs) Secondary (deficiency of a stimulating hormone from pituitary) 3. Altered tissue response Target organ resistance (e.g. DM, DI) 4. Extra glandular disorders Target organ overstimulation/hypersensitivity (e.g. AI disorders) 5. Non-functioning endocrine tumours Assessment of dysfunction 1. Basal hormone levels are measured in the blood and/or urine to establish whether the levels are low or high compared to the normal range Blood hormone levels Provide important information about the function of particular endocrine glands (e.g. gland hypo- or hypersecretion) May indicate the location of the abnormality/disease Urine tests Are needed to measure the free hormone and hormone metabolite levels secreted by the kidneys Assessment of dysfunction 2. Dynamic tests of endocrine function Involve collecting blood at specific time points according to evidence-based protocols Under supervision and sent to the laboratory quickly Two categories Stimulation tests: hyposecretion is suspected Suppression tests: hypersecretion is suspected 3. Endocrine imaging Consists of general radiology procedures (e.g. CT scans, MRI and ultrasound scans) Assess structure and function Differentiate among the possible causes of endocrine diseases Pertinent Investigations Adrenal tests Pancreatic tests Plasma cortisol Glucose tolerance ACTH stimulation Fasting Thyroid tests Postprandial TSH HbA1C T3/T4 Other Parathyroid tests Serum electrolytes PTH Urine ketones Serum calcium Urine/serum creatinine Serum phosphate Common Conditions Neurohypophysis Diabetes insipidus Pancreatic dysfunction (endocrine) Diabetes mellitus (T1DM, T2DM) Adrenal Cushing’s syndrome Hyperaldosteronism ( e.g. Conn’s syndrome) Addison’s Phaeochromocytoma Thyroid disease Hypo- and hyperthyroidism Parathyroid dysfunction Hyperparathyroidism Hypoparathyroidism Non-specific presentations of endocrine diseases Diabetes Insipidus (DI) Features Inability to concentrate the urine Production of large quantities of dilute (hypotonic) urine (5-30 L) Clinically manifests as polyuria, nocturia, and polydipsia Types Cranial (central) DI: Deficiency of ADH Nephrogenic DI: Unresponsive renal tubules (Resistance to ADH) Aetiology Cranial DI Pituitary surgery, head injury/trauma, idiopathic (autoimmune), CNS infections, CVA Nephrogenic DI Medications, genetic defects, chronic kidney disease DI Risk factors Pituitary surgery, tumours of the area, lesions of pituitary, trauma to brain, medication, other autoimmune diseases, FHx Hx/Ex Polyuria, polydipsia, nocturia, muscle twitching, visual defects Investigations Serum sodium Urine osmolality while normal or  Serum osmolality Normal serum glucose 24hr urine collection (7.0 mmol/L (126 mg/dL) Random plasma glucose >11.1 mmol/L (200 mg/dL) HbA1c >6.5% (48 mmol/mol) One abnormal test is diagnostic in symptomatic individuals Two values are needed in asymptomatic people Unreliable tests: Urine glucose (glycosuria): normal in early stages and moderately elevated BG Urine ketones (ketonuria): Also seen in starvation, vigorous exercise for a long period, eating a diet high in fat and low in carbohydrate DM Clinical presentation Asymptomatic Acute (within weeks) Subacute (months to years) Symptoms of hyperglycaemia Polyuria, polydipsia, polyphagia, weight loss/gain, fatigue, lethargy, blurred vision, tingling and numbness in the feet, erectile dysfunction, arterial disease, nausea and vomiting, abdominal pain, tachypnoea, skin infections, mood changes, pruritus vulvae or balanitis DM Insulin: a major regulator of metabolism and organ function Yee, Lisa & Mortimer, Joanne & Natarajan, Rama & Dietze, Eric & Seewaldt, Victoria. (2020). Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin. Frontiers in Endocrinology. 11. 10.3389/fendo.2020.00058. Acute complications of insulin deficiency DM – Management The goal is to Improve symptoms of hyperglycaemia Minimise the risks of long-term microvascular and macrovascular complications Prevent development of hypoglycaemia Patient education is the cornerstone of the management A multidisciplinary approach is usually needed In T1 DM an urgent treatment with insulin is required In T2 DM Dietary / lifestyle modification Oral/injectable anti-diabetic drugs Insulin DM – Management Blood glucose target levels Type I Preprandial: 4 – 6 mmol/L, postprandial*: 4 – 8 mmol/L Type II Preprandial: 4 – 7 mmol/L, postprandial: 5 – 10 mmol/L In a diabetic patient, at every consultation check BP (≤140/90 mmHg) Eyes (visual acuity and Fundus) for diabetic retinopathies Insulin injection sites for infections Hands Feet *Postprandial: 2 hours after meal DM Common abnormalities in hands Limited joint mobility which is a painless stiffness (prayer’s sign) Dupuytren's contracture Carpal tunnel syndrome Trigger finger (flexor tenosynovitis) Muscle-wasting/sensory changes Common abnormalities in feet Discoloration of the skin, localised infection and ulcers Charcot arthropathy Fungal infection may affect skin between toes, and nails Arterial insufficiency (diminished pulses) stocking & gloves distribution peripheral polyneuropathy Complications of DM Macrovascular CVD CVA PVD Microvascular Retinopathy Nephropathy Neuropathy Peripheral Autonomic Infections Cancers Symptoms of hypoglycaemia The Adrenal gland – Cortex Steroid hormones synthesis pathways Not Examinable Hypothalamus-pituitary-adrenal axis Cortisol Cortisol is BBIIG! Maintains Blood pressure (Na+ retention, K+ loss)  Bone formation (resorption of bone matrix) Anti-Inflammatory  Immune function  Gluconeogenesis (& proteolysis) Cushing's syndrome The clinical state of increased free circulating glucocorticoid. It can occur due to endogenous or exogenous causes: 70% Cushing's syndrome – S & S Cushing's syndrome – Investigations To confirm Cushing’s syndrome Serum cortisol level 24-hr urinary free cortisol Late night salivary cortisol Low-/high-dose dexamethasone suppression test To differentiate the cause ACTH morning plasma Pituitary MRI Adrenal/abdomen CT/MRI Additional points Normally, cortisol is higher in the morning and lower at night, this changes depending on work and sleep pattern If it does not drop at night, then think of ACTH overproduction in the pituitary, or tumour in the adrenal gland, or medications Remember: pregnancy, (chronic) stress and illness can increase cortisol level; while hypothyroidism and some drugs (e.g. Ketoconazole) can decrease it Be aware of “pseudo-Cushing’s syndrome” Cushing's syndrome Management Correct the causative factor Control complications such as diabetes, hypertension, and dyslipidaemia Prognosis Varies depend on the cause Most cases of Cushing's syndrome can be cured Some kinds of tumours may recur RAA System RAA System Hyperaldosteronism Increased production of aldosterone Aetiology Secondary hyperaldosteronism (Renin & Aldosterone) Inadequate renal perfusion (low blood pressure, diuretic therapy, cardiac failure, renal artery stenosis, etc.) Renin-secreting renal tumour (very rare) Primary hyperaldosteronism (Renin & Aldosterone) Adrenal adenoma secreting aldosterone (Conn's syndrome) Idiopathic bilateral adrenal hyperplasia Hx/Ex Asymptomatic (early stage) HTN & oedema (secondary to Na+) Headache (secondary to BP) Polyuria Muscle weakness & Paralysis (secondary to K+) Addison’s disease aka Primary hypoadrenalism is the destruction of the entire adrenal cortex Glucocorticoid, mineralocorticoid and gonadocorticoid production is severely reduced It must be ruled out in any patient with unexplained fatigue plus hyponatraemia or hypotension Aetiology (Common causes) Autoimmune Autoimmune Polyendocrine Syndromes (APS) Infections: Tuberculosis, HIV/AIDS Metastatic carcinoma Bilateral adrenalectomy Addison’s disease Clinical presentation Acute (adrenal crisis) Acute adrenal crisis is a medical emergency Acute circulatory shock (severe hypotension) plus hyponatraemia, hyperkalaemia and, in some instances, hypoglycaemia and hypercalcaemia Often precipitated by a stressful event Chronic Chronic fatigue and depression +/- other S & S (next slide) Asymptomatic with accidentally detected hyponatraemia Addison’s disease – S & S Addison’s disease Investigations Serum cortisol ACTH stimulation test Electrolytes (Na+ and K+) Adrenal auto-Ab Management Medical alert bracelet/necklace Oral glucocorticoids Patients should be instructed to increase the steroid replacement doses in stressful situations, such as infections, trauma, etc. Prognosis Lifelong steroid replacement therapy Adrenal crisis is a life-threatening emergency The Adrenal gland – Medulla Sympathetic NS stimulates the Medulla to produce and secrete catecholamines which are mainly adrenaline and noradrenaline Catecholamines: synthesis & metabolism Not Examinable COMT, catechol-O-methyl transferase; MAO, monoamine oxidase Phaeochromocytoma A catecholamine-secreting tumour arising from the adrenal medulla (80%) or elsewhere in the body Secretes adrenaline, noradrenaline and rarely dopamine The tumour is malignant in about 10% of cases Presents with headaches, anxiety, diaphoresis (hidrosis), palpitation, and severe HTN (mostly paroxysmal) Symptoms are usually episodic and tend to progress as the tumour grows Phaeochromocytoma Clinical manifestation Persistent hypertension Facial flushing Tachycardia Headaches Anxiety Hypermetabolism Long-term complications Cardiac and kidney disease Visual impairment Stroke Thyroid hormones & thyroid tests Thyroid produces and secrets three hormones: Thyroxin (T4) → more than %90 of all secreted hormones Triiodothyronin (T3) Almost all T4 is converted to T3 in the periphery, which is more potent (stronger) but less durable Calcitonin Thyroid function tests (TFTs) measure the level of TSH and thyroid hormones in the blood TSH T4/ Free T4 T3/ Free T3 Effects of thyroid hormones Goitre An enlargement of the thyroid gland Both hypothyroid and hyperthyroid states In hypothyroidism As a compensatory mechanism In hyperthyroidism As part of the primary pathophysiological process Classified as non-toxic or toxic, and diffuse or nodular Non-toxic goitre: enlarged gland but no clinical manifestations Toxic goitre: thyroid dysfunction A diffuse goitre: whole gland is enlarged A nodular goitre: one or more parts of the gland are enlarged Goitre An enlarged thyroid can be easily identified by palpation and, in some cases, by visual observation Source: Zimmerman, Jooste & Pandav (2008), Figure 2. Hypothyroidism Is insufficient production of thyroid hormones Primary (95%): Failure of the thyroid gland to produce thyroid hormones Secondary: Underproduction of TSH by the pituitary gland Primary hypothyroidism Hashimoto’s thyroiditis AI, the most common cause in West Lymphocytic infiltration and tissue destruction due to auto-Ab 5 – 10x more likely in females, 30 – 50 yrs old Iodine deficiency A major cause in developing countries (less common in the developed world) Postpartum thyroiditis Occurs in up to 10% of women after delivery, is usually a transient condition (2-4 months) Congenital (cretinism): permanent delayed development of the brain and major body systems Drug induced Amiodarone, Lithium,… Iatrogenic (anti-thyroid medications, Radioactive iodine ablation, thyroidectomy) Primary hypothyroidism Risk factors Female Middle age FHx Other autoimmune disorders Investigations  Serum TSH  Serum FT4 (or FT3) Presence of Auto-Abs Hypothyroidism Clinical manifestations Bradycardia Constipation Loss of appetite Lethargy Slowed mental function Hyporeflexia Fatigue Muscle weakness Cold intolerance and weight gain Thickened, dry and coarse skin Brittle and thinned out hair Hypothyroidism Management Levothyroxine (T4) Complications RARE myxoedema coma (is rare and a medical emergency) Heart problems Mental health problems Infertility Complications in pregnancy Prognosis Is generally excellent with full recovery upon adequate replacement of thyroid hormones Hyperthyroidism Is the state of thyroid over-activation Almost all cases (>99%) are primary Graves’ disease – most common AI, presents with ophthalmopathy and dermopathy Multinodular toxic goitre Solitary toxic nodule/adenoma Acute thyroiditis F:M = 5:1 Most common at the ages of 20 – 40 Hyperthyroidism Clinical manifestations Palpitations (and angina) Muscle weakness and fatigue Increased gastrointestinal motility (diarrhoea) Increased appetite (accompanied by weight loss) Intolerance to heat Nervousness Hyperreflexia Insomnia Fingernails and toenails can become loosened and may even detach from the nail bed Exophthalmos (for Graves’ disease only) Hyperthyroidism Graves’ disease The most common form of hyperthyroidism An autoimmune condition Autoantibodies mimic TSH at its receptors on the thyroid gland Leads to Production of thyroid hormones Exophthalmos (i.e. bulging eyes) differentiates Graves’ disease from other forms of hyperthyroidism Exophthalmos In exophthalmos, the eyeballs bulge forward (bilaterally) Inflammation and  connective tissue develop behind the eye sockets Source: Ralph Jr/Photo Researchers/Getty Images Australia Pty Ltd. Hyperthyroidism Investigations Prognosis  TSH Excellent with Tx  Free T4 Synthetic T4 is prescribed  Free T3 after surgery  Radioactive iodine uptake Management Anti-thyroid medications Radioactive iodine Then → Surgery Complications Bone mineral loss AF, CHF Thyroid storm Hypothyroidism vs hyperthyroidism Hypothyroidism Hyperthyroidism Cold intolerance Heat intolerance Weight gain (decrease appetite) Weight loss (increase appetite) Lethargy, fatigue, weakness Hyperactivity Constipation Diarrhoea Signs & Decreased reflexes Increase reflexes symptoms Myxoedema (facial/preorbital) Pretibial myxoedema (Graves’) Dry, cool skin, coarse brittle hair Warm moist skin, fine hair Bradycardia Palpitations, dysrhythmia Dyspnoea on exertion Investigation  TSH  TSH findings  Free T4  Free T4 (when primary) Calcium metabolism Parathyroid hormone Mg2+ is required for PTH secretion Hyperparathyroidism Primary hyperparathyroidism is mostly caused by a single adenoma (85%) Hx/Ex “Bones, stones, abdominal groans, and psychic moans” Fragile bones that easily fracture (osteoporosis) Bone and joint pain Kidney stones Investigations Abdominal pain  Serum calcium Depression or forgetfulness  Serum PTH Excessive urination  Serum (PO4) 3- Tiredness or weakness Frequent complaints of illness with no apparent cause Nausea, vomiting or loss of appetite Hypoparathyroidism Most common causes H&N radiation Thyroid surgery (total thyroidectomy)  Serum Mg2+ Deficiency in PTH results in hypocalcaemia which may present with Muscle twitches or spasm Paraesthesia (mostly perioral), Intermittent numbness Chvostek’s sign (tetany in severe cases) Mood swings and/or personality disturbances (seizure in severe cases) ECG changes Self-directed Study Topics IFG, IGT & Glycaemic index (GI) – Definitions Diabetic metabolic emergencies – Pathogenesis and clinical presentation Diabetic ketoacidosis (DKA) Hyperglycaemic hyperosmolar state (HHS, aka HONK) Gestational diabetes – Pathogenesis and Complications Metabolic syndrome – Definition and prognosis Multiple Endocrine Neoplasia: MEN I, MEN IIa, MEN IIb