Thyroid & Adrenal Disorders - Ccnc

The Endocrine System an overview

The Pituitary Gland

ACTH

TSH

FSH/LH

GH

Prolactin

ADH

Adrenals

Thyroid

Gonads

Liver

Mammary Glands

Kidneys

Milk

Resorption of water

Cortisol

Thyroxine Testosterone/ IGF Estradiol

C N S Input Hypothalamus Releasing Hormone Pituitary Trophic Hormone Peripheral Gland Hormones Target Gland

THYROID EMERGENCIES/DYSFUNCTION • Severe hyperthyroidism (thyroid storm) • Severe hypothyroidism (myxoedema coma) • Alteration in thyroid blood test results in non-thyroidal illness

SECRETION AND TRANSPORT OF THYROID HORMONES TSH Thyroid Gland

rT3

T4

T3 Active

THYROID HORMONE PROFILE --

TSH

Thyroid Gland

Thyroid hormone Euthyroid

THYROID HORMONE PROFILE IN HYPERTHYROIDISM --

TSH

Thyroid Gland

Thyroid hormone Hyperthyroid (Elevated free T4, Suppressed TSH)

THYROID HORMONE PROFILE in GRAVES’ DISEASE --

TSH

++ Thyroid Gland Thyroid Stimulating Immunoglobulin

Thyroid hormone Hyperthyroid (Elevated free T4, Suppressed TSH)

SEVERE HYPERTHYROIDISM (thyroid storm)

COMMON CAUSES OF HYPERTHYROIDISM • Autoimmune (Graves’ Disease, commonest) • Toxic Multinodular Goitre • Solitary Autonomous Nodule

Clinical Features of Hyperthyroidism • • • • • • • •

Heat intolerance Restlessness, irritability Tremor Palpitations, tachycardia Weight loss Increased Stool Frequency Increased Appetite Weakness

Graves’ DiseaseThe strained look, Exophthalmos, Vitiligo

Graves’ disease - acropachy and onycholysis

Graves’ disease Pretibial myxoedema

THYROID STORM Thyroid storm develops in the setting of untreated (undiscovered) or undertreated hyperthyroidism and is associated with precipitating factors such as: • infection • other acute medical illness • trauma • surgery The precipitating event should be sought for and treated as well

Thyroid Storm The clinical features of this life-threatening disorder include: • fever • neurologic changes ranging from agitation to confusion, delirium and coma.

Clinical features in thyrotoxicosis and thyroid storm: Thermoregulation Thyrotoxicosis

Thyroid Storm

• Warm, moist skin • Heat intolerance

• Fever

Clinical features in thyrotoxicosis and thyroid storm: CNS and Muscle Thyrotoxicosis

Thyroid Storm

• • • •

• • • •

Emotional lability Tremor Weakness Periodic Paralysis

Agitation Delirium Seizure Coma

Clinical features in thyrotoxicosis and thyroid storm: Nutrition Thyrotoxicosis

Thyroid Storm

• Increased appetite • Weight loss

• Severe weight loss • Vitamin deficiencies

Clinical features in thyrotoxicosis and thyroid storm: CVS Thyrotoxicosis

Thyroid Storm

• Tachycardia • Systolic hypertension • Atrial fibrillation

• Congestive heart failure • Arrthymia

Congestive Heart Failure in Patient with Severe Hyperthyroidism before and after treatment

Clinical features in thyrotoxicosis and thyroid storm: GIT Thyrotoxicosis

Thyroid Storm

• Hyperdefecation

• Vomiting • Diarrhoea • Jaundice

Biochemical Diagnosis • Elevated free T4 and suppressed TSH • Although free T4 tends to be higher in thyroid storm then in hyperthyroidism per se, this cannot be relied upon to make a diagnosis

Management of Thyroid Storm General Measures • • • •

Search for and treat any precipitating event Antipyretics Fluids, electrolytes replacement Nutrition

Management of thyroid storm Specific Measures • Inhibition of thyroid hormone synthesis • Inhibition of thyroid hormone release • Inhibition of T4 to T3 conversion • Inhibition of adrenergic effects

Inhibition of thyroid hormone synthesis • Propylthiouracil (or carbimazole, methimazole) by mouth • Propylthiouracil by nasogastric tube • Propylthiouracil per-rectally

Inhibition of thyroid hormone release • Intravenous sodium iodide • Oral Lugol’s iodine

Inhibition of T4 to T3 conversion • Glucocorticoids • Propylthiouracil • Beta-blockers

Inhibition of adrenergic effects • Propranolol -oral/intravenous • Esmolol - intravenous

SEVERE HYPOTHYROIDISM (Myxodema Coma)

THYROID HORMONE PROFILE IN HYPOTHYROIDISM --

TSH Thyroid Gland

Thyroid hormone

Primary Hypothyroid (Low free T4, Elevated TSH)

THYROID HORMONE PROFILE IN HYPOTHYROIDISM Pituitary --

TSH

Thyroid Gland

Thyroid hormone

Secondary Hypothyroid (Low free T4, TSH not elevated)

Causes of hypothyroidism Primary • Autoimmune - goitrous (Hashimoto’s) - Agoitrous • Previous thyroid ablation - radioiodine treatment - surgery

Causes of hypothyroidism Secondary to hypothalamo-pituitary dysfunction • Non TSH secreting pituitary tumour reducing TSH secretion • Irradiation e.g. previously for NPC • Previous pituitary surgery

Hypothyroidism - the coarse features, loss of outer part of eyebrows

MYXOEDEMA COMA This develops in the setting of untreated (undiscovered) hypothyroidism and is associated with precipitating events such as : • Infection • Other acute medical illness • Trauma • Surgery • Injudicious use of hypnotics/sedatives The precipitating event should be sought for and treated. Surveillance for respiratory depression and timely mechanical ventilation reduces mortality.

MYXOEDEMA COMA The clinical features of this life-threatening disorder include : • Mental obtundation • Respiratory depression

SYMPTOMS & SIGNS IN HYPOTHYROIDISM AND MYXOEDEMA COMA Thermoregulation Hypothyroidism

• Cold intolerance • Cool, dry skin

Myxoedema coma

• Hypothermia

SYMPTOMS & SIGNS IN HYPOTHYROIDISM AND MYXOEDEMA COMA CNS & Muscle Hypothyroidism

• • • • •

Fatigue Weakness Slow mentation Delayed reflexes Muscles cramps

Myxoedema coma

• Psychosis • Mental obtundation • Coma

SYMPTOMS & SIGNS IN HYPOTHYROIDISM AND MYXOEDEMA COMA CVS Hypothyroidism

• Bradycardia • Hypertension

Myxoedema coma

• Bradycardia • Pericardial effusion

SYMPTOMS & SIGNS IN HYPOTHYROIDISM AND MYXOEDEMA COMA GIT Hypothyroidism

• Constipation

Myxoedema coma

• Ileus • Megacolon

BIOCHEMICAL DIAGNOSIS Very low free T4 and significantly elevated TSH in myxoedma coma from primary hypothyroidism

MANAGEMENT OF MYXOEDEMA COMA General Measures • Search for and treat any precipitating event • Monitor respiratory function clinically and by pulse oximetry/ABG measurement • Fluids, electrolytes balance • Nutrition • Correct hypothermia

MANAGEMENT OF MYXOEDEMA COMA Specific Measures • Thyroid hormone replacement intravenous/nasogastric/oral

C N S Input Hypothalamus CRH Pituitary ACTH Peripheral Gland Cortisol Target Gland

CORTISOL / ACTH PROFILE --

ACTH

Adrenal Gland

Cortisol Eucortisolaemic

CORTISOL/ACTH PROFILE --

ACTH Adrenal Gland

Cortisol

Primary adrenocortical insufficiency (low cortisol and elevated ACTH)

CORTISOL/ACTH PROFILE IN HYPOADRENALISM Pituitary --

ACTH

Adrenal Gland Cortisol

Secondary adrenocortical insufficiency(Low cortisol, ACTH not elevated)

CAUSES OF ADRENOCORTICAL INSUFFICIENCY • Primary - autoimmune - infections e.g. TB, histoplasmosis - metastatic disease e.g. lympohma - haemorrhage e.g. sepsis, anticoagulant • Secondary to hypothalamo-pituitary disorder ( e.g. tumour, inflammation, irradiation, surgery) • Withdrawal from chronic exogenous glucocorticoids

Symptoms and signs of adrenocortical insuffceincy • Gastrointestinal symptoms including nausea,vomiting and diarrhoea • Haemodynamic effects including postural or frank hypotension • Electrolyte abnormalities including hyponatremia ( and possibly hyperkalemia) • Relative hypoglycemia

BIOCHEMICAL DIAGNOSIS • Electrolytes • Baseline cortisol, ACTH • Synacthen test

Baseline Cortisol and Mortality

Sam S et al. Clinical Endocrinology 2004. 60:29-35

Baseline Cortisol and Mortality

Sam S et al. Clinical Endocrinology 2004. 60:29-35

Baseline Cortisol and Mortality

Sam S et al. Clinical Endocrinology 2004. 60:29-35

Stratification Based on Synacthen Test

Annane D et al. JAMA 2000.283:1038-45

Stratification Based on Synacthen Test

Annane D et al. JAMA 2000.283:1038-45

MANAGEMENT OF ADRENOCORTICAL INSUFFICIENCY • Fluid, electrolytes replacement • Glucocorticoid replacement – intravenous – oral

Annane D et al. JAMA 2002. 288:862-71

Effect of Treatment with Low Dose Hydrocortisone & Fludrocortisone

Annane D et al. JAMA 2002. 288:86271

Effect of Treatment with Low Dose Hydrocortisone & Fludrocortisone

Annane D et al. JAMA 2002. 288:862-71

Hamrahian AH et al. NEJM 2004. 350:1629-38

Serum Free Cortisol in Critically Ill Patients

Serum Total & Free Cortisol in Critically Ill Patients Before and After Synacthen