Endocrine Emergencies


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Endocrine Emergencies

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  • I would like to thank everyone for coming today this is a talk on Endocrine Emergencies
  • This is a really extensive talk – I mean really big when you think about it in its subject matter So its going to be fast, however to get the most of it, you probable should download it from the SCHED website
  • This is Nick Cage in the Film Leaving Las Vegas about a screenwriter who goes to Las Vegas to Drink himself to death
  • Endocrine Emergencies

    1. 1. Endocrine Emergencies Dr Vincent Chan May 2014
    2. 2. Endocrine Emergencies • Glucose metabolism Disorders • Adrenal Disorders • Thyroid Disorder • Pituitary disorders • Parathyroid disorders
    3. 3. Glucose metabolism disorders • Hypoglycaemia • Diabetic ketoacidosis • Diabetic with unstable blood glucose • Alcoholic ketoacidosis • Hyperosmolar hyperglycaemic non-ketotic syndrome
    4. 4. Hypoglycaemia: Definition • A clinical syndrome characterized by • low plasma glucose level – less than 4 mmol/l (Diabetes Australia Definition) • Symptomatic sympathetic nervous system stimulation • CNS dysfunction
    5. 5. Hypoglycaemia: Causes • Reactive (postprandial) or fasting • Insulin-mediated or non–insulin-mediated • Drug-induced or nondrug-induced
    6. 6. Hypoglycaemia: Clinical Features • Surge in Autonomic activity – usually commence below BSL 3.33 mmol • Sweating • Nausea • Warm • Anxiety • Tremulousness • Palpitations • Hunger and Paraesthesia • Insufficient glucose supply to the Brain – usually commence below BSL 2.78 mmol • Headache • blurred vision • Confusion • difficulty speaking • seizures • coma
    7. 7. Hypoglycaemia: Diagnosis • Blood glucose level correlated with clinical findings • Response to dextrose administration • Sometimes 72 hours fasting • Sometimes insulin, C-peptide and pro-insulin levels
    8. 8. Hypoglycaemia: Treatment • Oral sugar or IV dextrose • 50% dextrose 50 to 100ml IV bolus • Continuous infusion of 5 to 10% dextrose solution • Glucagon SC or Im • 0.5mg if <20 kg or 1 mg >20kg • Treat underlying disorder
    9. 9. Diabetic ketoacidosis (DKA) • An acute metabolic complication of diabetes characterized by • hyperglycemia • hyperketonemia • metabolic acidosis • Occurs mostly in type 1 diabetes mellitus (DM) • Can be first hospital presentation with Newly diagnosed Type I DM
    10. 10. Diabetic ketoacidosis • Develops when insulin levels are insufficient to meet the body's basic metabolic requirements • Insulin deficiency can be • absolute - during lapses in the administration of exogenous insulin • relative - when usual insulin doses do not meet metabolic needs during physiologic stress
    11. 11. Diabetic ketoacidosis: Pathophysiology • Common physiologic stresses that can trigger DKA include • Acute infection (particularly pneumonia and UTI) • MI • Stroke • Pancreatitis • Trauma • Drugs implicated in causing DKA include • Corticosteroids • Thiazide diuretics • Sympathomimetics
    12. 12. Diabetic ketoacidosis: Pathophysiology • Insulin deficiency causes the body to metabolize triglycerides and muscle instead of glucose for energy • Serum levels of glycerol and free fatty acids (FFAs) rise because of unrestrained lipolysis • Glucagon stimulates mitochondrial conversion of FFAs into ketones • Ketogenesis proceeds in the absence of insulin • The major ketoacids produced are • acetoacetic acid • β-hydroxybutyric acid
    13. 13. Diabetic ketoacidosis: Pathophysiology • Hyperglycemia • osmotic diuresis – marked urinary losses of water and electrolytes. • Urinary excretion of ketones • additional losses of Na and K. • Hyponatraemia or Hypernatraemia • natriuresis • or rise due to excretion of large volumes of free water. • Marked Hypokalaemia • sometimes > 300 mmol/24 h. • However initial serum K is typically normal or elevated • extracellular migration of K in response to acidosis. • Becomes apparent • during treatment as insulin therapy drives K into cells. • If serum K is not monitored and replaced as needed, life-threatening hypokalemia may develop
    14. 14. Diabetic ketoacidosis: Symptoms and signs • Include those of hyperglycemia with the addition of nausea, vomiting, • particularly in children—abdominal pain. • Lethargy and somnolence • hypotensive and tachycardia from dehydration and acidosis • Kussmaul respirations – deep and rapid breaths compensate for acidemi • fruity breath due to exhaled acetone. • Fever - signifies underlying infection. • coma and death – if not treated timely
    15. 15. Diabetic ketoacidosis: Symptoms and signs • Acute cerebral oedema, a complication in about 1% of DKA patients, • occurs primarily in children and less often in adolescents and young adults. • Headache and fluctuating level of consciousness herald this complication in some patients, but respiratory arrest is the initial manifestation in others
    16. 16. Diabetic ketoacidosis: Diagnosis • Arterial pH <7.30 • Serum ketones • Urine test strips detect acetoacetic and not β-hydroxybutyric acid, which is usually the predominant ketoacid • Calculation of anion gap >12
    17. 17. Diabetic ketoacidosis: Treatment • Critical Care input is essential • Correction of fluid loss with intravenous fluids • Correction of hyperglycemia with insulin • Correction of electrolyte disturbances, particularly potassium loss • Correction of acid-base balance • Controversial - Sodium bicarbonate – severe acidosis ph less than 7.1 • Treatment of concurrent infection, if present • Vigilance for any concomitant process • Infection CVA, MI, sepsis or Deep vein thrombosis
    18. 18. Alcoholic Ketoacidosis: Definition • A metabolic complication of alcohol use and starvation characterized by • hyperketonemia • Raised anion gap metabolic acidosis • without significant hyperglycemia
    19. 19. Alcoholic Ketoacidosis: Pathophysiology • Alcohol diminishes hepatic gluconeogenesis and leads to • decreased insulin secretion • increased lipolysis, • impaired fatty acid oxidation, • Subsequent ketogenesis • Counter-regulatory hormones are increased and may further inhibit insulin secretion. • Plasma glucose levels are usually low or normal, but mild hyperglycemia sometimes occurs
    20. 20. Alcoholic Ketoacidosis: Symptom and Signs • Typically, an alcohol binge leads to vomiting and the cessation of alcohol or food intake for ≥ 24 h. • During this period of starvation, vomiting continues and abdominal pain develops, leading the patient to seek medical attention. • Pancreatitis may occur
    21. 21. Alcoholic Ketoacidosis: Diagnosis • Clinical evaluation • Exclude acute pancreatitis, methanol, ethylene glycol poisoning and Diabetic ketoacidosis • Calculation of anion gap • High AGAP metabolic acidosis, ketonaemia, low K Mg and Phophate • May be complicated by concurrent metabolic alkalosis due vomiting – relatively normal pH • Exclusion of other disorders
    22. 22. Alcoholic Ketoacidosis: Treatment • IV thiamin and other vitamins plus Mg • prevent development of Wernicke encephalopathy or Korsakoff psychosis. • IV 5% dextrose in 0.9% saline • Initial IV fluids should contain added water-soluble vitamins and Mg, with K replacement as required. • Ketoacidosis and GI symptoms usually respond rapidly.
    23. 23. Hyperosmolar hyperglycaemic nonketotic syndrome • Hyperosmolar hyperglycemic state (HHS) • Hyperosmolar non-ketotic coma (HONK • A complication of type 2 DM and has a mortality rate of up to 40%. • It usually develops after a period of symptomatic hyperglycemia in which fluid intake is inadequate to prevent extreme dehydration due to the hyperglycemia-induced osmotic diuresis
    24. 24. Hyperosmolar hyperglycaemic nonketotic syndrome • Precipitating factors include • Acute infections and other medical conditions • Drugs that impair glucose tolerance (glucocorticoids) or increase fluid loss (diuretics) • Non-adherence to diabetes treatment • Serum ketones are not present • type 2 DM produce enough insulin to suppress ketogenesis. • Absence of Ketones - significantly longer period of osmotic dehydration before presentation, therefore • plasma glucose (> 33 mmol/L]) • osmolality (> 320 mOsm/L) are • typically much higher than in diabetic ketoacidosis (DKA)
    25. 25. Hyperosmolar hyperglycaemic nonketotic syndrome: Symptoms and Signs • Altered consciousness - confusion disorientation to coma • extreme dehydration with or without pre-renal impairment, hyperglycemia, and hyperosmolality. • Focal or generalized seizures and transient hemiplegia • acute circulatory collapse • Myocardial infarction, aspiration pneumonia, acute renal failure, and acute respiratory distress syndrome • disseminated intravascular coagulation.
    26. 26. Hyperosmolar hyperglycaemic nonketotic syndrome: Diagnosis • Blood glucose level – very high • Serum osmolality- elevated • Urine should be tested for ketones. • Serum K levels are usually normal • Na may be low or high depending on volume deficits. BUN and serum creatinine levels are markedly increased. • Arterial pH is usually > 7.3, but occasionally mild metabolic acidosis develops due to lactate accumulation. • The average fluid deficit is 10 L, and acute circulatory collapse is a common cause of death. • Widespread thrombosis is a frequent finding on autopsy, and in some cases bleeding may occur as a consequence of disseminated intravascular coagulation. • Other complications include aspiration pneumonia, acute renal failure, and acute respiratory distress syndrome.
    27. 27. Hyperosmolar hyperglycaemic nonketotic syndrome: Treatment • IV 0.9% saline • 1Litre IV over 30 minutes • 1 Litre/Hour • Adjusted depending on BP cardiac, states and fluid input and output balance • Correction of any hypokalemia • IV insulin (as long as serum K is ≥ 3.3 mEq/L) • Target Blood sugar • Avoid rapid correction in osmolality – cerebral odema
    28. 28. Adrenal disorders • Acute adrenal insufficiency (adrenal crisis) • Congenital adrenal insufficiency • Cushing’s disease • Conn’s syndrome • Phaeochromocytoma
    29. 29. Addison Disease (Primary or Chronic Adrenocortical Insufficiency): Aetiology • 70% of cases due to idiopathic atrophy of the adrenal cortex, probably caused by autoimmune processes. • Remainder result from destruction of the adrenal gland by • granuloma (eg, TB, histoplasmosis), • tumor, • amyloidosis, • hemorrhage, or • inflammatory necrosis • Hypoadrenocorticism can also result from administration of drugs that block corticosteroid synthesis (eg, ketoconazole, the anesthetic etomidate • may coexist with diabetes mellitus or hypothyroidism in polyglandular deficiency syndrome • In children, the most common cause of primary adrenal insufficiency is congenital adrenal hyperplasia, but other genetic disorders are being increasingly recognized as causes
    30. 30. Addison Disease (Primary or Chronic Adrenocortical Insufficiency):Pathophysiology • Mineralocorticoid deficiency: • mineralocorticoids stimulate Na reabsorption and K excretion, • deficiency results in increased excretion of Na and decreased excretion of K, chiefly in urine but also in sweat, saliva, and the GI tract. • A low serum concentration of Na and a high concentration of K result. • Urinary salt and water loss cause severe dehydration, plasma hypertonicity, acidosis, decreased circulatory volume, hypotension, and, eventually, circulatory collapse. • However, when adrenal insufficiency is caused by inadequate ACTH production, electrolyte levels are often normal or only mildly deranged.
    31. 31. Addison Disease (Primary or Chronic Adrenocortical Insufficiency):Pathophysiology• Glucocorticoid deficiency • Insufficient carbohydrate is formed from protein; hypoglycemia and decreased liver glycogen result. • Weakness - deficient neuromuscular function. • Decreased Resistance to infection, trauma, and other stress • Myocardial weakness and dehydration reduce cardiac output, and circulatory failure can occur. • Decreased blood cortisol results in increased pituitary ACTH production and increased blood β-lipotropin, which has melanocyte-stimulating activity and, together with ACTH, causes the hyperpigmentation of skin and mucous membranes • Adrenal insufficiency secondary to pituitary failure (see Secondary Adrenal Insufficiency) does not cause hyperpigmentation.
    32. 32. Addison Disease (Primary or Chronic Adrenocortical Insufficiency): Symptoms and Signs • Weakness, fatigue, and orthostatic hypotension • Hyperpigmentation • especially on pressure points (bony prominences), skin folds, scars, and extensor surfaces. • Anorexia, nausea, vomiting, and diarrhoea • Decreased tolerance to cold, with hypo metabolism • Dizziness and syncope • Gradual onset and nonspecific nature of early symptoms often lead to an incorrect initial diagnosis of neurosis. • Weight loss, dehydration, and hypotension are characteristic of the later stages of Addison disease
    33. 33. Addison Disease (Primary or Chronic Adrenocortical Insufficiency): Adrenal crisis • Characterised by • Profound muscular weakness • Severe pain in the abdomen, lower back, or legs; • peripheral vascular collapse; • Renal failure • Body temperature may be low, although severe fever often occurs, particularly when crisis is precipitated by acute infection.
    34. 34. Critical illness-related corticosteroid insufficiency (CIRCI) • Form of adrenal insufficiency in critically ill patients • Blood corticosteroid levels which are inadequate for the severe stress response they experience (Relative Adrenal Insufficiency) • Suspected in patients with low blood pressure despite resuscitation with intravenous fluids and vasopressor drugs. • Surviving Sepsis Campaign guidelines advocate intravenous hydrocortisone only in adults with septic shock and refractory hypotension (Steroid rescue therapy) • The exact definition of this condition, the best ways to test for corticoid insufficiency in critically ill patients, and the therapeutic use of (usually low doses) of corticosteroids remains a subject of debate
    35. 35. Addison Disease (Primary or Chronic Adrenocortical Insufficiency): Diagnosis • Electrolytes • Serum cortisol • Serum ACTH • Sometimes ACTH stimulation testing Test Results That Suggest Addison Disease Test Result Blood chemistry Serum Na < 135 mEq/L Serum K > 5 mEq/L Ratio of serum Na:K < 30:1 Plasma glucose, fasting < 50 mg/dL (< 2.78 mmol/L) Plasma HCO3 < 15–20 mEq/L BUN > 20 mg/dL (> 7.1 mmol/L) Hematology Hct Elevated WBC count Low Lymphocytes Relative lymphocytosis Eosinophils Increased Imaging Evidence of •Calcification in adrenal area •Renal TB •Pulmonary TB
    36. 36. Short ACTH Stimulation Test • Short synacthen test: basal sample for cortisol • give 250 microgramme Synacthen i.v. or i.m. • sample for cortisol are taken at 30 mins and 60 mins • In healthy individuals, the basal plasma cortisol should exceed 170 nmol per litre and rise to at least 580 nmol per litre at 30 or 60 mins
    37. 37. Congenital adrenal insufficiency • Group of genetic disorders, each characterized by inadequate synthesis of cortisol, aldosterone, or both. • Congenital adrenal hyperplasia • autosomal recessive genetic defect in one of the adrenal enzymes • Impairs production of cortisol and or aldosterone • Where cortisol synthesis is absent or decreased, ACTH (corticotropin) release, normally suppressed by cortisol, is excessive
    38. 38. Congenital adrenal insufficiency • The most common forms, 21-hydroxylase deficiency and 11β- hydroxylase deficiency, precursors proximal to the enzyme block accumulate and are shunted into adrenal androgens. • The consequent excess androgen secretion causes varying degrees of virilization in external genitals of affected female fetuses; no defects are discernible in external genitals of male fetuses. • In some less common forms affecting enzymes other than 21- hydroxylase and 11β-hydroxylase, the enzyme block impairs androgen synthesis (dehydoepiandrosterone [DHEAS] or androstenedione). • As a result, virilization of male fetuses is inadequate, but no defect is discernible in female fetuses.
    39. 39. Congenital adrenal insufficiency • 21-Hydroxylase (CYP21A2) deficiency • causes defective conversion of adrenal precursors to cortisol and, in some cases, to aldosterone, resulting in virilization and sometimes severe hyponatremia and hyperkalemia. • Diagnosis is by measurement of cortisol, its precursors, and adrenal androgens, sometimes after ACTH administration. • Treatment is with a glucocorticoid plus, if needed, a mineralocorticoid and, for some female neonates with genital ambiguity, surgical reconstruction. • 1β-Hydroxylase (CYP11B1) deficiency • involves defective conversion of adrenal precursors to cortisol, resulting in virilization, hypernatremia, hypokalemia, and hypertension. • Diagnosis is by measurement of cortisol, its precursors, and adrenal androgens and sometimes by measuring 11-deoxycortisol and 11-deoxycorticosterone after ACTH administration. • Treatment is with a corticosteroid.
    40. 40. Cushing Syndrome: Definition • A constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. • Cushing disease is Cushing syndrome that results from excess pituitary production of ACTH, usually secondary to a pituitary adenoma.
    41. 41. Cushing syndrome: Aetiology • Hyperfunction of the adrenal cortex can be ACTH dependent or ACTH independent • ACTH-dependent hyperfunction may result from • Hypersecretion of ACTH by the pituitary gland • Secretion of ACTH by a nonpituitary tumor, such as small cell carcinoma of the lung or a carcinoid tumor (ectopic ACTH syndrome) • Administration of exogenous ACTH0 • ACTH-independent hyperfunction • usually results from therapeutic administration of corticosteroids or from adrenal adenomas or carcinomas. • Rare causes include primary pigmented nodular adrenal dysplasia (usually in adolescents) and macronodular dysplasia (in older patients)
    42. 42. Cushing syndrome: Symptoms and Signs • moon facies with a plethoric appearance, truncal obesity with prominent supraclavicular and dorsal cervical fat pads (buffalo hump), and, usually, very slender distal extremities and fingers. • Muscle wasting and weakness. • skin • thin and atrophy • Poor wound healing easy brusing • Purple abdominal striae • Hypertension, renal calculi, osteoporosis, glucose intolerance, reduced resistance to infection, and mental disturbances • Children - Cessation of linear growth. • Females with adrenal tumors – virllism hypertrichosis, temporal balding. menstrual irregularities.
    43. 43. Cushing syndrome: Diagnosis • Dexamethasone suppression test • Urinary free cortisol (UFC) level • ACTH levels; if detectable, provocative testing • Pituitary Imaging • CT – microadenomas • Gadolinium-enhanced MRI – most acurate
    44. 44. Diagnostic Tests In Cushing Syndrome Diagnostic Tests in Cushing Syndrome Diagnosis Serum Cortisol, 9 AM Salivary or Serum Cortisol, Midnight Urinary Free Cortisol Low-Dose or OvernightDexam ethasone High- DoseDexametha sone Corticotropin- Releasing Hormone ACTH Level Normal N N N* S S N N Cushing disease N or ↑ ↑ ↑ NS S N or ↑ N or ↑ Ectopic ACTH N or ↑ ↑ ↑ NS NS Flat ↑↑ Adrenal tumor N or ↑ ↑ ↑ NS NS Flat ↓ *May be elevated in non-Cushing conditions. Flat = no significant rise in ACTH or cortisol; N = normal; NS = nonsuppression; S = suppression; ↑↑= greatly increased; ↑= increased; ↓=decreased.
    45. 45. Cushing syndrome: Treatment • Metyrapone or ketoconazole • Suppress cortisol secretion • Surgery or radiation therapy to remove tumours
    46. 46. Primary Aldosteronism (Conn Syndrome) • Aldosterone is the most potent mineralocorticoid produced by the adrenals. • It causes Na retention and K loss. • In the kidneys, aldosterone causes transfer of Na from the lumen of the distal tubule into the tubular cells in exchange for K and hydrogen. • The same effect occurs in salivary glands, sweat glands, cells of the intestinal mucosa, and in exchanges between ICFs and ECFs
    47. 47. Primary Aldosteronism (Conn Syndrome) • Aldosterone secretion is regulated by the renin-angiotensin system and, to a lesser extent, by ACTH • Reduction in blood volume and flow in the afferent renal arterioles induces secretion of renin. • Renin transforms angiotensinogen from the liver to angiotensin I, which is transformed by ACE to angiotensin II • Angiotensin II causes secretion of aldosterone and, to a much lesser extent, secretion of cortisol and deoxycorticosterone; it also has pressor activity. • Na and water retention resulting from increased aldosterone secretion increases the blood volume and reduces renin secretion.
    48. 48. Primary Aldosteronism (Conn Syndrome) • Primary aldosteronism is caused by an adenoma, usually unilateral, of the glomerulosa cells of the adrenal cortex or, more rarely, by adrenal carcinoma or hyperplasia. • Adenomas are extremely rare in children, but the syndrome sometimes occurs in childhood adrenal carcinoma or hyperplasia. • In adrenal hyperplasia, which is more common among older men, both adrenals are overactive, and no adenoma is present
    49. 49. Primary Aldosteronism (Conn Syndrome) : Symptoms and Signs • Hypernatremia, hypervolemia, and a hypokalemic alkalosis • Causes episodic weakness, paraesthesia, transient paralysis, and tetany. • Diastolic hypertension and hypokalemic nephropathy with polyuria and polydipsia • In many cases, the only manifestation is mild to moderate hypertension. • Odema is uncommon
    50. 50. Primary Aldosteronism (Conn Syndrome); Diagnosis • Electrolytes • Plasma aldosterone • Plasma renin activity (PRA) • plasma aldosterone > 15 ng/dL (> 0.42 nmol/L) and low levels of PRA, with a ratio of plasma aldosterone (in ng/dL) to PRA (in ng/mL/h) > 20. – Primary Aldosteronism • Low levels of both PRA and aldosterone suggest nonaldosterone mineralocorticoid excess • High levels of both PRA and aldosterone suggest secondary hyperaldosteronism • Adrenal imaging • Bilateral adrenal vein catheterization (for cortisol and aldosterone levels)
    51. 51. Primary Aldosteronism (Conn Syndrome): Treatment • Surgical removal of tumors • Spironolactone or eplerenone for hyperplasia • Selective Aldosterone Blocker • Epleronone does not block androgen receptor – drug of choice in long-term treatment of men • Antihypertensive treaement • Required in about half of patients with hyperplasia
    52. 52. Pheochromocytoma • Catecholamine-secreting tumor of chromaffin cells typically located in the adrenals. • The catecholamines secreted include norepinephrine, epinephrine, dopamine, and dopa in varying proportions. • About 90% of pheochromocytomas are in the adrenal medulla, but they may also be located in other tissues derived from neural crest cells. • Pheochromocytomas in the adrenal medulla occur equally in both sexes, are bilateral in 10% of cases (20% in children), and are malignant in < 10%. • Of extra-adrenal tumors, 30% are malignant. • Occur at any age, peak incidence is between the 20s and 40s. • 25% due to germline mutations
    53. 53. Pheochromocytoma • Pheochromocytomas vary in size but average 5 to 6 cm in diameter. • They weigh 50 to 200 g, but tumors weighing several kilograms have been reported. • Rarely, they are large enough to be palpated or cause symptoms due to pressure or obstruction. • Regardless of the histologic appearance, the tumor is considered benign if it has not invaded the capsule and no metastases are found, although exceptions occur • May be part of the syndrome of familial multiple endocrine neoplasia (MEN) types 2A and 2B, in which other endocrine tumors (parathyroid or medullary carcinoma of the thyroid) coexist or develop subsequently
    54. 54. Pheochromocytoma: Signs and Symptoms • Hypertension - paroxysmal in 45% of patients • Tachycardia, diaphoresis, postural hypotension, tachypnea, cold and clammy skin, severe headache, angina, palpitations, nausea, vomiting, epigastric pain, visual disturbances, dyspnea, paresthesias, constipation, and a sense of impending doom. • Paroxysmal attacks may be provoked by palpation of the tumor, postural changes, abdominal compression or massage, induction of anesthesia, emotional trauma, unopposed β-blockade (which paradoxically increases BP by blocking β-mediated vasodilation), or micturition (if the tumor is in the bladder). • In elderly patients, severe weight loss with persistent hypertension is suggestive of pheochromocytoma. • Physical examination, except for the presence of hypertension, is usually normal unless done during a paroxysmal attack. • Retinopathy and cardiomegaly are often less severe than might be expected for the degree of hypertension, but a specific catecholamine cardiomyopathy can occur
    55. 55. Pheochromocytoma: Diagnosis • Suspected in patients with typical symptoms or particularly sudden, severe, or intermittent unexplained hypertension. • Plasma free metanephrines and or urinary metanephrines • Plasma free is 99% sensitive • Urinary metanephrine vanillylmandelic acid (VMA) and homovanillic acid (HVA) • Presence of urinary metanephrenis is 95% sensitive • Two or 3 normal results while the patient is hypertensive render the diagnosis extremely unlikely • Chest and abdomen imaging (CT or MRI) if catecholamine screen positive • Possibly nuclear imaging with 123I-metaiodobenzylguanidine (MIBG) • 85% of phaemochromcystoms uptake this isotope
    56. 56. Pheochromocytoma: Treatment • Hypertension control with combination of α-blockers and β-blockers • Phenoxybenzamine α-blockers initially and then β-blockers Propranolol • Surgical removal of tumour • Usually laprascopically • Using Phentolamine and nitroprusside to control hypertension
    57. 57. Thyroid disorders • Urgencies associated with thyroid disorders • Thyroid storm • Hypothyroid crisis
    58. 58. Thyroid storm • Acute hyperthyroidism that results from untreated or inadequately treated severe hyperthyroidism. • Elevated serum levels of free thyroid hormones, hypermetabolism and adrenergic overstimulation • Rare, occurring in patients with Graves' disease or toxic multinodular goiter (a solitary toxic nodule is a less common cause and generally causes less severe manifestations). • Precipitated by infection, trauma, surgery, embolism, diabetic ketoacidosis, or preeclampsia.
    59. 59. Thyroid storm: Symptoms and Signs • Florid Hyperthyroidism • Graves Disease – Goitre, Exophthalmos, Infiltrative dermopathy • Thyroiditis – • Multinodular goitre • Single Autonomous hyperfunctioning “hot” nodule • fever • marked weakness and muscle wasting • extreme restlessness with wide emotional swings, confusion, psychosis,coma * particularly elderly • nausea, vomiting, diarrhoea, and hepatomegaly with mild jaundice. • Tachycardia, Atrial fibrillation, Cardiovascular collapse and shock
    60. 60. Thyroid storm: Diagnosis • TSH • Suppressed in hyperthyroid patients except in TSH secreting pituitary ademoa or pituitary resistance to the normal inhibition by thyroid hormone • Free T4, plus either free T3 or total T3 • Elevated T4 but can be falsely normal in hypertheroid patients with a severe systemic illness and in T3 thyrotoxicosis • Sometimes radioactive iodine uptake • Uptake elevated if due to hormone over production • TSH Receptor Antibodies • Graves Disease
    61. 61. Thyroid storm: Treatment • Depends on cause but may include • Methimazole or propylthiouracil • Block thyroid perioxidase • Side-effects agranulocytosis and liver failure (esp with later) • β-Blockers • Propranolol, atenolol or metoprolol • Counteract adrenergic stimulatiomn • Iodine • Inhibits the release of T3 and T$ and inhibits the organification • Radioactive iodine • Treatment of choice for Graves Disease and Toxic nodular Goitre • Surgery • Recommended for Graved disease with pharmacetiucal treatment failure • Large Goitres • Toxic adenoma and muli-nodular goitres
    62. 62. Hypothyroidism • Hypothyroidism occurs at any age but is particularly common among the elderly. • It occurs in close to 10% of women and 6% of men > 65. • Although typically easy to diagnose in younger adults, it may be subtle and manifest atypically in the elderly
    63. 63. Hypothyroidism • Primary hypothyroidism • Due to disease in the thyroid; thyroid-stimulating hormone (TSH) is increased • Causes • autoimmune – Hashimoto’s thyroidtis • Post-therapeutic hypothyroidism – radioactive iodine therapy or surgery or antithyroid medication overtreatment • Iodine Deficiency • Lithium and Amiodarone
    64. 64. Hypothyroidism Secondary hypothyroidism • occurs when the hypothalamus produces insufficient thyrotropin-releasing hormone (TRH) or the pituitary produces insufficient TSH. • Sometimes, deficient TSH secretion due to deficient TRH secretion is termed tertiary hypothyroidism
    65. 65. Hypothyroidism: Symptoms and Signs • Primary hypothyroidism are often subtle and insidious • cold intolerance, constipation, forgetfulness, and personality changes • Modest weight gain is largely the result of fluid retention and decreased metabolismm. • deposition of proteinaceous ground substance • Facial puffiness, periorbital swelling, macroglossia, Carpal-tarsal syndrome • menorrhagia or secondary amenorrhea • The facial expression is dull; the voice is hoarse and speech is slow
    66. 66. Hypothyroidism • eyelids droop because of decreased adrenergic drive • hair is sparse, coarse, and dry • skin is coarse, dry, scaly, and thick. • The relaxation phase of deep tendon reflexes is slowed. • Hypothermia is common. • Dementia or frank psychosis (myxedema madness) • Carotenmia – palms and soles • Pericardial, pleural abdominal effusion.
    67. 67. Hypothyroidism • Elderly patients have significantly fewer symptoms than do younger adults, and complaints are often subtle and vague. • nonspecific geriatric syndromes— • confusion, anorexia, weight loss, falling, incontinence, and decreased mobility. • Muscular aches and weakness, often mimicking polymyalgia rheumatica or polymyositis, and an elevated CK level • May mimic dementia or parkinsonism
    68. 68. Hypothyroidism • Myxoedema coma • life-threatening complication of hypothyroidism • usually occurring in patients with a long history of hypothyroidism. • coma with extreme hypothermia (temperature 24° to 32.2° C), • areflexia, seizures, and respiratory depression with CO2 retention. • Precipitating factors include illness, infection, trauma, drugs that suppress the CNS, and exposure to cold • Fatal without rapid treatment
    69. 69. Hypothyroidism: Diagnosis • TSH • Most sensitive test • High in Primary and Generally low in Secondary • Free thyroxine (T4) • Serum T3 is not sensitive for Primary hypothyroidism • Sustained falls in TSH results in preferential synthesis and secretion of Free T3
    70. 70. Hypothyroidism: Treatment • l-Thyroxine, adjusted until TSH levels are in midnormal range • Various Thyroid hormone preparations available • Synthetic T4 (L Thyroxrine) preferred Myxedema coma T4 given IV Corticosteroids – central hypothyrism cannot be initially ruled out Supportive care as needed Conversion to oral T4 when patient is stable
    71. 71. Pituitary disorders • Generalized hypopituitarism • Central Diabetes Insipidus
    72. 72. Pituitary disorders • Generalized hypopituitarism refers to endocrine deficiency syndromes due to partial or complete loss of anterior lobe pituitary function. • Various clinical features occur depending on the specific hormones that are deficient. • Diagnosis involves imaging tests and measurement of pituitary hormone levels basally and after various provocative stimuli. • Treatment depends on cause but generally includes removal of any tumor and administration of replacement hormones
    73. 73. Central Diabetes insipidus • Deficiency of vasopressin (ADH) due to a hypothalamic-pituitary disorder (central DI [CDI]) • Primary • Genetic • Secondary • hypophysectomy, cranial injuries (particularly basal skull fractures), suprasellar and intrasellar tumors (primary or metastatic), • Langerhans cell histiocytosis (Hand- Schüller-Christian disease), • lymphocytic hypophysitis, • Granulomas (sarcoidosis or TB) • Vascular lesions (aneurysm, thrombosis) • Infections (encephalitis, meningitis
    74. 74. Central Diabetes insipidus: Clinical Signs and Diagnosis • Main clinical signs Polyuria and polydipsia • Diagnosis is by water deprivation test showing failure to maximally concentrate urine • Hourly urine collection until patient has lost more than 5% of intial body lady or develops orthostatic hypotension or postural tachycardia • Unable to concentrate urine to greater than plasma osmolality but able to increase their urine osmolaltity by >50% after vasopressin administration • Vasopressin levels and response to exogenous vasopressin help distinguish Central and Nephrogenic DI • Measured at end of water deprivation test
    75. 75. Central Diabetes insipidus: Treatment • Intranasal desmopressin or lypressin. • Desmopressin once daily - Lypressin TDS • Nonhormonal treatment includes use of diuretics (mainly thiazides) and vasopressin-releasing drugs, such as chlorpropamide. • Thiazides – reduce urine volume by reducing Effective Circulating colume and increasing proximal tubular resoprtion • Chlorpropamide – effective in some patients with partial CDI
    76. 76. Parathyroid disorders • Hyperparathyroidism/Hypercalc aemia • Hypoparathyroidism
    77. 77. Hypercalcemia In Brief •Total serum Ca concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum Ca > 5.2 mg/dL (> 1.30 mmol/L). •Principal causes include hyperparathyroidism, vitamin D toxicity, and cancer. •Clinical features include polyuria, constipation, muscle weakness, confusion, and coma. •Diagnosis is by serum ionized Ca and parathyroid hormone concentrations. •Treatment to increase Ca excretion and reduce bone resorption of Ca involves saline, Na diuresis, and drugs such as pamidronate
    78. 78. Hypoparathyroidism • Characterized by hypocalcemia and hyperphosphatemia and often causes chronic tetany. • Results from deficient parathyroid hormone (PTH), which can occur in autoimmune disorders or after the accidental removal of or damage to several parathyroid glands during thyroidectomy • Transient hypoparathyroidism is common after subtotal thyroidectomy
    79. 79. Hypoparathyroidism: Symptoms and Signs • Hypocalcemia is frequently asymptomatic. • The presence of hypoparathyroidism is often suggested by the clinical manifestations of the underlying disorder (eg, short stature, round facies, intellectual disability, basal ganglia calcification in type Ia pseudohypoparathyroidism • Neurologic manifestations: • Muscle cramps involving the back and legs are common. • mild, diffuse encephalopathy. • Papilledema
    80. 80. Hypoparathyroidism: Symptoms and Signs • Severe hypocalcemia with serum Ca < 7 mg/dL (< 1.75 mmol/L) may cause hyperreflexia, tetany, laryngospasm, or generalized seizures. • Tetany • Sensory symptoms consisting of paresthesias of the lips, tongue, fingers, and feet • Carpopedal spasm, which may be prolonged and painful • Generalized muscle aching • Spasm of facial musculature • Chvostek sign is an involuntary twitching of the facial muscles elicited by a light tapping of the facial nerve just anterior to the exterior auditory meatus • Trousseau sign is the precipitation of carpopedal spasm by reduction of the blood supply to the hand with a tourniquet or BP cuff inflated to 20 mm Hg above systolic BP applied to the forearm for 3 min
    81. 81. Hypoparathyroidism: Diagnosis • Estimation or measurement of ionized Ca • PTH • Low or even low-normal PTH concentrations are inappropriate and suggest hypoparathyroidism. • An undetectable PTH concentration suggests idiopathic hypoparathyroidism. • A high PTH concentration suggests pseudohypoparathyroidism or an abnormality of vitamin D metabolism. • High Serum Phosphate and Normal Alkaline Phosphatase
    82. 82. Hypoparathyroidism: Treatment • IV Ca gluconate for tetany • Oral Ca for postoperative hypoparathyroidism • Oral Ca and vitamin D for chronic hypocalcemia
    83. 83. The End • Questions?