Endocrine Flashcards

Question

What are the 8 Is precipitating DKA?

Answer 1

* Infection * Ischemia or Infarction * Iatrogenic (glucocorticoids) * Intoxication * Insulin missed * Initial presentation * Intra-abdominal process (e.g. pancreatitis, cholecystitis) * Intraoperative/perioperative stress

Answer 2

* Usually occurs in T1DM * Insulin deficiency with ↑ counterregulatory hormones (glucagon, cortisol, catecholamines, GH) * Can occur with lack of insulin (non-adherence, inadequate dosage, 1st presentation) or increased stress (surgery, infection, exercise) * Unrestricted hepatic glucose production → hyperglycemia → osmotic diuresis → dehydration and electrolyte disturbance → ↓ Na + (water shift to ECF causing pseudohyponatremia) * Fat mobilization → ↑ FFA → ketoacids → metabolic acidosis * Severe hyperglycemia exceeds the renal threshold for glucose and ketone reabsorption → glucosuria and ketonuria * Total body K⁺ depletion but serum K⁺ may be normal or elevated 2º to shift from ICF to ECF due to lack of insulin, ↑ plasma osmolality * Total body PO₄^3- depletion

Answer 3

* Polyuria, polydipsia, polyphagia with marked fatigue, N/V * Dehydration (orthostatic changes) * LOC may be ↓ with ketoacidosis or with high serum osmolality (osm \>330 mmol/L) * Abdominal pain * Fruity smelling breath * Kussmaul’s respiration

Answer 4

* ↑ BG (typically11-55 mmol/L), ↓ Na⁺ (2º to hyperglycemia → for every ↑ in BG by 10 mmol/L there is a ↓ in Na⁺ by 3 mEq/L) • Normal or ↑ K⁺ , ↓ HCO₃^– , ↑ BUN, ↑ Cr, ketonemia, ↓ PO₄^3- • ↑ osmolality

Answer 5

* Metabolic acidosis with ↑ AG, possible 2º respiratory alkalosis * If severe vomiting/dehydration there may be a metabolic alkalosis

Answer 6

+ve for glucose and ketones

Answer 7

* ABCs if patient is stuporous or comatose * Monitor degree of ketoacidosis with Anion Gap, not Blood Glucose or serum ketone level * Rehydration: * 1 L/h NS in first 2 h * after 1st 2 L, 300-400 mL/h 0.45% NaCl (continue NS if corrected sodium is falling faster than 3 mosm/kg water/h) * once BG reaches 13.9 mmol/L then switch to D5W * to maintain BG in the range of 13.9-16.6 mmol/L * Insulin therapy: * critical to resolve acidosis, not hyperglycemia * do not use with hypokalemia, until serum K⁺ is corrected to \>3.3 mEq/L * use only regular insulin (R) * maintain on 0.1 U/kg/h insulin R infusion * check serum glucose hourly * K⁺ replacement: * with insulin administration, hypokalemia may develop * if serum K⁺ \<3.3 mEq/L, hold insulin and give 40 mEq/L K⁺ replacement * when K⁺ 3.5-5.0 mEq/L add KCL 20-40 mEq/L IV fluid to keep K⁺ in the range of 3.5-5 mEq/L * HCO₃^–: * if pH \<7.0 or if hypotension, arrhythmia, or coma is present with a pH of \<7.1 give HCO₃^– in 0.45% NaCl * do not give if pH \>7.1 (risk of metabolic alkalosis) * can give in case of life-threatening hyperkalemia * ± mannitol (for cerebral edema)

Answer 8

* 2-5% mortality in developed countries * Serious morbidity from sepsis, hypokalemia, respiratory complications, thromboembolic complications, and cerebral oedema (the latter in children)

Answer 9

* Occurs in type 2 DM * Often precipitated by sepsis, stroke, MI, CHF, renal failure, trauma, drugs (glucocorticoids, immunosuppressants, phenytoin, diuretics), dialysis, recent surgery, burns * Partial or relative insulin deficiency decreases glucose utilization in muscle, fat, and liver while inducing hyperglucagonemia and hepatic glucose production * Presence of a small amount of insulin prevents the development of ketosis by inhibiting lipolysis * Characterized by hyperglycemia, hyperosmolality, and dehydration without ketosis * More severe dehydration compared to DKA due to more gradual onset and ↑duration of metabolic decompensation plus impaired fluid intake which is common in bedridden or elderly * Volume contraction → renal insufficiency → ↑ hyperglycemia, ↑ osmolality → shift of fluid from neurons to ECF → mental obtundation and coma

Answer 10

* Onset is insidious → preceded by weakness, polyuria, polydipsia * History of decreased fluid intake * History of ingesting large amounts of glucose containing fluids * Dehydration (orthostatic changes) * ↓ LOC → lethargy, confusion, comatose due to high serum osmolality * Kussmaul’s respiration is absent unless the underlying precipitant has also caused a metabolic acidosis

Answer 11

* ↑ BG (typically 44.4-133.2 mmol/L) * In mild dehydration, may have hyponatremia (spurious 2º to hyperglycemia → for every ↑ in BG by 10 mmol/L there is a ↓ in Na + by 3 mEq/L) * if dehydration progresses, may get hypernatremia * Ketosis usually absent or mild if starvation occurs * ↑ osmolality

Answer 12

* -ve for ketones unless there is starvation ketosis * Glycosuria

Answer 13

* ABCs if patient is stuporous or comatose * Rehydration: * IV fluids: 1 L/h NS initially * evaluate corrected serum Na⁺ * if corrected serum Na⁺ high or normal, switch to 0.45% NaCl (4-14 mL/kg/h) * if corrected serum Na⁺ low, maintain NS (4-14 mL/kg/h) * when serum BG reaches 13.9 mmol/L switch to D5W * K⁺ replacement: * less severe K⁺ depletion compared to DKA * if serum K⁺ \<3.3 mEq/L, hold insulin and give 40 mEq/L K⁺ replacement * if K⁺ is 3.3-5.0, give KCl 20-30 mEq/L IV fluid * if serum K⁺ ≥5.5 mEq/L, check K + every 2 h * Search for precipitating event * Insulin therapy: * use only regular insulin (R) * initially load 0.1 U/kg body weight insulin R bolus * maintenance 0.1 U/kg/h insulin R infusion or IM * check serum glucose hourly * in general lower insulin requirement compared to DKA

Answer 14

Overall mortality approaches 50% primarily because of the older patient population and underlying etiology/precipitant

Answer 15

Starvation or alcohol ketosis

Answer 16

* increased risk of CAD, ischemic stroke, and peripheral arterial disease secondary to accelerated atherosclerosis * CAD - coronary artery disease * risk of MI is 3-5x higher in those with DM compared to age-matched controls * CAD is the leading cause of death in type 2 DM * most patients with DM are considered “high risk” under the risk stratification for CAD * ischemic stroke * risk of stroke is approximately 2.5x higher in those with DM * level of glycemia is both a risk factor for stroke and a predictor of a poorer outcome in patients who suffer a stroke * HbA1c level is a significant and independent predictor of the risk of stroke * peripheral arterial disease * manifested by intermittent claudication in lower extremities, intestinal angina, foot ulceration * risk of foot gangrene is 30x higher in those with DM compared to age-matched controls * risk of lower extremity amputation is 15x higher in those with DM * treatment * tight blood pressure control (\<130/80 mmHg); especially for stroke prevention * tight glycemic control in early DM without established CVD * tight low density lipoprotein (LDL) cholesterol control (LDL 77 mg/dL [\<2.0 mmol/L]) * ACEI or angiotensin receptor blocker in high-risk patients * smoking cessation

Answer 17

Average fluid loss runs at 3-6 L in DKA, and 8-10 L in HHS

Answer 18

* Diabetic retinopathy * Diabetic nephropathy * Diabetic neuropathy * Peripheral sensory neuropathy * Motor neuropathy * Autonomic neuropathu

Answer 19

* type 1 DM: 25% affected at 5 yr, 100% at 20 yr * type 2 DM: 25% affected at diagnosis, 60% at 20 yr * leading cause of blindness in North America between the ages of 20-74 * most important factor is disease duration

Answer 20

* nonproliferative * asymptomatic but if macular involvement occurs vision may be impaired * microaneurysms, hard exudates, dot-blot and flame hemorrhages * preproliferative * macular edema, cotton wool spots, venous shunts and beading, intra-retinal microvascular abnormalities (IRMA) * proliferative * with neovascularization and fibrous scarring; great risk for loss of vision secondary to vitreous hemorrhage (floaters) and/or retinal detachment

Answer 21

* tight glycemic control (delays onset, decreases progression), tight lipid control, manage HTN, * smoking cessation * pan-retinal laser photocoagulation for treatment of neovascularization * vitrectomy * annual follow-up visits with an optometrist or ophthalmologist examination through dilated pupils whether symptomatic or not (immediate referral after diagnosis of type 2 DM; 5 yr after diagnosis of type 1 DM) * interval for follow-up should be tailored to severity of retinopathy

Answer 22

* DM-induced renal failure is the most common cause of renal failure in North America * 20-40% of persons with type 1 DM (after 5-10 yr) and 4-20% with type 2 DM have progressive nephropathy

Answer 23

* thickening of capillary basement membrane and glomerular mesangium resulting in glomerulosclerosis and renal insufficiency * diffuse glomerulosclerosis is more common than nodular intercapillary glomerulosclerosis (Kimmelstiel-Wilson lesions)

Answer 24

* serum creatinine * random urine test for albumin to creatinine ratio (ACR) plus urine dipstick test for all type 2 DM patients at diagnosis, then annually, and for postpubertal type 1 DM patients with ≥5 yr duration of DM

Answer 25

* initial changes include microalbuminuria, increased GFR (up to 140%) from hyperfiltration, enlarged kidneys * microalbuminuria: 30 μg/mg * macroalbuminuria: 300 μg/mg * progression over 15 yr to cause HTN, persistent proteinuria (macroalbuminuria), nephrotic syndrome, and renal failure * elevated HbA1c is an independent risk factor for progression to microalbuminuria

Answer 26

* tight glycemic control * tight blood pressure control (\<130/80 mmHg): can use either ACEI or ARB (often used first line for their CVD protection) * even in the absence of glycemic control ACEIs or ARBs reduce the level of albuminuria and the rate of progression of renal disease in normotensive and hypertensive patients with type 1 or type 2 DM * type 1 DM → CKD with either HTN or albuminuria → ACEIs 1st line; ARBs 2nd line * type 2 DM → CKD with HTN and albuminuria → ACEIs or ARBs (dose adjust if creatinine clearance (CrCl) \<60 mL/min) * consider use of non-dihydropyridine calcium channel blocker (e.g. diltiazem) in those unable to tolerate both ACEIs and ARBs * limit use of nephrotoxic drugs and dyes * renal failure may necessitate hemodialysis and renal transplant

Answer 27

Approximately 50% of patients within 10 yr of onset of type 1 DM and type 2 DM

Answer 28

* can have peripheral sensory neuropathy, motor neuropathy, or autonomic neuropathy * mechanism poorly understood * acute cranial nerve palsies and diabetic amyotrophy are thought to be due to ischemic infarction of peripheral nerve * the more common motor and sensory neuropathies are thought to be related to metabolic or osmotic toxicity secondary to increased sorbitol and/or decreased myoinositol (possible mechanisms include accumulation of advanced glycation endproducts [AGE], oxidative stress, protein kinase C, nerve growth factor deficiency)

Answer 29

128 Hz tuning fork or 10 g monofilament at diagnosis and annually in people with type 2 DM and after 5 yr duration of type 1 DM

Answer 30

* Paresthesias (tingling, itching), neuropathic pain, radicular pain, numbness, decreased tactile sensation * Bilateral and symmetric with decreased perception of vibration and pain/ temperature; especially true in the lower extremities but may also be present in the hands * Decreased ankle reflex * Symptoms may first occur in entrapment syndromes * e.g. carpal tunnel * May result in neuropathic ulceration of foot

Answer 31

* Less common than sensory neuropathy * Delayed motor nerve conduction and muscle weakness/atrophy * May involve one nerve trunk (mononeuropathy) or more (mononeuritis multiplex) * Some of the motor neuropathies spontaneously resolve after 6-8 wk * Reversible CN palsies: III (ptosis/ophthalmoplegia, pupil sparing), VI (inability to laterally deviate eye), and VII (Bell’s palsy) * Diabetic amyotrophy: refers to pain, weakness, and wasting of hip flexors or extensors

Answer 32

* Postural hypotension, tachycardia, decreased cardiovascular response to Valsalva maneuver * Gastroparesis and alternating diarrhea and constipation * Urinary retention and erectile dysfunction

Answer 33

* tight glycemic control * for neuropathic pain syndromes: tricyclic antidepressants (e.g. amitriptyline), pregabalin, duloxetine, anti-epileptics (e.g. carbamazepine, gabapentin), and capsaicin * foot care education * Jobst® fitted stocking and tilting of head of bed may decrease symptoms of orthostatic hypotension * treat gastroparesis with domperidone and/or metoclopramide (dopamine antagonists), erythromycin (stimulates motilin receptors) * medical, mechanical, and surgical treatment for erectile dysfunction

Answer 34

* Dermatologic * diabetic dermopathy: atrophic brown spots commonly in pretibial region known as “shin spots”, secondary to increased glycosylation of tissue proteins or vasculopathy * eruptive xanthomas secondary to increased triglycerides * necrobiosis lipoidica diabeticorum: rare complication characterized by thinning skin over the shins allowing visualization of subcutaneous vessels * Bone and Joint Disease * juvenile cheiroarthropathy: chronic stiffness of hand caused by contracture of skin over joints secondary to glycosylated collagen and other connective tissue proteins * Dupuytren’s contracture * bone demineralization: bone density 10-20% below normal * adhesive capsulitis (“frozen shoulder”) * Cataracts * subcapsular and senile cataracts secondary to glycosylated lens protein or increased sorbitol causing osmotic change and fibrosis * Infections: foot infections

Answer 35

C-peptide Increased = endogenous Decreased or normal = exogenous

Answer 36

A short peptide released into the circulation when proinsulin is cleaved to insulin

Answer 37

* Whipple’s triad * serum glucose 45 mg/dL (\<2.5 mmol/L) in males and 40 mg/dL (\<2.2 mmol/L) in females * neuroglycopenic symptoms * rapid relief provided by administration of glucose * adrenergic symptoms (typically occur first; caused by autonomic nervous system activity) * palpitations, sweating, anxiety, tremor, tachycardia * neuroglycopenic symptoms (caused by decreased activity of CNS) * dizziness, headache, clouding of vision, mental dullness, fatigue, confusion, seizures, coma

Answer 38

* UEC, LFTs, drugs/toxins, cortisol * if concerned about possible insulinoma: * blood work to be drawn when patient is hypoglycemic (e.g. during hospitalized 72 h fast) for glucose, serum ketones, insulin, pro-insulin, C-peptide, insulin antibodies

Answer 39

* for fasting hypoglycemia, must treat underlying cause * for post-prandial (reactive) hypoglycemia, frequent small feeds * treatment of hypoglycemic episode in the unconscious patient or patient NPO * D50W 50 mL (1 ampule) IV or 1 mg glucagon SC (if no IV available) * may need ongoing glucose infusion once BG \> 90 mg/dL (5 mmol/L)

Answer 40

* Elevated waist circumference * Elevated triglyceride levels: ≥1.7 mmol/L or on medical therapy * Reduced HDL:\<1.0 mmol/L in men, \<1.3 mmol/L in women OR on drug treatment * Elevated blood pressure: ≥130 systolic or ≥85 diastolic OR on medical therapy for HTN * Elevated fasting glucose: \>5.5 mmol/L or on medical therapy

Answer 41

2.2 - 2.6 mmol/L

Answer 42

* Stimulated by low serum Ca²⁺ and high serum PO₄^3-; inhibited by chronic low serum Mg²⁺, high serum Ca²⁺, and calcitriol. * Net effect: ↑ Ca²⁺, ↑Cacitriol, ↓PO₄^3-

Answer 43

* Source: * Dietary intake * Synthesized from cholesterol: UV on skin makes cholecalciferol (vitD3) → liver makes calcidiol (25-(OH)D3) → kidneys make calcitriol * Regulation: * Renal calcitriol production is stimulated by low serum PO₄^3- and PTH; inhibited by high serum PO₄^3- and calcitriol in negative feedback * Net effect: ↑Ca²⁺, ↑PO₄^3-

Answer 44

* Source: Thyroid C cells * Regulation: * Stimulated by pentagastrin (GI hormone) and high serum Ca²⁺; inhibited by low serum Ca²⁺ * Net effect: ↓Ca²⁺ (in pharmacologic doses), ↓PO₄^3-

Answer 45

Serum Ca2+ level \>2.6 mmol/L after correction for albumin.

Answer 46

1. Is the patient hypercalcemic? (correct for albumin) 2. Is the PTH high/normal or low? 3. If PTH is low, is phosphate high/normal or low? If phosphate is high/normal is the level of vitamin D metabolites high or low?

Answer 47

* Increased PTH secretion commonly due to: * parathyroid adenoma (81%) * lithium therapy * less often parathyroid carcinoma (4%) or parathyroid hyperplasia (15%)

Answer 48

Partial resistance to PTH action leads to parathyroid gland hyperplasia and increased PTH secretion, often in patients with renal failure and osteomalacia (due to low or low normal serum calcium levels)

Answer 49

Irreversible clonal outgrowth of parathyroid glands, usually in long-standing inadequately treated chronic renal failure on dialysis

Answer 50

* Surgical excision acts as a definitive treatment and is recommended for patients who are _symptomatic_. * For mild asymptomatic disease medical surveillance may be appropriate with annual serum calcium, creatinine, and BMD. * For _asymptomatic patients surgery_ is recommended for those who meet ≥1 of the following criteria: * Serum calcium concentration more than 0.25 mmol/L above the upper limit of normal * Creatinine clearance \<60 mL/min * BMD T-score \<-2.5 at hip, spine, or distal radius, and/or previous fragility fracture * Age \<50 yr

Answer 51

Bones, stones, groans, and psychic moans.

Answer 52

_Malignancy-associated hypercalcemia_ * Usually occurs in the later stages of disease * Most commonly seen in lung, renal, breast, ovarian, and squamous tumors, as well as lymphoma and multiple myeloma * Mechanisms: * Secretion of parathyroid hormone-related protein (PTHrP) which mimics PTH action by preventing renal calcium excretion and activating osteoclast-induced bone resorption * Cytokines in multiple myeloma * Calcitriol production by lymphoma * Osteolytic bone metastases direct effect * Excess PTH in parathyroid cancer

Answer 53

* Primary hyperparathyroidism * Malignancy: hematologic, humoral, skeletal metastases (\>90% from 1 or 2) * Renal disease: tertiary hyperparathyroidism * Drugs: calcium carbonate, milk alkali syndrome, thiazide, lithium, theophylline, vitamin A/D intoxication * Familial hypocalciuric hypercalcemia * Granulomatous disease: sarcoidosis, TB, Hodgkin's lymphoma * Thyroid disease: thyrotoxicosis * Adrenal disease: adrenal insufficiency, pheochromocytoma * Immobilisation

Answer 54

* ABCs: Insert large bore IV cannula and send blood for FBC, UEC, LFTs, calcium, lipase and TFT. * ECG monitor: * Bradycardia * Short GT interval with a widened QRS * Flattened T waves, atrioventricular block and cardiac arres * CXR: may show underlying cause. * Rehydrate: 0.9% NS 500ml/h * Frusemide 20-40 mg IV once urine output is established to maintain diuresis * Refer to medical team. * Bisphosphonates (diminishes bone resorption): max effect at 7 days * Corticosteroids in hypervitaminosis D and haematological malignancies (anti-tumour effect): acts in 5-10 days * Dialysis: last resort treatment

Answer 55

* **Paresthesias**: perioral, hands, and feet * **Chvostek’s sign**: percussion of the facial nerve just anterior to the external auditory meatus elicits ipsilateral spasm of the orbicularis oculi or orbicularis oris muscles * **Trousseau’s sign:** inflation of a blood pressure cuff above systolic pressure for 3 min elicits carpal spasm and paresthesia

Answer 56

* Hypocalcemia * Metabolic alkalosis (with hyperventilation) * Hypokalemia * Hypomagnesemia

Answer 57

* Chronic renal failure, acute pancreatitis * Rhadbomyolysis, tumour lysis syndrome, whole blood transfusion and toxic shock syndrome * primary respiratory alkolosis (hyperventilation) * Post-parathyroidectomy or thyroid surgery; autoimmune hypoparathyroidism

Answer 58

* Bone disease * Cardio: cardiovascular collapse, hypotesion unresponsive to fluids and vasopressors and dysrhythmias. * Neuro: acute seizures or tetany, basal ganglia calcification, parkinsonism, hemiballismus and choreathetosis.

Answer 59

* correct underlying disorder: * FBC, UEC, LFTs, creatine kinase, magnesium and lipase * ECG: * Qt interval prolongation, T wave inversion * AV block, torsade de point (cardiad arrest may ensue) * mild/asymptomatic (ionized Ca²⁺ \>0.8 mmol/L) * treat by increasing dietary Ca²⁺ by 1000 mg/d * calcitriol 0.25 µg/d * acute/symptomatic hypocalcemia (ionized Ca²⁺ \<0.7 mmol/L) * immediate treatment required - IV 0.9% NS 250ml/h * IV 10% calcium chloride 10-40 mL * goal is to raise Ca²⁺to low normal range (2.0-2.1 mmol/L) to prevent symptoms but allow maximum stimulation of PTH secretion * if PTH recovery not expected, requires long-term therapy with calcitriol and calcium * **do not correct hypocalcemia if asymptomatic and suspected to be transient**

Answer 60

* Primary testicular failure: * ↑LH and FSH, ↑FSH:LH ratio * ↓testosterone and sperm count

Answer 61

* Congenital: * Chromosomal defects (Klinefelter's, Noonan) * Cryptorchidism * Disorders of sexual development (DSD) * Bilateral anorchia (vanishing testicle syndrome) * Myotonic dystrophy * Mutation of FSH or LH receptor gene * Disorders of androgen synthesis * Germ cell defects * Sertoli cell only syndrome * Leydig cell aplasia/failure * Infection/Inflammation * Orchitis – TB, lymphoma, mumps, leprosy * Genital tract infection * Physical factors * Trauma, heat, irradiation, testicular torsion, varicocele * Drugs * Marijuana, alcohol, chemotherapy, ketoconazole, glucocorticoid, spironolactone * Autoimmune (antisperm antibodies) * Chronic systemic diseases (AIDS) * Idiopathic

Answer 62

* **Testicular size and consistency (soft/firm)** * Sperm count * LH, FSH, total, and/or bioavailable testosterone hCG stimulation * Karyotype

Answer 63

* Hypothalamic-pituitary axis failure: * ↓ LH + FSH * ↓ testosterone and sperm count

Answer 64

* Congenital * Kallman’s syndrome * Prader-Willi syndrome * Abnormal subunit of LH or FSH * Infection * Tuberculosis, meningitis * Endocrine * Adrenal androgen excess * Cushing’s syndrome * Hypo or hyperthyroidism * Hypothalamic-pituitary disease (tumor, hyperprolactinemia, hypopituitarism) * Drugs * Alcohol, marijuana, spironolactone, ketoconazole, GnRH agonists, androgen/oestrogen/progestin use, chronic narcotic use * Chronic illness * Cirrhosis, chronic renal failure, AIDS * Sarcoidosis, Langerhan's cell histiocytosis haemochromatosis * Critical illness * Surgery, MI, head trauma * Obesity * Idiopathic

Answer 65

* 47,XXY (most common) * 48,XXXY, 49,XXXXY

Answer 66

* Tall, slim, underweight * No features prepuberty * Postpuberty: male may suffer from developmental delay, long limbs, gynecomastia, lack of facial hair * Mild intellectual disability * Behavioral or psychiatric disorders – anxiety, shyness, aggressive behavior, antisocial acts

Answer 67

* Short stature, short webbed neck, low posterior hair line, wide carrying angle * Broad chest, widely spaced nipples * Lymphedema of hands and/or feet, cystic hygroma in newborn with polyhydramnios, lung hypoplasia * Coarctation of aorta, bicuspid aortic valve * Renal and cardiovascular abnormalities, increased risk of HTN * Less severe spectrum with mosaic * Mildly deficient to normal intelligence

Answer 68

45,X (most common)

Answer 69

* The decrease in sperm count is affected to a greater extent than the decrease in serum testosterone level * Likely to be associated with gynecomastia

Answer 70

* Associated with an equivalent decrease in sperm count and serum testosterone * Less likely to be associated with gynecomastia

Answer 71

* pregnancy and breastfeeding * **prolactinoma: most common** pituitary adenoma (prolactin-secreting tumors may be induced by oestrogens and grow during pregnancy) * pituitary masses with pituitary stalk compression causing reduced dopamine inhibition of prolactin release * primary hypothyroidism (increased TRH) * decreased clearance due to chronic renal failure or severe liver disease (prolactin is metabolized by both the kidney and liver) * medications with anti-dopaminergic properties are a common cause of high prolactin levels: antipsychotics (common), antidepressants, antihypertensives, anti-migraine agents (triptans/ergotamines), bowel motility agents (metoclopramide/domperidone), H₂-blockers (ranitidine) * macroprolactinemia (high molecular weight prolactin also known as big big prolactin)

Answer 72

* long-acting dopamine agonist: bromocriptine, cabergoline, or quinagolide (Norprolac®) * surgery ± radiation (rare) * prolactin-secreting tumors are very slow-growing and sometimes require no treatment * if medication-induced, consider stopping medication if possible * in certain cases if microprolactinoma and not planning on becoming pregnant, may consider OCP

Answer 73

* Infertility: failure of a couple to conceive after 12 mo of regular intercourse without use of contraception in women \<35 yr of age; and after 6 mo of regular intercourse without use of contraception in women ≥35 yr * History * Partner status re: infertility * Length of time for attempt to conceive * Prior successes with other partners * Ejaculation problems * Frequency of intercourse * Prev Surg, Med Hx, STD Hx * Hx orchitis? Cryptorchidism? * Hx toxic exposure? * Medications * Alcohol and illicit drug use * Heat exposure: bath, sauna, whirlpool * Smoking * P/E * General (height, weight, gynecomastia, masculine) * Testicular size and consistency * Varicocele? * Pituitary disease? * Thyroid disease? * Investigations * Should be considered for couples unable to conceive after 12 mo of unprotected and frequent intercourse; consider earlier evaluation if suggestive medical hx and physical, and in women ≥35 yr of age * Semen analysis x 2 (sperm count, morphology, motility) * Scrotal/testicular U/S (look for varicocele) * Blood work: LH, FSH, testosterone, prolactin, thyroid function tests, DNA fragmentation of sperm, karyotype, Y chromosome deletion * Test female partner * Treatment * No specific therapy for majority of cases * Treat specific causes * Consider: intrauterine insemination, IVF, therapeutic donor insemination, testicular aspiration of sperm, adoption

Answer 74

* High FSH (hypergonadotropic hypogonadism) * Gonadal dysgenesis * Abnormal sex chromosome (Turner’s XO) * Normal sex chromosome (46XX, 46XY) * Low FSH (hypogonadotropic hypogonadism) * Constitutional delay (most common) * Congenital abnormalities * Isolated GnRH deficiency * Pituitary failure (Kallman syndrome, head injury, pituitary adenoma, etc.) * Acquired * Endocrine disorders (type 1 DM) * Pituitary tumors * Systemic disorders (IBD, JRA, chronic infections, etc.)

Answer 75

* With hyperandrogenism: * PCOS * Autonomous hyperandrogenism (androgen secretion independent of the HPO axis) * Ovarian: tumor, hyperthecosis * Adrenal androgen-secreting tumor * Late onset or mild congenital adrenal hyperplasia (rare) * Without hyperandrogenism: * Hypergonadotropic hypogonadism (i.e. premature ovarian failure: high FSH, low estradiol) * Idiopathic * Autoimmune: type 1 DM, autoimmune thyroid disease, Addison’s disease * Iatrogenic: cyclophosphamide drugs, radiation * Hyperprolactinemia * Endocrinopathies: most commonly hyper or hypothyroidism * Hypogonadotropic hypogonadism (low FSH): * Pituitary compression or destruction: pituitary adenoma, craniopharyngioma, lymphocytic hypophysitis, infiltration (sarcoidosis), head injury, Sheehan’s syndrome * Functional hypothalamic amenorrhea (often related to stress, excessive exercise and/or anorexia)

Answer 76

No menses by age 13 in absence of 2ºvsexual characteristics or no menses byvage 15 with 2º sexual characteristics or no menses 2 yr after thelarche

Answer 77

No menses for \>6 mo or 3 cycles after documented menarche

Answer 78

Episodic vaginal bleeding occurring at intervals \>35 d

Answer 79

* β-hCG, hormonal workup (TSH, prolactin, FSH, LH, androgens, estradiol) * progesterone challenge to assess estrogen status * medroxyprogesterone acetate (Provera®) 10 mg PO OD for 10-14 d * any uterine bleed within 2-7 d after completion of Provera® is considered to be a positive test/withdrawal bleed * withdrawal bleed suggests presence of adequate estrogen to thicken the endometrium; thus withdrawal of progresterone results in bleeding * if no bleeding occurs, there may be inadequate estrogen (hypoestrogenism) or excessive androgens or progesterones (decidualization) * karyotype: indicated if premature ovarian failure or absent puberty * U/S to confirm normal anatomy, identify PCOS

Answer 80

* **A**rthralgia/Arthritis * **B**lood pressure raised * **C**arpal tunnel syndrome * **D**iabetes * **E**nlarged organs * **F**ield defect (visual)

Answer 81

* in children (before epiphyseal fusion) leads to gigantism * in adults (after epiphyiseal fusion) leads to acromegaly

Answer 82

* Dermatological: * thickening of skin * increased sebum production, acne, sebaceous cysts, * sweating * fibromata mollusca, acanthosis nigricans, * MSK * arthralgia, carpal tunnel syndrome, degenerative osteoarthritis * enlargement of hands and feet * coarsening of facial features * thickening of calvarium * prognathism (growth of jaw) * Endo: * thyromegaly * DM * Renal: * renal calculi * Cardioresp: * HTN * cardiomyopathy * obstructive sleep apnea, * GIT * colonic polyps

Answer 83

* normally GH is a catabolic hormone that acts to increase blood glucose levels * in growth hormone excess states secretion remains pulsatile but there is loss of hypoglycemic stimulation, glucose suppression, and the nocturnal surge * proliferation of bone, cartilage, soft tissues, organomegaly * insulin resistance and IGT

Answer 84

* glucose suppression test is the most specific test (75 g of glucose PO suppresses GH levels in healthy individuals but not in patients with acromegaly) * elevated serum insulin-like growth factor-1 (IGF-1) is usually first line diagnostic test

Answer 85

* symptoms: weakness, insomnia, mood disorders, impaired cognition, easy bruising, oligo-/amenorrhea, hirsutism, and acne (ACTH dependent) * signs: central obesity, round face, supraclavicular and dorsal fat pads, facial plethora, proximal muscle wasting, purple abdominal striae, skin atrophy, acanthosis nigricans, HTN, hyperglycemia, osteoporosis, pathologic fractures, hyperpigmentation, hyperandrogenism if ACTH-dependent

Answer 86

* Dexamethasone suppression test-overnight * Cortisol urine * ACTCH * UECs

Answer 87

* autonomous thyroid hormone production from a functioning adenoma that is hypersecreting T₃ and T₄ * may be singular (toxic adenoma) or multiple (toxic multinodular goiter [Plummer’s disease])

Answer 88

* goiter with adenomatous changes * tachycardia, heart failure, arrhythmia, weight loss, nervousness, weakness, tremor, and sweats * seen most frequently in elderly people, often with presentation of atrial fibrillation

Answer 89

* Symptoms suggestive of neck mass * Clinical lump in neck (including goitre or large nodule) * Nodule on other imaging modality * Cold nodules on nuclear scan (not necessarily high risk) * Suspicion of thyroid cancer

Answer 90

* If small - no treatment necessary * If large and causing mediastinal compression – surgery indicated * For multinodular goitre – radioactive iodine * Ablates hyperactive nodule without affecting ‘cold’ areas * Hypothyroidism uncommon * Safe, convenient, single dose * Long-term control without medication requirement

Answer 91

* Inflammation of the thyroid gland * Causes – Post-partum, post-viral, drugs (amiodarone, interferons, tyrosine kinase inhibitors), autoimmune (Hashimoto’s, may be preceded by thyrotoxicosis), radiation, idiopathic * Signs – if chronic see hypothyroid signs, if acute see hyperthyroid signs * Investigation * CRP/ESR, elevated thyroglobulin levels and depressed radioactive iodine intake * Determine the type of thyroiditis – test TSH and thyroid antibodies * Treatment – correct underlying cause, in the meantime beta-blockers can help lower heart rate and reduce tremors, and steroids to reduce inflammation if painful * Course – spontaneous resolution, may progress to hypothyroidism (transient or permanent)

Answer 92

* Depends on cause: * thionamides: PTU or MMI; MMI recommended (except in first trimester pregnancy) * β-blockers for symptom control * radioactive iodine thyroid ablation for Graves' disease * surgery in the form of hemi, sub-total, or complete thyroidectomy

Answer 93

* L-thyroxine (dose range: 0.05-0.2 mg PO OD _~1.6 µg/kg/d) * elderly patients and those with CAD: start at 0.025 mg daily and increase gradually every 6 wk (start low, go slow) * after initiating L-thyroxine, TSH needs to be evaluated in 6 wk; dose is adjusted until TSH returns to normal reference range * once maintenance dose achieved, follow-up TSH with patient annually * secondary/tertiary hypothyroidism * monitor via measurement of free T₄ (TSH is unreliable in this setting)

Answer 94

Remnant hyperlipidaemia (Type III hyperlipidaemia)

Answer 95

a state of inadequate cortisol and aldosterone production by the adrenal glands

Answer 96

* Autoimmune (70-90%) * Isolated adrenal insufficiency * Polyglandular autoimmune syndrome type I and II * Antibodies often directed against adrenal enzymes and 3 cortical zones * Infection: * TB (7-20%) (most common in developing world) * Fungal: histoplasmosis, paracoccidioidomycosis * HIV, CMV * Syphilis * Infiltrative: * Metastatic cancer (lung\>stomach\>esophagus\>colon\>breast); lymphoma * Sarcoidosis, amyloidosis, hemochromatosis * Vascular: * Bilateral adrenal hemorrhage * Sepsis (meningococcal, Pseudomonas) * Coagulopathy in adults or Waterhouse-Friderichsen syndrome in children * Thrombosis, embolism, adrenal infarction * Drugs: * Inhibit cortisol: ketoconazole, megestrol acetate * Increase cortisol metabolism: rifampin, phenytoin, barbiturates, heparin, coumadin * Others: * Adrenoleukodystrophy * Congenital adrenal hypoplasia (impaired steroidogenesis) * Familial glucocorticoid deficiency or resistance

Answer 97

* inadequate pituitary ACTH secretion * multiple etiologies (see Hypopituitarism), including withdrawal of exogenous steroids

Answer 98

* acute condition – can be life-threatening * IV NS in large volumes (2-3 L); add D5W if hypoglycemic from adrenal insufficiency * hydrocortisone 50-100 mg IV q6-8h for 24h, then gradual tapering * identify and correct precipitating factors * maintenance * hydrocortisone 15-20 mg total daily dose, in 2-3 divided doses, highest dose in the AM * Florinef® (fludrocortisone, synthetic mineralocorticoid) 0.05-0.2 mg PO daily if mineralocorticoid deficient increase dose of steroids 2-3 fold for a few days during moderate-severe illness (e.g. with vomiting, fever) * major stress (e.g. surgery, trauma) requires 150-300 hydrocortisone IV daily divided into 3 doses * medical alert bracelet and instructions for emergency hydrocortisone/dexamethasone IM/SC injection

Answer 99

* Tiredness * Weight gain * Feeling cold * Constipation * Brady cardia * Goitre * Slow relaxation of the tendon reflexes * Hoarse voice * A puffy facial appearance.

Answer 100

* Sudden penetrating pain in the legs, lower back or abdomen * Confusion, psychosis, slurred speech * Severe lethargy * Convulsions * Fever * Hyperkalemia * Hypercalcemia * Hypoglycemia * Hyponatremia * Hypotension * Hypothyroid * Severe vomiting and diarrhea, resulting in dehydration * Syncope

Answer 101

* neoplastic syndromes involving multiple endocrine glands * tumors of neuroectodermal origin * autosomal dominant inheritance with variable penetrance * genetic screening for RET proto-oncogene on chromosome 10 has long-term benefit in MEN II * early cure and prevention of medullary thyroid cancer

Answer 102

* Pituitary - anterior pituitary adenoma * Parathyroid * Entero-pancreatic endocrine * Pancreatic islet cell tumors * Gastrinoma * Insulinomas * Vasoactive intestinal peptide * (VIP)-omas * Glucagonoma * Carcinoid syndrome

Answer 103

* From pituitary: * Headache, visual field defects. Often non-secreting but may secrete GH (acromegaly) and PRL (galactorrhea, erectile dysfunction, decreased libido, amenorrhea) * From parathyroid: * Nephrolithiasis, bone abnormalities, MSK complaints, symptoms of hypercalcemia * From pancreas: * Epigastric pain (peptic ulcers and esophagitis), Hypoglycemia Secretory diarrhea * Rash, anorexia, anemia, diarrhea, glossitis, Flushing, diarrhea, bronchospasm

Answer 104

* Thyroid (\>90%) * Medullary thyroid cancer (MTC) * Adrenal medulla (40-50%) * Pheochromocytoma * Parathyroid (10-20%) * 1^o parathyroid hyperplasia

Answer 105

* Thyroid * MTC * Adrenal medulla * Pheochromocytoma * Neurons * Mucosal neuroma, intestinal * ganglioneuromas

Answer 106

* true gynecomastia refers to benign proliferation of the glandular component of the male breast, resulting in the formation of a concentric, rubbery, firm mass extending from the nipple(s) * pseudogynecomastia or lipomastia refers to enlargement of soft adipose tissue, especially seen in obese individuals and does not warrant further evaluation

Answer 107

* Physiologic * puberty * elderly (involutional) * neonatal (maternal hormone) * Pathologic * endocrinopathies: primary or secondary hypogonadism, hyperthyroidism, extreme hyperprolactinemia, adrenal disease * tumors: pituitary, adrenal, testicular, breast, ectopic production of hCG * chronic diseases: cirrhosis, renal, malnutrition (with refeeding) * drugs: estrogens and estrogen agonists, spironolactone, ketoconazole, cimetidine, digoxin, chemotherapy, marijuana, alcohol * congenital/genetic: Klinefelter’s syndrome, androgen insensitivity * other: idiopathic, familial

Answer 108

hormonal imbalance due to increased oestrogen activity (increased production, or increased availability of oestrogen precursors for peripheral conversion to oestrogen) or decreased androgen activity (decreased androgen production, binding of androgen to sex hormone binding globulin (SHBG), or androgen receptor blockage)

Answer 109

* laboratory: serum TSH, PRL, LH, FSH, testosterone, estradiol, LFTs, creatinine, hCG (if hCG is elevated need to locate the primary tumor) * CXR and CT of chest/abdomen/pelvis (to locate neoplasm) * testicular U/S to rule out testicular mass * MRI of hypothalamic-pituitary region if pituitary adenoma suspected

Answer 110

* initial observation for most men with gynecomastia * medical * correct the underlying disorder, discontinue responsible drug * androgens for hypogonadism * anti-estrogens: tamoxifen, clomiphene * surgical * usually required for macromastia; gynecomastia present for \>1 yr (fibrosis is unresponsive to medication); or failed medical treatment and for cosmetic purposes