Approach to Thyroid Nodule- all patients with thyroid nodules require evaluation of serum TSH and

ultrasound - any nodule >5 mm with suspicious sonographic features (particularly

microcalcifications) should undergo FNA - any nodule > 1 cm should undergo FNA - when performing repeat FNA on initially non-diagnostic nodules, U/S-guided

FNA should be employed - nuclear scanning has minimal value in the investigation of the thyroid nodule

Two Distinct Features of Primary Hypogonadism1. The decrease in sperm count is affected to a greater extent than the decrease in serum testosterone level 2. Likely to be associated with gynecomastiaTwo Features of Secondary Hypogonadism1. Associated with an equivalent decrease in sperm count and serumTestosterone 2. Less likely to be associated with gynecomastia

Upper to Lower (U!L) Segment Ratio is ...- Incr in achondroplasia, short limb syndromes, hypothyroid, storage diseases.- Dec in Marfan's, Klinefelter's, Kallman's syndromes, and testosterone def.

Polycystic Ovarian Syndrome - HAIR-AN : Hirsutism, HyperAndrogenism, Infertility, Insulin Resistance, Acanthosis Nigricans

Alcohol electrolyte abnormality : hypomagnesemia, hypophosphatemia,hypocalcemia, hypoglycemia, hypokalemia

metabolic causes of constipation • diabetes mellitus• hypothyroidism • hypercalcemia, hypokalemia, uremia

Vitamin 812 Deficiency Symptoms• Macrocytic anemia, pallor, SOB, fatigue, chest pain, palpitations• Confusion or change in mental status (if advanced)• Decreased vibration sense • Distal numbness and paresthesia• Weakness with UMN findings • Diarrhea, anorexia

Differential Diagnosis of Tetany- • Hypocalcemia • Metabolic alkalosis (with hyperventilation)- • Hypokalemia • Hypomagnesemia

Acquired Hypothyroidism- - most commonly Hashimoto's thyroiditis (autoimmune destruction of the thyroid) - signs and symptoms similar to hypothyroidism in adults, but also:o delayed bone age, decline in growth velocity, short stature, goiter o sexual pseudo precocity: early sexual development with short stature and

delayed bone age o does not cause permanent developmental delay

- treated with L-thyroxine 10 flg/kg/dGrowth hormone deficiency - height <3rd percentile decreased growth velocity- midline craniofacial anomalies episodes of hypoglycemia- delayed bone age, puberty

Frozen Shoulder (Adhesive Capsulitis)- Definition : disorder characterized by progressive pain

and stiffness of the shoulder usually resolving spontaneously after 18 months

- Mechanismo primary adhesive capsulitis idiopathic, usually

associated with diabetes mellitus, may resolve spontaneously in 9-18 months

o secondary adhesive capsulitis: poorer outcomes due to prolonged immobilization shoulder-hand syndrome: CRPS/RSD characterized by arm and shoulder

pain, decreased motion and diffuse swelling following myocardial infarction, stroke, shoulder trauma

- Clinical Features

Conditions Associated with anIncreased Incidence of Adhesive Capsulitis• Prolonged immobilization (most significant)• Female gender• Age >49 yrs• Diabetes mellitus (5x)• CeiVical disc disease• Hyperthyroidism• Stroke • MI • Trauma and surgery

o gradual onset (wks to months) of diffuse shoulder pain with:o decreased active and passive ROM, o pain worse at night and often prevents sleeping on affected side o increased stiffness as pain subsides: continues for 6-12 months after pain has

disappeared- INX : x-rays may be normal, or may show demineralization from disease- Treatmento active and passive ROM (physiotherapy)o NSAIDs and steroid injections if limited by paino manipulation under anesthesia and early physiotherapyo arthroscopy for debridement/decompression

Hypocalcaemia is most commonly caused by hypoparathyroidism, a deficiency or abnormal metabolism of vitamin D, acute or chronic renal failure, or hypomagnesaemia. In hypoparathyroidism, serum calcium is low, phosphate is high, and PTH is undetectable; renal function and concentrations of the 25-hydroxy and 1,25-dihydroxy metabolites of vitamin D are usually normal. The features of pseudohypoparathyroidism are similar to those of hypoparathyroidism except for PTH, which is markedly increased. In chronic renal failure, which is the most common cause of hypocalcaemia, phosphate is high and alkaline phosphatase, creatinine, and PTH are elevated; 25-hydroxy vitamin D3 is normal and 1,25-dihydroxy vitamin D3 is low. In vitamin D deficiency osteomalacia, serum calcium and phosphate are low, alkaline phosphatase and PTH are elevated, renal function is normal, and 25-hydroxy vitamin D3 is low. The most frequent artifactual cause of hypocalcaemia is hypoalbuminaemia, such as occurs in liver disease or the nephrotic syndrome.

Table 7 Hypocalcaemic clinical features of neuromuscular irritability --------------------------------------------------------------------------------Paraesthesia, usually of fingers, toes, and circumoral regions Tetany, carpopedal spasm, muscle cramps Chvostek's sign a Trousseau's sign b Seizures of all types (i.e. focal or petit mal, grand mal or syncope) Prolonged QT interval on ECG Laryngospasm Bronchospasm --------------------------------------------------------------------------------a Chvostek's sign is twitching of the circumoral muscles in response to gentle tapping of the facial nerve just anterior to the ear; it may be present in 10 per cent of normal individuals.

b Trousseau's sign is carpal spasm elicited by inflation of a blood pressure cuff to 20 mmHg above the patient's systolic blood pressure for

3 min.

hypokalemia (see Figure 12)- defin: normal IC “150-160 “ EC “3,5-5” o serum [K+] <3.5 mEq/Lo mild hypokalaemia, with serum potassium in the range 3.0 to 3.5 mmol/l,o serum potassium concentration less than 2.5 mmol/l

- Approach to Hypokalemiao 1. emergency measures: obtain ECG; if potentially life threatening, begin

treatment immediatelyo 2. rule out transcellular shifts of K+ as cause of hypokalemiao 3. assess contribution of dietary K+ intakeo 4. 24-h K+ excretion or spot urine K+ and urine creatinine (calculate urine

K+/Cr ratio; normal is approximately 4)

o 5. TTKG = transtubular potassium gradient= (Uk/Pk)/(UOSM/POSM)o 6. if renal K+ loss, check BP and acid-base status

o 7. may also assess plasma renin and aldosterone levels, serum [Mg2+]

- C/P o CVS

arrhythmias occur at variable levels of K+; more likely if digoxin use, hypomagnesemia, or CAD

ECG changes are more predictive of clinical picture than serum [K+]

U waves most important (low amplitude wave following a T wave) flattened or inverted T waves depressed ST segment prolongation of Q-T interval “predispose to torsades de point”

o Kid Nephrogenic DI make the collecting tubule resistant to ADH = polyuria

o CNS Lethargic irritability paraesthesia Ppt encephalopathy attacks

o MSK : myalgia , generalized weakness , muscle cramps o GI : N and V and constipation

- According to severity o Asymptomatic if mild o if severe:

with severe hypokalemia: P-R prolongation, wide QRS, arrhythmias; increases risk of digitalis toxicity “therefore digitalis is CI in hypoK”

muscle necrosis “rhabdomyolysis”, and rarely paralysis with eventual respiratory impairment

- Treatmento treat underlying causeo if urine output and renal function are impaired, correct with extreme cautiono risk of hyperkalemia with potassium replacement especially high in elderly,

diabetics, and patients with decreased renal functiono beware of excessive potassium repletion, especially if trans cellular shift

caused hypokalemiao if true K+ deficit, potassium repletion (decrease in serum [K+] of 1 mEq is

very roughly 100-200 mEq of total body loss) oral sources- food, tablets (K-Dur®), KCl liquid solutions IV - usually KCl in saline solutions, avoid dextrose solutions (may

exacerbate hypokalemia via insulin release) max. 40 mmoi!L via peripheral vein, 60 mmoi!L via central vein, max.

infusion 20 mmol!ho K+ -sparing diuretics (triamterene, spironolactone, amiloride) can prevent

renal K+ loss o restore Mg2+ if necessary bec “hypoK cause hypoMg”

hyperK Rhabdomyolysis, insulin deficiency,

Nausea, palpitations, muscle

Protect heart: Calcium gluconate

EGG: Peaked/narrow T wave, decreasedP wave, prolonged

metabolic acidosis

stiffness, areflexia

Shift K+ into cells: Insulin R, NaHC03, salbutamol

PR interval, wideningof QRS, AV block, V fib

hypoK

serum [K+] <3.5 mEq/L

Metabolic alkalosis, insulin, diuretics, anorexia, salbutamol, 1ry HyperAld

Nausea, vomiting, fatigue, muscle cramps “like tetany”, constipation,

K-Dur®, K+ sparing diuretics,IV solutions with 20-40 mEq KCI per liter over 3-4 h

EGG: U waves most important, flattened/inverted T waves, prolonged QT,depressed STMay need to restore Mg2+

NOTE : Acidosis diminishes potassium uptake by cells (Table 1) and causes hyperkalaemia. The increase in the plasma potassium concentration is greater with metabolic than respiratory acidosis, and occurs with hyperchloraemic but not with organic acid-induced forms “for eg lactate” of metabolic acidosis. Stimulation of insulin release by organic acids appears to account for this divergent response, explaining the pathophysiology of disturbed potassium homeostasis in diabetic ketoacidosis. At presentation, when insulin is deficient, potassium is redistributed in a fashion comparable with mineral acid-induced metabolic acidosis and patients are hyperkalaemic. However, the preceding kaliuresis (caused by polyuria) has rendered the body enormously deficient in potassium, and the plasma potassium concentration falls rapidly as soon as insulin is provided, allowing potassium to return to the cells. Indeed, dangerous hypokalaemia can develop if adequate potassium is not given during treatment.

Hyperkalemia- serum [K+] >5.0 mEq/L - Approach to Hyperkalemiao 1. emergency measures: obtain ECG, if life threatening begin treatment

immediatelyo 2. rule out factitious hyperkalemia; repeat blood testo 3. hold exogenous K+ (PO and IV), and any K+ retaining medicationso 4. assess potential causes of transcellular shifto 5. estimate GFR (calculate CrCl using Cockcroft-Gault)o 6. if normal GFR, calculate TTKG = (Uk/Pk) /(Uosm/Posm)

in setting of hyperkalemia, TTKG <7 =suggests decreased effective aldosterone function

in setting of hyperkalemia, TTKG > 7 = suggests normal aldosterone function

- sign and symptoms o usually asymptomatic but may develop symptoms o GI : nausea o CVS

palpitations ECG changes and

cardiotoxicity (do not correlate well with serum [K+]) peaked and narrow T waves decreased amplitude and eventual loss of P waves prolonged PR interval widening of QRS and eventual merging with T wave (sine-wave pattern)

AV block ventricular fibrillation, asystole

o MSK muscle weakness, muscle stiffness, ascending paralysis,

o CNS : paresthesias, areflexia, o resp : hypoventilation o renal

impaired renal ammonia-genesis and metabolic acidosis- Treatmento acute therapy is warranted if ECG changes are present, or if patient is

symptomatico tailor therapy to severity of increase in [K+] and ECG changes

[K+] <6.5 and normal ECG treat underlying cause, stop K+ intake, increase the loss of K+ via urine

and/or GI tract (see below) [K+] between 6.5 and 7.0, no ECG changes: add insulin to above regimen [K+] >7.0 and/or ECG changes: first priority is to protect the heart, add

calcium gluconate to aboveo 1. Protect the Heart

calcium gluconate 1-2 amps (10 mL of 10% solution) IV antagonizes cardiac toxicity of hyperkalemia, protects cardiac conduction

system, no effect on serum [K+] onset within minutes, lasts 30-60 min

o 2. Shift K+ into Cells regular insulin (Insulin R) 10-20 units IV, with 1-2 amp D50W (give

D50W before insulin) onset of action 15-30 min, lasts 1-2 h monitor capillary blood glucose q1h because of risk of hypoglycemia can repeat every 4-6 h

NaHC03 1-3 amps (given as 3 amps of 7.5% or 8.4% NaHC03 in 1L D5W) onset of action 15-30 min, transient effect, drives K+ into cells in

exchange for H+ more effective if patient has metabolic acidosis

β2-agonist (Ventolin®) in nebulized form (dose = 2 cc or 10 mg inhaled) or 0.5 mg IV onset of action 30-90 min, stimulates Na+/K+ ATPase caution if patient has heart disease as tachycardia may result from this

high dose of β agonist

o 3. Enhance K+ Removal from Body via urine (preferred approach)

furosemide (≥40 mg IV), may need IV NS to avoid hypovolemia fludrocortisone (synthetic mineralocorticoid) if suspect aldosterone

deficiency via gastrointestinal tract

cation-exchange resins: calcium resonium or sodium polystyrene sulfonate (Kayexalate®) (increasingly falling out of favor due to risk of colonic necrosis; works by binding Na+ in exchange for K+, and controversial how much K+ is actually removed - main benefit may be the diarrhea it causes) plus lactulose PO to avoid constipation (must ensure that patient has a bowel movement after resin is administered )

Kayexalate® enemas with tap water (and definitely not with sorbitol as rectal sorbitol can cause colonic necrosis)

dialysis (renal failure, life threatening hyperkalemia unresponsive to therapy)

hyperK Rhabdomyolysis, insulin deficiency, metabolic acidosis

Nausea, palpitations, muscle stiffness, areflexia

Protect heart: Calcium gluconateShift K+ into cells: Insulin R, NaHC03, salbutamol

EGG: Peaked/narrow T wave, decreasedP wave, prolonged PR interval, wideningof QRS, AV block, V fib

hypoK serum [K+] <3.5 mEq/L

Metabolic alkalosis, insulin, diuretics, anorexia, salbutamol,

Nausea, vomiting, fatigue, muscle cramps

K-Dur®, K+ sparing diuretics,IV solutions with 20-40 mEq KCIper liter over 3-4 h

EGG: U waves most important, flattened/inverted T waves, prolonged QT,depressed STMay need to restore Mg2+

Hypernatremia

Inadequate H20 intake (elderly/disabled or inappropriate excretion of H20 (diuretics, Li + Dl)

Lethargy, weakness, irritability, and edema. Seizures and coma occur with severe elevations of Na+levels I> 158 mmoVL)

Salt restrict and give free water No more then 12 mmoVL in 24 h dropin Na+ (0.5 mmoVL/h) due to risk ofcerebral edema, seizures, death

Hyponatremia Hypo-osmolar ldilutional e.g. CHF,cirrhosis, ascites) and hyper-osmolar(usually glucose)

Acute: Neurologic symptoms 2'to cerebral edema, headache,decreased LOG, depressed reflexes

Water restrictAcute: correct rapidly 3% NaCI1-2 cc/kg/hChronic: IV NS + furosemide

Limit total rise to 8 mmoVL in 24 h(0.5 mmoVL/h maximum) as patients areat risk of central pontine myelinolysis

Hypercalcemia

Hyper-PTH and malignancy accountfor approx. 90% of cases

Multisystem including CVS, Gl(groans), renaljstones),rheumatological. MSK (bones),psychiatric (moans)

Isotonic saline+furosemide ifhypervolemicBisphosphonates, dialysis, chelationlEOTA or oral phosphate)

Patients with more severe orsymptomatic hypercalcemia are usuallydehydrated and require saline hydrationas initial therapy

Hypocalcemia Iatrogenic, low Mg2+, liverdysfunction, 1' hypo-PTH

Laryngospam, hyperreflexia,parasthesia, tetany, Chvostek's andTrousseau's sign

Acute lionized Ca2+ <0.7 mM)requires immediate treatment: IVcalcium gluconate 1-2 g in 1 0-20 minfollowed by slow infusion

Prolonged QT interval can arise leadingto arrhythmia as can upper airwayobstruction

hypoMg serum magnesium <0.70 mmol!L (1.7 mg/dL)

GI losses• starvation/ malabsorption• vomiting/diarrhea• alcoholism• acute pancreatitis• excess renal loss• 2° hyperald due to cirrhosis and CHF• hyperglycemia• hypokalemia• hypercalcemia• loop and thiazide-type diuretics• nephrotoxic medications• proton-pump inhibitors

seizures, paresis, Chvostek and Trousseau signs, ECG changes (widened QRS, prolonged PR,T-wave abnormalities)

• treat underlying cause• Mg2+ IM/IV; cellular uptake of Mg2+ is slow, therefore repletion requires sustained correction• discontinue diuretics in patients requiring diuretics, use a K+ -sparing diuretic to minimize magnesuria

How often should you follow up on a patient with newly diagnosed hypothyroidism?EVIDENCE-BASED ANSWERSix to 8 weeks after the start of levothyroxine therapy you should reexamine patients and measure their serum thyroid-stimulating hormone (TSH) (strength of recommendation [SOR]: C, common practice and expert opinion). If thyroid function is normal at that time, examine the patient and measure serum TSH again in 4 to 6 months because clearance of levothyroxine increases in the euthyroid (normal) state (SOR: C, expert opinion).Once the proper maintenance dose of levothyroxine is achieved, evaluate the patient and obtain a serum TSH at least annually, or as clinically indicated (SOR: C, expert opinion).Evidence summaryThere is very little patient-oriented research to help answer this question. Virtually all of the literature is based on bench research and expert opinion.Wait at least 6 weeks to follow up after starting therapySerial serum TSH measurements are adequate to follow adults with newly diagnosed, uncomplicated primary hypothyroidism. However, serum thyroid hormone levels normalize before serum TSH. Serum thyroid hormone concentrations increase first, then the TSH secretion falls because of the negative feedback action of levothyroxine on the pituitary and hypothalamus. Levothyroxine has a 1-week plasma half-life; a steady state is achieved about 6 weeks (6 half-lives) after the start of treatment or a change in dose. The TSH level should, therefore, be evaluated no earlier than 6 weeks after initiating therapy or adjusting levothyroxine dosage.1,2 The full effects of thyroid hormone replacement on the TSH level may not become apparent until 8 weeks of therapy.3

FAST TRACKPatients older than 65 years must be monitored annually to avoid overreplacementCheck TSH 4 to 6 months after initial follow-upIf the initial dose doesn’t require adjustment, reevaluate the patient and measure serum TSH again in 4 to 6 months because levothyroxine clearance can increase after the euthyroid state is established.4 If a dosage change is needed, make adjustments every 6 weeks, based on serum TSH values, until TSH values return to the reference range. Successful treatment reverses all the signs and symptoms of hypothyroidism, although some neuropsychologic and biochemical abnormalities, such as depressed mood and lipid abnormalities, may persist for several months.3

Monitor stable patients annually, especially the elderly

Examine the patient and measure serum TSH annually after identifying the proper maintenance dose, more often if an abnormal result or a change in the patient’s status occurs.2 Certain situations such as pregnancy, initiation of new medications, or liver or kidney disease may require more frequent monitoring.Generally, once a stable maintenance dosage of levothyroxine is achieved, the dosage will remain adequate until the patient has a significant weight change or reaches his or her seventh or eighth decade.1 Although monitoring less often than once a year can be justified in younger adult patients whose weight is stable, patients older than 65 years must be monitored annually to avoid overreplacement. With age, thyroid binding may decrease, and the serum albumin level may decline. This can result in a 20% reduction in the dose of levothyroxine required.5,6

RecommendationsThe American Association of Clinical Endocrinologists (AACE) recommends reassessment and repeat lab work at least 6 weeks after any change in levothyroxine brand or dose. The AACE practice guidelines suggest follow-up with appropriate interim history, physical exam, and pertinent lab studies at 6 months, and then annually after the TSH level has normalized.7

----------Infections in patients with diabetes mellitus: A review of pathogenesisCONCLUSIONSInfectious diseases are more prevalent in individuals with DM. The main pathogenic mechanisms are: hyperglycemic environment increasing the virulence of some pathogens; lower production of interleukins in response to infection; reduced chemotaxis and phagocytic activity, immobilization of polymorphonuclear leukocytes; glycosuria, gastrointestinal and urinary dysmotility.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354930/