Endocrine Issues — USMLE Step 2 CK Notes

Hyperthyroidism

Excess thyroid hormone increases osteoclasts activity:

Hypercalcaemia —-> Decreased PTH —-> OSTEOPOROSIS

Hyperglycaemia and diarrhoea

HTN (d/t hyperdynamic circ caused by increased contractility and HR)

Lid lag, retraction (not exophthalmos, d/t sym stimulation of sup tarsal muscle)

Acute Thyrotoxicosis myopathy of proximal muscles (weakness)

Tx: Beta blocker for sx control; medical management is first line before RAI

RAI ==> permanent hypothyroidism within months in Graves pts only (diffuse uptake)

FETAL HYPERTHYROIDISM only seen in Graves -> TSHR antibodies cross placenta

Exophthalmos (proptosis): only seen in Graves -> lymphocytic infiltration

Impaired extraocular motion (diplopia, decreased convergence)-> orbital tissue expansion

Irritation (gritty sensation), redness, photophobia, pain and tearing

Thyroid Acropacy -> Nail clubbing (bulbous fingertip enlargement): Specific to GRAVES

Thyrotoxicosis with decreased Radioactive Iodine Uptake (RAIU): thyroiditis

Painless (silent) thyroiditis (variant of postpartum thyroiditis)

Associated with thyroid peroxidase Abs

Followed by hypothyroid state; self limited

Subacute (de Quervain) thyroiditis: post URTI; tender painful goiter w fever

Riedel thyroiditis: hard and painless thyroid (FIBROUS); Tx w tamoxifen

Amiodarone induced thyroiditis

Struma Ovarii

Iodine induced

Extensive thyroid cancer metastases

Tx for thyroiditis: NSAIDs; BBs and steroids (thyrotoxicosis sx)

Anti thyroid drugs used in moderate/severe and in prep for RAI tx

Also used in pregnant women and those with limited life expectancy (v old)

MOA is Inhibition of TPO (PTU also inhibits conversion of T3 to T4)

Methimaziole first line

PTU only if pregnant (1st Tri) or breastfeeding (M enters breast milk and fetotoxic): PM

Chronic Lymphocytic Thyroiditis: Hashimotos

Anti thyroid peroxidase and antithyroglobulin Abs

Sub clinical hypothyroidism: normal T4 and mild elevation in TSH

——> associated with increased risk of miscarriage

Tx: Levothyroxine even w/o sx if elevated anti TPO Abs

Hypothyroidism

Hoarseness d/t matrix GAG accumulation —->> can also cause coarse hair and skin

Soft tissue enlargement d/t mucinous infiltration (mucopolysaccharide): Carpal Tunnel Syndrome

Sx of depression; memory problems; paranoia and hallucinations —> myxedema madness Delayed relaxation of DTRs Pts on levothyroxine must increase dose if given oestrogen ===> increase TBG (decreased free ## T4)

Low T4 —-> stimulates ant pituitary —> increased TSH and Prolactin

—-> Prolactin inhibits FSH and LH production —-> Anovulation and AUB (menorrhagia)

Myxedema Coma (decompensated hypothyroidism)

Life threatening

Altered mental status, hypothermia, bradycardia, hypotension, hyponatraemia, hypoglycaemia,

Non pitting edema (myxedema)

Hashimotos Encephalitis

Reversible and rapidly progressive dementia w associated neuro sx

Dx: elevated TPO Abs and antithyroglobulin Abs

Ataxia, myoclonus, seizures, dysmetria etc

Nonspecific T2 abnormalities in subcortical white matter

CSF shows pleomorphic leukocytosis w elevated protein and norm glucose

Tx: high dose glucocorticoid

Sub clinical hypothyroid: norm T4 and high TSH

Euthyroid Sick syndrome

Low T3, normal T4 and TSH in setting of acute illness

D/t decreased conversion of T4 to T3

—-> acute illness: high cortisol, inflamm cytokines, starvation and medications (glucocorticoids)

Sheehan syndrome: Postpartum pituitary infarction Obstetric hemorrhage complicated by hypotension

Lactation failure d/t low prolactin

Amenorrhea, hot flashes and vaginal atrophy —>> low FSH/LH

Fatigue and bradycardia d/t low TSH

Anorexia, weight loss and hypotension d/t low ACTH

Decreased lean body mass d/t low GH

Central adrenal Insufficiency: Deficiency in ACTH

Can cause SIADH as cortisol is an inhibitor of ADH

Normal potassium (aldosterone unaffected)

No skin hyperpigmentation

Cushings: excess cortisol

Hyperandrogenism: Increased DHEA-S —> hirsutism

Hyperglycaemia -> DM sx

Bruisability d/t catabolism of connective tissue by cortisol; Wide, purplish striae

Cutaneous fungal infections: tinea versicolour, onchomycosis

Hypokalaemia and alkalosis d/t partial mineralocorticoid effects of cortisol

Muscle atrophy d/t cortisol catabolism of proximal skeletal muscle

Depression/anxiety

Skin hyperpigmentation if d/t ACTH excess

Dx: Overnight Low dose dexamethasone suppression test;

Cortisol: Serum morning or 24hr urinary cortisol excretion

High dose dexamethasone suppression test -> negative suppression is consistent with ectopic

CRH stimulation test-> ↑ACTH and cortisol is consistent with pituitary Cushing disease

No response is consistent with ectopic Cushing

CT Abdo

Familial Hypocalciuric Hypercalcaemia (FHH): Benign AD

Higher than normal calcium levels needed to suppress PTH d/t

Mutation in calcium sensing R —-> also results in increased calcium reabsorption in renal tubules

Ddx from HyperPTH via urine calcium/creatinine clearance ratio (UCCR)

Elevated DHEAS AND testosterone in androgen producing adrenal tumours

DHEAS is a dx marker, clinical features d/t conversion to Androstenedione and Testosterone

——> more potent androgens: virilisation

Conns Syndrome

Dx: Plasma aldosterone conc; plasma renin conc, renin:aldosterone ratio

====>> Confirmation: Aldosterone Suppression Test ====> adrenal imaging

Pheochromocytoma

Adrenal Medulla Tumour —-> similar tumours in non adrenal tissues termed paraganglionomas

Resistant HTN or HTN accompanied by increased glucose

Classic Triad: Episodic Headache, sweating and tachycardia

MEN2, NF1 and VHL association Dx: Elevated serum/urine metanephrine and catecholamine levels

Preop care: Phenoxybenzamine then propanolol

Acromegaly

Clinical suspicion —-> check IGF-1 Level —-> norm rules out acromegaly

High —->>>> Oral glucose suppression test ——> norm GH Suppression rules out acromegaly

Inadequate GH Suppression ——> MRI to check for pituitary mass

—-> no mass -> extrapituitary causes of acromegaly eg tumour and ectopic secretion

MRI not done first as incidental pituitary masses common and could skew dx

Osteoporosis

Colles fracture/dinner fork deformity

Risk for fragility fracture highest in those w previous fracture

Hyperparathyroidism: Cortical bone loss and DI (high Ca inhibits ADH)

Tertiary HyperPTH in CKD——> PTs hypertrophied and now perm active

Hypoparathyroidism

Hypocalcaemia w hyperphosphataemia —-> high phosphate induces calcium depositions

Deposits in BG —> extra pyramidal sx

Nephrocalcinosis and cataracts

Periosteal Reaction: Excess mineralisation of periosteum in response to irritation

D/t osteomyelitis; benign/malignant tumours and excessive Vitamin A

Diabetes

Basal Insulin at night: Long acting: Glargine and Detemir

Prandial: Bolus pre meal: Rapid Onset: Aspart and Lispro

Inpatient management: STOP ALL AT HOME DM MEDS (bar pump)

Major cause of primary HTN Autonomic Dysfunction is a complication: Gastroparesis tx with metaclopramide or erythromycin

——> gastroparesis can cause frequent hypoglycaemia d/t delayed intestinal absorption of glucose

CN Palsies: 3/4/6

DM: Fasting glucose >125 mg/dL and Hb A1c >6.4%

Check glycemic control every 3 months with goal of less or equal to 7.0% HbA1c

Screening:

LDL < 100; BP <130/80; TGs <150

Microalbuminaemia 30-300 in 24hrs ——>> ACEI

Annual eye and foot screen for proliferation retinopathy

Statin recommended for all 40 and over with diabetes (moderate intensity)

—->>> and those under 40 with ASCVD (high intensity)

Daily aspirin if 10 year CVD risk >10%

Effect of Intensive Glycaemic Control in T2DM

No change in macrovascular complications: Heart

Benefits microvascular complications eg Retinopathy and Nephropathy

Distal Sensory Peripheral Neuropathy in DM: Legs/feet still warm as no issue with blood supply

——-> ulcers d/t decreased sensation so pt does not realise and this worsens

Large fibre neuropathy:

Pressure, proprioception, vibration, light touch and balance ->>>> numbness + poor balance

Diminished/absent Ankle reflexes

Small Fibre neuropathy ——>> Burning and stabbing pain

Pain and temperature; Reduced pinprick sensation

Monofilament Test: Tests for peripheral neuropathy + Predicts future foot ulcers

Neuropathic pain: Gabapentin etc (Ca channel ligand) >SSRI/SNRI/TCAs >Tramadol

GLP1 agonists: Pancreatitis

Cause weight loss and decreased mortality if underlying CV disease

SGLT2 inhibitors: Hypotension and UTIs

Minor weight loss

DKA

Most deaths in children d/t cerebral oedema ——> presents 4-12hrs after starting tx. (Headache)

Vomiting and abdo pain

Kussmaul resp (deep, rapid breathing)

Dehydration

Sx d/t acidosis from ketone accumulation (d/t FA breakdown in liver)

Glucose >200; Bicarbonate <15; pH <7.3; AG >14

Management: Regular Insulin infusion + isotonic fluids with potassium —-> potassium used if K ## <5.3

Best index to monitor response to tx: Serum AG, electrolytes, venous pH and serum glucose

Hyperosmolar Hyperglycaemic state: Norm AG, norm pH and bicarbonate; No ketones

T2DM; Glucose >600

Gradual hyperglycaemic sx eg polyuria

Altered mentation d/t hyperosmolar state

Tx: Aggressive hydration with norm saline; IV Insulin; K if <5.3

Translocational hyponatraemia: Hyperosmolar hyperglycaemic state

High serum osmolality -> dehydration (d/t osmotic diuresis) + neuro dysfunc (lethargy; myoclonic jerks)

Hyperkalaemia present d/t solvent drag of IC K by fluid shifting into blood stream

Osteomyelitis

Polymicrobial infection d/t contiguous spread from foot ulcer

RF: Long standing wound (1-2 wks +)

Systemic sx; large ulcer; raised ESR; palpable bone in ulcer base

Dx: Bone biopsy and cultures

Tx: IV Piperacillin-Tazobactam and Vancomycin

Idiopathic central diabetes insipidus

• 50-100% increase in UOsm w/ DDAVP = Central DI

• UOsm > 600 after deprivation = functional ADH (suggests primary polydipsia)

Milk alkali syndrome: excessive intake of calcium and absorbable alkali

Hypercalcaemia w ALKALOSOIS (cf PTH): AKI w reduced GFR

Activation of calcium sensing receptors in kidney inhibits NaKCl cotransporter

-> Loss of sodium and free water (ADH activity also impaired)

Hypovolaemia—-> increases bicarb reabsorption

Metabolic alkalosis (augmented by consumption of alkali) + contraction alkalosis

Suppressed PTH, hypomagnesaemia (decreased renal reabsorption), hypophosphataemia (PO4

binding by CaCO3 in intestine)

Medications that increase risk of syndrome:

Thiazides (only cause mild hypercalcaemia in and of themselves)

ACEI/ARBs and NSAIDs (exacerbate AKI/GFR issue)

Tx: discontinue agent and give isotonic saline followed by furosemide

Metabolic Syndrome: 3/5 criteria needed:

Abdo obesity (M >40inches; F >35 inches)

Fasting glucose >100-110 —->>>> Impaired Fasting glucose: Insulin resistance key

pathogenesis

BP >130/80

Triglycerides >150

HDL M <40; F <50

Hypomagnesium

Hyperreflexia, tremor, torsades, seizures, muscle spasms