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