Endocrinology

diseases of abnormal carbohydrate metabolism characterized by hyperglycemia:

• impairtment of insulin secretion

• insulin peripheral resistance

Px: Autoimmune destruction of beta cells - absolute insulin insufficiency

Cx:

• Initial presentation: DKA

• Symptoms: polyuria, polydipsia, fatigue, weightloss

Subtype: latent autoimmune diabetes in adults (slower onset in adults)

Px: progressive insulin resistance w/ relative insulin deficiency

Cx:

• Asymptomatic, detected on routine labs

• Symptoms: polyuria, polydipsia, blurred vision, weight loss

Rare presentation: hyperosmolar hyperglycemic state (HHS) and occasional DKA

Diabetes

• FPG ≥ 7 mmol/L

• 2-hour OGTT ≥ 11.1 mmol/L

• A1C ≥ 6.5% (48 mmol/mol)

• Symptomatic hyperglycemia + random blood glucose ≥11.1mmol/L

Prediabetes

• FPG 5.6 - 6.9 mmol/L

• 2-hour OGTT 7.8 - 11 mmol/L

• A1C: 5.7-6.4 % 39-48 mmol/mol

BP: < 130/80

Glycemia:

• A1C <7%

• Pre-prandial glucose 4.4-7.2 mmol/L

• postprandial glucose < 10mmol/L

Dyslipedemia:

• LDL <3.9 mmol/L

• HDL <2.2 mmol/L

• Triglycerides <8.3mmol/L

Microalbuminuria: albumin-to-creatinine ration < 30mg/g (<3 mg/mmol)

DM1

• carbohydrate counting

• daily requirements of CH (prefered long-chain to avoid hypoglycemia)

• avoid excessive alcohol and monitor after physical activity

DM2

• Lifestyle and diet changes

Human insulin: regular and NPH

Insulin analogues

Basal bolus regimen:

• basal insulin (long-acting) for stable glucose levels

• bolus insulin (short-acting) for mealtime glucose spikes

Pros: mimics physiologic insulin secretion and reduces complications of DM1

Cons: frequent blood glucose monitoring and risk of hypoglycemia

Look at picture

DPP4-1 (-gliptin)

• sitagliptin and linagliptin

GLP-1 agonists (-tides)

• liraglutide, exenatide, semaglutide

Sulfonylureas (-ide)

• Glipizide, glimepiride, glicazide

Biguanides

• Metformin

Thiazolidirediones (TZD) (-glitazone)

• pliglitazone and rosiglitazone

SGLT-2-i (-gliflozin)

• Empagliflozin and canagliflozin

In patient with diabetes, blood sugar level <3.9 mmol/L

In patient without diabetes, blood sugar level <3.1 mmol/L

Autonomic symptoms (neurogenic)

• Tremors, palpitations, sweating, hunder, anxiety

Neuroglycopenic symptoms:

• dizziness, confusion, weakness, drowsiness, seizures, loss of conciousness

Immediate Tx:

• 15g of fast acting carbohydrate + evaluate after 15mins + repeat if needed

Severe cases:

• 25g of 50% dextrose (IV glucose)

• glucagon (s/c i/m i/n)

  
  

Life-threatening acute severe type of adrenal insufficiency

It’s acute adrenal insuficiency

Primary causes

• Bilateral adrenal hemorrhage

• Bilateral adrenal infarction

• Adrenalectomy

• Pituitary apoplexy

Secondary causes

• stress in underlying adrenl insufficiency

• abrupt discontinuation of prolonged glucocorticoid therapy

Adrenal hormone deficiency: cortisol (glucocorticoid) and aldosterone (mineralocorticoid) deficiencies

Glucocorticoid deficienies: diminished cardiovascular response to chatecolamines, leads to shock and poor stress response

Mineralocorticoid deficiency: sodium wasting and hypovolemia - hypotension and electrolyte disturnances

Cardiovascular collapse: severe hypotension, plase skin, shivering, hypovolemic shock

Electrolyte imbalences: hyponatremia, hyperkalemia, hypoglycemia, metabolic acidosis

Neurological symptoms: pain, nausea, vomiting

Systemic signs: fever, dehydration

• Serum cortisol (low levels in morning sample)

• ACTH stimulation test: failure of cortisol to rise in response to ACTH

• Imaging

  • CT/MRI of adrenals (primary causes)

  • MRI of hypothamalus and pituitry (secondary causes)

IMMEDIATE TX

1. Hydrocortisone (corticosteroid)

2. Fluid replacement (saline)

3. Metabolic imbalances (manage glucose and electrolytes)

Additionally

• Fludrocortisone (mineralocorticoid) if addisons disease

Primary: inadequate production of glucocorticoids, mineralocorticoids, androgens

central(secondary): inadequate production of CRH (hypothalamus) or ACTH (anterior pituitary)

• General: fatigue, weakness, weightloss, salt craving

• GIT: nausea, vomiting, diarrhea, constipation

• Cardiovascular: postural hypotension, syncope

• Neuropsych: depression, apathy, confusion

• Dermatological: hyperpigmentation, virtiligo

• Sexual: amenorrhea and loss of pubic hair in women

• Electrolyte imbalances:

  • Primary: low Na, high K, metabolic acidosis

  • Secondary: only low Na

Morning serum cortisol <3mcg/dl

ACTH stimulation test: failure to increase cortisol

Plasma ACTH:

• elevated in primary chronic adrenal insufficiency

• low or normal in central adrenal insufficiency

Additional tests:

• primary:

  • hyponatremia and hyperkalemia

  • elevated renin and low aldosterone

  • ct of adrenals

• central

  • mri of pituitary

Glucocorticoid replacemetn: hydrocortisone

Mineralocorticoid replacement: fludrocortisone

Androgen replacement in women: DHEA

Monitor: BP, weight, electrolytes, plasma renin

hypercortisolism due to chronic exposure to excessive glucocorticoids

ACHT independent

• cancers, and other adrenal diseases causing too much released of cortisol (glucocorticoids)

Iatrogenic/exogenous

• prolonged glucocorticoid therapy - suppression of HPA axis

confirm hypercotisolism + find Ex

Hyperaldosteronism due to autonomous overproduction of aldosterone :

• aldosterone producing adenoma

• bilateral adrenal hyperplasia

1. high aldosterone

2. na reabsorption and k excretion

3. hypertension and hypokalemia

4. aldosterone escape prevents further volume overload but sustains hypertension

• drug resistant hypertension

• hypokalemia

• hypernatremia

• metabolic alkalosis (hydrogen excretion)

• cardiovascular symptoms

• Kidney: hyperfiltration, kidney damage; albuminuria

• 
  

PAR ratio above 20

Unilateral disease:

laparoscopic adrenalectomy + monitor for adrenal insufficiency

Bilateral disease:

MRA (Spirinolactone)

• if that can’t be given then a k sparing diuretic (amiloride)

(we try not to take both adrenals out because it can lead to adrenal insufficiency)

Goals of tratment: control BP, correct hypokalemia, reduce symptoms, prevent cardiac and renal damage

autoimmune hypothyroidism

1. TSH receptor a/b

2. antibodies bind to receptors

3. increased thyroid hormone production + gland growth

• Systemic: heat intolerane, sweating, warm moist skin, weight loss w increased appetite

• Opthalmologic: proptosis, diplopia, periorbital edema SUPER SPECIFIC FOR GRAVES

• diffuse goiter: smooth non tender

• neuropsych and muscle: tremor, proximal myopathy, hyperflexia, irritable and insomnia

RAIU = radioiodine uptake

Reduce thyroid hormone synthesis + manage complications

• Methimazole + propranolol

Definitive therapies (risk of hypothyroidism)

• radioactive iodine (gradual thyroid destruction)

• total thyroidectomy

If pregnancy 1st trimester give PTU and then in 2nd and 3rd trimester go to methimazole

high dose antithyroid drugs + bb + glucocorticoids + supportive care

Primary Hypothyroidism

• autoimmune: hashimotos thyroiditis

• iodine deficiency

• post thyroidectomy or radioactive iodine therapy

• drugs: amiodarone, lithium, antithyroid drugs

Central Hypothyroidism

• pituitary or hypothalamic tumors, cancer, trauma, radiation…

Oral Leothyroxine (synthetic T4)

avoid overtreatment

IV levothyroxine and IV liothyronine + supportive care

(IV synthetic T3 and T4)

Excessive secretion of growth hormone from anterior pituitary leading to insulin-like growth factor

HAPPENS SLOWLY AND PROGRESSES OVER YEARS

• Somatic changes: coarse facial features, frontal bossing, enlarged nose and jaw with dental spacing, big hands and feet

• Metabolic: insulin resistance, hyperglycemia, DM, hyperlipidemia, hyperphosphatemia

• Skeletal and joints: arthritis, hypertrophic cartilage…

• Neuro: headaches, visual field defects due to tumor compression, carpal tunnel syndrome

• Cardiovascular: hypertension, ventricular hypertrophy…

Get pituitary MRI - find pituitary macroadenoma

Tumor is resectable?

Yes: transsphenoidal resection of adenoma

No: somatostatin analogues or GH receptor antagonists

Primary osteoporosis:

• Type 1: postmenopausal osteoporosis

• Type 2: senile osteoporosis

Secondary osteoporosis:

• drug induced

• Endocrine/metabolic causes (hypers: cortisolism, thyroidism, parathyroidism + hypogonadism) renal diseases, vit d metabolism

• smoking

• malabsorption / malnutrition

• low body weight

• physical inactivity

• advanced age or female

• family history

Bone Mineral Density measured by DEXA

Biomarkers:

• Primary osteoporosis: =Ca and = phosphate

• Secondary osteoporosis: depend on condition

• bone turnover:

  • resorption: urine deoxypyridinoline

  • formation: alkaline phosphatase, osteocalcin

Imaging: DEXA for BMD and Xray for fractures

Biphosphonades

+

• HRT for perimenopausal

• anabolic steroids for men w hypogonadism

Follow up with DEXA every 1-2 years

FRAX Tool Calculator

Combines clinical risk factors and BMD of femoral neck

10 year probability of major osteoporosis and hip fractures

Complication of DM:

• hyperglycemia

• Ketosis in blod or urine (beta hydroxybuterate)

• Metabolic acidosis

• Insufficient insulin

• Infections

• Stress and medical conditions

• substance abuse

Pharmacotherapy: liraglutide