Grave's disease

Condition

• Grave's disease

Definition

• Grave's disease named after Rober J Graves, is an autoimmune disease characterized by hyperthyroidism due to circulating autoantibodies.

History

• Female: Male ratio 5-10: 1
• Peak onset 40-60 years
• Diffuse, usually symmetrical goitre
• Graves ophthalmopahty
• Associated with other autoimmune diseases 
• The most frequent symptoms of thyrotoxicosis are nervousness, heat intolerance, palpitations, fatigue and weight loss (weight gain occurs in 10% people)

Examination

• Agitation 
• Sinus tachycardia 
• Fine tremor 
• Hyper-reflexia
• Graves ophthalmopathy 
• Pretibial myxodema 1-2 %
• thyroid acropachy (digital clubbing < 1%)

Investigation

• Blood test: Thyroid function test, TSH receptor Ab positive, TPO Ab often positive
• Radionuclide thyroid scan: normal or elevated diffuse uptake pattern

Management

• Oral medications
• Carbimazole 
• Propylthiouracil 
• Agranulocytosis is a rare but life threatening complication of both antithyroid drugs with an incidence of 0.2-0.5%. Most commonly happen in the first 3 months, but can happen at any time
• Severe hepatocellular inury occurs with propylthiouracil in 0.1% of patients treated with the drug, and approximately 10% of these patients develop liver failure resulting in either a liver transplant or death
• 4 weeks following initiation of therapy, clinical review with repeat thyroid function tests should be undertaken to avoid hypothyroidism
• Beta blockers may be used for symptom control. A nondihydropyridine calcium channel blocker (e.g. verapamil) can be used to control heart rate when beta blockers are not tolerated

References:

• http://www.racgp.org.au/afp/2012/august/evaluating-and-managing-patients-with-thyrotoxicosis/

Osteoporosis

Key points:

- Osteoporosis is under-recognised and under-treated, even in people who present with a minimal trauma fracture.

- A minimal trauma fracture is sufficient for a presumptive diagnosis of osteoporosis medicines can start prior to obtaining BMD results with dual energy x-ray absorptiometry (DXA).

- Guidelines recommend risk factor assessment and that modifiable risk factors be addressed in all postmenopausal women aged >45 years and men aged > 50 years.

- A full diagnostic investigation is indicated for:

• women> 50 YEARS and men> 60 years with other clinical risk factors 
• Patients > 45 years with a minimal trauma fracture or suspected vertebral fracture 
• patients who have causes of secondary osteoporosis (medical conditions or medicines such as long-term, high-dose corticosteroids)
• adults aged over 70 years 

- Clinical risk factors (CRFs), use the mneumonic of shattered 

Previous minimal trauma fracture, family history 

• S: steroid use (oral corticosteroid use > 5mg/day)
• H: hyperthyroidism, hyper parathyroidism and hypercalciuria 
• A: Alcohol and tobacco use 
• T: Thin (BMI < 22)
• T: Testosteron decrease (e.g. anti androgen ca, prostate Rx)
• E: Early menopause 
• R: renal or liver failure 
• E: Erosive/inflammatory bone disease (e.g. myeloma or rheumatoid arthritis)
• D: Dietary Calcium decrease/malabsorption , DM1 

- The strongest risk factor is age > 70. Peak bone mass is achieved by age 30. Bone loss occurs steadily from the age of about 40, with accelerated loss in perimenopausal period (4-6%) before slowing again after the age of 70 (1-2% per year).

- Basic investigations: DEXA, Ca, PO, ALP, FBE, UEC, LFT, myeloma screen if indicated

• Hip bone mineral density best predictor for hip fracture
• Lumbar spine bone mineral density best for monitoring treatment effect
• 
  

- Management:

• lifestyle measures
• quit smoking and reduce ETOH consumption 
• Weight bearing exercise may increase bone mineral density 
• Balance exercises such as tai chi reduce risk of falls 
• Calcium and vitamin D supplements 
• recommended dietary intake of calcium is between 1000 and 1300 mg per day, depending on age and sex
• Most Australians do not reach the recommended dietary intake so daily supplements of 500-600 mg of calcium are sometimes needed
• Safety of calcium is still a controversial topic as there is evidence that it may increase risks of MI
• Home based fall prevention program, with visual assessment and a home visit
• Medications 
• Bisphosphonates and Denosumab
• Criteria: minimal trauma fracture or age > 70 with T score <=-2.5
• Bisphosphonates: well tolerated, some significant side effects: oesophageal cancer? (not proven), osteonecrosis of the jaw (see dentist prior to commence treatment) and do not use with the other antiresorptive or anabolic agents
•  Denosumab: use with caution in patients with severely impaired kidney function as denosumab may exacerbate hypocalcaemia 
• Raloxifene 
• postmenopausal woman with a minimal trauma fracture and risk of vertebral fractures predominatly
• reduces vertebral fracture but not non vertebral fractures in postmenopausal women
• Reduces risk of breast cancer so suitable for women at high breast cancer risk
• Associated with increased risk of DVT or pulmonary embolism in meta-analyses
• Strontium ranelate
• Criteria: unable to tolerate other medications or contraindicated to other medications
• assess patient risk of developing CVD before treatment due to safety concerns in patients with history of CVD, embolism or stroke 
• Teriparatide 
• Reduces vertebral and non - vertebral fractures in postmenopausal women 
• limited evidence in men
• must be initiated by a consultant physician
• Vitamin D deficiency
• 600 IU per day for people under 70
• 800 IU per day of people over 70 
• 1000-2000 IU per day may be required for sun avoiders or those at high risk of deficiency
• Monitor treatment response and review therapy to encourage adherence
• BMD measurements 2 years after the commencement of therapy or 1-2 years after therapy changes significantly

Polycystic ovarian syndrome

Key points :

- It is the most common endocrinological disorder (12-18 % women in reproductive age)

- Presentations: Menstrual irregularity (>35 or < 21 day cycles), overweight, hirsutism, fertility issues, pre diabetes, gestational diabetes or early onset type 2 diabetes, not high risk ethnic groups (Asian, indigenous, Nth African)

- Rotterdam Diagnostic criteria:

• Requires 2 of 
• Oligo- or anovulation 
• Clinical and/or biochemical hyperandrogegism
• Polycystic ovaries; and exclusion of other aetiologies

- Differential diagnosis investigations: TSH, Prolactin and FSH (if premature menopause suspected), free testosterone, DHEAS, SHBG, 17 hydroxy progesterone, FSH, LH

- Total testosterone is often normal in PCOS. cFT is often elevated. 

- PCOS management areas include:

• Emotional health: depresion and anxiety is more common. Assess mental health is the key. 
• Lifestyle : aim for 5-10 % weight loss 
• Cardiometaboic health: Smoking cessation, check BP annually, lipid profile and OGTT every 2 years
• Weight management:5-10% weight loss 
• Fertility: weight loss if BMI > 25 is the first line treatment, metformin (500 mg daily, increase by 500 mg per fortnight up to 1500 mg - 2000 mg average dose) and clomiphene 
• Menstrual cycle regulation: lifestyle and metformin, OCP 
• Clinical hyperandrogenism (eg hirsutism): OCP, if OCP alone doesn't work after 6 months, then try anti androgen (spironolactone) 
• Sleep apnoea 

References:
https://jeanhailes.org.au/contents/documents/Resources/Tools/PCOS_GP_tool.pdf

Hypercalcaemia

I saw a patient today with a recently diagnosed Paget's disease. He thinks that he has had symptoms for years but none of the GPs picked it up despite multiple abnormal ALPs. Eventually it was picked up by a GP registrar when he presented with palpitations and she ordered a Calcium, Magnesium and Phosphate. Looking back to my practice, I always forget to order calcium when people presented with palpitations. When I remembered to order them, I don't think I have ever had one came back elevated. The followings are just some key points on Calcium homeostasis and hypercalcaemia.

Key points:

- Common presentations can be summarised as "Bones, stones, groans and psychic moans."
- Causes of metastatic calcification can be summarised using a mnemonic, " Parathormone"

• Parathormone (PTH) increase and causes of Ca increase eg. Sarcoidosis 
• Amyloidosis 
• Renal failure (relates to increase PO4)
• Addison's disease (adrenal calcification)
• TB nodes; Toxoplasmosis (CNS)
• Histoplasmosis (e.g. in lung)
• Overdose in vitamin D
• Raynaud's - associated diseases , e.g. SLE; CREST; Dermatomyositis
• Muscle primaries/leiomyosarcomas
• Ossifying metastases (osteosracoma) or ovarian mets
• Nephrocalcinosis
• Endocrine tumours (e.g. gastrinoma)

- a basic flowchart from oxford handbook of clinical medicine, I think this is a good place to start.

Reference:
Oxford handbook of clinical medicine 8th edition