Endocrine Flashcards
Outline your treatment of post-thyroidectomy hypocalcaemia.
Normal levels are 2.2 - 2.6 mmol/L
Check PTH
Decide on amount of Ca and Vit D to give based on Ca and PTH. Don’t need to check a vit D level; helps Ca reabsorption regardless of pre-existing levels.
Also check and replace magnesium as hypomagnesaemia frequently co-exists and potentiates the hypoparathyroidism effect
- if only Ca low and pt asymptomatic: give nothing or BD vit D
- if Ca low & PTH low & pt asympatomatic: BD vit D and calcium, then try to wean calcium
- if Ca & PTH low & pt symptomatic: BD vitD and TDS calcium
- if Ca ≤1.9 then give IV calcium too
- if Ca low & PTH unrecordable: BD vitD and TDS/QID Ca
- if Ca low & PTH unrecordable & pt symptomatic - likely needs IV too
- if not responding to oral regimen + IV boluses then may need IV infusion over 1-2days til bone stocks of calcium replenished the wean off IV (with cardiac monitoring)
Vitamin D used is 0.25mcg BD
Oral calcium used is 1g of elemental calcium BD/TDS/QID
IV calcium used is initially 1 ampoule of 10% calcium gluconate in 100mL of normal saline over 10mins
Infusion is 5 ampoules in 500mL over 6-8hours and don’t stop infusion suddenly; taper slowly depending on response and repeat Ca q6-12hrs while on infusion
Discharge on oral calcium with blood tests for Ca and PTH every 3-7 days depending on severity and planned weaning. Aim for Ca ~2.0; if too high into normal range no stimulus for remaining/reimplanted parathyroids to hypertrophy. PTH is a good guide to whether you can continue to wean calcium bc in some people PTs wake up suddenly
Outline your management of a patient with thyrotoxicosis who is pregnant.
- Confirm diagnosis
- Anti-TSH ABs ?Graves
- TSH, Free T4 and T3 levels
- FNA only if solitary nodule
- Optimum medical therapy
- PTU preferred in pregnancy
- 400mg PO TDS and taper
- Methimazole reserved if PTU fails
- Carbimazole associated with birth defects (imperforate anus)
- Reserve beta-blockers due to IUGR, fetal bradycardia, neonatal hypoglycaemia
- Propanolol is most studies
- I131 is contraindicated
- Note, if I131 used in the past then mother still has antibodies!
- PTU preferred in pregnancy
- Reserved surgical therapy
- Indicated when
- Medical therapy fails
- Intolerable side effects
- Non-compliant patient
- Aim for total thyroidectomy in 2nd trimester
- Indicated when
- Post-partum
- Note future pregancies may be complicated by remaining antiboides
- Grave’s may worsen post partum
- Follow up
- Routine TFTs on newborns
- Follow maternal TFTs for one year
What is the differential for a rapidly enlarging thyroid mass?
Painless:
- Anaplastic thyroid cancer
- Thyroid lymphoma
- Parapharyngeal sarcoma
Painful:
- Bleeding into pre-existing cyst
- Riedel’s (fibrotic) thyroiditis
- Suppurative thyroiditis
What are the radiologically suspicious features of a thyroid nodule on USS?
- Irregular margins
- Hypoechoic lesion
- Loss of a halo
- Internal vascularity
- Internal calcifications
- Increased height:width ratio
All of the above confer high score/risk as per the TIRADS classification (not widely used in USA).
What is the role of lymph node dissection in thyroid cancer?
Most surgeons would agree with the 2015 ATA consensus guidelines that CLND is recommended when there are clincally apparent metastases.
The role of prophylactic CLND is controversial. Weak evidence suggests a role for pCLND in PTC, T3/T4 tumours, and where there are positive lateral nodes.
NB: Secondary CLND can be performed in expert hands without added morbidity, and is recommended when proven recurrence in the central compartment is detected; if a CLND was note performed at the index procedure.
The indications for LLND are clear; compartmental LLND is recommended for proven metastatic lateral lymph nodes.
What are the indications and principles of Radioactive Iodine in thyroid cancer treatment?
In general can be used for
-
ablation - to assist follow-up (rarely used in Auckland; strong preference for completion thyroidectomy if RAI indicated rather than ablating but may be exceptions e.g. damaged RLN on other side
- and in pts w low risk DTC, disease surveillance may be accomplished w/o RAI ablation using neck USS & Tg w Tg antibody measurements while on thyroid hormone therapy
- adjuvant therapy (intended to improve DFS by theoretically destroying suspected but unproven residual dsiease, espec in pts at risk of disease recurrence
- therapy for persistent disease (intended to improve DSS and DFS by treating persistent disease in higher risk patients
Radioactive Iodine Ablation (RIA) is recommended for patients with high risk or some intermediate risk (ATA stratification) patients
- Known distant metastases
- Gross extrathyroidal extension
- Primary tumour >4cm
- Regional lymph node metastases
- High risk features on histology.
Radioiodine causes cytotoxicity by the emission of short path-length (1 to 2 mm) beta radiation. Iodine uptake is limited by sufficient iodine levels (diet, CT contrast, amiodarone) and so the patient must either be hypothyroid (so TSH increases - w/h thyroxine for 3-4wks prior to RAI therapy) or be given recombinent TSH. RCTs show little difference between the two approaches.
Outline the tumourgenesis of thyroid cancer.
RET (Re-arranged during Transfection) proto-oncogene mutation
- Characterises MEN IIa and IIb and fMTC
RAS (Rat Sarcoma) oncogene mutations
- Seen in 40-50% of PTC, FTC, and ATC
BRAF (B-Rapidly Accelerated Fibrosarcoma) proto-oncogene
- Most common genetic alteration in PTC
Outline the arguments for and against total thyroidectomy for thyroid cancer.
Firstly, total thyroidectomy is widely recommended for:
- Tumours >4cm
- Younger than 15, older than 45
- Past irradiation
- Bilateral nodularity
- Known mets
- Aggressive variant
For:
- Able to use I131
- Able to follow up with Tg
- Eliminates contralateral/multifocal cancer
- Slight increase in survival and reduced LR
Against:
- Increased surgical risk to RLN and parathyroids.
- ATA guidelines 2015 recommend lobectomy for tumours <1cm.
What are the indications for surgical treatment of thyrotoxicosis?
Manage jointly with endocrinologists; 6Ms
- Malignancy
- Medical therapy failure
- Mechnical compression
- Menacing consequences of I131 (pregnancy, eye disease, allergy)
- Mediastinal extension
- Marred beauty
What are the side effects of radioactive iodine therapy?
- Short term:
- anorexia, nausea, headache
- transient oligospermia/oligomenorrhoea
- sialadenitis
- neck swelling
- haematological/BM depression
- exacerbation of cardiac arrhythmias espec in older pts
- thyroid storm (rare)
- worsens Graves eye disease in 33%
- Long term:
- chronic sialadenitis
- xerostoma
- dental caries
- nasolacrimal duct obstruction
- pneumonitis
- leukaemia
- inc risk secondary malignancies: bone, breast, kidney, salivary glands
- men receiving cumulative RAI activities ≥400mCi should be counselled on potential risks of infertility
- Pregnancy must be avoided for 6-12 months
- Avoid children for ?one week following therapy.
- don’t give to breastfeeding women; defer until stopped breastfeeding or pumping for at least 3mo
What are the indications for surgical treatment of primary
hyperparathyroidism?
- SYMPTOMATIC OR
- Age <50
- Bone density: T score
- Calcium ≥0.25mmol above upper limit normal or CrCl <60
- Deposits - ie nephrolithiasis or nephrocalcinosis
- Expressed preference by pt
- Follow up/surveillance not a good option
What are the actions of parathyroid hormone?
PTH is secreted from the chief cells of the parathyroid glands in response to low serum calcium (2.12-2.65)
- Increases calcium absorption from gut
- Increases calcium reabsorption from DCT
- Increases calcium reabsorption from bone
- Promotes hydroxylation of 25-OH-Vit to 1,25-OH-Vit D in kidney (which also increases Ca from gut)
- Inhibits phosphate reabsorption from PCT
- Inhibits HCO3- resorption from PCT
What are the clinical manifestations of hyperparathyroidism?
“Stones, bones, abdominal groans, psychic moans, and fatigue-overtones”
Gastrointestinal:
- Nausea, vomiting, pancreatitis, weight loss, consitipation, anorexia
Cardiovascular:
- Hypertension, shortened Q-T, wide T-waves, bradycardia, heart block, arrhythmia, valvular calcifications
Renal:
- Nephrolithiasis, nephrocalcinosis, polyuria, polydipsia, renal colic, renal failure
Neuropsychiatric:
- Anxiety, headaches, tiredness, dementia, paranoia, confusion, depression, fatigue
Skeletal:
- Osteopenia, osteoporosis, osteitis fibrosa cystica.
Misc:
- Gout, corneal band keratopathy, calciphylaxis.
What are the indications for surgical treatment of secondary hyperparathyroidism (even if the calcium is high-normal)?
Who gets a sub-total versus total parathyroidectomy?
- Renal osteodystrophy
- Calciphylaxis
- Pruritis
- Impairs vascularity of transplant candidates
- Hyperphosphataemia
Patients who are transplant candidates should be considered for sub-total as their native glands should work once transplanted (i.e. secondary stimulus removed).
Describe the medical management of secondary hyperparathyroidism.
- Restrict phosphate in diet
- Phosphate binders
- Vitamin-D supplementation
- Calcimimetics (bind CSR and reduce PTH driven hypercalcaemia and hyperphosphatemia)
- Calcium supplements (losing calcium +++)
Describe peri-operative management of a patient undergoing surgery for a phaeochromocytoma.
- After diagnosis is established the focus is on pharmacological control of the adverse effects of circulating catecholamines
- Phenoxybenzamine, a non-competative, non-selective α-adrenergic receptor antagonist is used
- Commenced at 20mg BD and up-titrated until postural hypotension occurs
- Usually takes 2-4 weeks
- ß-blockers may also be required to counter the tachycardia or arrhythmias but not until α-adrenergic blockade is complete.
- Intraoperative careful handling
- Post-resection expect increased fluid +/- pressor requirements.
Describe the theory and methodology of Dexamethasone suppression tests.
Dexamethasone suppression tests are used to assess the status of the hypothalamic-pituitary-adrenal (HPA) axis and for the differential diagnosis of adrenal hyperfunction.
Low-dose DSTs are used to differentiate patients with Cushing’s syndrome from those that do not have Cushing’s syndrome. If the axis is normal, any supraphysiological dose should suppress ACTH.
High-dose DST are used to distinguish those that have a primary pituitary lesion (Cushing’s disease) from those that have an ectopic source of ACTH. In patients with a pituitary lesion, high supraphysiological doses are still capable of exerting negative feedback on ACTH production from the pituitary.
What is Nelson’s syndrome?
A syndrome characterised by a triad of hyperpigmentation, excessive ACTH production, and a corticotroph adenoma.
Seen in patients following bilateral adrenalectomy for Cushing’s disease. Loss of the negative feedback on the pituitary from circulating cortisol results in pituitary adenoma formation.
The incidence is reduced by prior radiotherapy to the pituitary.
What is Carcinoid syndrome?
Carcinoid syndrome describes a constellation of symptoms caused by release of vaso-active substances released by neuroendocrine tumours. Secretory diarrhoea is the most common feature of the syndrome, but flushing, bronchospasm, and right-sided valvular disease may occur.
These substances include serotonin, bradykinin, substance-P, prostaglandins, transforming growth factors, platelet-derived growth factors, and occasionally noradrenaline.
Mono-amine oxidase in the liver is usually capable of metabolising these substances, so the presence of carcinoid syndrome implies that there is either metastatic disease to the liver or that the primary is of non-gut origin (ovary, retroperitoneum).
What is the distribution of Neuroendocrine Tumours throughout the body?
- 30% extra-gastrointestinal (lung, thymus, gynae)
- 25-30% small intestine (cause most carcinoid syn.)
- 15% rectum
- 10% colon
- 5% appendix
- 5% stomach
- <2% duodenum
- <1% oesophagus
Describe the phenomenon of a “thyroid storm”
Thyroid storm is a rare, life-threatening condition characterized by severe clinical manifestations of thyrotoxicosis.
It is often precipitated by an acute event such as thyroid or nonthyroidal surgery, trauma, infection, an acute iodine load, or parturition.
Cardiovascular symptoms in many patients include tachycardia to rates that can exceed 140 beats/minute and congestive heart failure. Hypotension, cardiac arrhythmia, and death from cardiovascular collapse may occur. Hyperpyrexia, agitation, anxiety, delirium, psychosis, stupor, or coma are also common and are considered by many to be essential to the diagnosis.
What is goitre?
What causes goitre?
What are the histopathological features of goitre?
- The term goitre refers to abnormal growth of the thyroid gland. Goitres can be diffuse or nodular, depending on the cause, and may be associated with normal, decreased, or increased thyroid hormone production. The clinical manifestations vary with thyroid function and with the size and location of the goitre.
- Causes of goitre vary with geography; worldwide the most common cause is Iodine deficiency. In Iodine-replete countries such as New Zealand, the most common causes of goitre are multi nodular goitre, Graves’ disease, and Hashimoto’s disease. Rarer causes include medication induced goitre, tumours, infiltrative diseases, and thyroiditis.
- The pathophysiology of goitre in iodine-deficient patients is due to hyperplasia of the gland, due to increased circulating TSH, in order to increase production of thyroid hormone. In the iodine replete patient the pathophysiology is incompletely understood, but probably due to an imbalance of the growth factors acting on the thyroid.
- Macroscopically, multi nodular goitre presents as a heterogenous looking gland with nodules of varying size and colour. The capsule is intact and the nodules are typically themselves smooth.
- Microscopically, the nodules may contain areas of haemorrhage, calcification, or fibrosis due to the chronicity of the disease.
What is Graves’ disease?
- Graves’ disease is an autoimmune disease that may consist of hyperthyroidism, goiter, eye disease (orbitopathy), and occasionally a dermopathy referred to as pretibial or localized myxedema. Hyperthyroidism is the most common feature of Graves’ disease, affecting nearly all patients, and is caused by thyroid-stimulating hormone (TSH, thyrotropin)-receptor antibodies (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth (causing a diffuse goiter).
Describe the pathophysiology of Graves’ ophthalmopathy
- The predominant autoantibody in Graves’ is directed at the TSH receptor, which is also expressed on adipocytes and fibroblasts.
- Stimulation of the retro-ocular fibroblasts leads to hyperplasia, inflammation, and production of glycosaminoglycans with subsequent retro-ocular expansion
- The accumulation of hydrophilic GAG in turn leads to fluid accumulation, muscle swelling, and an increase in pressure within the orbit. These changes, together with retroocular adipogenesis, displace the eyeball forward, leading to extraocular muscle dysfunction and impaired venous drainage.