Endocrinology

Thyroid Gland

Introduction

Anatomy

The thyroid gland is situated in front of trachea made up of the isthmus and two lobes and a variant pyramidal lobe. Thyroid tissue may be found anywhere along its embryological origin along path of thryoglossal duct

Physiology

TRH (tripeptide) released by the hypothalamus acts on the anterior pituitary to induce TSH production and release. TSH released by the anterior pituitary is released into the blood stream and acts on the thyroid where it binds to cell receptors on thyroid cuboidal cells and activates adenylate cyclase and this stimulates all aspects of T4 production.

Thyroid Structure

Main histological and functional unit is thyroid follicle containing cuboidal cells containing colloid which consists of thyroglobulin. Between the follicles lie Parafollicular C cells which secrete calcitonin. Tyrosine is iodinated to T3 and T4 by thyroid peroxidase (blocked by Carbimazole/PPTU). T3 is the active form and T4 is converted to T3 peripherally and acts within the cell at intranuclear receptors. Thyroxine is able to cross the cell membrane. Both T4 and T3 act via negative feedback on both hypothalamus and pituitary to suppress TSH and TRH release.

Thyroid Function

  • Thyroxine: T4 (x10 more than T3) is released and protein bound to Thyroxine binding globulin, albumin and transthyretin
  • Triiodothyroinine: T3
  • Calcitonin

Hyperthyroidism

Definitions

It is useful to understand the difference between hyperthyroidism and thyrotoxicosis

  • Hyperthyroidism is sustained increase in thyroxine production and release by the thyroid gland
  • Thyrotoxicosis is the clinical syndrome caused by the effect of excessive thyroxine on peripheral tissues.

Causes of Thyrotoxicosis

  1. Graves's disease: Antibodies to the TSH (TSAb) receptor cause continuous stimulation of the gland to overproduce thyroxine. Goitre with overlying bruit may be found in a Young patient. Females > males. Lymphocytic infiltration and increased follicles.Associated findings specific to GD - Thyroid acropachy ? clubbing like appearance of fingers, Pretibial myxoedema, Eye disease ? exophthalmos, gritty eyes, photophobia, diplopia, can threaten vision, Worse in smokers
  2. Toxic adenoma/Toxic multinodular goitre: Are due to autonomously acting nodules
  3. Thyroiditis: Gland is tender with sore throat and possible viral type illness. It burns out with time. Long term hypothyroid. Biopsy shows giant cell inflammation. Some cases are clinically silent.
  4. Iatrogenic: Accidental or deliberate T4 intake
  5. Pituitary tumour: secreting TSH. Very rare.
  6. Struma ovarii: ectopic thyroid tissue in the ovary releases T4/T3
  7. Choriocarcinoma: releases B-HCG stimulates thyroid
  8. Iodine induced: e.g in radiocontrast ? Jod Basedow effect or Amiodarone which contains iodine

Clinical

  • Overactivity, Anxiety, palpitations, weight loss, heat intolerance, increased stool frequency (not really diarrhoea)
  • Proximal weakness, osteopenia, hypercalcaemia /calciuria, reduced or absent periods etc. weight loss
  • Presentation in the elderly can be delirium or apathy and non specific
  • Atrial fibrillation
  • Grave's disease : Eyes signs, Goitres, Thyroid acropachy
  • Thyroiditis : Neck pain and sore tender thyroid

Investigations

  • Low TSH < 0.04 and Raised T3/T4 or only T3 sometimes
  • In Graves there is an increased T3/T4 ratio
  • Graves : Antibodies to the TSH (TSAb) receptor
  • Antibodies to thyroglobulin may be seen with Grave?s disease and Hashimoto's thyroiditis.
  • Increased ESR/CRP with thyroiditis
  • Radioactive iodine uptake - Increased in all except thyroiditis and struma ovarii
  • Graves - Diffuse increased uptake on thyroid scanning
  • Toxic adenoma - hot nodule

Management

  • Symptom control ? Beta blocking drugs such as Propranolol helps palpations, tremor and heat intolerance
  • Manage AF is present and may need Warfarinisation.
  • Anti-thyroid medications - Carbimazole (Methimazole in US) or Propylthiouracil interfere with the incorporation of iodine by competitively competing for thyroid peroxidise
  • The most serious risk which is agranulocytosis which must be discussed with the patient and written instructions given and must be suspected if a patient develops fever or sore throat medical help must be sought.
  • Radioactive 131-Iodine: increasingly used as first line treatment with 80% cure rate and 95% if repeated. Main problem is late hypothyroidism It is contraindicated in pregnancy and breast feeding. Can set off airport alarms for a few weeks after.
  • Surgery - subtotal thyroidectomy rare nowadays. Indicated if concerns over malignancy, pregnancy or unable to take long term medications. It can cause recurrent laryngeal nerve damage and hypocalcaemia from removal of parathyroids
  • Graves : Will usually settle with time and antithyroid medications for 18 months
    • Relapse is common
    • Radioactive iodine is being used more so nowadays
    • There is a risk of hypothyroidism but thyroxine can easily be replaced
    • Eye disease - must stop smoking
    • Artificial tears to protect cornea
    • If sight threatened then steroids and decompressive surgery/radiotherapy.
    • Toxic multinodular goitre can sometimes cause tracheal narrowing and stridor ? check flow volume loop
    • CT/MRI of thoracic inlet
  • Nodules often also get radioactive iodine but need higher doses than Grave's disease.
  • Thyroiditis: symptom control and NSAIDs and sometimes steroids and should burn itself out and may become euthyroid and even hypothyroid requiring thyroxine replacement.

Thyroid storm

Introduction

  • Aggressive form of thyrotoxicosis
  • Can lead to heart failure

Clinical

  • Fever and tachycardia, AF and delirium
  • Cardiac failure, dehydration
  • Precipitant - surgery, infections, trauma

Investigations

  • FBC: WCC may be elevated especially if sepsis
  • Raised T4/T3 and Low TSH
  • ECG: AF, Flutter, Sinus Tachycardia. ST/T wave changes
  • Increased RAI uptake

Management

  • Rehydration and Beta blockade e.g. propranolol
  • Start Carbimazole or Propylthiouracil before Iodide
  • Iodide (Lugol's iodine) containing drugs blocks T4 formation and conversion to T3
  • Sedation may be needed for hyperactive delirium or agitation
  • Cooling and IV/Oral paracetamol
  • Avoid aspirin as can increase Free T4 by binding to thyroid binding globulin
  • Steroids may be needed if any suspected adrenal Insufficiency

Subclinical thyrotoxicosis

Clinical :

  • Long term increased risk of osteopaenia and AF

Investigations

  • Low TSH and High/Normal T3 and T4

Management

  • Needs ongoing follow up

Hypothyroidism

Causes

  • Hashimoto's thyroiditis : Autoimmune disease with a chronic lymphocytic thyroiditis
  • The gland becomes hard and firm
  • other autoimmune diseases may coexist.
  • Post Thyroidectomy, Post thyroiditis
  • Post Radioactive iodine Iodine deficiency
  • Inherited defects and Congenital agenesis of thyroid gland
  • Drugs - Amiodarone, carbimazole, PPTU, Lithium
  • Pituitary TSH deficiency

Clinical :

  • Cold intolerance, Tiredness, lethargy, weight gain, depression, bradycardia, constipation, heavy periods, hoarseness
  • Macroglossia, delayed reflexes, yellowish skin (cartotene), non pitting oedema
  • Accumulation of glycosaminoglycans causing myxoedema
  • Anaemia, Pericardial effusion, pleural effusion
  • Thyroid goitre may be present
  • Hard goitre in Hashimoto's

Investigations

  • Mild anaemia and macrocytosis, Mildly elevated CK, Hyponatraemia and raised Prolactin, raised cholesterol.
  • ECG : low voltage ? effusion
  • CXR : pericardial and pleural effusions
  • Low Free T3/T4 and elevated TSH
  • High titres of Antibodies to Thyroid peroxidase and thyroglobulin are seen in 90% of those with Hashimoto's thyroiditis which is useful.
  • ECG: Prolonged PR and low voltage

Management

  • L-Thyroxine is metabolised to T3 and should be replaced to a dose that normalises the TSH to 1 mU/L
  • T3 rarely used as shorter half life and expense though it is the active agent.
  • Usually start at 50 mcg/day and increase to normalise TSH
  • Typical dose 75-150 mcg od. Doses are increased more slowly in elderly and those with IHD as can precipitate angina. Start at 25 mcg od.
  • In the very rare pituitary causes treat any hypopituitarism before starting T
  • Most importantly Steroid replacement may be needed
  • Overtreatment can cause osteoporosis and AF.

Subclinical hypothyroidism

  • TSH elevated, Normal FT3 / FT4 and Thyroid autoantibdies may be present
  • Treat if TSH > 10 mU/L and autoantibody positive or significant symptoms
  • Myxoedema coma

    Introduction

    • Severe Hypothyroidism mortality may be up to 50%

    Causes

    • Precipitated by stress, surgery, intercurrent infection

    Clinical

    • Cold, hypothermia, Comatose, hypoventilation, stupor
    • Bradycardia, Constipation even paralytic ileus

    Investigations

    • TSH elevated and Low Free T4

    Management

    • IV fluids and ABCs and Cautious gradual rewarming
    • Replace T4 or T3 IV and then T4 orally/NG
    • Give IV Hydrocortisone as there may be adrenal insufficiency. T4 can precipitate an Addisonian crises due to local adrenal insufficiency

    Thyroid disease and Amiodarone

  • Amiodarone has a long half life of 100 days and contains large amounts of Iodine
  • Iodine acutely reduces Thyroid function
  • Can cause hypothyroidism and hyperthyroidism
  • Thyrotoxic - stop amiodarone and start carbimazole
  • Hypothyroid - start Thyroxine at 25 mcg od and titrate upwards slowly
  • High T4 and Normal TSH - repeat in 6-12 weeks
  • Thyroid nodules and masses

    Introduction

    • Always exclude malignancy especially in those with radiation exposure at higher risk.

    Causes

    • Multinodular goitre
    • Hashimoto?s thyroiditis (hard indurated gland)
    • Graves disease - enlarged diffuse vascular gland with a bruit overheard
    • Benign follicular adenomas
    • Simple thyroid cyst
    • Thyroid cancer

    Clinical

    • Hyperthyroid/Hypothyroid/Euthyroid
    • Malignancy - may be hard, local spread, lymph nodes, hoarseness
    • Dysphagia, Hoarseness, Stridor

    Investigations

    • Hyper - Raised T3/T4 TSH low
    • Hypo - Low T3/T4 and raised TSH
    • Normal TSH FT3 / FT4
    • Fine needle aspiration and cytology
    • Radioactive uptake - cold nodules may suggest malignancy
    • CT to assess mass lesions

    Management

    • Nothing for small benign nodules unless remove requested by patient.
    • Fine needle biopsy for nodules
    • Resection for large goitres

    Thyroid cancers

    Histological types

    • Papillary - Least aggressive with only local spread
    • Follicular - More aggressive with lung and bone secondaries
    • Medullary - from parafollicular cells part of MEN 2 syndrome. Calcitonin secreting
    • Anaplastic - locally destructive and aggressive with tracheal stenosis and stridor, dysphagia and hoarseness
    • Lymphoma (NHL) seen late following Hashimoto's thyroiditis with an expanding thyroid mass with local compressive symptoms

    Management

    • Papillary and follicular need localised resection e.g. lobectomy for small tumours followed by radioactive iodine therapy and suppressive doses of T4 to keep TSH low as these tumours have TSH receptors. Measure thyroglobulin levels as a tumour marker of recurrence,
    • Medullary - surgical resection and octreotide, radiotherapy and chemotherapy
    • Anaplastic - surgical debulking, radiotherapy: Prognosis very poor.
    • Lymphoma - staging, radiation, chemotherapy