Thyroid disorders..Part 1

Pratap Sagar Tiwari, MDLecturer, NMCTH

Anatomy

http://khalidalomari.weebly.com/blood-supply-and-venous-drainage.html

Vascular/Neural Anatomy

Superior thyroid artery external carotid artery, Inferior thyroid artery thyrocervical trunk, Thyroid ima artery subclavian artery.

superior thyroid veins internal jugular vein, Middle thyroid vein internal jugular veininferior thyroid veins left brachiocephalic vein.

Lymphatic drainage : the lateral deep cervical lymph nodes and the pre- and parathracheal lymph nodes.

Parasympathetic nerve input superior laryngeal nerve and recurrent laryngeal nerve.

Thyroid Histology

http://www.studyblue.com/notes/note/n/anatomy-lab-shit/deck/7511240

Histology

Follicles The thyroid is composed of spherical folliclesInside the follicles there is follicular lumen. It is surrounded by follicular cells and filled with colloid.Colloid is rich in a protein called thyroglobulin.

Thyroid epithelial cells(or "follicular cells")

The follicles are surrounded by a single layer of thyroid epithelial cells, which secrete T3 and T4.

Parafollicular cells(or "C cells")

Scattered among follicular cells and in spaces between the spherical follicles are another type of thyroid cell, parafollicular cells, which secrete calcitonin.

Thyroid hormone synthesis

Thyroid hormone synthesis• The thyroid secretes predominantly T4 and only a small

amount of T3. • Approximately 85% of T3 in blood is produced from T4 by a

family of monodeiodinase enzymes which are active in many tissues including liver, muscle, heart and kidney.

• T4 can be regarded as a pro-hormone, since it has a longer half-life in blood than T3 (approx. 1 wk compared with approx. 18 hrs).

• T4 binds and activates thyroid hormone receptors less effectively than T3.

• T4 can also be converted to the inactive metabolite, reverse T3.

Thyroid Binding Globulin

• Most of the thyroid hormones in the blood are attached to a protein called thyroid binding globulin (TBG).

• If there is an excess or deficiency of this protein it alters the T4 or T3 measurement but does not affect the action of the hormone.

• If a patient appears to have normal thyroid function, but an unexplained high or low T4, or T3, it may be due to an increase or decrease of TBG.

Radioactive iodine uptake (RAIU) test

• A low uptake of tracer by the thyroid gland: hyperthyroidism is caused by inflammation of the thyroid gland (thyroiditis) or taking too much thyroid medicine.

• A high uptake of tracer (spread evenly in the thyroid gland): hyperthyroidism is caused by Graves' disease.

• An uneven spread of tracer in the thyroid gland (with either low or high areas of uptake) :hyperthyroidism is caused by a multinodular goiter or a noncancerous (benign) tumor called a toxic adenoma.

• Thyroid Ultrasound: solid vs cyctic• Thyroid Scan: hot vs cold• Thyroid Needle Biopsy• Thyroid Antibodies(anti-TG, anti-TPO):

hashimoto• TSI Test: Graves’ disease

InterpretationT3 T4 TSH State

↔ ↔ ↔ Euthyroid

↑ ↑ ↓ Primary hyperthyroidism

↓ ↓ ↑ Primary hypothyroidism

↓ ↓ ↓ Secondary hypothyroidism

↑ ↑ ↑ Secondary hyperthyroidism

↔/↑ ↔/↑ ↔ Euthyroid hyperthyroxinemia

↔/↓ ↔/↓ ↔ Euthyroid hypothyroxinema

↔ ↔ ↑ Subclinical hypothyroidism

↔ ↔ ↓ Subclinical hyperthyroidism

Thyrotoxicosis

• Thyrotoxicosis describes a constellation of clinical features arising from elevated circulating levels of thyroid hormone.

• The most common causes are Graves' disease, multinodular goitre and autonomously functioning thyroid nodules (toxic adenoma).

Interpretation

Thyrotoxicosis: causesCommon causes

Graves' disease Iodide-induced (amiodarone, contrast)

Multinodular goitre Extrathyroidal sourceFactitious thyrotoxicosisStruma ovarii

Solitary thyroid adenoma TSH-inducedTSH-secreting pituitary adenomaChoriocarcinoma and hydatidiform mole

Thyroiditis (de Quervain's or Postpartum)

Follicular carcinoma ± metastases

ThyrotoxicosisSymptoms SIgns

Weight loss despite normal or increased appetite

Weight lossTremor

Heat intolerance Palmar erythema

Palpitations Sinus tachycardia

Dyspnoea Lid retraction, lid lag

Irritability, emotional lability

Fatigue, Sweating, Tremor

Less common

Osteoporosis, Diarrhoea, steatorrhoea Goitre with bruit, Atrial fibrillation, HF

Muscle weakness, Pruritus, Ankle swellingAlopecia

Systolic hypertension/increased pulse pressure

Amenorrhoea/oligomenorrhoeaInfertility, spontaneous abortion

Hyper-reflexia, Ill-sustained clonus, Proximal myopathy

Jod-Basedow phenomenon

• is hyperthyroidism following administration of iodine or iodide, either as a dietary supplement or as contrast medium.

• This phenomenon is thus iodine-induced hyperthyroidism, typically presenting in a patient with endemic goiter (due to iodine deficiency).

Graves' disease• is a syndrome that may consist of hyperthyroidism,

goiter, eye disease (orbitopathy), and occasionally a dermopathy referred to as pretibial myxedema.

• Hyperthyroidism is the mc feature of GD, affecting nearly all patients, and is caused by autoantibodies to the thyrotropin (TSH) receptor (TSHR-Ab)

• TSHR-Ab activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth (causing a diffuse goiter).

• The presence of TSHR-Abs in serum and orbitopathy on clinical examination distinguishes the disorder from other causes of hyperthyroidism.

Treatment optionsTherapy Advantages Disadvantages

ThionamidesMethimazoleCarbimazolePropylthiouracil

Chance of permanent remission

rash, arthralgias, GI, agranulocytosis, vasculitis (lupus-like syndrome), hepatitis (PTU)

Radioiodine Permanent resolution of hyperthyroidism

Permanent hypothyroidismoncogenic effects of radiation

Surgery Rapid, permanent cure of hyperthyroidism

Permanent hypothyroidismRisk of hypoparathyroidism, recurrent laryngeal nerve damage.

Antithyroid drugs

1. carbimazole 2. methimazole 3. Propylthiouracil• reduce the synthesis of new thyroid hormones

by inhibiting the iodination of tyrosine.• Carbimazole also has an immunosuppressive

action, leading to a reduction in serum TSHRAb concentrations.

• CI: Breastfeeding (propylthiouracil suitable)

B blockers• HT is a/w an increased number of ß-adrenergic receptors . The

ensuing increase in ß-adrenergic activity is responsible for many of the symptoms .

• It also explains the ability of ß-blockers to ameliorate rapidly many of the symptoms, including palpitations, tachycardia, tremulousness, anxiety, and heat intolerance .

• Propranolol in high doses (above 160 mg/day) also slowly decreases T3 concentrations by as much as 30 % , via inhibition of the 5'-monodeiodinase that converts T4 to T3.

• Start with atenolol 25 to 50 mg daily, and increase the dose as needed (up to 200 mg daily) to reduce pulse to under 90 bpm if bp allows.

• Patients should have their thyroid function assessed at 4-6 wks intervals until stabilized on maintenance thionamide therapy.

Iodinated contrast agents and iodine

• The oral radiocontrast agents sodium ipodate and iopanoic acid are potent inhibitors of the peripheral conversion of T4 to T3.

• When given in combination with methimazole (at doses of 500 to 1000 mg/day), they can rapidly ameliorate severe hyperthyroidism and can also be used to prepare a hyperthyroid patient for early surgery.

Thyrotoxicosis in pregnancy

• Propylthiouracil may be preferable to carbimazole since the latter might be associated with a skin defect in the child, known as aplasia cutis.

• In order to avoid fetal hypothyroidism and goitre, it is important to use the smallest dose of antithyroid drug (optimally < 150 mg /d) that will maintain maternal (and presumably fetal) free T4, T3 and TSH WNR.

Graves' ophthalmopathy (orbitopathy)

• The eye disease often associated with Graves' thyroid disease is referred to as Graves' ophthalmopathy.

• This condition is immunologically mediated.• Within the orbit (and the dermis) there is cytokine-mediated

proliferation of fibroblasts which secrete hydrophilic glycosaminoglycans.

• The resulting increase in interstitial fluid content, combined with a chronic inflammatory cell infiltrate, causes marked swelling and ultimately fibrosis of the extraocular muscles and a rise in retrobulbar pressure.

• The eye is displaced forwards (proptosis/ exophthalmos) and in severe cases there is optic nerve compression.

Features

• Ptosis, pseudo ptosis, strabismus (hypotropia, esotropia)

Mobius sign (poor convergence)Mobius sign (poor convergence)

26

Ballet signBallet sign

– restriction of one or more extra ocular musclesrestriction of one or more extra ocular muscles

– Initially due to edema , later fibrosis Initially due to edema , later fibrosis

– All 4 recti are involved but mainly IR and MRAll 4 recti are involved but mainly IR and MR

27

Restrictive myopathy

Elevation defect Abduction defect

Depression defect Adduction defect

28

• Upper lid retraction (Dalrymple sign) -Upper lid retraction (Dalrymple sign) -90%90%

29

Mechanisms for upper lid retraction

Up gaze restriction Proptosis

Fibrotic contracture of LPSSecondary over action of LPS-SR complexMuller muscle over action

30

Signs of eyelid retraction

• Bilateral lid retraction • No associated proptosis

• Bilateral lid retraction • Bilateral proptosis

• Lid lag in downgaze • Unilateral lid retraction • Unilateral proptosis

31

Lid lag on down gaze (von Graefe’s sign)

32

Glabellar furrows Eyelid edema

33

Stellwag sign (incomplete and infrequent blinking) Stellwag sign (incomplete and infrequent blinking) Goffroy sign (absent creases in the forehead on superior gaze) Goffroy sign (absent creases in the forehead on superior gaze) Enroth’s sign (eyelid fullness) Enroth’s sign (eyelid fullness)

Gifford’s signGifford’s sign

(difficulty in upper lid eversion )(difficulty in upper lid eversion )

34

Minimal staining

Ulceration

perforation

Corneal signs

Assessment of severity

• Class 0 — No symptoms or signs• Class I — Only signs, no symptoms (eg, lid

retraction, stare, lid lag)• Class II — Soft tissue involvement• Class III — Proptosis• Class IV — Extraocular muscle involvement• Class V — Corneal involvement• Class VI — Sight loss (optic nerve involvement)

End of slides

References:•Davidson 21st

•Uptodate 20.3•Medscape•Wikipedia•Eye signs pics taken from slides of :THYRIOD EYE DISEASEDr. Gyanendra Lamichhane,Lumbini Eye Institute,Bhairahawa ,Nepal