Hyperthyroidism & Hypothyroidism

Hyperthyroidism

&

Overview

1. Thyroid physiology

2. Hypothyroidism

3. Hyperthyroidism

4. Tumors

5. Case History 1-6

•

Failure of the gland to develop causes

congenital hypothyroidism.

• Under- or over-migration of the thyroid can

cause a lingual or

retrosternal thyroid

respectively.

• Failure of thyroglossal duct to atrophy can

lead to a

thyroglossal cyst.

Regulation of

Thyroid hormone

synthesis

TPO: Thyroid peroxidase MIT: monoiodotyrosine DIT: diiodotyrosine

TSH: 0.34–4.25 mU/L

free T4: 9–16 pmol/L

free T3: 3.7–6.5 pmol/L

Circulating Thyroid Hormones

• Thyroid hormones are almost entirely

bound to serum proteins

(in order of

decreasing affinity):

° Thyroxine-binding globulin (TBG)

° Thyroxine-binding pre-albumin (TBPA)

° Albumin

• The unbound fraction is tiny, yet

critical –

only free thyroid hormone

enters cells and

is biologically active:

° Free T4 (

fT4

)

∼

0.015% of total T4

° Free T3 (

fT3

)

∼

0.33% of total T3

° Circulating

half-life of T3,

∼

1–3

days

– needs to be prescribed several

times a day if used to achieve steady

levels

° Circulating

half-life of T4,

∼

5–7

days

– can be prescribed as single daily

dose

° Both fT4 and fT3 are measured by

immunoassay

•

T3 is more potent than T4

(

∼

2–10-fold

depending on response monitored)

Iodine and Selenium

2 billion people are iodine-deficient.

Increased prevalence of goiter and, when deficiency is severe, hypothyroidism and cretinism. Cretinism is characterized by mental and growth retardation.

Concomitant selenium deficiency may also contribute to the neurologic manifestations of cretinism.

Iodine supplementation of salt, bread, and other food substances.

Oversupply of iodine is associated with an increased incidence of autoimmune thyroid disease.

Recommended average daily intake of iodine is 150–250 ug/d for adults, 90–120 ug/d for children, and 250 ug/d for pregnant and lactating women.

Tests to determine the etiology

of thyroid dysfunction

1.Thyroid function tests (TSH, fT3, fT4)

2.TPO, TG, TSH antibodies

3. Thyroid ultrasound

- detection of nodules and cysts >3mm

- Fine Needle Aspiration Biopsy (FNAB)

4. Radioiodine uptake

- hot nodules: increased tracer uptake, almost never malignant

- cold nodules: decreased uptake, 5-10% malignant

Primary hypothyroidism

Goiter

°Autoimmune Hashimoto thyroiditis

° Iodine deficiency

° Drugs (e.g. lithium)

° Riedel thyroiditis

° Congenital hypothyroidism

No Goiter

°

Autoimmune atrophic thyroiditis

° Post-radioiodine ablation or surgery

° Post-thyroiditis (hypothyroidism is transient)

° Congenital hypothyroidism – hypoplasia

or aplasia

Secondary/Tertiary hypothyroidism:

Symptoms and signs of hypothyroidism

• Weight gain

• Cold intolerance, particularly at extremities • Fatigue, lethargy

• Depression

• Coarse skin and puffy appearance • Dry hair

• Hoarse voice • Constipation

• Menstrual irregularities (altered luteinizing hormone/follicle-stimulating hormone secretion)

• Possible goitre

• ‘Slow’ reflexes, muscles contract normally, but relax slowly

• Generalized muscle weakness and paraesthesia

• Bradycardia (with reduced cardiac output)

• Cardiomegaly (with possible pericardial effusion)

• Possible carpal tunnel syndrome

• Loss of outer third of eyebrows (reason unclear)

Hashimoto’s Thyroiditis

First disease to be recognized as an autoimmune disease (1912).

Atrophy of the thyroid follicles accompanied by oxyphil metaplasia, absence of colloid, and mild to moderate fibrosis.

4 per 1000 women - 1 per 1000 men, mean age of diagnosis is 60

Chronic lymphocytic thyroiditis.

Cell destruction is primarily mediated by the CD8+ cytotoxic T cells.

Thyroid peroxidase (TPO) and/or thyroglobulin (Tg) and TSH-R-blocking antibodies.

HLA-DR and CTLA-4 polymorphisms account for approximately half of the genetic susceptibility to autoimmune hypothyroidism.

Treatment - Clinical Hypothyroidism

Adult patients under 60 without evidence of heart disease may be started on 50–100 ug levothyroxine (T4) daily.

The dose is adjusted on the basis of TSH levels, with the goal of treatment being a normal TSH, ideally in the lower half of the reference range.

Check TSH after 2 months of treatment. Once stable, annual check.

Clinical response is slow to appear.

Treatment - Subclinical Hypothyroidism

No apparent clinical features of hypothyroidism.

No routine treatment when TSH levels are below 10 mU/L.

Risk to progress to overt hypothyroidism, particularly when the TSH level is elevated and TPO antibodies are present.

Starting with a low dose of levothyroxine (25–50 ug/d) with the goal of normalizing TSH.

Myxoedema coma

very severe hypothyroidism

Features

• Diminished mental function →

confusion→ coma

• Usually in the elderly

• Hypothermia

• Low cardiac output/cardiac failure

• Pericardial effusion

• Hyponatraemia and

hypoglycaemia

• Hypoventilation

Treatment

• Identify any precipitating cause (e.g.infection) • Gradual re-warming

• Supportive ITU management (protect airway in coma, oxygen, broad-spectrum antibiotics, cardiovascular monitoring, glucose, monitor urine output)

• Take blood for TFTs

• Treat with hydrocortisone until hypoadrenalism excluded • Thyroid hormone replacement – both oral

and intravenous T4 and T3 have been

advocated with no clear consensus (single IV bolus of 500ug levothyroxine + 50-100ug daily)

Hyperthyroidism

Thyroid overactivity causing increased circulating thyroid hormones -

Thyrotoxicosis

Viral infection

or overdose of oral thyroxine will cause

transient thyrotoxicosis

, but

this is not hyperthyroidism.

Most commonly hyperthyroidism has an

autoimmune origin

(Graves disease)

Other causes: autonomous thyroid nodule, amiodarone, TSH secreting pituitary

adenoma, pregnancy (hCG signalling via TSH receptor),

Graves disease

Thyroid-stimulating

IgG

antibodies that

activate the TSH receptor

on the follicular

cell surface.

10x women

than men.

Between 20 and 50 years of age.

Genetic factors: polymorphisms in HLA-DR,

CTLA-4

,

CD25

,

PTPN22

Treatment of Hyperthyroidism

1. Antithyroid Drugs:

- high dose of drug can be started (e.g. thiamazole 60 mg/day) and titrated down according to falling fT4 levels on TFTs.

- treat for 12–18 months and then to withdraw treatment to test for spontaneous remission - “Block and replace” regime

- Can cause agranulocytosis!!

2.

Surgery:

- Subtotal or total thyroidectomy

- Operating on an acutely overactive gland risks ‘thyroid storm’. - can damage the recurrent laryngeal nerve

- hypoparathyroidism

3.Radioiodine:

- Iodine-131

Case History

1-6

#1

A 45-year-old woman attended her doctor having felt ‘not quite right’ for the last 6 months. She was tired and her hair had been falling out. She had noticed her periods being heavy and

rather erratic and wondered whether she was entering the menopause. She had put on 5 kg during the last 6 months. The doctor did some blood tests: Na+ 134 mmol/L (134 mEq/L), K+ 3.8 mmol/L (3.8 mEq/L), urea 4.2 mmol/L (∼11.8 mg/dL), creatinine 95 μmol/L (∼1.1 mg/dL), TSH 23.4 mU/L, fT4 6.7 pmol/L (∼0.5 ng/dL), Hb 112 g/L, gonadotrophins were normal.

1. What is the endocrine diagnosis and why? 2. What is the treatment?

#2

A 32-year-old man attended his doctor having lost 10 kg in weight and with poor sleep. He felt on edge and had had difficulty concentrating at work. He smokes five cigarettes/day. Colleagues

had commented on his staring appearance. The doctor completes the history and examination and takes a blood test. He knew the likely diagnosis beforehand, however, the results provided

proof: TSH less than 0.01 mU/L, fT4 82.7 pmol/L (∼6.5 ng/dL), fT3 14.2 pmol/L (∼0.9 ng/dL).

1. What is the biochemical diagnosis and why?

2. What features of the examination could have implied the diagnosis without the blood test? 3. Describe a suitable management plan?

4. Once the thyrotoxicosis has settled, what definitive treatment of hyperthyroidism might be ill-advised at present?

#3

A 45-year-old woman attends her family doctor because of pain in her right eye, which has been weepy, sore, red and protuberant for the last 2 weeks. She also has pain behind her left eye which otherwise appears normal. She smokes 10 cigarettes/day. The doctor notices a scar on her neck.

1. Why is the scar of interest?

2. What is significant about the pain behind the left eye?

#4

An 81-year-old man was referred by the cardiologist with TSH less than 0.14 mU/L, fT4

32.4 pmol/L (∼2.5 ng/dL), and fT3 6.2 pmol/L (0.4 ng/dL). He has been taking amiodarone for the last 6 months for supraventricular arrhythmia. On questioning he has shortness of breath.

1. Give three possible causes of the mild thyrotoxicosis.

2. If considered to be hyperthyroidism, what treatment would restore euthyroidism? 3. Give one drug-related reason why the patient might be short of breath.

#5

A 55-year-old woman who had lived in the UK all her life attended her family doctor because of a sense of fullness in her neck. It had been present for at least 5 years and had not changed in nature but was perhaps minimally larger. The patient was worried. The doctor examined her and discovered a non-symmetrical firm mass either side of and close to the midline at the base of her

neck that moved on swallowing. There was no palpable lymphadenopathy. There was no family history of cancer. TSH 1.34 mU/L, fT4 13.4 pmol/L, fT3 4.7 pmol/L

(∼0.3 ng/dL).

1. What is the likely diagnosis?

2. What further investigation would help provide complete reassurance? 3. What follow-up might be suggested?

#6

A 48-year-old man presented to his family doctor with a swelling at the base of the neck that had come on over the last 3 months. He had had a hoarse voice for the last 2 weeks. TFTs were normal.

1. Is this presentation concerning?