A4- Thyroid and Adrenal Disease

Question 1

Answer 1

Question 2

The lobes of the thyroid contain _______ , the functional units of the thyroid gland.
•Interspersed between the follicles are __ cells, which secrete calcitonin.

Answer 2

The lobes of the thyroid contain follicles, the functional units of the thyroid gland.
•Interspersed between the follicles are C cells, which secrete calcitonin.

Question 3

• Follicles consist of a layer of epithelium
• Central cavities containing ____
• Major constituent of colloid is the large _________, ________
• Follicular cells are ____ dependent

Answer 3

• Follicles consist of a layer of epithelium
• Central cavities containing colloid
• Major constituent of colloid is the large glycoprotein, thyroglobulin
• Follicular cells are TSH dependent

Question 4

What is the Synthesis, Storage and Secretion of thyroid hormones

Answer 4

• Tyrosine and iodine are essential for synthesis of thyroid hormones.
• Both are taken up by the blood
• Tyrosine is synthesised by the body (in the thyroglobulin).
• Iodine is a dietary essential.
• Other endocrine glands secretes their hormones once produced, the thyroid gland stores considerable amount of the thyroid hormones in the colloid until needed.

Question 5

Steps in biosynthesis, storage
and secretion of thyroid
hormones

Answer 5

• Thyroglobulin produced by follicular cells and released into colloid in follicle lumen by exocytosis
• Iodide (I-) uptake by follicular cell from the blood, oxidation (I) and transferred to colloid
• Attachments of iodine into tyrosine residues on thyroglobulin in colloid forming di-and mono-iodotyrosine (DIT and MIT)
• Coupling processes between the iodinated tyrosine molecules to form T4 (2DIT) and T3 (DIT + MIT)

• Secretion (upon stimulation) of T4 and T3
occurs by endocytosis, fusion with a lysosome, uncoupling of T4 and T3 and diffusion out of the follicular cell into the blood and onto peripheral tissues

Question 6

Explain Thyroid hormone
biosynthesis

Answer 6

• Approximately, 90% of the hormones released from the thyroid gland initially appear in the form of T4.
• However, a majority of the T4 that is secreted from the thyroid gland is subsequently converted to T3.
• T3 is formed from monodeiodination of T4 in the thyroid and in peripheral tissues.
• T3 is 4 times more potent in its biologic form than T4 and is the major hormone that interacts with the target cells.

Question 7

Clinical features of thyrotoxicosis?

Answer 7

• Weight loss
• Sympathetic overactivity
• Goitre
• Thyroid eye signs

Question 8

Causes of thyrotoxicosis?

Answer 8

• Graves’ disease
• Toxic adenoma
• Multi-nodular goitre

Question 9

Medical and surgical management?

Answer 9

Medical
• Anti-thyroid medication (carbimazole, PTU)
• Beta-blockade
Surgical
• Sub-total thyroidectomy
• Total thyroidectomy
Radioiodine

Question 10

Symptoms of Hypothyroidism

Answer 10

• Fatigue
• Lethargy
• Weakness
• Cold intolerance
• Mental slowness
• Depression
• Dry skin
• Constipation
• Muscle cramps
• Irregular menses
• Infertility
• Mild weight gain
• Fluid retention
• Hoarseness

Question 11

Signs of Hypothyroidism

Answer 11

• Goitre (primary hypothyroidism only)
• Bradycardia
• Non-pitting edema
• Dry skin
• Delayed relaxation
• Hypertension
• Slow speech
• Slow movements
• Voice hoarseness

Question 12

Causes of Hypothyroidism

Answer 12

• Autoimmune (Hashimoto’s) thyroiditis
• Atrophic (common in elderly)
• Iodine 131 treatment
• pituitary

Question 13

Antibodies in hypothyroidism

Answer 13

Anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg )
antibodies (Hashimoto’s)

Question 14

Hypothyroidism: Therapy

what do you use?

Answer 14

L-Thyroxine (levothyroxine; T4)

Goals of replacement
• Alleviate symptoms
• Titrate T4 intake to normalize TSH (primary
hypothyroidism) or free T4 (secondary and tertiary
hypothyroidism)

Question 15

What is Thyroid Storm

Answer 15

Thyroid storm can be thought of as a “hyper-adrenergic” state, and many
of the symptoms of thyroid storm (hypertension, tachycardia,
palpitations, agitation, etc.) are best controlled with beta-blockade.

Question 16

Clinical Presentation of thyroid storm

Answer 16

Anxiety, restlessness, agitation, psychosis, confusion, obtundation, coma.
• Thyrotoxic myopathy
• Cardiovascular abnormalities include
-tachycardia, AF
-CHF
• GI symptoms
-Pre-event severe weight loss
-Hyperdefecation, diarrhea
-Anorexia, N/V

Question 17

Treatment of Thyroid Storm

Answer 17

Generally supportive:
• ABC’s, intubation for comatose patient
• IV fluids: Fluid resuscitation may be required in those with
volume depletion.
• Antipyretics prn
• Treat congestive failure/pulmonary edema per protocol: Diuretics
or digoxin may be required in patients with cardiac manifestations
• Treatment of any underlying precipitating factors

Question 18

Management of thyroid storm
Thyroid based therapies

Answer 18

1. Beta-blockade
2. Inhibition of thyroid hormone synthesis: anti-thyroid drugs (PTU)
3. Inhibition of thyroid hormone release (Lugol’siodine)
4. Block peripheral conversion of T4 to T3:
   • Dexamethasone 10 mg every 6 hours or hydrocortisone 100 mg
   every 8 hours.

Question 19

What is hypothyroidsima?

Answer 19

Hypothyroidism Chronic systemic disorder characterized by progressive slowing
of all bodily functions because of thyroid hormone deficiency.

❖Primary Intrinsic failure of the thyroid gland
❖Secondary Disease of the hypothalamus and/or pituitary gland

Question 20

Myxedema Refers to?

Answer 20

severe hypothyroidism. Non-pitting, dry, waxy swelling of
the skin and SC tissue

Question 21

What is

Myxedema Coma

Answer 21

Rare complication of hypothyroidism. Usually occurs in elderly
women, during the winter as a result of stress.

Question 22

Myxoedema Coma
Clinical features

Answer 22

Altered mental status, confusion, pyschosis
Coma, 25 % seizures
Hypothermia: temp <35 oC
Bradycardia
Respiratory failure with CO2
retention
Hypoglycaemia

Question 23

Cause of Myxoedema Coma

Answer 23

Drugs: sedatives, tranquillizers
Infection
Cerebrovascular accident
Trauma

Question 24

Myxoedema Coma
Investigations

Answer 24

Hyponatraemia
Hypoglycaemia
Anaemia
Raised CK
High TSH/low T4
Cortisol
↓pO2 ↑ pCO2
Blood and urine cultures

Question 25

Myxoedema Coma Treatment

Answer 25

Rewarm (space blanket) Correct BP Adequate ventilation Broad spectrum antibiotics Hydrocortisone 100mg IV tds IV T3 5-20 mcg daily for 3 days T4 25mcg daily

Question 26

Adrenal cortical layers and what do they secrete?

Answer 26

Question 27

Adrenal Cortex: Steroid Hormone Production

Answer 27

Question 28

Presentation of adrenal disease

Answer 28

**•Hypofunction •Hyperfunction**: • Cushings’ syndrome • Conn’s syndrome • Androgenisation **•Adrenal nodules/adenomas/masses**

Question 29

Adrenal Deficicency: Causes

Answer 29

**• Primary adrenal insufficiency** –chronic: undiagnosed or established and subjected to a major physiologic stress –acute: bilateral adrenal hemorrhage, sepsis (Waterhouse-Friederichsensyndrome) **•Secondary or tertiary adrenal insufficiency** –Less common as renin-angiotensin-aldosterone axis intact **• Exogenous glucocorticoids**

Question 30

When is it Adrenal deficiency/crisis

Answer 30

* Low Na * High K * Raised urea * Low glucose * Low random cortisol * Synacthen test

Question 31

Causes of Cushing’s syndrome Endogenous Causes vs Exogenous Causes

Answer 31

Endogenous Causes • 65% = pituitary • 25% = adrenals • 10% = ectopic source (small cell lung ca), non-pituitary, ACTH producing tumour Exogenous Causes • Iatrogenic Steroids (Asthma, RA, palliative) **Higher incidence in people with: DM, HTN, Obesity and Osteoporosis**

Question 32

Symptoms & Signs Cushings

Answer 32

Question 33

Differential Diagnosis: It’s not always Cushing’s Pseudo-Cushing’s

Answer 33

* Chronic severe anxiety and/or depression * Prolonged excess alcohol consumption * Obesity * Poorly controlled diabetes * HIV infection

Question 34

Diagnosis of Cushing’s Syndrome

Answer 34

•Obtain a careful history to exclude exogenous glucocorticoid use. •Perform at least two first-line biochemical tests to obtain the diagnosis: • Urine free cortisol (UFC) (at least two measurements) • 1-mg overnight Dexamethasone Suppression Test (ODST) • Longer low-dose Dexamethasone Suppression Test (LDDST) (2 mg/d for 48 h)

Question 35

Dexamethasone Suppression Test Explain results

Answer 35

Overnight Low dose = Baseline reading, Dex 1mg given at 11pm, measure cortisol at 9am • If cortisol low (\<50nmol/L) = normal • If cortisol high (\>50nmol/L) = investigate further –Cushing’s syndrome

Question 36

Ix for cushings?

Answer 36

If any positive - imaging: •CT of adrenals •MRI pituitary •IPSS (inferior petrosal sinus sampling) If ?ectopic: •CXR •CT =/- MRI of neck, thorax, abdomen •Functional imaging

Question 37

Management for cushings

Answer 37

Drug therapy remains very important for normalising cortisol levels. Medical treatment can also be used in patients who are unwilling or unfit for surgery. • Metyrapone, ketoconazole, and mitotane can all be used to lower cortisol by directly inhibiting synthesis and secretion in the adrenal gland. • The treatment of choice in most patients is surgical but the metabolic consequences increase the risk of surgery: • increased tissue fragility • poor wound healing • HTN and DM

Question 38

Surgical Treatment for cushings?

Answer 38

Pituitary tumours: • trans-sphenoidal microsurgery. • Radiation therapy may be used as an adjunct for patients who are not cured. • Bilateral adrenalectomy may be necessary with severe hypercortisolaemia. Adrenocortical tumours: • require surgical removal –can develop Nelsons Syndrome Removal of neoplastic tissue is indicated for ectopic ACTH production • Metastatic spread makes a surgical cure unlikely or impossible. • Bilateral adrenalectomy may be necessary with severe hypercortisolaemia.