Endocrine disease

Prepared by: Siti Norhaiza Binti Hadzir

Introduction• Endocrinology- the study of hormones,

which are secreted from specialized glands into the blood to influence the activity of cells at distance sites in the body.

Types of Hormones

• Peptides or proteins- hypothalamic factor (thyrotrophin releasing hormones), and pituitary gonadotropin.

• Amino acid derivatives- e.g thyroid hormones and adrenaline

• Steroid hormones- derivatives from cholesterol (e.g estrogen)

Measurement of Hormones

• Radioimmunoassay• Monoclonal antibodies

Endocrine Disease• Described as over or under secretion of

hormones• Failure of hormones responsiveness

OversecretionCushing’s disease where a pituitary adenoma secretes ACTH UnderscretionPrimary hypothyroidism where the thyroid gland is unable to make sufficient thyroid hormone despite continued stimulation by TSH

Failure of hormone responsivenessPseudohypoparathyroidism where pt become hypocalcemic despite elevated plasma PTH concentration because target organs lack a functioning receptor signaling mechanism

Examples of Endocrine Disease

The Pituitary Gland• The location• Anterior pituitary-hormone secreted• Posterior pituitary-hormone secreted• Hypersecretion-tumours (prolactin

secreting adenoma the most common)• Hypopituitarism-is uncommon; the clinical

presentation depends on the age, sex or the person.

Growth disorders• Growth in children can be divided into 3 i) rapid growth-1st 2 years –condition in

utero and nutrition ii) Steady growth-around 9 years-mainly

controlled by GH iii) puberty- sex hormones and GH-Other hormones involve in growth

Growth hormone insufficiency

• Is a rare cause of impaired physical growth.

• Test of GH insufficiency: - serum GH in response to exercise,

nocturnal sample - Stimulant (clonidine)• Treatment: genetically engineered GH for

children

Excessive growth• Extremely rapid linear growth (gigantism).

The condition is rare often due to pituitary tumor.

• Other causes; congenital adrenal hyperplasia, hyperthyroidism, inherited disorders.

• ↑GH later in life-Acromegaly due to pituitary adenoma

Diagnosis of Acromegaly• OGTT- a normal person will suppress GH

in plasma in response to glucose load.• Acromegaly-not suppress• ↑ IGF 1 • Treatment-surgery, radiotherapy, drugs

(octreotide-somastostatin analogue) and bromocriptine

The Thyroid Gland• The location• Thyroid hormone- thyroxine (T4) and tri-

iodothyronine (T3).• Most cells capable of taking up T4 and

deiodinating to the more biologically active T3.

• It is T3 which binds to receptors and triggers the end-organ effects of the thyroid hormones.

• T4 can be metabolized to reverse T3 (inactive)

Thyroid Hormone Action• Essential for the normal maturation and

metabolism of all the tissues in the body.

Plasma concentrationTotal (nmol/L) free (pmol/L)

Extent of protein binding

Half life (days)

T4 60-144 9.0-26.0 99.98 6-7

T3 1.0-2.9 3.0-9.0 99.66 1-1.5

Thyroid hormones in blood

Regulation of thyroid hormones

Hypothalamus

Anterior pituitary

Thyroid

TRH

TSH

T4 + T3

+

+

_

_

Thyroid Function Test• TSH (thyroid stimulating hormone)• Total T4 (bound hormone + free)• Free T4• TBG level• Free T3• Total T3 (bound hormone + free)• Titre of auto-antibodies to thyroid tissue

antigens

TRH test

• Involves intravenous injection of TRH and the measurement of pituitary TSH secreted in response to the stimulation.

• Purposes: i) Investigation of pituitary disorders ii) Investigation of hyperthyroidism

TSH

20 60Time (minutes)

TRH

TSH

20 60Time (minutes)

TRH

Normal response

Hyperthyroidism

Normal response

Secondary (pituitary) hypothyroid

Primary hypothyroid

Pituitary responses to TRH

Goitre• A goitre is an enlarged thyroid gland.• This may be associated with

hypofunction, hyperfunction or indeed normal concentrations of thyroid hormones in blood.

Hypothyroidism• 90% of cases of hypothyroidism occur as

a consequence of: - autoimmune destruction of the thyroid

gland (Hashimoto’s disease) - radioiodine or surgical treatment of

hyperthyroidism

Diagnosis of Hypothyroidism• Hypothyroidism is caused by a deficiency of thyroid hormones.• Primary hypothyroidism – failure of the

thyroid organ itself-elevated TSH concentration is diagnostic

• Secondary hypothyroidism-failure of pituitary to secrete TSH (less common).

• Treatment- thyroxine (tablet) therapy.

Non-thyroidal Illness• In systemic illness the normal regulation of

TSH, T4 and T3 secretion and subsequently metabolism of the thyroid hormones, is disturbed.

• ↑ T4 are converted to the reverse T3.• Reduction in thyroid hormone activity does

not result in an increased serum TSH concentration.

• TSH secretion is suppressed→ ↓ T4 and T3.• TBG decrease

Neonatal Hypothyroidism• The failure of the thyroid gland to develop

properly during early embryonic growth.• Children develop irreversible mental

retardation and characteristic feature of cretinism.

• The screening test- ↑ blood TSH concentration.

Hyperthyroidism• Hyperthyroidism can be result from: - Graves’ disease, diffuse toxic goitre - Toxic multinodular goitre - solitary toxic adenoma - thyroiditis - exogenously administered iodine and

iodine- containing drugs, e.g amiodarone - excessive T4 and T3 ingestion

Graves’ disease• An autoimmune disease in which

antibodies to the TSH receptor on the surface of the thyroid cells appear to mimic the action of the pituitary hormones.

• The normal regulatory controls on T4 synthesis and secretion are lacking.

• Pituitary secretion of TSH is completely inhibited by the ↑ conc. of thyroid hormones in the blood-eyelid retraction

Diagnosis

• Suppressed TSH concentration,↑ T4 and T3- primary hyperthyriodism

• Occasionally, biochemical confirmation of suspected hyperthyroidism will prove more difficult e.g in pregnancy.

Pt T4 nmol/L55-144)

T3 nmol/L(0.9-2.8)

TSH mU/L(0.35-5.0)

TBG mg/L (12-30)

Free T4 pmol/L(9-24)

Comment

1 130 2.0 3.4 25 18 Euthyroid

2 175 3.6 1.1 35 14 Euthyroid

3 190 5.0 <0.05 36 30 Hprthyroid

Thyroid hormone and binding protein results in pregnancy

Treatment• Anti-thyroid drugs (such as carbimazole

and propylthiouracil)- younger patient• Radioiodine-therapy with sodium I131is

commonly used in older pt. Most will require eventually require replacement thyroxine.

• Surgery-thyroidectomy

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