Endocrine disease

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Endocrine disease

• Prepared by Siti Norhaiza Binti Hadzir

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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.

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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)

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Measurement of Hormones

• Radioimmunoassay
• Monoclonal antibodies

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Endocrine Disease

• Described as over or under secretion of hormones
• Failure of hormones responsiveness

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Oversecretion Cushings disease where a pituitary adenoma secretes ACTH
Underscretion Primary hypothyroidism where the thyroid gland is unable to make sufficient thyroid hormone despite continued stimulation by TSH
Failure of hormone responsiveness Pseudohypoparathyroidism where pt become hypocalcemic despite elevated plasma PTH concentration because target organs lack a functioning receptor signaling mechanism
Examples of Endocrine Disease
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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.

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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

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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

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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

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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

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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)

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Thyroid Hormone Action

• Essential for the normal maturation and
  metabolism of all the tissues in the body.

Plasma concentration Total (nmol/L) free (pmol/L) Plasma concentration Total (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
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Regulation of thyroid hormones
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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

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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

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Pituitary responses to TRH
TRH
Primary hypothyroid
TSH
TSH
Normal response
Hyperthyroidism
Secondary (pituitary) hypothyroid
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60
Time (minutes)
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Goitre

• A goitre is an enlarged thyroid gland.
• This may be associated with hypofunction,
  hyperfunction or indeed normal concentrations of
  thyroid hormones in blood.

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Hypothyroidism

• 90 of cases of hypothyroidism occur as a
  consequence of
• - autoimmune destruction of the thyroid gland
  (Hashimotos disease)
• - radioiodine or surgical treatment of
  hyperthyroidism

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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.

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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

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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.

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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

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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

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Diagnosis

• Suppressed TSH concentration,? T4 and T3- primary
  hyperthyriodism
• Occasionally, biochemical confirmation of
  suspected hyperthyroidism will prove more
  difficult e.g in pregnancy.

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Pt T4 nmol/L 55-144) 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 lt0.05 36 30 Hprthyroid
Thyroid hormone and binding protein results in
pregnancy
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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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Thank you