Endocrine Diseases

Most endocrine glands are controlled by hormones produced in the anterior pituitary, themselves under control of substances produced in the hypothalamus. A variety of stimuli control pituitary and hypothalamic hormone release, especially feedback control from hormone levels from the target glands. Levels of pituitary hormones show a circadian rhythm.

Endocrine diseases can be broadly classified as:

Hormone excess

– primary overproduction by gland

– secondary to excessive trophic hormone

Hormone deficiency

– primary underproduction by gland, e.g. due to inflammation, post surgery

– secondary to insufficient trophic hormones

Hormone resistance

– target organ resistance

– failure to activate hormone

Effects of non-functioning tumours

– local pressure and invasion

– metastatic disease.

Pituitary Gland

The pituitary has two parts; the anterior (adenohypophysis) and the posterior (neurohypophysis).

Anterior Pituitary (Adenohypophysis)

The blood supply is via a portal system from the hypothalamus bringing peptides which stimulate or inhibit pituitary hormone production. The cells producing each hormone can be identified by immunohistochemistry (for stored hormone) or in situ hybridisation (for mRNA).

Posterior Pituitary

This is composed of neural tissue and secretes two hormones made in the hypothalamus (oxytocin and antidiuretic hormone).

Note

1. ACTH (39 amino acids long) is synthesised as part of a large molecule proopiomelanocortin (POMC) from which other molecules including melanocyte stimulating hormone (MSH) are derived.

2. Hypothalamic releasing hormones have been found for TSH (TRH), LH/FSH (GnRH), ACTH (CRH) and GH (GHRH); somatostatin inhibits release of GH.

Pituitary Hyperfunction

In most cases, this is associated with pituitary adenoma.

Pituitary adenomas are divided on the basis of size into macroadenomas (>10 mm) and microadenomas (<10 mm).

Small tumours present only if they produce excess hormones, while larger tumours may cause pressure effects (e.g. on optic chiasma, page 141) or with hypopituitarism due to destruction of normal pituitary. Occasionally haemorrhage into a pituitary adenoma causes raised intracranial pressure (pituitary apoplexy).

Hyperprolactinaemia

Prolactin secreting adenomas are often small. They cause amenorrhoea, infertility and occasionally galactorrhoea in younger women, but are usually asymptomatic in older women and men.

CUSHING’S SYNDROME is frequently due to an ACTH secreting adenoma when it is known as Cushing’s disease. The effects are described on p.634.

Hypopituitarism

Failure of pituitary secretion may affect one or several hormones. Causes include:

(a) Pituitary tumour.

(b) Pituitary surgery/cranial irradiation.

(c) Head injury.

(d) Hypothalamic dysfunction, including craniopharyngioma.

(e) Sheehan’s syndrome: is used as an example. It is still an important cause where obstetric services are poor.

This syndrome occurs in women and is due to ischaemic necrosis of the pituitary following post-partum haemorrhage. The normally low pressure in the pituitary portal vascular supply increases the susceptibility of the gland. The results vary with the extent of necrosis and may include the following:

In time, the peripheral endocrine organs – thyroid, adrenals, ovaries – show atrophy.

In childhood, growth hormone deficiency is a cause of dwarfism. Skeletal growth is diminished with retarded sexual development but normal intelligence. Hypothalamic GHRH deficiency may be responsible.

Note: Some individuals treated with human growth hormone have developed Creutzfeld–Jacob disease (p.555).

In adults, GH deficiency leads to lethargy, diminished muscle mass, obesity and premature atheroma.

Inflammation of the Pituitary Gland

Apart from involvement in acute meningitis, inflammation, acute or chronic, is uncommon. Tuberculosis, syphilis and sarcoidosis all rarely occur.

Thyroid Gland – Underactivity

The thyroid gland is under the control of the pituitary thyroid-stimulating hormone (TSH p.623).

T₄ can be regarded as a prohormone, which is converted to active T₃ by deiodination in liver, muscle and kidney.

Thyroid Hypofunction

Insufficient thyroid hormone is produced, resulting in myxoedema in adults and cretinism in children.

Adults – Myxoedema

Clinical signs

Basal metabolic rate reduced, weight gain.

Body temperature falls, cold intolerance.

Lethargy and apathy.

Appetite reduced.

Constipation.

Respiratory and heart rates reduced.

Diminished libido.

Lack of ovulation.

Skin thickened, non-pitting oedema due to increase in mucopolysaccharide ground substance.

Hair brittle, dry and falls out.

Blood cholesterol is raised.

TSH secretion is increased.

T₃ and T₄ blood levels low.

Causes

1. Autoimmune thyroiditis

(a) Atrophic form – so-called primary myxoedema – the commonest cause of hypothyroidism

(b) Hashimoto’s disease.

2. Severe iodine deficiency.

3. Dyshormonogenesis – inborn errors in the formation of thyroid hormones.

4. Anti-thyroid drugs, e.g. lithium

5. Excessive surgical resection of thyroid gland.

6. Treatment with radioiodine.

7. Hypopituitarism → reduced TSH.

Pathological changes in primary myxoedema

Children – Cretinism

Infants normal at birth, but abnormality appears within weeks.

Clinical Signs

Changes are irreversible unless treatment is given early. Two forms are recognised:

(1) endemic and

(2) sporadic cretinism.

Thyroid Gland – Overactivity

Endemic Cretinism

This occurs in districts where goitre is common due to iodine deficiency. The infantile thyroid is usually enlarged and nodular. Histologically, there are hyperplastic foci containing colloid which compress the intervening tissue. The incidence of this disorder has reduced following addition of iodine to salt.

Sporadic Cretinism

This is usually due to congenital hypoplasia or absence of the thyroid. Deaf mutism is often present.

Dyshormonogenesis

In this condition, cretinism is due to a congenital familial recessive enzyme defect leading to inability to complete the formation of thyroid hormone. The thyroid gland is enlarged and shows epithelial hyperplasia. TSH is increased.

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