Endocrine disease

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15 Endocrine disease

Pituitary disorders

The hypothalamus regulates many vital functions, including appetite, thirst, thermal regulation and sleep. It controls pituitary function by stimulatory and inhibitory factors and by hormones released via the pituitary stalk.

Many hormones are released in either a pulsatile or a circadian pattern and are regulated by feedback systems. Endocrine tests on serum/plasma take advantage of natural peaks and troughs in secretion, while stimulatory or suppression tests are used to investigate hormone deficiency or excess further.

Pituitary tumours

Pituitary tumours are a relatively common incidental finding in the general population; only a minority cause clinical problems, either due to uncontrolled secretion of pituitary hormones, or due to local compression effects. Tumours may be small (micro-adenomas, < 10 mm diameter) or large (macro-adenomas, > 10 mm) and the vast majority are benign.

Treatment

The aim of therapy is to:

Treatment (Table 15.1) options include surgery, radiotherapy and medical therapy, depending on the aetiology of the pituitary mass. Post-operative radiotherapy is used if significant tumour bulk remains after surgery or the underlying disease is still active. Radiotherapy results in a gradual decline of residual pituitary function over many years and must be monitored.

Table 15.1 Comparison of primary treatment for pituitary tumours

Treatment method Advantages Disadvantages
Surgical
Trans-sphenoidal adenomectomy or hypophysectomy Relatively minor procedure
Potentially curative for micro- and smaller macro-adenomas
Some extrasellar extensions may not be accessible
Risk of CSF leakage and meningitis
Trans-frontal Good access to suprasellar region Major procedure; danger of frontal lobe damage
High chance of subsequent hypopituitarism
Radiotherapy
External (40–50 Gy) Non-invasive
Reduces recurrence rate after surgery
Slow action, often over many years
Not always effective
Possible late risk of tumour induction
Stereotactic Precise administration of dose to lesion Long-term follow-up data limited
Yttrium implantation High local dose Only used in few centres
Medical
Dopamine agonist (e.g. bromocriptine) Non-invasive; reversible Usually not curative; significant side-effects in minority
Somatostatin analogue (octreotide) Non-invasive; reversible Usually not curative; expensive
Growth hormone receptor antagonist (pegvisomant) Highly selective Usually not curative; very expensive

Hypopituitarism

Compression of the pituitary gland by a mass lesion results in progressive loss of function. Growth hormone and gonadotrophins are usually the first hormones to be affected, followed by TSH and finally ACTH (panhypopituitarism). Prolactin levels may rise due to compression of the pituitary stalk and loss of dopaminergic inhibitory control.

Investigation of pituitary function

Basal serum investigations

Dynamic tests

Management

Options for hormone replacement regimes are given in Table 15.2.

Table 15.2 Replacement therapy for hypopituitarism

Axis Usual replacement therapies
Adrenal Hydrocortisone 15–40 mg daily (starting dose 10 mg on rising/5 mg lunchtime/5 mg evening)
(Normally no need for mineralocorticoid replacement)
Thyroid Levothyroxine 100–150 mcg daily
Gonadal  
Male Testosterone IM, orally, transdermally or implant
Female Cyclical oestrogen/progestogen orally or as patch
Fertility HCG plus FSH (purified or recombinant) or pulsatile GnRH to produce testicular development, spermatogenesis or ovulation
Growth Recombinant human growth hormone used routinely to achieve normal growth in children
Also advocated for replacement therapy in adults where growth hormone has effects on muscle mass and well-being
Thirst Desmopressin 10–20 mcg 1–3 times daily by nasal spray or orally 100–200 mcg 3 times daily
Carbamazepine, thiazides and chlorpropamide are very occasionally used in mild diabetes insipidus
Breast (prolactin inhibition) Dopamine agonist (e.g. cabergoline 500 mcg weekly)

FSH, follicle-stimulating hormone; GnRH, gonadotrophin-releasing hormone; HCG, human chorionic gonadotrophin.

Thyroid disorders

The thyroid hormones, T4 and T3, are produced within the thyroid gland. Synthesis and release are stimulated by TSH, which is released from the pituitary gland in response to the hypothalamic factor, TRH (thyrotrophin-releasing hormone) (Fig. 15.1). Predominantly, T4 is produced, but this is converted in the peripheral tissues (liver, kidney, muscle) to the more active T3. More than 99% of T4 and T3 circulate bound to plasma proteins, mainly thyroid-binding globulin (TBG).

Diagnosis of thyroid disease includes the clinical features, together with measurement of plasma TSH and thyroid hormones T4 and T3.

Hypothyroidism

Hyperthyroidism

Hyperthyroidism is common and is characterized by high levels of T3 and T4 with suppression of plasma TSH. Nearly all cases are due to intrinsic thyroid disease.

Clinical features

Weight loss, increased appetite, irritability, tremor and heat intolerance are classic symptoms of hyperthyroidism. A tachycardia with or without atrial fibrillation is a frequent presentation, particularly in the elderly. A goitre with a bruit occurs. Apathetic thyrotoxicosis occurs in elderly patients, in whom the clinical picture is more like hypothyroidism with few clinical signs of thyrotoxicosis.

Treatment (Table 15.3)

Propranolol is used to gain rapid control of thyrotoxic symptoms. High doses (up to 160 mg 3 times daily) may be required due to increased metabolism of the drug.

There are three main options and preference varies widely.

Antithyroid medications. Carbimazole initially 20 mg 3 times daily is the drug most commonly used in the UK. Its active metabolite, methimazole, is used preferentially in the USA. These drugs inhibit the formation of thyroid hormone and the clinical benefits can take up to 2 weeks to become apparent. Propylthiouracil 300–600 mg daily is occasionally used as an alternative, particularly during pregnancy and breast feeding. It has additional theoretical benefits in that it prevents peripheral conversion of T4 to T3. The major side-effect of these medications is agranulocytosis, and prior to commencing treatment patients should be told to seek medical help should severe mouth ulcers, sore throat or febrile illness occur. A white blood cell count is then urgently required. Antithyroid medication also reduces the immune processes and thus a trial of therapy for up to 18–24 months may result in remission of autoimmune thyrotoxicosis. Initially doses of antithyroid medications are high. There is then the option of dose reduction as the thyroid tests normalize, or the option of adding thyroxine to high-dose anti-thyroid medication (‘block and replace regimen’). A fall of T4 and T3 in response to treatment guides initial dose reductions (gradually reduce dose to 5 mg over 6 to 24 months if hyperthyroidism is controlled), as the TSH may remain suppressed for some time. Antithyroid medications will never lead to remission in toxic nodular disease, and while long-term antithyroid medications are an option, more definitive treatment is required.