PITUITARY HYPERSECRETION SYNDROMES - Clinical features, Investigations

Acromegaly and gigantism

Pituitary growth hormone (GH) is secreted in a pulsatile fashion under the control of two hypothalamic hormones: GH releasing hormone (GHRH) stimu-lates and somatostatin inhibits secretion. Ghrelin, which is synthesized in the stomach, also increases GH secretion. GH exerts its activity indirectly through the induction of insulin-like growth factor (IGF-1), which is synthesized in the liver and other tissues, or directly on tissues such as liver, muscle, bone or fat to induce metabolic changes. Excessive GH production leads to gigantism in children (if acquired before fusion of the epiphyses of the long bones) and acromegaly in adults. Acromegaly is rare and caused by a benign pituitary GH-producing adenoma in almost all cases. Males and females are affected equally and the incidence is highest in middle age.

Clinical features

Symptoms and signs are shown in Figure 14.5. The clinical manifestations of acromegaly can be divided into those due to local tumour expansion with compression of surrounding structures - headaches, visual field loss and hypopituitarism - and those due to the metabolic effects of excess GH secre-tion. Old photographs of the patient may be useful to demonstrate a change in appearance and physical features. The onset is insidious with many years between onset of symptoms and diagnosis. Inadequately treated acromegaly is associated with an increased mortality rate, particularly from cardio-vascular disease and cancer.

Investigations

■ Plasma GH levels may exclude acromegaly if undetectable but a detect-able value is non-diagnostic.

■ Serum IGF-1 levels are almost always raised in acromegaly, and fluctuate less than those of GH. A normal serum IGF-1 concentration is strong evidence that the patient does not have acromegaly.

■ Glucose tolerance test is diagnostic. If the serum IGF-1 concentration is high or equivocal, serum GH should be measured 2 hours after an oral glucose load. In a positive test there is failure of the normal suppression of serum GH below 1 mU/L. Some show a paradoxical rise.

Fig. 14.5 The symptoms and signs of acromegaly. Bold type indicates signs of greater discriminant value.

■ MRI scan of the pituitary will almost always reveal the adenoma.

■ Visual field defects are common and should be plotted by perimetry.

■ Pituitary function testing usually shows partial or complete hypo-pituitarism (p. 613).

■ Serum prolactin (see hyperprolactinaemia).

Management

Treatment is indicated in all except the elderly or those with minimal abnor-malities. The aim of therapy is to reduce the serum IGF-1 concentration to within the age-adjusted reference range and lower the mean GH level to below 5 mU/L (<2.5 ng/L); this has been shown to reduce mortality to normal levels. Complete cure is often slow to achieve. Hypopituitarism should be corrected and diabetes and/or hypertension treated conventionally.

Transsphenoidal surgical resection is the treatment of choice. Access to the pituitary is achieved through the nasal cavity, sphenoid sinus and sphenoid bone. Complications are hypopituitarism, diabetes insipidus, CSF rhinorrhoea and infection.

Medical therapy is normally used when surgery alone has failed to reduce GH and IGF-I levels to normal. Somatostatin analogues (octreotide and lanreotide) and dopamine agonists (bromocriptine or cabergoline) inhibit GH secretion. The latter do not work as well as the somatostatin analogues but are given orally rather than by subcutaneous or intramuscular injection. Pegvisomant, a GH-receptor antagonist, is reserved for treatment of patients in whom IGF levels cannot be reduced to safe levels with somatostatin analogues alone.

External radiotherapy is used after surgical excision is incomplete and in combination with medical treatment as the response is slow (10 years or more). Stereotactic radiotherapy is used in some centres. It is a more accu-rate technique of tumour localization and irradiation and there is less radiation to normal brain tissue.

Hyperprolactinaemia

Prolactin release is under tonic inhibition by dopamine from the hypothalamus and factors that increase prolactin secretion (e.g. TRH) are probably of less relevance (Fig. 14.2). There is a physiological increase in serum prolactin during pregnancy, lactation and severe stress.

Aetiology

The commonest cause of pathological hyperprolactinaemia is a prolactin-secreting pituitary adenoma (prolactinoma). Other pituitary or hypothalamic tumours may also cause hyperprolactinaemia by interfering with dopamine inhibition of prolactin release. Other causes are primary hypothyroidism (high TRH levels stimulate prolactin), drugs (metoclopramide, phenothiazines, oes-trogens, cimetidine) polycystic ovary syndrome and acromegaly (co-secretion of prolactin with GH by the tumour). Mildly increased serum prolactin levels (400-600 mU/L) may be physiological and asymptomatic but higher levels require investigation. Levels above 5000 mU/L always imply a prolactin-secreting pituitary tumour.

Clinical features

Hyperprolactinaemia stimulates milk production in the breast producing galactorrhoea (spontaneous flow of milk unassociated with childbirth or breast feeding), and inhibits GnRH causing oligo- or amenorrhoea, decreased libido, subfertility and erectile dysfunction in men. If there is a pituitary tumour there may be headache and visual field defects.

Investigations

■ Serum prolactin level. At least three measurements should be taken. Further tests are appropriate after physiological and drug causes have been excluded

■ Thyroid function tests, as hypothyroidism is a cause of hyper-prolactinaemia

■ MRI of the pituitary

■ Pituitary function and visual fields (clinical assessment and perimetry) should be checked if a prolactinoma is the cause.

Management

Causative drugs should be withdrawn if possible and hypothyroidism treated. Hyperprolactinaemia is controlled with a dopamine agonist such as caber-goline 500 μg once or twice a week judged on clinical response and prolactin levels. Bromocriptine has been longer established and is preferred if preg-nancy is planned. Definitive therapy is controversial and depends on the size of the tumour, the patient's wish for fertility and the facilities available. Surgi-cal removal of the tumour via a transsphenoidal approach (see acromegaly), combined with post-operative radiotherapy for large tumours, often restores normoprolactinaemia but there is a high rate of late recurrence (50% at 5 years). Small tumours (microadenomas) in asymptomatic patients may only need observation.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

Gastroenterology and nutrition

4. Liver, biliary tract and pancreatic disease

Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

8. Water, electrolytes and acid–base balance

WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology