ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL

Blood pressure is determined by cardiac output and peripheral resistance, and an increase in blood pressure may be due to an increase in one or both of these. In a few patients an underlying cause can be identified for hyperten-sion including endocrine causes (Table 14.17). However, in 90% of cases no cause can be found and patients are said to have essential hypertension. Young patients (<35 years), those with an abnormal baseline screening test (p. 482) or patients with malignant hypertension or hypertension resistant to conventional treatment (e.g. more than three drugs) should be screened for secondary causes.

The renin-angiotensin system

The renin-angiotensin-aldosterone system is illustrated in Figure 14.11. Angiotensin, an a2-globulin of hepatic origin, circulates in plasma. The enzyme renin is secreted by the kidney in response to decreased renal perfusion pressure or flow; it cleaves the decapeptide angiotensin I from angiotensinogen. Angiotensin I is inactive but is further cleaved by converting enzyme (present in lung and vascular endothelium) into the active peptide, angiotensin II, which has two major actions:

■ It causes powerful vasoconstriction (within seconds)

■ It stimulates the adrenal zona glomerulosa to increase aldosterone production.

Table 14.17 Endocrine causes of hypertension

Excessive production of

Renin

Renal artery stenosis, renin-secreting tumours

Aldosterone

Adrenal adenoma, adrenal hyperplasia

Mineralocorticoids

Cushing’s syndrome (cortisol is a weak mineralocorticoid)

Catecholamines

Phaeochromocytoma

Growth hormone

Acromegaly

Oral contraceptive pill (mechanism unclear)

Aldosterone causes sodium retention and urinary potassium loss (hours to days). This combination of changes leads to an increase in blood pressure, and the stimulus to renin production is reduced. Sodium deprivation or urinary loss also increases renin production, whereas dietary sodium excess will suppress production.

Primary hyperaldosteronism

This is a rare condition (<1% of all hypertension) where high aldosterone levels exist independently of the renin-angiotensin system. It is caused by an adrenal adenoma secreting aldosterone (Conn's syndrome) or by bilateral adrenal hyperplasia.

Clinical features

The major function of aldosterone is to cause an exchange transport of sodium and potassium in the distal renal tubule; that is, absorption of sodium (and hence water) and excretion of potassium. Hyperaldosteronism causes hypertension, resulting from expansion of intravascular volume, and hypokalaemia.

Investigations

■ Hypokalaemia is often but not always present.

■ Plasma aldosterone : renin ratio (ARR) is the initial screening test for primary hyperaldosteronism. Spirinolactone and eplerenone should be stopped 6 weeks before the test. A raised ratio does not confirm the diagnosis and further tests are then indicated to demonstrate inapprop-riate aldosterone secretion.

■ The diagnosis is made by demonstrating increased plasma aldosterone levels that are not suppressed with 0.9% saline infusion (2 L over 4 h) or fludrocortisone administration (a mineralocorticoid).

■ CT or MRI of the adrenals is used to differentiate adenomas from hyperplasia.

Management

An adenoma is removed surgically. Hypertension resulting from hyperplasia is treated with the aldosterone antagonist spironolactone or eplerenone (p. 350).

Phaeochromocytoma

This is a rare (0.1% of hypertension) catecholamine-producing tumour of the sympathetic nervous system; 10% are malignant and 10% occur outside the adrenal gland. Some are associated with multiple endocrine neoplasia (see below).

Clinical features

Symptoms may be episodic and include headache, palpitations, sweating, anxiety, nausea and weight loss. The signs, which may also be intermittent, include hypertension, tachycardia and pallor. There may be hyperglycaemia.

Investigations

■ A 24-hour urine collection for urinary catecholamines and metabolites (metanephrines) is a useful screening test; normal levels on three sepa-rate collections virtually exclude the diagnosis.

■ Raised levels of plasma catecholamines confirm the diagnosis.

■ Plasma chromogranin A (a storage vesicle protein) is raised.

■ CT/MRI is useful to localize the tumour.

■ Scintigraphy using meta-[131I]iodobenzylguanidine (mIBG), which is selectively taken up by adrenergic cells, is useful with extra-adrenal tumours.

Management

The treatment of choice is surgical excision of the tumour under a- and p-blockade using phenoxybenzamine and propranolol, which is started before the operation. These drugs can also be used long term where opera-tion is not possible.

Multiple endocrine neoplasia

The multiple endocrine neoplasia syndromes (MEN) are rare, but recogni-tion is important for both treatment and evaluation of family members -inheritance is autosomal dominant. MEN is the name given to the synchronous or metachronous (i.e. occurring at different times) occurrence of tumours involving a number of endocrine glands (Table 14.18). MEN type 1 is due to a mutation in the menin gene on chromosome 11; the normal protein product of this gene acts as a tumour suppressor. The genetic abnormality in MEN 2 lies within the Ret proto-oncogene on chro-mosome 10; the gene product plays a role in central and peripheral nerve development and function. Management involves surgical excision of the tumours if possible. Asymptomatic family members should be screened by measurement of serum calcium in MEN 1 (due to the high penetrance of hyperparathyroidism) and by genetic testing for Ret mutations in MEN 2 families. In a patient known to have MEN, constant surveillance is required for additional features of the syndrome, which may develop many years after the initial presentation.

Table 14.18 Multiple endocrine neoplasia (MEN) syndrome

Organ

Frequency

Tumours/clinical manifestations

Type 1

Functioning adenomas in:

Parathyroid

95%

Hypercalcaemia

Pituitary

30%

Prolactinoma, acromegaly, Cushing’s disease

Enteropancreatic tumours

60%

Gastrinoma, insulinoma, glucagonoma, VlPoma

Other:

Foregut carcinoids

10%

Thymic, bronchial gastric

Adrenal cortex adenomas

25%

Non-functional tumours

Cutaneous tumours

60%

Angioíibromas, collagenomas, lipomas

Type 2A

Medullary thyroid carcinoma

95%

Thyroid mass, diarrhoea, raised plasma calcitonin

Adrenal medulla

40%

Phaeochromocytoma

Parathyroid hyperplasia

10%

Hypercalcaemia

Type 2B

Like type 2A (but not parathyroid disease) with a typical phenotypic appearance: slim body habitus and neuromas of lips, tongue, and gastrointestinal tract

VIP, vasoactive intestinal polypeptide

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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

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

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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

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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
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HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

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Dermatology

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