Endocrine disease

The endocrine system refers to glands that release hormones (chemical messengers) directly into the blood stream through which they travel to affect distant organs. Most hormones are secreted into the systemic circulation but hypothalamic releasing hormones are released into the pituitary portal system to reach the pituitary gland. Exocrine glands, in contrast, secrete their prod-ucts into ducts to reach their target. The pancreas has both endocrine (glu-cagon, insulin and somatostatin secreted by a, p and s cells respectively in the islets of Langerhans) and exocrine (digestive enzymes such as amylase secreted by acinar cells into the small intestine via the pancreatic duct) functions.

Most hormones travel in the circulation bound to proteins but it is only the free hormone that is biologically active. However, concentrations of binding proteins may be altered by disease or drugs and affect the amount of free hormone. Once at the target organ, hormones act by binding to specific receptors either on the target cell surface or within the cell (e.g. thyroid hormones, cortisol). The result is a cascade of intra-cellular reactions within the target cell which frequently amplifies the original stimulus and leads ultimately to a response by the target cell. Some hormones, e.g. growth hormone and thyroxine, act on most tissues of the body. Others act on only one tissue, e.g. thyroid-stimulating hormone (TSH) and adrenocorticotrophin (ACTH) are secreted by the anterior pituitary and have specific target tissues, namely the thyroid gland and the adrenal cortex. Endocrine disease can involve all of the endocrine glands of the body as illustrated in Figure 14.1.

COMMON PRESENTING SYMPTOMS IN ENDOCRINE DISEASE

Hormones produce widespread effects upon the body and states of deficiency or excess typically present with symptoms that are generalized rather than focused on the anatomical location of the gland. Many of the presenting symptoms of endocrine disease are vague and non-specific, e.g. tiredness in hypothyroidism, weight loss or weight gain, increased thirst, anorexia and

malaise in Addison's disease, and the differential diagnosis is often wide. Precocious puberty or delayed puberty is often the result of a familial ten-dency, although hypothalamic-pituitary disease may present in this way, and endocrine investigations are usually undertaken.

The hypothalamus and pituitary

The hypothalamus contains many vital centres for functions such as appetite, thirst, thermal regulation and sleep/waking. It also plays a role in circadian rhythm, the menstrual cycle, stress and mood. Releasing factors produced in the hypothalamus reach the pituitary via the portal system, which runs down the pituitary stalk. These releasing factors stimulate or inhibit the production of hormones from distinct cell types (e.g. production of growth hormone by acidophils), each of which secretes a specific hormone in response to unique hypothalamic stimulatory or inhibitory hormones. The anterior pituitary hormones, in turn, stimulate the peripheral glands and tissues. This pattern is illustrated in Figure 14.2. The posterior pituitary acts as a storage organ for antidiuretic hormone (ADH, also called vasopressin) and oxytocin, which are synthesized in the supraoptic and paraventricular nuclei in the anterior hypothalamus and pass to the posterior pituitary along a single axon in the pituitary stalk. ADH is discussed on page 645; oxytocin produces milk ejection and uterine myometrial contractions.

Control and feedback

Most hormone systems are controlled by some form of feedback; an example is the hypothalamic-pituitary-thyroid axis (Fig. 14.3). Thyrotrophin-releasing hormone (TRH), secreted in the hypothalamus, stimulates TSH secretion from the anterior pituitary into the systemic circulation. TSH in turn, stimulates the synthesis and release of thyroid hormones from the thyroid gland and the peripheral conversion of T4 to T3, (the more active hormone). Circulating thyroid hormone feeds back on the pituitary, and possibly the hypothalamus, to suppress the production of TSH and TRH, and hence bring about a fall in thyroid hormone secretion. This is known as a ‘negative feedback' system and represents the most common mechanism for regulation of circulating hormone levels. Conversely, a fall in thyroid hormone secretion (e.g. after thyroidectomy) leads to increased secretion of TSH and TRH. A patient with a hormone-producing tumour fails to show negative feedback and this is useful in diagnosis, e.g. the dexamethasone suppression test in the diagnosis of Cushing's syndrome (see later).

Other factors influencing hormone secretion are circadian rhythms (e.g. cortisol levels are highest in the early morning), physiological stress/acute illness (producing rapid increases in cortisol, growth hormone, prolactin and adrenaline (epinephrine)) and feeding and fasting (insulin is increased and growth hormone decreased after ingestion of food).

Fig. 14.3 The hypothalamic-pituitary-thyroid feedback system.

Fig. 14.3 The hypothalamic–pituitary–thyroid feedback system.

Pituitary space-occupying lesions and tumours

Benign pituitary tumours (adenomas) are the most common form of pituitary disease. Symptoms arise as a result of inadequate hormone production, excess hormone secretion, or from local effects of a tumour.

Underproduction

This is the result of disease at either a hypothalamic or a pituitary level, and it results in the clinical features of hypopituitarism (p. 613).

Overproduction

There are three major conditions usually caused by secretion from pituitary adenomas:

■ Growth hormone (GH) excess - causing acromegaly in adults and gigant-ism in children

■ Prolactin excess - causing galactorrhoea or clinically silent

■ Excess ACTH secretion - Cushing's disease and Nelson's syndrome.

Fig. 14.4 A sagittal section of the pituitary fossa showing the anatomical relationships.The cavernous sinus lies lateral to the pituitary and is seen on a coronal view.

Local effects

Local pressure on, or infiltration of, surrounding structures (Fig. 14.4):

■ Optic chiasm causing a bitemporal hemianopia (p. 726)

■ Cavernous sinus with III, IV and VI cranial nerve lesions

■ Bony structures and the meninges causing headache

■ Hypothalamic centres: obesity, altered appetite and thirst, precocious puberty in children

■ The ventricles, causing interruption of cerebrospinal fluid flow and hydrocephalus.

Investigation

The purpose of investigation of a suspected pituitary mass is to confirm the diagnosis (usually by MRI of the pituitary), to determine if there is local pressure and infiltration (by clinical examination and plotting the visual fields using perimetry), and to assess for hormone overproduction (discussed under the respective diseases) and/or underproduction (see hypopituitarism). Most mass lesions of the pituitary are adenomas. The history, physical examination and MRI imaging help to exclude other rarer causes, e.g. craniopharyngioma, secondary deposits, sarcoidosis, Wegener's granuloma and cystic lesions.

Hypopituitarism

Deficiency of hypothalamic-releasing hormones or pituitary hormones may be either selective or multiple. Multiple deficiencies usually result from tumour growth or other destructive lesions. There is a progressive loss of function, with GH and gonadotrophins (FSH and LH) being affected first and TSH and ACTH last. Rather than prolactin deficiency, hyperprolactinaemia occurs relatively early because of loss of tonic inhibitory control by dopamine (see Fig. 14.2). Panhypopituitarism is a deficiency of all anterior pituitary hormones. Vasopressin and oxytocin secretion will only be affected if the hypothalamus is involved by either hypothalamic tumour or by extension of a pituitary lesion.

Aetiology

The commonest cause of hypopituitarism is a pituitary or hypothalamic tumour, or treatment of the tumour by surgical removal or radiotherapy (Table 14.1).

Table 14.1 Causes of hypopituitarism

Neoplastic

Traumatic

Primary tumour (pituitary or hypothalamus)

Skull fracture

Secondary deposits, especially breast

Surgery

Lymphoma

Infiltrations

Infective

Sarcoidosis

Basal meningitis e.g. tuberculosis

Haemochromatosis

Encephalitis

Syphilis

Others

  Radiation damage

Vascular

Chemotherapy

Pituitary apoplexy

Empty sella syndrome

Sheehan’s syndrome

Carotid artery aneurysms

Functional

  Anorexia

Immunological

Starvation

Pituitary antibodies

Emotional deprivation

Congenital
Kallmann’s syndrome

Clinical features

These depend on the extent of hypothalamic-pituitary deficiencies. Gonado-trophin deficiency results in loss of libido, amenorrhoea (absent menstruation) and erectile dysfunction, whereas hyperprolactinaemia results in galactor-rhoea (spontaneous flow of milk unassociated with childbirth or breast feeding) and hypogonadism. Deficiency of GH produces short stature in children but in adults it is often clinically silent, although it may result in significant impairment in well-being and work capacity. Secondary hypothy-roidism and adrenal failure lead to tiredness, slowness of thought and action, and mild hypotension. Longstanding hypopituitarism may give the classic picture of pallor with hairlessness (alabaster skin). Particular syndromes related to hypopituitarism are:

■ Congenital deficiency of gonadotrophin-releasing hormone (GnRH) -Kallmann's syndrome (p. 631)

■ Sheehan’s syndrome - pituitary infarction following severe postpartum haemorrhage. Rare in developed countries

■ Pituiary apoplexy - rapid enlargement of a pituitary tumour due to infarc-tion or haemorrhage. There is severe headache and sudden severe visual loss, sometimes followed by acute life-threatening hypopituitarism

■ ‘Empty sella’ syndrome - radiologically the sella turcica (the bony struc-ture that surrounds the pituitary) appears devoid of pituitary tissue. In some cases, the pituitary is actually placed eccentrically and function is usually normal. In others there is pituitary atrophy (after injury, surgery or radiotherapy) and associated hypopituitarism.

Investigation

Each axis of the hypothalamic-pituitary system requires separate investiga-tion. The presence of normal gonadal function (ovulatory menstruation or normal libido/erections) suggests that multiple defects of the anterior pituitary are unlikely. Tests range from measurement of basal hormone levels to stimulatory tests of the pituitary and tests of feedback for the hypothalamus (see under individual endocrine systems).

Management

Steroid and thyroid hormones are essential for life and are given as oral replacement drugs (e.g. 15-40 mg hydrocortisone daily in divided doses, 100-150 μg levothyroxine daily) with the aim of restoring clinical and bio-chemical normality. Androgens and oestrogens are replaced for symptomatic control. If fertility is desired, LH and FSH analogues are used. GH therapy should be given to the growing child under appropriate specialist supervision and it may also produce substantial benefits to the GH-deficient adult in terms of work capacity and psychological well-being. Two warnings are necessary:

■ Thyroid replacement should not commence until normal glucocorticoid function has been demonstrated or replacement steroid therapy initiated, as an adrenal ‘crisis' may otherwise be precipitated.

■ Glucocorticoid deficiency masks impaired urine concentrating ability. Diabetes insipidus is apparent after steroid replacement, the steroids being necessary for excretion of a water load.

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

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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
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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

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