A physician is obligated to consider more than a diseased organ, more even than the whole man—he must view the man in his world.
Hormones control so many aspects of body function that the manifestations of endocrine disease are protean. Symptoms can include changes in body weight, appetite, bowel habit, hair distribution, pigmentation, sweating, height and menstruation, as well as galactorrhoea (unexpected breast-milk production—in men and women), polydipsia, polyuria, lethargy, headaches and loss of libido and erectile dysfunction. Back pain and loss of height caused by vertebral fractures may be symptoms and signs of osteoporosis, which has endocrine and non-endocrine causes. Many of these symptoms have other causes as well and must be carefully evaluated. On the other hand, the patient may know which endocrine organ or group of endocrine organs has been causing a problem. Histories of thyroid disease and diabetes mellitus are particularly common. A list of common symptoms associated with various endocrine diseases is presented in List 27.1. In this chapter some of the important symptoms associated with endocrine disease are discussed.
An increased appetite associated with weight loss classically occurs in thyrotoxicosis (due to an increase in metabolic activity) or uncontrolled diabetes mellitus (due to loss of glucose in the urine). An increased appetite with weight gain may occur in Cushing’s syndrome (effects of excessive glucocorticoids), hypoglycaemia or hypothalamic disease. A loss of appetite with weight loss can occur with adrenal insufficiency but is also seen in anorexia nervosa and with gastrointestinal disease (particularly malignancy). A loss of appetite with weight gain can occur in hypothyroidism (reduced metabolic activity).
Diarrhoea and an increase in the frequency of bowel movements are associated with hyperthyroidism and adrenal insufficiency, while constipation may occur in hypothyroidism and hypercalcaemia.
Increased sweating is characteristic of hyperthyroidism, phaeochromocytoma, hypoglycaemia and acromegaly, but may also occur in anxiety states and at the menopause.
Hirsutism refers to an increased growth of body hair in women. The clinical evaluation and differential diagnosis are presented on page 375. The absence of facial hair in a man suggests hypogonadism, while temporal recession of the scalp hair in women occurs with androgen excess. The decrease in adrenal androgen production that occurs as a result of hypogonadism, hypopituitarism or adrenal insufficiency can cause loss of axillary and pubic hair in both sexes.
This common symptom can be due to a number of different diseases. Patients with hypothyroidism, Addison’s disease and diabetes mellitus can present with this problem. Anaemia, connective tissue diseases, chronic infection (e.g. HIV, infective endocarditis), drugs (e.g. sedatives, diuretics causing electrolyte disturbances), chronic liver disease, renal failure and occult malignancy and depression may also result in lethargy.
The skin becomes coarse, pale and dry in hypothyroidism, and dry and scaly in hypoparathyroidism. Flushing of the skin of the face and neck occurs in the carcinoid syndrome (due to the release of vasoactive peptides from the tumour). Soft-tissue overgrowth occurs in acromegaly and skin tags called molluscum fibrinosum may appear in the axillae. Acanthosis nigricans can also occur in acromegaly and in insulin-resistant states including Cushing’s syndrome and polycystic ovarian syndrome. Xanthelasmata may be present in patients with diabetes or hypothyroidism.
Onycholysis occurs in Graves’ disease, and Cushing’s syndrome is associated with spontaneous ecchymoses, thin skin and purple striae.
Increased pigmentation may be reported in primary adrenal insufficiency, Cushing’s syndrome or acromegaly. Decreased pigmentation occurs in hypopituitarism. Localised depigmentation is characteristic of vitiligo, which may be associated with certain endocrine diseases such as Hashimoto’sa disease, hypothyroidism and Addison’s disease (autoimmune adrenal insufficiency) and other autoimmune conditions.
Tallness may occur in children for constitutional reasons (tall parents) or, rarely, may reflect growth hormone excess (leading to gigantism), gonadotrophin deficiency, Klinefelter’sb syndrome, Marfan’s syndrome or generalised lipodystrophy. Short stature can also result from endocrine disease, as discussed on page 374.
A persistent inability to attain or sustain penile erections may occasionally be due to primary hypogonadism or to secondary hypogonadism due to hyperprolactinaemia or hypopituitarism. More often, it is related to endothelial dysfunction (vascular disease) and emotional disorders. Autonomic neuropathy (e.g. in diabetes mellitus or alcoholism), spinal cord disease or testicular atrophy can also cause this problem.
Hyperprolactinaemia (usually the result of pituitary adenoma) can cause galactorrhoea in up to 80% of women and 30% of men. Galactorrhoea in men occurs from a normal-appearing male breast.
Failure to menstruate is termed amenorrhoea. Primary amenorrhoea is defined as a failure to start menstruating by 17 years of age. True primary amenorrhoea may result from ovarian failure (e.g. X chromosomal abnormalities such as Turner’s syndrome) or from pituitary or hypothalamic disease (e.g. tumour, trauma or idiopathic disease). Excess androgen production or systemic disease (e.g. malabsorption, chronic kidney disease, obesity) can also result in primary amenorrhoea. Apparent primary amenorrhoea may also occur if menstrual flow cannot escape: for example, if there is an imperforate hymen.
Secondary amenorrhoea is defined as the cessation of menstruation for 6 months or more. Pregnancy and menopause are common causes. The polycystic ovarian syndrome, hyperprolactinaemia, virilising syndromes or hypothalamic or pituitary disease can also result in this problem, as can use of the contraceptive pill or psychiatric disease and loss of weight of any cause, but especially with anorexia nervosa.
Polyuria is defined as a urine volume of more than 3 litres/day. Patients who report urinary frequency may find it difficult to tell if large volumes of urine are being passed. Causes include diabetes mellitus (due to excessive filtration of glucose, a poorly resorbed solute); diabetes insipidus (due to inadequate renal water conservation from a central deficiency of antidiuretic hormone, or a lack of renal responsiveness to this hormone); primary polydipsia, where a patient drinks excessive water (due to psychogenic or hypothalamic disease or drugs such as chlorpromazine or thioridazine or just simple eccentricity); hypercalcaemia; and tubulointerstitial or cystic renal disease.
A previous history of any endocrine condition must be uncovered. This includes surgery on the neck for a goitre. A partial thyroidectomy or radio-iodine (131I) treatment in the past can lead to eventual hypothyroidism. The same may apply to radiation of the thyroid for carcinoma. A woman may have been diagnosed with diabetes mellitus after the birth of a large baby. There may be a past history of hypertension, which is occasionally due to an endocrine condition (e.g. phaeochromocytoma, Cushing’s syndrome or Conn’s syndrome). Previous thyroid surgery can be associated with hypoparathyroidism because of surgical damage to the parathyroid glands. Previous head injury may be a cause of pituitary or hypopituitary damage.
Previous treatment of a patient’s thyroid problems may have included the use of anti-thyroid drugs, thyroid hormone or radioactive iodine. Surgery on the adrenals or pituitary may have been performed and this may leave the patient with decreased adrenal or pituitary function.
Patients with diabetes mellitus have an important chronic condition. Treatment may be with diet, insulin or oral hypoglycaemic agents. One must determine how well the patient understands the condition, and whether he or she understands the principles of the diabetic diet and adheres to it. Find out how the blood sugar levels are monitored and whether or not the patient adjusts the insulin dose. Most patients should be able to monitor their own blood sugar levels at home using a glucometer. There is now good evidence that tight control of blood sugar levels reduces the incidence of diabetic complications. Patients should have records of home blood sugar measurements, and may know the results of tests such as the haemoglobin A1c (a measure of average blood sugar levels) and of tests of renal function and for protein in the urine.
The patient should be aware of the need for care of the feet and eyes to help prevent complications. Most diabetics have regular ophthalmological reviews, often using retinal photography. There may be a history of laser treatment for proliferative diabetic retinopathy.
Patients with hypopituitarism or hypoadrenalism may be on glucocorticoid (steroid) replacement; the latter also require mineralocorticoid replacement. Details of the patient’s dosage schedule should be obtained.
Patients may know of a diagnosis of osteoporosis.c This may have been made following spontaneous fractures or as a result of screening tests for bone density, vitamin D levels or serum calcium.
Many of these conditions are chronic and their complications are serious. How well the patient copes with various problems and the conditions at home and work will have an important effect on the success of treatment.
There may be a history in the family of thyroid conditions or diabetes mellitus. Occasionally, a family history of a multiple endocrine neoplasia (MEN) syndrome may be obtained. These are rare autosomal-dominant conditions. They include pituitary tumours, medullary carcinoma of the thyroid, hyperparathyroidism, phaeochromocytoma and pancreatic islet cell tumours.