21.4 — Thyroid and Other Endocrine Diseases

Someone is tired, has gained weight, feels cold, has dry skin, and is a little low.

That description fits an underactive thyroid, and it also fits ordinary modern life, which is why the condition is so often attributed to stress, work, or getting older — sometimes for years.

And the treatment is a single tablet a day that restores everything.

That gap between how vague the symptoms are and how good the treatment is runs through the whole of this chapter.

The thyroid

A butterfly-shaped gland in the front of the neck, producing thyroxine (T4) and the more active triiodothyronine (T3) (Chapter 12.3).

These hormones set the metabolic rate of essentially every cell. Which is why thyroid disease affects everything — heart rate, temperature, weight, bowels, skin, hair, mood, memory and periods.

The control loop: the pituitary releases TSH, which tells the thyroid to produce hormone. Thyroid hormone feeds back and suppresses TSH.

Which produces the fact that makes thyroid blood tests confusing at first:

A high TSH means an underactive thyroid. The pituitary is shouting because the gland is not responding.

A low TSH means an overactive thyroid. The pituitary has gone quiet because there is too much hormone already.

TSH moves in the opposite direction to the thyroid, and it is a far more sensitive indicator than the hormone level itself, which is why it is the first test.

Hypothyroidism — underactive

Around 1 to 2 percent of people, and far commoner in women — roughly 5 to 10 times.

Symptoms: fatigue, weight gain, cold intolerance, constipation, dry skin, hair thinning, hoarse voice, muscle aches, slowed thinking, low mood, heavy periods, and slow-relaxing reflexes.

And a subtle one worth knowing: raised cholesterol. An unexplained rise in cholesterol should prompt a thyroid test, because treating the thyroid corrects it.

Causes:

Hashimoto's thyroiditis — autoimmune destruction of the gland, the commonest cause where iodine intake is adequate. Antibodies against thyroid peroxidase are found.

Iodine deficiency — the commonest cause worldwide. The thyroid cannot make hormone without iodine, and salt iodisation is one of the most successful public health measures ever implemented, having prevented a vast amount of goitre and, more importantly, the intellectual disability caused by iodine deficiency in pregnancy.

After treatment for an overactive thyroid, or after surgery or radiotherapy to the neck.

Drugs — lithium, amiodarone, and some immunotherapies.

Congenital — which is why newborns are screened, because untreated congenital hypothyroidism causes permanent intellectual disability and treatment from the first weeks prevents it entirely. This is one of the highest-value screening tests in existence.

Treatment: levothyroxine, once daily.

Taken on an empty stomach, ideally 30 to 60 minutes before food, because absorption is reduced by food.

And a practical list of things that block absorption if taken at the same time: calcium, iron, and some antacids and proton pump inhibitors. Separate them by four hours.

Dose adjusted by TSH, checked around 6 to 8 weeks after any change, because the system takes that long to settle.

In pregnancy the requirement rises by around 25 to 50 percent, and it should be increased as soon as pregnancy is confirmed, because thyroid hormone is essential for fetal brain development in the first trimester before the baby's own thyroid works (Chapter 4.6).

Subclinical hypothyroidism — raised TSH with normal hormone levels. Treated when TSH is well above range, when antibodies are present, in pregnancy or when trying to conceive, and where symptoms are clear. Otherwise it is frequently monitored, because many cases do not progress.

And the honest note on persistent symptoms: a proportion of people on levothyroxine with normal blood tests still feel unwell. The reasons are debated, and combination T4/T3 treatment has not shown clear benefit in trials while remaining used by some. The fair position is that the complaint is real, the explanation is unsettled, and other causes — anaemia, B12 deficiency, coeliac disease, sleep apnoea, depression — should be looked for rather than assuming the thyroid explains everything.

Hyperthyroidism — overactive

Symptoms: weight loss despite a good appetite, heat intolerance, sweating, palpitations, tremor, anxiety and irritability, frequent bowel movements, insomnia, and lighter or absent periods.

In older people it can present quietly, with atrial fibrillation, weight loss or heart failure as the only features, and be missed entirely.

Causes:

Graves' disease — the commonest. An autoimmune condition where antibodies stimulate the TSH receptor, so the thyroid is driven continuously.

And it has features no other cause has: eye disease — bulging eyes, grittiness, double vision, in a minority sight-threatening — because the same antibodies affect the tissue behind the eye. Smoking makes the eye disease substantially worse, which is the strongest reason for someone with Graves' to stop.

Toxic nodules — one or more autonomous lumps producing hormone regardless of TSH.

Thyroiditis — inflammation releasing stored hormone. Produces a temporary overactive phase, then frequently an underactive phase, then recovery. It does not respond to the drugs that block hormone production, because nothing is being produced — the hormone is leaking out of a damaged gland. Distinguishing it matters, because the treatment is different.

Treatment:

Carbimazole or propylthiouracil, blocking hormone synthesis.

A safety point worth knowing: these drugs rarely cause agranulocytosis — a sudden loss of infection-fighting white cells. Anyone taking them who develops a sore throat, fever or mouth ulcers should stop the drug and have an urgent blood count. That instruction is given at the start of treatment and is worth remembering.

Beta blockers for symptom control while waiting for the drugs to work.

Radioactive iodine — taken up by the thyroid and destroying it. Effective, and usually results in hypothyroidism requiring lifelong replacement, which is an acceptable trade. Avoided in pregnancy and in active eye disease.

Surgery — for large goitres, suspected cancer, or where other treatments are unsuitable.

Thyroid storm — a rare, life-threatening emergency: fever, severe tachycardia, agitation, confusion and heart failure, usually precipitated by infection, surgery or stopping medication. Treated in intensive care.

Thyroid lumps and cancer

Thyroid nodules are extremely common — found in a large proportion of people if you scan for them — and the great majority are benign.

Assessed by ultrasound and, where indicated, a needle biopsy.

Thyroid cancer, when it occurs, has an unusually good outlook. Papillary and follicular types, which are the majority, have excellent long-term survival with surgery and where needed radioactive iodine.

Medullary and anaplastic types are less common and more serious.

And a genuine problem worth knowing: over-diagnosis. Widespread scanning finds small papillary cancers that would never have caused harm, and some countries have seen large rises in diagnosis with no change in mortality — which means people are being treated for something that was never going to hurt them. Active surveillance rather than immediate surgery is increasingly offered for very small low-risk tumours.

The adrenal glands

Small glands sitting on top of the kidneys, producing cortisol, aldosterone and adrenaline (Chapter 12.4).

Cushing's syndrome — too much cortisol

The commonest cause by far is prescribed steroids, which is worth stating first because it is preventable and reversible.

Features: weight gain concentrated on the trunk and face, with thin arms and legs; a rounded face; purple stretch marks; easy bruising; thin skin; muscle weakness, particularly getting out of a chair; high blood pressure; diabetes; osteoporosis; and mood change.

The distinguishing pattern from ordinary weight gain is the combination of gaining weight centrally while losing muscle from the limbs, which does not happen in simple obesity.

Other causes: a pituitary tumour producing ACTH — Cushing's disease specifically; an adrenal tumour; or a tumour elsewhere producing ACTH.

Treated by removing the cause, and by reducing steroid doses where that is the cause.

Addison's disease — too little cortisol

Rare, easily missed, and potentially fatal, which is why it is worth knowing.

Symptoms are vague: fatigue, weight loss, poor appetite, nausea, dizziness on standing, salt craving, and muscle and joint pain.

And one specific sign: darkening of the skin, particularly in skin creases, scars and the inside of the mouth — because the pituitary produces excess ACTH trying to stimulate the failing adrenal, and ACTH also stimulates pigment cells.

Adrenal crisis is the emergency: severe weakness, vomiting, abdominal pain, confusion, very low blood pressure and collapse, frequently triggered by infection, injury or surgery.

Treatment is immediate hydrocortisone and intravenous fluids, and it must not wait for test results. Delay kills.

Ongoing treatment: hydrocortisone and fludrocortisone replacement.

And the sick day rules are the crucial part: the dose is doubled during illness with fever, and an emergency injection is given for vomiting, injury or collapse. Everyone with Addison's should carry an emergency injection kit and a medical alert card, and household members should know how to use it.

The same applies to anyone on long-term steroids, whose adrenal glands become suppressed and cannot mount a stress response — which is why long-term steroids must never be stopped abruptly.

Other adrenal conditions

Primary aldosteronism — excess aldosterone causing high blood pressure and sometimes low potassium.

And it is far commoner than once thought — perhaps 5 to 10 percent of hypertension — and it is potentially curable, either by removing an adenoma or by a specific drug. Which makes it worth testing for in resistant hypertension, hypertension with low potassium, or hypertension at a young age.

Phaeochromocytoma — a rare adrenaline-producing tumour causing episodes of severe high blood pressure, headache, sweating and palpitations. Curable by surgery.

The pituitary

The gland at the base of the brain controlling most of the others (Chapter 12.2).

Pituitary tumours are almost always benign, and they cause problems in three ways:

By producing a hormone: prolactinoma, causing milk production, absent periods and infertility, and treated with tablets rather than surgery, which shrink it effectively; acromegaly from excess growth hormone in adults, causing enlargement of the hands, feet and jaw over years and frequently diagnosed by comparing old photographs; and Cushing's disease.

By pressing on surrounding structures — classically the optic chiasm sits directly above, so the characteristic visual loss is of the outer half of each visual field (Chapter 11.11), which people notice as bumping into things at the sides.

By destroying normal pituitary tissue, causing deficiency of the hormones it should be producing.

Diabetes insipidus — not related to diabetes mellitus, and named only because both cause large urine volumes. A lack of antidiuretic hormone, or kidney resistance to it, causing enormous urine output and intense thirst (Chapter 10.3). Treated with desmopressin.

The parathyroids

Four small glands behind the thyroid, controlling calcium (Chapter 12.3).

Primary hyperparathyroidism — usually a single benign adenoma producing too much hormone, so calcium is pulled from bone and reabsorbed by the kidney.

Often found incidentally on a blood test. Symptoms, when present, are summarised in the old phrase "bones, stones, abdominal groans and psychic moans" — bone pain and thinning, kidney stones, abdominal discomfort and constipation, and low mood or poor concentration.

Treated by removing the adenoma, which is curative.

Hypoparathyroidism — usually after thyroid surgery. Low calcium causing tingling around the mouth and in the fingers, muscle cramps, and in severe cases spasm of the larynx and seizures. Treated with calcium and activated vitamin D.

The theme worth carrying

Endocrine conditions are the ones most often mistaken for ordinary life — tiredness, weight change, low mood, poor concentration.

They are diagnosed by blood tests rather than by how convincing the story is.

And they are among the most rewarding conditions to treat, because replacing a missing hormone or removing an excess one frequently returns a person completely to themselves.

What the next page fixes

Chapter 21.5 covers autoimmune and rheumatic disease — why the immune system attacks the body, and why this field has changed more than almost any other in the last twenty years.