Patient A — hypothyroidism with simple goitre. Deficiency of iodine in the diet results in hypothyroidism and enlargement of the thyroid gland, commonly called goitre. Since thyroid hormones regulate the basal metabolic rate and control the metabolism of carbohydrates, proteins and fats, too little hormone lowers the metabolic rate — hence the sluggishness and weight gain. The iodine-poor soil explains the dietary deficiency.

Patient B — hyperthyroidism, specifically exopthalmic goitre (Graves’ disease). This is characterised by enlargement of the thyroid gland, protrusion of the eyeballs, increased basal metabolic rate and weight loss. Hyperthyroidism arises from cancer of the thyroid gland or from the development of nodules, raising the rate of synthesis and secretion of thyroid hormones to abnormally high levels.

Why both are enlarged. Enlargement is not a measure of hormone output. In deficiency the gland enlarges while failing to produce enough hormone; in Graves’ disease it enlarges while producing far too much. The diagnostic information lies in the accompanying signs — metabolic rate, weight, and eye protrusion — not in the size of the gland.

The three routes. PTH acts on bones and stimulates bone resorption (dissolution/demineralisation); it stimulates reabsorption of Ca²⁺ by the renal tubules; and it increases Ca²⁺ absorption from the digested food.

Why one is insufficient. The three routes address three different fates of calcium: the body's store (bone), its losses (urine) and its intake (food). Acting only on the store would raise blood calcium but do nothing to stop it being lost in urine or to bring in more from the diet, so the store would simply keep draining. By acting on all three at once, PTH both raises the level now and improves the long-term balance.

If only the bone route existed. Every episode of low blood calcium would be corrected at the expense of the skeleton, with no compensating gain from diet and no reduction of urinary loss. Repeated demineralisation would progressively weaken the bones — a state resembling the decreased bone mass and increased chances of fractures you met as osteoporosis in Chapter 17. The three-route design protects the skeleton precisely by not relying on it alone.

And the counter-hormone. Along with TCT, which lowers blood calcium, PTH plays a significant role in calcium balance in the body — balance requiring a hormone in each direction.

The thymus gland plays a major role in the development of the immune system. It secretes the peptide hormones called thymosins, which play a major role in the differentiation of T-lymphocytes that provide cell-mediated immunity, and which also promote the production of antibodies to provide humoral immunity.

The thymus is degenerated in old individuals, resulting in a decreased production of thymosins. As a result the immune responses of old persons become weak — both arms of immunity are affected, since thymosins contribute to cell-mediated as well as humoral immunity.

With fewer properly differentiated T-lymphocytes and a weaker antibody response, the same exposure to a pathogen is more likely to produce illness in an elderly person than in a young adult. Note that this is an example of an endocrine change producing a systemic consequence: nothing is wrong with the immune cells themselves, but the hormone that directs their differentiation has declined.

The unifying role is timekeeping. Melatonin plays a very important role in the regulation of the 24-hour (diurnal) rhythm of our body.

Most body processes are not constant through the day — they rise and fall on a daily cycle. Sleep and wakefulness are the most obvious, and body temperature follows a clear daily curve. But metabolism must also anticipate periods of feeding and fasting; pigmentation responds to the daily light cycle; the menstrual cycle is itself a longer rhythm that must be timed; and immune defence is more effective if its activity is coordinated with the daily pattern of exposure and rest.

A hormone that carries the body's daily time signal will therefore appear to influence all of these, not because it separately controls sleep, temperature, metabolism and immunity, but because it tells each of them when. This also fits its source: the pineal gland lies on the dorsal side of the forebrain, well placed to receive information about the light cycle.

The odd one out is thyrocalcitonin (TCT).

The contrast: thyroxine (T₄) and triiodothyronine (T₃) are iodothyronines synthesised by the follicular cells and requiring dietary iodine; they regulate the basal metabolic rate, support red blood cell formation, control the metabolism of carbohydrates, proteins and fats, and influence water and electrolyte balance. TCT, by contrast, is a protein hormone, needs no iodine, and has one specific job — it regulates the blood calcium levels, lowering them, and works along with PTH from the parathyroid glands in calcium balance.

Why one gland does both. An endocrine gland is defined by its anatomy, not by a single function, and the same organ can house different cell populations with different secretory products. This is a recurring theme of the chapter: the pancreas holds exocrine tissue alongside α- and β-cells with opposite effects on blood sugar; the adrenal gland holds a medulla and a cortex with quite different hormones. The practical lesson for study is to learn hormones by their cells of origin and their targets, not merely by the name of the gland.