Endocrine Glands

The bulk of the anterior pituitary is the pars distalis: cords of secretory epithelial cells separated by sinusoidal fenestrated capillaries. When the pathologist stains the slide, two populations jump out — cells that take up dye (chromophils) and cells that look pale and empty (chromophobes). Within the chromophils, those that prefer acidic dyes go pink (acidophils) and those that prefer basic dyes go purple-blue (basophils). The whole exam pattern for this section is built on that one tinctorial split.

Acidophils make up roughly forty percent of the pars distalis and they secrete only two hormones — growth hormone (somatotrophs) and prolactin (lactotrophs or mammotrophs). Basophils are fewer (about ten percent) but carry the other four anterior-pituitary hormones: TSH, ACTH, FSH and LH. Chromophobes are pale because they are either resting/degranulated chromophils or undifferentiated stem cells — not a separate hormone line. Whenever an exam asks “which hormone do basophils not make?” the answer is GH, because GH is an acidophil product.

Behind the cell types is the wiring. The hypothalamus sits above the gland, but its releasing and inhibiting hormones never reach the systemic blood. Instead they drip from hypothalamic neurons into a primary capillary plexus in the median eminence; that plexus drains into portal venules running down the pituitary stalk; the venules open into the secondary plexus bathing the pars distalis. The whole thing is called the hypothalamo-hypophyseal portal system and it concentrates hypothalamic hormones one hundred-fold before they ever touch a pituitary cell.

A small pars intermedia sits between front and back, often a thin row of basophil-like cells around colloid-filled cysts (the residue of Rathke’s pouch lumen). A thinner pars tuberalis wraps the upper stalk. Neither is heavily tested in the TMU exam — recognise them, then move on.

Turn the slide to the posterior lobe and the picture changes completely. There are almost no cell bodies — just a pale tangle of unmyelinated axons, scattered glial nuclei, and capillaries. The axons belong to magnocellular neurons whose cell bodies sit far above in the hypothalamus: the supraoptic nucleus (mostly antidiuretic hormone, ADH) and the paraventricular nucleus (mostly oxytocin). They synthesise their hormone in the cell body, package it with a carrier protein called neurophysin, and ship the granules down the axon by axonal transport. The pars nervosa is just where the axon terminates and the hormone is finally released into the blood.

Along the way you will see beaded swellings in the axons — these are Herring bodies. They are not separate cells; they are dilated axon terminals stuffed with neurosecretory granules, waiting for an action potential to trigger release. The other nuclei you see scattered between the axons belong to pituicytes: modified astrocyte-like glia that simply support the axons.

• Unmyelinated axons of hypothalamic neurons (supraoptic → ADH; paraventricular → oxytocin) + glial pituicytes + capillaries.
• Herring bodies = dilated axon terminals storing neurosecretory granules.

The thyroid is the only endocrine gland in the body that stores its hormone outside the cell, and that single design quirk explains everything about its histology. The structural unit is the follicle: a hollow sphere lined by one layer of simple cuboidal follicular cells, with the lumen completely filled by a pink-staining gel called colloid. The colloid is iodinated thyroglobulin — the hormone precursor — sitting safely outside the cells, weeks of hormone supply already pre-made.

When TSH from the basophils tells the thyroid to release hormone, the follicular cell pinches a drop of colloid back into itself, digests the thyroglobulin in lysosomes, and frees T₄ and T₃ into the basal capillary network. The taller the cell looks under the microscope, the more active it is — in hyperthyroid Graves disease the cells go columnar and the colloid gets eaten back to thin scallops; in hypothyroid Hashimoto disease the cells flatten and the colloid heaps up. The histology literally shows you the patient’s TFTs.

Wedged between the follicles — or in the basal part of the follicular epithelium — are pale, larger cells with no contact with colloid. These are the parafollicular cells (also called C cells). They are not derived from the same endoderm as the follicular cells; they migrated in from the neural crest. They secrete calcitonin, a peptide that lowers blood calcium by inhibiting osteoclasts. Calcitonin is a minor calcium hormone in adult humans, but it matters clinically because C cells give rise to medullary thyroid carcinoma.

Four pinhead-sized glands sit on the back of the thyroid, embedded in or just behind its capsule. They were discovered late in history because they were always mistaken for thyroid tissue — until surgeons realised that removing them caused fatal hypocalcaemic tetany. The parathyroid is the body’s minute-to-minute calcium thermostat, and its histology reflects how relentlessly it works.

Inside, you see two cell types in cords with a fenestrated capillary network. Chief (principal) cells are small and dark, with the typical protein-secreting machinery of RER and Golgi. They secrete parathyroid hormone (PTH), which raises blood calcium by stimulating osteoclasts, increasing renal calcium reabsorption and activating vitamin D to absorb calcium from the gut. Oxyphil cells are larger, brightly eosinophilic and crammed with mitochondria. Their function is still uncertain after a century of staring at them; they appear after puberty and increase with age. With age you also see clusters of adipocytes infiltrating the gland — a normal finding, not pathology.

Sweep through the cortex from outside in and you cross three zones in fixed order: glomerulosa, fasciculata, reticularis. Each zone has a different cell arrangement, a different cytochrome P450 enzyme set, and a different steroid output. This is the textbook’s “GFR = Salt, Sugar, Sex” pattern, and it shows up on almost every histology paper.

The zona glomerulosa is the outermost thin band — small cells in rounded clusters or arches. They are the only adrenal cells that express aldosterone synthase and they answer to angiotensin II through the renin-angiotensin system, not to ACTH. Their product is the mineralocorticoid aldosterone, which makes the kidney retain sodium and excrete potassium.

The zona fasciculata is the broadest middle zone, easily fifty to seventy percent of the cortex. Its cells run in long straight cords, two cells thick, with sinusoidal capillaries between. They look pale and foamy because their cytoplasm is packed with lipid droplets — hence the affectionate nickname spongiocytes. They make the glucocorticoid cortisol in answer to ACTH from the corticotroph basophils.

The zona reticularis is the innermost cortical band, with anastomosing cords of darker cells. They have less lipid (most has been used up making steroids) and accumulate brown lipofuscin pigment with age, which is why the zone looks dusky. Their product is weak androgens, principally DHEA, which the periphery converts to testosterone and oestrogen.

Cut deep enough into the adrenal and the cortical cords end abruptly at the central medulla. The cells here are large and basophilic, arranged in clumps around capillaries and central veins. They go brown when fixed in chromate salts — the reaction that earned them the name chromaffin cells. Genetically they are modified postganglionic sympathetic neurons: the embryo planned to make them into ganglion cells, then decided to drop the axon and turn them into endocrine cells instead. They are innervated directly by preganglionic sympathetic fibres, and a single sympathetic discharge dumps a flood of adrenaline (about 80%) and noradrenaline (about 20%) straight into the central vein.

Why is the medulla buried inside the cortex? Because cortisol from the fasciculata washes through the medullary sinusoids on its way out, and one of cortisol’s side jobs is to induce phenylethanolamine-N-methyltransferase, the enzyme that converts noradrenaline to adrenaline. Without high cortisol exposure, the medulla makes mostly noradrenaline. Anatomy and biochemistry beautifully reinforce each other.

You already met the islets of Langerhans in Unit 11 with the exocrine pancreas; they reappear here because they are endocrine. Pale islands of cords sit scattered among the dark exocrine acini, each ringed by a fenestrated capillary basket. The four cell types are not distinguishable on routine H&E — you need immunohistochemistry — but the proportions are worth remembering: B (β) cells about 70% → insulin, A (α) cells about 20% → glucagon, D (δ) cells about 5% → somatostatin, and PP cells → pancreatic polypeptide. The B cells lie centrally; the A cells form a rim at the periphery.

Tucked at the back of the third ventricle, the pineal is a tiny cone of nervous tissue, no bigger than a grain of rice. Its main cells are the pinealocytes — modified neurons with long branched processes — which secrete melatonin at night and quietly in the day. Light hitting the retina is the cue: optic information runs to the suprachiasmatic nucleus, then down a sympathetic chain to the pineal, and noradrenaline switches off melatonin production. Block the light path and the pineal pumps melatonin out around the clock — which is why melatonin tablets help jet lag.

Scattered between pinealocytes are astrocyte-like interstitial cells, and clumped throughout are pale concretions of calcium phosphate called corpora arenacea or brain sand. They appear in childhood, grow with age, and have no known function — but radiologists love them: on a plain skull X-ray the calcified pineal is a midline marker, and lateral shift signals a mass.