Normal pituitary gland, gross

The normal adult pituitary, situated in the sella turcica, weighs about 1 g. Embryologically, the anterior pituitary (▼) (adenohypophysis) is derived from an upward evagination of the oral cavity, called Rathke pouch . The posterior pituitary (▲) (neurohypophysis) is derived from the diencephalon and consists of modified glial cells (pituicytes) and their axons extending down the pituitary stalk (♦) (seen here superiorly) from supraoptic and paraventricular hypothalamic nuclei. The adenohypophysis has a dual blood supply, with a hypophyseal portal system and small perforating arteries. Seen inferiorly at the right, the neurohypophysis appears at the bottom.

Normal pituitary, microscopic

The neurohypophysis, which resembles neural tissue because it is composed of modified glial cells along with the axons of hypothalamic nerve cell bodies, is on the left . The neurohypophyseal hormones oxytocin and vasopressin (antidiuretic hormone) are synthesized in the hypothalamus and transported along axons to the neurohypophysis, from where they are released into the bloodstream and carried systemically to act on cells in target tissues. The highly vascularized adenohypophysis is on the right .

Normal pituitary, microscopic

At higher magnification the adenohypophysis has pink acidophils (◄) that produce prolactin (lactotrophs) and growth hormone (somatotrophs). The dark-purple basophils (▼) produce luteinizing hormone and follicle-stimulating hormone (gonadotrophs), thyroid-stimulating hormone (thyrotrophs), and adrenocorticotropic hormone (corticotrophs). The paler cells are the chromophobes (▲). As in all endocrine glands, there is prominent vascularity with many capillaries into which the hormones are secreted for distribution throughout the body. The secretions of these cells are under control of hypothalamic-releasing factors, which are all positive acting except for dopamine, which inhibits lactotrophs.

Pituitary macroadenoma, MRI

This T1-weighted sagittal MR image shows a large bright pituitary mass (►) larger than 1 cm. Pituitary adenomas arise in the adenohypophysis. They may be null cell adenomas producing a mass effect, but without detectable hormonal secretion, or composed of either acidophils or basophils secreting an excess of one hormone (or, less commonly, several hormones). Overall, the most common types of pituitary adenomas (and their clinical outcomes) include prolactinoma (amenorrhea-galactorrhea in women, decreased libido in men), followed by null cell adenoma, corticotroph adenoma (Cushing disease), gonadotroph adenoma (paradoxical hypogonadism), and somatotroph adenoma (acromegaly in adults and gigantism in children). About 3% of pituitary adenomas are associated with multiple endocrine neoplasia type 1.

Pituitary macroadenoma, MRI and diagram

This T1-weighted MR image in axial view shows a bright pituitary macroadenoma (▲). Macroadenomas by their size can erode the sella turcica to produce headaches and impinge on the optic chiasm to produce visual field defects, most commonly bitemporal hemianopsia, as shown by the visual field diagram.

Pituitary macroadenoma, gross

This large pituitary macroadenoma (▲) impinges on the ventricular system, as seen here, with subsequent elevation in intracranial pressure producing symptoms of headache, nausea, and vomiting. Occasionally, there can be acute hemorrhage into the adenoma to increase the mass effect. Some pituitary adenomas have mutations in GNAS that result in activation of the α subunit of a G-stimulatory protein, increasing cyclic adenosine monophosphate production that drives cellular proliferation. About 5% of these adenomas arise with familial syndromes with mutations such as multiple endocrine neoplasia type 1 .

Pituitary adenoma, microscopic

Note solid (left) and fetal (right) patterns of monotonous, fairly uniform rounded cells and abundant capillary vessels. The most common pituitary adenoma (30% of cases) in adults secretes prolactin, whereas 20% are null cell adenomas that do not secrete a hormone, but can exert a mass effect, diminish pituitary function (hypopituitarism), or have a “stalk section” effect to disrupt prolactin-inhibiting factor release into the anterior pituitary, leading to hyperprolactinemia. Growth hormone–secreting adenomas are most common in children, but less common in adults.

Craniopharyngioma, MRI and microscopic

This coronal MR image shows an expansile suprasellar mass (►) derived from adamantinomatous Rathke pouch remnants eroding surrounding structures. Microscopically, there are cystic spaces (♦), and nests of squamoid cells (■) are surrounded by columnar cells. Although histologically benign, these neoplasms are difficult to eradicate because of their location and their extension into surrounding tissues. Some arise in childhood, and some in older adults. They can produce headache, visual field defects, and hypopituitarism. Those < 3 cm in diameter have a better prognosis.

Normal thyroid in situ, gross

The thyroid gland is positioned over the anterior trachea. It normally has a reddish brown, firm appearance and is normally difficult to palpate on physical examination. The adult thyroid gland weighs 10 to 30 g. There is a right lobe (◄), a left lobe (►), and a connecting isthmus (from which a small pyramidal lobe may project superiorly along the track of the embryologic thyroglossal duct). The thyroid in embryogenesis is derived from an evagination of the foramen cecum of the tongue that migrates downward along the thyroglossal duct to a position over the thyroid cartilage in the anterior neck. The C cells scattered between thyroid follicles are derived from neural crest and produce calcitonin. A small amount of dietary iodine is needed for thyroid hormone synthesis. Mostly T ₄ is released, but peripherally T ₄ is deiodinated within cells to the more biologically active T ₃ . Both T ₃ and T ₄ increase the basal metabolic rate, including anabolic and catabolic processes. Adult goiter with myxedema may be due to dietary iodine deficiency; in infants and children, hypothyroidism is manifested as cretinism.

Normal thyroid, microscopic

This gland is composed of round follicles lined by cuboidal epithelial cells (►) and filled with pink colloid, a storage product containing thyroglobulin that is metabolized to release thyroid hormones (T ₄ and T ₃ ) under the influence of thyroid-stimulating hormone released from the anterior pituitary thyrotrophs, which sense levels of circulating thyroid hormone. Thyroid hormone acts on nuclear thyroid hormone receptor in target cells to up-regulate transcription of proteins that drive carbohydrate and lipid metabolism, while also stimulating protein synthesis.

Normal C cells, microscopic

This immunohistochemical stain of normal thyroid with antibody to calcitonin identifies the C cells by the brown reaction product. The C cells (parafollicular cells) of the thyroid interstitium are located between the follicles, adjacent to the epithelium of follicles. The C cells secrete calcitonin, which can inhibit resorption of bone by osteoclasts and reduce the serum calcium, but which has a much smaller role to play in calcium hemostasis than parathyroid hormone.

Hashimoto thyroiditis, microscopic

This autoimmune disease can be associated with HLA-DR3 and HLA-DR5 alleles. It results in chronic inflammation characterized by infiltrates of CD8+ and CD4+ T lymphocytes forming much of the lymphoid infiltrates, including a lymphoid follicle (♦) seen here. Initially, there can be painless enlargement of the thyroid. The thyroid follicles gradually become atrophic, and the epithelial cells undergo Hürthle cell change, with abundant pink cytoplasm. Laboratory findings include antithyroglobulin and antimicrosomal (thyroid peroxidase) antibodies detected in serum. Polymorphisms in both CTLA4 and PTPN22 are present in many cases, along with other autoimmune manifestations.

Hashimoto thyroiditis, gross

There is relentless destruction of thyroid follicles over the years, with eventual atrophy, so that the thyroid is often not palpable when a patient presents with myxedema from hypothyroidism, and the serum thyroid-stimulating hormone is elevated. Early in the course of this disease, there may be transient hyperthyroidism from excessive release of thyroid hormones from follicles damaged by inflammation. Other autoimmune diseases, such as Addison disease or pernicious anemia, may also occur. There is an increased risk for subsequent development of B-cell non-Hodgkin lymphoma.

Granulomatous thyroiditis, microscopic

Also known as de Quervain disease, this uncommon form of thyroiditis begins with diffuse painful thyroid enlargement. It most often occurs in the fourth to the sixth decades, and is more common in women, similar to other thyroid diseases. Note the marked acute inflammation along with lymphocytes, macrophages, and prominent giant cells (♦). There is incomplete destruction of thyroid follicles. This condition typically follows a viral infection that activates cytotoxic T lymphocytes. It usually follows a course of 1 to 3 months during which transient hyperthyroidism or hypothyroidism along with fever can occur. Most patients recover completely within months and remain euthyroid.

Graves disease, microscopic

At low magnification, this thyroid hyperplasia is characterized by many papillary infoldings (►) within follicles. This is an autoimmune disease in which autoantibodies to thyroid-stimulating hormone receptors stimulate growth of follicular epithelial cells and stimulate adenylate cyclase to increase thyroid hormone output. There is an association with the HLA-DR3 allele. The entire thyroid gland becomes diffusely enlarged to double or triple normal size. Patients can manifest β-adrenergic excess with fever, diarrhea, heat intolerance, tachycardia, weight loss, tremor, and nervousness. Exophthalmos and infiltrative dermopathy (pretibial myxedema) are additional clinical features.

Graves disease, microscopic

At higher magnification, the tall columnar appearance of the hyperplastic follicular epithelial cells is evident. Small, clear vacuoles (▼) appear next to each cell, indicating increased processing of colloid to produce increased output of thyroid hormone leading to hyperthyroidism. The feedback on the adenohypophyseal thyrotrophs decreases the serum thyroid-stimulating hormone, but the serum T ₄ remains high. Antithyroid antibodies may be present. An uncommon but serious complication is “thyroid storm” with malignant hyperthermia. Graves disease can be treated by a β-adrenergic blocker, antithyroid drugs, and by subtotal thyroidectomy.

Thyroid with colloid cysts, gross

This non-neoplastic cyst is one of the most common lesions to produce a palpable nodule of the thyroid gland. The cyst is filled with colloid and surrounded by flattened cuboidal epithelium. It is just an exaggerated follicle in an otherwise normal thyroid. Patients are euthyroid. Seen here is a larger colloid cyst (▲) anteriorly and inferiorly in the left lower lobe and a smaller cyst (►) laterally in the right lower lobe. Such nodules can mimic a neoplasm on physical examination or imaging studies. They can mimic a nodular goiter, although the overall size of the thyroid is not enlarged here. By radionuclide imaging, this would be a “cold” nodule, as are most neoplastic and non-neoplastic thyroid nodules.

Thyroid, multinodular goiter, CT scan

This enlarged thyroid surrounds the trachea and contains several nodular areas (♦) with diminished attenuation (brightness). The patient was euthyroid, the most typical clinical picture accompanying goiter. The painless enlargement produces discomfort and cosmetic deformity to the neck. Multinodular goiters usually arise after many years from simple goiters. Simple goiters may be endemic in populations with decreased dietary iodine intake. Sporadic goiters can be due to goitrogens in foods such as Brussels sprouts, cauliflower, cassava, and turnips (favorites of mine, but perhaps not yours) that interfere with thyroid hormone synthesis. Most patients with goiters remain euthyroid. Inborn errors of metabolism that interfere with thyroid hormone production are rare, but can lead to goiter with cretinism in children.

Thyroid, multinodular goiter, gross and scintigraphic scan

Multinodular goiters are often asymmetric, although both lobes can become enlarged, and most patients remain euthyroid, bothered only by the mass effect. Larger masses may be removed because of fixed airway obstruction, dysphagia, or superior vena cava syndrome. In about 10% of patients, a hyperfunctioning “toxic” nodule (Plummer syndrome) may develop, producing excessive T ₄ and causing hyperthyroidism. Such a “hot” nodule (◄) with increased activity on radionuclide scintigraphic scanning is shown in the right panel .

Thyroid, goiter, microscopic

The enlarged thyroid follicles in this goiter are lined with inactive, flattened epithelial cells and filled with abundant stored pink colloid. The process starts as a simple, diffuse, nontoxic goiter, typically from reduced thyroid hormone production and increase in thyroid-stimulating hormone driving thyroid enlargement to compensate. Over time, there can be irregular nodular growth with fibrosis, hemorrhage, and calcification in areas of cystic change. The irregular growth and enlargement may mimic thyroid carcinoma. Patients often remain euthyroid. Mutations in thyroid-stimulating hormone-receptor signaling pathway ( TSHR or GNAS ) may lead to autonomous growth and function of a nodule within a goiter.

Thyroid, follicular neoplasm, gross

This cross-section through a resected lobe of thyroid gland reveals an encapsulated round neoplasm with a uniform pale brown appearance, surrounded by a rim of darker red normal thyroid (▲). This neoplasm typically manifests as a painless mass. This mass is often diagnosed on microscopic examination as a “follicular neoplasm” because in 10% of cases, although it is benign histologically, such a lesion proves to act in a malignant fashion. A follicular neoplasm forms a palpably firm nodule and is more common in middle-aged women. Most are hypofunctioning “cold” nodules on radionuclide scanning.

Thyroid, follicular neoplasm, microscopic