Endocrine (COMPLETE)

Where is the pituitary gland located?

In the sella turcica at the base of the brain

What are the two major divisions of the pituitary gland?

Anterior pituitary (adenohypophysis)

Posterior pituitary (neurohypophysis)

What is the embryologic origin of the anterior pituitary?

Derived from developing oral cavity epithelial cells

• Specifically Rathke pouch

What is the embryologic origin of the posterior pituitary?

Develops from neural tissue extending from the hypothalamus

What does the anterior pituitary primarily do?

Produces hormones that stimulate the production of hormones from:

• Thyroid

• Adrenal

• Gonads

• Breast

What are the three major staining categories of anterior pituitary cells?

Basophils

Eosinophilic/acidophilic cells

Chromophobes

What is this?

Normal pituitary

What hormone does a somatotroph produce?

Growth hormone (GH)

What hormone does a lactotroph produce?

Prolactin (PRL)

What hormone does a corticotroph produce?

Adrenocorticotropic hormone (ACTH)

Pro-opiomelanocortin (POMC)

Melanocyte-stimulating hormone (MSH)

What hormone does a thyrotroph produce?

Thyroid-stimulating hormone (TSH)

What hormones do mammosomarotrophs produce?

GH

Prolactin

What hormones are produced by gonadotrophs?

FSH

LH

What does FSH do in women?

Stimulates the formations of graafian follicles in the ovary

What does LH do in women?

Induces ovulation

Formation of corpora lutea in the ovary

What does FSH/LH do in men?

Regulate spermatogenesis

Testosterones production

What is this showing?

Normal anterior pituitary gland

• Basophilic cells (blue)

  • Thyrotroph, gonadatroph, corticotroph

• Eosinophilic cells (red)

  • Somatotroph, lactotroph

• Chromophobes (yellow)

  • Non-staining → no hormones

What is the major distinction between anterior and posterior pituitary hormone production?

Anterior pituitary → Synthesizes and secretes its own hormones

Posterior pituitary → Stores and releases hormones synthesized in the hypothalamus

What is the posterior pituitary composed of?

Modified glial cells and axonal processes extending from the hypothalamus

Which two hormones are stored and released by the posterior pituitary?

ADH (vasopressin)

Oxytocin

Where are ADH and oxytocin synthesized?

In the hypothalamus

What is the major effect of ADH?

Promotes renal water reabsorption

What happens when ADH production/release is deficient?

Diabetes insipidus

• Characterized by excessive urination due to inability to adequately concentrate urine

  • Kidneys cannot resorb water from water

What happens with excessive ADH secretion?

SIADH — Syndrome of inappropriate ADH secretion

ADH overproduction — Excessive renal reabsorption of water

What malignancy is classically associated with ectopic ADH production?

Small-cell carcinoma of the lung

What are the three major ways pituitary tumors can cause disease/tumors?

Local mass effects

Excess hormone production

Decreased hormone production

What is the difference between a functioning and nonfunctioning pituitary tumor?

Functioning → Produces excess biologically active hormone

Nonfunctioning → Does NOT produce clinically significant excess hormone and often presents because of mass effect (LARGE at discovery)

What age group is typical for pituitary tumors according to the lecture?

Approximately 35–60 years old

What is this showing?

A typical pituitary adenoma

What is this historically showing?

Pituitary adenoma

• Large, nonfunctioning adenoma

(Notice the ONE cell type)

What is another word for an pituitary adenoma?

Pituitary neuroendocrine tumors (PitNETs)

Pituitary neuroendocrine tumors primarily arise from which part of the pituitary?

The anterior pituitary

What is the most common functional consequence of pituitary adenomas?

Hyperpituitarism

• Excessive production of pituitary hormones

What other major pituitary pathologies besides adenomas are mentioned in the lecture?

Hyperplasia

Carcinoma

What is a pituitary microadenoma?

A pituitary adenoma less than 1 cm in diameter

What is a pituitary macroadenoma?

A pituitary adenoma 1 cm or larger

What is a major local mass effect of a large pituitary tumor?

Compression of surrounding structures

• Particularly the optic chiasm → Cause bitemporal hemianopia

What is the most common functioning pituitary adenoma?

Prolactinoma (lactotroph adenoma)

What hormone is released by prolactinoma/lactotroph adenoma?

Prolactin

What are the classic syndromes of prolactinoma/lactotroph adenoma?

Galactorrhea

Amenorrhea (females)

Sexual dysfunction

Infertility

What does a somatotroph adenoma secrete?

Growth hormone (GH)

What are the classic syndromes of somatotroph adenoma?

Gigantism (children)

Acromegaly (adults)

What hormones are released in excess by mammosomatotroph adenoma?

GH

Prolactin

What are the classic syndromes of mammosomatotroph adenoma?

Combined features of GH and prolactin excess

What hormones are released by corticotroph adenoma?

ACTH

Other POMC-derived peptides

What are the classic syndromes of corticotroph adenoma?

Cushing syndrome

Hyperpigmentation (light-skinned individuals)

What hormone is released by thyrotroph adenoma?

TSH

What is the classic syndrome of thyrotroph adenoma?

Hyperthyroidism

What is the key distinction between Cushing disease and Cushing syndrome?

Cushing disease → Specifically refers to a pituitary ACTH-secreting tumor

Cushing syndrome → Refers to excess cortisol from any cause

What hormones are secreted by gonadotroph adenomas?

FSH

LH

What are the classic syndromes of gonadotroph adenomas?

Ovarian hyperstimulation

Menstrual irregularities in women

Testicular enlargement in males

Precocious puberty in adolescents

What is a null cell pituitary adenoma?

A pituitary tumor that lacks evidence of a specific hormone-producing cell lineage

Is generally nonfunctioning

What distinguishes a pituitary carcinoma from a pituitary adenoma/PitNET?

Metastatic spread establishes the diagnosis of carcinoma

What are the two major disorders associated with abnormal ADH secretion?

Diabetes insipidus → too little ADH

SIADH → too much ADH

What can cause ADH deficiency?

Neoplasms or inflammation

• Involving the hypothalamic/posterior pituitary system

What is the basic gross anatomy of the thyroid?

Two lobes

• Connected via an isthmus

Located below and anterior to the larynx

What is the basic structural unit of the thyroid?

The thyroid follicle

What type of cells line thyroid follicles?

Cuboidal OR low-columnar follicular epithelial cells

What protein is synthesized by thyroid follicular cells and stored within follicles?

Thyroglobulin

In what form is thyroglobulin stored?

As colloid within thyroid follicles

Where are thyroid hormones produced?

Produced within the follicular epithelial cells

• Using thyroglobulin within the follicle

Which thyroid cells produce calcitonin?

Parafollicular C cells

What is thyrotoxicosis?

A hypermetabolic state caused by elevated circulating thyroid hormone levels

What are the three major causes of hyperthyroidism?

1. Graves disease

2. Hyperfunctioning multinodular goiter

3. Hyperfunctioning thyroid adenoma

What happens to TSH in primary hyperthyroidism?

TSH decreases because of negative feedback from elevated thyroid hormone

What is the single best laboratory test for evaluating thyroid function?

Serum TSH

What are common skin findings in hyperthyroidism?

Skin is soft, warm, and flushed

• Due to:

  • Increased blood flow

  • Heat intolerance

  • Excessive sweating

Why can diarrhea occur in hyperthyroidism?

Increased thyroid hormone causes rapid gastrointestinal transit

What are some GI symptoms of hyperthyroidism?

Diarrhea

Malabsorption

Steatorrhea

(Due to rapid transit time)

What cardiovascular findings are characteristic of hyperthyroidism?

Palpitations

Tachycardia

What neuromuscular/psychiatric findings can occur in hyperthyroidism?

Anxiety

Tremor

Proximal muscle weakness

What eye finding is classically associated with Graves disease/hyperthyroidism?

Exophthalmos/exophthalmia (bulging eyes)

What happens to TSH in primary hyperthyroidism?

TSH decrease

What happens to TSH in primary hypothyroidism?

TSH increases because thyroid hormone levels are low

What is myxedema?

The clinical syndrome associated with severe hypothyroidism

• Particularly in adults

A severe form of cutaneous and dermal swelling associated with low thyroid hormone levels

What are classic clinical findings (myxedema) of hypothyroidism?

Fatigue

Apathy

Mental sluggishness

Constipation

Cool skin

What is the congenital root cause of hypothyroidism?

A congenital iodine deficiency

Why is the skin cool in hypothyroidism?

Due to a decrease in blood flow

What is the classic clinical association with severe congenital hypothyroidism?

Cretinism

• With impaired physical and mental development

What are the primary causes of hypothyroidism?

Surgery, radiation exposure → Loss of thyroid tissue

Thyroiditis → Destruction of follicles

Iodine deficiency → ↓synthesis of thyroid hormone

Drugs → interfere with normal synthesis

Dyshormonogenetic goiter → Congenital defect in synthesis

Genetic defects in thyroid development

Thyroid hormone resistance (mutation)

What are the secondary causes of hypothyroidism?

Pituitary failure → Defective TSH production

Hypothalamic failure → Defective TSH production

What is thyroiditis?

Inflammation of the thyroid gland

• With several distinct etiologies and clinical presentations

What is Hashimoto thyroiditis?

A chronic autoimmune thyroiditis that commonly causes hypothyroidism

What antibodies are classically associated with Hashimoto thyroiditis?

Anti-thyroid peroxidase (anti-TPO)

Anti-thyroglobulin

What are the classic microscopic features of Hashimoto thyroiditis?

Prominent mononuclear inflammation

• Lymphoid germinal centers

Hürthle cell metaplasia

Atrophic thyroid epithelium

What is an important neoplastic association with Hashimoto thyroiditis?

Increased risk of thyroid MALT lymphoma

What is the common pathogenesis of Hashimoto thyroiditis?

Autoimmune response against thyroid antigens

• Destruction of the gland by CTLs and cytokine-mediated inflammation

What are the clinical features of Hashimoto thyroiditis?

Painless diffuse enlargement of the thyroid

Progressive hypothyroidism

What is the common pathogenesis of subacute granulomatous (de Quervain) thyroiditis?

Postulated to be viral infection of host response to a virus

(A self-limited disease)

What is the characteristic microscopic finding in subacute granulomatous (de Quervain) thyroiditis?

Disrupted follicles

Inflammation

Multinucleated giant cells surrounding thyroid colloid

What are the clinical features of subacute granulomatous (de Quervain) thyroiditis?

Acute onset of:

• Neck pain

• Fever

• Variable thyroid enlargement

• Transient hypothyroidism

• A painful/tender thyroid, often following a viral upper respiratory infection

Eventual recovery → (6-8 weeks) normal function

What is the common pathogenesis of painless thyroiditis?

Presumed autoimmune

• Circulating antithyroid peroxidase antibodies

• Family hx

• Postpartum period

(also referred to as subacute lymphocytic thyroiditis)

What is the characteristic microscopic finding in painless thyroiditis?

Lymphocytic inflammation

• Sometimes with germinal centers

LACK the commonly prominent fibrosis and Hurthle cells

What are the clinical features of painless thyroiditis?

Painless neck mass (goiter)

Often a transient hyperthyroid phase

• Followed by hypothyroidism

• Eventual recovery

What is the common pathogenesis of Reidel thyroiditis?

IgG4-related disease

What is the characteristic microscopic finding in Reidel thyroiditis?

Extensive fibrosis with scattered lymphoplasmacytic infiltrates with IgG4-positive B cells

• Often extend BEYOND the thyroid capsule

What are the clinical features of Reidel thyroiditis?

Hard, fixed thyroid mass

• Usually euthyroid

What can the hard thyroid mass of Reidel thyroiditis clinically stimulate?

A thyroid carcinoma

What is this?

A normal thyroid

What is this demonstrating?

Thyroiditis