Adrenal gland

(Adrenal glands)
Last updated: Feb 18, 2020
QBANK SESSION
LEARNED

Summary
The adrenal gland is a paired retroperitoneal organ located on the upper pole of each kidney. It receives its arterial supply from the superior, middle,
and inferior suprarenal arteries and drains into the right and left suprarenal veins. The adrenal gland has two layers: the adrenal cortex (outer layer),
which is derived from the mesoderm, and the adrenal medulla (inner layer), which is derived from neural crest cells. The adrenal medulla is
composed of chromaffin cells, which secrete catecholamines (norepinephrine, epinephrine, dopamine). The adrenal cortex consists of three layers:
the zona glomerulosa, the zona fasciculata, and the zona reticularis, which are responsible for the synthesis of mineralocorticoids, glucocorticoids,
and androgens (precursors for estrogen and testosterone) respectively. Mineralocorticoids regulate renal sodium and water reabsorption and
potassium excretion, while glucocorticoids play an important role in glucose metabolism. Diseases of the adrenal glands include adrenal
insufficiency (due to an infection, hemorrhage, autoimmune destruction), hyperaldosteronism (due to hyperplasia, adenoma),
and hypercortisolism (due to hyperplasia, adenoma, exogenous administration).
NOTES
FEEDBACK

Gross anatomy
Overview
 Two endocrine glands that produce steroid hormones and adrenaline
 Size: height and thickness ∼ 5 cm; width 1–2 cm

 Location
o Primary retroperitoneal organs

o Each gland is located superior to the upper pole of the kidney

o Enclosed by the renal fascia and adipose capsule of the kidney

 Embryology
o Adrenal cortex: derived from mesoderm

o Adrenal medulla: derived from the neural crest

 Function
 Adrenal cortex: outer layer that produces steroid hormones

 Adrenal medulla: inner part of the gland that produces catecholamines

Vasculature
 Arterial blood supply
o Superior suprarenal artery (from the inferior phrenic artery)

o Medial suprarenal artery (from the abdominal aorta)

o Inferior suprarenal artery (from the renal artery)

 Venous drainage
o Right suprarenal vein into the inferior cava vein

o Left suprarenal vein into the left renal vein

 Lymph drainage: left aortic lymph nodes; right caval lymph nodes

The left suprarenal vein merges into the left renal vein; the right suprarenal vein merges directly into the inferior vena cava!

Innervation
 Sympathetic: major and minor splanchnic nerves

 Parasympathetic: vagal nerve

NOTES
FEEDBACK

Microscopic anatomy
Adrenal cortex
  Surrounded by a fibrous capsule

 Layers of the cortex

o Zona glomerulosa

 Description: cells arranged in oval clusters surrounded by connective tissue from the fibrous capsule

 Function: mineralocorticoid synthesis

o Zona fasciculata

 Description: cells arranged in straight columns that are separated by small fibrous septa

 Function: glucocorticoid synthesis

o Zona reticularis

 Description: small cells arranged in an irregular netlike formation surrounded by connective tissue and capillaries

 Function: androgen synthesis

GFR → MGA = The layers of the adrenal cortex from outside to inside are GFR (G = Zona Glomerulosa, F = Zona Fasciculata, R = Zona
Reticularis). They are the Managing General Agents of some hormone synthesis.
Adrenal medulla
 Large chromaffin cells with many secretory granules (catecholamine storage)
o Chromaffin cells originate in the neural crest and migrate to the paraganglia and adrenal medulla during embryonic
development.
o Tumors originating from chromaffin cells are called pheochromocytomas.

 Function: synthesis of catecholamines

The cells of the adrenal medulla are modified sympathetic cells that are controlled by cholinergic synapses.
NOTES
FEEDBACK

Hormones of the adrenal cortex

Common synthesis pathway for all steroid hormones: cholesterol (precursor) → pregnenolone via cholesterol desmolase
MAXIMIZE TABLETABLE QUIZ

Hormone Site of Function Feedback control Associated

productio disorders
n

Mineralocorticoids: aldosterone  Zona  Regulation of renal  Renin-angiotensin-  Primary

glomerul sodium and water aldosterone system hyperaldostero
osa reabsorption and nism
potassium excretion  Adrenal
 See the section insufficiency
“Mineralocorticoids”  Congenital
below for details adrenal
hyperplasia

Glucocorticoids: cortisol  Zona  Metabolism: mobilize  CRH → ↑ secretion  Cushing

fascicula energy reserves of ACTH in the pituitary syndrome
ta gland → ↑ secretion
 High  Adrenal
of glucocorticoids and andr
dosage: immunosuppres insufficiency
ogens in the adrenal cortex
sive and antiphlogistic  Congenital
effect adrenal
 See cortisol for details hyperplasia

Androgens: dehydroepiandrosteron  Zona  Precursor  Adrenal

e (DHEA) reticulari for estrogen and testoste insufficiency
 Hormone Site of Function Feedback control Associated
productio disorders
n

s rone  Congenital
adrenal
 See the section
hyperplasia
“Androgens” for details

Going from outside to inside, the hormones produced in each layer: The deeper you go, the sweeter it gets: Salt (Na and mineralocorticoids, zona
+

glomerulosa), Sugar (glucocorticoids, zona fasciculata), and Sex (androgens, zona reticularis)
The RAAS regulates the release of mineralocorticoids!

NOTES
FEEDBACK

Mineralocorticoids
General
 Mineralocorticoids: aldosterone

 Site of synthesis: zona glomerulosa

Synthesis
MAXIMIZE TABLETABLE QUIZ

Biosynthesis of aldosterone

Steps Precursor Enzyme Product

1.  Pregnenolone  3β-hydroxysteroid dehydrogenase  Progesterone

Biosynthesis of aldosterone

Steps Precursor Enzyme Product

2.  Progesterone  21-hydroxylase (defective enzyme results in the most common form  11-
of congenital adrenal hyperplasia, deoxycorticosterone
with hypoaldosteronism, hypocortisolism, infant salt wasting, female
pseudohermaphroditism and precocious puberty in males)

3.  11-  11β-hydroxylase and aldosterone synthase (defective enzyme results  Corticosterone

deoxycorticosterone in congenital adrenal hyperplasia,
with hypoaldosteronism, hypocortisolism, female
pseudohermaphroditism)

4.  Corticosterone  Aldosterone synthase  Aldosterone

Regulation: renin-angiotensin-aldosterone system (RAAS)

 Positive feedback
o ↑ Angiotensin II: renal hypoperfusion (e.g., hypotension, stimulation of β receptors in the kidney)
1

→ kidneys release renin → renin converts angiotensinogen (produced in the liver) to angiotensin I (AT I) → conversion
of AT I to angiotensin II through angiotensin-converting enzyme (ACE, mostly produced in the lungs) → angiotensin
II acts as a strong vasoconstrictor and induces the secretion of aldosterone by the adrenal cortex
o ↑ Serum potassium concentration

 Negative feedback: ANP

 Function
 Mechanism: binds to intracellular mineralocorticoid receptors in the distal tubule and collecting duct of the kidney
o ↑ Na /K -ATPase in the basolateral membrane → transports Na out and K into the tubule cells
+ + + +

o ↑ Apical H -ATPase
+

o ↑ Na channels ENaC (epithelial natrium channel) and K channels ROMK (renal outer medullary potassium channel) in the
+ +

luminal membrane

 Effect: ↑ Na resorption; ↑ H O resorption; ↑ K excretion; ↑ H excretion → ↑ extracellular fluid, ↑ blood pressure, ↓

+
2
+ +

K , ↑ pH
+

Aldosterone stimulates the sodium and water retention and potassium excretion in the kidney!
NOTES
FEEDBACK

Glucocorticoids
General
 Glucocorticoids: mainly cortisol

 Site of synthesis: zona fasciculata

 Important cofactor: Vitamin C

Synthesis
MAXIMIZE TABLETABLE QUIZ

Steps Precursor Enzyme Product

1 Pregnenolone  Pregnenolone  17α-hydroxylase  17-

. pathway hydroxypregnenolon
e
Steps Precursor Enzyme Product

Progesterone pathwa  Pregnenolone  3β-hydroxysteroid dehydrogenase  Progesterone

y

2 Pregnenolone  17-  3β-hydroxysteroid dehydrogenase  17-

. pathway hydroxypregnenolon hydroxyprogesterone
e

Progesterone pathwa  Progesterone  17α-hydroxylase

y

3 Common pathway  17-  21-hydroxylase (defective enzyme results in the  11-deoxycortisol

. hydroxyprogesterone most common form of congenital adrenal
hyperplasia

4 Common pathway  11-deoxycortisol  11-β-hydroxylase (defective enzyme results  Cortisol

. in congenital adrenal hyperplasia,
with hypoaldosteronism, hypocortisolism, femal
e pseudohermaphroditism)
o Metyrapone inhibits this reaction

Regulation: hypothalamic-pituitary gland-adrenal cortex feedback mechanism

 Mechanism: corticotropin-releasing hormone (CRH) → ↑ secretion of adrenocorticotropic hormone (ACTH) in the pituitary
gland → ↑ secretion of glucocorticoids in the adrenal cortex

 Positive feedback: trigger CRH release

 o Pain, stress (psychological/physical)

o Pyrogens, adrenaline, histamine

o Hypoglycemia, hypotension

 Negative feedback: glucocorticoids

 Circadian rhythm: early morning ↑ serum CRH levels → ↑ cortisol levels

Cortisol inhibits the secretion of CRH and ACTH via negative feedback, which, in turn, results in a decrease in cortisol secretion.

Function
 Metabolism: mobilize energy reserves
o ↑ Gluconeogenesis: to maintain blood glucose levels

o ↑ Glycogen synthesis: to maintain glucose storage

o ↑ Protein catabolism

o ↑ Lipolysis

o ↑ Appetite

o ↑ Insulin resistance

o Inhibitory effect on bone metabolism and stimulation of bone degradation: direct inhibition of osteoblastic activity and
inhibition of osteoclast apoptosis

 Immunosuppression and antiphlogistic effect: complex mechanisms

o ↓ Lymphocytes, eosinophils, and monocytes

o ↑ RBCs, ↑ Platelets, ↑ Neutrophil granulocytes (overall WBC increases)

 o Inhibition of T-cell and B-cell responses

o Inhibition of cytokine synthesis and secretion (e.g., IL-2)

o ↓ Mast cell activation and histamine release

 ↓ Wound healing

 Permissive effect on catecholamines (e.g., increase in blood pressure

 Mild mineralocorticoid effect: increase in blood pressure, potassium excretion

 Clinical use of glucocorticoids in the treatment of inflammatory and autoimmune conditions and allergic reactions (see
learning card on glucocorticoids)

NOTES
FEEDBACK

Androgens
General
 Androgens: intermediate sex steroids in the adrenal cortex
o Dehydroepiandrosterone (DHEA)

o DHEAS (Dehydroepiandrosterone sulfate)

o Androstenedione

 Site of synthesis: zona reticularis

In both men and women, DHEA and androstenedione are produced in the adrenal cortex, which are precursors
for testosterone and estrogen. Testosterone is produced by Leydig cells in the testes in men and, to a lesser degree, ovarian stroma in women.
Synthesis
 17α-hydroxylase: converts pregnenolone → 17-hydroxypregnenolone → dehydroepiandrosterone (DHEA)
o Defective enzyme → rare form of congenital adrenal hyperplasia that results in male pseudohermaphroditism and delayed
puberty in females

 3β-hydroxysteroid dehydrogenase: converts DHEA → androstenedione

 DHEA and intermediates (e.g., androstenedione) are secreted by the adrenal cortex

 Further processing occurs in the target tissue: gonads, brain, adipose tissue

, skin, bone, placenta (see function below)

Regulation: hypothalamic-pituitary gland-adrenal cortex feedback mechanism

 Corticotropin-releasing hormone (CRH) → ↑ secretion of adrenocorticotropic hormone (ACTH) in the pituitary gland → ↑
secretion of androgens in the adrenal cortex
Function
 Mechanism: Adrenal androgens (DHEA and androstenedione) serve as precursors of:

1. More potent androgens

 Androstenedione → testosterone

 Testosterone → dihydrotestosterone (DHT) via 5α-reductase

 Defective 5α-reductase → 5α-reductase deficiency

 5α-reductase inhibitors (e.g., finasteride) inhibit the conversion → used to treat BPH

 DHT is a potent form of testosterone

 Causes hair follicles to transform into terminal hair in androgen sensitive areas
  Upper lip, chin, upper abdomen, and back.

 Idiopathic hirsutism affects 5-10% of female patients

 10% of cases arise from hyperandrogenism of adrenal origins

2. Estrogen (in men and postmenopausal women

 Aromatase: converts testosterone → estradiol and androstenedione → estrone

 Effects of androgens
o Male sexual differentiation during embryonic development

o Male pubertal development of secondary sexual characteristics (e.g., growth spurt, increased muscle mass, penile growth,
deepening of the voice, Adam's apple growth, acne)
o Spermatogenesis

o Increased libido

o Anabolic effects on muscles and bones

o Stimulate erythropoiesis (↑ RBCs)

o Influence behavior (e.g., aggression)

 Effects of estrogen
o Female sexual differentiation during embryonic development

o Female pubertal development of secondary sexual characteristics

o See Estrogen and associated diseases for details

Generally, the effects of androgens in women only become apparent in cases of androgen excess (e.g., PCOS, androgen-secreting tumors).
References: [1][2][3]

NOTES
FEEDBACK

Hormones of the adrenal medulla: catecholamines

 General
 Catecholamines: norepinephrine, epinephrine, dopamine

 Site of synthesis
o Regions of the CNS

o Chromaffin cells of the adrenal medulla

o Postganglionic adrenergic neurons

 Stimuli
o Sympathetic activation ("fight and flight")

o Cortisol from the adrenal cortex

Synthesis
MAXIMIZE TABLETABLE QUIZ

Step Precursor Enzyme Product

1. 1 Hydroxylation
st
Phenylalanine  Phenylalanine hydroxylase Tyrosine
 Cofactor: Tetrahydrobiopterin (THB)

2. 2 Hydroxylation
nd
Tyrosine  Tyrosine hydroxylase DOPA (3,4-
Dihydroxyphenylalanine)
 Cofactor: THB

3. Decarboxylation DOPA  DOPA decarboxylase Dopamine

 Cofactor: Pyridoxal phosphate (Vitamin B6)

4. Hydroxylation of the β-C- Dopamine  Dopamine β-monooxygenase Norepinephrine

Atom  Cofactor: vitamin C

5.Methylation Norepinephrin  Phenylethanolamine-N-Methyltransferase Epinephrine

e (PNMT)
 Step Precursor Enzyme Product

o Cortisol induces expression of PNMT

 Cofactor: S-Adenosylmethionine (SAM)

Epinephrine has the shortest half-life of the catecholamines.

Stress results in an increased production of catecholamines and glucocorticoids.

Degradation
 Enzymatic degradation via catecholamine-O-methyltransferase (COMT) and monoamine oxidase (MAO)
o MAO inhibitors (antidepressant drugs) prevent the degradation of catecholamines in the CNS → elevated concentration
of catecholamines in synaptic cleft → improve depressive symptoms

 End-stage metabolite: vanillylmandelic acid (VMA)

o VMA has diagnostic value: elevated urinary excretion in patients with pheochromocytoma and neuroblastoma

The end-stage metabolite of epinephrine and norepinephrine is vanillylmandelic acid. Urinary excretion of VMA has diagnostic value
in pheochromocytoma and neuroblastoma!
Function
 Sympathetic activation → fight-or-flight reaction

 Mechanism: catecholamines bind to various adrenergic receptors (with differing functions depending on the respective G
protein; see table below) located on different organs and tissue → trigger specific responses with the ultimate goal to
prepare for a fight-or-flight reaction

MAXIMIZE TABLETABLE QUIZ

Overview of peripheral adrenergic receptors

Recepto G Signal transduction Location Effect

r protein

α 1 Gq Stimulation of phospholipase C:  Vasculature  ↑ Contraction of smooth

PIP → IP und DAG → ↑ Ca
2 3
2+
(skin and GI tract) muscles → vasoconstriction

 GI tract  ↑ Constriction of sphincters

 Bladder

α 2 Gi Inhibition of adenylate cyclase:  White adipose tissue  ↓ Lipolysis

↓ cAMP
 GI tract  ↓ Muscular contraction
 Bladder

 Pancreas  ↓ Insulin secretion

β 1 Gs Stimulation of adenylate cyclase:  Heart  ↑ Heart rate

↑ cAMP  ↑ Contractility
 ↑ Conductivity

 Kidney  ↑ Renin secretion

β 2  Vasculature (coronary  ↓ Contraction of smooth musculature →

vessels, skeletal vasodilatation and bronchodilatation
muscles)
 Bronchi

 Liver  ↑ Glycogenolysis
 Skeletal muscles
 Overview of peripheral adrenergic receptors

Recepto G Signal transduction Location Effect

r protein

 White adipose tissue  ↑ Lipolysis

 Pancreas  ↑ Insulin secretion

 Uterus  Tocolysis

β 3  Brown adipose tissue  ↑ Lipolysis

NOTES
FEEDBACK

Clinical significance
Important diseases associated with the adrenal cortex
 Hypocortisolism

 Hypercortisolism

 Primary hyperaldosteronism (Conn syndrome)

 Congenital adrenal hyperplasia (CAH)

 Androgen-secreting tumors
Important diseases associated with the adrenal medulla
 Pheochromocytoma

 Neuroblastoma

General endocrinology
(Endocrinology)
Last updated: Dec 10, 2019
QBANK SESSION
 CLINICAL SCIENCES
LEARNED

Summary
Endocrinology is the field of medicine concerned with endocrine tissue (e.g., the pituitary gland, thyroid gland, adrenals, testicles, and ovaries),
metabolic diseases, and to an extent, nutritional medicine. Endocrine tissue is responsible for producing and secreting hormones, which influence the
function of certain cells and organs. Hormone secretion is controlled by highly regulated pathways that involve cell signaling and positive or negative
feedback. Disruption to these pathways can lead to an imbalance of hormones, resulting in various pathological conditions involving hyperactive or
hypoactive glands (e.g., hyperthyroidism or hypothyroidism, respectively). One complex pathway is known as the hypothalamic-pituitary axis, which
is the main focus in this learning card. An understanding of these hormone pathways is important for determining the next best step of management,
particularly when interpreting changes in hormone levels and the results of suppression or stimulation tests.

NOTES
FEEDBACK

Overview of endocrinological diseases

This learning card focuses on the hypothalamic-pituitary axis. Other important hormones and metabolic diseases are discussed in their respective
learning cards.

 Metabolic diseases
o Diabetes mellitus

o Osteoporosis (see calcium homeostasis)

o Metabolic syndrome

 Diseases of the endocrine glands of the hypothalamic-pituitary axis

o Pituitary gland

 Hypopituitarism

 Prolactinoma
  Acromegaly

 Diabetes insipidus
o Adrenal cortex

 Hypocortisolism

 Hypercortisolism

 Primary hyperaldosteronism

 Congenital adrenal hyperplasia

o Thyroid gland

 Hypothyroidism

 Hyperthyroidism
o Gonads

 Hypogonadotropic hypogonadism

 Hypergonadotropic hypogonadism

 Aging endocrine system

NOTES
FEEDBACK

Basics of endocrinology
Hormone
 Definition: Hormones are endogenous messengers that are produced in glands or single cells. They are responsible
for signal transduction and influence the function and metabolic rate of other organs and cells. Complex regulatory circuits
normally control their secretion.

 Hormones can be categorized based on their signaling pathways:

o Paracrine hormones: affect the neighboring cells through diffusion

o Autocrine hormones: affect the secreting cell itself

 o Endocrine hormones: are secreted into the bloodstream to reach their targets

 Based on their chemical nature:

o Steroid hormones: derived
from cholesterol (e.g., testosterone, progesterone, estrogen, glucocorticoids, mineralocorticoids)
o Amine hormones: derived from a single amino acid such as phenylalanine, tyrosine,
or tryptophan (e.g., catecholamines, thyroid hormones (T3 and T4))
o Peptide/protein hormones: derived from a few or many amino
acids (e.g., oxytocin, vasopressin, prolactin, glucagon, insulin)

 Based on their biochemical properties:

o Lipophilic hormones: steroid hormones and thyroid hormones
o Hydrophilic hormones: peptide/protein hormones and amine hormones (except for thyroid hormones!)

Hydrophilic hormones (e.g., catecholamines) are stored in secretory granules and are released when needed. Lipophilic hormones (e.g.,
adrenocortical steroid hormones) pass into the bloodstream once synthesized. They are not stored by cells.
Degradation of hormones

 Steroid hormones and thyroid hormones: inactivation and conjugation in the liver and excretion in bile

 Catecholamines: enzymatic degradation and excretion in urine (e.g., vanillylmandelic acid)

 Peptide/protein hormones: proteolytic degradation mainly in the liver and kidneys

Feedback control mechanisms
Hormones are controlled by different feedback mechanisms. Take the simplified feedback mechanism of the antidiuretic hormone (ADH) as an
example:
1. Receptors in the hypothalamus measure plasma osmolality (measuring system).

2. If the osmolality exceeds a set point, the neural pituitary gland excretes ADH (controlled variable).

3. ADH increases renal reabsorption of water (process unit).

4. Receptors in the hypothalamus detect falling osmolality and reduce ADH secretion, which decreases the amount of water
reabsorption in the kidneys.
 Diagnosis of endocrine diseases
The following methods may be used:

 Direct measurement of hormone blood levels (e.g., measuring prolactin blood level upon clinical suspicion of prolactinoma)

 Stimulation of glands to detect underactivity (e.g., ACTH stimulation test for Addison's disease = chronic adrenal
insufficiency)

 Inhibition of glands to detect hyperactivity (e.g., dexamethasone suppression test for Cushing's
syndrome = hypercortisolism)

 Imaging of glands to determine:

o Morphological abnormalities (e.g., thyroid ultrasound

)
o Functional abnormalities (e.g., thyroid scintigraphy for autonomous thyroid nodule)

 Specific laboratory studies (e.g., determination of thyrotropin receptor antibodies, or HbA for diabetes mellitus)
1c

References: [1][2]

NOTES
FEEDBACK

Hypothalamus and pituitary gland

Hypothalamus
 Ventral part of the diencephalon (forebrain) composed of several nuclei

 Regulates hormonal pathways and autonomic functions (e.g., control of body temperature and food intake)

 Hormones of the hypothalamus mostly affect hormonal secretion of the anterior pituitary gland.
o Exceptions: antidiuretic hormone (ADH) and oxytocin
  Produced in the hypothalamus → axonal transport in association with neurophysins to posterior pituitary gland for
storage → released into circulation as needed

 There are two types of hormones: releasing hormones (increase hormonal secretion from the pituitary gland) and inhibiting
hormones (decrease hormonal secretion from the pituitary gland)
 For more information on the anatomy of the hypothalamus, see the learning card for diencephalon.
Pituitary gland (hypophysis)
 Located in a midline depression of the sphenoid bone (sella turcica) in the middle cranial fossa
 Connects to the hypothalamus through the pituitary stalk (infundibulum)

 Divided into two parts:

o Anterior pituitary gland (= adenohypophysis)

o Posterior pituitary gland (= neurohypophysis)

Overview of hypothalamic-pituitary axis
Hypothalamic-(anterior) pituitary axis

 The anterior pituitary produces two different types of hormones:

o Tropic hormones → affect cells indirectly by stimulating other endocrine glands first

o Nontropic hormones → direct effect on cells

Tropic hormones
MAXIMIZE TABLETABLE QUIZ
 Hypothalamus Pituitary gland Endocrine target
organ

Hypothalamic-pituitary- CRH (corticotropin-releasing  ACTH (adrenocorticotropic  Adrenal cortex

adrenal axis hormone) hormone)

Hypothalamic-pituitary- TRH (thyrotropin-releasing  TSH (thyroid-stimulating hormone)  Thyroid gland

thyroid axis hormone)

Hypothalamic-pituitary- GnRH (gonadotropin-releasing  Gonadotropins  Gonads

gonadal axis hormone) o LH (luteinizing hormone)
o ♀: Ovaries
o FSH (follicle-stimulating
hormone)
o ♂: Testicles

Nontropic hormones
MAXIMIZE TABLETABLE QUIZ

Hypothalamus Pituitary gland Main effect

Hypothalamic- GHRH (growth hormone-  GH (growth  Stimulates growth and has

pituitary- releasing hormone) hormone, somatotropin) an anabolic effect on the body
somatotropic axis  Direct effects of GH:
o ↓ Glucose uptake into cells
o ↑ Lipolysis
o ↑ Protein synthesis in muscle
o ↑ Production of IGF
 Hypothalamus Pituitary gland Main effect

Somatostatin (growth hormone–  Inhibits release of GH  Opposes effects of GHRH

inhibiting hormone)
 GI tract: suppresses release
of: gastrin, cholecystokinin, secretin, VIP

Hypothalamic- TRH (thyrotropin-releasing  Prolactin (secreted  Breast tissue: growth and lactation
pituitary- hormone, thyroliberin): by lactotropic cells)
prolactin axis stimulates secretion
of prolactin in the pituitary gland

Dopamine, also called PIH

(prolactin-inhibiting hormone):
inhibits secretion of prolactin in
the pituitary gland

MSH-RH (melanocyte-stimulating  MSH (melanocyte-  Skin: hyperpigmentation due to

hormone-releasing hormone) stimulating hormone) stimulation of melanocytes

Melanocyte-inhibiting hormone

Hormones of the hypothalamus-(posterior) pituitary axis

 The posterior pituitary gland (= neurohypophysis) stores and secretes two peptide hormones from the hypothalamus
o Antidiuretic hormone (ADH, vasopressin): regulation of free water balance (and blood pressure)

 Reabsorption of water (→ antidiuretic effect) via insertion of water channels (aquaporins) into the renal convoluted
tubule (through V2 receptors)
  At higher levels: vasoconstriction (through V1 receptors)
o Oxytocin: induces uterine contractions and the release of milk

Important diseases associated with the hypothalamus and pituitary gland

 Hypopituitarism

 Prolactinoma

 Acromegaly

 Diabetes insipidus

 SIADH

References: [3][4][5][6][7][8][9]

NOTES
FEEDBACK

Adrenal cortex
The adrenal cortex consists of three distinct layers

 Zona glomerulosa: produces mineralocorticoids

 Zona fasciculata: produces glucocorticoids (see cortisol for effects)

 Zona reticularis: produces androgens (see dehydroepiandrosterone for effects)

For more information see the learning card for hormones of the adrenal cortex
NOTES
FEEDBACK

Thyroid gland
Thyroid hormones
 The thyroid gland secretes two thyroid hormones: T (triiodothyronine) and T (thyroxine, tetraiodothyronine).
3 4
 More T is produced than T but T is less potent.
4 3 4

o Peripheral 5'-deiodinase in the blood converts T into the biologically active T .

4 3

o T is therefore considered a hormonal precursor (prohormone).

4

o Half of the T4 is processed into biologically inactive T3 (reverse T3).

 The half-life of T is about one day (∼ 20 hours), whereas the half-life of T is about one week (∼ 190 hours). This
3 4

longer half life makes T suitable for use as a depot form that can be used replacement therapy.
4

 Furthermore, the C cells of the thyroid gland produce calcitonin, which regulates calcium balance.

Physiological effects of thyroid hormones

 ↑ Basal metabolic rate (↑ oxygen consumption, and ↑ body temperature)

 Stimulation of carbohydrate metabolism

 Anabolism of proteins (in high doses: catabolism of proteins)

 Induces either lipolysis or liponeogenesis depending on metabolic status

 Permissive effect on catecholamines (particularly via β receptors)

 In children: stimulation of bone growth

 CNS effects
o Perinatal period: maturation of the brain (therefore, hypothyroidism screening is very important!)

o Adulthood:

 Hyperthyroidism: hyperexcitability, irritability

 Hypothyroidism: somnolence, slowed speech, impaired memory

 Reproductive effects
o Fertility

o Ovulation and menstruation

Feedback control mechanisms
  Hypothalamus: TRH (thyrotropin-releasing hormone, thyroliberin) → stimulates secretion of TSH (thyroid-
stimulating hormone, thyrotropin) in the pituitary gland → stimulates release of T (triiodothyronine) and T (thyroxine,
3 4

tetraiodothyronine) in the thyroid gland

o Stimuli: exposure to extreme cold, stress

o Inhibition

 T /T inhibit TRH and TSH, which as a result inhibits T /T secretion and iodine uptake
3 4 3 4

 Somatostatin, dopamine, and glucocorticoids inhibit the production of TSH.

Important diseases associated with the thyroid gland

 Hypothyroidism

 Hyperthyroidism
References: [7][10][11][12]

NOTES
FEEDBACK

Gonads
Physiological effects of LH, FSH, and sex hormones

 ♀ : Ovaries

o FSH: follicular maturation → ↑ estrogen (see effects of estrogen and associated diseases)

o LH: ↑ estrogen, ovulation, and ↑ progesterone

 ♂ : Testicles

o FSH: production of sperm, ↑ inhibin

 o LH: stimulation of Leydig cells → ↑ production of testosterone

 Effects of testosterone

 Development of male sexual characteristics during puberty

 Spermatogenesis

 Increased libido

 Anabolic effects

 Bone formation, growth

 Muscle-building effects

Feedback control mechanisms

 Hypothalamus: GnRH → stimulates release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone) in
the pituitary gland → the effects of LH and FSH on the gonads are different in men and women
o Stimuli: pulsatile release of GnRH starting at puberty

o Inhibition of GnRH, LH, and FSH secretion by:

 Androgen, estrogen, progesterone

 Inhibin

 Secretion is regulated by central neuromodulators.

Important diseases associated with the gonads
 Hypogonadotropic hypogonadism

 Hypergonadotropic hypogonadism
 Drugs that act on the hypothalamic-pituitary-gonadal axis
 GnRh agonists

 GnRh antagonists
 OCPs

 Spironolactone

 Ketoconazole

 SERM

 Anastrazole

 Finasteride

 Flutamide

 Clomiphene

 Cyproterone

References: [11]

NOTES
FEEDBACK

Regulation of appetite
 Key hormones:
o Leptin: A hormone predominantly produced in adipose tissue that is a key mediator of long-term regulation of food intake
and body weight and inhibits hunger.
 o Neuropeptide Y (NPY): A neurotransmitter primarily stored in the hypothalamus that has several functions in the central
and peripheral nervous systems, including:

 Appetite stimulation

 Regulation of anxiety-related behavior

 Neuronal excitability
o Ghrelin: A hormone secreted by the stomach that stimulates appetite. Levels increase during fasting states and decrease
after intake of food.

Regulation of hunger: occurs in the lateral nucleus of the hypothalamus

o Stimulated by:

 Ghrelin

 Neuropeptide Y (NPY)
o Inhibited by: leptin (produced in adipose tissue) → decreases NPY

 Regulation of satiety: occurs in the ventromedial nucleus of the hypothalamus

o Stimulated by:

 Cholecystokinin (short-term effect via inhibition of gastric emptying and food intake)

 Leptin (long-term)

 Polyphagia: excessive hunger (e.g., due to hyperthyroidism, hypoglycemia)

Ghrelin makes you a gluttonous gremlin. Leptin makes you thin!

Metabolic syndrome
Last updated: Dec 10, 2019
QBANK SESSION
CLINICAL SCIENCES
LEARNED

Summary
Metabolic syndrome describes a constellation of medical conditions which increase the risk for several health problems, primarily cardiovascular
disease, type 2 diabetes, and fatty liver.These conditions include insulin resistance (considered the main risk factor), hypertension, dyslipidemia, and
abdominal obesity. The primary goal in treating metabolic syndrome is therefore to initiate lifestyle changes, which include dietary modifications and
physical exercise. These measures often result in lowered blood pressure and triglyceride levels, as well as increased insulin sensitivity. Symptoms
that do not respond sufficiently to these changes, such as persistent hypertension or hyperglycemia, are treated with drugs (e.g., ACE
inhibitors, metformin).
NOTES
FEEDBACK

Definition
Metabolic syndrome
 Presence of ≥ 3 of the following conditions (or already receiving medical treatment for them)
o Insulin resistance: fasting glucose ≥ 100 mg/dL

o Elevated blood pressure: ≥ 130/85 mm Hg

o Elevated triglycerides: ≥ 150 mg/dL

o Low HDL-C: in men < 40 mg/dL; in women < 50 mg/dL

o Abdominal obesity: waist circumference ≥ 102 cm in men; ≥ 88 cm in women

Obesity
MAXIMIZE TABLETABLE QUIZ

Weight Status Body Mass Index (BMI)

Underweight < 18.5

Normal or Healthy Weight 18.5–24.9

Overweight ≥ 25–29.9

Class I Obesity 30–34.9

Class II Obesity 35–39.9

 Weight Status Body Mass Index (BMI)

Class III Obesity ≥ 40

References: [1][2][3][4]

NOTES
FEEDBACK

Treatment
 First-line: lifestyle modifications
o Dietary changes: calorie restriction, healthy foods (e.g., fruit/vegetables, protein-rich, unsaturated fats, sodium-restricted)

o Physical activity: minimum of 30 minutes moderate exercise per day (2.5 hours per week) , which
increases insulin sensitivity, lowers blood pressure, and promotes weight loss

 Medical therapy: treat hypertension (e.g., ACE inhibitors), diabetes mellitus, and dyslipidemia (e.g., with statins)

 Bariatric surgery: if BMI ≥ 40 and no success with dietary and lifestyle changes
o Sleeve gastrectomy (most common): large part of the greater curvature is removed, so that the
remaining stomach resembles a sleeve
o Roux-en-Y gastric bypass (2 most common): Roux-en-Y
nd

References: [1][5][6][7]

NOTES
FEEDBACK

Complications
Metabolic syndrome is associated with increased risk of:

 Cardiovascular disease

 Type 2 diabetes

 Non-alcoholic steatohepatitis → increased risk of developing liver cirrhosis and hepatocellular carcinoma

We list the most important complications. The selection is not exhaustive.

Thyroid gland and parathyroid glands
Last updated: Jun 14, 2020
QBANK SESSION
LEARNED

Summary
The thyroid gland is a butterfly-shaped endocrine gland located inferior to the larynx and anterior to the trachea. The thyroid gland develops from the
fusion of the median thyroid anlage with the two lateral thyroid anlages, which are derived from the pharyngeal pouches. The thyroid gland receives
its arterial supply from the superior and inferior thyroid arteries and drains into the superior, middle, and inferior thyroid veins. The thyroid
gland secrets thyroid hormones, which regulate body metabolism and growth, and calcitonin, which lowers serum calcium and phosphate through
inhibition of osteoclasts. Hormone synthesis occurs in the epithelial lining of the thyroid follicles. The epithelial lining consists of follicular
(thyroid epithelial) cells, which synthesize thyroid hormone, and parafollicular (C) cells, which synthesize calcitonin.
The parathyroid glands are four, oval-shaped endocrine glands located on the posterior surface of the thyroid gland. They are derived from the third
and fourth pharyngeal pouches. The parathyroid glands receive their arterial supply from the inferior thyroid arteries and drain into
the thyroid venous plexus. The parathyroid chief cells secrete parathyroid hormone, which maintains serum calcium and phosphate homeostasis and,
furthermore, antagonizes the effect of calcitonin by increasing serum calcium and decreasing serum phosphate. The recurrent laryngeal
nerves, parathyroid glands, sympathetic trunks, and the nerves of the carotid sheath are at risk of injury during thyroid surgery.
NOTES
FEEDBACK

Thyroid gland
Overview
 Characteristics: butterfly-shaped, unpaired endocrine gland composed of two lobes

 Location
o Located anteriorly in the lower part of the neck

o Extends from C5–T1

o Surrounded by pretracheal fascia (along with pharynx, trachea, esophagus)

o Relations of the thyroid gland

 Anteriorly: strap muscles (i.e., sternohyoid, sternothyroid, thyrohyoid, and omohyoid muscles)
  Medially: the trachea, esophagus, recurrent laryngeal nerve (RLN), and the external branch of the superior laryngeal
nerve

 Posteriorly: the parathyroid glands

cricoid cartilage, lower thyroid cartilage, and the carotid sheath with its contents (i.e., internal jugular vein, vagus
nerve, and common carotid artery)

 Function: produce thyroid hormones that are essential for regulating metabolism and growth (see general endocrinology)

Damage to the recurrent laryngeal nerves, parathyroid glands, sympathetic trunks, and even the nerves of the carotid sheath is possible
during thyroidectomy because of the thyroid's location in the anterior neck.

NOTES
FEEDBACK

Gross anatomy
Gross anatomy
 The thyroid gland is made up of a left lobe and a right lobe connected by an isthmus.
 An ascending pyramidal lobe is present in ∼ 50% of the population.

 The thyroid gland is encapsulated by:

o Pretracheal fascia (false/surgical capsule)

o Internal capsule: An inner connective tissue covering that cannot be separated from the gland (true capsule).

 Forms septae, dividing the gland into lobes and lobules.

 Vasculature and innervation
MAXIMIZE TABLETABLE QUIZ

Vessel Supplies

Arterial  Superior thyroid artery (paired) of external carotid artery  Superior and anterior portions of the
supply gland
 Superior parathyroid glands

 Inferior thyroid artery(paired) from the thyrocervical trunk (branch  Posterior and inferior portions of the
of subclavian artery) gland
 Inferior parathyroid glands

 Thyroid ima artery (unpaired) from the brachiocephalic trunk of the arch  Anterior surface and isthmus
of aorta

Venous  Superior thyroid veins  Drain into internal jugular vein

drainage  Middle thyroid veins

 Inferior thyroid veins  Drain into the right and

left brachiocephalic veins

 Lymphatics
o Paratracheal nodes

o Deep cervical nodes

 Innervation
 o Vagus nerve (parasympathetic)

o Superior, middle, and inferior cervical ganglia of the sympathetic trunk

The inferior thyroid artery runs close to the recurrent laryngeal nerve and the superior thyroid artery close to the superior laryngeal nerve. Both
nerves are at risk during thyroid surgery!

NOTES
FEEDBACK

Microscopic anatomy
Lobules of thyroid gland
 Main component: thyroid follicles
o Smallest functional units

o Spheric, vesicular components of the thyroid gland lined with epithelium

o Follicular lumen (central cavity) filled with colloid: storage of thyroglobulin, the thyroid hormone precursor

o Epithelium contains two cell types

 Thyroid epithelial cells

 C cells

 Interfollicular spaces are filled by reticular connective tissue, fenestrated capillaries (facilitate the release of hormones into
the blood), lymphatic vessels, adipocytes, and sympathetic nerves.

MAXIMIZE TABLETABLE QUIZ

 Cell type Characteristics Function

Thyroid epithelial
cell (= follicular cells)
 Appearance: basophilic cuboidal epithelium
 Occurence: arranged in spherical follicles
surrounding colloid
 Surface receptor: TSH receptors
 Take up amino acids and iodine on their basolateral side
from blood
 Synthesize, secrete, and store thyroglobulin and thyroid
peroxidase
o Stored in iodine-rich, gelatinous thyroid colloid

C cells (parafollicular  Appearance: large pale-staining cells
cells) between thyrocytes
 Occurrence: found along the basement
membrane of the thyroid epithelium, which
surrounds the follicles and has no direct contact
with the follicular lumen
 Surface receptor: calcium-sensing receptors
(CaSR)
 Hormone production and storage in granules
o Procalcitonin → proteolytic cleavage of N- and C-
terminal peptide → calcitonin
o Also secretes several neuroendocrine peptides in
smaller quantities such
as serotonin, somatostatin, dopamine, TRH,
and motilin

NOTES
FEEDBACK

Function
The thyroid gland produces thyroid hormones, which stimulate metabolism and growth, as well as calcitonin, which decreases bone resorption and is
involved in plasma calcium homeostasis.
Calcitonin
 Function: lowers calcium in serum (see disorders of calcium balance)
o Bones: inhibits osteoclast activity

o Kidneys: increases excretion of calcium and phosphate

 o Intestine: lowers calcium absorption

o The physiological role of calcitonin is low as bone and calcium metabolism are mainly regulated by the parathyroid
hormone and vitamin D.

 Clinical significance
o Important as a tumor marker for medullary thyroid cancer

o Acts as a synthetic analog for the treatment of osteoporosis (minimizes bone resorption)

o The precursor procalcitonin plays an increasingly important role as a marker for bacterial infection (e.g., sepsis).
Thyroid hormones
Thyroid hormone synthesis
The thyroid hormones T (triiodothyronine) and T (thyroxine, tetraiodothyronine) are synthesized by thyrocytes in the thyroid follicles.
3 4

1. Thyroglobulin, an iodine-free hormone precursor, is stored in the follicular lumen.

2. Iodide is actively taken up by thyrocytes and transported into the follicular lumen.

3. Here, thyroid peroxidase catalyzes the iodination of tyrosine residues of thyroglobulin, creating precursors
monoiodotyrosine (MIT) and diiodotyrosine (DIT) and eventually the thyroid hormones.
4. To release T and T , the iodinated thyroglobulin must be taken up again by thyrocytes, where it is broken down
3 4

by lysosomes, thus releasing attached T and T . 4 3

5. T and T are then transported out of the thyrocyte into the blood.
4 3

Detailed steps of thyroid hormone synthesis

MAXIMIZE TABLETABLE QUIZ

Steps Description Site

1. Synthesis 1. Thyroglobulin (TG) is produced in the rough ER of the follicular cells. Thyrocyte → follicular lumen
of thyroglobulin (TG)
2. TG is packed in vesicles in the Golgi apparatus.
3. TG is released into the follicular lumen via exocytosis.
Steps Description Site

2. Uptake of iodide 1. Basolateral transport Blood vessel

→ thyrocyte → follicular
o Na /I -symporter: Uptake of iodide by thyrocytes
+ −

lumen
2. Apical transport
o Pendrin: Iodine diffuses to the apex of the cell and is transported
into the follicular lumen via the Pendrin transporter.

3. Iodination  Thyroid peroxidase (TPO) In follicular lumen

of thyroglobulin 1. Oxidation of iodide (I → I ) -
2

2. Organification of the generated I by covalently linking it with

2

the tyrosine residues present in TG.

 Generates single (TG + H O + I = monoiodotyrosine, MIT) or
2 2 2

double-iodinated species of tyrosine (TG-MIT + H O + I = 2 2 2

diiodotyrosine, DIT)
3. Coupling reaction: conjugation of iodinated tyrosine residues
 Two DIT molecules form tetraiodothyronine (T4)
 One MIT and one DIT form triiodothyronine (T3)
 NADPH-oxidase: apical enzyme that generates H O for thyroid 2 2

peroxidase
o Reaction: NADPH + H + O → NADP + H O
+
2
+
2 2

4. Storage  Bound to thyroglobulin In follicular lumen

5. Release 1. Reuptake of iodinated TG in thyrocytes via endocytosis Thyrocyte → fenestrated

capillary network
2. Fusion of endocytosis vesicles with lysosome
3. Proteolytic enzymes cleave TG to release T3, T4, DIT, and MIT
4. T (∼ 20%) and T (∼ 80%) are released into the blood (via the MCT8
3 4

transporter)
5. Deiodinase removes the iodine from the MIT and DIT
 Steps Description Site

o Iodine is then redistributed to the intracellular I pool

-

(iodine salvage).

Thyroxine hormone is produced from tyrosine and iodine.

TPO is stimulated by TSH and inhibited by propylthiouracil, methimazole, and excess iodine (Wolff-Chaikoff effect), resulting in high or low levels
of thyroid hormones, respectively.
Transport and degradation
Thyroid hormones are lipophilic; most of the circulating thyroid hormones are inactive and bound to transport proteins. Only a very small fraction (∼
0.3%) is unbound and biologically active.

 Transport proteins
o Primarily thyroxine-binding globulin (TBG)
o Transthyretin: transports thyroxine and retinol

o Albumin

 Degradation (liver): sulfation/glucuronidation (biotransformation) → excretion via bile

Effect
In general, thyroid hormones increase the metabolic rate: oxygen and energy consumption as well as thermogenesis increase under their influence.
See thyroid hormones in the general endocrinology learning card for more information regarding their functionality.
MAXIMIZE TABLETABLE QUIZ
 Target organ Effect

Heart  ↑ Expression of cardiac β-receptors:

o ↑ Heart rate
o ↑ Stroke volume
o ↑ Cardiac output
o ↑ Contractility

Lungs  Stimulation of the respiratory center

 ↑ Oxygenation due to increased lung perfusion

Skeletal muscle  Increased development of type II muscle fibers (fast-twitch muscle fibers), which are capable of fast and
powerful contractions

Metabolism  ↑ Basal metabolic rate due to ↑ expression of Na /K ATPase in many tissues → ↑ oxygen consumption, ↑
+ +

body temperature, and ↑ RR

 Anabolism of proteins (in high doses: catabolism of proteins)
 Induces either lipolysis or liponeogenesis depending on metabolic status
 Stimulation of carbohydrate metabolism (↑ glucose reabsorption, ↑ gluconeogenesis, ↑ glycogen synthesis, ↑
glucose oxidation)

Growth during  Stimulation of bone growth via:

childhood o Induction of chondrocytes, osteoblasts, and osteoclasts.
o Promotion of synthesis and secretion of growth hormone
 Maturation of the nervous system

Thermoregulation  Thermogenesis

Regulation
Like the adrenal steroid hormones, the thyroid hormones are under the control of the hypothalamic-pituitary axis.
Thyroid-stimulating hormone (TSH) from the pituitary gland stimulates the basolateral uptake of iodine, as well as the biosynthesis and release
of thyroid hormones.
TSH levels are very sensitive to thyroid hormone dysfunction. If thyroid hormone levels are very high, TSH can fall below detection limits and if
they are very low, TSH increases markedly. Therefore, serum TSH is an important parameter for assessing thyroid function and is usually the first
step in thyroid diagnostics.
NOTES
FEEDBACK

Embryology
 The thyroid gland develops in the first trimester of pregnancy from the fusion of the median thyroid anlage with the
two lateral thyroid anlages derived from the pharyngeal pouches
o Median thyroid anlage

 An endodermal thickening in the floor of the primordial pharynx between the 1 and 2 pharyngeal pouches
st nd

 This thickening becomes the thyroid diverticulum (see below)

 Differentiates into the follicular cells of the thyroid gland (i.e., the major portion of the lobes and isthmus of the thyroid
gland)
o Lateral thyroid anlagen (ultimobranchial bodies)

 Paired endodermal cell thickenings derived from the 4 branchial pouch

th

 Fuse with the median thyroid anlage

 Differentiate into the parafollicular C cells of the thyroid gland

o Thus, both follicular cells and C cells arise from pharyngeal endoderm

 Thyroid diverticulum
 o A thyroid gland precursor that originates from the floor of the primordial pharynx

o It is located initially at the middle of the floor of the pharynx, near the base of the tongue, i.e., foramen caecum (tongue).

o It descends down the neck, forming the thyroglossal duct, to settle into its adult anatomical position.

o The thyroglossal duct usually obliterates after the thyroid gland has descended.

 However, in about 50% of people, the distal portion of the duct remains as a clinically unremarkable pyramidal lobe of
extra thyroid tissue

 Thyroglossal cyst: caused by a persistent thyroglossal duct (see congenital neck masses for more details)
o The foramen cecum of the tongue remains

During embryological thyroid migration, remnants of thyroid tissue can remain in the tongue (lingual thyroid) or along the migration
path. Ectopic thyroid should always be considered when performing surgical procedures involving thyroid tissue.
Follicular cells arise mainly from the median thyroid anlage!
Parafollicular C cells arise mainly from the lateral thyroid anlage!

References: [1][2][3]

NOTES
FEEDBACK

Clinical significance
 Goiter

 Hypothyroidism
o Iodine deficiency

o Congenital hypothyroidism (cretinism)

o Wolff-Chaikoff effect
 o Hashimoto thyroiditis

o Riedel thyroiditis

o Postpartum thyroiditis

o Subacute thyroiditis (e.g., de Quervain)

 Hyperthyroidism
o Graves disease

o Thyroid adenoma

o Toxic multinodular
goiter
o Thyrotoxicosis and thyroid storm

o Drug-induced: amiodarone, lithium

o Jod-Basedow phenomenon

o Thyrotropic pituitary adenoma

o Struma ovarii

o Iodine excess

 Thyroid nodules (e.g., thyroid cysts)

 Thyroid cancer
o Papillary thyroid cancer

o Follicular thyroid cancer

o Anaplastic thyroid cancer

o Medullary thyroid cancer

 MEN 2A

 MEN 2B
  Antithyroid drugs

 Thyroid surgery
NOTES
FEEDBACK

Parathyroid glands
Overview
 Characteristics
o There are four, oval-shaped endocrine glands embedded in the posterior surface of the thyroid gland

 Two superior parathyroid glands: located near the superior pole of the thyroid gland at the junction of cricoid
and thyroid cartilages.

 Two inferior parathyroid glands: located in the area between the inferior poles of the thyroid lobes and the superior
mediastinum.

 Function: secretion of parathyroid hormone (PTH) in response to low calcium serum levels

 Vasculature
o Arterial supply: inferior thyroid arteries

o Venous drainage: thyroid plexus of veins

o Lymphatic drainage: deep cervical nodes, paratracheal nodes

 Innervation: thyroid branches of the cervical ganglia

Microscopic anatomy
 Cell types
 o Adipocytes (∼ 50%)

o Parathyroid cells (parathyroid chief cells)

 Polygonal, hormone-secreting cells with round nucleus

 Produce and secrete PTH

 Have calcium-sensing receptors (CaSR), which detect changes in calcium concentration and modulate PTH secretion
o Oxyphil cells: red/pink cytoplasm; function not clear

Function
 See calcium homeostasis (PTH increases serum calcium and decreases serum phosphate)
o High extracellular calcium → activation of calcium-sensitive receptors → ↓ PTH excretion

o Low extracellular calcium → inhibition of calcium-sensitive receptors → ↑ PTH excretion

Embryology
 Superior parathyroid glands: derived from the fourth pharyngeal pouch

 Inferior parathyroid gland: derived from the third pharyngeal pouch

DiGeorge syndrome is a congenital T-cell immunodeficiency that is caused by microdeletion at chromosome 22 (22q11.2). The deletion leads to
defective development of the third and fourth pharyngeal pouches, resulting in aplastic parathyroids and hypocalcemia due to PTH deficiency.
Clinical significance
  Hyperparathyroidism

 Hypoparathyroidism

 Pseudohypoparathyroidism

 Thyroidectomy

 Familial hypocalciuric hypercalcemia

 Nelson syndrome

 MEN 1

 MEN 2A

 Osteitis fibrosacystica

 Renal osteodystrophy

Surgery of the thyroid and parathyroid glands can result in destroyed or removed parathyroid glands due to their variable position. This may result
in hypoparathyroidism and hypocalcemia.