Scenario 16: Patrick's Pituitary Flashcards
Describe the axis which leads to cortisol secretion and the feedback loops in place to control this
Trauma/stress causes CRH release which causes anterior pituitary feedback causing ACTH release causing cortisol release. Cortisol acts on the anterior pituitary and CRH release in a negative feedback loop
What are some classic signs of Grave’s disease?
Goitre, exophthalmos, upper eyelid retraction, pretibial myxoedema, thickening of skin due to glycosaminoglycan deposition and the classic signs of hyperthyroidism
What are Herring bodies?
Accumulation of hormones within an axon
What is the main hormone released by the thyroid gland?
T4 which is converted to T3 in the periphery
What is the blood supply to the thyroid gland?
Superior and inferior arteries arising from external carotid and subclavian artery
What kind of receptors do peptide hormones bind to?
Cell membrane receptors
What controls growth hormone release?
Hypothalamic hormones- somatostatin and negative feedback from growth hormone releasing hormone
What is the inactive version of cortisol?
Cortisone
What are the symptoms of hypothyroidism?
Cold intolerance, dry skin, weight gain, constipation, hoarse voice, slow reflexes, coarse hair and skin, hypercholesterolemia, puffiness
What are the symptoms of diabetes insipidus?
Polyuria, polydipsia, with no change in urinary glucose
How are steroid hormones synthesised?
ACTh acts on a G-protein coupled receptor (MC2R) to activate adenylate cyclase which increases cAMP levels. This in turn activates PKA which activates cholesterol ester hydrolase (CEH) which liberates cholesterol from lipid droplets. There is also a stimulation of cholesterol 2022 hydroxylase also referred to as desmolase, the rate limiting enzyme. Steroid hormones are then formed from cholesterol
What are the shapes of left and right adrenal glands respectively?
Right: pyramidal, Left: crescent shaped
How can we test for growth hormone function?
GH stimulation test- fast for 12 hours then give insulin or arginine which should cause an increase in GH secretion.
GH suppression test- fast for 12 hours then give glucose drink which should suppress GH stimulation
What is the histological appearance of cells which secrete steriod hormones?
Lots of sER, mitochondria and lipid droplets
How can we assess hormone levels?
Bioassays of biologically active hormone, radioimmunoassay of hormone
What stimulates the gonads to produce testosterone/estradiol?
LH/FSH (lutenising hormone/follicle stimulating hormone)
Which cells regulate the secretion of the anterior pituitary?
Neuroendocrine cells of the hypothalamus whose axons project to the median eminence
What is the shape of thyroid gland?
2 pear shaped lateral lobes connected by an isthmus in the midline
What do glucocorticoids increase the production of?
Annexin-1, which inhibits PLA
How are T4 levels controlled?
Feedback, tissue action, hormone metabolism and fecal excretion
How does thyroid hormone interact with it’s receptors?
Interacts with nuclear receptors, enters cells by diffusion or by specific carrier. T3 enters nucleus and binds to thyroid receptor. Hormone receptor complex binds to thyroid hormone responsive element on DNA
What do the parathyroid glands secrete?
Secretes parathyroid hormone stimulates Ca2+ mobilisation
Describe the shape of a glycoprotein hormone and give some examples
A & B chains with carbohydrate e.g. lutenizing hormone, FSH, TSH, hCG
What forms the posterior pituitary in development?
The neurohypophysis (posterior pituitary) is a downgrowth from the floor of dicencephalon of the brain
What is the appearance of the adrenal medulla?
Modified sympathetic ganglion, large polyhelical cells in clumps or cords
What are the weak androgens secreted by the adrenal gland?
Dehydroepiandrosterone and it’s sulphate and androsteredione
What does the thyroid release in the thyroid axis?
Thyroxine and tridothyronine (T4 and T3)
What does the hypothalamus release in the thyroid axis?
Thyrotrophin releasing hormone
What do thyroid hormones cause?
Increase O2 and heat production, cardiac contractility, sensitivity to catecholamines, maintain hypoxia and hypercapnia drive in respiratory centre, increase gut motility, erythropoiesis, bone turnover, protein turnover and increase muscles mass, cholesterol degradation, metabolic turnover of hormones and drugs
What does oxytocin do?
Uterus contraction, milk ejection from mammary gland
What activates vasopressin receptor V2 where is it found and what does it do?
Adenyl cyclase, DCT/collecting duct, insert aquaporins to increase H2O permeability
What are the main cell types of the islet of Langerhans and what do each of them secrete?
A cells: glucagon
B cells: insulin
D cells: somatostatin
F or PP cells: pancreatic polypeptide
What is the treatment for Hashimoto’s thyroditis?
T4 or liothyronine (T3)
What stimulates secretions from the posterior pituitary?
For AVP it is changes in body water, hypoosmolarity, hypothalamic osmoreceptors, plasma volume, baroreceptors.
For oxytocin- it is parturition and lactation
What does AVP do?
Maintains blood pressure via actions on blood vessels, fluid balance, water absorption, vasoconstriciton
Give an example of a autocrine hormone
Interleukins
How can we treat acromegaly?
Treated by trans sphenoidal surgery, D2 agonists (cabergoline and bromocriptine) octrestride (long acting somatostatin) lanreotide (analogues SSTR2 agonists) pasineotide (SSTR5 agonist)/
What is myxoedema and how is it treated?
Iodine deficiency causing non-toxic goitre which should be treated with iodine supplements
Give an example of a neurocrine hormone
Neurotransmitters e.g. acetylcholine
What kind of receptors do steroid hormones bind to?
Intracellular receptors
What are amine hormones derived from?
Tyrosine or tryptophan derived
What does the adrenal medulla secrete and what stimulates this?
Secretes NA and adrenaline after stimulation from cholinergic preganglionic sympathetic input from greater and lesser splanchnic nerves via coeliac ganglion
How does growth hormone act?
Via GH receptor and insulun-like-growth factor synthesis in the liver
What is a hormone?
A biactive molecule which is secreted and travels in the blood to the target cell
What is Grave’s disease?
An autoimmune disorder where TSAb produce prolonged stimulation of TSH receptors
What is the cellular organisation of the parathyroid glands?
Densely packed small chief or principal cells arranged in irregular chords around blood vessels
How does a G protein coupled receptor work?
The G protein binds and increases cAMP, switches on gene transcription, adrenaline binds and PKA catalyses
What causes goitre?
Increased TSH secretion caused by goitrogens such as kelp, cabbage, cassava, lithium, local waters and cough mixtures
What activates vasopressin receptor V1b (V3) where is it found and what does it do?
Phospholipase C, corticotrophs, increase ACTH release
What is Hashimoto’s thyroditis?
Autoimmune disease, antibodies to thyroglobulin or thyroid peroxidase formed by body
What are the actions of growth hormone?
Growth of long bones at epiphyses, increase size of viscera, anti-insulin effects, anabolic for protein growth, catabolic for fat and carbohydrate growth
Where do the cell bodies of the neurones of the posterior pituitary lie?
In the supraoptic and paraventricular nuclei of the hypothalamus
What are the parts of the posterior pituitary?
Pars nervosa and the infundibulum
What stimulates the adrenals to produce cortisol?
ACTH (adrenocorticotropic hormone)
How does thyroglobulin accumulate in the follicles of thyroid epithelium?
Accumulates as collid, follicular cells take up iodide which is oxidised to iodine. The iodine is convalently attached to the tyrosines of thyroglobulin within the lumen of the follicle
What is the histological appearance of the adrenal cortex?
Loads of sER, lipid droplets, pale and frothy
What are the symptoms of hyperthyroidism?
Anxiety, tachycardia, sweating, tremor, heat intolerance, palpitations, eye signs, fatigue, atrial fibrillation, weight loss
What do thyroid hormones control?
Control heart rate, heat production, calorie control, metabolism, digestion, bone turnover, critical to brain development
What is the manifestation of hypersecretion of growth hormone?
Gigantism if before epiphyses fusion, acromegaly if after fusion
What controls the release of adrenocorticotrophic hormone (ACTH)?
Corticotrophin from hypothalamus and cortisol via negative feedback
What are the metabolic effects of glucocorticoids?
Decrease glucose uptake, decrease glucose use, increase gluconeogenesis, hyperglycaemia, decrease protein synthesis, increase protein breakdown, decrease Ca2+ absorption in gut and increase excretion by kidney decrease osteoblast activity, increase osteoclast activity
What are the symptoms of Addison’s disease?
Muscular weakness, low blood pressure, depression, anorexia, weight loss, hypoglycaemia, hyperpigmentation, GI disturbances, postural symptoms, salt cravings, hypotension
What drugs can reduce the symptoms of Grave’s disease?
B-blockers like propanolol
How can we treat small stature?
Recombinant hGh (somatotroph) or recombinant hIGF-1 (mecasemerin)
What are the symptoms of hypopituitarism
Fatigue, weight gain, low libido, amenorrhea, dry hair/skin
How can we test anterior pituitary function?
Challenge tests- physiological stimulus/inhibitor
What does hypersecretion of vasopressin cause?
Fluid retention, hyponatraemia, seen with Oat cell carcinoma of lung
What supports the axons of the posterior pituitary?
Glial like cells called pituicytes
What are the treatments for Cushing syndrome? (5 drugs)
Metyrapone: 11b hydroxylase inhibitor
Ketoclonazone (withdrawn in Europe): inhibits steroid biosynthesis
Pasireotide (somatostatin analogue): SSTR5 agonist
Cabergoline (dopamine D2 agonist)
Mifeprestone: glucocorticoid receptor antagonist
Where is the pituitary gland located?
In the pituitary fossa of the sphenoid bone in a bone cavity called the sella turnica related to the oculomotor nerve
Which steroid receptor does cortisol have a higher affinity for?
Mineralocorticoid rather than glucocorticoid
Where do exocrine glands secrete?
Onto the body surface
What are the basophil cells of pars distalis and what do they secrete?
The basophils are the thyrotrophs which secrete TSH, the corticotrophs which secrete ACTH and the gonadotrophs which secrete FSH and LH
What controls prolactin release?
Dopamine inhibits, PRF stimulates,
What is the manifestation of hyposecretion of growth hormone?
Short stature if before epiphyses fusion, after fusion there is growth hormone deficiency
What are the acidophil cells of pars distalis and what do they secrete?
The acidophils are the somatotrophs which secrete GH, and the mammotrophs which secrete PL,
How do steroid hormones interact with their receptors?
They enter cells via diffusion and bind to cytoplasmic receptors. This leads to dissociation of Heat Shock Protein (hsp90) from the receptor. The hormone-receptor complex dimerises and is translocated to the nucleus here the hormone binds to hormone responsive element of DNA increasing mRNA production and therefore protein synthesis
What is Cushing’s syndrome?
Increased cortisone levels causing bruising, poor wound healing, muscle wasting, thinning of skin, increase abdominal fat (buffalo hump) moon face, osteoporosis, obesity, appetite increases, susceptibility to infection worsens, infertility in women
How are thyroid epithelium cells arranged?
Into follicles
What is the histological appearance of parafollicular/C cells?
Larger and more rounded than follicle cells
How are ADH and oxytocin made?
In cell bodies of neurones of the posterior pituitary as a larger protein which is transported to axon terminals, released into sinusoids when stimulated.
What can excess secretion of androgens cause in women?
Hirsutism and virilsation
What is Addison’s disease?
Chronic adrenal insuffciency
What is the appearance and function of the zona glomerulosa of the adrenal cortex?
Cells in rounded clusters surrounded by capillaries. Secrete mineralcorticoids- mainly aldesterone
What does TRH do and where is it released from?
Stimulates thyrotrophs in anterior pituitary to produce TSH. Released from hypothalamus
What kind of receptors do steroid hormones interact with?
Nuclear receptors
Give an example of a neuroendocrine hormone
Dopamine
How do we treat hyperprolactinaemia?
D2 agonists- cabergoline and bromocriptine
What is the histological appearance of pars distalis?
Cords of cuboidal/polygonal epithelial secretory cells clustered around large fenestrated sinusoids
What forms the anterior pituitary in development?
The adenohypophysis (anterior pituitary) is an upgrowth of ectoderm/endoderm from the embryonic cavity (Rathke’s pouch)
What is the function of adrenocorticotrophic hormone (ACTH)?
Stimulates secretion of glucocorticoids and has extra adrenal activities
What are the chromophobes cells of pars distalis?
Resting/reserve cells
Which enzyme converts cortisol to cortisone?
IIBHSD2 isoform of IIBhydroxysteriod dehydrogenase
What connects the pituitary to the floor of the III ventricle?
The pituitary stalk (infundibulum)
What are steroid hormones derived from?
Cholesterol
What drugs would be used to treat syndrome of inappropriate ADH secretion?
Demeclocycline (a tetracycline) Disrupts ADH signalling
Conivaptan- V1a/V2 receptor antagonist
Tolvaptan- V2 receptor antagonist
Which enzyme organificates iodine?
Thyroid perioxidase in the presence of H2O
What does the binding of thyroid hormone to a cell cause?
Increases mRNA production, NaKATPase levels, O2 consumption, protein synthesis, ATP turnover, adrenoreceptors
What is POMC a precursor for in the hypothalamus?
ACTH, B-endophin, N-terminal peptide, B-MSH, B-LPH, Y-melanocyte stimulating hormone, GLIP, Y-LPH
How is iodinated thyroglobulin released as T4 and T3?
On stimulation by TSH from the anterior pituitary follicular cells endocytose the iodinated thyroglobulin and break it down in lysosomes. They release the iodinated tyrosine derivatives as tetra-iodothyronine (T4) and tri-iodothyronine (T3)
How does a ligand coupled receptor work?
Ligand binds, PLC translocates, DAG and IP3 increase, Ca2+ leaves endoplasmic reticulum, PKC increases
Give an example of a paracrine hormone
Histamine
Where are parathyroid glands found?
Embedded onto the posterior border of the thyroid glands
What are the advantages of a portal system for regulation of the anterior pituitary?
Need less releasing hormone, there is a more immediate response, some hormone can be re used elsewhere for other purposes
What are the anti-inflammatory effects of glucocorticoids?
Stops redness, heat, pain, swelling, increases wound healing, repair and proliferation
Give an example of a endocrine hormone
Insulin
What does the pituitary release in the thyroid axis?
Thyroid stimulating hormone (TSH)
What stimulates the breast to lactate?
PRL (prolactin)
How do neuroendocrine cells of the hypothalamus regulate secretion by the anterior pituitary?
Discharge into capillaries of the pituitary portal vessels ending into the capillaries which bathe the anterior pituitary
Which hormones are derived from tyrosine?
Dopamine, adrenaline, thyrosine
What stimulates the thyroid to produce thyroxine?
TSH
What stimulates growth hormone secretion?
Episodic related to exercise, stress (physical or psychological) sleep, postprandial, glucose decline, drug induced, hypoglycaemia, amino acid infusions, small peptide hormones, monoaminergic stimuli
What do parafollicular/C cells secrete?
Calcitonin which inhibits Ca2+ mobilisation
What does a lesion of optic chiasm/pituitary tumour cause in visual fields?
Bitemporal hemianopia
What is the histological appearance of cells which secrete peptide hormones?
Lots of endoplasmic reticulum, golgi and secretory vesicles
What does hyposecretion of vasopressin cause?
Diabetes insipidus, antral (neurogenic) peripheral (nephrogenic)
Which part of the pituitary gland is glandular and what are its parts?
The anterior pituitary with pars distalis, pars tuberculis, pars intermedia
What stimulates the liver to produce IGF-1?
GH (growth hormone)
What is secreted by the pars intermedia?
Melanocyte stimulating hormone which increases skin pigmentation
What are the symptoms of a lesion of the optic chiasm?
Headache, vision disturbances, diplopia
Where is vasopressin receptor V1a found and what activates it?
Phospholipase C, blood vessels, vasoconstriction
What are primary, secondary and tertiary thyroid diseases related to?
Primary- thyroid disorder
Secondary- pituitary disorder
Tertiary- hypothalamic disorder
What do glucocorticoids decrease the production of?
Expression of COX-2, cytokine production, complement in plasma, NO production, histamine release, IgG production
Where are parafollicular/C cells found?
Scattered cells found within the follicular epithelium of the thyroid gland or as clusters between the follicles
Describe the histological appearance of the pars tuberalis.
Thin layer of cuboidal cells, mostly gonadotrophs
How are the cells of the islets of Langerhans arranged?
Cells are smaller and more lightly stained than exocrine cells and arranged in irregular cords around capillaries
When would the adrenal glands increase in size?
In times of stress for example terminal illness
What non-medical interventions can be undertake in Grave’s disease?
Radioiodine to destroy thyroid follicular cells, partial thyroidectomy
What does the posterior pituitary secrete?
Arginine, vasopressin and oxytocin
Where do endocrine glands secrete?
Hormones into the blood
How will the collid change with thyroid hormone release?
If thyroid hormones are being made and not released the collid with increase, if there is demand for hormones the collid will decrease
What is the appearance and function of the zona reticularis of the adrenal cortex?
Cells arranged in irregular cords. Secrete glucocorticoids and small quantities of sex steroids
How does the thyroid gland develop?
Arises from a diverticulum on the floor of the primitive pharynx just caudal to the site of the future tongue opening at the base of the tongue as the foramen caecum
Which enzyme converts cortisone to cortisol?
IIBHSD1 isoform of IIBhydroxysteriod dehydrogenase
What happens in hyperprolactinaemia?
Galactorrhoea (milk from breast), gynaecomastia (male breasts) infertility (males and females)
How is Grave’s disease treated with antithyroid drugs, what is the treatment time and what are the side effects?
Antithyroid drugs: carbimazole, propylthiouracil (inhibits thyroid perioxidase propylthiouracil also prevents peripheral conversion of T4 to T3) 4-8 weeks until euthyroid then reduce to maintenance dose for 12-18 months. Side effects: neutropenia and angranulocytosis
What is the appearance and function of the zona fasciculata of the adrenal cortex?
Cells in straight cords, running radially. Secrete glucocorticoids, mainly cortisol. Glucose lipid and protein metabolism
What are the functions of the thyroid gland?
Development (neural in foetus, growth of young child) metabolism (BMR) concentrates iodine for incorporation into thyroid hormones
What are some conditions relating to hyperfunction of the adrenal gland?
Adrenal Cushing syndrome, primary hyperaldosteronism, pheochromocytoma,
What are some conditions relating to hypofunction of the adrenal gland?
Hypothalmo-pityitary disease, primary adrenal failure, congenital adrenal hyperplasia
What is the histological appearance of the adrenal gland?
Migrating neural crest cells colonise the developing adrenal gland, forming the medulla. Cells similar to sympathetic nerve cells
What are some possible causes of primary adrenal insufficiency?
Autoimmune, granulomatous infection, hemorrhage, fungal infection, AIDs, congenital adrenal hyperplasia, metastatic disease, adrenalectomy, toxic drugs
What are some possible causes of secondary adrenal insufficiency?
Cessation of exogenous steroids, hypothalamus pituitary hypofunction, surgery, radiotherapy, tumours, genetics
How can we diagnose primary adrenal failure?
ACTH level elevated, hyperkalaemia, lack of response to Synacthen (synthetic ACTH), high plasma renin, reduced circulating volume and aldosterone deficiency
How can we treat emergency adrenal failure?
Give ICU care, fluids, sodium, IV hydrocortisone at high dose
What is the maintenance treatment for adrenal failure?
Glucocorticoid, mineralocorticoid, DHEA
What is congenital adrenal hyperplasia?
Recessive defect in cortisol biosynthesis leads to elevated ACTH, adrenomegaly and excess of androgens
What are the symptoms of congenital adrenal hyperplasia?
Salt wasting, precocious puberty in boys, masculinisation of females leading to ambiguous gender at birth
What are the symptoms of steroid-21-hydroxylase deficiency congenital adrenal hyperplasia?
Urogenital sinus, labial fusion, scrotilisation of labia majora, clitoromegaly, penile enlargement, bone age advancement, rapid growth, acne, hirsutism, menstrual abnormalities, infertility
What are the treatments of congenital adrenal hyperplasia?
Ideally in utero, use glucocorticoids to suppress ACTH, anti-androgens, mineralocorticoids, reconstructive surgery (controversial0
