Scenario 16: Patrick's Pituitary Flashcards
1
Q
Describe the axis which leads to cortisol secretion and the feedback loops in place to control this
A
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
2
Q
What are some classic signs of Grave’s disease?
A
Goitre, exophthalmos, upper eyelid retraction, pretibial myxoedema, thickening of skin due to glycosaminoglycan deposition and the classic signs of hyperthyroidism
3
Q
What are Herring bodies?
A
Accumulation of hormones within an axon
4
Q
What is the main hormone released by the thyroid gland?
A
T4 which is converted to T3 in the periphery
5
Q
What is the blood supply to the thyroid gland?
A
Superior and inferior arteries arising from external carotid and subclavian artery
6
Q
What kind of receptors do peptide hormones bind to?
A
Cell membrane receptors
7
Q
What controls growth hormone release?
A
Hypothalamic hormones- somatostatin and negative feedback from growth hormone releasing hormone
8
Q
What is the inactive version of cortisol?
A
Cortisone
9
Q
What are the symptoms of hypothyroidism?
A
Cold intolerance, dry skin, weight gain, constipation, hoarse voice, slow reflexes, coarse hair and skin, hypercholesterolemia, puffiness
10
Q
What are the symptoms of diabetes insipidus?
A
Polyuria, polydipsia, with no change in urinary glucose
11
Q
How are steroid hormones synthesised?
A
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
12
Q
What are the shapes of left and right adrenal glands respectively?
A
Right: pyramidal, Left: crescent shaped
13
Q
How can we test for growth hormone function?
A
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
14
Q
What is the histological appearance of cells which secrete steriod hormones?
A
Lots of sER, mitochondria and lipid droplets
15
Q
How can we assess hormone levels?
A
Bioassays of biologically active hormone, radioimmunoassay of hormone
16
Q
What stimulates the gonads to produce testosterone/estradiol?
A
LH/FSH (lutenising hormone/follicle stimulating hormone)
17
Q
Which cells regulate the secretion of the anterior pituitary?
A
Neuroendocrine cells of the hypothalamus whose axons project to the median eminence
18
Q
What is the shape of thyroid gland?
A
2 pear shaped lateral lobes connected by an isthmus in the midline
19
Q
What do glucocorticoids increase the production of?
A
Annexin-1, which inhibits PLA
20
Q
How are T4 levels controlled?
A
Feedback, tissue action, hormone metabolism and fecal excretion
21
Q
How does thyroid hormone interact with it’s receptors?
A
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
22
Q
What do the parathyroid glands secrete?
A
Secretes parathyroid hormone stimulates Ca2+ mobilisation
23
Q
Describe the shape of a glycoprotein hormone and give some examples
A
A & B chains with carbohydrate e.g. lutenizing hormone, FSH, TSH, hCG
24
Q
What forms the posterior pituitary in development?
A
The neurohypophysis (posterior pituitary) is a downgrowth from the floor of dicencephalon of the brain
25
What is the appearance of the adrenal medulla?
Modified sympathetic ganglion, large polyhelical cells in clumps or cords
26
What are the weak androgens secreted by the adrenal gland?
Dehydroepiandrosterone and it's sulphate and androsteredione
27
What does the thyroid release in the thyroid axis?
Thyroxine and tridothyronine (T4 and T3)
28
What does the hypothalamus release in the thyroid axis?
Thyrotrophin releasing hormone
29
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
30
What does oxytocin do?
Uterus contraction, milk ejection from mammary gland
31
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
32
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
33
What is the treatment for Hashimoto's thyroditis?
T4 or liothyronine (T3)
34
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
35
What does AVP do?
Maintains blood pressure via actions on blood vessels, fluid balance, water absorption, vasoconstriciton
36
Give an example of a autocrine hormone
Interleukins
37
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)/
38
What is myxoedema and how is it treated?
Iodine deficiency causing non-toxic goitre which should be treated with iodine supplements
39
Give an example of a neurocrine hormone
Neurotransmitters e.g. acetylcholine
40
What kind of receptors do steroid hormones bind to?
Intracellular receptors
41
What are amine hormones derived from?
Tyrosine or tryptophan derived
42
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
43
How does growth hormone act?
Via GH receptor and insulun-like-growth factor synthesis in the liver
44
What is a hormone?
A biactive molecule which is secreted and travels in the blood to the target cell
45
What is Grave's disease?
An autoimmune disorder where TSAb produce prolonged stimulation of TSH receptors
46
What is the cellular organisation of the parathyroid glands?
Densely packed small chief or principal cells arranged in irregular chords around blood vessels
47
How does a G protein coupled receptor work?
The G protein binds and increases cAMP, switches on gene transcription, adrenaline binds and PKA catalyses
48
What causes goitre?
Increased TSH secretion caused by goitrogens such as kelp, cabbage, cassava, lithium, local waters and cough mixtures
49
What activates vasopressin receptor V1b (V3) where is it found and what does it do?
Phospholipase C, corticotrophs, increase ACTH release
50
What is Hashimoto's thyroditis?
Autoimmune disease, antibodies to thyroglobulin or thyroid peroxidase formed by body
51
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
52
Where do the cell bodies of the neurones of the posterior pituitary lie?
In the supraoptic and paraventricular nuclei of the hypothalamus
53
What are the parts of the posterior pituitary?
Pars nervosa and the infundibulum
54
What stimulates the adrenals to produce cortisol?
ACTH (adrenocorticotropic hormone)
55
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
56
What is the histological appearance of the adrenal cortex?
Loads of sER, lipid droplets, pale and frothy
57
What are the symptoms of hyperthyroidism?
Anxiety, tachycardia, sweating, tremor, heat intolerance, palpitations, eye signs, fatigue, atrial fibrillation, weight loss
58
What do thyroid hormones control?
Control heart rate, heat production, calorie control, metabolism, digestion, bone turnover, critical to brain development
59
What is the manifestation of hypersecretion of growth hormone?
Gigantism if before epiphyses fusion, acromegaly if after fusion
60
What controls the release of adrenocorticotrophic hormone (ACTH)?
Corticotrophin from hypothalamus and cortisol via negative feedback
61
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
62
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
63
What drugs can reduce the symptoms of Grave's disease?
B-blockers like propanolol
64
How can we treat small stature?
Recombinant hGh (somatotroph) or recombinant hIGF-1 (mecasemerin)
65
What are the symptoms of hypopituitarism
Fatigue, weight gain, low libido, amenorrhea, dry hair/skin
66
How can we test anterior pituitary function?
Challenge tests- physiological stimulus/inhibitor
67
What does hypersecretion of vasopressin cause?
Fluid retention, hyponatraemia, seen with Oat cell carcinoma of lung
68
What supports the axons of the posterior pituitary?
Glial like cells called pituicytes
69
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
70
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
71
Which steroid receptor does cortisol have a higher affinity for?
Mineralocorticoid rather than glucocorticoid
72
Where do exocrine glands secrete?
Onto the body surface
73
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
74
What controls prolactin release?
Dopamine inhibits, PRF stimulates,
75
What is the manifestation of hyposecretion of growth hormone?
Short stature if before epiphyses fusion, after fusion there is growth hormone deficiency
76
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,
77
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
78
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
79
How are thyroid epithelium cells arranged?
Into follicles
80
What is the histological appearance of parafollicular/C cells?
Larger and more rounded than follicle cells
81
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.
82
What can excess secretion of androgens cause in women?
Hirsutism and virilsation
83
What is Addison's disease?
Chronic adrenal insuffciency
84
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
85
What does TRH do and where is it released from?
Stimulates thyrotrophs in anterior pituitary to produce TSH. Released from hypothalamus
86
What kind of receptors do steroid hormones interact with?
Nuclear receptors
87
Give an example of a neuroendocrine hormone
Dopamine
88
How do we treat hyperprolactinaemia?
D2 agonists- cabergoline and bromocriptine
89
What is the histological appearance of pars distalis?
Cords of cuboidal/polygonal epithelial secretory cells clustered around large fenestrated sinusoids
90
What forms the anterior pituitary in development?
The adenohypophysis (anterior pituitary) is an upgrowth of ectoderm/endoderm from the embryonic cavity (Rathke's pouch)
91
What is the function of adrenocorticotrophic hormone (ACTH)?
Stimulates secretion of glucocorticoids and has extra adrenal activities
92
What are the chromophobes cells of pars distalis?
Resting/reserve cells
93
Which enzyme converts cortisol to cortisone?
IIBHSD2 isoform of IIBhydroxysteriod dehydrogenase
94
What connects the pituitary to the floor of the III ventricle?
The pituitary stalk (infundibulum)
95
What are steroid hormones derived from?
Cholesterol
96
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
97
Which enzyme organificates iodine?
Thyroid perioxidase in the presence of H2O
98
What does the binding of thyroid hormone to a cell cause?
Increases mRNA production, NaKATPase levels, O2 consumption, protein synthesis, ATP turnover, adrenoreceptors
99
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
100
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)
101
How does a ligand coupled receptor work?
Ligand binds, PLC translocates, DAG and IP3 increase, Ca2+ leaves endoplasmic reticulum, PKC increases
102
Give an example of a paracrine hormone
Histamine
103
Where are parathyroid glands found?
Embedded onto the posterior border of the thyroid glands
104
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
105
What are the anti-inflammatory effects of glucocorticoids?
Stops redness, heat, pain, swelling, increases wound healing, repair and proliferation
106
Give an example of a endocrine hormone
Insulin
107
What does the pituitary release in the thyroid axis?
Thyroid stimulating hormone (TSH)
108
What stimulates the breast to lactate?
PRL (prolactin)
109
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
110
Which hormones are derived from tyrosine?
Dopamine, adrenaline, thyrosine
111
What stimulates the thyroid to produce thyroxine?
TSH
112
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
113
What do parafollicular/C cells secrete?
Calcitonin which inhibits Ca2+ mobilisation
114
What does a lesion of optic chiasm/pituitary tumour cause in visual fields?
Bitemporal hemianopia
115
What is the histological appearance of cells which secrete peptide hormones?
Lots of endoplasmic reticulum, golgi and secretory vesicles
116
What does hyposecretion of vasopressin cause?
Diabetes insipidus, antral (neurogenic) peripheral (nephrogenic)
117
Which part of the pituitary gland is glandular and what are its parts?
The anterior pituitary with pars distalis, pars tuberculis, pars intermedia
118
What stimulates the liver to produce IGF-1?
GH (growth hormone)
119
What is secreted by the pars intermedia?
Melanocyte stimulating hormone which increases skin pigmentation
120
What are the symptoms of a lesion of the optic chiasm?
Headache, vision disturbances, diplopia
121
Where is vasopressin receptor V1a found and what activates it?
Phospholipase C, blood vessels, vasoconstriction
122
What are primary, secondary and tertiary thyroid diseases related to?
Primary- thyroid disorder
Secondary- pituitary disorder
Tertiary- hypothalamic disorder
123
What do glucocorticoids decrease the production of?
Expression of COX-2, cytokine production, complement in plasma, NO production, histamine release, IgG production
124
Where are parafollicular/C cells found?
Scattered cells found within the follicular epithelium of the thyroid gland or as clusters between the follicles
125
Describe the histological appearance of the pars tuberalis.
Thin layer of cuboidal cells, mostly gonadotrophs
126
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
127
When would the adrenal glands increase in size?
In times of stress for example terminal illness
128
What non-medical interventions can be undertake in Grave's disease?
Radioiodine to destroy thyroid follicular cells, partial thyroidectomy
129
What does the posterior pituitary secrete?
Arginine, vasopressin and oxytocin
130
Where do endocrine glands secrete?
Hormones into the blood
131
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
132
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
133
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
134
Which enzyme converts cortisone to cortisol?
IIBHSD1 isoform of IIBhydroxysteriod dehydrogenase
135
What happens in hyperprolactinaemia?
Galactorrhoea (milk from breast), gynaecomastia (male breasts) infertility (males and females)
136
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
137
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
138
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
139
What are some conditions relating to hyperfunction of the adrenal gland?
Adrenal Cushing syndrome, primary hyperaldosteronism, pheochromocytoma,
140
What are some conditions relating to hypofunction of the adrenal gland?
Hypothalmo-pityitary disease, primary adrenal failure, congenital adrenal hyperplasia
141
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
142
What are some possible causes of primary adrenal insufficiency?
Autoimmune, granulomatous infection, hemorrhage, fungal infection, AIDs, congenital adrenal hyperplasia, metastatic disease, adrenalectomy, toxic drugs
143
What are some possible causes of secondary adrenal insufficiency?
Cessation of exogenous steroids, hypothalamus pituitary hypofunction, surgery, radiotherapy, tumours, genetics
144
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
145
How can we treat emergency adrenal failure?
Give ICU care, fluids, sodium, IV hydrocortisone at high dose
146
What is the maintenance treatment for adrenal failure?
Glucocorticoid, mineralocorticoid, DHEA
147
What is congenital adrenal hyperplasia?
Recessive defect in cortisol biosynthesis leads to elevated ACTH, adrenomegaly and excess of androgens
148
What are the symptoms of congenital adrenal hyperplasia?
Salt wasting, precocious puberty in boys, masculinisation of females leading to ambiguous gender at birth
149
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
150
What are the treatments of congenital adrenal hyperplasia?
Ideally in utero, use glucocorticoids to suppress ACTH, anti-androgens, mineralocorticoids, reconstructive surgery (controversial0
