disorders of the endocrine

Question 1

Treatment of endocrine dysregulation

Answer 1

Hyposecretion
Hormone replacement.
i. Steroid and thyroid hormones can be given orally so replacement is straightforward.
ii. Peptide hormones must be injected and are more challenging.
iii. Insulins

Hypersecretion
Surgical removal of over-active gland.
Irradiation of over-active gland.
Hormone receptor blockers.
e.g. beta-blockers used to limit effects of noradrenaline and adrenaline produced by a pheochromocytoma tumour of the adrenal medulla.

Ectopic hormone secretion
Surgical removal of tumour producing hormone.
Target organ insensitivity/resistance
E.g. Type II diabetes and medications to treat T2DM

Question 2

what is Prolactinoma
what can it cause
treatment

Answer 2

It is a noncancerous tumor of the pituitary gland.
Increased production of a hormone called prolactin.
The major effect of a prolactinoma is decreased levels of some sex hormones — namely, estrogen and testosterone.

Can cause vision difficulties, infertility and other problems.
In females, prolactinoma can cause:
Irregular menstrual periods or no menstrual periods
Milky discharge from the breasts when not pregnant or breastfeeding
Painful intercourse due to vaginal dryness
Acne and excessive body and facial hair growth
In males, prolactinoma can cause:
Erectile dysfunction
Decreased body and facial hair
Smaller muscles
Enlarged breasts

It can usually be treated with medications e.g., dopamine agonists to bring the prolactin level down into the standard range and shrink the tumor.
Drugs namely cabergoline and bromocriptine.
In some cases, surgery to remove the tumor might be an option.
The type of surgery you have will depend largely on the size and extent of tumor:
Nasal surgery
The procedure involves removing the tumor through the nose (nasal cavity). This surgery is called transsphenoidal surgery
Transcranial surgery
If the tumor is large or has extended to nearby brain tissue, a procedure known as a craniotomy is used.

Question 3

what is the direct action of growth hormone

Answer 3

Direct actions (i.e. in response to GH per se):-
Generally antagonistic to insulin => diabetogenic effects
Reduce glucose transport into cells increase plasma glucose
Increase lipolysis => increase plasma FFAs
Increased amino acid (AA) transport into muscle => increase muscle growth
=> decrease plasma AA, urea

Question 4

what is indirect actions of growth hormones

Answer 4

Indirect actions mediated by insulin-like growth factors (IGFs)
IGF-I and -II are peptides of MW ~8000
IGFs = “somatomedins”
GH promotes IGF production by liver
IGF promotes:-
Linear growth of bones (stimulates cartilage growth plates)
Growth/cell proliferation of soft tissues, viscera

Question 5

what is Disorders of GH secretion and their treatments

Answer 5

Dwarfism
Growth hormone (GH) deficiency in childhood due to hypopituitarism .
Too little GH in childhood

Gigantism
GH-secreting pituitary tumour resulting in GH excess
Growth hormone over-secretion in childhood (prepuberty).
Very tall stature in young

Acromegaly
Growth hormone over-secretion in adulthood.
Thickening of bones and soft tissues
Coursening of features
Distortion of facial features

treatments
Dwarfism
Replacement therapy with human GH.
Recombinant protein – Somatropin given by injection.

Gigantism
Surgical removal of pituitary and/or suppression of GH secretion using somatostatin analogues lanreotide and octreotide.

Acromegaly
Surgical removal of pituitary.
Use of somatostatin analogues GH receptor antagonist – Pegvisomant.

Question 6

what is Laron syndrome

Answer 6

10 year-old
95 cm tall (equivalent to 3 year-old)
Serum GH levels higher than normal but Serum IGF-1 undetectable
Caused by mutation in GH receptor
Can be treated with IGF-1

Question 7

what is a Disorder of the Anti-diuretic hormone (ADH) and its symtoms - hypo-secretion

Answer 7

Hyposecretion
Leads to Diabetes Insipidus
Reduced ADH leads toless water re-uptake (distal nephron) resulting in:
Increased urination
Increased plasma osmolality
Dehydration

Symptoms
Polyurea – copious, dilute urine (<20L/day!)
Polydipsia- thirst and excessive drinking
Causes
Neurogenic – brain trauma
Nephrogenic – kidney insensitivity

Question 8

Diabetes Insipidus treatment

Answer 8

Replacement therapy with synthetic ADH analogue (Desmopressin)
Usually given as a nasal spray but can be given by injection (IV, SC, IM) and also an orally active form (much larger doses).

Question 9

Disorder of the Anti-diuretic hormone (ADH - hyper secretion
causes
symptoms

Answer 9

Hypersecretion
Syndrome of inappropriate ADH (SIADH)

Symptoms
Decrease in frequency of urination
Excessive fluid retention

Causes
Physiological - Cold, stress, anxiety, pain, trauma
Pathological – ADH secreting tumour
Primary Ectopic e.g. lungs, colon, prostate
Brain disorder/damage

Question 10

SIADH treatment

Answer 10

Limit fluid intake to 500ml/day
Tumor removal
Treatment with antibiotic e.g. Demeclocycline.
Democlocycline has a side effect of blocking action of ADH at kidney

Question 11

what does oxytocin do?

Answer 11

Causes contraction of uterine smooth muscle.
Used to induce uterine contractions during parturition (drug:“syntocin”)
Also involved in “milk ejection reflex” by causes contraction of smooth muscle-type cells myo-epithelial cells) surrounding milk ducts of mammary gland.
A lack of oxytocin in a nursing mother would prevent the milk-ejection reflex and prevent breastfeeding.
Low oxytocin levels have been linked to autism and autistic spectrum disorders (e.g. Asperger syndrome)– a key element of these disorders being poor social functioning.

Question 12

what are symptoms of low oxytocins

Answer 12

Symptoms of low oxytocin:
Lack of warmth in social situations, socially isolated.
Absence of smiles.
Disturbed easily by other people.
Low sex drive.
Less intense or lack of orgasms.
Lack of ejaculation in males.
Pale skin.
Cold hands and feet.

Question 13

what is oxytocin replacement therapy

Answer 13

Taking oxytocin sublingual tablets as part of a hormone replacement therapy treatment plan may help restore levels of this essential hormone.
High oxytocin levels ‘trigger oversensitivity to emotions of others’.

Question 14

Hormones of the adrenal gland

Answer 14

Secreted by the adrenal medulla:
Adrenaline (=epinephrine: USA).

Secreted by adrenal cortex
Aldosterone.
Cortisol

Question 15

what is the role of aldestrone

Answer 15

Maintains balance of Na/K in blood.

Question 16

what is the role of cortisol and effects

Answer 16

Secreted by adrenal cortex
Essential for adaptation to stress.
Mobilizes glucose
Anti-inflammatory actions (at high levels).

Cortisol modulates carbohydrate, fat and protein metabolism.
Opposes effects of insulin: in muscle, adipose and lymphoid tissues it is catabolic (in the liver it stimulates storage of glycogen (anabolic).
Increases plasma glucose levels by stimulating gluconeogenesis (synthesis of glucose from non-carbohydrate) in the liver.
Decreases glucose utilisation in other tissues.
Increased plasma glucose is used for the production of glycogen -important for the maintenance of liver glycogen during prolonged fasting.
Stimulates appetite (note central obesity in Cushing syndrome).
Anti-inflammatory, suppresses tissue responses to injury, decreases number of circulating lymphocytes, decreased antibody production.
The anti-inflammatory effects have lead to the widespread use of glucocorticoids in medicine. E.g Prednisone.

Question 17

what is Cushing syndrome
symptoms
treatment

Answer 17

Normally caused by a benign tumour of the pituitary (Cushing disease).
May be as a result of excess CRH production which drives ACTH secretion which in turn stimulates excess release of cortisol. e.g. from a CRH-producing tumour (relatively rare).
May be as a result of excess ACTH production from an ACTH-producing tumour “ectopic tumour”- most frequently in the lung.
Adrenal tumour
Cushing syndrome is most often an extreme side-effect of steroid medication.

Symptoms
Central obesity
Thinning of the skin
Bruising (due to capillary fragility)
Hypertension (stimulates aldosterone production)
Muscle and bone wasting

treatment
Reduce steroid medication
Surgical removal of the tumour.

Question 18

what is the advice for corticosteriod

Answer 18

To limit risk of adrenal atrophy or Cushing’s syndrome advise “Lowest dose for shortest time, avoiding repeated doses and oral formulations”.
Take dose in morning to avoid sleep disturbance.
Take measures to protect bone health if need high dose or prolonged use.
Avoid sudden withdrawal, if have been taking for more than 3 weeks, high, oral dose, repeated doses to avoid side effects of steroid withdrawal and adrenal crisis.
Without tapering, steroid withdrawal can lead muscle weakness, fatigue, headaches, insomnia, vomiting, hypotension.

Question 19

what is Addison’s Disease
symptoms
treatment

Answer 19

Loss of adrenal function – often autoimmune

Symptoms include:
Tiredness and weakness.
Anorexia and vomiting (diagnosis often confused with anorexia nervosa) due to lack of cortisol.
Loss of sodium reabsorption in the distal tubule of the kidney leads to low sodium and high potassium levels in the plasma.
This leads eventually to hypotension and collapse.
High levels of ACTH are secreted to try to compensate.
Patients become hyperpigmented - especially in skin creases.

treatment
Administration of mineralocorticoids such as 9a-fluorocortisol.
Administration of hydrocortisone to replace cortisol.

Question 20

Disorders of the endocrine part of the Pancreas

Answer 20

Insulinoma
Insulinomas are tumors on the pancreas that results in too much insulin. When this happens, blood sugar levels drop.
Insulinomas are rare and usually benign.
Signs and symptoms of an insulinoma usually include confusion, heart palpitations, excess sweating, weakness, and fatigue.
Patients may find that their symptoms are reduced—and they feel better—after eating or drinking, which often leads to weight gain.

Diabetes mellitus (DM) – Will be discussed in separately*.